Ashan Gunarathne

Ischemic Stroke in South Asians A Review of the Epidemiology, Pathophysiology, and Ethnicity-Related Clinical Features

Within the United Kingdom, mortality from stroke is higher among South Asians compared to European whites. The reasons for this excess cerebrovascular risk in South Asians remain unclear. The aim of this review is to present a comprehensive and systematic overview of the available literature relating to ischemic stroke among South Asian populations identifying distinct features of stroke epidemiology in this group. Summary of Review— A high frequency of lacunar strokes is a familiar pattern among South Asians, which suggests a greater prevalence of small-vessel disease in South Asians. This may be a consequence of abnormal metabolic and glycemic processes. In addition, stroke mortality among South Asians appears to be explained by glycemic status, which is an independent predictor of long-term stroke mortality. Within India, there is a perceptible rural–urban gradient in stroke prevalence, underlying the dangers of the rapid transition in socioeconomic circumstances seen across the Indian subcontinent. Conclusions— This review emphasizes the importance of further research into ischemic stroke for South Asians given their higher cardiovascular disease burden and necessity for targeted healthcare approaches.

Glycemic Status Underlies Increased Arterial Stiffness and Impaired Endothelial Function in Migrant South Asian Stroke Survivors Compared to European Caucasians. Pathophysiological Insights From the West Birmingham Stroke Project

Background— The pathophysiology of an increased risk of cerebrovascular disease mortality among South Asians (SA) remains unclear. Indices of arterial stiffness and endothelial dysfunction are independent markers of vascular disease, having both prognostic and diagnostic implications. We hypothesized that there are ethnic variations in indices of arterial stiffness and endothelial dysfunction between SA and European Caucasian (EC) stroke patients, which may underline a poorer prognosis in the former, and further investigated promoters of vessel wall abnormalities. Methods— Using a cross-sectional approach, a total of 100 SA stroke survivors were prospectively recruited from the ongoing West Birmingham Stroke Project. Indices of vessel wall characteristics (arterial stiffness and endothelial function [change in reflective index]) were measured noninvasively using the digital volume pulse analysis technique in a temperature-controlled environment, using a direct standardized approach. SA stroke subjects were compared to 60 EC stroke survivors, 60 SA with risk factors, and 73 healthy controls. Results— Among stroke patients, both ethnic groups were comparable for cardiovascular risk profile, except for more diabetes mellitus in SA (P=0.007) subjects and a higher prevalence of atrial fibrillation in EC (P=0.04) subjects. According to the TOAST and Bamford classifications, SA subjects had more small vessel (P=0.04) and lacunar infarctions (P=0.01). SA subjects had higher measurements of arterial stiffness (P<0.001) and impaired endothelial-dependent vascular function (change in reflective index %; P<0.001). On univariate analysis, endothelial function was negatively correlated with fasting plasma glucose (r=−0.4; P<0.001) and total cholesterol level (r=−0.2; P<0.001). On multivariate analysis, glycemic status was independently associated with impaired endothelial function (P=0.008) and increased arterial stiffness (P<0.001) among SA subjects. Conclusion— SA stroke survivors had more small vessel disease-related cerebrovascular events compared to EC subjects. Underlying glycemic status in SA subjects had an adverse impact on the vascular system, leading to abnormal vessel wall characteristics.

Impact of mean arterial blood pressure on higher arterial stiffness indices in South Asians compared to white Europeans.

Background The pathophysiology of excessive premature coronary heart disease mortality among South Asians living in Britain remains unclear. We hypothesized that higher measures of arterial stiffness among South Asians compared with their white European counterparts would reflect an earlier progression of atherosclerosis, even in the absence of established coronary heart disease risk indices. Methods Arterial stiffness was measured by digital volume pulse photoplethysmography in 90 healthy South Asians and compared with 62 matched white Europeans in a temperature-controlled environment using a direct, standardized approach. Results Both ethnic groups were comparable for coronary heart disease risk profiles and had similar 10-year coronary heart disease risk estimates, but South Asians had a greater mean (SD) stiffness index compared with white Europeans [9.39 (0.22) vs. 8.43 (0.23) m/s; P = 0.007]. On linear regression analysis, mean arterial blood pressure (β = 0.06; P = 0.03) and age (β = 0.11; P = 0.002) were independent predictors of arterial stiffness in South Asians. Among white Europeans, age was an independent predictor of arterial stiffness (β = 0.05; P = 0.01). Conclusion Healthy South Asians have increased systemic arterial stiffness measured by stiffness index compared with white Europeans. There was an adverse and disproportional impact of age and mean arterial pressure on the vascular system in South Asians. Increased indices of arterial stiffness may explain their increased susceptibility to coronary heart disease.

Elevated angiogenin levels in chronic heart failure

Background. Abnormal indices of angiogenesis have been reported in chronic heart failure (CHF). We tested the hypothesis that circulating angiogenin (a potent inducer of neovascularization in vivo) is higher in CHF patients compared with controls and associated with indices of CHF severity: brain natriuretic peptide (BNP), Simpsons left ventricular ejection fraction (EF), and New York Heart Association (NYHA) class. Methods. Using a cross-sectional approach, we measured serum angiogenin and BNP levels in 109 consecutive patients with CHF (85 males; mean age 60 (standard deviation (SD) 10 yrs) and 112 asymptomatic controls with normal cardiac function and related levels to echocardiographic parameters. Results. Angiogenin was significantly higher in CHF patients compared to controls (P<0.001). On univariate analysis, angiogenin was positively associated with age, plasma glucose, insulin, and BNP (all P<0.001); and negatively correlated with diastolic blood pressure (P=0.04) and EF (P=0.002). Angiogenin levels increased in an ordinal fashion with NYHA class, exaggerated by the presence of diabetes mellitus (pseudo R2=0.15, P<0.001). In multivariate analysis, angiogenin levels were only associated with deteriorating NYHA classification (beta=0.14 (95% confidence interval (CI) 0.09–0.19), P<0.001). Angiogenin was also a modest discriminator for the presence of CHF (area under the curve 0.72; 95% CI 0.62–0.82), P<0.001). Conclusion. Angiogenin is related to worsening heart failure severity (NYHA classification), with the highest levels in NYHA class III. Further research is warranted to determine the validity of angiogenin in a diagnostic and prognostic capacity in CHF.

It's time to reappraise recruitment of South Asians to clinical trials.

Despite a policy of inclusiveness in health care, the United Kingdom has made little progress in improving overall health among marginalised groups.1 There is a pressing need for clinical studies among South Asian, black, and other ethnic minority groups to aid the development of targeted strategies to prevent cardiovascular disease. A 1991 study, for example, showed that South Asians—then 4% of the total UK population—bore a disproportionately high burden of mortality from coronary heart disease and stroke.2 Health issues associated with the ageing of Britain’s ethnic minority population mean that new policy initiatives are urgently needed. Despite this urgency, however, this group is very rarely the focus of clinical investigations to prevent the adverse consequences of this disease burden. The reasons often given for South Asians’ lack of access to clinical trials include language difficulties, poorer access to health care, deprivation, alleged institutional discrimination, and a lack of cross cultural understanding and cultural competence.3 The South Asian population in the West Midlands, for …

151 ASSESSING ARTERIAL STIFFNESS TO IDENTIFY UNEXPECTED CARDIOVASCULAR RISK

Background: Pulse wave velocity [PWV] is recognised as an independent cardiovascular risk factor (1), increasing in proportion to severity of arterial disease. Design and methods: We assessed the application in clinical practice of the validated oscillometric Arteriograph device (Unimedic), which estimates pulse wave velocity (PWA) from pulse wave analysis, using a brachial cuff method to record pulse waves. We used the device in 271 in-patients and out-patients (age 19–96) with a wide range of cardiovascular risk factors (CVRFs), including hypertension, hyperlipidaemia, smoking, diabetes mellitus and chronic kidney disease, estimated aortic PWV 5.2–17.5m/sec. The method was simple to learn and rapid to perform, each reading taking around 2 minutes to complete. The method was well-tolerated, with no subject refusing to have the measurements. Systolic and diastolic pressures were obtained with all Arteriograph readings. Typically up to 5 recordings (∼10 minutes) were needed to obtain at least 2 PWV readings: in a series of 164 recordings in 22 patients, PWV readings were not obtained in 56 of the measurements, most commonly associated with overweight. In 79 patients (70% with hypertension) formally scored, the proportion of patients classified as “low” risk by scoring systems but identified as high CVD risk by PWV was: Framingham: 27%; HeartScore: 25%; Pocock: 56%. Conclusions: A standard clinical protocol should allow for 10 minutes to obtain sufficient PWV measurements to guide clinical management. In our practice PWV obtained using this method identified that at least 25% of patients had under-estimated high cardiovascular risk based on classical CVRFs. Reference:2007 Guidelines for the Management of Arterial Hypertension. The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC). J Hypertens 2007; 25:1105–1187.

120 Disparity in cardiovascular risk stratification between a novel non-invasive arterial stiffness method and three conventional risk scores in a high risk population

Background Current international guidelines for predicting cardiovascular disease (CVD) risk include non-invasive assessment of arterial stiffness. We aimed to evaluate how estimates of pulse wave velocity (PWV), calculated using a new, rapid, validated non-invasive device, compare with traditional risk scores in discriminating patients at increased risk of CVD. Subjects and Methods: We used a non-invasive oscillometric device (Arteriograph, Unimedic Ltd) to estimate PWV in patients with and without established CVD (n=80, 79% male; mean age 67±1(SEM)years). Risk factors included hypertension (70%), hypercholesterolaemia (65%), type 2 diabetes mellitus (35%) and current smoking (18%). 59% had clinical ischaemic heart disease. Individuals were categorised as ‘high’ or ‘low’ CVD risk according to published thresholds using 3 established methods (Framingham (JBS2) risk charts, European Society of Cardiology (ESC) HeartScore® and the Pocock risk score). Data were analysed using SPSS (version 14.0). The study was approved by the local research ethics committee. Results PWV was positively correlated (Spearman) with increasing risk estimated by all three scoring systems (Framingham rs = 0.420, p = 0.001; HeartScore rs = 0.394, p = 0.000; Pocock rs = 0.305, p = 0.006). For all three scoring systems, in at least 25% of subjects assessed as low risk, PWV indicated CVD high risk (Framingham: 27%; HeartScore: 25%; Pocock: 44%). In contrast, around half of our subjects identified as ‘high’ risk by conventional risk scores, were identified as in the low CVD risk category when assessed by PWV (Framingham: 49%; HeartScore: 47%; Pocock: 50%). Conclusion We observed important disagreement in the stratification of CVD risk in a high risk population by an index of arterial stiffness compared with commonly used risk scores. One interpretation of our data is that combination of non-invasive measurements of arterial stiffness with classical CVD risk scoring systems may improve stratification in high risk populations. However, further prospective work is needed to determine clinical outcomes for patients misclassified by assessment of arterial stiffness compared with classical risk scoring. This will help to test the clinical utility of combined risk scoring and arterial stiffness, in producing finer CVD risk stratification.

Response to Letter by De Silva et al

Response: We are thankful for the helpful comments from De Silva and colleagues with respect to our review on “Ischemic Stroke in South Asians” published in Stroke (2009;40:e415–e423). In Table 1, with reference to De Silva …