Cardiorenal Syndrome and Depressive Symptoms: Exploring the Mood-Kidney Link With Heart Failure Risk in a Post-hoc Analysis of SPRINT.

Authors

Sydney E Hartsell, Stavros G Drakos, Robert E Boucher, Amara Sarwal, James C Fang, Guo Wei, Augustine Takyi, George Bissada, Jincheng Shen, Srinivasan Beddhu

Published in

Kidney medicine. Volume 8. Issue 7. Pages 101390. Epub May 06, 2026.

Abstract

Depression is a potential pathophysiologic pathway in type 4 cardiorenal syndrome, ie chronic kidney disease (CKD) resulting in chronic heart failure (HF). We investigated whether depressive symptoms and CKD are independent predictors of HF and whether they augment HF risk when they present together.
A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT).
Participants with baseline Patient Health Questionnaire-9 (PHQ-9) data and without baseline HF (N =8,930).
Depressive symptom severity (baseline PHQ-9 0, 1-4, and 5-27) and CKD (estimated glomerular filtration rate of < 60 mL/min/1.73m²).
Incident HF events (pre-specified adjudicated secondary SPRINT outcome).
Multivariable Cox proportional hazards regression models and generalized linear models related PHQ-9 and CKD status to HF events on relative and absolute scales.
PHQ-9 scores of 0, 1-4, and ≥ 5 were present in 3,086 (34.6%), 3,775 (42.3%), and 2,069 (23.2%) participants, respectively and baseline CKD in 2,155 (24%). There were 177 HF events over 33,358 person-years. In a multivariable Cox regression model, both CKD (HR 1.60; 95% CI, 1.13-2.28) and PHQ-9 ≥ 5 (HR vs PHQ-9 = 0: 1.92; 95% CI, 1.24-2.98) were independent HF risk factors. In another Cox model, compared to those with PHQ-9 = 0 and no CKD, those with both CKD and PHQ-9 ≥5 had 3.45 times the hazard of HF (HR 3.45, 95% CI 1.70, 7.03) with other subgroups in between. There was no evidence of a synergistic interaction, but they appeared to be additive. Results were largely consistent on the absolute risk scale.
Bias from post-hoc observational use of data, clinical trial selection bias.
Both CKD and depressive symptoms are independent and additive risk factors for HF. Patients with both CKD and a higher burden of depressive symptoms are at greater risk of HF.

PMID:
42375688
Bibliographic data and abstract were imported from PubMed on 30 Jun 2026.

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