Twenty-year follow-up of Dutch familial hypercholesterolaemia cohort finds no link between Lp(a) and arterial stiffness (J Clin Med 2025)

Background and Aims: Elevated lipoprotein(a) [Lp(a)] and familial hypercholesterolemia (FH) are both inherited dyslipidemias that are independently associated with cardiovascular disease. Surrogate markers to assess signs of atherosclerosis, such as arterial stiffness, might be useful to evaluate the cardiovascular risk in young patients. The aim of this study is to evaluate the contribution of Lp(a) to arterial stiffness, as measured by carotid pulse wave velocity (cPWV) in young adults with FH. Methods: For this cross-sectional study, 214 children with FH who participated in a randomized controlled trial between 1997 and 1999 on the efficacy and safety of pravastatin were eligible. After 20 years, these patients were invited for a hospital visit, including cPWV assessment (by 4D flow MRI) and Lp(a) measurement. Linear mixed-effects models were used to evaluate the association between Lp(a) and cPWV. Results: We included 143 patients (mean [standard deviation] age: 31.8 [3.2] years) from 108 families. Median (interquartile range) cPWV was 1.62 (1.31-2.06) m/s. Both the unadjusted (ß = -0.0014 m/s per 1 mg/dL increase in Lp(a), 95% CI: -0.0052 to 0.0023, p = 0.455) and adjusted model (ß = -0.0005 m/s per 1 mg/dL increase in Lp(a), 95% CI: -0.0042 to 0.0032, p = 0.785) showed no significant association between Lp(a) and cPWV. Conclusions: Our findings indicate that Lp(a) levels are not associated with carotid arterial stiffness in young adults with FH. Possibly, High Lp(a) might cause atherosclerosis by mechanisms beyond arterial stiffness in young adults. Other surrogate markers of early signs of atherosclerosis may be more suitable to evaluate the Lp(a)-mediated contribution to atherosclerosis in young FH patients.