Distribution of cardiovascular health by individual- and neighborhood-level socioeconomic status: Findings from the Jackson Heart Study

BACKGROUND: Data demonstrate a positive relationship between socioeconomic status (SES) and cardiovascular health (CVH). OBJECTIVE: To assess the association between individual- and neighborhood-level SES and CVH among participants of the JHS (Jackson Heart Study), a community-based cohort of African Americans in Jackson, Mississippi. METHODS: We included all JHS participants with complete SES and CVH information at the baseline study visit (n = 3,667). We characterized individual- and neighborhood-level SES according to income (primary analysis) and education (secondary analysis), respectively. The outcome of interest for these analyses was a CVH score, based on 7 modifiable behaviors and factors, summed to a total of 0 (worst) to 14 (best) points. We utilized generalized estimating equations to account for the clustering of participants within the same residential areas to estimate the linear association between SES and CVH. RESULTS: The median age of the participants was 55 years, and 64% were women. Nearly one-third of eligible participants had individual incomes \u3c$20,000 and close to 40$25,480). Adjusted for age, sex, and neighborhood SES, there was an average increase in CVH score of 0.31 points associated with each 1-category increase in individual income. Similarly, each 1-category increase in neighborhood SES was associated with a 0.19-point increase in CVH score. These patterns held for our secondary analyses, which used educational attainment in place of income. These data did not suggest a synergistic effect of individual- and neighborhood-level SES on CVH. CONCLUSIONS: Our findings suggest a potential causal pathway for disparities in CVH among vulnerable populations. These data can be useful to the JHS community to empower public health and clinical interventions and policies for the improvement of CVH

Dysfunction in the βII Spectrin-Dependent Cytoskeleton Underlies Human Arrhythmia.

Background: The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked with cardiac pathologies including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction in cardiac electrical activity is not well understood, and often overlooked in the cardiac arrhythmia field. Methods and Results: Here, we uncover a new mechanism for the regulation of cardiac membrane excitability. We report that βII spectrin, an actin-associated molecule, is essential for the post-translational targeting and localization of critical membrane proteins in heart. βII spectrin recruits ankyrin-B to the cardiac dyad, and a novel human mutation in the ankyrin-B gene disrupts the ankyrin-B/βII spectrin interaction leading to severe human arrhythmia phenotypes. Mice lacking cardiac βII spectrin display lethal arrhythmias, aberrant electrical and calcium handling phenotypes, and abnormal expression/localization of cardiac membrane proteins. Mechanistically, βII spectrin regulates the localization of cytoskeletal and plasma membrane/sarcoplasmic reticulum protein complexes that include the Na/Ca exchanger, RyR2, ankyrin-B, actin, and αII spectrin. Finally, we observe accelerated heart failure phenotypes in βII spectrin-deficient mice. Conclusions: Our findings identify βII spectrin as critical for normal myocyte electrical activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology

Defects in Cytoskeletal Signaling Pathways, Arrhythmia, and Sudden Cardiac Death

Ankyrin polypeptides are cellular adapter proteins that tether integral membrane proteins to the cytoskeleton in a host of human organs. Initially identified as integral components of the cytoskeleton in erythrocytes, a recent explosion in ankyrin research has demonstrated that these proteins play prominent roles in cytoskeletal signaling pathways and membrane protein trafficking/regulation in a variety of excitable and non-excitable cells including heart and brain. Importantly, ankyrin research has translated from bench to bedside with the discovery of human gene variants associated with ventricular arrhythmias that alter ankyrin–based pathways. Ankyrin polypeptides have also been found to play an instrumental role in various forms of sinus node disease and atrial fibrillation. Mouse models of ankyrin deficiency have played fundamental roles in the translation of ankyrin-based research to new clinical understanding of human sinus node disease, atrial fibrillation, and ventricular tachycardia