Elevated Lp(a) doubles cardiovascular risk in familial hypercholesterolaemia but not in familial combined hyperlipidaemia, where diabetes dominates instead, 909-patient study finds (Nutr Metab Cardiovasc Dis 2025)

Original title: Lipoprotein(a) in familial dyslipidemias: The effect on cardiovascular prognosis in patients with familial hypercholesterolemia or familial combined hyperlipidemia

Nutr Metab Cardiovasc Dis · 23 January 2025 · 7

Skoumas I, Andrikou I, Simantiris S, Grigoriou K, Dima I, Terentes-Printzios D, Papanikolaou A, Akinosoglou K, Tsioufis K, Vlachopoulos C

This study followed 909 cardiovascular-disease-free patients with heterozygous familial hypercholesterolaemia (FH, n = 433, mean age 44.2 years) or familial combined hyperlipidaemia (FCH, n = 476, mean age 49.0 years) over a mean 10 years, to compare cardiovascular prognosis and Lp(a)'s prognostic role between these two familial dyslipidaemias. Major cardiovascular events occurred in 6.6% of the total population, more often in FH than FCH (8.1% vs. 5.5%, P = 0.03), and FH patients had over double the cardiovascular risk of FCH patients (HR 2.17, 95% CI 1.10-4.26, P = 0.02). In FH patients, elevated baseline Lp(a) (30 mg/dL or above) independently predicted adverse cardiovascular events beyond LDL cholesterol (HR 2.37, 95% CI 1.41-4.90, P = 0.02), whereas in FCH patients Lp(a) showed no independent prognostic value; instead, baseline diabetes tripled cardiovascular risk in FCH patients (HR 3.56, 95% CI 1.19-11.33, P = 0.03). The authors conclude Lp(a) and diabetes play distinct, disorder-specific prognostic roles across these two common familial dyslipidaemias.

Original abstract

Background And Aims: Familial dyslipidemias are associated with increased cardiovascular risk. Increased lipoprotein(a) [Lp(a)] is considered as the most prevalent monogenic lipid disorder. The objective of the study was to identify the cardiovascular prognosis of patients with familial dyslipidemias (heterozygous familial hypercholesterolemia (FH) or familial combined hyperlipidemia (FCH)), without cardiovascular disease at baseline, investigating in parallel the effect of Lp(a).

Methods And Results: 909 patients with FH (n = 433, mean age 44.2 ± 12.8 years) or FCH (n = 476, mean age 49.0 ± 11.1 years) were evaluated during a mean period of 10 years. The main endpoint was the composite of major cardiovascular events. The incidence of major cardiovascular events in the total population was 6.6 %, while greater in patients with FH compared to patients with FCH (8.1 % vs 5.5 %, p = 0.03). Multiple Cox regression analysis revealed that FH patients had greater cardiovascular risk compared to FCH patients (HR 2.17, 95 % CI 1.10-4.26, p = 0.02). In FH patients, increased baseline Lp(a) (≥30 mg/dl) was an independent predictor of adverse cardiovascular events (HR 2.37 95 % CI 1.41-4.90, p = 0.02), whereas in FCH patients was not. In FCH patients the presence of diabetes at baseline was a strong independent prognosticator of adverse cardiovascular events (HR 3.56 95 % CI 1.19-11.33, p = 0.03), after adjustment for confounders.

Conclusions: FH patients demonstrate double cardiovascular risk compared to FCH patients. In FH patients increased Lp(a) doubles the cardiovascular risk, beyond low density lipoprotein cholesterol. In FCH patients the presence of diabetes triples the cardiovascular risk, beyond Lp(a) which does not seem to convey an independent prognostic value.

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