Am J Med. 2026 Oct 7:S0002-9343(26)00708-4. doi: 10.1016/j.amjmed.2026.09.038. Online ahead of print.
ABSTRACT
BACKGROUND: Elevated systolic blood pressure (SBP) is associated with paradoxically lower mortality in heart failure with reduced ejection fraction (HFrEF), but whether this reflects underlying pathophysiology or residual confounding remains uncertain. Because higher SBP is also a risk factor for kidney failure, we tested the hypothesis that a higher risk of kidney failure despite lower mortality would support a pathophysiological explanation for this mortality paradox.
METHODS: We assembled a propensity score-matched cohort of 59,834 patients with HFrEF, hypertension, and no baseline kidney failure. The 29,917 pairs with SBP ≥130 versus <130 mmHg were balanced on 77 baseline characteristics. Outcomes were two-year all-cause mortality and incident kidney failure. Cox regression estimated associations of SBP ≥130 mmHg with outcomes, and restricted cubic splines assessed nonlinearity across the SBP continuum.
RESULTS: All-cause mortality occurred in 24.9% of patients with SBP <130 mmHg and 23.0% of patients with SBP ≥130 mmHg (HR associated with SBP ≥130 mmHg, 0.91; 95% CI, 0.88-0.94). Corresponding rates for kidney failure were 1.0% and 1.5% (HR, 1.44; 95% CI, 1.24-1.66). SBP had a nonlinear association with mortality (P<0.001 for nonlinearity), with progressively higher risk at SBP below 130 mmHg but no higher risk above 130 mmHg. The association with kidney failure was linear (P=0.68 for nonlinearity) with progressively higher risk above 130 mmHg.
CONCLUSIONS: In patients with HFrEF, elevated SBP is associated with lower mortality but a higher risk of kidney failure. These opposing cardiac and renal associations support a pathophysiological explanation for the inverse relationship between SBP and mortality in HFrEF.
PMID:42843696 | DOI:10.1016/j.amjmed.2026.09.038