Familial hypercholesterolemia and cardiovascular disease in older individuals

Abstract

Background and aims: Familial hypercholesterolemia (FH) is characterized by high LDL-cholesterol (LDL-C) and early atherosclerotic cardiovascular disease (ASCVD). With a lipid lowering therapy (LLT), most individuals with FH may have a longer ASCVD-free survival. However, there is scant data about older individuals with FH.

Methods: We compared characteristics of genetically defined FH older individuals with age-matched non-FH counterparts.

Results: From 4111 genotyped individuals, 462 older than 60 years were included (198 positive and 264 negative for FH variants). There were no differences regarding median age [%25; 75%] 66.0 (62.0; 71.0) and 66.0 (62.2; 71.0) years, p = 0.68 for FH and non-FH, respectively. In both groups, there was a higher frequency of females, however, there were more males in the FH group 37.4% vs. 24.2%, p = 0.002. No differences were seen between FH and non-FH in LLT use: 88.5% vs. 91.5%, p = 0.29. Despite a longer LLT duration in FH patients (with 11.0 (7.0; 20.0) vs. 7.0 (3.0; 13.0) years, p < 0.001), treatment was started late in both groups: at 54.0 (47.0; 61.0) and 59.0 (52.0; 64.0) years, p < 0.001, in FH and non-FH, respectively. FH had greater frequencies of previous and early ASCVD (40.9% vs. 27.3%, p = 0.002, and 22.2% vs. 9.0%, p < 0.001). In FH, male sex [HR (95%CI)] 2.67 (1.50-4.73), p = 0.001, and LLT onset age 0.96 (0.93-0.99), p = 0.009, were independently associated with ASCVD.

Conclusions: Among hypercholesterolemic older individuals participating in a cascade screening program, the genetic diagnosis of FH was associated with higher ASCVD rates, emphasizing the relevance of a monogenic defect as the cause of long-lasting hypercholesterolemia and ASCVD risk, particularly in men.

Keywords: Ageing; Atherosclerosis; Cardiovascular disease; Cholesterol; Familial hypercholesterolemia; Monogenic disease; Older individuals; Statins.