ORCID Profile
0000-0002-5369-5446
Current Organisations
Princess Alexandra Hospital
,
University of Queensland
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Publisher: Springer Science and Business Media LLC
Date: 22-03-2018
DOI: 10.1007/S10741-018-9693-0
Abstract: Heart failure (HF) and atrial fibrillation (AF) frequently coexist, and they can beget one another due to similar factors and shared pathophysiology. These pathophysiologic changes promote the episodes of AF, while they in turn predispose to the exacerbation of HF. In this review, we will discuss pathophysiological mechanisms shared by AF and HF. Patients with concomitant HF and AF are at a particularly high risk of thromboembolism, which contribute to even worse symptoms and poorer prognosis. Vitamin K antagonists (VKA) (warfarin) were the traditional medication in AF patients for the prevention of stroke, whereas the advance of novel non-VKA oral anticoagulants (NOACs) (dabigatran, apixaban, rivaroxaban, and edoxaban) is challenging these standard prescriptions. NOACs' potential advantages over warfarin, including fixed dosing regimens, wide therapeutic window, and more sustained anticoagulant response, promote clinicians to consider these novel agents in the first place. However, some data suggested patients with AF and HF may receive different therapeutic response than those with AF alone in anticoagulant treatment. Accordingly, we aim to assess the potential role of oral anticoagulants, especially NOACs, in the management of patients with concomitant AF and HF.
Publisher: Cambridge University Press (CUP)
Date: 06-09-2021
DOI: 10.1017/S1368980021003864
Abstract: Previous studies of sociodemographic and lifestyle correlates of dietary patterns among young adults have primarily focused on physical activity and smoking, with inconclusive results. This study aims to examine the associations between a broader range of lifestyles of young adults and their patterns of food consumption. Cross-sectional. Brisbane, Australia. The data set are from a long running birth cohort study which commenced in 1981. Details of dietary intake and sociodemographic and lifestyle factors were from the 21-year follow-up of the Mater-University of Queensland Study of Pregnancy (MUSP) birth cohort. The effective cohort ( n 2665, 57 % women) is of young adult offspring. Usual dietary intake was assessed using a Food Frequency Questionnaire (FFQ). Data on sociodemographic and lifestyle variables were obtained from self-reports. Western and prudent dietary patterns were identified for the combined cohort of women and men using principal components analysis. Multivariable linear regression models were used to examine the associations between lifestyle variables and dietary patterns adjusting for potential confounders. Results from multivariable adjusted models showed that physical activity, watching TV and smoking were strongly associated with each dietary pattern alcohol consumption and BMI showed weaker associations ( P 0·05 for all). Our study describes a clustering of unhealthy lifestyles in young adults. Young adults with unhealthy lifestyles less often adhere to a healthy prudent dietary pattern and more often an unhealthy Western pattern. Dietary preferences are enmeshed in a lifestyle matrix which includes physical activity, sedentary activity, smoking and alcohol consumption of young adults.
Publisher: Oxford University Press (OUP)
Date: 06-1999
DOI: 10.1016/S0895-7061(99)00004-7
Abstract: A Gly460Trp variant of the cytoskeletal protein alpha-adducin has recently been implicated in the etiology of essential hypertension (HT) in a study involving southern European whites. We attempted to replicate this finding in a well-characterized, extensively studied group of 112 white Australians with essential HT, with strong family history (two HT parents), early-onset, moderate to severe disease, and of British extraction. Controls were 196 normotensive (NT) white subjects whose parents were both NT older than age 50 years. A mismatch polymerase chain reaction method involving BanII was developed for genotyping. Frequency of the Trp460 allele was 0.23 in the HT and 0.24 in the NT groups (chi2 = 0.2, P = .7). No association was observed with blood pressure, body mass index, age, plasma renin, angiotensinogen, angiotensin converting enzyme, cholesterol, triglycerides, or HDL or LDL cholesterol. Our results therefore provide no support for a role for the alpha-adducin variant in hypertension, at least in our severely affected Anglo-white group with strong family history of HT.
Publisher: Wiley
Date: 15-04-2011
DOI: 10.1002/JCU.20820
Abstract: Recurrent pulmonary embolism (PE) in prothrombotic patients with patent foramen ovale (PFO) is not considered a setting for elective PFO closure. We describe a 35-year-old woman with known PFO, recurrent PE on warfarin, and Klippel-Trenaunay syndrome-a condition with predisposition for thromboembolism-who suffered concurrent saddle PE and devastating stroke with further impending paradoxical embolus across the PFO. Optimal management in patients with biatrial thromboembolus caught in transit across PFO is challenging. Patients with recurrent PE, prothrombotic states, and PFO should be considered for PFO closure. Prompt diagnosis of impending paradoxical embolus with echocardiography and consideration of surgical removal and PFO closure are critical.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.CJCA.2018.05.002
Abstract: Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot. Although EAT volume is associated with the incidence and burden of atrial fibrillation (AF), its role in subclinical left atrial (LA) dysfunction is unclear. This study aims to evaluate the relationships between EAT volumes, LA function, and LA global longitudinal strain. One hundred and thirty people without obstructive coronary artery disease or AF were prospectively recruited into the study in Australia and underwent cardiac computed tomography and echocardiography. EAT volume was quantified from cardiac computed tomography. Echocardiographic 3-dimensional (3D) volumetric measurements and 2D speckle-tracking analysis were performed. Using the overall median body surface area-indexed total EAT volume (EATi), the study cohort was ided into 2 groups of larger and smaller EATi volume. Subjects with larger EATi volume had significantly impaired LA reservoir function (3D LA ejection fraction, 46.1% ± 8.9% vs 49.0% ± 7.0%, P = 0.044) and reduced LA global longitudinal strain (37.6% ± 10.2% vs 44.1% ± 10.7%, P < 0.001). Total EATi volume was a predictor of impaired 2D LA global longitudinal strain (standardized β = -0.204, P = 0.034), reduced 3D LA ejection fraction (standardized β = -0.208, P = 0.036), and reduced 3D active LA ejection fraction (standardized β = -0.211, P = 0.017). Total EATi volume, rather than LA EATi volume, was the more important predictor of LA dysfunction. Indexed EAT volume is independently associated with subclinical LA dysfunction and impaired global longitudinal strain in people without obstructive coronary artery disease or a history of AF.
Publisher: BMJ
Date: 10-2019
DOI: 10.1136/BMJOPEN-2019-031627
Abstract: Previous studies in cardiac patients noted that early patient follow-up with general practitioners (GPs) after hospital discharge was associated with reduced rates of hospital readmissions. We aimed to identify patient, clinical and hospital factors that may influence GP follow-up of patients discharged from a tertiary cardiology unit. Single centre retrospective cohort study. Australian metropolitan tertiary hospital cardiology unit. 1079 patients discharged from the hospital cardiology unit within 3 months from May to July 2016. GP follow-up rates (assessed by telephone communication with patients’ nominated GP practices), demographic, clinical and hospital factors predicting GP follow-up. We obtained GP follow-up data on 983 out of 1079 (91.1%) discharges in the study period. Overall, 7, 14 and 30-day GP follow rates were 50.3%, 66.5% and 79.1%, respectively. A number of patient, clinical and hospital factors were associated with early GP follow-up, including pacemaker and defibrillator implantation, older age and having never smoked. Documented recommendation for follow-up in discharge summary was the strongest predictor for 7-day follow-up (p .001). After discharge from a cardiology admission, half of the patients followed up with their GP within 7 days and most patients followed up within 30 days. Patient and hospital factors were associated with GP follow-up rates. Identification of these factors may facilitate prospective interventions to improve early GP follow-up rates.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.CJCA.2016.06.009
Abstract: Although epicardial adipose tissue (EAT) volume is associated with increased incidence of coronary artery disease (CAD), its role in myocardial systolic dysfunction is unclear. The present study aimed to identify independent determinants of EAT volume in patients without obstructive CAD, and to evaluate the association between EAT volume (vs other measures of obesity) and myocardial systolic strain analysis. We prospectively recruited 130 patients without obstructive CAD on contrast-enhanced cardiac computed tomography imaging and normal left ventricular ejection fraction on 3-dimensional (3D) echocardiography. EAT volume was quantified from cardiac computed tomography imaging, and 3D multidirectional (longitudinal, circumferential, radial, and area) strain were measured. The mean EAT volume was 97.5 ± 43.7 cm EAT volume is independently associated with impaired myocardial systolic function despite preserved 3D left ventricular ejection fraction and absence of obstructive CAD, and might play a significant role in the pathophysiology of diabetic, obesity, and metabolic heart disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2003
DOI: 10.1097/00004872-200307000-00022
Abstract: The CYP11B2 locus is an important candidate region in essential hypertension (HT). We therefore investigated CYP11B2 polymorphisms T-344C, T4986C and A6547G for association with essential HT. This included haplotype analysis and measurement of plasma aldosterone levels. The three single nucleotide polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis of genomic DNA from 146 HT and 291 normotensive (NT) white subjects of Anglo-Celtic descent, in whom parental blood pressure status was the same as the subjects'. Genotype and allele frequencies in HTs and NTs were compared by chi2 analysis. Linkage disequilibrium and haplotype frequencies were estimated by the program 'snphap'. Phenotype-genotype relationships were tested using one-way analysis of variance. The T-344C variant was associated with HT (chi2 = 7.4, P = 0.0064). This association was confined to female HTs (P = 0.0061 for genotypes, P = 0.0013 for alleles). A strong association with HT was also seen for the A6547G variant (P = 0.0015), being greatest in females (P < 0.0001). No association was seen for the T4986C variant. Haplotype analysis of the three single nucleotide polymorphisms across eight different haplotype combinations showed a significant association with HT (chi2 = 24, seven degrees of freedom, P < 0.001). No significant tracking of plasma aldosterone with genotype was observed. The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in females of the Anglo-Celtic population studied. This was reinforced by haplotype analysis.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.CJCA.2014.10.029
Abstract: The World Health Organization and the American Diabetes Association recommend a level of glycated hemoglobin (HbA1c) ≥ 6.5% as diagnostic for diabetes. However, concordance between fasting plasma glucose (FPG) and HbA1c levels in acutely unwell patients is unknown. Furthermore, the prognostic value of HbA1c for left ventricular (LV) dysfunction is unclear. This study aimed to evaluate the concordance between HbA1c levels and FPG in consecutive patients with acute ST-elevation MI (STEMI) and compare their prognostic value in predicting LV dysfunction and elevated filling pressures on echocardiography. A total of 142 patients with a first incidence of STEMI were prospectively recruited. LV diastolic function was defined as mean septal and lateral early diastolic velocities (average e') filling pressure was the ratio of transmitral E velocity to average e' (average E/e'). Mean FPG and HbA1c levels were 7.7 ± 2.8 mmol/L and 6.5% ± 1.6%, respectively. Of 109 patients without previous diabetes, HbA1c levels identified an additional 18 patients (16.5%) as having diabetes, and the concordance with FPG was poor. Between diabetic and nondiabetic patients, there were no differences in LV end-diastolic volume (116 ± 37 vs 118 ± 43 mL P = 0.78), end-systolic volume (69 ± 33 vs 68 ± 35 mL P = 0.93), and ejection fraction (42 ± 12 vs 44 ± 11% P = 0.49). On multivariable analyses, average e' was independently associated with HbA1c (β = -0.161 P = 0.045) but not FPG (P = 0.82). Similarly, average E/e' was independently associated with HbA1c (β = 0.168 P = 0.04) but not FPG (P = 0.32). Receiver operating characteristic curve analysis showed that an HbA1c cutoff of 6.4% (area under the curve, 0.68 P = 0.002) was associated with an elevated LV filling pressure. Only HbA1c was independently associated with impaired LV diastolic function and increased filling pressures after STEMI.
Publisher: Japanese Society of Hypertension
Date: 2003
Abstract: The gene SAH (chromosome 16p12.3) is of interest in the etiology of human hypertension. In Caucasians a PstI restriction fragment length polymorphism (RFLP) of SAH has been correlated with body weight in in iduals with hypertension. To extend this finding we carried out a case-control study of several recently identified polymorphisms in SAH: 1) an insertion/deletion of TTTAA at nucleotide --1037 in the promoter 2) an insertion/deletion of two Alu like sequences in intron 1 and 3) an A-G variant in intron 12 located 7 bp upstream from exon 13. Subjects were 121 hypertensives with 2 hypertensive parents and 178 normotensives whose parents were both normotensive. All were Anglo-Celtic Caucasians and 51% of the hypertensives were overweight (body mass index (BMI)>25 kg/m2). The SAH promoter and intron 1 variants, but not the intron 12 or PstI RFLP, were in linkage disequilibrium (LD) (D'=100%, p<0.001). We found no association between any of the polymorphisms and hypertension. However, the frequency of the minor allele of the intron 1 polymorphism (0.20) was higher in overweight than in normal weight hypertensives (0.07) (p=0.013). This association was supported by the weak tracking of plasma lipid variables with this allele (p values=0.01-0.04), although these lost their statistical significance after correction for multiple comparisons. In conclusion, the present data offers support for variation in SAH having a role in predisposition to overweight in hypertensives.
Publisher: Elsevier BV
Date: 03-2020
Publisher: SAGE Publications
Date: 2021
DOI: 10.1177/20420986211027451
Abstract: Medication harm can lead to hospital admission, prolonged hospital stay and poor patient outcomes. Reducing medication harm is a priority for healthcare organisations worldwide. Recent Australian studies demonstrate cardiovascular (CV) medications are a leading cause of harm. However, they appear to receive less recognition as ‘high risk’ medications compared with those classified by the medication safety acronym, ‘APINCH’ (antimicrobials, potassium, insulin, narcotics, chemotherapeutics, heparin). Our aim was to determine the scale and type of medication harm caused by CV medications in healthcare. A narrative review of adult ( years) medication harm literature identified from PubMed and CINAHL databases was undertaken. Studies with the primary outcome of measuring the incidence of medication harm were included. Harm caused by CV medications was described and ranked against other medication classes at four key stages of a patient’s healthcare journey. Where specified, the implicated medications and type of harm were investigated. A total of 75 studies were identified, including seven systematic reviews and three meta-analyses, with most focussing on harm causing hospital admission. CV medications were responsible for approximately 20% of medication harm however, this proportion increased to 50% in older populations. CV medications were consistently ranked in the top five medication categories causing harm and were often listed as the leading cause. CV medications are a leading cause of medication harm, particularly in older adults, and should be the focus of harm mitigation strategies. A practical approach to generate awareness among health professionals is to incorporate ‘C’ (for CV medications) into the ‘APINCH’ acronym. Patient harm from cardiovascular medications Background • Harm from medications can cause poor patient outcomes. • Certain medications have been identified as ‘high risk’ and are known to cause high rates of harm. • ‘High risk’ medications are included in medication guidelines used by health professionals. • Cardiovascular medications (e.g. blood pressure and cholesterol medications) are important and have many benefits. • Recent studies have found cardiovascular medications to cause high rates of harm. • Cardiovascular medication harm is often under-recognised in clinical practice. • Some guidelines do not consider cardiovascular medications to be ‘high risk’. Method • This review investigated the extent of harm caused by cardiovascular medications in adults across four healthcare settings: (1) at the time of hospital admission (2) during hospital admission (3) after hospital and (4) readmission to hospital. • Harm caused by cardiovascular medications was ranked against other medication classes. • We investigated the type of cardiovascular medications to cause harm and the type of harm caused. Results • Seventy-five studies were reviewed across 41 countries. • Cardiovascular medications were ranked within the top five medications to cause harm. • Cardiovascular medications were a leading cause of harm in each healthcare setting investigated. • Harm caused by cardiovascular medications was common in older adults ( years). • Cardiovascular medications often caused preventable harm. • Medications to treat high blood pressure and abnormal heart rhythms were the most common causes of harm. • We reported kidney injury, electrolyte changes and low blood pressure as common types of harm. Conclusion • Increased focus on cardiovascular medications in clinical practice is needed. • Health professionals need to carefully prescribe and frequently review cardiovascular medications, especially in older adults. • Patient and health professional discussions should be based on both the benefits and harms of cardiovascular medications. • Cardiovascular medications should be included in all ‘high risk’ medication guidelines.
Publisher: Wiley
Date: 04-2020
DOI: 10.1111/PACE.13899
Publisher: Frontiers Media SA
Date: 12-05-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
DOI: 10.1161/CIRCIMAGING.117.007372
Abstract: Current understanding of metabolic heart disease consists of a myriad of different pathophysiological mechanisms. Epicardial adipose tissue (EAT) is increasingly recognized as metabolically active and associated with adverse cardiovascular outcomes. The present study aimed to investigate the effect of increased EAT volume index on left ventricular (LV) myocardial fat content and burden of interstitial myocardial fibrosis and their subsequent effects on LV myocardial contractile function. A total of 40 volunteers (mean age, 35±10 years 26 males) of varying body mass index (25.0±4.1 kg/m 2 range, 19.3–36.3 kg/m 2 ) and without diabetes mellitus or hypertension were prospectively recruited. EAT volume index, LV myocardial fat content, and extracellular volume were quantified by magnetic resonance imaging. LV myocardial contractile function was quantified by speckle tracking echocardiography global longitudinal strain on the same day as magnetic resonance imaging examination. Mean total EAT volume index, LV myocardial fat content, and extracellular volume were 30.0±19.6 cm 3 /m 2 , 5.06%±1.18%, and 27.5%±0.5%, respectively. On multivariable analyses, increased EAT volume index and insulin resistance were independently associated with both increased LV myocardial fat content content and higher burden of interstitial myocardial fibrosis. Furthermore, increased EAT volume index was independently associated with LV global longitudinal strain. Increased EAT volume index and insulin resistance were independently associated with increased myocardial fat accumulation and interstitial myocardial fibrosis. Increased EAT volume index was associated with detrimental effects on myocardial contractile function as evidenced by a reduction in LV global longitudinal strain.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.HLC.2016.04.017
Abstract: Coronary vasospasm is an uncommon, but perhaps under-recognised, cause of cardiac arrest. We present a novel case of an exercise-induced out-of-hospital cardiac arrest due to coronary vasospasm, captured on a heartrate monitor, and discuss the management options for this condition.
Publisher: CSIRO Publishing
Date: 2020
DOI: 10.1071/AH18160
Abstract: This case study describes the development, implementation and review of a sustainable and culturally sensitive procedure for a hospital-funded discharge medicine subsidy for Aboriginal and Torres Strait Islander patients registered with the Closing the Gap (CTG) program discharging from a public hospital. A 7-day fully subsidised medication supply was approved to be offered to Aboriginal and Torres Strait Islander patients admitted under cardiac care teams, including cardiology and cardiothoracic surgery patients. Patients were offered the option of a 7-day supply free of cost to them or a full Pharmaceutical Benefits Scheme (PBS) supply if preferred. A general practitioner (GP) appointment was organised within 7 days of discharge to ensure patients received ongoing supply of their medications as well as timely clinical review after discharge. Over a 34-month period from September 2015 to June 2018, 535 Aboriginal and Torres Strait Islander patients were admitted to the hospital under cardiac care teams. Of these patients, 296 received a subsidised discharge medication supply with a total cost of A$6314.56 to the hospital over the trial period, with a mean cost of A$21.26 per discharge. The provision of subsidised medications through the CTG program has improved the continuity of care for Aboriginal and Torres Strait Islander patients. The culturally sensitive approach is well received and has allowed smooth transition back to the community. This site-specific and state-based funding model was found to be financially sustainable at a public hospital. What is known about the topic?The CTG PBS program is not applicable to discharge prescriptions from public hospitals. As such, patients are required to either leave the hospital with no medicines or leave the hospital with medicines for which they have to pay full PBS price. This creates a huge financial barrier to the care for CTG-registered patients in the acute care setting. What does this paper add?A sustainable solution to the problem was found via a state-funded model while providing a supportive team to ensure GP follow-up and continuity of care after discharge. What are the implications for practitioners?If similar approvals are granted and supported at other public hospital sites, practitioners will be afforded one less barrier to provide patient-centred care for Aboriginal and Torres Strait Islander patients.
Publisher: Wiley
Date: 05-11-1999
DOI: 10.1002/(SICI)1096-8628(19991105)87:1<53::AID-AJMG11>3.0.CO;2-I
Abstract: Linkage with essential hypertension has been claimed for a microsatellite marker near the angiotensinogen gene (AGT chromosome 1q42), as has association for the AGT variants M235T, G(-6)A and A(-20)C. To more rigorously evaluate AGT as a candidate gene for hypertension we performed sibpair analysis with multiple microsatellite markers surrounding this locus and using more sophisticated analysis programs. We also performed an association study of the AGT variants in unrelated subjects with a strong family history (two affected parents). For the linkage study, single and multiplex polymerase chain reaction (PCRs) and automated genescan analysis were conducted on DNA from 175 Australian Anglo-Celtic Caucasian hypertensives for the following markers: D1S2880-(2.1 cM)-D1S213-(2.8 cM)-D1S251-(6.5 cM)-AGT-(2.0 cM) -D1S235. Statistical evaluation of genotype data by nonparametric methods resulted in the following scores: Single-point analysis - SPLINK, P > 0.18 APM method, P > 0.25 ASPEX, MLOD 0. 24 Multipoint analysis - MAPMAKER/SIBS, MLOD 0.35. Exclusion scores of Lod -4.1 to -5.1 were obtained for these markers using MAPMAKER/SIBS for a lambda(s) of 1.6. The association study of G(-6)A, A(-20)C and M235T variants in 111 hypertensives with strong family history and 190 normotensives with no family history showed significant linkage disequilibrium between particular haplotypes, but we could find no association with hypertension. The present study therefore excludes AGT in the etiology of hypertension, at least in the population of Australian Anglo-Celtic Caucasians studied.
Publisher: AMPCo
Date: 02-2013
DOI: 10.5694/MJA12.11620
Publisher: Springer Science and Business Media LLC
Date: 07-2020
Publisher: BMJ
Date: 03-2021
DOI: 10.1136/BMJOPEN-2020-043304
Abstract: Cardiovascular disease (CVD) represents a significant burden of disease for Aboriginal and Torres Strait Islander people, a population that continues to experience a lower life expectancy than other Australians. The aim of the Better Cardiac Care Data Linkage project is to describe patient care pathways and to identify disparities in care and health outcomes between Aboriginal and Torres Strait Islander people and other Queensland residents diagnosed with CVD in the state of Queensland. This is a population-based retrospective cohort study using linked regional, state and national health and administrative data collections to describe disparities in CVD healthcare in primary and secondary prevention settings and during hospitalisation. The CVD cohort will be identified from the Queensland Hospital Admitted Patient Data Collection for admissions that occurred between 1 July 2010 and 31 June 2016 and will include relevant International Classification of Disease codes for ischaemic heart disease, congestive heart failure, stroke, acute rheumatic fever and rheumatic heart disease. Person-level data will be linked by Data Linkage Queensland and the Australian Institute of Health and Welfare (AIHW) in accordance with ethical and public health approvals to describe the patient journey prior to, during and post the hospital admission. This project will focus largely on descriptive epidemiological measures and multivariate analysis of clinical care standards and outcomes for Aboriginal and Torres Strait Islander people compared with other Queenslanders, including identification of risk factors for suboptimal care and change over time. Variation in care pathways and patient outcomes will be compared by Indigenous status, sex, age group, remoteness of residence, year of index hospitalisation and socioeconomic status. Cox models for time-to-event data and mixed models or generalised estimating equations for longitudinal data will be used to measure change over time where temporal effects exist. Ethical approval has been granted by Human Research Ethics Committees of the Prince Charles Hospital (HREC/15/QPCH/289) and the AIHW (EO2016-1-233). The Northern Territory Department of Health and Menzies School of Health Research have also provided reciprocal ethical approval of the project (HREC 2019–3490). The deidentified results will be summarised in a report and shared with investigators, advisory groups, Queensland Health and key stakeholders. Findings will be disseminated through workshops, conferences and will be published in peer-reviewed journals.
Publisher: Elsevier BV
Date: 07-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-02-2002
Abstract: Background — Elevated pulse pressure is associated strongly with adverse cardiovascular outcome however, the genetic basis of this condition is unknown. This study examined whether genotypic variation in the extracellular matrix protein fibrillin-1, the Marfan gene, was associated with aortic stiffening and therefore could contribute to cardiovascular risk associated with pulse pressure elevation in coronary disease. Methods and Results — Patients (n=145 113 men), 62±9 years of age (mean±SD), with angiographically confirmed coronary disease, were studied. Carotid applanation tonometry was used to assess central blood pressures, and in conjunction with Doppler velocimetry, to assess aortic input and characteristic impedance. Fibrillin-1 genotype was characterized by a variable nucleotide tandem repeat and 2 single-nucleotide polymorphisms. The variable nucleotide tandem repeat was a good predictor of underlying haplotypes with 3 genotypes (2-2, 2-4, and 2-3) accounting for 86% of the population. The 2-3 genotype had higher input impedance ( P =0.002), characteristic impedance ( P =0.005), and carotid pulse pressure ( P =0.002) compared with the 2-2 and 2-4 genotypes. Disease severity assessed by previous angioplasties and the number of patients with a stenosis % was also greater in the 2-3 genotype. Furthermore, in a multivariate analysis, fibrillin-1 genotype and central pulse pressure were independent of conventional risk factors in determining coronary disease severity. There was no difference in age, sex ratio, body mass index, smoking status, cholesterol level, or medication among the 3 genotypes. Conclusions — Although a causative link has not been shown, these data are consistent with an important role for fibrillin-1 genotype in cardiovascular risk associated with large-artery stiffening and pulse pressure elevation in in iduals with coronary disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2004
DOI: 10.1161/01.HYP.0000143844.81979.61
Abstract: β 2 -Adrenergic receptor gene and neuropeptide Y gene may potentially influence lipid metabolism and overall energy balance. Therefore, we examined associations of these genes with lipid fractions and obesity-related phenotypes in hypertensive subjects. A total of 638 white in iduals from 212 Polish families with clustering of essential hypertension were phenotyped for cardiovascular risk determinants. Each subject was genotyped for functional polymorphisms of β 2 -adrenergic receptor gene (Arg16Gly and Gln27Glu) and neuropeptide Y (Leu7Pro). Of 3 common haplotypes of β 2 -adrenergic receptor gene, Arg16Gln27 was overtransmitted to offspring with elevated levels of total cholesterol ( Z =2.2 P =0.026) and LDL-cholesterol ( Z =3.2 P =0.002). In idually, Leu7Pro was not associated with any of the metabolic phenotypes in family-based tests or case-control analyses. However, in the presence of Arg allele of Arg16Gly and Gln allele of Gln27Glu, homozygosity for Leu variant of the Leu7Pro polymorphism was associated with 2.1-increased odds ratio (confidence interval, 1.10 to 3.81 P =0.024) of elevated LDL in hypertensive subjects, independent of age, gender, body mass index, adjusted blood pressures, antihypertensive therapy, and use of nonselective β-blockers and diuretics. Consistently, there was a significant multilocus association among variants of Arg16Gly, Gln27Glu, and Leu7Pro in hypertensive probands with elevated LDL (cases P =0.028) but not in hypertensive subjects with normal LDL (controls). This study revealed an association of LDL-cholesterol with β 2 -adrenergic receptor gene haplotype and provided evidence for epistatic interaction between β 2 -adrenergic receptor gene and neuropeptide Y gene in determination of LDL-cholesterol in patients with essential hypertension.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 18-08-2010
Publisher: Springer Science and Business Media LLC
Date: 11-2003
DOI: 10.1023/B:GENE.0000003683.42395.51
Abstract: Bactrocera neohumeralis and Bactrocera tryoni are closely related tephritid fruit fly species. B. neohumeralis mates throughout the day (in bright light) and B. tryoni mates at dusk. The two species can also be distinguished by the colour of their calli (prothoracic sclerites) which are brown and yellow, respectively. The F1 hybrids can mate both in bright light just before dusk and during dusk and have calli that are partly brown and partly yellow. The F2 hybrids have a wider range of callus patterns and mating occurs more widely in the day as well as at dusk. We directly selected hybrid stocks for mating time, creating 'early' (day-mating) and 'late' (dusk-mating) lines. As an apparently inadvertent consequence, the two types of line respectively had predominantly brown and predominantly yellow calli and thus came to closely resemble the original two species in both behaviour and appearance. Lines that were evenly selected (half for day and half for dusk) essentially retained the mating pattern of F2 hybrids. Selection for callus colour alone also affected the distribution of mating times in a predictable way. We propose a genetical model to account for the results and discuss them in the light of the apparent maintenance of species integrity in nature.
Publisher: Elsevier BV
Date: 02-2003
Publisher: Wiley
Date: 30-12-2002
DOI: 10.1002/GEPI.10216
Abstract: Association mapping in linked regions is a current major approach for the identification of genes for complex diseases. Loci contributing to linkage, even with small values of sibling recurrence risk (lambda(s)), may be equivalent to substantial underlying genetic effects for association studies. For disease alleles with a frequency as low as 1%, highly reliable association studies (80% power for significance level alpha=10(-6)) require only 277, 781, and 1289 families or cases and controls for loci detected with lambda(s) of 1.5, 1.1, and 1.05, respectively, under a multiplicative genetic model. Under alternative models, provided epistatic effects are minor, larger achievable s le sizes will provide sufficient power to map almost any disease gene that may have initially contributed to linkage.
Publisher: Elsevier BV
Date: 11-2014
Abstract: The presence of entrapped lung changes the appropriate management of malignant pleural effusion from pleurodesis to insertion of an indwelling pleural catheter. No methods currently exist to identify entrapped lung prior to effusion drainage. Our objectives were to develop a method to identify entrapped lung using tissue movement and deformation (strain) analysis with ultrasonography and compare it to the existing technique of pleural elastance (PEL). Prior to drainage, 81 patients with suspected malignant pleural effusion underwent thoracic ultrasound using an echocardiogram machine. Images of the atelectatic lower lobe were acquired during breath hold, allowing motion and strain related to the cardiac impulse to be analyzed using motion mode (M mode) and speckle-tracking imaging, respectively. PEL was measured during effusion drainage. The gold-standard diagnosis of entrapped lung was the consensus opinion of two interventional pulmonologists according to postdrainage imaging. Participants were randomly ided into development and validation sets. Both total movement and strain were significantly reduced in entrapped lung. Using data from the development set, the area under the receiver-operating curves for the diagnosis of entrapped lung was 0.86 (speckle tracking), 0.79 (M mode), and 0.69 (PEL). Using respective cutoffs of 6%, 1 mm, and 19 cm H2O on the validation set, the sensitivity/specificity was 71%/85% (speckle tracking), 50%/85% (M mode), and 40%/100% (PEL). This novel ultrasound technique can identify entrapped lung prior to effusion drainage, which could allow appropriate choice of definitive management (pleurodesis vs indwelling catheter), reducing the number of interventions required to treat malignant pleural effusion.
Publisher: Oxford University Press (OUP)
Date: 06-2005
DOI: 10.1016/J.AMJHYPER.2004.12.010
Abstract: We report here the results of the GENIHUSS study (GENetic Investigation of Hypertension Undertaken in Sydney Sibships)-a genome-wide scan to identify loci linked to essential hypertension (HT). Subjects were Anglo-Celtic Australian sibpairs resident in or near Sydney, Australia, with onset of HT before age 60 years (mean, 44 +/- 13 SD years). A 10-cM scan involving 400 microsatellite markers and 252 HT sibpairs was followed by fine mapping of the most promising locus using 296 HT sibpairs (481 in iduals from 200 families). Multipoint and two-point nonparametric linkage analyses were performed using MAPMAKER/SIBS, GENEHUNTER II, and SPLINK. Suggestive loci were found on chromosomes 1 (4 cM) and 4 (129 cM). The chromosome 4 locus coincided with a QTL for systolic blood pressure (BP) in the Australian Victorian Family Heart Study, and the locus on chromosome 1 contains the chloride channel gene CLCNKB and tumor necrosis factor receptor 2 gene TNFRSF1B, which have each shown association with HT. Our study adds to findings of HT loci emanating from genome scans.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2002
DOI: 10.1161/01.HYP.0000029105.21202.FE
Abstract: A region on human chromosome 5 (5q31.1-qter) contains several genes that encode important blood pressure regulators and thus is a good candidate for analysis of linkage and association with hypertension. We recruited 638 in iduals from 212 Polish pedigrees with clustering of essential hypertension. These subjects were genotyped for 11 microsatellite markers that span this region to test for linkage to essential hypertension and systolic and diastolic blood pressures. The segment of this region of ≈7 cM delineated by D5S1480 and D5S500 markers was linked to blood pressures in multipoint analysis. In 2-point analysis, D5S1480—the marker in close proximity to β 2 -adrenergic receptor gene—reached the maximal linkage to essential hypertension and adjusted systolic and diastolic blood pressures, implicating this gene as a positional candidate for further association studies. Arg16Gly, Gln27Glu, and Thr164Ile—3 functional single nucleotide polymorphisms within the β 2 -adrenergic receptor gene—were tested for association with essential hypertension. None of these polymorphisms showed a significant association with essential hypertension, separately or in the haplotype analysis. This study provided evidence of linkage of 5q31.1-5qter region to essential hypertension in the European population. Moreover, it implicated the chromosomal segment in close proximity to D5S1480 and D5S500. The detailed analysis of 3 single nucleotide polymorphisms does not support the role of the β 2 -adrenergic receptor gene as a major causative gene for the detected linkage.
Publisher: Public Library of Science (PLoS)
Date: 06-02-2015
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.NUMECD.2022.01.030
Abstract: The extent to which dietary patterns influence the risk of abnormal blood lipids throughout young adulthood remains unclear. The aim was to investigate whether early young adulthood dietary patterns predict the risk of abnormal blood lipids during later young adulthood. We used data from a long running birth cohort study in Australia. Western dietary pattern rich in meats, processed foods and high-fat dairy products and prudent pattern rich in fruit, vegetables, fish, nuts, whole grains and low-fat dairy products were derived using principal component analysis at the 21-year follow-up from dietary data obtained using a food frequency questionnaire. After 9-years, fasting blood s les of all participants were collected and their total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterols and triglyceride (TG) levels were measured. Abnormal blood lipids were based on clinical cut-offs for total, LDL and HDL cholesterols, and TG and relative distributions for total:HDL and TG:HDL cholesterols ratios. Log-binomial models were used to estimate risk of each outcome in relation to dietary patterns. Greater adherence to the Western pattern predicted increased risks of high LDL (RR: 1.47 95%CI: 1.06, 2.03) and TG (1.90 1.25, 2.86), and high ratios of total:HDL (1.48 1.00, 2.19) and TG:HDL (1.78 1.18, 2.70) cholesterols in fully adjusted models. Conversely, a prudent pattern predicted reduced risks of low HDL (0.58 0.42, 0.78) and high TG (0.66 0.47, 0.92) and high total:HDL (0.71 0.51, 0.98) and TG:HDL (0.61 0.45, 0.84) cholesterols ratios. This is the first prospective study to show greater adherence to unhealthy Western diet predicted increased risks of abnormal blood lipids, whereas healthy prudent diet predicted lower such risks in young adults. Addressing diets in early course may improve cardiovascular health of young adults.
Publisher: American Diabetes Association
Date: 03-2004
DOI: 10.2337/DIABETES.53.3.852
Abstract: Several lines of evidence suggest the involvement of the human endogenous retrovirus (HERV)-K18 in the etiology of type 1 diabetes. HERV-K18 encodes for a T-cell superantigen (SAg). T-cells with T-cell receptor Vβ7 chains reactive to the SAg and HERV-K18 mRNA were enriched in the tissues at the onset of the disease. HERV-K18 transcription and SAg function in cells capable of efficient presentation are induced by proinflammatory stimuli such as viruses and interferon-α and may trigger progression of disease to insulitis or from insulitis to overt diabetes. Allelic variation of HERV-K18 or the DNA flanking it, the CD48 gene, could modulate genetic susceptibility. Analysis of 14 polymorphisms in the locus using 754 diabetic families provided positive evidence of association of three variants belonging to a single haplotype (P = 0.0026), present at 21.8% frequency in the population. Genotype analysis suggested a dominantly protective effect of this haplotype (P = 0.0061). Further genetic and functional analyses are required to confirm these findings.
Publisher: Society of Nuclear Medicine
Date: 15-06-2016
DOI: 10.2967/JNUMED.115.169870
Abstract: Our aim was to determine the feasibility of Target-to-background SUV ratio and percentage myocardial
Publisher: Springer Science and Business Media LLC
Date: 27-05-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-10-2007
DOI: 10.1161/CIRCULATIONAHA.107.710293
Abstract: Background— The distal portion of the long arm of chromosome 5 is linked to hypertension and contains functional candidate blood pressure–regulating genes. Methods and Results— Tightening the grid of microsatellite markers under this quantitative trait locus in the Silesian Hypertension Study (629 in iduals from 207 Polish hypertensive families) provided enhanced support for linkage of this region to blood pressure (maximal Z =3.51, P =0.0002). The fine mapping, comparative genomics, and functional prioritization identified fibroblast growth factor 1 gene (FGF1) as the positional candidate. Linkage disequilibrium mapping based on 51 single nucleotide polymorphisms spanning the locus showed no overlap between 3 independent haploblocks of FGF1 and the adjacent extragenic chromosomal regions. Single and multilocus family-based analysis revealed that genetic variation within FGF1 haploblock 1 was associated with hypertension and identified a common intronic single nucleotide polymorphism, rs152524, as the major driver of this association ( P =0.0026). Real-time quantitative polymerase chain reaction and Western blotting analysis of renal tissue obtained from subjects undergoing unilateral nephrectomy showed an increase in both mRNA and protein FGF1 expression in hypertensive patients compared with normotensive controls. Renal immunohistochemistry revealed that FGF1 was expressed exclusively within the glomerular endothelial and mesangial cells. Conclusions— Our data demonstrate that genetic variation within FGF1 cosegregates with elevated blood pressure in hypertensive families and that this association is likely to be mediated by upregulation of renal FGF1 expression. The results of our study will need to be replicated in other cohorts.
Publisher: Public Library of Science (PLoS)
Date: 10-04-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2011
Publisher: Wiley
Date: 02-01-2015
DOI: 10.1111/ECHO.12877
Abstract: Right ventricular (RV) function assumes prognostic significance in various disease states, but RV geometry is not amenable to volumetric assessment by two-dimensional echocardiography. Intra-ventricular pressure rate of rise (dP/dt) predicts myocardial contractility and adjusting for the maximal regurgitant velocity (Vmax) corrects for preload. We examined the relationship of noninvasive tricuspid dP/dt and dP/dt/Vmax with RV ejection fraction (RVEF) by cardiac magnetic resonance imaging (CMR) as a measure of RV function. Fifty CMRs and echocardiograms performed within 30 days were included. Tricuspid regurgitation (TR) spectral Doppler trace was analyzed offline. TR dP/dt was calculated using simplified Bernoulli equation (dP/dt between 1 and 2 m/sec). dP/dt/Vmax was calculated as a ratio of dP/dt and TR Vmax . RV end-diastolic (EDV) and end-systolic volumes (ESV) were obtained from contouring of steady-state-free precession axial stack CMR images RVEF was calculated as [(RVEDV - RVESV)/RVEDV] × 100. RVEF >42% was considered normal. Majority of studies were suitable for analysis. Median age was 48 years (IQR = 36-63) 56.4% were female (n = 22/39). There was correlation between dP/dt and RVEF (r(2) = 0.51, P < 0.01) which improved with dP/dt/Vmax (r(2) = 0.59, P 400 mmHg/sec had a positive predictive value of 91%, sensitivity and specificity of 74% and 84% respectively for normal RVEF. Inter-observer agreement and repeatability analysis showed no significant difference. Tricuspid dP/dt correlates well with CMR RVEF. A dP/dt of more than 400 mmHg/sec strongly predicts normal RVEF. Adjusting for preload (dP/dt/Vmax) further improves this correlation.
Publisher: Springer Science and Business Media LLC
Date: 22-01-2002
DOI: 10.1038/NG825
Publisher: Cold Spring Harbor Laboratory
Date: 05-2003
DOI: 10.1101/GR.563703
Abstract: Patterns of linkage disequilibrium (LD) in the human genome are beginning to be characterized, with a paucity of haplotype ersity in “LD blocks,” interspersed by apparent “hot spots” of recombination. Previously, we cloned and physically characterized the low-density lipoprotein-receptor-related protein 5 ( LRP5 ) gene. Here, we have extensively analysed both LRP5 and its flanking three genes, spanning 269 kb, for single nucleotide polymorphisms (SNPs), and we present a comprehensive SNP map comprising 95 polymorphisms. Analysis revealed high levels of recombination across LRP5 , including a hot-spot region from intron 1 to intron 7 of LRP5 , where there are 109 recombinants/Mb (4882 meioses), in contrast to flanking regions of 14.6 recombinants/Mb. This region of high recombination could be delineated into three to four hot spots, one within a 601-bp interval. For LRP5 , three haplotype blocks were identified, flanked by the hot spots. Each LD block comprised over 80% common haplotypes, concurring with a previous study of 14 genes that showed that common haplotypes account for at least 80% of all haplotypes. The identification of hot spots in between these LD blocks provides additional evidence that LD blocks are separated by areas of higher recombination. [Supplementary material: primers are available from our Web site: www-gene.cimr.cam.ac.uk/todd/human_data.shtml .]
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2004
DOI: 10.1097/00004872-200405000-00014
Abstract: To perform association studies of polymorphisms of the potential candidate essential hypertension (HT) genes GRK4, PTP1B and HSD3B1. Subjects consisted of 168 unrelated, Caucasian essential hypertensive (HT) patients and 312 normotensive (NT) controls. Biological power was increased by ensuring subjects in each group had parents with the same blood pressure (BP) status as theirs. Three GRK4gamma variants (R65L, A142V and A486V), one HSD3B1 variant (T<---C Leu) and one PTP1B variant (1484insG) were genotyped by polymerase chain reaction and restriction enzyme digestion or by homogenous MassEXTEND Assay. The V allele of the A486V variant of GRK4gamma, but not the R65L or A142V variants, showed an association with HT (P = 0.02). The V allele was also associated with an elevation in systolic blood pressure (SBP) (P = 0.002). Although the L65 and the V142 alleles tracked with elevation in diastolic (DBP), this was seen only in male HTs (P = 0.009 P = 0.002, respectively). Haplotype frequencies differed between the HT and NT groups, particularly for the R, V, V haplotype combination of R65L, A142V and A486V, respectively. Neither of the HSD3B1 or PTP1B variants were associated with HT. Genetic variation in GRK4gamma was associated with HT in the subjects studied.
Publisher: Oxford University Press (OUP)
Date: 07-2004
Publisher: Oxford University Press (OUP)
Date: 12-2003
DOI: 10.1093/HMG/DDG337
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.BBRC.2005.03.203
Abstract: Susceptibility to the autoimmune disease type 1 diabetes has been linked to human chromosome 6q27 and, moreover, recently associated with one of the genes in the region, TATA box-binding protein (TBP). Using a much larger s le of T1D families than those studied by others, and by extensive re-sequencing of nine other genes in the proximity, in which we identified 279 polymorphisms, 83 of which were genotyped in up to 725 T1D multiplex and simplex families, we obtained no evidence for association of the TBP CAG/CAA (glutamine) microsatellite repeat sequence with disease, or for nine other genes, PDCD2, PSMB1, KIAA1838, DLL1, dJ894D12.4, FLJ25454, FLJ13162, FLJ11152, PHF10 and CCR6. This study also provides an exon-based tag single nucleotide polymorphism map for these 10 genes that can be used for analysis of other diseases.
Publisher: Elsevier BV
Date: 2004
Publisher: Springer Science and Business Media LLC
Date: 25-04-2003
Publisher: Informa UK Limited
Date: 16-03-2017
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for William Wang.