Lipoprotein (a) and new-onset type-2 diabetes in patients with familial combined hyperlipidemia: a 9 years follow-up study

Abstract

Abstract Background Elevated lipoprotein(a) [Lp(a)] levels have been related with increased cardiovascular (CV) risk in the general population. However, its relationship with type-2 diabetes and CV risk in patients with Familial Combined Hyperlipidemia (FCH) is rather unclear. Thus, the aim of our study was to investigate the prognostic role of Lp(a) regarding new-onset type-2 diabetes and major adverse cardiovascular outcomes in patients with FCH. Methods 485 patients from the outpatient lipid clinic of our hospital (301 males,mean age 49.8±10.8 years, 35%smokers, 16% with diabetes mellitus), without history of CV disease, who fulfilled the FCH criteria participated in the study. Participants were evaluated for a mean follow-up period of 8.9±7.5 years with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of plasma glucose, lipid profile, and levels of Lp(a). All subjects were on lipid-lowering medication (statin and ezetimibe or fibrate) during the follow-up period. The endpoints of our study was new-onset diabetes and the composite of major CV events (coronary artery disease events and stroke). Results The incidence of new-onset diabetes during the follow-up period was 10% (n=42). The group of patients with new-onset diabetes (n=42) had lower levels of Lp(a) at baseline compared to those without new-onset diabetes (n=376) (23.8±19.2 vs 32.9±39.5 mg/dl, p=0.01). Also, those with new-onset diabetes had a lower percentage of increased Lp(a) levels (≥30 mg/dl) at baseline compared to those without new-onset diabetes (21% vs 34%). Multiple Cox regression analysis revealed that increased Lp(a) (≥30 mg/dl) is an independent predictor of lower diabetes incidence during the follow-up period (HR 0.39, 95% CI 0.17–0.90), after adjustment for confounding factors. Moreover, the incidence of new-onset CV events in the total population was 6.4% (n=31).In the group of patients with increased Lp(a) levels at baseline (≥30 mg/dl, n=159, 33%) there was a trend towards a greater incidence of CV events during the follow-up period, compared to the group of patients with lower Lp(a) levels (<30 mg/dl, n=326, 67%), although the difference between the two groups was not statistically significant (8.8% vs 5.1%, p=0.1). Conclusions In patients with FCH, increased baseline Lp(a) is an independent predictor of lower incidence of new-onset type-2 diabetes after an almost 9 years follow-up period. Moreover, increased Lp(a) seems to convey an increased CV risk also in patients with FCH. Funding Acknowledgement Type of funding sources: None.