Abstract 9323: Molecular Defects Are Not Associated With Occurrence of Cardiovascular Events in Older Individuals With Familial Hypercholesterolemia on Lipid Lowering Therapy

Abstract

Introduction: Familial hypercholesterolemia (FH) is a genetic disorder associated with early onset atherosclerotic cardiovascular disease (ASCVD). However, lipid lowering therapies (LLT) may change FH natural history. There is scant data about elderly (≥60 years) with FH. Hypothesis: FH molecular defect may not influence on ASCVD risk after LLT in older individuals. Methods: Older hypercholesterolemic individuals were divided into 4 groups (2X2) according to the presence (FH +) or not of genetic variants (FH-) and previous or not clinical ASCVD (ASCVD+ and ASCVD-). Association of biomarkers with ASCVD onset was tested using Cox models. Results: From 4,111 genotyped individuals, 377 (9.1%) were elderly [age 66 (63; 71)] years, 28.9% men, 42.7% FH+, LDL-C on LLT 144 (109; 200) mg/dL, median LLT duration 9 (5;16) years. Overall ASCVD was present in 32.1%, and 62.1% and 34.5% had ASCVD of early onset in FH+ and FH- respectively. FH-/ASCVD+ (n=161), FH+/ASCVD- (n=95), FH-/ASCVD+ (n=55) and FH+/ASCVD+(n=66) were followed by 4.8(7;3) years and 51 new ASCVD events (2.8/100 patients/year) occurred. No differences were seen regarding age, hypertension, body mass index, current use, duration, and intensity of LLT and LDL-C at the last follow-up visit. In univariate analysis there was an association of male gender (p = 0.002), presence of genetic variants (p = 0.006), diabetes (p = 0.006), smoking (p = 0.028) and previous ASCVD (p = 0.000) with new ASCVD event. There was no association of LLT and current or previous lipid profile, except with HDL-C at diagnosis (p=0.014), with ASCVD event. Table 1 shows that after multivariate analysis the genetic defect was not associated with occurrence of ASCVD events. Conclusion: Although FH is associated with a higher risk of early ASCVD even when compared to other hypercholesterolemics, in older individuals after LLT the presence of genetic defects was not associated with the occurrence of new events.