Systolic Blood Pressure and Pulse Pressure in Heart Failure: Pooled Participant-Level Analysis of Four Trials

Background

Hypertension is common in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), and current guidelines recommend treating systolic blood pressure (SBP) to a target below 130 mmHg. However, data supporting treatment to this target is limited. Additionally, pulse pressure (PP), a marker of aortic stiffness, has been associated with increased risk of cardiovascular events, but its prognostic impact in HFpEF has not been extensively studied.

Objectives

This study aimed to explore the impact of baseline SBP and PP on cardiovascular outcomes in patients with HFmrEF or HFpEF.

Methods

I-PRESERVE, TOPCAT-Americas, PARAGON-HF and DELIVER were global, randomized clinical trials testing irbesartan, spironolactone, sacubitril/valsartan and dapagliflozin respectively, against either a placebo or an active comparator (valsartan, in PARAGON-HF), in patients with HF and a left ventricular ejection fraction ≥40% (in DELIVER) or ≥45% (in the other trials). The relationship between continuous baseline SBP and PP, and the primary endpoint (first HF hospitalization or cardiovascular death) was analyzed with restricted cubic splines. We further evaluated the prognostic impact of SBP categories (<120, 120-129, 130-139, ≥140 mmHg) and PP quartiles on the primary endpoint.

Results

A total of 16,950 patients (mean age 71±9 years, 49% male, mean SBP 131±15 mmHg, mean PP 55±14 mmHg) were included. The relationship between SBP and the primary endpoint was J-shaped, with the lowest risk at 120-130 mmHg. A similar pattern was found for PP, with the lowest risk at 50-60 mmHg. The highest SBP category (reference: 120-129 mmHg) and PP quartile (reference: 46-54 mmHg) were associated with a higher risk of the primary outcome (HR: 1.22; 95% CI: 1.10-1.34; HR: 1.22; 95% CI: 1.11-1.34, respectively). Higher PP was associated with greater cardiovascular risk, regardless of SBP.

Conclusions

Our analysis of a large pooled dataset from four clinical trials, including over 16,900 patients with HFmrEF/HFpEF, indicates a J-shaped relationship between both SBP and PP, and cardiovascular risk. The lowest risk was observed at SBP levels between 120 and 130 mmHg and PP values between 50 and 60 mmHg.