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. Author manuscript; available in PMC: 2026 Sep 1.
Published before final editing as: Am J Med. 2026 Aug 25:S0002-9343(26)00610-8. doi: 10.1016/j.amjmed.2026.08.010

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

Matthew K Park 1,2, Finnian R Mc Causland 1,2, Katherine Scovner Ravi 1,2
PMCID: PMC13528739  NIHMSID: NIHMS2206338  PMID: 42641979

Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.

Keywords: antidepressants, cardiovascular disease, chronic kidney disease, depression, inflammation, selective serotonin reuptake inhibitors

BACKGROUND

Chronic kidney disease affects nearly 36 million Americans (more than 1 in 7 adults)1 and is the 9th leading cause of death in the United States.2 The burden of cardiovascular disease is disproportionately high in patients with chronic kidney disease, with cardiovascular mortality rates 2–5 times higher than those of age-matched individuals with normal kidney function.3 Among patients with chronic kidney disease stage 4 and 5, approximately 40–50% of deaths are attributed to cardiovascular causes, highlighting the urgent need to identify modifiable risk factors in this population.4

Chronic systemic inflammation represents a cardiovascular risk factor in patients with chronic kidney disease.5 Elevated serum concentrations of inflammatory biomarkers are observed in patients with chronic kidney disease,6 and have been shown to predict future cardiovascular events, independent of traditional risk factors.7, 8 Among these markers, high-sensitivity C-reactive protein (hsCRP) has been validated for predicting cardiovascular outcomes and is widely available in clinical practice.9–11 Despite ongoing efforts, effective therapeutic interventions targeting this pathway remain limited.12

Selective serotonin reuptake inhibitors (SSRIs) have demonstrated anti-inflammatory properties in both preclinical and clinical studies in depressed patient populations,13 but whether these anti-inflammatory effects could translate into cardiovascular benefits in patients with chronic kidney disease remains unknown. With depression affecting 20–30% of individuals with mild to moderate kidney disease,14, 15 antidepressant medications, particularly SSRIs, are commonly prescribed in this population.16 Understanding whether SSRIs are associated with a different relationship between inflammatory markers and cardiovascular outcomes could have important implications. To address this, we analyzed data from the Chronic Renal Insufficiency Cohort (CRIC) to evaluate whether associations between inflammatory markers and the composite outcome of all-cause mortality, myocardial infarction, or stroke differed by SSRI use in chronic kidney disease.

METHODS

Study design and population

The Chronic Renal Insufficiency Cohort (CRIC) is a prospective, multicenter study funded by the National Institute of Diabetes and Digestive and Kidney Diseases. The methods of this study have been described.17–19 In brief, the study enrolled 3,939 subjects from 2003 to 2008, an additional 1,500 from 2013 to 2018, then recruited an additional 125 Hispanic/Latino patients in a subsequent study phase.20 Patients were aged 21–74 and had mild to moderate chronic kidney disease (estimated glomerular filtration rate (eGFR) 20–70 mL/min/1.73 m2). Exclusion criteria included institutionalization (e.g., imprisonment or nursing home residency), inability to provide consent, inability to participate in study procedures, New York Heart Association class III or IV heart failure at baseline, cirrhosis, HIV and/or AIDS, pregnancy, prior history of dialysis, prior organ or bone marrow transplant, immunosuppressive therapy for primary renal disease or vasculitis within the preceding 6 months, previous chemotherapy or alkylating agents for systemic cancer other than non-melanoma skin cancer in the preceding 2 years, polycystic kidney disease, or participation in another research study. For this study, we excluded participants with missing SSRI medication data, missing or implausible follow-up time, and/or missing hsCRP data, resulting in a primary analytic sample of 5,500 participants. In secondary analyses, we examined a composite inflammation score, which was available in 3,798 participants and ranged from 0–5, calculated by assigning 1 point for each elevated inflammatory marker: hsCRP >3 mg/L, fibrinogen >350 mg/dL, interleukin-6 ≥6 pg/mL, tumor necrosis factor-alpha ≥7 pg/mL, and interleukin-1-beta ≥0.39 pg/mL. Follow-up continued until death, withdrawal of consent, loss to follow-up, or end of the follow-up period (January 2023). Written informed consent was provided by all participants. The Institutional Review Boards at all participating centers approved and oversaw the CRIC study procedures.

Exposure and outcome variables

Inflammatory biomarkers were measured from baseline blood samples at the CRIC Central Laboratory using standardized protocols that have been described.21–23 hsCRP was the primary exposure of interest. In secondary analyses, we examined the composite inflammation score. The use of SSRIs was ascertained through standardized medication inventory conducted by trained study personnel at baseline.

The outcome of interest was time to the composite outcome of non-fatal myocardial infarction, non-fatal stroke, or all-cause mortality. Cardiovascular death was incompletely captured in CRIC;24 therefore all-cause mortality was used. In secondary analyses, the individual components of the composite outcome (non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality) were also evaluated as independent (first) time-to-event outcomes (as such, the sum of the individual events was greater than the frequency of the first composite event). Events were centrally adjudicated by trained physicians using standardized protocols with dual physician review of medical records.19

Statistical analyses

Continuous variables were examined graphically and summarized as mean (± standard deviation) for normally distributed variables or median [25th to 75th percentile] for non-normally distributed variables. Categorical variables were summarized as proportions. Unadjusted and adjusted Cox proportional hazards models were fit to explore the association of hsCRP and the inflammation score with the composite outcome; interaction terms were used to explore for differential associations according to the baseline use of SSRIs. The multivariable model adjusted for age, sex, race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, Other), baseline history of myocardial infarction or revascularization, stroke, heart failure, diabetes mellitus, hypertension, estimated glomerular filtration rate (eGFR, based on the Chronic Kidney Disease Epidemiology Collaboration (EPI) equation),25 hemoglobin, serum albumin, log-transformed high-sensitivity troponin T, log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed urine protein per 24 hours, baseline use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), beta blockers, calcium channel blockers, diuretics, statins, depression severity (Beck Depression Inventory), and markers of healthcare utilization and engagement (having ever been seen by nephrology and lifestyle modifications i.e., salt restriction, weight loss, exercise, or alcohol reduction).26 We performed sensitivity analyses excluding participants with baseline history of myocardial infarction, coronary revascularization, or stroke. In an additional sensitivity analysis, we examined whether the association between log-transformed hsCRP and the composite outcome differed according to antidepressant class, comparing participants prescribed SSRIs (with or without other antidepressants), those prescribed non-SSRI antidepressants only, and those not prescribed any antidepressant.

The proportional hazards assumption was assessed using Schoenfeld residual tests and was satisfied for all primary exposure variables including log-transformed hsCRP, inflammation score, SSRI use, and their interaction terms. A two-sided p-value <0.05 was considered to be statistically significant. Analyses were completed using Stata MP (version 19.0, Stata Corp., College Station, Texas). Missing data was not imputed.

RESULTS

Baseline characteristics

Of the 5,625 participants in the cohort, 125 patients were excluded; 41 were missing information regarding SSRI prescription status, 52 were missing baseline hsCRP levels, and 36 had unavailable follow-up time. Baseline characteristics of included and excluded patients are shown in Supplementary Table 1. Of the included participants in the primary analyses, mean age was 60 ± 11 years, 44% were female, and 43% were non-Hispanic Black. Compared with participants not prescribed SSRIs, those prescribed SSRIs were more likely to be female and non-Hispanic White and had a higher prevalence of myocardial infarction/prior coronary revascularization, stroke, and diabetes. They had higher eGFR, NT-proBNP, hsCRP, and IL-6 levels, and lower 24-hour urine protein and high-sensitivity troponin T. Participants prescribed SSRIs were less likely to use ACEi/ARBs or calcium channel blockers and were more likely to use beta-blockers and statins. They also had higher depressive symptom severity and were less likely to have received prior nephrologist care (Table 1). SSRI use, independent of hsCRP, was non-significantly associated with the composite outcome (aHR 1.15, 95% CI 0.99, 1.34).

Table 1.

Baseline Characteristics According to SSRI Use

Not Prescribed SSRI Prescribed SSRI
n=4901 n=599
Age, years 60 ± 11 60 ± 9
Female, n(%) 2072 (42%) 325 (54%)
Race/Ethnicity, n(%)
Non-Hispanic White 1895 (39%) 340 (57%)
Non-Hispanic Black 2173 (44%) 181 (30%)
Hispanic 833 (17%) 78 (13%)
Myocardial Infarction/Prior Revascularization, n(%) 1014 (21%) 167 (28%)
Stroke, n(%) 481 (10%) 77 (13%)
Heart Failure, n(%) 457 (9%) 68 (11%)
Diabetes, n(%) 2499 (51%) 335 (56%)
Hypertension, n(%) 4248 (87%) 510 (85%)
eGFR - Chronic Kidney Disease Epidemiology Collaboration Equation, mL/min/1.73 m2 48 ± 16 50 ± 15
Hemoglobin, g/dL 12.7 ± 1.8 12.6 ± 1.6
Serum Albumin, g/dL 3.9 ± 0.5 4.0 ± 0.4
24-hour urine protein (g/24 h) 0.2 [0.1, 0.9] 0.2 [0.1, 0.6]
High-sensitivity troponin T (pg/mL) 12.6 [6.0, 24.1] 9.8 [4.6, 20.7]
N-terminal pro-B-type natriuretic peptide (pg/mL) 148.6 [61.8, 409.1] 173.3 [74.6, 464.8]
High-sensitivity CRP, mg/L 2.6 [1.1, 6.1] 3.1 [1.3, 8.0]
Fibrinogen, mg/dL 403.8 [338.2, 480.4] 404.1 [342.2, 476.0]
IL-6, pg/mL 1.9 [1.1, 3.1] 2.1 [1.3, 3.4]
TNF-α, pg/mL 2.2 [1.5, 3.2] 2.2 [1.6, 3.3]
IL-1β, pg/mL 0.2 [0.1, 1.3] 0.1 [0.1, 1.2]
Depression severity (BDI), n(%)
Minimal 4079 (86%) 374 (64%)
Mild-moderate 564 (12%) 176 (30%)
Severe 103 (2%) 39 (7%)
ACEi or ARB, n(%) 3403 (69%) 387 (65%)
Beta blocker, n(%) 2386 (49%) 325 (54%)
Calcium channel blocker, n(%) 2056 (42%) 221 (37%)
Diuretic, n(%) 2718 (55%) 328 (55%)
Statin, n(%) 2809 (57%) 383 (64%)
Nephrologist care, n(%) 3117 (64%) 350 (58%)
Lifestyle modification, n(%) 4550 (93%) 561 (94%)
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Results are presented as mean ± standard deviation, or median [25th-75th percentiles] for continuous variables.

Abbreviations: SSRI, selective serotonin reuptake inhibitor; NT-proBNP, N-terminal pro–B-type natriuretic peptide; CRP, C-reactive protein; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; eGFR, estimated glomerular filtration rate; BDI, Beck Depression Inventory; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker.

Association of hsCRP with the Composite Outcome

Among 5,500 participants, 2,506 composite outcome events occurred over a mean follow-up of 9.2 years. In adjusted models, higher log-transformed hsCRP levels were associated with increased risk of the composite outcome (per 1-unit: aHR 1.10, 95% CI 1.06, 1.15) (Table 2).

Table 2.

Association of Log-Transformed hsCRP with the Composite Outcome (Death, Myocardial Infarction, or Stroke)

Exposure Model Events/N HR per 1-unit (95% CI) p-value
Log hsCRP Unadjusted 2506/5500 1.14 (1.10, 1.18) <0.001
Adjusted 1809/3524 1.10 (1.06, 1.15) <0.001
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Adjusted model includes covariates for demographics (age, sex, race/ethnicity); comorbidities (history of myocardial infarction or revascularization, stroke, congestive heart failure, diabetes, hypertension); kidney function (eGFR); laboratory parameters (hemoglobin, albumin, log-transformed 24-hour urine protein); cardiac biomarkers (log-transformed high-sensitivity troponin T and log-transformed NT-proBNP); depression severity (Beck Depression Inventory); cardiovascular medications (ACE inhibitors or ARBs, beta blockers, calcium channel blockers, diuretics, statins); and healthcare utilization and engagement (nephrologist care and engagement in lifestyle modification).

Differential association of hsCRP with cardiovascular outcomes by SSRIs

The association between hsCRP and the composite outcome differed according to SSRI use (P-interaction <0.01). Among participants not using SSRIs, log-transformed hsCRP was associated with the composite outcome (aHR 1.12, 95% CI 1.08, 1.17 per 1-unit); among users of SSRIs, no significant association was observed (aHR 0.91; 95% CI 0.80, 1.05) (Table 3). Sensitivity analyses excluding participants with baseline myocardial infarction, revascularization or stroke showed similar patterns (aHR 1.11, 95% CI 1.05, 1.17 per 1-unit among non-users; aHR 0.95; 95% CI 0.78, 1.15 per 1-unit among SSRI users; P-interaction=0.06, Supplementary Table 2).

Table 3.

Effect Modification of the Association Between Log-Transformed hsCRP and the Composite Outcome (Death, Myocardial Infarction, or Stroke) by SSRI Use

Exposure Medication Status Events/N HR per 1-unit (95% CI) p-interaction
Log hsCRP (Unadjusted) No SSRI 2202/4901 1.16 (1.12, 1.20) <0.01
SSRI 304/599 0.98 (0.89, 1.08)
Log hsCRP (Adjusted) No SSRI 1599/3162 1.12 (1.08, 1.17) <0.01
SSRI 210/362 0.91 (0.80, 1.05)
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Adjusted model includes covariates for demographics (age, sex, race/ethnicity); comorbidities (history of myocardial infarction or revascularization, stroke, congestive heart failure, diabetes, hypertension); kidney function (eGFR); laboratory parameters (hemoglobin, albumin, log-transformed 24-hour urine protein); cardiac biomarkers (log-transformed high-sensitivity troponin T and log-transformed NT-proBNP); depression severity (Beck Depression Inventory); cardiovascular medications (ACE inhibitors or ARBs, beta blockers, calcium channel blockers, diuretics, statins); and healthcare utilization and engagement (nephrologist care and engagement in lifestyle modification). P-interaction values are derived from the interaction terms.

In secondary analyses examining individual components of the composite outcome, the association of hsCRP with all-cause death differed according to SSRI use in the adjusted model (P-interaction = 0.04). Among participants not using SSRIs, log-transformed hsCRP was associated with death (aHR 1.14, 95% CI 1.09, 1.19 per 1-unit), while among SSRI users, no significant association was observed (aHR 1.05; 95% CI 0.92, 1.19). For myocardial infarction, the point estimate among non-SSRI users was directionally consistent with this pattern (aHR 1.15, 95% CI 1.05, 1.26), while no significant association was observed among SSRI users (aHR 0.92, 95% CI 0.60, 1.40); the interaction was not statistically significant (P-interaction=0.46). For stroke, the interaction was statistically significant (P-interaction=0.01); hsCRP was not associated with stroke among non-SSRI users (aHR 1.10, 95% CI 0.98, 1.24), while among SSRI users, higher hsCRP was associated with a significantly lower risk of stroke (aHR 0.56, 95% CI 0.33, 0.96; Supplementary Table 3).

Association of inflammatory score with the composite outcome

In secondary analyses among the 3,798 participants with complete inflammatory marker data, in the adjusted model, higher inflammation scores were associated with a higher risk of the composite outcome (per 1-point: aHR 1.14, 95% CI 1.08, 1.19) (Supplementary Table 4).

Differential association of inflammation score with cardiovascular outcomes by SSRIs

The association between the inflammation score and the composite outcome differed according to SSRI use (P-interaction = 0.04). Among participants not using SSRIs, the inflammation score was associated with the composite outcome (aHR 1.15, 95% CI 1.09, 1.20 per 1-point); among users of SSRIs, no significant association was observed (aHR 0.95; 95% CI 0.81, 1.11 per 1-point) (Supplementary Table 5). Sensitivity analyses excluding participants with baseline myocardial infarction, coronary revascularization or stroke showed similar patterns of association among SSRI users and non-users, though the interaction term was not significant (P-interaction = 0.27) (Supplementary Table 6).

Sensitivity Analysis by Antidepressant Class

The association between hsCRP and the composite outcome differed according to antidepressant class (P-interaction <0.01). Among participants not prescribed any antidepressant, log-transformed hsCRP was associated with the composite outcome (aHR 1.11, 95%CI 1.07, 1.16 per 1-unit); among SSRI users, no significant association was observed (aHR 0.91; 95%CI 0.80, 1.05); and among non-SSRI antidepressant users, a significant association was observed (aHR 1.24; 95% CI 1.05, 1.48) (Supplementary Table 7).

DISCUSSION

In this large prospective cohort of patients with chronic kidney disease, the association between inflammatory markers and mortality and major adverse cardiovascular events differed according to baseline SSRI use, with higher hsCRP and inflammation scores associated with greater risk among non-users but not among SSRI users.

In patients with chronic kidney disease, the uremic milieu promotes inflammatory activation through multiple mechanisms, including impaired clearance of inflammatory mediators, oxidative damage,27 and metabolic acidosis,28 leading to sustained vascular injury.29 While the biological pathways are not entirely understood, prospective studies provide evidence that SSRIs may influence inflammatory markers. For example, in patients with newly diagnosed depression, treatment with fluoxetine or escitalopram for two months reduced CRP levels independent of changes in symptoms of depression.30 A systematic review and meta-analysis of 22 studies including 827 patients with major depressive disorder further demonstrated that SSRI treatment decreased multiple inflammatory markers, including IL-6, TNF-α, and IL-1β, with moderate effect sizes.31 Although a randomized trial in patients with chronic kidney disease found no change in hsCRP with sertraline over 12 weeks,32 the broader literature suggests that SSRIs may possess anti-inflammatory properties that could vary by specific agent and duration of exposure. Our findings should also be interpreted in the context of a prior CRIC analysis reporting higher mortality and hospitalization among antidepressant users.33 That study, however, evaluated antidepressants as a class rather than SSRIs specifically, and it did not assess differential effects by inflammatory burden. Notably, in a sensitivity analysis stratified by antidepressant class, the attenuation of inflammation-associated cardiovascular risk was restricted to SSRI users and was not observed among users of non-SSRI antidepressants, which argues against confounding by indication as the primary explanation for our findings and may suggest a mechanism specific to serotonergic pathways.

The diminished association between inflammation and cardiovascular risk among SSRI users may reflect the interconnected nature of neuropsychiatric and inflammatory pathways. The nervous system and immune system interact through multiple mechanisms, including the hypothalamic-pituitary-adrenal axis,13 vagus nerve-mediated cholinergic anti-inflammatory pathways,34 and sympathetic nervous system modulation of immune cell function.35–37 Serotonin receptors are expressed on various immune cells including T cells, B cells, monocytes, and macrophages, and serotonin itself can directly modulate cytokine production and immune cell activation.38 Through these pathways, medications that modulate neurotransmitter systems, such as SSRIs, may affect inflammatory processes. This neuroimmune framework provides a possible mechanistic explanation for our observation that the relationship between inflammatory markers and cardiovascular events differed according to SSRI use. Rather than viewing medications solely through their primary therapeutic indication, understanding their pleiotropic effects across interconnected physiologic systems may reveal opportunities to optimize outcomes in vulnerable populations such as those with chronic kidney disease. However, as noted above, our data cannot exclude the possibility that SSRI use is instead, or additionally, associated with non-inflammatory pathways of cardiovascular risk, and the neuroimmune mechanism we describe here should therefore be considered one of several possible explanations for our findings.

In secondary analyses of individual components, hsCRP was associated with death among non-SSRI users but not among SSRI users, consistent with the findings of the composite outcome. For myocardial infarction, although the interaction was not significant, the point estimates were directionally consistent with this pattern. This non-significant finding possibly reflects insufficient power, given the low number of myocardial infarction events. For stroke, the interaction was statistically significant; however, the pattern was counterintuitive: hsCRP was not associated with risk among non-SSRI users, while among SSRI users, higher hsCRP was associated with a lower risk of stroke. However, given the overall paucity of stroke events, we urge caution in deriving any meaningful interpretation from this analysis.

Sensitivity analyses excluding participants with baseline myocardial infarction, revascularization, or stroke showed similar subgroup-specific associations, although the interaction did not reach conventional levels of statistical significance (P-interaction = 0.06). Although the inflammation score interaction did not reach significance, the effect showed consistent directional associations in the point estimates, and the lack of significance may also reflect reduced statistical power due to the smaller sample size in the inflammation score analyses.

Our study has several strengths. The CRIC study prospectively followed a large, ethnically diverse cohort of patients with chronic kidney disease for a long duration with comprehensive baseline characterization. However, several limitations should be acknowledged. While we adjusted for multiple known risk factors as well as for proxies of healthcare utilization and engagement, as with all observational studies, the possibility of residual confounding remains. Additionally, the attenuated association between hsCRP and the composite outcome among SSRI users cannot be definitively attributed to an anti-inflammatory mechanism. Given the observed interaction, a potential alternative interpretation is that the association of SSRI use with outcomes differs according to the degree of inflammation. This should be considered when interpreting our findings. The study population consisted of patients with mild to moderate chronic kidney disease, which may limit generalizability to patients with more advanced kidney disease or to those requiring kidney replacement therapy. Furthermore, though CRIC includes an indicator of cardiovascular mortality, it is only available for a subset of deaths,24 and we therefore explored all-cause mortality. However, given that cardiovascular disease accounts for a large proportion of deaths in patients with chronic kidney disease,4 all-cause mortality may still capture a substantial proportion of cardiovascular outcomes. Our analysis was limited to baseline measurements, precluding assessment of serial inflammatory changes or dose-response relationships with SSRI therapy. Lastly, while individual SSRI agents were documented, sample sizes were too small for agent-specific analyses. This is an important limitation as SSRIs vary in QT-prolonging effects,39 which may counteract potential anti-inflammatory benefits. Agent-specific prospective studies are needed to determine whether cardiovascular outcomes differ by SSRI use before considering SSRIs for risk reduction.

In conclusion, the association between hsCRP and major adverse cardiovascular events differed by SSRI use in patients with chronic kidney disease, with higher hsCRP associated with a higher risk of all-cause death, myocardial infarction, or stroke among non-users but not among users of SSRIs. Because this was an observational study, causality cannot be determined, and the mechanism underlying the differential association of inflammation with outcomes remains uncertain; it may reflect anti-inflammatory effects of SSRIs, a non-inflammatory pathway by which SSRIs influence cardiovascular risk, or both. Further mechanistic and interventional studies are warranted to determine whether certain SSRIs could reduce inflammation-related cardiovascular risk in patients with chronic kidney disease.

Supplementary Material

Supplementary Material

HIGHLIGHTS.

  • Inflammation was associated with higher cardiovascular risk among patients not using SSRIs.

  • This association was not observed among patients using SSRIs.

  • Results were similar for hsCRP and a composite inflammation score.

  • The differential association was not observed with non-SSRI antidepressants.

Funding Sources:

Dr. Ravi reports research funding from the NIH (K23 DK127248, R03 DK144241).

Footnotes

Conflict of Interest Statements: Matthew Park and Katherine Ravi have nothing to disclose. Dr. Mc Causland reports research fees from Novartis, Lexicon, AstraZeneca, NIH, paid directly to his institution; consulting fees from Aquapass, GSK, and Zydus Therapeutics; expert witness fees from Rubin-Anders Scientific, Covington & Burling LLC; travel/speakers fees from Bayer and Global Learning Collaborative; he serves as a DSMB member for the TwoPlus trial; his spouse reports research funding from Lexicon Pharmaceuticals paid directly to her institution; consulting fees from Vera Therapeutics and Alexion; serving on DSMB for AstraZeneca.

All authors had access to the data and a role in writing the manuscript.

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