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

Abstract

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 (Pϭ0.007) subjects and a higher prevalence of atrial fibrillation in EC (Pϭ0.04) subjects. According to the TOAST and Bamford classifications, SA subjects had more small vessel (Pϭ0.04) and lacunar infarctions (Pϭ0.01). SA subjects had higher measurements of arterial stiffness (PϽ0.001) and impaired endothelialdependent vascular function (change in reflective index %; PϽ0.001). On univariate analysis, endothelial function was negatively correlated with fasting plasma glucose (rϭϪ0.4; PϽ0.001) and total cholesterol level (rϭϪ0.2; PϽ0.001).On multivariate analysis, glycemic status was independently associated with impaired endothelial function (Pϭ0.008) and increased arterial stiffness (PϽ0.001) 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. (Stroke. 2009;40:2298-2306.)

Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction

“…Brachial artery FMD and aortic PWV were negatively correlated in the whole population. This finding is in agreement with previous studies performed in mixed populations comprising healthy individuals and patients with different cardiovascular risk factors or established coronary artery disease [3,7,8], also including diabetic patients [4][5][6]. Multiple regression analysis, including vascular determinants of FMD such as baseline brachial artery diameter and hyperaemic shear stress, showed that endotheliumdependent vasodilation remained per se an independent predictor of aortic PWV.…”

“…In particular, endothelium-derived factors such as NO [1] and endothelin-1 [2] have been proposed as physiological modulators of arterial stiffness in healthy individuals. An inverse correlation between endothelial dysfunction and arterial stiffness has been reported in cross-sectional studies performed in mixed cohorts including healthy participants as well as patients with isolated systolic hypertension [3], type 2 diabetes [4][5][6] and coronary artery disease [7][8][9], although conflicting results were obtained in healthy participants [10,11]. Preliminary studies have suggested that vascular correlates of arterial stiffness measurements might differ in patients with cardiovascular risk factors in comparison with healthy individuals [12], also depending on atherosclerotic burden [9], so that studies mixing different populations might be misleading.…”

Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

“…26 Endothelium might have a role in this sense, given the fact that nitric oxide signaling is an important factor in local cerebral blood flow regulation, and that it has been used as a marker to show endothelial dysfunction and decreased vasodilation in response to external stimuli such as hypercapnia or salbutamol in patients with lacunar infarction, compared with controls. 27,28 Second, it has been hypothesized that cerebral SVD may be considered as a systemic condition resulting from dysfunction of arteriolar perfusion. 29 Interestingly, there is now evidence pointing to a systemic endothelial dysfunction in patients with cerebral SVD, as indicated by several studies in which endothelial changes have been measured in other vascular beds other than the brain.…”

Epidemiology of Macrovascular Complications of Diabetes in South Asians and Comparison with Other Ethnicities

“…In the case control INTERHEART study in which risk factors for acute MI were analysed in 52 countries, diabetes was more prevalent in patients with MI from five South Asian countries than rest of the world (9.5% and 7.2%, respectively) [21]. South Asian stroke survivors had higher measurements of arterial stiffness (P<0.001) and impaired endothelial-dependent vascular function (p<0.001) than white Caucasians in West Birmingham Stroke Project and these were associated with glycemic status on multivariate regression analysis [22].…”