9364 The Deleterious Synergy Of Aldosterone And LDL Cholesterol On Major Cardiovascular Events In Chronic Kidney Disease

Abstract Disclosure: M. Solomon: None. A. Vaidya: None. S.S. Waikar: None. A. Verma: None. Background: Elevated aldosterone and low-density lipoprotein (LDL) are both known risk factors for major cardiovascular events (MACE) in chronic kidney disease (CKD). Method: The synergistic impact of aldosterone and LDL on incident MACE was investigated among 3453 participants in the Chronic Renal Insufficiency Cohort. The primary exposure was the interaction between aldosterone and LDL as continuous variables. We also evaluated the same interaction after categorizing each variable by the median. The primary outcome was MACE [defined as the composite of heart failure (HF), myocardial infarction (MI), or stroke, whichever occurred first]. Cox proportional hazard models and confounder-adjusted survival curves were developed after adjustment for demographic, metabolic, renal, and laboratory parameters to ensure a robust interpretation of results. Results: Over a median follow-up period of 8.9 years, 1,030 participants experienced major cardiovascular events (MACE). There was a statistically significant linear interaction between aldosterone and low-density lipoprotein (LDL) in predicting incident MACE (P = 0.005). In adjusted models, participants with aldosterone and LDL levels greater than the median had a 32% increased risk of MACE (HR 1.32, 95% CI 1.08-1.61) compared to those with values below the median. The 10-year absolute risk difference for MACE was 5.8% (95% CI 1.3 -10.3) comparing individuals with aldosterone and LDL greater than the median with those below the median. Conclusion: The combination of elevated aldosterone levels and elevated LDL cholesterol imparts a heightened risk for major cardiovascular events in CKD. These findings emphasize the potential value of mineralocorticoid receptor antagonism or aldosterone synthase inhibition in combination with LDL-lowering to mitigate adverse cardiovascular events in CKD. Presentation: 6/3/2024