Abstract
BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging cardiovascular risk factor; evidence-based blood pressure (BP) management strategies for this population remain limited. We aimed to evaluate the efficacy and safety of a multifaceted intervention anchored by intensive BP control (< 130/80 mmHg) in patients with MAFLD using data from the China Rural Hypertension Control Project (CRHCP) trial. METHODS: This study is a post hoc analysis of the CRHCP trial, an open-label, cluster-randomized controlled trial conducted from 2018 to 2023 across 326 villages in China. Adults aged ≥ 40 years with hypertension were eligible. Participants were randomized in a 1:1 ratio to receive either intensive BP control (target < 130/80 mmHg) or usual care. MAFLD was diagnosed using the hepatic steatosis index (HSI ≥ 36) combined with metabolic criteria. The primary outcome was a composite of stroke, myocardial infarction, heart failure, or cardiovascular death; secondary outcomes included individual components of the primary outcome and all-cause death. The CRHCP trial is registered with ClinicalTrials.gov NCT03527719. RESULTS: A total of 29,624 participants (12,912 with MAFLD) were included in this analysis. The mean (SD) age was 63.2 (9.2) years, and 18,348 (61.9%) were female. During 48-month follow-up, risk reductions for composite CVD with intensive BP control were similar in patients with MAFLD (adjusted HR, 0.69; 95% CI, 0.61-0.78; P < 0.001) and those without MAFLD (HR, 0.70; 95% CI, 0.63-0.77; P < 0.001), with comparable reductions in stroke and cardiovascular death (adjusted HR for patients with MAFLD, 0.72; 95% CI, 0.55-0.95; P = 0.019; adjusted HR for patients without MAFLD, 0.63; 95% CI, 0.53-0.76; P < 0.001). All-cause mortality declined in patients without MAFLD (adjusted HR, 0.84; 95% CI, 0.76-0.93; P < 0.001) but not significantly in those with MAFLD (adjusted HR, 0.93; 95% CI, 0.79-1.09; P = 0.366), though the interaction was not significant (P for interaction = 0.601). There was an increased risk of hypotension in patients with or without MAFLD. Subgroup analyses confirmed consistent benefits. CONCLUSIONS: This study demonstrates that multifaceted intensive BP control at < 130/80 mmHg significantly reduces the risk of cardiovascular disease in patients with MAFLD. These findings provide preliminary evidence for BP management in patients with MAFLD and require confirmation in future prospective clinical trials.