Joint control of LDL-C, Lp(a) and CRP erases the excess cardiovascular risk of steatotic liver disease in a 291,995-person UK Biobank cohort (Nutr Metab Cardiovasc Dis 2026)

Original title: Joint control of low-density lipoprotein cholesterol, lipoprotein(a), and high-sensitivity C-reactive protein in relation to risk of cardiovascular disease in adults with steatotic liver disease

Nutr Metab Cardiovasc Dis · 27 March 2026 · 7

Zhang S, Borné Y, Ma L, Huang T, Qi L

Prospective UK Biobank cohort of 291,995 adults (77,187 MASLD, 22,190 MetALD, 5474 ALD, 187,144 without steatotic liver disease, SLD) followed for a median 12 years (24,251 CVD events), testing whether joint control of LDL-C, Lp(a) and hs-CRP removes the excess cardiovascular risk of SLD subtypes. Compared with zero risk factors controlled, having all three within target range lowered CVD risk in MASLD (HR 0.65, 95% CI 0.58-0.72), MetALD (HR 0.61, 0.49-0.76) and ALD (HR 0.57, 0.35-0.93). With all three factors controlled, SLD subtypes showed no excess CVD risk, and ALD even lower risk, compared with non-SLD controls, a reassuring result that needs confirmation outside UK Biobank's largely European-ancestry population.

Original abstract

Background And Aims: We examined whether the excess cardiovascular disease (CVD) risk among adults with steatotic liver disease (SLD) subtypes could be reduced or eliminated through joint control of low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], and high-sensitivity C-reactive protein (hs-CRP).

Methods And Results: This prospective cohort study included 291,995 participants from the UK Biobank, comprising 77,187 with metabolic dysfunction-associated steatotic liver disease (MASLD), 22,190 with metabolic dysfunction and alcohol-associated liver disease (MetALD), 5474 with alcohol-associated liver disease (ALD), and 187,144 without SLD. Cox proportional hazards models were used to assess CVD risk associated with numbers of LDL-C, Lp(a), and hs-CRP controlled within the target range. During 12 years of median follow-up, 24,251 CVD events were documented, with 19,661 coronary heart disease and 5600 stroke. Among individuals with various SLD subtypes, those with all three factors controlled had the lowest risks of CVD, with HRs (95% CIs) of 0.65 (0.58, 0.72) in MASLD, 0.61 (0.49, 0.76) in MetALD, and 0.57 (0.35, 0.93) in ALD when comparing to zero-factor control. In addition, among individuals with SLD subtypes achieving all three factors within target ranges, the HRs (95% CIs) of CVD were 0.97 (0.88, 1.07) in MASLD, 0.90 (0.75, 1.08) in MetALD, and 0.63 (0.42, 0.95) in ALD, as compared with non-SLD controls. Similar association patterns were observed for coronary heart disease and stroke.

Conclusions: Participants with various SLD subtypes who had optimally controlled LDL-C, Lp(a), and hs-CRP showed no excess or even lower risk of CVD as compared with the general population.

Trial Registered: Not available.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.