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

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.