Role and Mechanism of Blood Pressure Variability in Risk of Heart Failure

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Project Summary/Abstract Blood pressure variability (BPv) is increasingly appreciated as a risk factor for cardiovascular disease. However, few studies have examined the relationship between BPv and heart failure (HF), a serious condition with increasing prevalence in the US. Moreover, in those studies that have indicated a role for BPv in HF risk, several issues merit systematic exploration, including the potential importance of diastolic BPv, contributions of various antihypertensive medication classes to BPv, and further understanding of mechanisms linking BPv to risk of HF. Here, leveraging two complementary data sources—the longitudinal Multi-Ethnic Study of Atherosclerosis (MESA) and the Veterans Affairs’ electronic medical records (VA-EMR), we propose to conduct a comprehensive investigation of the role of BPv in risk of HF guided by the following aims: In Aim 1, we will examine the relationship between visit-to-visit systolic and diastolic BPv and risk of clinically and radiologically identified HF in the MESA cohort. (1a) We will determine the association of BPv with clinical and MRI assessments of HF and whether this differs by baseline determinants including sex, diabetes status, and race/ethnicity. (1b) Then, we will examine potential mechanisms by which BPv may influence HF. We will test whether effects of BPv are enhanced in the setting of lower blood pressure, underlying ischemia, and dips rather than elevations in DBP. We will further assess whether BPv is related to structural changes of HF as measured by MRI imaging. In Aim 2, we will examine the real-world relationship between BPv and risk of HF among participants in the VA national database. (2a) We will examine this in the whole cohort and then test whether the association differs by baseline determinants such as sex, diabetes status, CVD status, and race/ethnicity. The extensive medication database will be used to examine how the BPv association with HF differs by medication class. (2b) To explore mechanisms by which BPv may influence HF, we will examine BPv in those with progressively lower mean blood pressure, evaluate dips rather than rises in DBP and determine whether the relationship is altered in those with underlying ischemia or prior myocardial infarction. In sum, this project is a definitive study of the relationship between BPv and HF. It will help identify those at greatest risk from BPv, potentially improve risk stratification, and by providing evidence for potential mechanisms of injury will lead to improved blood pressure recommendations and treatment strategies.