Association of Midlife Cardiovascular Risk Factors with Risk of Heart Failure Subtypes Later in Life.

Abstract Background Independent associations between cardiovascular risk factor exposures during midlife and later life development of HF with preserved ejection fraction (HFpEF) vs. reduced EF (HFrEF) have not been previously studied. Methods We pooled data from four US cohort studies (ARIC, CHS, Health ABC, and MESA) and imputed annual risk factor trajectories for body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), LDL and HDL cholesterol, and glucose starting from age 40 years. Time-weighted average exposures to each risk factor during midlife and later life were calculated and analyzed for associations with the development of HFpEF or HFrEF. Results A total of 23,861 participants were included (mean age at first in-person visit 61.8 ±10.2 years; 56.6% female). During a median follow up of 12 years, there were 3,666 incident HF events, of which 51% had EF measured, including 934 with HFpEF and 739 with HFrEF. High midlife SBP and low midlife HDL were associated with HFrEF, and high midlife BMI, SBP, pulse pressure, and glucose were associated with HFpEF. After adjusting for later life exposures, only midlife pulse pressure remained independently associated with HFpEF. Conclusions Midlife exposure to cardiovascular risk factors are differentially associated with HFrEF and HFpEF later in life. Having a higher pulse pressure during midlife is associated with a greater risk for HFpEF but not HFrEF, independent of later life exposures.