Three areas of emphasis:

1. Microvascular contributions to ischemia. Most research on human ischemic diseases has focused on atherosclerosis. Methods have not been available to study contributions of the arterioles. However, retinal arteriolar changes may independently predict stroke, cerebral white matter disease, and dementia. They also appear to predict CHD, but only in women, consistent with the natural history of CHD in women.

2. CHD prevention potential. In 1910-20, William Osler and Paul Dudley White recognized but rarely saw angina pectoris. A review of the 20th century rise in CHD incidence, the Seven Countries Study, and other studies of special populations suggests that CHD may be more preventable than suggested by contemporary clinical trials or risk-factor equations. Yet recently discovered risk factors add little to overall prediction. However risk prediction, though similar in blacks and whites, is much more effective in women than men, and the substantial incidence in even those men who are at low-risk holds the promise of undiscovered risk factors. A key unrealized predictor may be lifetime diet, which may effect plasma cholesterol levels more than suggested by available short-term dietary trials. This may help explain the 20th century CHD rise. Programmed overfeeding of farm animals, which has been steadily optimized over the last century, raises the fat content of meat and has a markedly adverse effect on meat fatty acid composition. These considerations affect our views regarding the limits of CHD prediction and have broad implications for the scope of future CHD research on prevention.

3. Subclinical atherosclerosis. Postprandial triglyceridemia is related to asymptomatic carotid atherosclerosis independent of fasting lipids, presumably due to atherogenic remnant lipoproteins. Lipids, smoking, and diabetes operate at different, defined stages of atherogenesis and clinical disease and have different associations with compensatory arterial enlargement. Inflammatory factors may be particularly associated with plaque erosion or rupture. The goal of this research is more targeted approaches to preventing atherosclerosis progression and conversion to clinical disease.

Epidemiology;arteriosclerosis;ARIC;MESA;cognitive impairment

Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: the ARIC Study. Circulation 2001;104:1108-13

Sharrett AR, Heiss G, Chambless LE, Boerwinkle E, Coady SA, Folsom AR, Patsch W. Metabolic and lifestyle determinants of postprandial lipemia differ from those of fasting triglycerides: the ARIC Study. Arterioscler Thromb Vasc Biol 2001;21:275-281

Golden SH, Folsom AR, Coresh J, Sharrett AR, Szklo M, Brancati FL. Risk factor clusters related to insulin resistance and their synergistic effects on subclinical atherosclerosis: the ARIC Study. Diabetes 2002;51:3069-76

Wong TY, Klein R. Sharrett AR, Nieto FJ, Boland LL, Couper DJ, Mosley TH, Klein BEK, Hubbard LD, Szklo M. Retinal microvascular abnormalities and cognitive impairment in middle-aged persons - The ARIC Study. Stroke 2002;33:1487-92

Wong TY, Klein R, Sharrett AR, Couper DJ, Klein BEK, Liao D-P, Hubbard LD, Mosley TH. Cerebral white matter lesions, retinopathy and risk of stroke, the ARIC Study. JAMA 2002;288:67-74

Chambless LE, Folsom AR, Sharrett AR, Sorlie P, Couper D, Szklo M, Nieto J. Coronary Heart Disease prediction in the ARIC Study. J Clin Epidemiol 2003;56:880-890

Mora S, Redberg RF, Cui Y, Whiteman MK, Flaws JA, Sharrett AR, Blumenthal RS.. Ability of exercise testing to predict cardiovascular and all-cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study. JAMA. 2003;290:1600-1607

Shahar E, Chambless LE, Rosamond WD, Boland LL, Ballantyne CM, McGovern PG, Sharrett AR. Plasma lipid profile and incident ischemic stroke - The ARIC Study. Stroke 2003;34:623-31

Wong TY, Mosley TH, Jr., Klein R, Klein BEK, Sharrett AR, Couper DJ, Hubbard MAT. Retinal microvascular changes and MRI signs of cerebral atrophy in healthy, middle-aged people. Neurology. 2003;61:806-811

Sharrett AR, Coady SA, Folsom AR, Couper DJ, Heiss G. Smoking and diabetes differ in their associations with subclinical atherosclerosis and coronary heart disease – the ARIC Study. Atherosclerosis 2004;172:143-9

Cooper LS, Wong TY, Klein R, Sharrett AR, Bryan RN, Hubbard LD, Couper DJ, Heiss G, Sorlie PD. Retinal Microvascular Abnormalities and MRI-Defined Subclinical Cerebral Infarction: The Atherosclerosis Risk in Communities Study. Stroke 2006 January;37(1):82-6.

Folsom AR, Chambless LE, Ballantyne CM, Coresh J, Heiss G, Wu KK, Boerwinkle E, Mosley TH, Jr., Sorlie P, Diao G, Sharrett AR. An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study. Arch Intern Med 2006 July 10;166(13):1368-73.

Hozawa A, Folsom AR, Sharrett AR, Payne TJ, Chambless LE. Does the impact of smoking on coronary heart disease differ by low-density lipoprotein cholesterol level?: the Atherosclerosis Risk in Communities (ARIC) Study. Circ J 2006 September;70(9):1105-10.

Mora S, Szklo M, Otvos JD, Greenland P, Psaty BM, Goff DC, Jr., O'Leary DH, Saad MF, Tsai MY, Sharrett AR. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2006 June 9;.

Sharrett AR, Ding J, Criqui MH, Saad MF, Liu K, Polak JF, Folsom AR, Tsai MY, Burke GL, Szklo M. Smoking, diabetes, and blood cholesterol differ in their associations with subclinical atherosclerosis: The Multiethnic Study of Atherosclerosis (MESA). Atherosclerosis 2006;.186(2):441-7.

Wong TY, Kamineni A, Klein R, Sharrett AR, Klein BE, Siscovick DS, Cushman M, Duncan BB. Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study. Arch Intern Med 2006 November 27;166(21):2388-94.

Longstreth WT, Jr., Larsen EK, Klein R, Wong TY, Sharrett AR, Lefkowitz D, Manolio TA. Associations between Findings on Cranial Magnetic Resonance Imaging and Retinal Photography in the Elderly. Am J Epidemiol 2007;165(1):78-84.

Volcik K, Ballantyne CM, Pownall HJ, Sharrett AR, Boerwinkle E. Interaction effects of high-density lipoprotein metabolism gene variation and alcohol consumption on coronary heart disease risk: the atherosclerosis risk in communities study. J Stud Alcohol Drugs 2007 July;68(4):485-92.