Lipoprotein(a) concentrations and cardiovascular disease in patients with chronic kidney disease: Results from the German Chronic Kidney Disease study

Background: Lipoprotein(a) (Lp(a)) is a causal, genetically determined risk factor for cardiovascular disease (CVD) in the general population. Patients with chronic kidney disease (CKD) have an increased CVD risk and elevated Lp(a) concentrations. Only a few studies on Lp(a) were performed in persons with mild-to-moderate CKD; none of them used genetic variants to explore potential causal associations.

Objectives: This study aims to investigate the association of measured and genetically predicted Lp(a) concentrations on prevalent and incident CVD events in the German Chronic Kidney Disease (GCKD) study.

Methods: The study included 5043 participants of European ancestry with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m² or an eGFR >60 mL/min/1.73 m² in the presence of overt albuminuria with a follow-up of 6.5 years.

Results: With each 10 mg/dL higher Lp(a) concentration, odds for prevalent CVD (1290 events) increased 1.065-fold (95%CI: 1.042-1.088, p < 0.001). The risk was significantly higher in patients with Lp(a) ≥50 mg/dL but most pronounced in Lp(a) ≥70 mg/dL (odds ratio = 1.775 [1.409-2.231], p < 0.001) compared to Lp(a) <30 mg/dL. Each 10 mg/dL higher Lp(a) concentration and Lp(a) ≥70 mg/dL increased the risk for incident 3-point major adverse cardiovascular events (MACEs) (474 events): hazard ratio [HR] = 1.037 [1.009-1.067], p = 0.009 and HR = 1.335 [1.001-1.781], p = 0.050), respectively. Similar results were obtained for 4-point MACE (653 events). Analyses based on apo(a) isoforms and genetically predicted Lp(a) concentrations led to even stronger associations.

Conclusions: In patients with mild-to-severe CKD, elevated Lp(a) concentrations and genetic determinants of Lp(a) concentrations are significantly associated with CVD at baseline and during follow-up, independent of traditional risk factors.