Retinal vascular caliber and extracranial carotid disease in patients with acute ischemic stroke: the Multi-Centre Retinal Stroke (MCRS) study.
ABSTRACT Previous studies show that both retinal vascular caliber and carotid disease predict incident stroke in the general population, but the exact relationship between these 2 microvascular and macrovascular structural risk factors is unclear. We studied the relationship between retinal vascular caliber and carotid disease in patients presenting with acute ischemic stroke.
We conducted a cross-sectional study of patients with acute ischemic stroke recruited from 3 centers (Melbourne, Sydney, Singapore). The caliber of retinal arterioles and venules was measured from digital retinal photographs. Severe extracranial carotid disease was defined as stenosis >or=75% or occlusion determined by carotid Doppler using North American Symptomatic Carotid Endarterectomy Trial-based criteria.
Among the 1029 patients with acute stroke studied, 7% of the population had severe extracranial carotid disease. Retinal venular caliber was associated with ipsilateral severe carotid disease (P<0.001 in multivariate models). Patients with wider retinal venular caliber were more likely to have severe ipsilateral carotid disease (multivariable-adjusted OR, 3.81; 95% CI, 1.80 to 8.07, comparing the largest and smallest venular caliber quartiles). The retinal venular caliber-carotid disease association remained significant in patients with large artery stroke.
In patients with acute stroke, retinal venular widening was strongly associated with ipsilateral severe extracranial carotid disease. Our findings suggest concomitant retinal and cerebral microvascular disease may be present in patients with carotid stenosis or occlusion disease. The pathogenesis of stroke due to carotid disease may thus be partially mediated by microvascular disease.
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ABSTRACT: 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.Journal of Human Hypertension advance online publication, 6 October 2011; doi:10.1038/jhh.2011.88.Journal of human hypertension 10/2011; · 2.80 Impact Factor
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ABSTRACT: Retinal vein occlusion (RVO) is the most frequent retinal vascular disease after diabetic retinopathy in which arterial risk factors are much more relevant than venous factors. The objective was to evaluate the role of risk factors in the development of the first episode of RVO. One hundred patients with RVO [mean age 56 years, 42% females and mean body mass index (BMI) 27.5 kg/m(2) ] were recruited consecutively from the outpatient clinic of a tertiary hospital in Valencia (Spain). All subjects underwent clinical assessment including anthropometric and blood pressure measurements and laboratory test including homocysteine, antiphospholipid antibodies (aPLAs) and thrombophilia studies. In half of the subjects, a carotid ultrasonography was performed. Three control populations matched by age, sex and BMI from different population-based studies were used to compare the levels and prevalence of arterial risk factors. One cohort of young patients with venous thromboembolic disease was used to compare the venous risk factors. Blood pressure levels and the prevalence of hypertension were significantly higher in the RVO population when compared with those for the general populations. There was also a large proportion of undiagnosed hypertension within the RVO group. Moreover, carotid evaluation revealed that a large proportion of patients with RVO had evidence of subclinical organ damage. In addition, homocysteine levels and prevalence of aPLAs were similar to the results obtained in our cohort of venous thromboembolic disease. The results indicate that hypertension is the key factor in the development of RVO, and that RVO can be the first manifestation of an undiagnosed hypertension. Furthermore, the majority of these patients had evidence of atherosclerotic disease. Among the venous factors, a thrombophilia study does not seem to be useful and only the prevalence of hyperhomocysteinaemia and aPLAs is higher than in the general population.International Journal of Clinical Practice 02/2014; · 2.43 Impact Factor
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ABSTRACT: C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations. Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry. Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10(-8)) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058). Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease.PLoS ONE 01/2013; 8(7):e67650. · 3.73 Impact Factor