Baseline and on-statin treatment lipoprotein(a) levels for predicting cardiovascular events in patients with familial hypercholesterolemia

Background and aims: Lipoprotein(a) [Lp(a)] has been considered as a causal risk factor for cardiovascular disease (CVD) in the general population and levels vary in different ethnicities. However, no systemic analysis is currently available regarding the relation of plasma Lp(a) levels to cardiovascular events (CVEs) in Chinese patients with heterozygous familial hypercholesterolemia (HeFH). Methods: Three hundred and ninety-three patients with HeFH undergoing Lp(a) measurement at baseline were consecutively enrolled and followed prospectively for an average of 36.5 months. Lp(a) levels were determined using an immunoturbidimetry assay. Cox regression analysis with adjusted hazard ratios (HRs) and Kaplan-Meier analysis were used to evaluate the prognostic value of Lp(a) on CVEs. Results: Thirty-five events occurred during follow-up. Lp(a) was significantly higher in patients with CVEs (53.3 mg/dL versus 31.7 mg/dL, p < 0.001). In Kaplan-Meier analysis, patients with upper tertile of Lp(a) had a significant lower event-free survival (p = 0.004). After adjusting for confounding risk factors, per log unit increase in baseline Lp(a) was independently associated with CVEs [HR: 2.03(1.28-3.21), p = 0.002]. HRs remained unchanged after accounting for hard endpoints and did not vary too much in several relevant subgroups. Adding Lp(a) to the Cox model led to a significant improvement in C-statistic, net reclassification and integrated discrimination. Moreover, HR for upper versus lower tertile of change in Lp(a) was 2.68 (1.11-6.48) for CVEs after one year. Conclusions: Both baseline and on-statin treatment Lp(a) levels were associated with an increased risk of CVEs in patients with HeFH, suggesting that Lp(a) measurement might clinically help further risk stratification of FH patients.