Inflammation, Lp(a) and cardiovascular mortality: results from the LURIC study

Lipoprotein(a) [Lp(a)] concentrations have been associated with cardiovascular risk. Recent studies suggested an interaction between systemic inflammation assessed via high-sensitivity C-reactive protein (hsCRP) and Lp(a). This study aimed to evaluate whether Lp(a), hsCRP, and interleukin-6 (IL-6) levels are associated with cardiovascular mortality in a German hospital-based cohort.

Data were drawn from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, including 3,316 patients undergoing coronary angiography. Lp(a) was measured by immunoturbidimetry and categorized into three strata (< 50 mg/dL, n = 2668; 50-100 mg/dL, n = 482; > 100 mg/dL, n = 163). HsCRP was measured by immunonephelometry and categorized by intervals (1st < 1 mg/L, 2nd 1-2 mg/L and 3rd interval > 2 mg/L). IL-6 was measured by ELISA and categorized into two groups (1st < 3.2 ng/L, 2nd ≥ 3.2 ng/L). The primary outcome was cardiovascular disease (CVD) mortality, analyzed using Cox proportional hazards models and logistic regression.

Participants were predominantly male, with a mean age of 62.6 years. Extremely high Lp(a) (> 100 mg/dL) was associated with increased cardiovascular mortality (HR 1.5, 95% CI 1.06-2.12) compared to Lp(a) < 50 mg/dl. Both hsCRP (> 2 mg/L, HR 1.39, 95% CI 1.08-1.79 third vs. first interval) and more so IL-6 (HR 1.92, 95% CI 1.64-2.23, upper vs. lower half), were independently associated with higher CVD mortality. While hsCRP did not increase the Lp(a)-CVD mortality in stratified analysis, high IL-6 conferred an increased risk at Lp(a) levels > 100 mg/dL (HR 1.25, 95% CI 1.09-1.44).

HsCRP and IL-6 are associated with cardiovascular mortality. Markedly elevated Lp(a) is associated with an increased risk of cardiovascular mortality in the context of high systemic inflammation. Anti-inflammatory treatments may provide additional therapeutic benefits for individuals with high Lp(a).