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.

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.

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. METHODS: First-time onset acute ischemic stroke patients (n = 120) and controls (n = 207) with no past history of stroke were compared. Allele specific gene amplification and restriction fragment length polymorphism (RFLP) analysis were used to determine the genotype and allelic frequencies in both groups. Plasma homocysteine (Hcy) and nitrite levels were measured. RESULTS: No significant association of NOS3 polymorphisms with ischemic stroke was noted. The TT genotype of the MTHFR C677T polymorphism was significantly associated with ischemic stroke (P = 0.004). Elevated plasma Hcy levels were also significantly associated with ischemic stroke (P = 0.001). CONCLUSIONS: The TT genotype of C677T polymorphism in the MTHFR gene contributes to genetic susceptibility of acute ischemic stroke in a Singapore population.

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. METHODS: Amongst the 229 prospectively recruited acute ischaemic stroke patients, we measured carotid-femoral PWV using applanation tonometry and the inflammatory marker serum ESR. RESULTS: Carotid-femoral PWV was significantly higher amongst patients with MetS (P = 0.002), increased waist circumference (P = 0.010), raised blood pressure (P < 0.001) and abnormal glycemia (P = 0.002); and increased with the number of MetS components (P = 0.002). In a sub-group of 199 patients, carotid-femoral PWV was significantly correlated with serum ESR (P < 0.001). In multivariate regression analysis including serum ESR and MetS as variables, carotid-femoral PWV was independently associated with higher ESR (P = 0.002) but not with MetS (P = 0.139). CONCLUSIONS: Arterial stiffness is significantly associated with MetS amongst ischaemic stroke patients, and inflammation appears to be involved in this relationship.

Profile and associations of central pulse wave velocity and central pulse pressure among ischemic stroke patients.

Arterial stiffness, a known risk factor for atherosclerosis, can be measured directly with carotid-femoral pulse wave velocity (CPWV) and indirectly with central pulse pressure (CPP). We aimed to compare central and brachial pulse pressures, and to profile CPWV and CPP among ischemic stroke patients. We studied 198 consecutive prospective ethnic Chinese and South Asian ischemic stroke patients, measuring brachial pressures, central pressures and CPWV under standardized conditions using established methods. The mean CPWV was 11.6 +/- 3.2 m/s and CPP was 64 +/- 28 mmHg. CPP was significantly lower than brachial pulse pressure. CPWV and CPP were both independently associated with older age and hypertension. Among ischemic stroke patients, brachial pulse pressure cannot be used as a surrogate for CPP. Older age and hypertension are associated with arterial stiffening.

Arterial stiffness is associated with raised levels of the inflammatory marker erythrocyte sedimentation rate among ischaemic stroke patients.

We studied the relationship of arterial stiffness, measured by carotid-femoral pulse wave velocity and inflammation, measured by serum erythrocyte sedimentation rate among 334 ischaemic stroke patients. There was a significant correlation between carotid-femoral pulse wave velocity and erythrocyte sedimentation rate (P = 0.001), a relationship independent of age, hypertension, diabetes and smoking. Arterial stiffness and inflammation are associated among ischaemic stroke patients and are independent of established vascular risk factors.