Time-averaged cumulative blood pressure and cardiovascular outcomes in heart failure with preserved ejection fraction: analysis from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial

To determine whether time-averaged cumulative blood pressure (cumBP) is associated with the risk of cardiovascular outcomes among patients with heart failure with preserved ejection fraction.Three thousand, three hundred and thirty participants from Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were included in this analysis with a median follow-up of 3 years. CumBP, expressed as mmHg-years, was the sum of mean BP for each pair of successive examinations multiplied by the time. Time-averaged cumBP was calculated by dividing cumBP by total exposure time, also expressed as mmHg. Clinical outcomes of our study including primary endpoint, all-cause death, cardiovascular death and heart failure hospitalization. Multivariable Cox hazard regression models and a restricted cubic spline model were used to assess the association and linearity between time-averaged cumBP and adverse outcomes.There is a U-shaped relationship between time-averaged cumBP and primary endpoint, all-cause death, cardiovascular death and heart failure hospitalization among participants with HFpEF, with the nadir risk around 120-129 mmHg of SBP and 70-79 mmHg of DBP after adjusting for confounding variables. Treatment with spironolactone did not affect the association significantly. The finding remained robust across sensitivity analyses.Higher or lower time-averaged cumBP was significantly associated with a higher risk of adverse events. Control of time-averaged cumulative BP within a reasonable range was an important component of hypertension management in HFpEF.