15289-s-bos

5 73 | Lp(a) and AoVC in FH Introduction Aortic valve calcification (AVC), characterized by calcium deposition and thickening of the aortic valve, is a significant risk factor for aortic valve stenosis and cardiovascular disease (CVD). AVC prevalence in the elderly population (> 75 years old) is approximately 50% and 25% of them develop aortic valve stenosis [1]. AVC prevalence and severity are associated with coronary artery disease (CAD) [2], all-cause mortality [3] and aortic stenosis [4]. AVC shares several risk factors with atherosclerosis including age, male gender, dyslipidemia, smoking, hypertension, diabetes and obesity [5]. In heterozygous familial hypercholesterolemia (FH) patients, the onset and progression of valvular calcification are not completely explained by the above-mentioned risk factors, particularly not in statin-treated FH patients, whose low density lipoprotein (LDL)-cholesterol levels are markedly reduced, compared to the untreated condition. Additional risk factors for valvular calcification in these patients remain to be identified. Lipoprotein(a) [Lp(a)] is an LDL-like particle with an extra protein named apolipoprotein(a) [apo)(a)], covalently bound to apolipoprotein B-100 (apoB). Lp(a) concentrations are largely genetically determined by variations in the kringle IV (KIV) repeat number in the LPA gene encoding for apo(a) [6]. The apo(a) size is inversely associated with plasma Lp(a) levels: KIV repeat numbers below 23 are associated with, on average, elevated plasma Lp(a) levels [6]. Elevated plasma Lp(a) levels are considered a major risk factor for CVD in the general population [7, 8] as well as in FH patients [9-11]. It has been suggested that Lp(a) mediates CVD via its effects on atherosclerotic stenosis, fibrinolysis and wound healing [12]. A recent genome wide association study reported an association of a SNP in the LPA gene and plasma Lp(a) concentrations with AVC and aortic stenosis across multiple ethic groups [13]. Moreover, plasma Lp(a) levels have been associated with calcific aortic valve disease and accumulation of apo(a) has been observed in early lesions of aortic valve stenosis [14-16]. The aim of this study was to investigate whether Lp(a) concentrations and the KIV repeat copy number variation are associated with AVC in a cohort of asymptomatic statin-treated heterozygous FH patients.