Plasma Serotonin and Cardiovascular Outcomes in Chronic Kidney Disease

BACKGROUND: Platelet‐poor plasma serotonin levels are associated with adverse cardiovascular outcomes. Although plasma serotonin levels increase in chronic kidney disease, the cardiovascular implications remain unknown. METHODS AND RESULTS: In 1114 participants from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we evaluated the association between plasma serotonin, categorized as undetectable, intermediate, and high (≥20 ng/mL) levels, and cross‐sectional findings on echocardiography, including left ventricular hypertrophy, left ventricular ejection fraction, and pulmonary hypertension. We also analyzed whether serotonin was associated with time‐to‐event cardiovascular outcomes, including heart failure hospitalization and atherosclerotic cardiovascular disease (ASCVD) events, in addition to mortality. Because selective serotonin reuptake inhibitors decrease plasma serotonin levels, we specifically evaluated the influence of selective serotonin reuptake inhibitor use in the relationship between serotonin and outcomes. Plasma serotonin level inversely correlated with estimated glomerular filtration rate and directly correlated with blood pressure. High plasma serotonin was associated with left ventricular hypertrophy (adjusted odds ratio, 2.74 [95% CI, 1.11–7.41]). In contrast, undetectable plasma serotonin level was associated with the highest risk of heart failure (adjusted hazard ratio [HR], 2.26 [95% CI, 1.40–3.66]) and ASCVD events (adjusted HR, 1.96 [95% CI, 1.15–3.32]). CONCLUSIONS: In a large chronic kidney disease cohort, plasma serotonin levels correlated with blood pressure, and elevated serotonin levels were associated with left ventricular hypertrophy. In contrast, undetectable plasma serotonin was associated with the highest risk of heart failure and ASCVD events.