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Cardiorenal Syndrome and Depressive Symptoms: Exploring the Mood-Kidney Link With Heart Failure Risk in a Post-hoc
Sydney E Hartsell1,2,3, Stavros G Drakos2,3,4, Robert E Boucher1,2
1Division of Nephrology & Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, Utah.
Insights
Chronic kidney disease (CKD) and depressive symptoms are independent risk factors for heart failure (HF). Patients with both conditions face a significantly increased risk of developing HF, highlighting the need for integrated care.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Psychiatry
Background:
- Type 4 cardiorenal syndrome involves chronic kidney disease (CKD) leading to chronic heart failure (HF).
- Depression is a potential contributing factor in the pathophysiology of CKD-related HF.
- The combined impact of depressive symptoms and CKD on HF risk requires further investigation.
Purpose of the Study:
- To determine if depressive symptoms and CKD are independent predictors of incident heart failure (HF).
- To assess whether depressive symptoms and CKD augment HF risk when present concurrently.
- To investigate the additive or synergistic effects of CKD and depression on HF development.
Main Methods:
- A post-hoc analysis of data from the Systolic Blood Pressure Intervention Trial (SPRINT).
- Included 8,930 participants without baseline HF, assessing depressive symptoms via Patient Health Questionnaire-9 (PHQ-9) and CKD status.
- Utilized multivariable Cox proportional hazards regression models to analyze the association between PHQ-9 scores, CKD, and incident HF events.
Main Results:
- Both CKD (Hazard Ratio [HR] 1.60) and severe depressive symptoms (PHQ-9 ≥ 5, HR 1.92) were independently associated with increased HF risk.
- Participants with both CKD and severe depressive symptoms had a 3.45-fold increased hazard of HF compared to those with neither condition.
- The risk factors appeared to act additively rather than synergistically.
Conclusions:
- Chronic kidney disease (CKD) and significant depressive symptoms are independent risk factors for heart failure (HF).
- The presence of both CKD and depressive symptoms significantly elevates the risk of HF.
- Integrated management strategies addressing both cardiovascular and mental health are crucial for high-risk patients.
Rationale & Objective:
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.
Study Design:
A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT).
Setting & Participants:
Participants with baseline Patient Health Questionnaire-9 (PHQ-9) data and without baseline HF (N =8,930).
Predictors:
Depressive symptom severity (baseline PHQ-9 0, 1-4, and 5-27) and CKD (estimated glomerular filtration rate of < 60 mL/min/1.73m2).
Outcome:
Incident HF events (pre-specified adjudicated secondary SPRINT outcome).
Analytical Approach:
Multivariable Cox proportional hazards regression models and generalized linear models related PHQ-9 and CKD status to HF events on relative and absolute scales.
Results:
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.
Limitations:
Bias from post-hoc observational use of data, clinical trial selection bias.
Conclusions:
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.
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