Michele McGrady

Heart failure, ventricular dysfunction and risk factor prevalence in Australian Aboriginal peoples: the Heart of the Heart Study

Background Limited strategies have been developed to evaluate and address the alarming discrepancy in early mortality between Indigenous and non-Indigenous populations. Objective To assess heart failure (HF), HF risk factors and document cardiac characteristics in an Australian Aboriginal population. Design, setting, participants Adults were enrolled across six Aboriginal communities in Central Australia. They undertook comprehensive cardiovascular assessments, including echocardiography, to determine HF status, asymptomatic ventricular dysfunction and underlying risk factor profile. Results Of 436 participants (mean age 44±14 years; 64% women) enrolled, 5.3% (95% CI 3.2% to 7.5%) were diagnosed with HF, only 35% of whom had a pre-existing HF diagnosis. Asymptomatic left ventricular dysfunction (ALVD) was seen in 13% (95% CI 9.4% to 15.7%) of the population. Estimates of HF risk factor prevalence were as follows: body mass index (BMI) ≥30 kg/m2 42%, hypertension 41%, diabetes mellitus 40%, coronary artery disease (CAD) 7% and history of acute rheumatic fever or rheumatic heart disease 7%. In logistic regression analysis (after adjustment for age and gender), HF was associated with CAD (OR=9.6, p<0.001), diabetes (OR=5.4, p=0.002), hypertension (OR=4.8, p=0.006), BMI ≥30 kg/m2 (OR=2.9, p=0.02), acute rheumatic fever or rheumatic heart disease (OR=5.6, p=0.001) and B-type natriuretic peptide (OR=1.02, p<0.001). Conclusion The burden of HF, ALVD and risk factors in this population was extremely high. This study highlights potentially modifiable targets on which to focus resources and screening strategies to prevent HF in this high-risk Indigenous population.

Cardiometabolic risk and disease in Indigenous Australians: The heart of the heart study

OBJECTIVES This study assessed the burden and determinants of cardiovascular and metabolic risk in a community sample of high risk Indigenous Australians. BACKGROUND Indigenous Australians are over-represented in the most disadvantaged strata of Australian society. The role of psychosocial and socioeconomic factors in patterning cardiometabolic disease in this population is unclear. METHODS The Heart of the Heart Study was a cross sectional study of 436 Aboriginal adults from remote, urban and peri-urban communities around Alice Springs (Northern Territory, Australia). Participants underwent detailed assessments of socio-demographic, psychosocial, cardiovascular and metabolic status. RESULTS Individuals with depression were twice as likely to have cardiovascular disease (OR 2.03; 1.07-3.88; p<0.05). Chronic kidney disease (39.7%, 37.2% and 18.2%) and diabetes (28.4%, 34.0% and 19.2%) were more common in peri-urban and remote compared to urban communities. Cardiovascular disease did not vary across locations (p=0.069), but coronary artery disease did (p=0.035 for trend). Unemployed individuals were more likely to have cardiovascular disease (OR 2.32; 1.33-4.06; p<0.001). Socioeconomic gradients in coronary artery disease, all cardiovascular disease and diabetes, as measured by income, operated differentially across locations (p for location/socioeconomic status interactions 0.002; 0.01 and 0.04 respectively). CONCLUSION Participants had high rates of pre-existing cardiovascular disease, diabetes and chronic kidney disease. Cardiovascular risk in these communities was associated with psychosocial factors and socioeconomic indicators. However, gradients operated differentially across location. These data provide a strong foundation for better understanding key drivers of increased levels of cardiovascular and other common forms of non-communicable disease in Indigenous people.

Most individuals with treated blood pressures above target receive only one or two antihypertensive drug classes

A significant proportion of individuals taking antihypertensive therapies fail to achieve blood pressures <140/90 mmHg. In order to develop strategies for improved treatment of blood pressure, we examined the association of blood pressure control with antihypertensive therapies and clinical and lifestyle factors in a cohort of adults at increased cardiovascular risk.

A meta-analysis of echocardiographic measurements of the left heart for the development of normative reference ranges in a large international cohort : the EchoNoRMAL study

AIM To develop age-, sex-, and ethnic-appropriate normative reference ranges for standard echocardiographic measurements of the left heart by combining echocardiographic measurements obtained from adult volunteers without clinical cardiovascular disease or significant cardiovascular risk factors, from multiple studies around the world. METHODS AND RESULTS The Echocardiographic Normal Ranges Meta-Analysis of the Left heart (EchoNoRMAL) collaboration was established and population-based data sets of echocardiographic measurements combined to perform an individual person data meta-analysis. Data from 43 studies were received, representing 51 222 subjects, of which 22 404 adults aged 18-80 years were without clinical cardiovascular or renal disease, hypertension or diabetes. Quantile regression or an appropriate parametric regression method will be used to derive reference values at the 5th and 95th centile of each measurement against age. CONCLUSION This unique data set represents a large, multi-ethnic cohort of subjects resident in a wide range of countries. The resultant reference ranges will have wide applicability for normative data based on age, sex, and ethnicity.

N-terminal B-type natriuretic peptide and the association with left ventricular diastolic function in a population at high risk of incident heart failure: results of the SCReening Evaluation of the Evolution of New-Heart Failure Study (SCREEN-HF)

Impaired diastolic function is associated with increased morbidity and mortality, but antecedents and predictors of progression to heart failure (HF) are not well understood. We examined associations between NT‐proBNP, HF risk factors, and diastolic function in a population at high risk for incident HF.

Contemporary predictors of coronary artery disease in patients referred for angiography.

Aims Risk stratification is often used to determine the need and priority for coronary angiography. We investigated the contemporary value of Framingham and SCORE risk models, individual risk factors, B-type natriuretic peptide and high-sensitivity C-reactive protein (hs-CRP) in the current era of intensive risk management. Methods and results Coronary artery disease (CAD) was obstructive (≥ 50% stenosis) in 328 of 539 patients referred for elective diagnostic coronary angiography (61%). Lower rates of smoking, more exercise and lower cholesterol were noted in those with angiographic CAD, compatible with risk factor modification in these patients. Framingham and SCORE were associated with CAD both in patients with and without prior cardiovascular disease (CVD). In multivariate analysis only age, male sex, diabetes, chest pain and prior CVD were independent predictors of CAD; odds ratio 1.74 per 10 years (95% confidence interval: 1.34-2.27), 5.48 (3.36-8.92), 2.57 (1.44-4.60), 1.69 (1.02-2.81) and 2.61 (1.65-4.12), respectively. Classification of disease was not improved by B-type natriuretic peptide or hs-CRP when added to conventional risk factors, although the latter seems to have value in patients without earlier CVD and low-density lipoprotein-cholesterol of less than 3.4 mmol/l; the adjusted odds ratio for hs-CRP ≥ 2 mg/l in this sub-group was 2.49 (1.12-5.51, P = 0.024). Conclusion Framingham and SCORE risk models can be used in clinical practice to predict angiographic coronary disease although risk factor modification limits the predictive value of smoking, blood pressure, lipid profiles and cardiac biomarkers. Eur J Cardiovasc Prev Rehabil 17:280-288

Stable and unstable angina: Identifying novel markers on circulating leukocytes.

There is currently no blood‐based test that can rapidly and objectively distinguish between chest pain which is initiated by increased myocardial oxygen demand (stable angina pectoris (SAP)) and chest pain initiated due to decreased coronary blood flow (unstable angina pectoris (UAP)). Since leukocytes play an active role in the progression of coronary artery disease (CAD), we hypothesize these can provide novel markers of SAP and UAP. Here we use a microarray of 82 cluster of differentiation (CD) antibodies (plus controls) to selectively immobilize peripheral blood mononuclear cells. We find that the pattern of leukocyte immobilization from patients with CAD significantly differs from healthy donors. Within the CAD group, 15 SAP patients exhibited significant (p<0.05) changes in 8 of 82 CD antibody spots compared to 19 age‐matched healthy blood donors. An additional ten CD antigens differed between healthy donors and patients with UAP (p<0.05). Furthermore, seven CD antibody spots are significantly different between SAP and UAP patients. These preliminary data suggest it is now appropriate to undertake a larger clinical trial to test the hypothesis that these antibody microarrays can monitor the progression from SAP to UAP.

NT-proB natriuretic peptide, risk factors and asymptomatic left ventricular dysfunction: results of the SCReening Evaluation of the Evolution of New Heart Failure study (SCREEN-HF).

BACKGROUND We assessed left ventricular dysfunction in a population at high risk for heart failure (HF), and explored associations between ventricular function, HF risk factors and NT-proB natriuretic peptide (NT-proBNP). METHODS AND RESULTS 3550 subjects at high risk for incident HF (≥60 years plus ≥1 HF risk factor), but without pre-existing HF or left ventricular dysfunction, were recruited. Anthropomorphic data, medical history and blood for NT-proBNP were collected. Participants at highest risk (n = 664) (NT-proBNP highest quintile; >30.0 pmol/L) and a sample (n = 51) from the lowest NT-proBNP quintile underwent echocardiography. Participants in the highest NT-proBNP quintile, compared to the lowest, were older (74 years vs. 67 years; p < 0.001) and more likely to have coronary artery disease, stroke or renal impairment. In the top NT-proBNP quintile (n = 664), left ventricular systolic impairment was observed in 6.6% (95% CI: 4 to 8%) of participants and was associated with male gender, coronary artery disease, hypertension and NT-proBNP. At least moderate diastolic dysfunction was observed in 24% (95% CI 20 to 27%) of participants and was associated with diabetes and NT-proBNP. In this high risk population, NT-proBNP was associated with left ventricular systolic impairment (p < 0.001) and moderate to severe diastolic dysfunction (p < 0.001) after adjustment for age, gender, coronary artery disease, diabetes, hypertension and obesity. CONCLUSION A high burden of ventricular dysfunction was observed in this high risk group. Combining NT-proBNP and HF risk factors may identify those with ventricular dysfunction. This would allow resources to be focused on those at greatest risk of progression to overt HF.

Screening: the new frontier in heart failure management.

Heart failure is a major health problem throughout the world, with attendant high morbidity, mortality, and cost to the healthcare system. Population estimates of heart failure prevalence vary between 2 and 10%, depending on the population, and rise exponentially with age [1,2]. Fifty percent or more of those with identifiable left ventricular (LV) dysfunction are asymptomatic, undiagnosed, and presumably untreated [3–7]. Prevalence rates may be even greater in selected populations, particularly those with a very high prevalence of known risk factors for the condition, such as hypertension, myocardial ischemia, diabetes mellitus, chronic kidney disease, and obesity. Effective therapies exist to treat both symptomatic and asymptomatic left ventricular systolic dysfunction (ALVSD) [8–10], and therapeutic gains may be greater in the early stages of disease. Treatment of end-stage disease with therapies such as implantable defibrillators, biventricular pacing, assist devices, and transplantation is of limited benefit and is exceedingly costly. Consequently, strategies aimed at early diagnosis and intervention represent a far more effective and cost-effective approach to reducing progression in the individual patient and overall burden of disease in the community. Indeed, early diagnosis and treatment are advocated by all major heart failure guidelines [1,2,11]. Based on the above considerations, screening for heart failure and ALVSD is an attractive option, permitting earlier institution of therapies and potentially improving quality of life and survival. Multiple population screening strategies have been investigated, including the use of clinical parameters (symptoms and signs), electrocardiography (ECG), cardiac biomarkers, and echocardiography. None have shown a clear cost-effective benefit when used alone. Heart failure with preserved ejection fraction (HFPEF) and asymptomatic diastolic dysfunction are also highly prevalent and associated with poor clinical outcomes. Early detection is complex, and diagnosis is difficult even with the use of Doppler echocardiography and Btype natriuretic peptide (BNP) measurement. Moreover, treatment of these conditions remains largely empirical. There is evidence that increased LV mass correlates with poorer cardiovascular outcomes and mortality, and that regression of LV mass correlates with improved outcomes. There is, however, no single randomized, placebocontrolled trial that definitively supports this contention. Thus, the argument for screening for HFPEF may not be as strong as for disorders of systolic LV function. So how best to screen populations for heart failure and ALVSD (systolic and diastolic)? Echocardiography, the gold standard for documenting ventricular dysfunction,

Determinants of coronary arterial flow-mediated dilatation following percutaneous coronary intervention.

Objective: It has previously been observed that coronary diameter may increase following relief of flow‐limiting obstruction. Flow mediated dilatation (FMD) is a fundamental adaptive mechanism for arteries, which is dependent on intact endothelial function. We thus aimed to characterize whether the degree of this flow‐mediated dilatation was related to risk factors, which may impair endothelial function. Design: We measured coronary diameter with quantitative angiography before and after relief of chronic total or subtotal (≥99%) occlusion in 171 patients, in which TIMI‐0 or TIMI‐1 flow was rapidly restored to TIMI‐3 (with attendant increase in flow hypothesized to result in FMD). Patients: Of the 171 patients, 73% were male, 62% were current or ex‐smokers, 47% were diabetic, 53% had hypertension, 64% had dyslipidemia (documented hypercholesterolemia or total cholesterol >5.0 mg/dL) and 65% were taking statin therapy. Results: Mean vessel diameter was 2.8 ± 0.7 mm and flow‐mediated dilatation measured 15.1% ± 20.1% in target vessel, compared with 1.6 ± 3.1 in control vessels (P < 0.05). FMD was strongly and inversely related to baseline vessel diameter (r = −0.48, P < 0.001). The degree of vessel dilation correlated negatively with the presence of diabetes (r = −0.33, P < 0.001), smoking (r = −0.30, P < 0.001) and extent of coronary artery disease (CAD, r = −0.17, P = 0.01) and positively with the use of statins (r = 0.27, P = 0.001). These factors, apart from extent of CAD, remained significant predictors of FMD on multivariate analysis. Conclusions: FMD occurs in human coronary arteries following restoration of flow. The magnitude of FMD appears related to vascular risk factors and their treatment.