ORCID Profile
0000-0002-6933-4637
Current Organisation
Karolinska Institutet
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Publisher: Elsevier BV
Date: 2013
DOI: 10.1038/KI.2012.327
Abstract: Fibroblast growth factor-23 (FGF23), a regulator of mineral metabolism, has been linked to cardiovascular disease in chronic kidney disease. As community-based data of the longitudinal association between FGF23 and cardiovascular events are lacking, we investigated a possible relationship in 727 men of the Uppsala Longitudinal Study of Adult Men population-based cohort (mean age 77 years). During a median follow-up of 9.7 years, 110 participants died of cardiovascular causes. In Cox regression models adjusted for age and established cardiovascular risk factors, higher serum FGF23 was associated with a significantly increased risk for cardiovascular mortality (hazard ratio (HR) per increased s.d. of 1.36). This relationship remained significant, albeit attenuated, after adjustment for glomerular filtration rate (GFR) (HR 1.21). FGF23 was also associated with all-cause mortality, although the association was weaker than that with cardiovascular mortality, and it was nonsignificant in fully adjusted multivariate models. Spline analysis suggested a log-linear relationship between FGF23 and outcome. Participants with a combination of high FGF23 (>60 pg/ml), low GFR (<60 ml/min), and micro-/macro-albuminuria (albumin/creatinine ratio above 3 mg/ml) had an almost eightfold increased risk compared with participants without these abnormalities. Thus, a higher FGF23 level is associated with an increased cardiovascular mortality risk in the community. Clinical trials are needed to determine whether FGF23 is a modifiable risk factor.
Publisher: Public Library of Science (PLoS)
Date: 25-02-2019
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 2015
Publisher: SAGE Publications
Date: 07-04-2017
Abstract: We aimed to study the association between neighborhood socioeconomic status at the age of 40 years and risk of ischemic stroke before the age of 50 years. All in iduals in Sweden were included if their 40th birthday occurred between 1998 and 2010. National registers were used to categorize neighborhood socioeconomic status into high, middle, and low and to retrieve information on incident ischemic strokes. Hazard ratios and their 95% confidence intervals were estimated. A total of 1,153,451 adults (women 48.9%) were followed for a mean of 5.5 years (SD 3.5 years), during which 1777 (0.30%) strokes among men and 1374 (0.24%) strokes among women were recorded. After adjustment for sex, marital status, education level, immigrant status, region of residence, and neighborhood services, there was a lower risk of stroke in residents from high-socioeconomic status neighborhoods (hazard ratio 0.87, 95% confidence interval 0.78–0.96), and an increased risk of stroke in adults from low-socioeconomic status neighborhoods (hazard ratio 1.16, 95% confidence interval 1.06–1.27), compared to their counterparts living in middle-socioeconomic status neighborhoods. After further adjustment for hospital diagnoses of hypertension, diabetes, heart failure, and atrial fibrillation prior to the age of 40, the higher risk in neighborhoods with low socioeconomic status was attenuated, but remained significant (hazard ratio 1.12, 95% confidence interval 1.02–1.23). In a nationwide study of in iduals between 40 and 50 years, we found that the risk of ischemic stroke differed depending on neighborhood socioeconomic status, which calls for increased efforts to prevent cardiovascular diseases in low socioeconomic status neighborhoods.
Publisher: Elsevier BV
Date: 2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-01-2023
Abstract: The study aimed to show the relationship between a large number of circulating metabolites and subsequent cardiovascular disease (CVD) and subclinical markers of CVD in the general population. In 2278 in iduals free from CVD in the EpiHealth study (aged 45–75 years, mean age 61 years, 50% women), 790 annotated nonxenobiotic metabolites were measured by mass spectroscopy (Metabolon). The same metabolites were measured in the PIVUS (Prospective Investigation of Vasculature in Uppsala Seniors) study (n=603, all aged 80 years, 50% women), in which cardiac and carotid artery pathologies were evaluated by ultrasound. During a median follow‐up of 8.6 years, 107 in iduals experienced a CVD (fatal or nonfatal myocardial infarction, stroke, or heart failure) in EpiHealth. Using a false discovery rate of 0.05 for age‐ and sex‐adjusted analyses and P .05 for adjustment for traditional CVD risk factors, 37 metabolites were significantly related to incident CVD. These metabolites belonged to multiple biochemical classes, such as amino acids, lipids, and nucleotides. Top findings were dimethylglycine and N‐acetylmethionine. A lasso selection of 5 metabolites improved discrimination when added on top of traditional CVD risk factors (+4.0%, P =0.0054). Thirty‐five of the 37 metabolites were related to subclinical markers of CVD evaluated in the PIVUS study. The metabolite 1‐carboxyethyltyrosine was associated with left atrial diameter as well as inversely related to both ejection fraction and the echogenicity of the carotid artery. Several metabolites were discovered to be associated with future CVD, as well as with subclinical markers of CVD. A selection of metabolites improved discrimination when added on top of CVD risk factors.
Publisher: Elsevier BV
Date: 07-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2017
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.ATHEROSCLEROSIS.2012.07.008
Abstract: Endothelial dysfunction is prevalent among in iduals with chronic kidney disease. However, the association between glomerular filtration rate and endothelial function in the community is unclear and needs to be investigated in the general population. In the community-based Prospective Investigation of the Vasculature of Uppsala Seniors study (PIVUS, n = 952, mean age 70, women 49.3%), we investigated cross-sectional associations between estimated cystatin C-based glomerular filtration rate (eGFR), and 3 measures representing different aspects of endothelial function (endothelial-dependent vasodilation [EDV], endothelial independent vasodilatation [EIDV], and flow-mediated dilatation [FMD]). We also performed pre-specified sub-group analyses in participants with normal eGFR (>60 ml/min/1.73 m(2)). In the whole cohort, 10 ml/min/1.73 m(2) higher eGFR was associated with 3% higher EDV (p = 0.001) and 2% higher EIDV (p = 0.007), adjusted for age and sex. The associations were attenuated and no longer statistically significant after adjusting for established cardiovascular risk factors. In participants with eGFR >60 ml/min/1.73 m(2), 10 ml higher eGFR was associated with 2% higher EDV (p = 0.04) after adjusting for sex and age. eGFR was not associated to FMD in any model or sub-s le. This community-based study suggests that eGFR is associated with endothelial function also in persons with normal kidney function, but that this association is largely explained by confounding by established cardiovascular risk factors. Thus, our data do not support the notion of a direct causal interplay between renal and vascular function prior to the development of CKD.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2021
DOI: 10.1161/CIRCGEN.120.002963
Abstract: It is known that certain cardiovascular diseases (CVD) are associated, like atrial fibrillation and stroke. However, for other CVDs, the links and temporal trends are less studied. In this longitudinal study, we have investigated temporal epidemiological and genetic associations between different CVDs. The ULSAM (Uppsala Longitudinal Study of Adult Men 2322 men aged 50 years) has been followed for 40 years regarding 4 major CVDs (incident myocardial infarction, ischemic stroke, heart failure, and atrial fibrillation). For the genetic analyses, publicly available data were used. Using multistate modeling, significant relationships were seen between pairs of all of the 4 investigated CVDs. However, the risk of obtaining one additional CVD differed substantially both between different CVDs and between their temporal order. The relationship between heart failure and atrial fibrillation showed a high risk ratio (risk ratios, 24–26) regardless of the temporal order. A consistent association was seen also for myocardial infarction and atrial fibrillation but with a lower relative risk (risk ratios, 4–5). In contrast, the risk of receiving a diagnosis of heart failure following a myocardial infarction was almost twice as high as for the reverse temporal order (risk ratios, 16 versus 9). Genetic loci linked to traditional risk factors could partly explain the observed associations between the CVDs, but pathway analyses disclosed also other pathophysiological links. During 40 years, all of the 4 investigated CVDs were pairwise associated with each other regardless of the temporal order of occurrence, but the risk magnitude differed between different CVDs and their temporal order. Genetic analyses disclosed new pathophysiological links between CVDs.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.ATHEROSCLEROSIS.2016.09.014
Abstract: Cardiovascular diseases account for the largest fraction of smoking-induced deaths. Studies of smoking in relation to cardiovascular-related protein markers can provide novel insights into the biological effects of smoking. We investigated the associations between cigarette smoking and 80 protein markers known to be related to cardiovascular diseases in two community-based cohorts, the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 969, 50% women, all aged 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 717, all men aged 77 years). Smoking status was self-reported and defined as current smoker, former smoker or never-smoker. Levels of the 80 proteins were measured using the proximity extension assay, a novel PCR-based proteomics technique. We found 30 proteins to be significantly associated with current cigarette smoking in PIVUS (FDR<5%) and ten were replicated in ULSAM (p < 0.05). Matrix metalloproteinase-12 (MMP-12), growth/differentiation factor 15 (GDF-15), urokinase plasminogen activator surface receptor (uPAR), TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), lectin-like oxidized LDL receptor 1 (LOX-1), hepatocyte growth factor (HGF), matrix metalloproteinase-10 (MMP-10) and matrix metalloproteinase-1 (MMP-1) were positively associated, while endothelial cell-specific molecule 1 (ESM-1) and interleukin-27 subunit alpha (IL27-A) showed inverse associations. All of them remained significant in a subset of in iduals without manifest cardiovascular disease. The findings of the present study suggest that cigarette smoking may interfere with several essential parts of the atherosclerosis process, as evidenced by associations with protein markers representing endothelial dysfunction, inflammation, neointimal formation, foam cell formation and plaque instability.
Publisher: American Diabetes Association
Date: 17-09-2010
DOI: 10.2337/DC10-0955
Abstract: The existence of an obese subgroup with a healthy metabolic profile and low diabetes risk has been proposed yet long-term data are lacking. We aimed to investigate associations between combinations of BMI categories and metabolic syndrome and risk of type 2 diabetes in middle-aged men. At age 50, cardiovascular risk factors were assessed in 1,675 participants without diabetes in the community-based Uppsala Longitudinal Study of Adult Men (ULSAM) study. According to BMI/metabolic syndrome status, they were categorized as normal weight (BMI & kg/m2) without metabolic syndrome (National Cholesterol Education Program criteria, n = 853), normal weight with metabolic syndrome (n = 60), overweight (BMI 25–30 kg/m2) without metabolic syndrome (n = 557), overweight with metabolic syndrome (n = 117), obese (BMI & kg/m2) without metabolic syndrome (n = 28), and obese with metabolic syndrome (n = 60). We investigated the associations between BMI/metabolic syndrome categories at baseline and diabetes incidence. After 20 years, 160 participants had developed diabetes. In logistic regression models adjusting for age, smoking, and physical activity, increased risks for diabetes were observed in the normal weight with metabolic syndrome (odds ratio 3.28 [95% CI] 1.38–7.81 P = 0.007), overweight without metabolic syndrome (3.49 [2.26–5.42] P & 0.001), overweight with metabolic syndrome (7.77 [4.44–13.62] P & 0.001), obese without metabolic syndrome (11.72 [4.88–28.16] P & 0.001), and obese with metabolic syndrome (10.06 [5.19–19.51] P & 0.001) categories compared with the normal weight without metabolic syndrome category. Overweight or obese men without metabolic syndrome were at increased risk for diabetes. Our data provide further evidence that overweight and obesity in the absence of the metabolic syndrome should not be considered a harmless condition.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-07-2017
DOI: 10.2215/CJN.08780816
Abstract: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence. We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS n =687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM n =360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations. In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2*, CD40L receptor, TNF receptor 1*, placenta growth factor*, thrombomodulin*, urokinase plasminogen activator surface receptor*, growth/differentiation factor 15*, macrophage colony-stimulating factor 1, fatty acid-binding protein*, cathepsin D, resistin, kallikrein 11*, C-C motif chemokine 3, proteinase-activated receptor 1*, cathepsin L, chitinase 3-like protein 1, TNF receptor 2*, fibroblast growth factor 23*, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with * above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts. Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.
Publisher: Elsevier BV
Date: 09-2014
Publisher: Wiley
Date: 28-01-2017
DOI: 10.1111/ECI.12722
Abstract: We have recently shown that being physically active (PA) counteracts, but not eliminates the increased risk of future cardiovascular disease in overweight and obese subjects. To investigate this further, we studied the impact of being normal weight, overweight and obese on multiple markers of subclinical cardiovascular disease in relation to physical activity. At age 70, 1016 subjects were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Being PA was defined as performing regular heavy exercise (self-reported). According to body mass index (BMI)/PA groups, the participants were categorized as PA/normal weight (BMI < 25 kg/m Physically active subjects with obesity showed impaired vasoreactivity in the forearm resistance vessels, increased left ventricular mass and impaired left ventricular systolic and diastolic functions, together with impaired coagulation/fibrinolysis when compared to PA/normal-weight subjects (P < 0·05 to <0·001). The majority of these disturbances were seen also in PA/overweight subjects when compared to PA/normal-weight subjects (P < 0·05 to <0·001). Our data provide additional support for the notion that an increased level of self-reported physical activity does not fully eliminate the deleterious cardiovascular consequences associated with overweight and obesity.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2006
DOI: 10.1161/01.STR.0000249056.24657.8B
Abstract: Background and Purpose— The impact of lipometabolic and glucometabolic disturbances on stroke incidence remains to be characterized in detail. We investigated relations of a comprehensive panel of baseline lipometabolic and glucometabolic variables to incident fatal and nonfatal stroke or transient ischemic attack (TIA), and stroke subtypes. Methods— A community-based prospective study of 2313 middle-aged men invited to a health survey at age 50. Results— During a follow-up of up to 32 years, 421 developed stroke or TIA. In Cox proportional hazards analyses adjusting for treatment with cardiovascular drugs at baseline, 1-standard deviation increases in body mass index, systolic and diastolic blood pressures, serum proinsulin, and lipoprotein(a) were associated with 11 to 35% increased risk for subsequent stroke/TIA. Electrocardiographic left ventricular hypertrophy and smoking were also associated with a higher risk for stroke/TIA. Essentially the same variables were related to brain infarction/TIA. Higher proportions of palmitic (16:0), palmitoleic (16:1), and oleic acid (18:1) in cholesterol esters were associated with an increased risk, whereas a higher proportion of linoleic acid (18:2 n-6) was protective against stroke/TIA. Further adjusting all models also for hypertension, diabetes, the metabolic syndrome, serum cholesterol, atrial fibrillation, cardiovascular disease, smoking, and physical activity, essentially the same pattern was observed. Conclusions— Indices of an unhealthy dietary fat intake and a high serum lipoprotein (a) level predicted fatal and nonfatal stroke/TIA independently of established risk factors in a community-based s le of middle-aged men followed for 32 years.
Publisher: Oxford University Press (OUP)
Date: 09-05-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2011
DOI: 10.1161/ATVBAHA.110.221572
Abstract: Although obesity without metabolic disturbances has been regarded as harmless, we have recently shown that obese subjects without the metabolic syndrome (MetS) has an increased risk of cardiovascular (CV) disorders and mortality during long-term follow-up. To investigate the basis for that increased risk, we studied the impact of obesity without MetS on multiple markers of subclinical CV disease. At age 70, 1016 subjects were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors study. According to body mass index (BMI)/MetS status, they were categorized as normal weight (BMI kg/m 2 ) without MetS (National Cholesterol Education Program criteria, n=319), normal weight with MetS (n=19), overweight (BMI 25 to 29.9 kg/m 2 ) without MetS (n=333), overweight with MetS (n=94), obese (BMI ≥30 kg/m 2 ) without MetS (n=102), and obese with MetS (n=118). Several different measurements of endothelial reactivity, arterial compliance (plethysmography and ultrasound), carotid artery atherosclerosis, and echocardiography were performed, and 7 markers of coagulation/fibrinolysis were measured. Subjects with obesity without MetS showed impaired vasoreactivity, a more echolucent carotid artery wall, increased left ventricular mass and function together with impaired coagulation/fibrinolysis compared with normal-weight subjects without the MetS ( P .05 to 0.001). The majority of these disturbances were also seen in overweight subjects without the MetS. In contrast to some previous studies, our data do not support that obesity without MetS is a benign condition, because obesity without MetS was associated with impairments in multiple markers of subclinical CV disease. This was also the case for overweight subjects without the MetS.
Publisher: Wiley
Date: 30-05-2019
DOI: 10.1002/EHF2.12453
Publisher: Springer Science and Business Media LLC
Date: 06-06-2018
DOI: 10.1038/S41598-018-26701-0
Abstract: Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 ± 0.6 years), plasma s les obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic cl method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10- and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10- or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
DOI: 10.1161/ATVBAHA.113.301218
Abstract: Current guidelines do not support the use of genetic profiles in risk assessment of coronary heart disease (CHD). However, new single nucleotide polymorphisms associated with CHD and intermediate cardiovascular traits have recently been discovered. We aimed to compare several multilocus genetic risk score (MGRS) in terms of association with CHD and to evaluate clinical use. We investigated 6 Swedish prospective cohort studies with 10 612 participants free of CHD at baseline. We developed 1 overall MGRS based on 395 single nucleotide polymorphisms reported as being associated with cardiovascular traits, 1 CHD-specific MGRS, including 46 single nucleotide polymorphisms, and 6 trait-specific MGRS for each established CHD risk factors. Both the overall and the CHD-specific MGRS were significantly associated with CHD risk (781 incident events hazard ratios for fourth versus first quartile, 1.54 and 1.52 P .001) and improved risk classification beyond established risk factors (net reclassification improvement, 4.2% and 4.9% P =0.006 and 0.017). Discrimination improvement was modest (C-index improvement, 0.004). A polygene MGRS performed worse than the CHD-specific MGRS. We estimate that 1 additional CHD event for every 318 people screened at intermediate risk could be saved by measuring the CHD-specific genetic score in addition to the established risk factors. Our results indicate that genetic information could be of some clinical value for prediction of CHD, although further studies are needed to address aspects, such as feasibility, ethics, and cost efficiency of genetic profiling in the primary prevention setting.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2014
DOI: 10.1161/ATVBAHA.113.303062
Abstract: Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited. Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003–0.08 P =0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33–1.88 P .0001). Results were similar when including fatal atherosclerotic disease in the outcome. In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.
Publisher: Mary Ann Liebert Inc
Date: 02-2017
Abstract: Obesity and its associated metabolic complications continue to increase worldwide. We investigated the development of metabolic syndrome (MetS) during aging in relation to body mass index (BMI) and exercise habits. We assigned special emphasis to the metabolic stability in in iduals with obesity, but without MetS, a condition often referred to as metabolically healthy obesity. Cross-sectional analysis was carried out in a s le of 19,129 men and women aged 45-75 years from the EpiHealth study. In addition, longitudinal analyses were carried out in the ULSAM study (2322 men at baseline followed from age 50 to age 77) and in the PIVUS study (1016 men and women at baseline followed from age 70 to age 80). Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m MetS prevalence and number of MetS components increased with age in all three s les. The PIVUS study showed that high baseline BMI, low baseline physical activity, and increasing BMI during follow-up were related to increasing MetS prevalence and increasing numbers of MetS components during follow-up. One-third to half of in iduals initially belonging to the obesity without MetS category acquired MetS during aging. MetS prevalence increased during aging, especially in in iduals with high BMI, low level of physical activity, and weight gain. Obesity without MetS was not a stable condition over time as many of those in iduals gained metabolic disturbances during aging.
Publisher: Cold Spring Harbor Laboratory
Date: 30-12-2021
DOI: 10.1101/2021.12.23.21268179
Abstract: The human gut microbiota produces a variety of small compounds, some of which enter the bloodstream and impact host health. Conversely, various exogenous nutritional and pharmaceutical compounds affect the gut microbiome composition before entering circulation. Characterization of the gut microbiota–host plasma metabolite interactions is an important step towards understanding the effects of the gut microbiota on human health. However, studies involving large and deeply phenotyped cohorts that would reveal such meaningful interactions are scarce. Here, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for detailed characterization of the fecal microbiota and plasma metabolome, respectively, of 8,584 participants invited at age 50 to 64 of the Swedish CArdioPulmonary bioImage Study (SCAPIS). After adjusting for multiple comparisons, we identified 1,008 associations between species alpha ersity and plasma metabolites, and 318,944 associations between specific gut metagenomic species and plasma metabolites. The gut microbiota explained up to 50% of the variance of in idual plasma metabolites (mean of 4.7%). We present all results as the searchable association atlas “GUTSY” as a rich resource for mining associations, and exemplify the potential of the atlas by presenting novel associations between oral medication and the gut microbiome, and microbiota species strongly associated with levels of the uremic toxin p-cresol sulfate. The association atlas can be used as the basis for targeted studies of perturbation of specific bacteria and for identification of candidate plasma biomarkers of gut flora composition.
Publisher: Wiley
Date: 23-11-2010
DOI: 10.1111/J.1365-2796.2010.02309.X
Abstract: the results of experimental studies suggest that vitamin D deficiency activates the renin-angiotensin system and predisposes to hypertension. Results of previous epidemiological studies investigating the association between 25-hydroxyvitamin D [25(OH)D] status and hypertension have not been consistent, perhaps because of their sole reliance on office blood pressure (BP) measurements leading to some misclassification of hypertension status. No previous studies have examined the association between 25(OH)D status and confirmed hypertension assessed with both office and 24-h BP measurements. in this cross-sectional study, we investigated 833 Caucasian men, aged 71 ± 0.6 years, to determine the association between plasma 25(OH)D concentrations, measured with high-pressure liquid chromatography mass spectrometry, and the prevalence of hypertension. We used both supine office and 24-h BP measurements for classifying participants as normotensive or confirmed hypertensive participants with inconsistent classifications were excluded. in a multivariable adjusted logistic regression model, men with 25(OH)D concentrations <37.5 nmol L(-1) had a 3-fold higher prevalence of confirmed hypertension compared to those with ≥ 37.5 nmol L(-1) 25(OH)D (odds ratio = 3.3, 95% CI: 1.0-11.0). our results show that low plasma 25(OH)D concentration is associated with a higher prevalence of confirmed hypertension.
Publisher: Mary Ann Liebert Inc
Date: 04-2017
Abstract: Many lifestyle factors have been associated with the metabolic syndrome (MetS). However, most of these studies have not considered the potential impact of obesity and have often only investigated one lifestyle factor at the time. We aimed to investigate the interplay between body mass index (BMI) and MetS with respect to multiple lifestyle factors. BMI and MetS [National Cholesterol Education Program (NCEP)/Adult Treatment Panel III criteria] were assessed in a s le of 18,880 subjects aged 45-75 years from the population-based EpiHealth study. Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m Prevalent MetS (23% in the s le) was associated with less physical activity (P < 0.0001), more TV watching (P < 0.0001), more years of smoking (P < 0.0001), lower education level (P = 0.007), and experiencing a poor general quality of life (P < 0.0001). These lifestyle factors were all associated with MetS, independently of each other and independently of BMI. Similar results were generated when number of MetS components and presence/absence of in idual MetS components were used as outcomes. This cross-sectional study identified alterations in a number of lifestyle factors associated with MetS independently of each other and independently of BMI. Future longitudinal studies are needed to assess causal and temporal relationships between lifestyle factors and MetS development.
Publisher: Massachusetts Medical Society
Date: 05-09-2013
Publisher: American Medical Association (AMA)
Date: 20-07-2005
Abstract: Diabetes and obesity are established risk factors for congestive heart failure (CHF) and are both associated with insulin resistance. To explore if insulin resistance may predict CHF and may provide the link between obesity and CHF. The Uppsala Longitudinal Study of Adult Men, a prospective, community-based, observational cohort in Uppsala, Sweden. We investigated 1187 elderly (>or=70 years) men free from CHF and valvular disease at baseline between 1990 and 1995, with follow-up until the end of 2002. Variables reflecting insulin sensitivity (including euglycemic insulin cl glucose disposal rate) and obesity were analyzed together with established risk factors (prior myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and serum cholesterol level) as predictors of subsequent incidence of CHF, using Cox proportional hazards analyses. First hospitalization for heart failure. One hundred four men developed CHF during a median follow-up of 8.9 (range, 0.01-11.4) years. In multivariable Cox proportional hazards models adjusted for established risk factors for CHF, increased risk of CHF was associated with a 1-SD increase in the 2-hour glucose value of an oral glucose tolerance test (hazard ratio [HR], 1.44 95% confidence interval [CI], 1.08-1.93), fasting serum proinsulin level (HR, 1.29 95% CI, 1.02-1.64), body mass index (HR, 1.35 95% CI, 1.11-1.65), and waist circumference (HR, 1.36 95% CI, 1.10-1.69), whereas a 1-SD increase in cl glucose disposal rate decreased the risk (HR, 0.66 95% CI, 0.51-0.86). When adding cl glucose disposal rate to these models as a covariate, the obesity variables were no longer significant predictors of subsequent CHF. Insulin resistance predicted CHF incidence independently of established risk factors including diabetes in our large community-based s le of elderly men. The previously described association between obesity and subsequent CHF may be mediated largely by insulin resistance.
Publisher: Oxford University Press (OUP)
Date: 09-12-2008
Abstract: We examined if circulating levels of cardiac troponin-I (cTnI) predict subsequent heart failure in the community. Using Cox proportional hazards models, we examined the risk of a first hospitalization for heart failure during a maximum of 11.4 years in a community-based s le of 1089 70-year-old men without heart failure, valvular disease, or electrocardiographic left ventricular hypertrophy. Adjusting for smoking, systolic blood pressure, antihypertensive medication use, diabetes, body mass index, serum cholesterol, and myocardial infarction before baseline or during follow-up, 0.01 microg/L higher cTnI conferred a hazard ratio (HR) of 1.26 (95% confidence interval 1.15-1.38) for subsequent heart failure. Persons with cTnI > or =0.03 microg/L had an HR of 5.25 (2.00-13.77) compared with persons with cTnI <0.01 microg/L. Adjusting additionally for serum NTproBNP attenuated the estimates somewhat [HR 1.22 (1.11-1.34) per 0.01 microg/L of cTnI]. Excluding persons with myocardial infarction before baseline and censoring at time of myocardial infarction during follow-up, 0.01 microg/L higher cTnI was associated with a multivariable-adjusted HR of 1.31 (1.16-1.47) for heart failure. In a community-based s le, a direct measure of cardiomyocyte damage, cTnI, indicated a substantially increased risk of heart failure, accounting for other risk factors. Studies investigating the clinical utility of measuring cTnI in asymptomatic in iduals are warranted.
Publisher: Elsevier BV
Date: 10-2010
Abstract: Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death. We aimed to examine how vitamin D status relates to overall and cause-specific mortality. The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs). During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% ( 98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89 95% CI: 1.21, 2.96) but not high (HR: 1.33 95% CI: 0.69, 2.54) concentrations indicated higher risk. Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality.
Publisher: Elsevier BV
Date: 02-2019
Publisher: The Endocrine Society
Date: 03-2009
DOI: 10.1210/JC.2008-1772
Abstract: Context: Skeletal muscle morphology and function are strongly associated with insulin sensitivity. Objective: The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity. Design, Settings, and Participants: This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study. Main Outcome Measures: Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin cl technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies. Results: In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (β, 0.30 per 50 capillaries per square millimeter increase P = 0.041) and higher proportion of type I muscle fibers (β, 0.27 per 10% increase P = 0.036) but declined with a higher proportion of type IIb fibers (β, −0.39 per 10% increase P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (β difference, 0.041 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (β difference, −0.053 95% confidence interval −0.107, −0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models. Conclusions: Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in in iduals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-11-2022
DOI: 10.1161/CIRCULATIONAHA.122.060700
Abstract: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Observational analyses were conducted using in idual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values or mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR mL·min –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
Publisher: American Medical Association (AMA)
Date: 28-06-2006
Abstract: High blood pressure is the most important risk factor for congestive heart failure (CHF) at a population level, but the relationship of an altered diurnal blood pressure pattern to risk of subsequent CHF is unknown. To explore 24-hour ambulatory blood pressure characteristics as predictors of CHF incidence and to investigate whether altered diurnal blood pressure patterns confer any additional risk information beyond that provided by conventional office blood pressure measurements. Prospective, community-based, observational cohort in Uppsala, Sweden, including 951 elderly men free of CHF, valvular disease, and left ventricular hypertrophy at baseline between 1990 and 1995, followed up until the end of 2002. Twenty-four-hour ambulatory blood pressure monitoring was performed at baseline, and the blood pressure variables were analyzed as predictors of subsequent CHF. First hospitalization for CHF. Seventy men developed heart failure during follow-up, with an incidence rate of 8.6 per 1000 person-years at risk. In multivariable Cox proportional hazards models adjusted for antihypertensive treatment and established risk factors for CHF (myocardial infarction, diabetes, smoking, body mass index, and serum cholesterol level), a 1-SD (9-mm Hg) increase in nighttime ambulatory diastolic blood pressure (hazard ratio [HR], 1.26 95% confidence interval [CI], 1.02-1.55) and the presence of "nondipping" blood pressure (night-day ambulatory blood pressure ratio > or =1 HR, 2.29 95% CI, 1.16-4.52) were associated with an increased risk of CHF. After adjusting for office-measured systolic and diastolic blood pressures, nondipping blood pressure remained a significant predictor of CHF (HR, 2.21 95% CI, 1.12-4.36 vs normal night-day pattern). Nighttime ambulatory diastolic blood pressure and nondipping blood pressure were also significant predictors of CHF after exclusion of all participants who had an acute myocardial infarction before baseline or during follow-up. Nighttime blood pressure appears to convey additional risk information about CHF beyond office-measured blood pressure and other established risk factors for CHF. The clinical value of this association remains to be established in future studies.
Publisher: BMJ
Date: 15-05-2006
Publisher: Elsevier BV
Date: 09-2016
Publisher: Wiley
Date: 11-2010
Abstract: In experimental studies parathyroid hormone (PTH) has been associated with underlying causes of heart failure (HF) such as atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis. In iduals with increased levels of PTH, such as primary or secondary hyperparathyroidism patients, have increased risk of ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse prognosis in patients with overt HF. However, the association between PTH and the development HF in the community has not been reported. In a prospective, community-based study of 864 elderly men without HF or valvular disease at baseline (mean age 71 years, the ULSAM study) the association between plasma (P)-PTH and HF hospitalization was investigated adjusted for established HF risk factors (myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S-phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical activity, glomerular filtration rate, and blood draw season). During follow-up (median 8 years), 75 in iduals were hospitalized due to HF. In multivariable Cox-regression analyses, higher P-PTH was associated with increased HF hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12-1.77, P = 0.003). Parathyroid hormone also predicted hospitalization in participants without apparent ischaemic HF and in participants with normal P-PTH. In a large community-based s le of elderly men, PTH predicted HF hospitalizations, also after accounting for established risk factors and mineral metabolism variables. Our data suggest a role for PTH in the development of HF even in the absence of overt hyperparathyroidism.
Publisher: Wiley
Date: 02-10-2017
DOI: 10.1002/EJHF.980
Abstract: To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology. Proteomic profiling (proximity extension assay) was performed in two community-based prospective cohorts of elderly in iduals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0-70.3) years, 80 events] and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9-78.1) years, 90 events]. Twenty-nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF-15), T-cell immunoglobulin and mucin domain 1 (TIM-1), tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), spondin-1 (SPON1), matrix metalloproteinase-12 (MMP-12), follistatin (FS), urokinase-type plasminogen activator surface receptor (U-PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF-15, U-PAR, MMP-12, TRAIL-R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM-1 was positively associated with worsened diastolic function (P < 0.02 for all). Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly in iduals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.
Publisher: Springer Science and Business Media LLC
Date: 12-07-2017
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1016/J.JACC.2005.07.059
Abstract: Our objectives were to explore novel metabolic risk factors for development of heart failure (HF). In the past decade, considerable knowledge has been gained from limited s les regarding novel risk factors for HF, but the importance of these in the general population is largely unexplored. In a community-based prospective study of 2,321 middle-aged men free from HF and valvular disease at baseline, variables reflecting glucose and lipid metabolism and variables involved in oxidative processes were compared with established risk factors for HF (prior myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, obesity, and serum cholesterol) using Cox proportional hazards analyses. During a median follow-up time of 29 years, 259 subjects developed HF. In a multivariable Cox proportional hazards backward stepwise model, a 1-SD increase of fasting proinsulin (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.15 to 1.66) and apolipoprotein B/A-I-ratio (HR 1.27, 95% CI 1.09 to 1.48) increased the risk, whereas a 1-SD increase in serum beta-carotene (HR 0.79, 95% CI 0.66 to 0.94) decreased the risk of HF. These variables also remained significant when adjusting for acute myocardial infarction during follow-up. Novel variables reflecting insulin resistance and dyslipidemia, together with a low beta-carotene level, were found to predict HF independently of established risk factors. If confirmed, our observations could have large clinical implications, as they may offer new approaches in the prevention of HF.
Publisher: Informa UK Limited
Date: 12-06-2018
DOI: 10.1080/14017431.2018.1483080
Abstract: Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community. We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966 mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively). Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001) ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts. Conclusion Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.
Publisher: Massachusetts Medical Society
Date: 15-05-2008
Publisher: BMJ
Date: 07-2008
Abstract: Insulin resistance independently predicts heart failure and coronary disease, and has been related to thick left ventricular walls, mainly in studies of hypertensive s les not fully accounting for the influence of blood pressure. This study investigated whether the metabolic syndrome and insulin resistance are related to left ventricular geometry independently of blood pressure. Cross-sectional study. A community-based s le of 820 70-year-old men and women (the Prospective Investigation of the Vasculature in Uppsala Seniors, PIVUS) free from valvular disease, heart failure and myocardial infarction. Relations of the National Cholesterol Education Program-defined metabolic syndrome and homeostasis model assessment of insulin resistance (HOMA-IR) to echocardiographic left ventricular geometry. Models were adjusted for sex, height, intra-arterial systolic and diastolic blood pressures, and antihypertensive medication. Left ventricular mass index was increased in persons with the metabolic syndrome in the total s le (49.7 (SD 13.1) vs 39.7 (SD 11.5) g/m(2.7), p<0.001) and in subgroups of normotensive and hypertensive persons, mainly accounted for by an increased relative wall thickness. HOMA-IR was related to left ventricular mass index in the total s le (r = 0.31 p<0.001) and in hypertensive persons, but with borderline significance in normotensive persons. HOMA-IR was related to relative wall thickness in the total s le (r = 0.27 p<0.001), in normotensive and hypertensive persons. Left ventricular mass and relative wall thickness were increased in persons with the metabolic syndrome and were related to HOMA-IR in a large population-based s le of men and women of the same age, accounting for covariates including intra-arterial blood pressure levels.
Publisher: Public Library of Science (PLoS)
Date: 21-10-2016
Publisher: Springer Science and Business Media LLC
Date: 03-01-2019
DOI: 10.1038/S41467-018-07867-7
Abstract: Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 in iduals of erse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.
Publisher: Oxford University Press (OUP)
Date: 18-02-2011
DOI: 10.1093/NDT/GFQ848
Abstract: Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in in iduals without CVD in the community is scarce. We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths). Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole s le and in men without CVD at baseline [subs le without CVD: UAER hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01 eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR 6 μg/min and eGFR < 45 mL/min/1.73 m(2) significantly improved IDI (0.047, P < 0.001). UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14177
Publisher: Elsevier BV
Date: 07-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-05-2001
DOI: 10.1161/01.CIR.103.19.2346
Abstract: Background —The increased risk associated with left ventricular hypertrophy (LVH) diagnosed echocardiographically (Echo-LVH) or electrocardiographically (ECG-LVH) is well known, but the clinically relevant question of how much additional prognostic information would be provided by echocardiographically assessing LVH if a subject’s ECG-LVH and hypertension status are known has not been addressed. Methods and Results —We investigated whether Echo-LVH and ECG-LVH predicted total and cardiovascular mortality and morbidity independently of each other and of other cardiovascular risk factors by using a population-based s le of 475 men investigated at age 70 with a median follow-up time of 5.2 years. Echocardiographic left ventricular mass index (LVMI) predicted total mortality (hazards ratio [HR] 1.44, 95% CI 1.09 to 1.92, for a 1-SD increase in LVMI) and cardiovascular mortality (HR 2.38, 95% CI 1.52 to 3.73) independently of ECG-LVH and other cardiovascular risk factors. ECG-LVH, defined as Cornell product μV · s, predicted total mortality (HR 2.89, 95% CI 1.41 to 5.96) independently of LVMI and other cardiovascular risk factors. Thus, Echo-LVH and ECG-LVH provided complementary prognostic information, especially in hypertensive subjects. Conclusions —Echo-LVH and ECG-LVH predict mortality independently of each other and of other cardiovascular risk factors, implying that Echo-LVH and ECG-LVH in part carry different prognostic information. Therefore, to fully assess the increased risk associated with these conditions, both ECG and echocardiography should be performed.
Publisher: Oxford University Press (OUP)
Date: 03-10-2013
Abstract: While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk. Population-based cohort study. We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a s le of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week). During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men. Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.
Publisher: Wiley
Date: 16-11-2017
DOI: 10.1111/JOIM.12703
Abstract: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health. We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418). In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay. Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10 The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.
Publisher: Elsevier BV
Date: 09-2018
Publisher: Springer Science and Business Media LLC
Date: 25-11-2027
Publisher: Elsevier BV
Date: 03-2014
Publisher: Elsevier BV
Date: 09-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-01-2018
Abstract: The knowledge of the impact of cardiovascular risk factors at different ages has mainly been based on different studies performed at different ages. This study aimed to investigate the change in impact of traditional cardiovascular risk factors over the aging process in subjects followed for 4 decades. In the ULSAM (Uppsala Longitudinal Study of Adult Men) study, 2322 men originally investigated in 1970 to 1974 have been followed regarding cardiovascular diseases until the end of 2013. This cohort has been investigated physically at ages 50, 60, 70, 77, and 82 years regarding body mass index, low‐density lipoprotein‐ and high‐density lipoprotein‐cholesterol, triglycerides, systolic blood pressure and diastolic blood pressure, fasting glucose, and smoking. These data were used to model the interactions between risk factors and age regarding incident myocardial infarction (n=540), ischemic stroke (n=343), or heart failure (n=397). Significant interactions were observed between age and the set of traditional risk factors regarding all 3 outcomes ( P .05 for all). Generally, a decline in the rate ratios was seen with aging for most risk factors, being most pronounced for body mass index regarding myocardial infarction and for systolic blood pressure regarding ischemic stroke and heart failure. However, low‐density lipoprotein‐cholesterol was significantly related to incident myocardial infarction, whereas both body mass index and fasting glucose were significantly related to incident heart failure also at a high age. Using a longitudinal design in middle‐aged men spanning 4 decades showed that the impact of traditional cardiovascular risk factors generally declined with aging. However, some of the risk factors remained significantly associated with incident cardiovascular disease also at old age.
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.CARDFAIL.2006.05.010
Abstract: Studies of socioeconomic factors as predictors of heart failure (HF) are few and have given opposing results. Further, it is unknown if these factors predict incident HF independently of myocardial infarction and other established risk factors for HF. In a community-based cohort of 2314 middle-age men free from HF, valvular disease, and previous myocardial infarction at baseline, socioeconomic factors were examined as predictors for HF using Cox proportional hazards analyses. In multivariable Cox proportional hazards models adjusted for established risk factors for HF (hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, serum cholesterol, and interim myocardial infarction), low occupational classification (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.03-2.35 for low vs. high occupational classification), low education level (HR 1.98, 95% CI 1.07-3.68 for elementary school vs. college exam) and being unmarried (HR 1.44, 95% CI 0.99-2.10 for being unmarried vs. being married) increased the risk of HF. High occupational classification and high education level decreased, and being unmarried increased, the risk of subsequent HF in middle-age men, via mechanisms largely independent of established risk factors for HF, including an interim myocardial infarction. Further studies are needed to understand the mechanisms behind these associations.
Publisher: Oxford University Press (OUP)
Date: 28-10-2016
Abstract: Background The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR). Methods We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men ( n = 662 mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors ( n = 757 mean age 75 years 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication. Results Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate ( p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes. Conclusions We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.CYTO.2007.05.014
Abstract: Common carotid artery intima-media thickness (CCA-IMT) is a valid index of atherosclerosis, which is viewed as an inflammatory disease. It is unknown if various modes of inflammation (cyclooxygenase [COX]-mediated, cytokine-mediated), oxidative stress and anti-oxidants are independently related to CCA-IMT. We investigated cross-sectional relations between CCA-IMT measured by B-mode ultrasound and COX-mediated inflammation (as measured by 15-keto-dihydro-prostaglandin F(2alpha) [PGF(2alpha)], cytokine-mediated inflammation (interleukin-6 [IL-6], high sensitivity C-reactive protein [hsCRP] and serum amyloid A protein [SAA]), oxidative stress (8-iso-PGF(2alpha), an F(2)-isoprostane a non-enzymatic, free radical-induced product of arachidonic acid), and tocopherols (anti-oxidants) in a small subset of a population-based s le of elderly men (n=234) stating no use of anti-inflammatory medications. In a backward-stepwise regression analysis of correlates of CCA-IMT (with PGF(2alpha), hsCRP, IL-6, SAA, F(2)-isoprostanes, tocopherols, diabetes, body mass index (BMI), beta-blocker, statin treatment, smoking, hypertension and cholesterol), PGF(2alpha), CRP, beta-blocker treatment, diabetes and BMI were independently associated with CCA-IMT. There were no associations between F(2)-isoprostanes or tocopherols and CCA-IMT in this study. This study suggests both COX- and cytokine-mediated inflammation to be independently associated with increased CCA-IMT, implying that there might be more than one mode of inflammation involved in atherogenesis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2015
DOI: 10.1161/STROKEAHA.115.010829
Abstract: Emerging technologies have made it possible to simultaneously evaluate a large number of circulating proteins as potential new stroke risk markers. We explored associations between 85 cardiovascular proteins, assessed by a proteomics chip, and incident ischemic stroke in 2 independent cohorts of elderly (Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS]: n=977 50% women, mean age=70.1 years, 71 fatal/nonfatal ischemic stroke events during 10.0 years and Uppsala Longitudinal Study in Adult Men [ULSAM]: n=720, mean age=77.5 years, 75 ischemic stroke events during 9.5 years). The proteomics chip uses 2 antibodies for each protein and a polymerase chain reaction step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations. In PIVUS, 16 proteins were related to incident ischemic stroke using a false discovery rate of 5%. Of these, N-terminal pro-B-type natriuretic peptide ( P =0.0032), adrenomedullin ( P =0.018), and eosinophil cationic protein ( P =0.0071) were replicated in ULSAM after adjustment for established stroke risk factors. In predefined secondary meta-analyses of in idual data, interleukin-27 subunit α, growth/differentiation factor 15, urokinase plasminogen activator surface receptor, tumor necrosis factor receptor superfamily member 6, macrophage colony-stimulating factor 1, and matrix metalloproteinase-7 were also potential risk markers for ischemic stroke after adjustment for multiple comparisons ( P .0006). The addition of N-terminal pro-B-type natriuretic peptide, adrenomedullin, and eosinophil cationic protein to a model with established risk factors increased the C-statistic from 0.629 to 0.689 ( P =0.001). Our data suggest that large-scale proteomics analysis is a promising way of discovering novel biomarkers that could substantially improve the prediction of ischemic stroke.
Publisher: Springer Science and Business Media LLC
Date: 05-10-2014
DOI: 10.1038/NG.3097
Publisher: BMJ
Date: 08-09-2016
DOI: 10.1136/HEARTJNL-2016-309764
Abstract: Apart from several established clinical risk factors for atrial fibrillation (AF), a number of biomarkers have also been identified as potential risk factors for AF. None of these have so far been adopted in clinical practice. To use a novel custom-made proteomics chip to discover new prognostic biomarkers for AF risk. In two independent community-based cohorts (Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (978 participants without AF, mean age 70.1 years, 50% women, median follow-up 10.0 years) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n=725, mean age 77.5 years, median follow-up 7.9 years)), ninety-two plasma proteins were assessed at baseline by a proximity extension assay (PEA) chip. Of those, 85 proteins showed a call rate >70% in both cohorts. Thirteen proteins were related to incident AF in PIVUS (148 events) using a false discovery rate of 5%. Of those, five were replicated in ULSAM at nominal multivariable p value (123 events, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), fibroblast growth factor 23 (FGF-23), fatty acid-binding protein 4 (FABP4), growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6)). Of those, NT-pro-BNP and FGF-23 were also associated with AF after adjusting for established AF risk factors. In a prespecified secondary analysis pooling the two data sets, T-cell immunoglobulin and mucin domain 1 (TIM-1) and adrenomedullin (AM) were also significantly related to incident AF in addition to the aforementioned five proteins (Bonferroni-adjustment). The addition of NT-pro-BNP to a model with established risk factors increased the C-statistic from 0.605 to 0.676 (p<0.0001). Using a novel proteomics approach, we confirmed the previously reported association between NT-pro-BNP, FGF-23, GDF-15 and incident AF, and also discovered four proteins (FABP4, IL-6, TIM-1 and AM) that could be of importance in the development of AF.
Publisher: Springer Science and Business Media LLC
Date: 22-06-2014
DOI: 10.1038/NG.3014
Publisher: Springer Science and Business Media LLC
Date: 03-08-2017
Publisher: Springer Science and Business Media LLC
Date: 27-02-2017
DOI: 10.1038/SREP43538
Abstract: Cardiovascular complications determine morbidity/mortality in chronic kidney disease (CKD). We hypothesized that progressive CKD drives the release of cathepsin-S (Cat-S), a cysteine protease that promotes endothelial dysfunction and cardiovascular complications. Therefore, Cat-S, soluble tumor-necrosis-factor receptor (sTNFR) 1/2 and glomerular filtration rate (GFR) were measured in a CKD mouse model, a German CKD-cohort (MCKD, n = 421) and two Swedish community-based cohorts (ULSAM, n = 764 and PIVUS, n = 804). Association between Cat-S and sTNFR1/2/GFR was assessed using multivariable linear regression. In the mouse model, Cat-S and sTNFR1/2 concentrations were increased following the progressive decline of GFR, showing a strong correlation between Cat-S and GFR (r = −0.746, p 0.001) and Cat-S and sTNFR1/sTNFR2 (r = 0.837/0.916, p 0.001, respectively). In the human cohorts, an increase of one standard deviation of estimated GFR was associated with a decrease of 1.008 ng/ml (95%-confidence interval (95%-CI) −1.576–(−0.439), p 0.001) in Cat-S levels in MCKD in ULSAM and PIVUS, results were similar. In all three cohorts, Cat-S and sTNFR1/sTNFR2 levels were associated in multivariable linear regression (p 0.001). In conclusion, as GFR declines Cat-S and markers of inflammation-related endothelial dysfunction increase. The present data indicating that Cat-S activity increases with CKD progression suggest that Cat-S might be a therapeutic target to prevent cardiovascular complications in CKD.
Publisher: Oxford University Press (OUP)
Date: 26-10-2018
Abstract: To study association between country of birth and risk of first-onset atrial fibrillation (AF) in first- and second-generation immigrants to Sweden under 45 y of age. The study population included all in iduals (n = 3 248 457) under the age of 45 y in Sweden, including immigrants (n = 722 249). AF was defined as first registered diagnosis in the National Patient Register. Association between country of birth and risk of AF was assessed by Cox regression, calculating HRs and 95% CIs, using Swedish-born in iduals as referents. All models were stratified by sex, and in different models were adjusted for age, area of residence in Sweden, educational level, marital status, neighbourhood socioeconomic status and co-morbidity(ies). A higher fully adjusted HR of incident AF was found in the total s le of first-generation immigrants, 1.44 (95% CI 1.35 to 1.54), in males born in Denmark, Lebanon and Iraq, and in females born in Turkey and Iraq. Lower HRs were found in male and female immigrants from Latin America and Iran, and female immigrants from Finland. Among second-generation immigrants, the fully adjusted HR was significantly lower, 0.70 (95% CI 0.58 to 0.83). Clinicians may show a greater awareness of AF in some groups of younger immigrants to enable early diagnosis.
Publisher: S. Karger AG
Date: 2019
DOI: 10.1159/000497063
Abstract: b i Background: /i /b Our aim was to study the association between the country of birth and incident end-stage kidney disease (ESKD) in several immigrant groups in Sweden, using in iduals born in Sweden or with Swedish-born parents as referents. b i Methods: /i /b A cohort study of first- and second-generation immigrants residing in Sweden between January 1, 1998 and December 31, 2012 was performed. Outcomes were defined as having at least one registered diagnosis of ESKD in the National Patient Register. The incidence of ESKD in different immigrant groups was used in the Cox regression models to estimate hazard ratios (HRs) and 95% CIs. All models were stratified by sex and adjusted for age, geographical residence, educational level, marital status, and neighbourhood socioeconomic status. b i Results: /i /b Compared to their referents, higher incidence rates and HRs of ESKD (HR 95% CI) were observed in general among foreign-born men (1.10 1.04–1.16) and women (1.12 1.04–1.21) but not among second-generation immigrants (persons born in Sweden with foreign-born parents). A particularly high incidence was noted among men and women from East-European countries, as well as from non-European regions. A lower incidence of ESKD was noted among men from Finland. b i Conclusions: /i /b We observed substantial differences in incidence of ESKD between immigrant groups and the Swedish-born population, which may be clinically relevant when monitoring preventive measures in patient subgroups with a higher risk of deteriorating kidney disease, and suggest higher attention to hypertension and diabetes control in immigrants. Mechanisms attributable to the migration process or ethnic differences may lead to an increased risk of ESKD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
DOI: 10.1161/ATVBAHA.113.301704
Abstract: Experimental data imply that endostatin, a proteolytically cleaved fragment of collagen XVIII, could be involved in the development of cardiovascular disease and cancer. Prospective data concerning the relation between circulating endostatin and mortality are lacking. Accordingly, we aimed to study associations between circulating endostatin and mortality risk. Serum endostatin was analyzed in 2 community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS women 50%, n=931 mean age, 70 years median follow-up, 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM n=748 mean age, 77 years median follow-up, 9.7 years). During follow-up, 90 participants died in PIVUS (1.28/100 person-years at risk), and 417 participants died in ULSAM (6.7/100 person-years at risk). In multivariable Cox regression models adjusted for age and established cardiovascular risk factors, 1 SD higher ln(serum endostatin level) was associated with a hazard ratio of mortality of 1.39 and 95% confidence interval, 1.26 to 1.53, on average in both cohorts. In the ULSAM cohort, serum endostatin was also associated with cardiovascular mortality (177 deaths hazard ratio per SD of ln[endostatin] 1.45, 95% confidence interval [1.25–1.71]) and cancer mortality (115 deaths hazard ratio per SD of ln[endostatin] 1.35, 95% confidence interval [1.10–1.66]). High serum endostatin was associated with increased mortality risk in 2 independent community-based cohorts of the elderly. Our observational data support the importance of extracellular matrix remodeling in the underlying pathophysiology of cardiovascular disease and cancer.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-08-2023
DOI: 10.1161/CIRCULATIONAHA.123.063914
Abstract: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography–based measures of coronary atherosclerosis and to explore relevant clinical correlates. We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal s les, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva. The mean age of the study s le was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with % occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis ( P ×10 –5 ). Associations were largely similar across coronary computed tomography angiography–based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score. This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.ATHEROSCLEROSIS.2013.01.009
Abstract: Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known. This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes. U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFRCysC) but not urinary Albumin (u-Alb). A combination of low eGFRCysC (≤60 mL/min), high u-Alb (≥3 mg/mmol Cr) and high u-NGAL (≥1.19 μg/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs.1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFRCysC or u-Alb. This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-04-2017
Abstract: The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.
Publisher: Elsevier BV
Date: 12-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-01-2010
DOI: 10.1161/CIRCULATIONAHA.109.887521
Abstract: Background— The purpose of this study was to investigate associations between combinations of body mass index (BMI) categories and metabolic syndrome (MetS) and the risk of cardiovascular disease and death in middle-aged men. Methods and Results— At age 50 years, cardiovascular risk factors were assessed in 1758 participants without diabetes in the community-based Uppsala Longitudinal Study of Adult Men (ULSAM). According to BMI-MetS status, they were categorized as normal weight (BMI kg/m 2 ) without MetS (National Cholesterol Education Program criteria n=891), normal weight with MetS (n=64), overweight (BMI 25 to 30 kg/m 2 ) without MetS (n=582), overweight with MetS (n=125), obese (BMI kg/m 2 ) without MetS (n=30), or obese with MetS (n=66). During follow-up (median 30 years), 788 participants died, and 681 developed cardiovascular disease (composite of cardiovascular death or hospitalization for myocardial infarction, stroke, or heart failure). In Cox proportional-hazards models that adjusted for age, smoking, and low-density lipoprotein cholesterol, an increased risk for cardiovascular disease was observed in normal-weight participants with MetS (hazard ratio 1.63, 95% confidence interval 1.11 to 2.37), overweight participants without MetS (hazard ratio 1.52, 95% confidence interval 1.28 to 1.80), overweight participants with MetS (hazard ratio 1.74, 95% confidence interval 1.32 to 2.30), obese participants without MetS (hazard ratio 1.95, 95% confidence interval 1.14 to 3.34), and obese participants with MetS (hazard ratio 2.55, 95% confidence interval 1.81 to 3.58) compared with normal-weight in iduals without MetS. These BMI-MetS categories significantly predicted total mortality rate in a similar pattern. Conclusions— Middle-aged men with MetS had increased risk for cardiovascular events and total death regardless of BMI status during more than 30 years of follow-up. In contrast to previous reports, overweight and obese in iduals without MetS also had an increased risk. The present data refute the notion that overweight and obesity without MetS are benign conditions.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-04-2022
DOI: 10.1161/CIRCULATIONAHA.121.056663
Abstract: Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets. We investigated the observational and causal associations of 90 cardiovascular proteins, which were measured using affinity-based proteomic assays. First, we estimated the associations of 90 cardiovascular proteins with incident heart failure by means of a fixed-effect meta-analysis of 4 population-based studies, composed of a total of 3019 participants with 732 HF events. The causal effects of HF-associated proteins were then investigated by Mendelian randomization, using cis -protein quantitative loci genetic instruments identified from genomewide association studies in more than 30 000 in iduals. To improve the precision of causal estimates, we implemented an Mendelian randomization model that accounted for linkage disequilibrium between instruments and tested the robustness of causal estimates through a multiverse sensitivity analysis that included up to 120 combinations of instrument selection parameters and Mendelian randomization models per protein. The druggability of candidate proteins was surveyed, and mechanism of action and potential on-target side effects were explored with cross-trait Mendelian randomization analysis. Forty-four of ninety proteins were positively associated with risk of incident HF ( P .0×10 –4 ). Among these, 8 proteins had evidence of a causal association with HF that was robust to multiverse sensitivity analysis: higher CSF-1 (macrophage colony-stimulating factor 1), Gal-3 (galectin-3) and KIM-1 (kidney injury molecule 1) were positively associated with risk of HF, whereas higher ADM (adrenomedullin), CHI3L1 (chitinase-3-like protein 1), CTSL1 (cathepsin L1), FGF-23 (fibroblast growth factor 23), and MMP-12 (matrix metalloproteinase-12) were protective. Therapeutics targeting ADM and Gal-3 are currently under evaluation in clinical trials, and all the remaining proteins were considered druggable, except KIM-1. We identified 44 circulating proteins that were associated with incident HF, of which 8 showed evidence of a causal relationship and 7 were druggable, including adrenomedullin, which represents a particularly promising drug target. Our approach demonstrates a tractable roadmap for the triangulation of population genomic and proteomic data for the prioritization of therapeutic targets for complex human diseases.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-09-2008
Publisher: Public Library of Science (PLoS)
Date: 11-12-2014
Publisher: Springer Science and Business Media LLC
Date: 24-08-2019
Publisher: Elsevier BV
Date: 09-2017
Publisher: Oxford University Press (OUP)
Date: 10-06-2014
DOI: 10.1093/NDT/GFU199
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-09-2010
Publisher: Elsevier BV
Date: 06-2010
Publisher: American Diabetes Association
Date: 16-11-2021
DOI: 10.2337/DB20-1120
Abstract: Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity and circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data were generated with nontargeted ultraperformance liquid chromatography coupled to time-of-flight mass spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N = 1,135), PIVUS (N = 970), and TwinGene (N = 2,059). We assessed associations of general adiposity measured as BMI and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We used MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N = 7,373), the CHARGE Consortium (N = 8,631), the Framingham Heart Study (N = 2,076), and the DIRECT Consortium (N = 3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (P value & .05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid, and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The results of the replication effort provided support for a causal association of adiposity with reduced levels of arachidonic acid (P value = 0.03). Adiposity is associated with variation of large parts of the circulating metabolome however, further investigation of causality is required in well-powered cohorts.
Publisher: Public Library of Science (PLoS)
Date: 14-09-2017
Publisher: Oxford University Press (OUP)
Date: 09-08-2011
Abstract: Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure. Two independent Swedish prospective cohorts the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based s le of 1076 elderly men, and the Construction Workers Cohort (CWC), a s le of 118,425 never-smoking male construction workers. Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure. In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use. Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.
Publisher: Wiley
Date: 04-2013
Abstract: There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk. This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81 95% confidence interval 1.01-3.29 P < 0.05). Participants with a combination of low GFR ( 128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001). Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.
Publisher: Springer Science and Business Media LLC
Date: 10-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2013
DOI: 10.1161/HYPERTENSIONAHA.113.02250
Abstract: Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS women 51% n=812 mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM n=785 mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS years, ULSAM years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23–0.61 P .001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher 95% confidence interval, 0.35–0.80 P .001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio ( P .03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in in iduals with hypertension.
Publisher: American Diabetes Association
Date: 11-12-2012
DOI: 10.2337/DC12-0494
Abstract: To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based s le of elderly men without diabetes. Serum cathepsin S, insulin sensitivity (euglycemic-hyperinsulinemic cl ), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up. After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase −0.09 [95% CI −0.14 to −0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08–2.01], P = 0.01). Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.
Publisher: Public Library of Science (PLoS)
Date: 30-07-2013
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.JACC.2005.02.066
Abstract: Our objective was to explore inflammation, measured as erythrocyte sedimentation rate (ESR), as a predictor for the development of heart failure (HF). In recent years, evidence of the importance of inflammation in the pathophysiology of HF has emerged, and various inflammatory markers have been found to predict future HF. Erythrocyte sedimentation rate is an inexpensive and easily accessible marker of systemic inflammation, but to this date it is unknown whether ESR predicts subsequent HF. In a community-based prospective study of 2,314 middle-aged men free from HF, myocardial infarction, and valvular disease at baseline, ESR was analyzed in multivariable models together with established risk factors for HF (hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, obesity, and serum cholesterol) and hematocrit. A total of 282 men developed HF during a median follow-up time of 30 years. In Cox proportional hazards analyses, ESR was an independent predictor of HF (hazard ratio 1.46 for highest quartile vs. the lowest, 95% confidence interval 1.04 to 2.06). This observation remained significant when also adjusting for interim myocardial infarction during follow-up. Erythrocyte sedimentation rate was a significant predictor of HF, independent of established risk factors for HF, and interim myocardial infarction after three decades of follow-up in a population-based s le of middle-aged men. Our findings indicate that inflammation occurs early in the process leading to HF and that ESR could be used to evaluate this process.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2019
Publisher: Informa UK Limited
Date: 02-11-2018
Publisher: American Medical Association (AMA)
Date: 23-11-2005
Publisher: Mary Ann Liebert Inc
Date: 10-2018
Publisher: Elsevier BV
Date: 08-2015
Publisher: American Medical Association (AMA)
Date: 14-09-2011
Abstract: Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer. However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking. To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women. Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM n = 1009 mean age: 71 years baseline period: 1991-1995 median follow-up: 12.6 years end of follow-up: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS n = 987 50% women mean age: 70 years baseline period: 2001-2004 median follow-up: 7.9 years end of follow-up: 2010). Serum s les were used to measure cathepsin S. Total mortality. During follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P = .009 PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P = .04). In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37] P = .01) and cancer mortality (148 deaths HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10] P = .01). Among elderly in iduals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk. Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.
Publisher: Springer Science and Business Media LLC
Date: 27-09-2012
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.ATHEROSCLEROSIS.2009.02.029
Abstract: Our aim was to examine relations of serum retinol-binding protein 4 (RBP4) to cardiovascular risk factors, and prevalent metabolic syndrome (MetS) and cardiovascular disease (CVD) in a large community-based s le of elderly. We evaluated cross-sectional relations of serum RBP4 to cardiovascular risk factors including anthropometrical measures, blood pressure, lipid measures, fasting glucose and insulin, body fat distribution including truncal fat by dual-energy x-ray absorptiometry (DXA), homeostasis model assessment insulin resistance (HOMA-IR) and prevalent MetS in one thousand eight 70-year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in five hundred seven 82-year old men from Uppsala Longitudinal Study of Adult Men (ULSAM). In ULSAM, we also examined associations with prevalent CVD. RBP4 concentrations were positively correlated with serum triglycerides (r=0.30 P<0.0001 in both s les), whereas correlations with body mass index (BMI), waist circumference, sagittal abdominal diameter, total and truncal fat mass, total cholesterol, fasting glucose and HOMA-IR were weak. In multivariable-adjusted models, RBP-4 was associated with MetS (odds ratio (OR), 1.16 and 1.33 95% confidence interval (CI), 0.99-1.37 and 1.05-1.67 per 1-standard deviation (SD) increase in PIVUS and ULSAM, respectively), and prior cerebrovascular disease (OR, 1.37 95% CI, 1.00-1.88 per 1-SD increase in ULSAM), but not with prior myocardial infarction. In elderly, RBP4 concentrations were associated with MetS and its components in both sexes, and prior cerebrovascular disease in men. These findings are consistent with the hypothesis that circulating RBP4 could be a marker of metabolic complications and possibly also atherosclerosis and overt CVD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
DOI: 10.2215/CJN.11901113
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-06-2021
Abstract: The aim is to study common etiological pathways for 3 major cardiovascular diseases (CVD), as reflected in multiple proteins. Eighty‐four proteins were measured using the proximity extension technique in 870 participants in the PIVUS (Prospective Investigation of Uppsala Seniors Study) cohort on 3 occasions (age 70, 75, and 80 years). The s le was followed for incident myocardial infarction, ischemic stroke or heart failure. The same proteins were measured in an independent validation s le, the ULSAM (Uppsala Longitudinal Study of Adult Men) cohort in 595 participants at age 77. During a follow‐up of up to 15 years in PIVUS and 9 years in ULSAM, 222 and 167 in iduals experienced a CVD. Examining associations with the 3 outcomes separately in a meta‐analysis of the 2 cohorts, 6 proteins were related to incident myocardial infarction, 25 to heart failure, and 8 proteins to ischemic stroke following adjustment for traditional risk factors. Growth differentiation factor 15 and tumor necrosis factor‐related apoptosis‐inducing ligand receptor 2 were related to all 3 CVDs. Including estimated glomerular filtration rate in the models attenuated some of these relationships. Fifteen proteins were related to a composite of all 3 CVDs using a discovery/validation approach when adjusting for traditional risk factors. A selection of 7 proteins by lasso in PIVUS improved discrimination of incident CVD by 7.3% compared with traditional risk factors in ULSAM. We discovered and validated associations of multiple proteins with incident CVD. Only a few proteins were associated with all 3 diseases: myocardial infarction, ischemic stroke, and heart failure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2013
DOI: 10.2215/CJN.09570912
Abstract: Circulating fibroblast growth factor-23 is associated with adverse cardiovascular outcomes in CKD and non-CKD in iduals, but the underlying mechanism remains unclear. This study tested whether this association is independent of mineral metabolism and indices of subclinical cardiovascular pathology. The prospective association between fibroblast growth factor-23 and major cardiovascular events (a composite of hospital-treated myocardial infarction, hospital-treated stroke, or all-cause mortality) was investigated in the community-based Prospective Investigation of the Vasculature in Uppsala Seniors ( n =973 mean age=70 years, 50% women) using multivariate logistic regression. Subjects were recruited between January of 2001 and June of 2004. During follow-up (median=5.1 years), 112 participants suffered a major cardiovascular event. In logistic regression models adjusted for age, sex, and estimated GFR, higher fibroblast growth factor-23 was associated with increased risk for major cardiovascular events (odds ratio for tertiles 2 and 3 versus tertile 1=1.92, 95% confidence interval=1.19–3.09, P .01). After additional adjustments in the model, adding established cardiovascular risk factors, confounders of mineral metabolism (calcium, phosphate, parathyroid hormone, and 25(OH)-vitamin D), and indices of subclinical pathology (flow-mediated vasodilation, endothelial-dependent and -independent vasodilation, arterial stiffness, and atherosclerosis and left ventricular mass) attenuated this relationship, but it remained significant (odds ratio for tertiles 2 and 3 versus tertile 1=1.69, 95% confidence interval=1.01–2.82, P .05). Fibroblast growth factor-23 is an independent predictor of cardiovascular events in the community, even after accounting for mineral metabolism abnormalities and subclinical cardiovascular damage. Circulating fibroblast growth factor-23 may reflect novel and important aspects of cardiovascular risk yet to be unraveled.
Publisher: American Diabetes Association
Date: 08-2008
DOI: 10.2337/DC08-0369
Abstract: OBJECTIVE—To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic in iduals with normal GFR. RESEARCH DESIGN AND METHODS—We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic cl ) and cystatin C–based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. RESULTS—Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69–1.68] P & 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443 P & 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR & ml/min per 1.73 m2) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40–0.84] P & 0.004). CONCLUSIONS—Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2018
DOI: 10.1161/ATVBAHA.118.311440
Abstract: Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in in iduals from the general population. We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029 52% women median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors n=790 51% women all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men n=551 all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate .05 were further tested in PIVUS and ULSAM, where a P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima–Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels. Our comprehensive analysis of plasma proteins and lipid fractions of 3370 in iduals from the general population provides new information about lipid metabolism.
Publisher: Cold Spring Harbor Laboratory
Date: 14-06-2022
DOI: 10.1101/2022.06.10.22276241
Abstract: Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. In animal models, OSA has been shown to alter the gut microbiota however, little is known about such effects in humans. Here, we used respiratory polygraphy data from 3,570 in iduals aged 50–64 from the Swedish CardioPulmonary bioImage Study (SCAPIS) and deep shotgun metagenomics to identify OSA-associated gut microbiota features. We found that OSA-related hypoxia parameters were associated with 128 bacterial species, including positive associations with Blautia obeum and Collinsela aerofacines . The latter was also associated with increased systolic blood pressure. Further, the cumulative time in hypoxia was associated with nine gut microbiota metabolic pathways, including propionate production from lactate, a biomarker of hypoxia. In conclusion, in this first large-scale study on gut microbiota alterations in OSA, we found that OSA-related hypoxia is associated with specific microbiota features. Our findings can direct future research on microbiota-mediated health effects of OSA.
Publisher: Elsevier BV
Date: 2017
Publisher: Oxford University Press (OUP)
Date: 06-03-2007
Abstract: To investigate associations of urinary albumin excretion rate (UAER) and heart failure (HF) incidence in a community-based s le. In a prospective study of 70-year-old men free from HF at baseline (n = 1106), UAER (from timed overnight s les) was analysed with established risk factors for HF [acute MI before baseline, acute MI during follow-up (modelled as a time-dependent covariate), hypertension, diabetes, left ventricular hypertrophy, smoking, body mass index, and glomerular filtration rate] and more recently described risk factors [high-sensitive C-reactive protein and insulin sensitivity (cl glucose disposal rate)] as predictors of HF incidence. Ninety-eight participants developed HF during a median follow-up of 9.0 years. In Cox proportional hazards models adjusted for established and novel risk factors for HF, a 1 SD increase in log UAER increased the risk of HF in in iduals without anti-hypertensive treatment (hazard ratio 1.49 95% CI 1.13-1.98 P = 0.005). Furthermore, UAER remained an independent predictor of HF, also in participants without diabetes at baseline or myocardial infarction at baseline or during follow-up. There were no significant associations between UAER and HF incidence in in iduals with anti-hypertensive treatment. Our observations support the notion that low-grade albuminuria is a marker for subclinical cardiovascular damage that predisposes to future HF in the community.
Publisher: Springer Science and Business Media LLC
Date: 13-01-2017
Publisher: Wiley
Date: 2019
Abstract: Vitamin D deficiency has been associated with risk of overt cardiovascular disease (CVD), but associations with subclinical disease are not well characterized. Hence, we examined associations of circulating vitamin D concentrations and left ventricular (LV) geometry and function by echocardiography at baseline and after 5 years in a community-based study. In the PIVUS study, we measured serum 25-dihydroxyvitamin-D (25-OH D) at age 70 and performed echocardiography including LV mass, wall thickness, end-diastolic diameter, end-systolic diameter (LVESD), left atrial diameter, fractional shortening, ejection fraction, isovolumic relaxation time, and E/A ratio at both age 70 and 75. We included 870 participants (52% women) without prior myocardial infarctions, heart failure, or prevalent valvular disease. After adjusting for potential confounders, 25-OH D at baseline was found to be significantly associated with LVESD, fractional shortening, and ejection fraction (β, -0.42 mm, P = 0.03 β, 0.70%, P = 0.03 and β, 0.91% P = 0.01, respectively), per 1 SD increase in 25-OH D (SD = 20 nmol/L) at baseline. In longitudinal analyses, vitamin D levels at baseline were not significantly associated with change in LV geometry and function after 5 years. In our community-based study among the elderly, we found higher circulating vitamin D concentrations to be associated cross-sectionally with better LV systolic function and smaller LVESD at baseline. The association persisted after adjusting for several potential confounders, including cardiovascular risk factors and calcium, phosphate, and parathyroid hormone levels. Randomized clinical trials are needed to establish firmly or refute a causal relationship between vitamin D levels and changes in LV geometry and function.
Publisher: Oxford University Press (OUP)
Date: 20-01-2015
Abstract: We aimed to investigate associations between combinations of body mass index (BMI)-categories, levels of physical activity and long-term risk of cardiovascular disease. At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI 30 kg/m(2), n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 in iduals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent. Although physical activity was beneficial at all levels of BMI regarding the risk of future cardiovascular disease, there was still a substantial increased risk associated with being overweight or obese during 30 years of follow-up.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1038/KI.2013.553
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.ATHEROSCLEROSIS.2015.07.023
Abstract: We used a proteomics array to simultaneously measure multiple proteins that have been suggested to be associated with atherosclerosis and related them to plaque prevalence in carotid arteries in a human population-based study. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS n = 931, 50% women, all aged 70 years), the number of carotid arteries with plaques was recorded by ultrasound. Levels of 82 proteins were assessed in plasma by a proximity extension assay (Proseek Multiplex CVD, Olink Bioscience, Uppsala, Sweden) and related to carotid measures in a regression framework. Following adjustment for multiple testing with Bonferroni correction, seven of the proteins were significantly related to the number of carotid arteries affected by plaques in sex-adjusted models (osteoprotegrin, T-cell immunoglobulin and mucin domain (TIM)-1, growth/differentiation factor 15 (GDF-15), matrix metalloprotease-12 (MMP-12), renin, tumor necrosis factor ligand superfamily member 14 (TNFSF14) and growth hormone). Of these, renin (odds ratio [OR], 1.30 95% confidence interval [CI], 1.13-1.49 per standard deviation increase), growth hormone (OR, 1.24 95% CI, 1.08-1.43), osteoprotegerin (OR, 1.22 95% CI, 1.05-1.43) and TNFSF14 (OR, 1.17 95% CI, 1.01-1.35) were related to plaque prevalence independently of each other and traditional cardiovascular risk factors. A novel targeted proteomics approach using the proximity extension technique discovered several new associations of candidate proteins with carotid artery plaque prevalence in a large human s le.
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1016/S0021-9150(03)00283-1
Abstract: Most previous studies of associations between insulin sensitivity and common carotid artery (CCA) atherosclerosis have been conducted in small s les, have not used direct measurement of insulin sensitivity, and have yielded inconclusive results. We investigated associations of CCA intima-media thickness (IMT) and diameter (CCA-D) measured by B-mode ultrasound and insulin sensitivity measured by the euglycemic hyperinsulinemic cl test together with risk factors of the insulin resistance syndrome in a community-based s le of 493 elderly men. The cl glucose disposal rate was an independent predictor of CCA-IMT in multivariate models adjusting for blood pressure, smoking, serum cholesterol, and body mass index (1% decrease in CCA-IMT for a 1 unit increase in glucose disposal rate, P=0.009). Glucose disposal rate was significantly related to CCA-D in univariate (r=-0.11, P=0.02) but not in multivariate models. In conclusion, this study is the first to establish impaired insulin sensitivity, measured by the euglycemic hyperinsulinemic cl test, as an independent predictor of CCA-IMT in a population-based s le of elderly men.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2018
Publisher: Wiley
Date: 15-09-2009
DOI: 10.1111/J.1365-2796.2009.02122.X
Abstract: To define the optimal glomerular filtration rate (GFR) cut off for discriminating the risk of myocardial infarction or cardiovascular death. Prospective longitudinal observational study. A community-based cohort. A total of 2176 nondiabetic 50-year-old men without cardiovascular disease. The men were followed until age 70. GFR was estimated at baseline using the Cockcroft-Gault formula. The optimal GFR cut-off points for discriminating risk of a fatal or nonfatal myocardial infarction and cardiovascular death were defined as the GFR levels maximizing integrated discrimination improvement (IDI). Fatal or nonfatal myocardial infarction, cardiovascular death. During follow-up, 264 men experienced a fatal or nonfatal myocardial infarction, and 218 died of cardiovascular disease. The IDI-defined optimal GFR cut offs in this study were 98 mL min(-1) for discriminating myocardial infarction risk and 92 mL min(-1) for discriminating risk of cardiovascular death. In Cox proportional hazard models adjusting for established risk factors, the myocardial infarction risk was substantially higher in men with GFR below versus above 98 mL min(-1) [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.3-2.3, P < 0.001], and the risk of cardiovascular death was doubled in men with GFR below versus above 92 mL min(-1) (HR 2.1, 95% CI 1.5-3.0, P < 0.001). The GFR cut-off point for optimal discrimination of cardiovascular risk in the general population may be higher than previously suggested.
Publisher: Public Library of Science (PLoS)
Date: 19-01-2011
Publisher: The Endocrine Society
Date: 09-2010
DOI: 10.1210/JC.2010-0328
Abstract: Objective: Cathepsin S has been suggested provide a mechanistic link between obesity and atherosclerosis, possibly mediated via adipose tissue-derived inflammation. Previous data have shown an association between circulating cathepsin S and inflammatory markers in the obese, but to date, community-based reports are lacking. Accordingly, we aimed to investigate the association between serum levels of cathepsin S and markers of cytokine-mediated inflammation in a community-based s le, with prespecified subgroup analyses in nonobese participants. Methods: Serum cathepsin S, C-reactive protein (CRP), and IL-6 were measured in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men mean age 71 years, n = 991). CRP and IL-6 were also measured at a reexamination after 7 yr. Results: After adjustment for age, body mass index, fasting plasma glucose, diabetes treatment, systolic blood pressure, diastolic blood pressure, hypertension treatment, serum cholesterol, serum high-density lipoprotein cholesterol, prior cardiovascular disease, smoking, and leisure time physical activity, higher cathepsin S was associated with higher CRP (regression coefficient for 1 sd increase, 0.13 95% confidence interval 0.07–0.19 P & 0.001) and higher serum IL-6 (regression coefficient for 1 sd increase, 0.08 95% confidence interval 0.01–0.14 P = 0.02). These associations remained similar in normal-weight participants (body mass index & kg/m2, n = 375). In longitudinal analyses, higher cathepsin S at baseline was associated with higher serum CRP and IL-6 after 7 yr. Conclusions: These results provide additional evidence for the interplay between cathepsin S and inflammatory activity and suggest that this association is present also in normal-weight in iduals in the community.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-05-2021
DOI: 10.1161/ATVBAHA.120.315597
Abstract: To identify causal pathophysiological mechanisms for atherosclerosis and incident cardiovascular events using protein measurements. Carotid artery atherosclerosis was assessed by ultrasound, and 86 cardiovascular-related proteins were measured using the Olink CVD-I panel in 7 Swedish prospective studies (11 754 in iduals). The proteins were analyzed in relation to intima-media thickness in the common carotid artery (IMT-CCA), plaque occurrence, and incident cardiovascular events (composite end point of myocardial infarction or ischemic stroke) using a discovery/replication approach in different studies. After adjustments for traditional cardiovascular risk factors, 11 proteins remained significantly associated with IMT-CCA in the replication stage, whereas 9 proteins were replicated for plaque occurrence and 17 proteins for incident cardiovascular events. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and MMP (matrix metalloproteinase)-12 were associated with both IMT-CCA and incident events, but the overlap was considerably larger between plaque occurrence and incident events, including MMP-12, TIM-1 (T-cell immunoglobulin and mucin domain 1), GDF (growth/differentiation factor)-15, IL (interleukin)-6, U-PAR (urokinase plasminogen activator surface receptor), LOX-1 (lectin-like oxidized LDL [low-density lipoprotein] receptor 1), and TRAIL-R2 (TNF [tumor necrosis factor]-related apoptosis-inducing ligand receptor 2). Only MMP-12 was associated with IMT-CCA, plaque, and incident events with a positive and concordant direction of effect. However, a 2-s le Mendelian randomization analysis suggested that increased MMP-12 may be protective against ischemic stroke ( P =5.5×10 −7 ), which is in the opposite direction of the observational analyses. The present meta-analysis discovered several proteins related to carotid atherosclerosis that partly differed in their association with IMT-CCA, plaque, and incident atherosclerotic disease. Mendelian randomization analysis for the top finding, MMP-12, suggests that the increased levels of MMP-12 could be a consequence of atherosclerotic burden rather than the opposite chain of events.
Publisher: American Medical Association (AMA)
Date: 05-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-01-2021
Abstract: The molecular mechanisms involved in atrial fibrillation are not well known. We used plasma metabolomics to investigate if we could identify novel biomarkers and pathophysiological pathways of incident atrial fibrillation. We identified 200 endogenous metabolites in plasma/serum by nontargeted ultra‐performance liquid chromatography coupled to time‐of‐flight mass spectrometry in 3 independent population‐based s les (TwinGene, n=1935, mean age 68, 43% females PIVUS [Prospective Investigation of the Vasculature in Uppsala Seniors], n=897, mean age 70, 51% females and ULSAM [Uppsala Longitudinal Study of Adult Men], n=1118, mean age 71, all males), with available data on incident atrial fibrillation during 10 to 12 years of follow‐up. A meta‐analysis of ULSAM and PIVUS was used as a discovery s le and TwinGene was used for validation. In PIVUS, we also investigated associations between metabolites of interest and echocardiographic indices of myocardial geometry and function. Genome‐wide association studies were performed in all 3 cohorts for metabolites of interest. In the meta‐analysis of PIVUS and ULSAM with 430 incident cases, 4 metabolites were associated with incident atrial fibrillation at a false discovery rate %. Of those, only 9‐decenoylcarnitine was associated with incident atrial fibrillation and replicated in the TwinGene s le (288 cases) following adjustment for traditional risk factors (hazard ratio, 1.24 per unit 95% CI, 1.06–1.45, P =0.0061). A meta‐analysis of all 3 cohorts disclosed another 4 significant metabolites. In PIVUS, 9‐decenoylcarnitine was related to left atrium size and left ventricular mass. A Mendelian randomization analysis did not suggest a causal role of 9‐decenoylcarnitine in atrial fibrillation. A nontargeted metabolomics analysis disclosed 1 novel replicated biomarker for atrial fibrillation, 9‐Decenoylcarnitine, but this acetylcarnitine is likely not causally related to atrial fibrillation.
Publisher: Wiley
Date: 02-2007
DOI: 10.1016/J.EJHEART.2006.05.012
Abstract: Sleep disturbances are associated with manifest heart failure (HF). However, the relationship between sleep disturbances and incident HF has been less studied. To investigate self-reported sleep disturbances as predictors of HF in a longitudinal, community-based cohort of 2314 middle-aged men. Data on self-reported sleep disturbances, as well as established risk factors for HF were collected and analyzed using Cox proportional hazards analyses. In multivariable Cox proportional hazards models adjusted for established risk factors for HF, the presence at baseline of sleep disturbances (hazard ratio [HR], 1.52 95% confidence interval [CI], 1.16-1.99 p=0.002) was an independent risk factor for HF. There was evidence of effect modification between BMI and sleep disturbances. In multivariable-adjusted models, sleep disturbance (HR, 1.58 95% CI, 1.13-2.21 p=0.008) was an independent risk factor for HF in overweight participants (BMI>25), but not in normal-weight participants (BMI< or =25). All results remained similar in a sub-s le excluding all participants suffering from a myocardial infarction during follow-up. Self-reported sleep disturbances imply an increased risk of subsequent HF in overweight middle-aged men, via mechanisms largely independent of established risk factors for HF, including an interim myocardial infarction.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.ATHEROSCLEROSIS.2014.09.005
Abstract: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers. The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years). In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatings TNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified in iduals with increased risk of mortality among those with high as well as low levels of systemic inflammation. An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.
Publisher: Wiley
Date: 10-2005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-06-2009
DOI: 10.1161/CIRCULATIONAHA.108.808733
Abstract: Background— Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking. Methods and Results— The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38 95% confidence interval, 1.18 to 1.60 P .001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH ( .8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L normal glomerular filtration rate, mL · min −1 · 1.73 m −2 and without vitamin D deficiency, plasma 25-OH vitamin D .5 nmol/L). Interestingly, elevated plasma PTH ( .27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality. Conclusions— Plasma PTH levels predict cardiovascular mortality in the community, even in in iduals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.
Publisher: American Medical Association (AMA)
Date: 02-2008
DOI: 10.1001/ARCHNEUROL.2007.57
Abstract: Beta amyloid (Abeta) protein accumulates in the brains of in iduals with Alzheimer disease (AD) and is detectable in cerebrospinal fluid and plasma. To examine plasma levels of Abeta peptides Abeta(40) and Abeta(42) as predictors of incident AD and other types of dementia. Prospective, population-based cohort study. The Uppsala Longitudinal Study of Adult Men. Plasma Abeta(40) and Abeta(42) levels were analyzed as predictors of incident AD in 1045 men at age 70 years and 680 men at age 77 years using Cox proportional hazards analyses. Alzheimer disease and other types of dementia were diagnosed by standardized screening, clinical evaluation, and medical record review. Hazard ratios of AD (primary outcome) and vascular dementia or other dementia (secondary outcomes) according to baseline levels of plasma Abeta(40) and Abeta(42). From the age of 77 years at baseline, 46 in iduals developed AD at follow-up (median, 5.3 years). A low plasma Abeta(40) level at age 77 years was associated with higher incidence of AD. The multivariate-adjusted hazard ratio was 4.87 (95% confidence interval, 1.63-14.6) for the lowest Abeta(40) tertile compared with the highest tertile. On follow-up from age 70 years at baseline (median, 11.2 years), 82 in iduals developed AD. Plasma Abeta(40) and Abeta(42) levels measured at age 70 years were not significantly associated with incident AD. Low plasma Abeta(40) levels predicted incident AD in elderly men independently of potential confounders. Plasma Abeta(42) levels were not significantly associated with AD incidence. The clinical value of Abeta measurement in plasma remains to be established in future studies.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2010
DOI: 10.1161/ATVBAHA.109.196675
Abstract: Objective— Hyperphosphatemia is a cardiovascular risk factor in patients with chronic kidney disease. Relations of circulating calcium (Ca) and phosphorus (Pi) to long-term mortality risk in the community require further investigation. Methods and Results— Associations of serum Ca and Pi to mortality were evaluated in a community-based cohort of 2176 men (mean age, 50.1 years). During follow-up (median, 29.8 years), 1009 men died, and 466 of these deaths resulted from cardiovascular causes. In Cox proportional hazards models, serum Pi and [Ca×Pi] were independent predictors of total mortality (hazard ratio per SD, 1.06 95% CI, 1.01–1.12 P =0.03 1.07 95% CI, 1.01–1.12 P =0.01) and cardiovascular mortality (1.10 95% CI, 1.02–1.18 P =0.01 1.10 95% CI, 1.03–1.19 P =0.008). Serum Ca was associated with risk of total mortality (1.08 95% CI, 1.01–1.16 P =0.02) and noncardiovascular mortality (1.10 95% CI, 1.01–1.21 P =0.04). Results were consistent after multivariate adjustments in subs les of in iduals with estimated glomerular filtration rate mL/min and low-to-normal serum Ca and Pi. Conclusion— Circulating Ca and Pi levels are associated with risks of total, cardiovascular, and noncardiovascular mortality in the community, and their conjoint effects are additive. Additional studies are warranted to evaluate whether Ca and Pi are modifiable risk factors in the general population.
Publisher: Wiley
Date: 08-2005
Publisher: Elsevier BV
Date: 08-2005
DOI: 10.1016/J.NUMECD.2004.10.002
Abstract: Our knowledge on the development of left ventricular diastolic dysfunction is scarce. Thus, we aimed to investigate the relationship between left ventricular diastolic function and a wide variety of cardiovascular risk factors, including dietary factors using both cross-sectional and longitudinal data with 20 years follow-up. A population-based cohort of 505 50-year-old men was examined with determinations of blood pressure, insulin, glucose and fatty acid composition of serum cholesterol esters. A reinvestigation 20 years later also included hyperinsulinaemic euglycaemic cl , 7-day diet record and Doppler echocardiography with determination of left ventricular diastolic function (early (E) and late (A) peak mitral velocities and left atrial diameter). Blood pressure both at age 50 and 70 was negatively correlated to the E/A ratio (r=-0.15, p<0.001 and r=-0.23, p<0.001) at age 70. Insulin resistance at age 50 and 70 were negatively correlated to the A-wave and left atrial diameter at follow-up. A fatty acid profile indicating a diet high in saturated fats at age 50 was correlated to an increased left atrial diameter 20 years later and the dietary intake of fat was negatively correlated to the E/A ratio (r=-0.09, p<0.05) at age 70. All findings were independent of myocardial infarction and cardiovascular medication. Apart from blood pressure, insulin resistance and dietary fat intake predicted left ventricular diastolic function after 20 years. These findings suggest that both hemodynamic and metabolic factors may play a role for left ventricular diastolic function and disclose new possibilities for prevention of left ventricular diastolic dysfunction.
Publisher: Massachusetts Medical Society
Date: 06-07-2017
Publisher: Elsevier BV
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14132
No related grants have been discovered for Johan Ärnlöv.