Fung-Peng Woon

South Asian Patients With Ischemic Stroke Intracranial Large Arteries Are the Predominant Site of Disease

Background and Purpose— South Asians are the most prevalent ethnic group in the world. Intracranial disease is the most common vascular lesion worldwide. Methods— We prospectively studied 200 consecutive ethnic South Asian patients with acute ischemic stroke in Singapore. Results— Intracranial large-artery disease was prevalent among 54% of all stroke subtypes and was independently associated with hypertension and higher serum erythrocyte sedimentation rate. Conclusions— Among ethnic South Asian patients with ischemic stroke, intracranial large arteries are the predominant site of disease.

PINK1 mutations in sporadic early‐onset Parkinson's disease

Pathogenic PINK1 mutations have been described in PARK6‐linked Parkinsons disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early‐onset Parkinsons disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1‐positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon–intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1‐positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.

Association of acute ischemic stroke with the MTHFR C677T polymorphism but not with NOS3 gene polymorphisms in a Singapore population

Background and purpose:  The association of polymorphisms in the nitric oxide synthase 3 (NOS3) gene (T‐786C, variable number tandem repeats 4A/B/C, and G894T) and in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) with acute ischemic stroke have been reported.

Retinal microvascular changes and subsequent vascular events after ischemic stroke.

Objectives: Retinal microvasculature changes are associated with vascular events including stroke in healthy populations. It is not known whether retinal microvascular changes predict recurrent vascular events after ischemic stroke. We examined the relationship between retinal microvascular signs and subsequent vascular events in a prospective cohort of 652 acute ischemic stroke patients admitted to a tertiary hospital in Singapore from 2005 to 2007. Methods: Retinal photographs taken within 1 week of stroke onset were assessed in a masked manner for quantitative and qualitative measures. Follow-up data over 2–4 years were obtained by standardized telephone interview and then were verified from medical records. Predictors of recurrent vascular events (cerebrovascular, coronary, vascular death, and composite vascular events) were determined using Cox regression models. Results: Follow-up data over a median of 29 months were obtained for 89% (652 patients) of the cohort. After adjustment for covariates including traditional risk factors and index stroke etiology, patients with severe arteriovenous nicking (AVN) were more likely to have a recurrent cerebrovascular event (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.20–4.33) compared with those without AVN. Patients with severe focal arteriolar narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR 2.75, 95% CI 1.14–6.63) or subsequent composite vascular event (HR 2.77, 95% CI 1.31–5.86) compared to those without FAN. Conclusions: Retinal microvascular changes predicted subsequent vascular events after ischemic stroke, independent of traditional risk factors and stroke subtype. Thus, retinal imaging has a potential role in predicting the risk of recurrent vascular events after ischemic stroke and in understanding novel vascular risk factors.

Arterial Stiffness is associated with intracranial large artery disease among ethnic Chinese and South Asian ischemic stroke patients.

Objective Intracranial large artery disease (ICLAD) is a common stroke subtype that carries a poor prognosis. We studied the association of arterial stiffness, a recognized risk factor for atherosclerosis and ICLAD among ethnic Chinese and South Asian ischemic stroke patients. Methods In this prospective study, we recruited consecutive ischemic stroke patients of Chinese and South Asian ethnicity. ICLAD was assessed by transcranial color-coded Doppler or magnetic resonance angiographic studies. Arterial stiffness was measured by carotid-femoral pulse wave velocity (cPWV). Results Among the 268 patients studied, the prevalence of ICLAD was 54% and median cPWV was 11.4 m/s (interquartile range 9.0–13.6 m/s). Patients with ICLAD had higher cPWV compared with those without (median 11.7 vs. 11.0 m/s, P = 0.015). In multivariate analysis, patients with ICLAD were significantly more likely to have cPWV measurements in the highest quintile (>14.1 m/s) compared with patients without ICLAD independently of other covariates [odds ratio 2.21, P = 0.038]. Conclusion This study revealed a novel association between arterial stiffness and ICLAD among ischemic stroke patients. The findings suggest that arterial stiffness may be involved in the pathophysiology of ICLAD. Future studies should investigate the effects of reducing arterial stiffness among stroke patients with ICLAD.

Associations of Retinal Microvascular Signs and Intracranial Large Artery Disease

Background and Purpose— Intracranial large artery disease (ICLAD) is a major cause of ischemic stroke. Retinal microvascular changes are associated with stroke, including small vessel cerebral disease and extracranial carotid disease. We examined the relationship between ICLAD and retinal microvascular changes. Methods— This is a prospective cohort of 802 acute ischemic stroke patients. Retinal changes were assessed from photographs by graders masked to clinical data. ICLAD was evaluated using prespecified criteria. Results— ICLAD was not associated with ipsilateral retinal arteriolar/venular caliber, focal arteriolar narrowing, or arteriovenous nicking. Severe enhanced arteriolar light reflex was independently associated with any ICLAD (P=0.006) and severe ICLAD (P<0.001). Conclusion— Enhanced arteriolar light reflex, but not retinal vessel caliber, was related to ICLAD. These data suggest that retinal microvascular signs have specific associations with large cerebral vessel disease.

Metabolic Syndrome Is Associated with Intracranial Large Artery Disease among Ethnic Chinese Patients with Stroke

BACKGROUND The association of metabolic syndrome (MetS) and intracranial large artery disease (ICLAD) has been described, but only in cohorts of ethnic Korean patients with stroke. We investigated the relationship of MetS and ICLAD among ethnic Chinese patients. METHODS This is a prospective study of consecutive ethnic Chinese patients with acute ischemic stroke living in Singapore. ICLAD was diagnosed on transcranial color-coded Doppler or magnetic resonance angiography. RESULTS Among the 135 patients studied, the frequency of MetS was higher among patients with ICLAD (39% v 16%, P = .003). This association was independent of age, hypertension, and diabetes (P = .003), and individual MetS criteria (P = .004). The prevalence of ICLAD positively correlated with the number of MetS criteria fulfilled (P = .021). CONCLUSIONS Our findings of an association between MetS and ICLAD among ethnic Chinese patients with stroke concur with findings among ethnic Korean patients. This validation provides a basis for further investigation into the pathophysiologic link between MetS and ICLAD.

Arterial stiffness, metabolic syndrome and inflammation amongst Asian ischaemic stroke patients

Background and purpose:  Arterial stiffness and metabolic syndrome (MetS) are risk factors for ischaemic stroke. We studied the association of arterial stiffness, measured by carotid–femoral pulse wave velocity (PWV) and MetS amongst ischaemic stroke patients. We also investigated the role of inflammation measured by serum erythrocyte sedimentation rate (ESR) in the metabolic syndrome–arterial stiffness relationship.

The relationship between aortic stiffness and changes in retinal microvessels among Asian ischemic stroke patients.

Large-artery stiffness is a risk factor for stroke, including cerebral small-vessel disease. Retinal microvascular changes are thought to mirror those in cerebral microvessels. We investigated the relationship between aortic stiffness and retinal microvascular changes in Asian ischemic stroke patients. We studied 145 acute ischemic stroke patients in Singapore who had aortic stiffness measurements using carotid–femoral pulse wave velocity (cPWV). Retinal photographs were assessed for retinal microvessel caliber and qualitative signs of focal arteriolar narrowing, arteriovenous nicking and enhanced arteriolar light reflex. Aortic stiffening was associated with retinal arteriolar changes. Retinal arteriolar caliber decreased with increasing cPWV (r=−0.207, P=0.014). After adjusting for age, gender, hypertension, diabetes, mean arterial pressure and small-vessel stroke subtype, patients within the highest cPWV quartile were more likely to have generalized retinal arteriolar narrowing defined as lowest caliber tertile (odds ratio (OR) 6.84, 95% confidence interval (CI) 1.45–32.30), focal arteriolar narrowing (OR 13.85, CI 1.82–105.67), arteriovenous nicking (OR 5.08, CI 1.12–23.00) and enhanced arteriolar light reflex (OR 3.83, CI 0.89–16.48), compared with those within the lowest quartile. In ischemic stroke patients, aortic stiffening is associated with retinal arteriolar luminal narrowing as well as features of retinal arteriolosclerosis.

Ethnic South Asian ischaemic stroke patients have a higher prevalence of a family history of vascular disease compared to age, gender and diabetes-matched ethnic Chinese subjects

Family history is a known non-modifiable risk factor of stroke. We aimed to compare the frequency of a family history of vascular disease between ethnic South Asian and Chinese stroke patients. We studied consecutive ethnic South Asian and Chinese ischaemic stroke patients matched for age, gender and presence of diabetes. Among the 152 matched pairs, ethnic South Asian ischaemic stroke patients had a higher frequency of vascular family history (IHD OR 3.465 p<0.001; CVD OR 1.754 p=0.059; and either IHD or CVD OR 2.169 p=0.003) compared to matched ethnic Chinese patients, independent of past IHD history and stroke subtype. In the ethnic South Asian cohort, patients < or = 60 years old had a higher frequency of a family history of IHD (37% vs 13%, p<0.001), CVD (34% vs 15%, p=0.005) and either IHD or CVD (52% vs 25%, p<0.001) compared to those >60 years. Family history of vascular disease is common among ethnic South Asian ischaemic stroke patients, particularly among those < or = 60 years old. We postulate that the higher frequency of a vascular family history among ethnic South Asians compared to ethnic Chinese may be explained by genetic, environmental and lifestyle influences, or interactions between these factors.