Abstract
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity in hypertension. However, the impact of NAFLD and related fibrosis on hypertension and its control of cardiovascular disease (CVD) and mortality outcomes remains unclear.
METHODS: Participants with hypertension were sourced from two cohorts, with 12 907 individuals from the National Health and Nutrition Examination Survey (NHANES) and 120 639 from the UK Biobank (UKBB). Mendelian randomization analyses explored the causal relationship among hypertension, NAFLD, and CVD. Cox regression models estimated the hazard ratios for CVD and mortality associated with NAFLD (defined by fatty liver index) and liver fibrosis (defined by fibrosis-4 index or NAFLD fibrosis score).
RESULTS: The NHANES documented 3376 deaths over a median follow-up of 8.5 years, and the UKBB documented 15 864 deaths, 4062 incident ischemic strokes, and 5314 incident myocardial infarctions over a median follow-up of 13.5 years. The hazard ratios for CVD and mortality increased in accordance with NAFLD grading (ischemic stroke, 1.16 [95% CI, 1.01-1.33]; myocardial infarction, 1.64 [95% CI, 1.44-1.86] in UKBB; and all-cause mortality, 1.29 [95% CI, 1.09-1.54] in NHANES). High-risk fibrosis increased the hazard ratios for all-cause mortality by 91% and ischemic stroke by 42% in patients with NAFLD in UKBB and for all-cause mortality by 95% in NHANES. NAFLD partially mediates the risk of hypertension for incident CVD and mortality (NHANES, 6.45% of all-cause mortality; UKBB, 5.17% of all-cause mortality; and 8.20% of myocardial infarction).
CONCLUSIONS: NAFLD and related liver fibrosis are associated with a higher risk of incident CVD and mortality in hypertensives. NAFLD and related liver fibrosis seem to partially mediate hypertension-induced CVD and mortality.