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: 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 07/2013; 8(7):e67650. DOI:10.1371/journal.pone.0067650 · 3.53 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; 68(7). DOI:10.1111/ijcp.12390 · 2.54 Impact Factor
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ABSTRACT: Current research suggests that retinal arterial changes such as arteriovenous nicking and arterial narrowing are pathologically distinct from atherosclerosis. Other studies have found a positive correlation between retinal changes and systemic atherosclerosis. However, limited recent histopathologic evidence assessing atherosclerosis in the central retinal artery exists. We investigated atherosclerosis in the central retinal artery and how it correlates to atherosclerosis in the carotid and coronary arteries. Twenty-two cadavers (12 males, 10 females) were dissected, obtaining one orbit, one carotid artery, and one coronary artery from each. The specimens were sectioned and stained for histologic analysis by light microscopy using hematoxylin and eosin, Verhoeff's elastic, and Gomori's trichrome stains. The degree of atherosclerosis was graded from absent, or I (least severe) to VIII (most severe) based on the current American Heart Association guidelines. Atherosclerotic changes were present in the central retinal, coronary, and carotid arteries. A positive correlation was found between the central retinal artery and the carotid artery (r = 0.23, P = 0.15), the central retinal artery and the coronary artery (r = 0.31, P = 0.08), and the carotid artery and the coronary artery (r = 0.45, P = 0.02). The presence of low-grade atherosclerosis in the central retinal artery is prevalent in a population of advanced vascular disease. However, central retinal artery atherosclerotic lesion severity is poorly correlated with disease severity in the carotid and coronary arteries. Anat Rec, 2014. © 2014 Wiley Periodicals, Inc.The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 08/2014; 297(8). DOI:10.1002/ar.22945 · 1.53 Impact Factor