@article {713, title = {In the elderly, interleukin-6 plasma levels and the -174G>C polymorphism are associated with the development of cardiovascular disease.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {22}, year = {2002}, month = {2002 Dec 01}, pages = {2066-71}, abstract = {

OBJECTIVE: Interleukin (IL)-6-mediated inflammation is involved in cardiovascular disease (CVD). We assessed IL-6 levels and the -174G>C genotype in a case-control study of men and women (average age 73 years) within the Cardiovascular Health Study.

METHODS AND RESULTS: Cases included incident angina, myocardial infarction (MI), and stroke (5-year follow-up), prevalent MI, and MRI-detectable infarcts. A control group and a group free of subclinical CVD were used for comparison. The -174C allele was associated with higher C-reactive protein (11\% higher, P=0.02), fibrinogen (3\% higher, P=0.02), and IL-6 (5\% higher; P=0.16). IL-6 was associated with increased atherosclerosis when the control group was compared with the group free of subclinical CVD. No further association with CVD events was found when case groups were compared with the control group. Compared with its absence, presence of the -174C allele was associated with risk of MRI infarcts (odds ratio 1.5).

CONCLUSIONS: IL-6 levels differentiated those with subclinical CVD from those without. Although the -174C allele was not associated with incident events, associations of the genotype with inflammation and MRI infarcts, combined with the plasma IL-6 results, suggest that IL-6 may chronically predispose an individual to develop atherosclerosis.

}, keywords = {Age Factors, Aged, Biomarkers, Cardiovascular Diseases, Case-Control Studies, Cytosine, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genotype, Guanine, Health Surveys, Humans, Inflammation, Interleukin-6, Linear Models, Male, Polymorphism, Genetic, Predictive Value of Tests, Promoter Regions, Genetic}, issn = {1524-4636}, doi = {10.1161/01.atv.0000040224.49362.60}, author = {Jenny, Nancy S and Tracy, Russell P and Ogg, Malcolm S and Luong, Le Ahn and Kuller, Lewis H and Arnold, Alice M and Sharrett, A Richey and Humphries, Steve E} } @article {734, title = {The prevalence and risk factors of retinal microvascular abnormalities in older persons: The Cardiovascular Health Study.}, journal = {Ophthalmology}, volume = {110}, year = {2003}, month = {2003 Apr}, pages = {658-66}, abstract = {

PURPOSE: To describe the prevalence of retinal microvascular characteristics and their associations with atherosclerosis in elderly, nondiabetic persons.

DESIGN AND PARTICIPANTS: Population-based, cross-sectional study comprising 2050 men and women aged 69 to 97 years without diabetes, living in four communities.

METHODS: Participants underwent retinal photography and standardized grading of retinal microvascular characteristics, including retinopathy (e.g., microaneurysms, retinal hemorrhages), focal arteriolar narrowing, and arteriovenous nicking. In addition, calibers of retinal arterioles and venules were measured on digitized photographs to obtain an estimate of generalized arteriolar narrowing. Atherosclerosis and its risk factors were obtained from clinical examination and laboratory investigations.

MAIN OUTCOME MEASURES: Prevalence of retinal microvascular abnormalities and their associations with measures of atherosclerosis.

RESULTS: The prevalence of retinal microvascular abnormalities was 8.3\% for retinopathy, 9.6\% for focal arteriolar narrowing, and 7.7\% for arteriovenous nicking. All retinal lesions were associated with hypertension (odds ratios [OR] were 1.8 for retinopathy, 2.1 for focal arteriolar narrowing, 1.5 for arteriovenous nicking, and 1.7 for generalized arteriolar narrowing). After controlling for age, gender, race, mean arterial blood pressure, and antihypertensive medication use, retinopathy was associated with prevalent coronary heart disease (OR, 1.7), prevalent myocardial infarction (OR, 1.7), prevalent stroke (OR, 2.0), presence of carotid artery plaque (OR, 1.9), and increased intima-media thickness of the common carotid (OR, 2.3; fourth vs. first quartile) and internal carotid (OR, 1.8; fourth vs. first quartile) arteries. In contrast, focal arteriolar narrowing, arteriovenous nicking, and generalized arteriolar narrowing were not associated with any measures of atherosclerosis.

CONCLUSIONS: Retinal microvascular abnormalities are common in older persons without diabetes and are related to hypertension. Retinopathy is associated with prevalent coronary heart disease, stroke, and carotid artery thickening, but focal and generalized arteriolar narrowing and arteriovenous nicking are not related to most measures of atherosclerosis. These data suggest that retinal microvascular abnormalities reflect processes associated with hypertension but distinct from atherosclerosis.

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, Coronary Artery Disease, Cross-Sectional Studies, Female, Humans, Hypertension, Male, Prevalence, Retinal Diseases, Retinal Vessels, Risk Factors, United States}, issn = {0161-6420}, doi = {10.1016/S0161-6420(02)01931-0}, author = {Wong, Tien Yin and Klein, Ronald and Sharrett, A Richey and Manolio, Teri A and Hubbard, Larry D and Marino, Emily K and Kuller, Lewis and Burke, Gregory and Tracy, Russell P and Polak, Joseph F and Gottdiener, John S and Siscovick, David S} } @article {826, title = {Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities \& Cardiovascular Health studies.}, journal = {Ophthalmology}, volume = {112}, year = {2005}, month = {2005 Apr}, pages = {540-7}, abstract = {

OBJECTIVE: To examine the associations of retinal vein occlusion and arteriolar emboli with cardiovascular disease.

DESIGN: Population-based cross-sectional study.

PARTICIPANTS: Pooled from the Atherosclerosis Risk in Communities Study (n = 12,642; mean age, 60 years) and the Cardiovascular Health Study (n = 2824; mean age, 79 years).

METHODS: Retinal vein occlusion and arteriolar emboli were identified from a single nonmydriatic retinal photograph using a standardized protocol. Photographs were also graded for arteriovenous nicking and focal arteriolar narrowing. All participants had a comprehensive systemic evaluation, including standardized carotid ultrasonography.

MAIN OUTCOME MEASURES: Retinal vein occlusion and arteriolar emboli.

RESULTS: Prevalences of retinal vein occlusion and arteriolar emboli were 0.3\% (n = 39 cases) and 0.2\% (n = 34 cases), respectively. After adjusting for age, retinal vein occlusion was associated with hypertension (odds ratio [OR], 2.96; 95\% confidence interval [CI], 1.43-6.14), systolic blood pressure (BP) (OR, 4.12; 95\% CI, 1.40-12.16; highest quartile vs. lowest), diastolic BP (OR, 2.64; 95\% CI, 1.07-6.46; highest quartile vs. lowest), carotid artery plaque (OR, 5.62; 95\% CI, 2.60-12.16), body mass index (OR, 3.88; 95\% CI, 1.23-12.18; highest quartile vs. lowest), plasma fibrinogen (OR, 3.29; 95\% CI, 1.08-10.02; highest quartile vs. lowest), arteriovenous nicking (OR, 4.09; 95\% CI, 2.00-8.36), and focal arteriolar narrowing (OR, 5.17; 95\% CI, 2.59-10.29). After adjusting for age, retinal arteriolar emboli were associated with hypertension (OR, 3.14; 95\% CI, 1.44-6.84), systolic BP (OR, 3.46; 95\% CI, 1.13-10.65; highest quartile vs. lowest), prevalent coronary heart disease (OR, 2.33; 95\% CI, 1.01-5.42), carotid artery plaque (OR, 4.62; 95\% CI, 1.85-11.57), plasma lipoprotein (a) (OR, 3.69; 95\% CI, 1.20-11.41; highest quartile vs. lowest), plasma fibrinogen (OR, 3.09; 95\% CI, 0.98-9.76; highest quartile vs. lowest), and current cigarette smoking (OR, 3.08; 95\% CI, 1.47-6.47). Approximately a quarter of participants with retinal vein occlusion and arteriolar emboli had evidence of carotid artery plaque as defined from ultrasound.

CONCLUSIONS: Retinal vein occlusion and retinal arteriolar emboli are associated with carotid artery disease, hypertension, and other cardiovascular risk factors.

}, keywords = {Aged, Aged, 80 and over, Arterioles, Blood Pressure, Cardiovascular Diseases, Carotid Stenosis, Coronary Artery Disease, Cross-Sectional Studies, Embolism, Female, Fibrinogen, Humans, Hypertension, Lipoprotein(a), Male, Meta-Analysis as Topic, Middle Aged, Retinal Artery, Retinal Vein Occlusion, Risk Factors}, issn = {1549-4713}, doi = {10.1016/j.ophtha.2004.10.039}, author = {Wong, Tien Yin and Larsen, Emily K Marino and Klein, Ronald and Mitchell, Paul and Couper, David J and Klein, Barbara E K and Hubbard, Larry D and Siscovick, David S and Sharrett, A Richey} } @article {929, title = {Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Nov 27}, pages = {2388-94}, abstract = {

BACKGROUND: Small vessel disease may contribute to the risk of cardiovascular disease in older persons. We describe the relation of retinal vascular caliber to incident coronary heart disease (CHD) and stroke in elderly persons.

METHODS: Prospective population-based cohort study composed of 1992 men and women aged 69 to 97 years living in 4 US communities. Retinal arteriolar and venular calibers were measured from retinal photographs using a computer-assisted method. Incident CHD and stroke events were ascertained using standardized methods.

RESULTS: After 5 years of follow-up, there were 115 incident CHD events and 113 incident stroke events. Participants with larger retinal venular caliber had a higher incidence of CHD (11.7\%; 95\% confidence interval [CI], 8.7\%-15.8\%, vs 8.1\%; 95\% CI, 5.7\%-11.6\%), comparing largest with smallest venular caliber quartiles, and stroke (8.4\%; 95\% CI, 6.0-11.7, vs 5.8\%; 95\% CI, 3.9-8.4). At multivariable analysis, controlling for age, sex, race, arteriolar caliber, systolic and diastolic blood pressure, diabetes, glucose concentration, cigarette smoking, pack-years of smoking, and high-density-lipoprotein and low-density lipoprotein cholesterol levels, larger retinal venular caliber was associated with incident CHD (rate ratio, 3.0; 95\% CI, 1.6-5.7, comparing largest with smallest venular caliber quartiles; P(trend) = .001) and incident stroke (rate ratio, 2.2; 95\% CI, 1.1-4.3; P(trend) = .02). Additional adjustment for C-reactive protein and common and internal carotid artery intimal-media thickness had minimal effect on these associations. At multivariable analysis, smaller retinal arteriolar caliber was associated with incident CHD (rate ratio, 2.0; 95\% CI, 1.1-3.7, comparing largest with smallest arteriolar caliber quartiles; P = .03) but not stroke (rate ratio,1.1; 95\% CI, 0.5-2.2; P = .73).

CONCLUSION: Larger retinal venular caliber is independently associated with risk of cardiovascular disease in elderly persons.

}, keywords = {Aged, Aged, 80 and over, Algorithms, Cardiovascular Diseases, Cohort Studies, Female, Humans, Image Processing, Computer-Assisted, Incidence, Male, Photography, Prospective Studies, Retinal Diseases, Retinal Vein, Retinal Vessels, Risk Factors, Stroke, United States}, issn = {0003-9926}, doi = {10.1001/archinte.166.21.2388}, author = {Wong, Tien Yin and Kamineni, Aruna and Klein, Ronald and Sharrett, A Richey and Klein, Barbara E and Siscovick, David S and Cushman, Mary and Duncan, Bruce B} } @article {921, title = {Associations between findings on cranial magnetic resonance imaging and retinal photography in the elderly: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {165}, year = {2007}, month = {2007 Jan 01}, pages = {78-84}, abstract = {

Associations between findings on cranial magnetic resonance imaging (MRI) and retinal photographs have been described mostly in middle-aged people. In the Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal photography between 1991 and 1999. Associations were sought between MRI findings and four findings of retinal microvascular disease: retinopathy, focal arteriolar narrowing, arteriovenous nicking, and the arteriovenous ratio--the last based upon semiautomated measurements of arterioles and venules. After controlling for age and gender, the authors found associations between MRI findings and the smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts (odds ratio = 1.18, 95\% confidence interval: 1.05, 1.34; p = 0.007), white matter grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio = 1.26, 95\% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter grade (odds ratio = 1.12, 95\% confidence interval: 0.98, 1.29; p = 0.09). Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95\% confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95\% confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension and diabetes had minimal effect. Evidence of small vessel disease in the retina increases the likelihood of finding it in the brain. Associations were less prominent in this elderly population than have been described in middle-aged people.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Arteriosclerosis, Cerebral Infarction, Female, Humans, Leukoaraiosis, Longitudinal Studies, Magnetic Resonance Imaging, Male, Microcirculation, Photography, Retina, Retinal Diseases, Retinal Vessels, Risk Assessment, Risk Factors}, issn = {0002-9262}, doi = {10.1093/aje/kwj350}, author = {Longstreth, Wt and Larsen, Emily K Marino and Klein, Ronald and Wong, Tien Yin and Sharrett, A Richey and Lefkowitz, David and Manolio, Teri A} }