@article {850, title = {Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study.}, journal = {Stroke}, volume = {36}, year = {2005}, month = {2005 Sep}, pages = {1830-4}, abstract = {

BACKGROUND AND PURPOSE: The association of light to moderate alcohol consumption with risk of ischemic stroke remains uncertain, as are the roles of potentially mediating factors and modification by apolipoprotein E (apoE) genotype.

METHODS: We studied the prospective association of alcohol consumption and risk of ischemic stroke among 4410 participants free of cardiovascular disease at baseline in the Cardiovascular Health Study, a population-based cohort study of older adults from 4 US communities. Participants reported their consumption of alcoholic beverages yearly.

RESULTS: During an average follow-up period of 9.2 years, 434 cases of incident ischemic stroke occurred. Compared with long-term abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95\% CI, 0.63 to 1.13), 0.75 (95\% CI, 0.53 to 1.06), 0.82 (95\% CI, 0.51 to 1.30), and 1.03 (95\% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14 drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower risks among drinkers than abstainers in apoE4-negative participants but higher risks among drinkers than abstainers among apoE4-positive participants. We could not identify candidate mediators among lipid, inflammatory, and prothrombotic factors.

CONCLUSIONS: In this study of older adults, the association of alcohol use and risk of ischemic stroke was U-shaped, with modestly lower risk among consumers of 1 to 6 drinks per week. However, apoE genotype may modify this association, and even moderate alcohol intake may be associated with an increased risk of ischemic stroke among apoE4-positive older adults.

}, keywords = {Aged, Alcohol Drinking, Apolipoproteins E, Brain Infarction, Brain Ischemia, Cohort Studies, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genotype, Humans, Hypertension, Inflammation, Ischemia, Lipids, Male, Middle Aged, Multivariate Analysis, Myocardial Infarction, Prospective Studies, Risk, Risk Factors, Stroke, Substance-Related Disorders, Thrombosis, Time Factors, Vascular Diseases}, issn = {1524-4628}, doi = {10.1161/01.STR.0000177587.76846.89}, author = {Mukamal, Kenneth J and Chung, Hyoju and Jenny, Nancy S and Kuller, Lewis H and Longstreth, W T and Mittleman, Murray A and Burke, Gregory L and Cushman, Mary and Beauchamp, Norman J and Siscovick, David S} } @article {985, title = {USF1 gene variants, cardiovascular risk, and mortality in European Americans: analysis of two US cohort studies.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {27}, year = {2007}, month = {2007 Dec}, pages = {2736-42}, abstract = {

OBJECTIVE: A common haplotype of the upstream transcription factor 1 gene (USF1) has been associated with decreased susceptibility to familial combined hyperlipidemia (FCHL) and, paradoxically, with increased risk of cardiovascular disease (CVD) and all-cause mortality.

METHODS AND RESULTS: We assessed associations between USF1 tagSNPs, CVD risk factors, and aging-related phenotypes using data from 2 large population-based cohorts, Coronary Artery Risk Development in Young Adults (CARDIA) and the Cardiovascular Health Study (CHS), comprising younger and older adults, respectively. In CARDIA, each additional copy of the FCHL low-risk allele was associated with 2.4 mg/dL lower levels of LDL cholesterol (P=0.01) and decreased risk of subclinical atherosclerosis as assessed by coronary artery calcium (odds ratio 0.79; 95\%CI 0.63 to 0.98). Whereas there was little association between USF1 genotype and metabolic or CVD traits in older adults from CHS, the USF1 low-risk dyslipidemia allele was associated with higher plasma C-reactive protein and interleukin (IL)-6 levels and with increased risk of mortality, particularly attributable to noncardiovascular causes.

CONCLUSIONS: There appears to be a complex and possibly age-dependent relationship between USF1 genotype, atherosclerosis phenotypes, and CVD risk. USF1 may influence mortality through pathways distinct from atherosclerosis. Alternatively, linkage disequilibrium with neighboring polymorphisms in other genes such as F11R may be responsible for the observed USF1 genotype-phenotype associations in older adults.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Aging, Blood Glucose, C-Reactive Protein, Calcium, Cardiovascular Diseases, Carotid Artery, Common, Cohort Studies, Coronary Artery Disease, Coronary Vessels, European Continental Ancestry Group, Female, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Hyperlipidemia, Familial Combined, Insulin, Interleukin-6, Linkage Disequilibrium, Lipids, Male, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States, Upstream Stimulatory Factors}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.107.154559}, author = {Reiner, Alexander P and Carlson, Christopher S and Jenny, Nancy S and Durda, J Peter and Siscovick, David S and Nickerson, Deborah A and Tracy, Russell P} }