ORCID Profile
0000-0002-2751-1770
Current Organisations
Oxford University Hospitals NHS Trust
,
University of Oxford
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Publisher: BMJ
Date: 04-02-2011
Abstract: Although statins significantly decrease the incidence of cardiovascular disease (CVD), residual CVD risk remains high. This may partly be due to uncorrected atherogenic dyslipidaemia. The driving force behind atherogenic dyslipidaemia is hypertriglyceridaemia, which results from hepatic oversecretion and/or hypocatabolism of triglyceride-rich lipoproteins, and is typical of type 2 diabetes and metabolic syndrome. Persistent atherogenic dyslipidaemia in patients treated with a statin according to low-density lipoprotein-cholesterol goals may be corrected with niacin, fibrates or n-3 fatty acids. Clinical trial evidence to inform best practice is limited, but new data support adding fenofibrate to a statin. A consistent feature of fibrate clinical trials is the specific benefit of these agents in dyslipidaemic patients and the improvement in diabetic retinopathy with fenofibrate. Ongoing clinical trials may provide good evidence for adding niacin to a statin. Low-dose n-3 fatty acids could be used routinely after a myocardial infarction, but the value of higher doses of n-3 fatty acids in reducing CVD risk remains to be demonstrated.
Publisher: Oxford University Press (OUP)
Date: 11-2011
DOI: 10.1136/PGMJ.2010.204990REP
Abstract: Although statins significantly decrease the incidence of cardiovascular disease (CVD), residual CVD risk remains high. This may partly be due to uncorrected atherogenic dyslipidaemia. The driving force behind atherogenic dyslipidaemia is hypertriglyceridaemia, which results from hepatic oversecretion and/or hypocatabolism of triglyceride-rich lipoproteins, and is typical of type 2 diabetes and metabolic syndrome. Persistent atherogenic dyslipidaemia in patients treated with a statin according to low-density lipoprotein-cholesterol goals may be corrected with niacin, fibrates or n–3 fatty acids. Clinical trial evidence to inform best practice is limited, but new data support adding fenofibrate to a statin. A consistent feature of fibrate clinical trials is the specific benefit of these agents in dyslipidaemic patients and the improvement in diabetic retinopathy with fenofibrate. Ongoing clinical trials may provide good evidence for adding niacin to a statin. Low-dose n–3 fatty acids could be used routinely after a myocardial infarction, but the value of higher doses of n-3 fatty acids in reducing CVD risk remains to be demonstrated.
Publisher: Springer Science and Business Media LLC
Date: 07-04-2013
DOI: 10.1038/NG.2606
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2003
DOI: 10.1161/01.STR.0000047123.14312.3E
Abstract: Background and Purpose— Although it is recognized that in heterozygous familial hypercholesterolemia, large extracranial carotid vessels are affected by atherosclerosis, the risk of fatal stroke after treatment with cholesterol-lowering therapy remains uncertain. The goal of this study was to determine the risk of fatal stroke in patients with treated familial hypercholesterolemia. Methods— A cohort of 1405 men and 1466 women with definite or possible heterozygous familial hypercholesterolemia was recruited from 21 outpatient lipid clinics in the United Kingdom. Patients were followed up prospectively from 1980 to 1998 for 22 992 person-years for a median duration of 7.9 years (interquartile range, 4.9 to 12.0 years). The mortality rate was calculated, and the standardized mortality ratio for men and women 20 to 79 years of age was derived from the ratio of the observed deaths to the number expected in the general population of England and Wales (standardized mortality ratio=100 for the standard population). Results— A total of 169 deaths occurred 9 (5.3%) were a result of stroke. The mortality rate from stroke was 0.39 per 1000 person-years (95% confidence interval, 0.18 to 0.74), and the standardized mortality ratio for fatal stroke was nonsignificantly lower than in the general population (79 95% CI, 36 to 150). Conclusions— The results suggest that patients with treated familial hypercholesterolemia are not at increased risk of fatal stroke. However, the possibility cannot be excluded that untreated in iduals are at increased risk, which would be consistent with the evidence that familial hypercholesterolemia is a panvascular disease.
Publisher: Springer Science and Business Media LLC
Date: 17-07-2023
DOI: 10.1038/S41366-023-01339-9
Abstract: No large-scale studies have compared associations between body composition and cardiovascular risk factors across multi-ethnic populations. Population-based surveys included 30,721 Malay, 10,865 Indian and 25,296 Chinese adults from The Malaysian Cohort, and 413,737 White adults from UK Biobank. Sex-specific linear regression models estimated associations of anthropometry and body composition (body mass index [BMI], waist circumference [WC], fat mass, appendicular lean mass) with systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), triglycerides and HbA1c. Compared to Malay and Indian participants, Chinese adults had lower BMI and fat mass while White participants were taller with more appendicular lean mass. For BMI and fat mass, positive associations with SBP and HbA1c were strongest among the Chinese and Malay and weaker in White participants. Associations with triglycerides were considerably weaker in those of Indian ethnicity (eg 0.09 [0.02] mmol/L per 5 kg/m 2 BMI in men, vs 0.38 [0.02] in Chinese). For appendicular lean mass, there were weak associations among men but stronger positive associations with SBP, triglycerides, and HbA1c, and inverse associations with LDL-C, among Malay and Indian women. Associations between WC and risk factors were generally strongest in Chinese and weakest in Indian ethnicities, although this pattern was reversed for HbA1c. There were distinct patterns of adiposity and body composition and cardiovascular risk factors across ethnic groups. We need to better understand the mechanisms relating body composition with cardiovascular risk to attenuate the increasing global burden of obesity-related disease.
Publisher: Springer Science and Business Media LLC
Date: 04-05-2008
DOI: 10.1038/NG.140
Publisher: Public Library of Science (PLoS)
Date: 06-06-2013
Publisher: Cold Spring Harbor Laboratory
Date: 04-07-2020
DOI: 10.1101/2020.07.03.20145599
Abstract: To estimate the prevalence, incidence and predictors of cardiovascular disease (CVD) risk factors in the Vellore Birth Cohort, South India. Prospective, cohort study Population-based cohort of rural and urban communities in and around Vellore city in South India Non-migrant in iduals (n= 962, male 519) were studied at two time points 13.6 years apart i) 1998-2002 (baseline, mean age 28.2 years) and ii) 2013-2014 (follow-up, mean age 41.7 years). Prevalence and incidence of CVD risk factors (obesity, central obesity, type 2 diabetes (T2D), hypertension, hypercholesterolemia and hypertriglyceridemia) studied at baseline (1998-2002) and follow-up (2013-2014), prevalence in comparison with the Non-Communicable Disease Risk Collaboration (global) data, incidence in comparison with another Indian cohort from New Delhi (NDBC), and baseline predictors of incident CVD risk factors. The prevalence at 28 and 42 years was 17% and 51% for overweight/obesity, 19% and 59% for central obesity, 3% and 16% for T2D, 2% and 19% for hypertension and 15% and 30% for hypertriglyceridemia. The prevalence of T2D at baseline and follow-up and hypertension at follow-up was comparable with or exceeded that in high income countries despite lower obesity rates. The incidence of most risk factors was lower in Vellore than in the NDBC. Waist circumference strongly predicted incident T2D, hypertension and hypertriglyceridemia. A high prevalence of CVD risk factors was evident at a young age among Indians compared with high and upper-middle income countries, with rural rates catching up with urban estimates. Adiposity predicted higher incident CVD risk, but the prevalence of hypertension and T2D was higher given a relatively low obesity prevalence in global terms. Our findings highlight a high burden of CVD risk factors at younger age with increasing trends observed among rural residents, similar to urban South Indians. Therefore, strategies to prevent CVD should be strengthened in both rural and urban settings to minimise health inequalities and should start young. None Cardiovascular disease (CVD) risk burden is increasing in Low- and middle-income countries and contributes significantly to the overall morbidity and mortality. Nation-wide data from India demonstrate heterogeneity in the prevalence of CVD risk factors within the country there is very little incidence data. The prevalence of CVD risk factors in India is comparable with or exceeds that in high income countries like USA and Europe, even though obesity levels are lower. Adiposity at baseline, particularly waist circumference, is a strong predictor of incident risk factors. The prevalence of CVD risk factors is higher in rural than urban communities, but the incidence is comparable or higher in the rural setting indicating that the rural population are catching up
Publisher: Public Library of Science (PLoS)
Date: 26-06-2009
Publisher: Public Library of Science (PLoS)
Date: 31-07-2014
Publisher: Wiley
Date: 10-2010
DOI: 10.1002/PDI.1511
Publisher: Cold Spring Harbor Laboratory
Date: 23-03-2018
DOI: 10.1101/286617
Abstract: Multiple sclerosis is a common, complex neurological disease, where almost 20% of risk heritability can be attributed to common genetic variants, including identified by genome-wide association studies (Patsopoulos et al., 2017). Multiple strands of evidence suggest that the majority of the remaining heritability is also due to the additive effects of in idual variants, rather than epistatic interactions between these variants, or mutations exclusive to in idual families. Here, we show in 68,379 cases and controls that as much as 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common variant signals, which highlight a key role for regulatory T cell homeostasis and regulation, IFNγ biology and NFκB signaling in MS pathogenesis. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS.
Publisher: Research Square Platform LLC
Date: 29-07-2022
DOI: 10.21203/RS.3.RS-1832470/V1
Abstract: Genome-wide association studies (GWAS) in predominately European-ancestry (EUR) populations have identified numerous genetic variants associated with adiposity-related traits. An emerging challenge is the limited transferability of genetic scores constructed based on GWAS results from one ancestry for trait prediction in other ancestries. We performed trans-ancestry meta-analysis (TAMA) for eight adiposity-related traits using genetic data from 96,124 East Asian (EAS) and 443,359 EUR in iduals. We identified genomic regions significantly associated with one or more traits. Despite EAS comprising only ~20% of the study population, genetic scores constructed from the trans-ancestry (TA) results accounted for between 30% and 79% more variation in the adiposity traits in EAS compared with scores derived from the EUR GWAS alone. Furthermore, TA scores also modestly improved variance explained in African/African American, Hispanic and South Asian populations. Our findings highlight the utility of TAMA for increasing variance explained by genetic scores across populations of different ancestries.
Publisher: BMJ
Date: 10-2020
DOI: 10.1136/BMJDRC-2020-001782
Abstract: India has high mortality rates from cardiovascular disease (CVD). Understanding the trends and identifying modifiable determinants of CVD risk factors will guide preventive strategies and policy making. CVD risk factors (obesity, central obesity, and type 2 diabetes (T2D), hypertension, hypercholesterolemia and hypertriglyceridemia) prevalence and incidence were estimated in 962 (male 519) non-migrant adults from Vellore, South India, studied in: (1) 1998–2002 (mean age 28.2 years) and (2) 2013–2014 (mean age 41.7 years). Prevalence was compared with the Non-Communicable Disease Risk Collaboration (global) data. Incidence was compared with another Indian cohort from New Delhi Birth Cohort (NDBC). Regression analysis was used to test baseline predictors of incident CVD risk factors. The prevalence at 28 and 42 years was 17% (95% CI 14% to 19%) and 51% (95% CI 48% to 55%) for overweight/obesity, 19% (95% CI 17% to 22%) and 59% (95% CI 56% to 62%) for central obesity, 3% (95% CI 2% to 4%) and 16% (95% CI 14% to 19%) for T2D, 2% (95% CI 1% to 3%) and 19% (95% CI 17% to 22%) for hypertension and 15% (95% CI 13% to 18%) and 30% (95% CI 27% to 33%) for hypertriglyceridemia. The prevalence of T2D at baseline and follow-up and hypertension at follow-up was comparable with or exceeded that in high-income countries despite lower obesity rates. The incidence of most risk factors was lower in Vellore than in the NDBC. Waist circumference strongly predicted incident T2D, hypertension and hypertriglyceridemia. A high prevalence of CVD risk factors was evident at a young age among Indians compared with high and upper middle income countries, with rural rates catching up with urban estimates. Adiposity predicted higher incident CVD risk, but the prevalence of hypertension and T2D was higher given a relatively low obesity prevalence. Preventive efforts should target both rural and urban India and should start young.
Publisher: Informa UK Limited
Date: 08-2011
DOI: 10.1586/ERC.11.61
Abstract: Recent epidemiology attests that hypertriglyceridemia may be a causal risk factor for cardiovascular disease (CVD). The specific atherogenicity of hypertriglyceridemia relates to the accumulation in plasma of triglyceride-rich lipoprotein remnants. Hypertriglyceridemia also drives a 'global' atherogenic dyslipidemic profile, which is frequent in high-risk cardiovascular patients, such as Type 2 diabetics. Elevated triglyceride in fasting or nonfasting blood s les should be a trigger for assessing atherogenic components of the lipid profile, particularly HDL-cholesterol, non-HDL-cholesterol and apoB. Residual risk of CVD remains high in statin-treated diabetic patients owing to persistent atherogenic dyslipidemia, which is not fully corrected by these agents nor by the addition of ezetimibe. Hypertriglyceridemia may then be targeted with niacin, fibrates or n-3 fatty acids, after correcting aggravating factors, especially obesity and hyperglycemia. Fibrates consistently decrease coronary events in dyslipidemic patients in outcome studies. New evidence supports adding fenofibrate to a statin in Type 2 diabetics with residual hypertriglyceridemia and low HDL-cholesterol extrapolating from a recent meta-analysis, a 15% reduction in triglycerides could translate into a further 15% reduction in coronary events. Ongoing clinical trials may provide new evidence for adding niacin to a statin. The value of higher doses of n-3 fatty acids in reducing CVD risk remains to be demonstrated. The high triglyceride/low HDL nexus is an under-recognized risk factor for CVD that merits more detailed clinical assessment and treatment, particularly in patients with Type 2 diabetes already receiving a statin.
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14177
Publisher: Springer Science and Business Media LLC
Date: 18-05-2201
DOI: 10.1038/NG.3304
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14132
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Fredrik Karpe.