Synergistic effect of lipoprotein (a) and C-reactive protein on prognosis of familial hypercholesterolemia

OBJECTIVE: The synergistic effect of lipoprotein (a) [Lp(a)] and C-reactive protein (CRP) on major adverse cardiovascular events (MACE) among patients with familial hypercholesterolemia (FH) is unknown. This study aimed to investigate the relations between Lp(a) and CRP levels and MACE in patients with FH whose Lp(a) levels are elevated. METHODS: We retrospectively investigated associations between genotypes and phenotypes, including low-density lipoprotein (LDL) cholesterol level and the occurrence of MACE among patients with FH (N = 786, male/female: 374/412). A Cox proportional hazard model was used to identify factors associated with MACE, adjusting for traditional risk factors. Patients with FH were divided into four groups, based on their Lp(a) and CRP levels, and assessed using Kaplan–Meier curves. RESULTS: The median follow-up was 12.6 years (interquartile range [IQR], 9.5–17.9 years). During follow-up, 129 MACE were observed. Median Lp(a) and CRP levels were 21.4 (10.9–38.3) mg/dL and 0.20 (0.11–0.29) mg/dL, respectively. Under these conditions, natural log-transformed Lp(a) and CRP were not associated with MACE (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.91–1.25; P = 0.220; and HR, 1.12; CI, 0.96–1.28; P = 0.190, respectively). However, in Group 4, Lp(a) and CRP were significantly associated with MACE (HR, 2.44; CI, 1.42–3.46; P = 1.8 × 10(−7)). CONCLUSIONS: In patients with FH, Lp(a) was significantly associated with MACE only when the CRP level was elevated. Patients with FH whose Lp(a) and CRP levels are elevated should be treated aggressively.