The St. Louis African American health-heart study: methodology for the study of cardiovascular disease and depression in young-old African Americans.

BACKGROUND: Coronary artery disease (CAD) is a major cause of death and disability worldwide. Depression has complex bidirectional adverse associations with CAD, although the mechanisms mediating these relationships remain unclear. Compared to European Americans, African Americans (AAs) have higher rates of morbidity and mortality from CAD. Although depression is common in AAs, its role in the development and features of CAD in this group has not been well examined. This project hypothesizes that the relationships between depression and CAD can be explained by common physiological pathways and gene-environment interactions. Thus, the primary aims of this ongoing project are to: a) determine the prevalence of CAD and depression phenotypes in a population-based sample of community-dwelling older AAs; b) examine the relationships between CAD and depression phenotypes in this population; and c) evaluate genetic variants from serotoninP and inflammatory pathways to discover potential gene-depression interactions that contribute significantly to the presence of CAD in AAs. METHODS/DESIGN: The St. Louis African American Health (AAH) cohort is a population-based panel study of community-dwelling AAs born in 1936-1950 (inclusive) who have been followed from 2000/2001 through 2010. The AAH-Heart study group is a subset of AAH participants recruited in 2009-11 to examine the inter-relationships between depression and CAD in this population. State-of-the-art CAD phenotyping is based on cardiovascular characterizations (coronary artery calcium, carotid intima-media thickness, cardiac structure and function, and autonomic function). Depression phenotyping is based on standardized questionnaires and detailed interviews. Single nucleotide polymorphisms of selected genes in inflammatory and serotonin-signaling pathways are being examined to provide information for investigating potential gene-depression interactions as modifiers of CAD traits. Information from the parent AAH study is being used to provide population-based prevalence estimates. Inflammatory and other biomarkers provide information about potential pathways. DISCUSSION: This population-based investigation will provide valuable information on the prevalence of both depression and CAD phenotypes in this population. The study will examine interactions between depression and genetic variants as modulators of CAD, with the intent of detecting mechanistic pathways linking these diseases to identify potential therapeutic targets. Analytic results will be reported as they become available.

Osteopontin promoter polymorphism is associated with increased carotid intima-media thickness.

BACKGROUND: Osteopontin (OPN)-transgenic mice exhibit increased carotid artery intima-media thickness (CIMT), smooth muscle cell proliferation, and atheroma formation. METHODS: An association of the human T-66G promoter variant with CIMT was examined in Caucasian adults grouped according to metabolic syndrome criteria: present (+MetS; n = 70) or absent (-MetS; n = 70). RESULTS: The G-allele frequency was 22%. For the entire cohort, the G group (TG and GG) was associated with significantly lower age-adjusted and gender-adjusted CIMT compared with the TT group (P = .008); similar analysis by metabolic syndrome group found a significant difference only in the -MetS group (P = .018). Stepwise multivariate regression showed that after age and waist circumference, the T-66G variant was the next most predictive of CIMT (P = .007). These data suggest that in a normoglycemic environment, human vascular OPN gene expression contributes to arterial structure, an effect diminished in dysmetabolic states. CONCLUSION: Humans with the OPN -66 TT genotype, particularly those without metabolic syndrome, exhibit thicker CIMT.