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The association between lipoprotein(a) and major adverse cardiac and cerebrovascular events (MACCE) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) is influenced by renal function, according to a new study. It may be mediated.¹

Among over 10,000 patients undergoing PCI, elevated Lp(a) was significantly associated with increased risk of MACCE in patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 However, the association was weakened and decreased in patients with mild glomerular filtration rate. For normal kidney function.

“To improve risk stratification of CAD patients with elevated Lp(a), simultaneous measurement of renal function is warranted,” said Junqing Yuan of the National Center for Cardiovascular Diseases, Chinese Academy of Medicine, and Peking Union Medical College. wrote the research team led by .

Previous evidence supports a causal role of elevated Lp(a) in the development of cardiovascular disease (CVD). European Society of Cardiology guidelines recommend starting her Lp(a) measurement at least once in a lifetime to identify cardiovascular risk.² Chronic kidney disease (CKD) is also rising as a prominent cause of the global CVD burden. Decreasing eGFR increases CVD prevalence in parallel with increased cardiac mortality risk.³

However, it remains unclear how renal dysfunction affects the relationship between Lp(a) and cardiovascular risk in CAD patients.¹ In the current analysis, Yuan and colleagues investigated the influence of Lp(a) across levels of renal function and the combined effect of Lp(a) and renal dysfunction on cardiovascular outcomes in CAD patients undergoing PCI.

This post hoc analysis was based on a large prospective observational cohort that enrolled 10,724 adults who underwent PCI from January to December 2013 at a Chinese cardiovascular center hospital. After excluding her 289 patients due to missing baseline creatinine and her Lp(a) data, her 10,435 patients of East Asian ethnicity were included in the analysis.

Participants were classified into three groups by baseline eGFR level according to the National Kidney Foundation classification: normal renal function (>90 ml/min/1.73 m2), mild renal impairment (60–90 ml/min/1.73 m2), and moderate to severe renal impairment (<60 ml/min/1.73 m2).

Follow-up data were obtained at 1 month, 2 months, 1 year, 2 years, and 5 years after discharge by researchers blinded to baseline data. The primary endpoint of the analysis was MACCE, defined as the combination of all-cause death, nonfatal myocardial infarction, ischemic stroke, and unplanned revascularization.

Of the study population, 62% had normal renal function, 34% had mild renal impairment, and 4% had moderate to severe renal impairment. At baseline, median eGFR and Lp(a) were 94.1 ml/min/1.73 m2 and 185.4 mg/dl, respectively. A total of 2144 (20.5) MACCE events occurred during a median follow-up of 5.1 years.

After multivariate adjustment, the researchers found that higher Lp(a) levels were significantly associated with higher risk of MACCE (≥30 vs. <30 mg/dL; hazard ratio) [HR], 1.12; 95% CI, 1.03 - 1.23). On the other hand, a significant association between Lp(a) and higher risk of MACCE was confirmed only in patients with eGFR <60 ml/min/1.73 m2 (HR, 1.31; 95% CI, 1.08 to 1.60 ).

In the group with increased Lp(a), the MACCE rate was significantly higher in the renal dysfunction group (eGFR 60-90 ml/min/1.73 m²: 24.1% vs. 19.9%; P = .004; eGFR <60 ml/min/1.73 m²: 39.3% vs. 26.5%; P = .008). This finding was not observed in patients with normal renal function (19.9% ​​vs. 19.1%; P = .470).

Yuan et al. identified a significant interaction on MACCE between renal category and Lp(A) (P = .026). Only individuals with both eGFR < 60 ml/min.1.73 m2 and elevated LP(a) had significantly higher risk and cumulative incidence of MACCE (adjusted HR, 1.92; 95% CI, 1.43 to 2.57) .

“Since CKD also induces a pro-inflammatory state and vascular calcification, the mechanism underlying our findings may be an amplification of the pro-inflammatory and pro-calcification effects (mainly due to oxidized phospholipids) of Lp(a) in CKD. “is a significant risk factor for CVD,” the researchers wrote.

References

1. _{Zeng G, Zhu P, Yuan D et al. Renal function modifies the association between lipoprotein(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a prospective cohort study. Clin Kidney J. 2024;17(3):sfae032. Published February 9, 2024. doi:10.1093/ckj/sfae032}
2. _{Mach F, Baigent C, Catapano AL, et al.2019 ESC/EAS Guidelines for the Management of Dyslipidemia: Lipid Modification to Reduce Cardiovascular Risk [published correction appears in Eur Heart J. 2020 Nov 21;41(44):4255]. euro heart j. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455}
3. _{Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. lancet. 2013;382(9889):339-352. doi:10.1016/S0140-6736(13)60595-4}