Stroke In South Asians Research Articles

NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke

The genetic factors of stroke in South Asians are largely unexplored. Exome-wide sequencing and association analysis (ExWAS) in 75 K Pakistanis identified NM_000435.3(NOTCH3):c.3691 C > T, encoding the missense amino acid substitution p.Arg1231Cys, enriched in South Asians (alternate allele frequency = 0.58% compared to 0.019% in Western Europeans), and associated with subcortical hemorrhagic stroke [odds ratio (OR) = 3.39, 95% confidence interval (CI) = [2.26, 5.10], p = 3.87 × 10−9), and all strokes (OR [CI] = 2.30 [1.77, 3.01], p = 7.79 × 10−10). NOTCH3 p.Arg231Cys was strongly associated with white matter hyperintensity on MRI in United Kingdom Biobank (UKB) participants (effect [95% CI] in SD units = 1.1 [0.61, 1.5], p = 3.0 × 10−6). The variant is attributable for approximately 2.0% of hemorrhagic strokes and 1.1% of all strokes in South Asians. These findings highlight the value of diversity in genetic studies and have major implications for genomic medicine and therapeutic development in South Asian populations.

Mendelian Randomization and Bayesian Colocalization Analysis Implicate Glycoprotein VI as a Potential Drug Target for Cardioembolic Stroke in South Asian Populations.

Circulating plasma proteins are clinically useful biomarkers for stroke risk. We examined the causal links between plasma proteins and stroke risk in individuals of South Asian ancestry. We applied proteome-wide Mendelian randomization and colocalization approaches to understand causality of 2922 plasma proteins on stroke risk in individuals of South Asian ancestry. We obtained genetic instruments (proxies) for plasma proteins from the UK Biobank (N=920). Genome-wide association studies summary data for strokes (N≤11 312) were sourced from GIGASTROKE consortium. Our primary approach involved the Wald ratio or inverse-variance-weighted methods, with statistical significance set at false discovery rate <0.1. Additionally, a Bayesian colocalization approach assessed shared causal variants among proteome, transcriptome, and stroke phenotypes to minimize bias from linkage disequilibrium. We found evidence of a potential causal effect of plasma GP6 (glycoprotein VI) levels on cardioembolic stroke (odds ratio [OR]Wald ratio=2.53 [95% CI, 1.59-4.03]; P=9.2×10-5, false discovery rate=0.059). Generalized Mendelian randomization accounting for correlated single nucleotide polymorphisms (SNPs), with the P value threshold at P<5×10-8 and clumped at r2=0.3, showed consistent direction of effect of GP6 on cardioembolic stroke (ORgeneralized inverse-variance-weighted=2.21 [95% CI, 1.46-3.33]; P=1.6×10-4). Colocalization analysis indicated that plasma GP6 levels colocalize with cardioembolic stroke (posterior probability=91.4%). Multitrait colocalization combining transcriptome, proteome, and cardioembolic stroke showed moderate to strong evidence that these 2 traits colocalize with GP6 expression in the coronary artery and brain tissues (multitrait posterior probability>50%). The potential causal effect of GP6 on cardioembolic stroke was not significant in European populations (ORinverse-variance-weighted=1.08 [95% CI, 0.93-1.26]; P=0.29). Our joint Mendelian randomization and colocalization analyses suggest that genetically predicted GP6 is potentially causally associated with cardioembolic stroke risk in individuals of South Asian ancestry. As genetic data on individuals of South Asian ancestry increase, future Mendelian randomization studies with larger sample size for plasma GP6 levels should be implemented to further validate our findings. Additionally, clinical studies will be necessary to verify GP6 as a therapeutic target for cardioembolic stroke in South Asians.

Diabetes mellitus and obesity among South Asians with ischemic stroke across three countries.

Diabetes mellitus and central obesity are more common among South Asian populations than among White British people. This study explores the differences in diabetes and obesity in South Asians with stroke living in the United Kingdom, India, and Qatar compared with White British stroke patients. The study included the UK, Indian, and Qatari arms of the ongoing large Bio-Repository of DNA in Stroke (BRAINS) international prospective hospital-based study for South Asian stroke. BRAINS includes 4580 South Asian and White British recruits from UK, Indian, and Qatar sites with first-ever ischemic stroke. The study population comprises 1751 White British (WB) UK residents, 1165 British South Asians (BSA), 1096 South Asians in India (ISA), and 568 South Asians in Qatar (QSA). ISA, BSA, and QSA South Asians suffered from higher prevalence of diabetes compared with WB by 14.5% (ISA: 95% confidence interval (CI) = 18.6-33.0, p < 0.001), 31.7% (BSA: 95% CI = 35.1-50.2, p < 0.001), and 32.7% (QSA: 95% CI = 28.1-37.3, p < 0.001), respectively. Although WB had the highest prevalence of body mass index (BMI) above 27 kg/m2 compared with South Asian patients (37% vs 21%, p < 0.001), South Asian patients had a higher waist circumference than WB (94.8 cm vs 90.8 cm, p < 0.001). Adjusting for traditional stroke risk factors, ISA, BSA, and QSA continued to display an increased risk of diabetes compared with WB by 3.28 (95% CI: 2.53-4.25, p < 0.001), 3.61 (95% CI: 2.90-4.51, p < 0.001), and 5.24 (95% CI: 3.93-7.00, p < 0.001), respectively. South Asian ischemic stroke patients living in Britain and Qatar have a near 3.5-fold risk of diabetes compared with White British stroke patients. Their body composition may partly help explain that increased risk. These findings have important implications for public health policymakers in nations with large South Asian populations.

Exploring the Poststroke Experiences and Needs of South Asian Communities Living in High-Income Countries: Findings from a Scoping Review.

Despite the high prevalence of stroke among South Asian communities in high-income countries, a comprehensive understanding of their unique experiences and needs after stroke is lacking. This study aimed to synthesize the literature examining the experiences and needs of South Asian community members impacted by stroke and their family caregivers residing in high-income countries. A scoping review methodology was utilized. Data for this review were identified from seven databases and hand-searching reference lists of included studies. Study characteristics, purpose, methods, participant characteristics, results, limitations, recommendations, and conclusions were extracted. Data were analyzed using descriptive qualitative analysis. In addition, a consultative focus group exercise with six South Asian community members who had experienced a stroke and a program facilitator was conducted to inform the review interpretations. A total of 26 articles met the inclusion criteria and were analyzed. Qualitative analysis identified four descriptive categories: (1) rationale for studying the South Asian stroke population (e.g., increasing South Asian population and stroke prevalence), (2) stroke-related experiences (e.g., managing community support versus stigma and caregiving expectations), (3) stroke service challenges (e.g., language barriers), and (4) stroke service recommendations to address stroke service needs (e.g., continuity of care). Several cultural factors impacted participant experiences, including cultural beliefs about illness and caregiving. Focus group participants from our consultation activity agreed with our review findings. The clinical and research recommendations identified in this review support the need for culturally appropriate services for South Asian communities across the stroke care continuum; however, more research is necessary to inform the design and structure of culturally appropriate stroke service delivery models.

Ischaemic stroke in South Asians: The BRAINS study.

Studies on stroke in South Asian populations are sparse. The aim of this study was to compare differences in age of onset of ischaemic stroke in South Asian patients living in the United Kingdom and South Asian patients living in India versus White British stroke patients. We studied the UK and Indian arms of the ongoing BRAINS study, an international prospective hospital-based study of South Asian stroke patients. The BRAINS study includes 4038 South Asian and White British patients with first-ever ischaemic stroke, recruited from sites in the United Kingdom and India. Of the included patients, 1126 were South Asians living in India (ISA), while 1176 were British South Asian (BSA) and 1736 were White British (WB) UK residents. Patients in the ISA and BSA groups experienced stroke 19.5 years and 7.2 years earlier than their WB counterparts, respectively (mean [interquartile range] age: BSA 64.3[22]years vs. ISA 52.0[18]years vs. WB 71.5[19]years; p < 0.001). Patients in the BSA group had higher rates of hypertension, diabetes mellitus and hypercholesterolaemia than those in the ISA and WB groups. After adjustment for traditional stroke risk factors, an earlier age of stroke onset of 18.9 years (p < 0.001) and 8.9 years (p < 0.001) was still observed in the ISA and BSA groups, respectively. In multivariable stepwise linear regression analysis, ethnicity accounted for 24.7% of the variance in early age onset. Patients in the BSA and ISA groups experienced ischaemic stroke approximately 9 and 19 years earlier, respectively, than their WB counterparts. Ethnicity is an independent predictor of early age of stroke onset. Our study has considerable implications for public health policymakers in countries with sizable South Asian populations.

Prevalence and correlates of carotid artery stenosis in a cohort of Sri Lankan ischaemic stroke patients

BackgroundLarge artery atherosclerotic disease is an important cause of stroke, accounting for 15–46% of ischaemic strokes in population-based studies. Therefore, current guidelines from west recommend urgent carotid imaging in all ischaemic strokes or transient ischaemic attacks and referral for carotid endarterectomy. However, the clinical features and epidemiology of stroke in Asians are different from those in Caucasians and therefore the applicability of these recommendations to Asians is controversial. Data on the prevalence of carotid artery stenosis (CAS) among South Asian stroke patients is limited. Therefore, we sought to determine the prevalence and associated factors of significant CAS in a cohort of Sri Lankan patients with ischaemic stroke.MethodsWe prospectively studied all ischaemic stroke patients who underwent carotid doppler ultrasonography admitted to the stroke unit of a Sri Lankan tertiary care hospital over 5 years. We defined carotid stenosis as low (< 50%), moderate (50–69%) or severe (70–99%) or total-occlusion (100%) by North American Symptomatic Trial Collaborators (NASCET) criteria. We identified the factors associated with CAS ≥ 50% and ≥ 70% by stepwise multiple logistic regression analysis.ResultsA total of 550 ischaemic stroke patients (326 (59.3%) male, mean age was 58.9 ± 10.2 years) had carotid doppler ultrasonography. Of them, 528 (96.0%) had low-grade, 12 (2.2%) moderate and 7 (1.3%) severe stenosis and 3 (0.5%) had total occlusion. On multivariate logistic regression, age was associated with CAS ≥ 50% (OR 1.12, p = 0.001) and CAS ≥ 70% (OR 1.14, p = 0.016), but none of the other vascular risk factors studied (sex, hypertension, diabetes mellitus, smoking, past history of TIA, stroke or ischemic heart disease) showed significant associations.ConclusionsCarotid stenosis is a minor cause of ischemic stroke in Sri Lankans compared to western populations with only 4.0% having CAS ≥ 50 and 3.5% eligible for carotid endarterectomy. Our findings have implications for the management of acute strokes in Sri Lanka.

Emerging Risk Factors for Stroke: What Have We Learned From Mendelian Randomization Studies?

Establishing new approaches for the prevention and treatment of stroke relies on identifying modifiable risk factors that contribute to the development of this complex disease. Mendelian randomization (MR) studies, analogous to naturally occurring randomized trials, can assess causality of potentially modifiable biomarkers and offer new insights into biological pathways. Stroke is the second leading cause of death worldwide and the chief determinant of long-term disability. Stroke is a heterogeneous disease arising from several distinct underlying pathologies and is typically classified as ischemic or hemorrhagic, and further subclassified using imaging data. Ischemic stroke (IS), including its 3 main subtypes: small vessel disease, large vessel disease, and cardioembolic stroke, accounts for ≈80% of stroke and is the result of an interrupted blood supply, leading to localized areas of ischemia in the brain. Small vessel disease may be a consequence of nonatherosclerotic, as well as atherosclerotic, mechanisms that result in an occlusion of the small perforating arteries, whereas large vessel disease results from occlusions or emboli from plaque rupture in larger vessels, such as a carotid artery. Cardioembolic stroke arises typically from emboli from the heart. By contrast, hemorrhagic stroke is a consequence of intracerebral hemorrhage (bleeding into the brain) or subarachnoid hemorrhage (bleeding into the subarachnoid space). These diverse stroke subtypes have distinct underlying pathologies reflecting different risk factor distributions. MR studies, using genetic variants as instrumental variables, afford a powerful approach to assessing causality of risk factors and avoid biases inherent in observational studies, including confounding and reverse causation. This review considers the contribution of MR studies to stroke epidemiology and their relevance to understanding risk factors and new therapeutic targets for stroke. Meta-analyses of large prospective studies have enhanced our knowledge of classical and emerging risk factors for stroke.1–4 Classical risk factors for stroke include nonmodifiable characteristics, …

Abstract TP176: Stroke Recurrence Among South Asians With diabetes in Ontario, Canada

Introduction: South Asians have earlier cardiovascular disease onset and higher stroke mortality than non-South Asians, but disparities in long-term outcomes after stroke in patients with diabetes are not well described. We compared risk of cardiovascular outcomes after first ischemic stroke between South Asian and non-South Asian patients with diabetes. Hypothesis: We hypothesized that South Asian stroke patients with diabetes were younger and had higher stroke recurrence, even accounting for competing risk of death. Methods: Using population-based health care databases in Ontario, Canada, we selected all patients with diabetes hospitalized with first ischemic stroke between April 1, 2002 and March 31, 2012, and assigned South Asian vs. non-South Asian ethnicity using a validated surname algorithm. Kaplan-Meier survival analysis and competing risk models estimated risk of death, stroke, and myocardial infarction. The primary predictor was ethnicity; models were adjusted for demographics and vascular risk factors. Sensitivity analysis including adjustment for medication use was performed in those aged &gt;=65 years. Results: There were 25495 diabetics with first ischemic stroke; 840 were South Asian and were younger, more often male, had lower income, and had shorter Ontario residency compared to non-South Asians. South Asians had higher incidence and cumulative risk of recurrent stroke (Figure). In adjusted competing risk models, recurrent stroke risk was increased among South Asians compared to non-South Asians (HR 1.17 [95% CI 1.00-1.38]) in the whole cohort and in those aged &gt;=65 years, both with adjustment for medication use (HR 1.23 [1.01-1.50]) and without (1.27 [1.04-1.54]). Conclusions: In this large population-based study, South Asian stroke patients with diabetes had higher recurrent stroke risk compared to non-South Asians, despite younger age. Further research and targeted interventions are needed to reduce stroke burden in South Asians.

Ethnic Differences in Associations Between Blood Pressure and Stroke in South Asian and European Men.

It is unknown whether associations between blood pressure (BP) and stroke vary between Europeans and South Asians, despite higher stroke rates in the latter. We report findings from a UK cohort study of 1375 European and 1074 South Asian men, not receiving antihypertensive medication, aged 40 to 69 years at baseline (1988-1991). Assessment included BP, blood tests, anthropometry, and questionnaires. Incident stroke was established at 20 years from death certification, hospital and primary care records, and participant report. South Asians had higher systolic BP, diastolic BP, and mean arterial pressure than Europeans, and similar pulse pressure. Associations between systolic BP or diastolic BP and stroke were stronger in South Asians than Europeans, after adjustment for age, smoking status, waist/hip ratio, total/high-density lipoprotein-cholesterol ratio, diabetes mellitus, fasting glucose, physical activity, and heart rate (systolic BP: Europeans [odds ratio, 1.22; 95% confidence interval, 0.98-1.51], South Asians [1.56; 1.24-1.95]; ethnic difference P=0.04; diastolic BP: Europeans [0.90; 0.71-1.13], South Asians [1.68; 1.32-2.15]; P<0.001). Hemodynamic correlates of stroke risk differed by ethnicity: in combined models, mean arterial pressure but not pulse pressure was detrimentally associated with stroke in South Asians, whereas the converse was true for Europeans. The combination of hyperglycemia and hypertension appeared particularly detrimental for South Asians. There are marked ethnic differences in associations between BP parameters and stroke. Undue focus on systolic BP for risk prediction, and current age and treatment thresholds may be inappropriate for individuals of South Asian ancestry.

Mean arterial pressure is a stronger predictor of stroke in South Asian than European men, independent of other cardiometabolic risk factors; the SABRE study

Background: Stroke risk is greater in South Asians than Europeans. We sought to compare associations between blood pressure (BP) and stroke by ethnicity and determine how BP contributes to ethnic differences in disease. Methods: Population sample of 1510 European and 1195 South Asian men recruited between 1988-1991, mean age 52 7yrs. Incident fatal and nonfatal strokes were captured over 20 years of follow-up. Cox models demonstrated associations between mean arterial BP (MAP) and stroke. Results: South Asians had more incident strokes than Europeans (5.6 (4.7,6.7) versus 4.7 (4.0,5.6) per 1000 person years, age-adjusted hazard ratio:1.40 (1.08,1.76), pZ0.01) and higher MAPs than Europeans (97 12 versus 93 12mmHg, p<0.0001). MAP was more strongly associated with stroke in South Asians than Europeans, (HR (95% CI): 1.59(1.35,1.86) versus 1.19(1.00,1.43) respectively, ethnicity interaction pZ0.03), even accounting for receipt of anti-hypertensive medication (1.57(1.32,1.86 versus 1.10(0.91,1.32), interaction pZ0.03). The ethnic difference in impact of MAP diminished after further adjustment for smoking, waist circumference, HDL, fasting glucose, HOMA2IR, HbA1c and heart rate (1.40(1.12,1.75) versus 1.15(0.92,1.42), interaction pZ0.24). However, the greater effect of MAP on stroke in South Asians persisted when this latter model was restricted to people not receiving anti-hypertensive medications, (1.57(1.26,1.96) versus 1.08(0.85,1.37), interaction pZ0.02). Adjustment for MAP could not account for the excess stroke risk in South Asians (1.27 (1.00, 1.62) pZ0.05), nor could other risk factors. Conclusions: MAP had a greater impact on stroke risk in South Asians than Europeans, but could not account for their excess stroke risk, alone or in conjunction with additional risk factors.

Detailed Analysis of Gene Polymorphisms Associated with Ischemic Stroke in South Asians

The burden of stroke is disproportionately high in the South Asian subcontinent with South Asian ethnicity conferring a greater risk of ischemic stroke than European ancestry regardless of country inhabited. While genes associated with stroke in European populations have been investigated, they remain largely unknown in South Asians. We conducted a comprehensive meta-analysis of known genetic polymorphisms associated with South Asian ischemic stroke, and compared effect size of the MTHFR C677T-stroke association with effect sizes predicted from homocysteine-stroke association. Electronic databases were searched up to August 2012 for published case control studies investigating genetic polymorphisms associated with ischemic stroke in South Asians. Pooled odds ratios (OR) for each gene-disease association were calculated using a random-effects model. We identified 26 studies (approximately 2529 stroke cases and 2881 controls) interrogating 33 independent genetic polymorphisms in 22 genes. Ten studies described MTHFR C677T (108 with TT genotype and 2018 with CC genotype) -homocysteine relationship and six studies (735 stroke cases and 713 controls) described homocysteine-ischemic stroke relationship. Risk association ORs were calculated for ACE I/D (OR 5.00; 95% CI, 1.17–21.37; p = 0.03), PDE4D SNP 83 (OR 2.20; 95% CI 1.21–3.99; p = 0.01), PDE4D SNP 32 (OR 1.57; 95% CI 1.01–2.45, p = 0.045) and IL10 G1082A (OR 1.44; 95% CI, 1.09–1.91, p = 0.01). Significant association was observed between elevated plasma homocysteine levels and MTHFR/677 TT genotypes in healthy South Asians (Mean difference (ΔX) 5.18 µmol/L; 95% CI 2.03–8.34: p = 0.001). Our results demonstrate that the genetic etiology of ischemic stroke in South Asians is broadly similar to the risk conferred in Europeans, although the dataset is considerably smaller and warrants the same clinical considerations for risk profiling.

Abstract P126: Risk Factor Profiles of South Asians with Cerebrovascular Disease: Findings from a Community-Based Prevalence Study in Semiurban Pakistan

Background There is a paucity of population based data about the coexistent prevalence of risk factors for stroke in South Asians. Methods In this cross sectional survey performed in an urban slum, individuals 35 years of age or older were invited for participation through simple random sample drawn from baseline census data. For each participant a systematic history and examination was performed to confirm the following risk factors: Diabetes, Hypertension, Obesity, Tobacco Use, Coronary Artery Disease, Family History of Coronary Artery Disease and/or Stroke. Cerebrovascular events (stroke and TIA) were verified by a vascular neurologist. We report the association of risk factor groups and the presence of contemporaneous cerebrovascular event (CVE). Results Five hundred and forty five individuals (49.4% females 269 out of 545) participated in the study. Cerebrovascular event (Stroke and /or TIA) were found in “21.8% (119 out of 545)” individuals. Obesity was found to be the predominant risk factor, occurring in “56.9% (310 out of 545)”, followed by total hypertension “52.1% (284 out of 545)” and tobacco use respectively “39% (213 out of 545)”. There were “63.3% (345 out of 545) individuals with two or more risk factors, with the majority of these being women (54.6%). CVE increased in percentage with quantitative increase in risk factors, with 13% of CVE in individuals with no risk factors to 85.7% CVE among those with 5 risk factors. The combination of Hypertension, Diabetes, Obesity and cigarette smoking conferred the highest odds at 4.9 (p=0.039). Conclusion A systematic screening within South Asians with cerebrovascular disease will uncover multiple preventable risk factors.

Risk Factor Profiles of South Asians with Cerebrovascular Disease

There is a paucity of population based data about the coexistent proportions of risk factors for stroke in South Asians. In this cross sectional survey performed in an urban slum, individuals 35 years of age or older were invited for participation through a simple random sample drawn from baseline census data. For each participant a systematic history and examination was performed to confirm the following risk factors: diabetes, hypertension, obesity, tobacco use, coronary artery disease, family history of coronary artery disease and/or stroke. Cerebrovascular events (stroke and TIA) were verified by a vascular neurologist. We report the association of risk factor groups and the presence of contemporaneous cerebrovascular event. Five hundred and forty-five individuals (49.4% females) participated in the study. One hundred and nineteen (21.8%) individuals had a cerebrovascular event (stroke and /or TIA). Obesity was found to be the predominant risk factor, occurring in 310 individuals (56.9%), followed by total hypertension (284; 52.1%) and tobacco use respectively (213; 39%). Cerebrovascular event increased in percentage with quantitative increase in risk factors. Cerebrovascular event prevalence was 14.3% with one risk factor, 22% with two, 27% with three, 33% with four, and 86% with five risk factors respectively. The combination of 4 risk factors (hypertension, diabetes, obesity and cigarette smoking) conferred the highest odds of having cerebrovascular event at 4.9 (P 0.03). South Asians in an urban slum often have multiple modifiable risk factors for cerebrovascular event, increasing numbers of risk factors increase the risk of stroke and TIA.

The First Indian-Origin Family with Genetically Proven Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)

We report the first family of Indian origin known to be affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Seventeen members of the family spanning 3 generations had neurologic syndromes compatible with CADASIL, of whom 5 were genetically confirmed carriers of the Notch3 gene R141C mutation in exon 4 (421(C→T) and 141(Cys→Arg)). Our report highlights that CADASIL not only occurs sporadically in South Asians, but also may account for stroke in South Asians with a strong family history. Furthermore, the similarity of clinical presentations described here to those typical for Caucasian case series suggests that the CADASIL phenotype is preserved across racial groups.

South Asians have adverse cerebrovascular haemodynamics, despite equivalent blood pressure, compared with Europeans. This is due to their greater hyperglycaemia

South Asians have a 1.5-fold increased stroke mortality compared with Europeans, despite similar blood pressures (BP). We hypothesized that it is the greater hyperglycaemia in South Asians that increases stroke risk, by adversely affecting cerebrovascular haemodynamics. A population-based sample of 149 Europeans and 151 South Asians underwent metabolic profiling and concurrent measurement of finger BP using a Finapres and middle cerebral artery (MCA) blood flow velocity using transcranial Doppler ultrasound. Cerebrovascular autoregulation, cerebrovascular resistance [resistive index (RI) and pulsatility index (PI)] were calculated. Means of cerebrovascular haemodynamic measures were compared by ethnicity, with the introduction of explanatory variables to a regression model to determine which variable could best account for ethnic differences. Cerebrovascular resistance (RI) was 12.9 × 10(3) (0.9-24.8, P = 0.04) greater in South Asians than Europeans. Systolic, diastolic and mean MCA velocities were also higher in South Asians (mean velocity 41.4 ± 8.0 cm/s vs 38.0 ± 8.0 cm/s, respectively, P = 0.001). Low frequency gain, a measure of autoregulation, was worse in South Asians compared with Europeans (0.50 ± 0.01 cm/s mm/Hg vs 0.45 ± 0.01 cm/s mm/Hg, P = 0.01). RI positively correlated with HbA(1c) (r = 0.184; P < 0.01). Adjustment for BP could not explain the higher RI in South Asians, but adjustment for HbA(1c) abolished the ethnic difference in RI (5.8 × 10(3) (-6.5 to 18.1, P = 0.4). Cerebrovascular resistance and autoregulation are worse in South Asians than in Europeans, despite equivalent resting BP. The greater hyperglycaemia in South Asians accounts for their adverse cerebrovascular resistance. This could explain excess stroke in South Asians but requires testing in longitudinal studies.

Effects of Intensive Blood Pressure Control in the Management of Patients With Type 2 Diabetes Mellitus in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

To appreciate the importance of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial,1 one needs to remember that the systolic blood pressure (BP) target currently recommended by major guidelines for diabetic patients, that is, 130 mm Hg, except in the Appropriate Blood Pressure Control in Diabetes Study (ABCD) normotensive trial,7 which consisted of only a few hundred patients and had changes in creatinine clearance as the primary end point. Thus, ACCORD represents the only large-scale randomized trial that provides information on what happens to the cardiovascular risk of diabetic patients when SBP is reduced to 130 mm Hg as a result of randomization to the usual (rather than the tight) BP control treatment strategy. Thus, the message from ACCORD to guidelines and clinical practice is that in diabetic patients it is not necessary to adopt …

The risk factors for stroke in south Asians identified

The risk factors for stroke in south Asians identified

Ischemic Stroke in Ethnic South Asians

To the Editor: The article by Gunarathne et al on “Ischemic Stroke in South Asian”1 is timely in providing a review of the epidemiology of stroke in ethnic South Asians, the largest ethnic group in the world. We would like to clarify the key findings of our article, “Ischemic Cerebrovascular Disease: Difference Between Ethnic South Asians and Ethnic Chinese Patients,”2 referenced by Gunarathne et al in the article. As described, we compared ethnic South Asian patients with ischemic cerebrovascular disease with ethnic Chinese counterparts in Singapore. Contrary to the statement in Table 1 and …

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 …

Glycemic Status Underlies Increased Arterial Stiffness and Impaired Endothelial Function in Migrant South Asian Stroke Survivors Compared to European Caucasians

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. 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. 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. 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.