Lipid-lowering Therapy and Predictors of сcardiovascular Outcomes in Patients with heterozygous Familial Hypercholesterolemia

Abstract

Introduction and purpose. Familial hypercholesterolemia (FH) – is a common genetic disorder charac-terized by increased low-density lipoprotein cholesterol (LDL-C) and premature ischemic heart disease (IHD). The purpose of the study was to evaluate the achievement of LDL-C treatment target and the frequency of cardiovascular events in patients with heterozygous FH according to RENAISSANCE registry.
Material and methods. The study included 271 people (median age [interquartile range] was 55 [44; 63] years; 40% were men, median follow-up 27 months) with definite and probable FH from RENAISSANCE registry: 138 (64%) subjects had a high risk of developing cardiovascular disease and 77 (36%) individuals had a very high risk. Duplex scans with evaluation of maximum stenosis was initially performed in all patients. At follow-up blood lipids profile was measured, therapeutic effectiveness of hypolipidemic agents was evaluated, frequency of cardiovascular events including myocardial infarction, stroke, revascularization procedures and IHD hospitalizations were investigated.
Results. At follow-up 114 (53%) patients were on hypolipidemic therapy. LDL-C treatment targets < 2.6 mmol/l was reached by 11 (23%) patients of high risk, 4 (6%) patients of very high risk had LDL-C < 1.8 mmol/l of those one had LDL-C < 1.5 mmol/l. Younger age, absence of IHD, arterial hypertension, xanthomas and family history of premature IHD were associated with low compliance with hypolipidemic therapy. Follow-up was obtained for 215 (80%) patients, 31 (11%) people were contacted by phone, 25 (9%) persons were lost to follow up. 12 (4.9%) patients experienced cardiovascular events. Cox regression analysis showed that patients with IHD and with maximum carotid stenosis more than 30% had relative risk (RR) for cardiovascular events nine times higher (RR 9.01; 95% confidence interval (Cl) 2.44–33.29; p = 0.0001; RR 9.37; 95% CI 3.01–29.17; p = 0.008, respectively). Patients with lipoprotein(a) [Lp(a)] ≥ 50 mg/dl had RR 4,02 (95% Cl 1.96–13.39; p = 0.013).
Conclusion. The RENAISSANCE registry showed that patients with heterozygous FH had poor adherence to hypolipidemic therapy and very rare achievement of LDL-C. IHD, maximum stenosis of carotid artery ≥ 30% and Lp(a) level ≥ 50 mg/dl were independently associated with increasing relative risk of cardiovascular events.