Gurbir S. Bhatia

Heart failure—the importance of ethnicity

Heart failure is a major public health problem in the Western world. Aetiological factors involved in its development include hypertension, diabetes, and ischaemic heart disease—all of which differ in prevalence, and possibly mechanism, between patients of differing ethnicity. Unfortunately, epidemiological and therapeutic trials have involved almost exclusively white populations, and evidence from these trials cannot necessarily be assumed to be generalisable to populations that include high proportions of patients from other ethnic origins. This review will discuss the mechanistic and therapeutic differences that exist in heart failure between those of European origin, and patients from the major ethnic minority groups of the UK.

An 8-year follow-up study of acute admissions with heart failure in a multiethnic population

In 1994, we reported a cross‐sectional survey of acute heart failure admissions to a city centre hospital serving a multiethnic population and found ethnic differences in aetiological factors and short‐term (in‐patient) mortality. We analysed long‐term mortality data for this original survey cohort after 8 years’ follow‐up. At 8 years’ follow‐up, the total mortality was 90.5% amongst Europeans and 87.0% amongst non‐Europeans (log rank test, P=0.0705). The non‐European patients had significantly better survival at all time points until 6 years, after which the survival curves start to converge. In univariate analysis, age <75.6 years (that is, the median age of the whole cohort), use of beta‐blockers, use of ACE inhibitors, and absence of atrial fibrillation were significantly associated with increased survival. In addition, patients who had had an echocardiographic examination had significantly prolonged survival when compared to those who did not. Using a Cox multiple regression analysis, age, renal impairment, atrial fibrillation, absence of echocardiography, absence of beta‐blockers or ACE inhibitor use (and not ethnicity) remained significant predictors of mortality at 8 years. While this follow‐up study has suggested that survival following admission for acutely decompensated heart failure is not different between different ethnic groups when corrected for age, it is clear from the younger age of heart failure patients from ethnic minority groups and the relatively high prevalence, that the burden of heart failure is greater in these populations. Future observational and therapeutic trials in heart failure should include sufficient numbers of participants from ethnic minority groups to ensure that the results can be applied to the population at risk.

Hibernating myocardium in heart failure.

Ischemic left ventricular systolic dysfunction may result from myocardial necrosis or from hypocontractile areas of viable myocardium. In some cases, recovery of contractility may occur on revascularization – this reversibly dysfunctional tissue is commonly referred to as hibernating myocardium. Observational data suggest that revascularization of patients with ischemic left ventricular systolic dysfunction and known viable myocardium provides a survival benefit over medical therapy. Identification of viable, dysfunctional myocardium may be especially worthwhile in deciding which patients with ischemic left ventricular systolic dysfunction will benefit from revascularization procedures. Randomized, prospective trials evaluating this are currently ongoing. This review will provide an overview of the complex pathophysiology of viable, dysfunctional myocardium, and will discuss outcomes after revascularization. Of the techniques used to determine the presence of hibernating myocardium, functional methods such as stress echocardiography and cardiac magnetic resonance appear more specific, but less sensitive, than the nuclear modalities, which assess perfusion and metabolic activity. Currently, the availability of all methods is variable.

Plasma indices of angiogenesis in rheumatoid disease: relationship to cardiovascular risk factors and cardiac function.

INTRODUCTION Rheumatoid Disease (RD) is associated with increased rates of cardiovascular disease (CVD). Angiogenesis is central to RD, and well-recognized in CVD. We hypothesised that plasma levels of two indices associated with angiogenesis, vascular endothelial growth factor (VEGF) and angiogenin, would be higher among RD patients compared to healthy controls (HC), would relate to CVD risk factors, calculated 10-year coronary heart disease (CHD) and stroke risk scores. METHODS 144 clinic patients with established RD and 63 HC were recruited in a cross-sectional study. RD patients were grouped according to the presence (RD-CVD, n=73 or absence (non-CVD RD; n=71) of CVD risk factors. Angiogenin and VEGF levels were quantified by ELISA. RESULTS There were no significant differences for VEGF or angiogenin, between RD-CVD, non-CVD RD and HC groups (p=NS). Calculated risks for both CHD (p=0.017) and stroke (p=0.016) were higher when RD-CVD was compared to non-CVD RD and HC. Upon multivariate analysis, methotrexate use (p=0.006) and prior mycocardial infarction (MI) (p=0.034) were associated with higher angiogenin levels; body mass index (BMI) (p=0.034) and presence of RD (p=0.029) itself predicted lower levels. For RD patients, serum creatinine (p<0.001) and CRP levels, VEGF levels, and NSAID/COX2 inhibitor use (all p<0.05) were independently associated with CHD risk; plasma VEGF and serum creatinine levels were independently associated with stroke risk (p<0.05). CONCLUSIONS Although levels of angiogenin were not significantly different between HC and RD patients, RD may have some influence on their variation. Methotrexate use and prior MI predicted higher angiogenin levels, whilst levels of VEGF were negatively associated with 10-year CHD and stroke risk.

Plasma indices of endothelial and platelet activation in Rheumatoid Disease: Relationship to cardiovascular co-morbidity

BACKGROUND Rheumatoid Disease (RD) is associated with ischaemic heart disease (IHD). We sought to investigate whether abnormalities of endothelial function and platelet activation in patients with established RD were related to co-morbid cardiovascular risk factors. METHODS In a cross-sectional study, RD patients with no cardiac risk factors and normal cardiac function (RD, n=73), those with cardiovascular disease or risk factors and normal cardiac function (RD-risk, n=59), and those with left ventricular systolic dysfunction (RD-LVSD, n=21) were recruited, and compared to healthy controls (HC, n=76). Plasma levels of von Willebrand factor (vWF, an index of endothelial damage/dysfunction), soluble E-selectin (sE-sel, a marker of endothelial activation), and soluble P-selectin (sP-sel, an index of platelet activation) were studied. RESULTS Plasma levels of vWF and sP-sel (but not sE-sel) were significantly higher among 153 RD patients compared to controls (p=0.002 and p<0.001, respectively). Levels of vWF progressively rose with increasing cardiovascular risk across the four subgroups (p for trend<0.001). Previous IHD was independently associated with vWF levels, and diabetes mellitus (DM) was similarly associated with all three markers. RD itself and beta-blocker use were associated with sP-sel. CONCLUSION Plasma levels of vWF and sP-sel are higher among RD patients. Levels of vWF were particularly influenced by cardiac risk factor status, and associated with known IHD and DM.

Rheumatoid disease and the heart: from epidemiology to echocardiography.

Rheumatoid disease (RD) is a common chronic inflammatory condition associated with progressive joint destruction. Sufferers of RD experience reduced life expectancy, reflected in the increased standardised mortality rates reported in several studies over the last 50 years. Most studies indicate that the increased mortality affecting this population is mainly due to cardio-vascular disease. Epidemiological data have revealed an increased risk of developing ischaemic heart disease and heart failure in RD. The increased risk of ischaemic heart disease may result from traditional risk factors but data suggest that RD may confer risk independently. Although pericardial involvement, valvopathy and myocarditis are the most well-recognised cardiac manifestations of RD, and constitute a rheumatoid heart disease, these features are relatively benign. The current prevalence of rheumatoid heart disease in the era of early administration of disease-modifying therapy requires evaluation.

Evaluation of B-type Natriuretic Peptide for validation of a heart failure register in primary care

BackgroundDiagnosing heart failure and left ventricular systolic dysfunction is difficult on clinical grounds alone. We sought to determine the accuracy of a heart failure register in a single primary care practice, and to examine the usefulness of b-type (or brain) natriuretic peptide (BNP) assay for this purpose.MethodsA register validation audit in a single general practice in the UK was carried out. Of 217 patients on the heart failure register, 56 of 61 patients who had not been previously investigated underwent 12-lead electrocardiography and echocardiography within the practice site. Plasma was obtained for BNP assay from 45 subjects, and its performance in identifying echocardiographic abnormalities consistent with heart failure was assessed by analysing area under receiver operator characteristic (ROC) curves.Results30/217 were found to have no evidence to suggest heart failure on notes review and were probably incorrectly coded. 70/112 who were previously investigated were confirmed to have heart failure. Of those not previously investigated, 24/56 (42.9%) who attended for the study had echocardiographic left ventricular systolic dysfunction. A further 8 (14.3%) had normal systolic function, but had left ventricular hypertrophy or significant valve disease. Overall, echocardiographic features consistent with heart failure were found in only 102/203 (50.2%). BNP was poor at discriminating those with and without systolic dysfunction (area under ROC curve 0.612), and those with and without any significant echocardiographic abnormality (area under ROC curve 0.723).ConclusionIn this practice, half of the registered patients did not have significant cardiac dysfunction. On-site echocardiography identifies patients who can be removed from the heart failure register. The use of BNP assay to determine which patients require echocardiography is not supported by these data.

Drug development and the importance of ethnicity: lessons from heart failure management and implications for hypertension.

Heart failure is a common condition, associated with both poor prognosis and poor quality of life. In contrast to all other cardiovascular diseases, the prevalence of heart failure is increasing in the western world, and is likely to continue to do so as the population ages. In the UK, a significant proportion of patients with heart failure come from South Asian and African Caribbean ethnic groups. A large body of evidence exists that there may be epidemiological and pathophysiological differences between patients with heart failure from different ethnic groups. Treatments such as ACE inhibitors, which are now part of standard heart failure therapy, have an evidence base consisting of trials in patients of almost exclusively white ethnicity. Such treatments may not be equally effective in patients from other ethnic groups. This review will discuss the current evidence for heart failure management with respect to ethnicity, and consider the implications for future drug development and implications for antihypertensive therapy.

Should Heart Failure Be Treated with Antithrombotic Drugs

Congestive heart failure (CHF) is increasing in prevalence in Western society and is associated with considerable morbidity and mortality, including a high risk of venous thromboembolism and stroke. In addition, up to 50% of CHF sufferers die of sudden cardiac death, of which a major mechanism may be thrombotic coronary occlusion leading to myocardial infarction. Thus, antithrombotic therapy would be expected to provide a substantial morbidity and mortality benefit to these patients. However, clinical evidence to support this hypothesis is limited and inconsistent. Aspirin is routinely used in patients with CHF secondary to ischaemic heart disease; however, as yet, no randomised trials of long-term aspirin therapy in CHF have been reported. Since warfarin therapy is associated with a definite risk of bleeding, anticoagulation should be considered only on a case-by-case basis for patients with CHF and additional risk factors (including atrial fibrillation, previous thromboembolic stroke and mural thrombus formation) until more definitive evidence is available.