Association of Lipoprotein(a) with cardiovascular and all-cause mortality in China: a cohort study based on cardiorenal improvementNT-II
G Yuan, X Lu, Z Yuan, Z Huang, H Huang, Y Ling, H Ruan, W Zhang, J Deng, W Guo, S Chen, J L, J Chen, Y LAbstract
Background
Lipoprotein(a) [Lp(a)] is a well-recognized hazard indicator for cardiovascular disease (CVD) and all-cause mortality. Higher Lp(a) levels are robustly correlated with adverse cardiovascular outcomes. However, Lp(a) exhibits notable ethnic heterogeneities, with most epidemiological studies conducted primarily in Western populations and relatively limited data from Asian cohorts. This paucity of evidence may influence the accurate evaluation and tailored intervention of Lp(a) in Asians.
Objective
The purpose of this research is to analyze the link between Lp(a) levels and the hazard of cardiovascular mortality and all-cause mortality in individuals aged ≥18 years with confirmed coronary artery disease (CAD). We further sought to elucidate the threshold effect of Lp(a) to identify possible intervention targets and strategies for this high-risk population.
Method
This retrospective cohort study incorporated 51,489 patients aged ≥18 years (mean age 62.7 years, 23.5% female) with baseline CAD from the Cardiorenal Improvement-II Study (CIN II) database of Guangdong Provincial People's Hospital. The relationship between Lp(a) concentrations and CVD mortality and all-cause mortality was evaluated. Incidence rates of the outcomes were compared across three Lp(a) categories defined by boundary values of 30 mg/dL and 50 mg/dL, as well as across Lp(a) quartiles. We employed restricted cubic spline (RCS) modeling on Lp(a) concentrations versus outcomes. Independent associations were evaluated through multivariable Cox proportional hazards models. Mediation analysis was used to detect potential pathways mediating the effect of Lp(a) on outcomes.
Result
During a median follow-up of 5.2 years（interquartile range, 2.9 –8.1 years）, 3,883 cardiovascular deaths (7.54%) and 8,332 all-cause deaths (16.18%) occurred. Restricted cubic spline analysis demonstrated a positive dose-response relationship between Lp(a) levels and the risks of cardiovascular and all-cause mortality. After multivariable adjustment, relative to the control category (Lp(a) below 30 mg/dL), patients with 30–50 mg/dL Lp(a) exhibited a 32% higher risk of CV mortality (hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.20–1.45, P < 0.001) and a 42% higher risk in the Lp(a) ≥50 mg/dL group (HR: 1.42, 95% CI: 1.31–1.54, P < 0.001). The mediation analysis revealed that high-sensitivity C-reactive protein (hs-CRP) mediated 3.54% of the effect of Lp(a) on cardiovascular mortality and fibrinogen (FIB) mediated 23.8% of the effect (both P for proportion < 0.001). Parallel links were observed for all-cause mortality.
Conclusions
Among Asian individuals diagnosed with baseline CAD, Lp(a) ≥30 mg/dL is linked to a considerably higher risk of cardiovascular and all-cause mortality, with this risk increasing progressively with higher Lp(a).Abstract Illustration