Epidemiologic studies revealed that long-term increases in blood pressure variability are associated with cardiovascular damage, and with an increased incidence of cardiovascular events and mortality independent of elevated mean blood pressure. There are compelling data on the role of genetics in hypertension. The relationship between common genetic variants and arterial blood pressure variability has not been tested before in any American population.
The specific aims of the proposed study are:
Aim A) To locate SNPs associated with Visit-to-Visit Blood Pressure Variability. Hypothesis A) There are SNPs associated with Visit-to-Visit Blood Pressure Variability.
Aim B) To locate shared SNPs that regulate both Visit-to-Visit Blood Pressure Variability and Mean Arterial Blood Pressure. Hypothesis B) There are shared SNPs that regulate both Visit-to-Visit Blood Pressure Variability and Mean Arterial Blood Pressure.
Aim C) To locate shared SNPs regulating both Visit-to-Visit Blood Pressure Variability and Cardiovascular Diseases. Hypothesis C) There are shared SNPs that regulate both Visit-to-Visit Blood Pressure Variability and Cardiovascular Diseases. To achieve the previously stated aims, we will analyze the Genome-Wide-Association data of Cardiovascular Health Study and Women's Health Initiative studies; we plan to use (1) Mixed Linear Models, (2) Principle components, and (3) Random Effect Han's-Eskin's models to adjust for population stratification and account for racial-genes heterogeneity. This study is innovative: (1) No one has ever located SNPs regulating both Visit-to-Visit Blood Pressure Variability and Mean arterial blood pressure. (2) We are trying to map shared SNPs between Visit-to-Visit Blood Pressure Variability and Cardiovascular Diseases (Pleiotropy) for the first time. The proposed study is important because the discovery of such variants and genetic regions is a stepping stone to uncover biological insights to identify new pharmacological targets for decreasing blood pressure variability; this in turn will lead to novel prevention strategies to reduce the growing public health burden of blood pressure variability-related cardiovascular disease.
Visit-to-Visit Blood Pressure Variability (VVBPV) is strongly associated with cardiovascular morbidity and mortality. This study is novel because we expect to identify SNPs regulating VVBPV; this discovery is important because it will fill critical gaps i our current knowledge about the genetic foundation of VVBPV. This in turn could lead to novel prevention and curative strategies to reduce the growing public health burden of visit-to-visit blood pressure variability-related cardiovascular disease.
