Inflammation-Associated Cardiovascular Risk Differs According to SSRI Use in Patients with Chronic Kidney Disease

Patients with chronic kidney disease experience cardiovascular mortality rates 2-5 times higher than the general population, partly driven by chronic inflammation. Selective serotonin reuptake inhibitors (SSRIs) possess anti-inflammatory properties, but whether their use is associated with lower levels of inflammation-associated cardiovascular disease in chronic kidney disease is unclear.

We analyzed 5,500 participants from the Chronic Renal Insufficiency Cohort using Cox regression to evaluate whether associations of inflammation (high-sensitivity C-reactive protein, hsCRP, and a composite inflammation score) with a composite of all-cause death, myocardial infarction, or stroke differed by SSRI use. Models adjusted for demographics, cardiovascular comorbidities, estimated glomerular filtration rate, albumin, hemoglobin, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, log-transformed 24-hour urine protein, cardiovascular medications, depression severity, and healthcare utilization and engagement.

Mean age was 60 ±11 years, 44% were female, and 43% were Black, and 11% used SSRIs. Over mean follow-up of 9.2 years, 2,506 (46%) experienced the composite outcome. Higher log-transformed hsCRP was associated with increased risk (per 1-unit increase: adjusted hazard ratio (aHR) 1.10, 95% confidence interval (CI) 1.06, 1.15), differing by SSRI use (P-interaction <0.01; aHR 1.12; 95%CI 1.08, 1.17 among non-users vs 0.91; 95%CI 0.80, 1.05 among SSRI users). Similar patterns were noted for a composite inflammatory score (P-interaction=0.04; aHR 1.15; 95%CI 1.09, 1.20 among non-users vs 0.95; 95%CI 0.81, 1.11 among SSRI users).

Inflammatory markers were associated with cardiovascular risk in chronic kidney disease only among non-users of SSRIs. Future studies should explore the mechanisms underlying this differential association and whether SSRIs could be leveraged to reduce cardiovascular risk.