The effect of LP(a) in patients with heterozygous familial hypercholesterolemia on coronary plaque burden and calcium score determined by CT

Abstract

Rationale: People with heterozygous familial hypercholesterolemia (FH) have a genetic predisposition for developing premature cardiovascular disease (CVD). However the clinical phenotype of FH has a high variability which is due to metabolic and environmental factors. One of the metabolic factors that increase the risk for pre-mature CVD might be Lp(a). Previous studies have identified Lp(a) as an independent risk factor for cardiovascular disease. The goal of our study was to analyze the association between calcium scores and coronary plaque burden in relation with plasma Lp(a) levels in patients with FH and to study whether this association was similar in men and women. Methods and results: From February 2008 until June 2011 145 (93 men, age 52+/-8) patients with a clinical diagnosis of FH visiting the outpatient clinic for lipid disorders in the Medical Centre were included. These patients underwent a CT coronary angiography to determine the coronary plaque burden and calcium score. From 131 (84 men, age 53+/-8) of these patients blood was collected and Lp(a) levels were measured. Lp(a) levels were subsequently related to total coronary calcium score(TCS) and coronary plaque burden. Coronary plaque burden is described as diseased coronary segment score per patient (DSS). DDS and TCS were analyzed in a group with low Lp(a) <0,300 g/L and with high Lp(a) >1,000 g/L levels, adjusted for sex, using the Mann-Whitney U test. In men no significant differences in DSS (p=0,960) and TCS (p=0,400) were found if Lp(a) was determined. In women significantly higher DSS (p=0,022) and TCS (p=0,004) were found in the high-Lp(a) group. Conclusion: Our data show a higher amount of DSS and TCS in women with high Lp(a) levels in comparison with women with a low Lp(a). In men no difference in DSS and TCS is found between high and low Lp(a) groups. We show that serum levels of Lp(a) is associated with disease severity in FH women and not in FH men. Clinical relevance: High LP(a) levels in FH women are associated with advanced subclinical atherosclerosis. Therefore, we can identify a high risk subgroup in which we should attain an even more strict cardiovascular risk reduction.