Lipoprotein(a) is associated with higher DNA damage in patients with heterozygous familial hypercholesterolemia

Abstract

Abstract Heterozygous familial hypercholesterolemia (HeFH) is a frequent autosomal-dominant inherited disorder associated with premature cardiovascular disease (CVD). HeFH subjects have a higher lipoprotein(a) (Lp(a)) concentration than the general population. Patients with FH are exposed to elevated levels of LDL from birth and ox-LDL may induce other oxidation pathways. The aim of the study was to determine the levels of markers of oxidative stress, and DNA damage in patients with HeFH and describe the effect of Lp(a) on the resulting damage. Higher DNA damage was identified in patients with HeFH compared the normolipidemic and CVD was associated with higher damage (determined by comet assay). Oxidative stress markers are elevated in HeFH patients (determined by comet assay); however, only ox-LDL was higher in the CVD group and its level correlated with DNA damage. Patients with HeFH show a positive correlation between the levels of DNA damage and Lp(a). Higher levels of Lp(a) are associated with greater DNA damage, especially in patients with HeFH and CVD. In HeFH patients, the optimal cut-off point of Lp(a) level associated with CVD is > 25nmol/L, i.e. much lower than for the general population. However this cut-off point needs validation in a larger group of HeFH patients.