Prognostic role of lipoprotein(a) in atherosclerotic cardiovascular disease risk from a perspective on current risk stratification

Abstract

Lipoprotein(a) [Lp(a)] is an emerging predictor for atherosclerotic cardiovascular disease (ASCVD) but the association from a perspective on current risk stratification was unknown. A cohort of 9944 Chinese patients with ASCVD was recruited and refined into very-high-risk (VHR) and non-VHR subgroups according to current guideline. Lp(a) plasma levels were divided by its concentration (<30, 30-50, 50-75, and ≥75 mg/dL) and percentile zones (<25th, 25-50th, 50-75th, 75-90th, ≥90th). Cardiovascular events (CVEs) occurred during an average of 38.5 months' follow-up were recorded. We found that Lp(a) was increased with risk stratification of ASCVD increasing. Prevalence of CVEs had a significantly increasing trend with gradients of Lp(a) elevation in VHR but not in non-VHR subgroup. The adjusted HRs (95%CIs) for CVEs were 1.75(1.25-2.46) in the highest group of Lp(a) ≥75 mg/dL compared with the group of Lp(a) <30 mg/dL as the reference in overall patients, 2.18(1.32-3.58) in VHR subgroup and 1.43(0.93-2.18) in non-VHR subgroup, respectively. The adjusted HRs (95%CIs) at the highest grade of Lp(a) levels (≥90th) were 1.72(1.19-2.50) in overall population, 2.83(1.53-5.24) in VHR subgroup and 1.38(0.86-2.12) in non-VHR subgroup, respectively. These findings suggested that Lp(a) might contribute more to CVEs risk in VHR subgroup of ASCVD.

Keywords: Chinese; atherosclerotic cardiovascular disease; lipoprotein(a); risk stratification.

FIGURE 1

The flowchart of the present study. ASCVD, atherosclerotic cardiovascular disease; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate.

FIGURE 2

Distribution of Lp(a) levels in each group according to current risk stratification of ASCVD. Percentages of the population with Lp(a) of <30, 30−50, 50−75, 75−100, and ≥100 mg/dL, and values of Lp(a) according to percentiles (25th, 50th, 75th, 90th, and 95th), respectively. Lp(a), lipoprotein(a); VHR, very‐high‐risk.

FIGURE 3

Proportions of CVEs in different risk‐stratification group across Lp(a) distribution. (A) Lp(a) stratified by its concentration (<30, 30−50, 50−75, and ≥75 mg/dL). (B) Lp(a) stratified by its percentile zones (<25th, 25−50th, 50−75th, 75−90th, and ≥90th). CVE, cardiovascular event; Lp(a), lipoprotein(a); VHR, very‐high‐risk.

FIGURE 4

Values of Lp(a) evaluated by its concentrations to current risk stratification in CVEs prediction. Lp(a) plasma levels were divided by its concentration (<30, 30−50, 50−75, and ≥75 mg/dL). Univariate and multivariate Cox proportional hazards regression analyses were performed. Multivariate models adjusted for age, sex, BMI, SBP, DM, LDL‐C levels, current smoking, and medications at enrollment. CVE, cardiovascular event; CI, confidence interval; HR, hazard ratio; Lp(a), lipoprotein(a).

FIGURE 5

Values of Lp(a) evaluated by its percentiles to current risk stratification in CVEs prediction. Lp(a) plasma levels were divided by its percentile zones (<25th, 25−50th, 50−75th, 75−90th, and ≥90th). Univariate and multivariate Cox proportional hazards regression analyses were performed. Multivariate models adjusted for age, sex, BMI, SBP, DM, LDL‐C levels, current smoking, and medications at enrollment. CVE, cardiovascular event; CI, confidence interval; HR, hazard ratio; Lp(a), lipoprotein(a).