Lipoprotein(a) is a Promising Residual Risk Factor for Long-Term Clinical Prognosis in Peripheral Arterial Disease

Abstract

Objectives: We investigated the relationship between plasma lipoprotein(a) [Lp(a)] level and long-term prognosis, cardiovascular events, or pure leg events (LE) in patients with peripheral arterial disease (PAD). Materials and Methods: We prospectively enrolled 1104 PAD patients. The endpoints were LE, cerebrovascular- or cardiovascular-related death (CVRD), all-cause death (ACD), and major adverse cardiovascular events (MACE). Results: The incidences of LE, CVRD, ACD, and MACE were correlated with Lp(a) level (P<0.05). Lp(a) was positively correlated with low-density lipoprotein cholesterol and C-reactive protein (CRP) and negatively correlated with estimated glomerular filtration rate (eGFR). In the Cox multivariate regression analysis, high Lp(a), CRP, age, low ankle-brachial pressure index (ABI), eGFR, albumin, critical limb ischemia (CLI), cerebrovascular disease (CVD), and diabetes were associated with LE; high Lp(a), age, CRP, low ABI, body mass index, eGFR, albumin, CLI, coronary heart disease (CHD), CVD, and diabetes were associated with CVRD; high Lp(a), CRP, age, low ABI, eGFR, albumin, CLI, and CVD were associated with ACD; and high Lp(a), CRP, age, low eGFR, albumin, CLI, CHD, and diabetes were associated with MACE (P<0.05). Statins improved all endpoints (P<0.01). Conclusion: Lp(a) was a significant residual risk factor for LE, CVRD, ACD, and MACE in PAD patients.

Keywords: all-cause mortality; limb events; lipoprotein(a); major adverse cardiovascular event; peripheral arterial disease.

Fig. 1 (a) Cumulative incidence of pure leg events (LE) according to lipoprotein(a) levels is demonstrated with significant difference between L1 and L2 (P=0.038). (b) Cumulative incidence of cardiovascular- or cerebrovascular-related death (CVRD) according to lipoprotein(a) levels is demonstrated with significant difference between L1 and L2 (P=0.015).

Fig. 2 (a) Cumulative incidence of all-cause death (ACD) according to lipoprotein(a) levels is demonstrated with significant difference between L1 and L2 (P=0.002). (b) Cumulative incidence of major adverse cardiovascular events (MACE) according to lipoprotein(a) levels is demonstrated with significant difference between L1 and L2 (P=0.003).