P5334A 15-year follow-up of 315 patients with familial hypercholesterolemia from the North-West region of Russia

• Published in: European Heart Journal
• Main Authors: Konstantinov, V, Kuznetsova, T, Korneva, V, Serebrenitskaya, M
• Format: Article in Journal/Newspaper
• Language: English
• Published: Oxford University Press (OUP) 2019
• Subjects: Cardiology and Cardiovascular Medicine; karelia*
• Online Access: http://dx.doi.org/10.1093/eurheartj/ehz746.0302; http://academic.oup.com/eurheartj/article-pdf/40/Supplement_1/ehz746.0302/30202011/ehz746.0302.pdf

Abstract Familial hypercholesterolemia (FH) is one of the most common inherited diseases that lead to premature atherosclerosis and coronary heart disease (CHD). Aim of the study to ascertain genetic and environmental factors influencing the time course of FH during a 15-year follow-up in a large FH cohort from the North-West region of Russia. We screened more than 1ehz746.0302 high risk patients in order to reveal FH in Saint-Petersburg and Petrozavodsk using DLCN criteria. In most patients DNA analysis was also performed. Definite FH (≥8 according to DLCN) was found in 315 patients (221 - in Saint-Petersburg, 94 - in Petrozavodsk). These patients were followed-up for 15 years and more. CHD was more frequent in male patients, patients older than 60 years of age and was associated with higher levels of total cholesterol, LDL cholesterol, lower levels of HDL cholesterol, arterial hypertension, smoking and higher DLCN scoring. Patients without CHD had lowest LDL/HDL ratio (5.2±0.45) whereas patients with stable and progressive CHD had LDL/HDL ratio - 7.7±0.89 and 10.4±0.78, respectively (p≤0.05). Genetic study revealed only 1 homozygous patient and 1 patient with apoB-100 (FDP) gene mutation. Only 1 case of FH-North Karelia mutation that is typical for Finland was found in Petrozavodsk. Most of revealed mutations in LDL-receptor gene were unique i.e. found only in 1 family. This suggest the absence of a strong founder effect associated with FH in the North-West Region of Russia. Due to high heterogeneity of FH-causing mutations we failed to establish interrelations between type of LDL-receptor gene mutations and severity of atherosclerosis and CHD time course. 14% of FH patients didn't take any hypolipidemic medications at the onset of the follow-up, whereas 61% took statins and 25% statin + ezetimibe. Homozygous patient was treated both with statin, ezetimibe, evolocumab and LDL-apheresis. Nevertheless, 26% of the treated group didn't achieve the target LDL-C levels. It is interesting that 40% of patients who didn't reach LDL-goals were current smokers (compared with 5% of patients who reached LDL-goals). 33 patients (10.5%) died during the follow-up mostly due to cardiovascular complications. Death rates in FH patients were strongly associated with age, male sex, LDL/HDL ratio, smoking and effectiveness of hypolipidemic treatment. FH is strongly associated with high CHD risk; the time course of FH is much more favourable in females, in patients with low LDL/HDL ratio and free of other modifiable risk factors. Type of LDL-receptor gene mutation doesn't influence lipid levels or clinical manifestations of FH.