Impact of type 2 diabetes on the incidence of cardiorenal syndromes and on subsequent clinical outcomes: a propensity-matched nationwide analysis
Authors: Fauchier L , Maisons V , Fauchier G , Herbert J , Angoulvant D , Ducluzeau P H , Halimi J M 
Published: October 2022

Abstract

Background
Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiac diseases and renal dysfunction. Whether T2DM increases the risk of cardiorenal syndromes (CRS) subtypes to a similar extent, and whether the risk of deleterious outcomes after CRS is modified by diabetes are poorly known.

Methods
In a nationwide cohort study including 5,123,193 patients seen in French hospitals in 2012 with at least 5 years of follow-up (or dying earlier), we assessed the incidence of CRS subtypes, and then the impact of T2DM in patients with CRS on the risk of death, cardiovascular death, heart failure (HF), myocardial infarction (MI) and end-stage kidney disease (ESKD) during follow-up (27,735,205 person-years). Patients with history of dialysis, kidney transplantation or type 1 DM were excluded of the analysis. We performed 1:1 propensity matching on baseline characteristics including age, sex, risk factors, cardiovascular and non-cardiovascular comorbidities for patients with T2DM or no T2DM. The model by Fine and Gray was used for analyzing the competing risks for clinical events and all-cause death with sub-distribution hazard ratios (sHR).

Results
Among the 5,123,193 patients, 4,605,236 (91.2%) had neither HF nor CKD baseline. Among them, 391,186 (8.1%) had T2DM and 380,581 of them were matched 1:1 with 380,581patients with no T2DM. During follow-up, CRS occurred in 42,375 patients (incidence 0.98%/year): acute, i.e. type 1,3 or 5 CRS n=9,438, 22%; type 2 (cardiorenal) CRS n=21,075, 50%; type 4 (renocardiac) CRS n=11,862, 28%). In multivariable analysis, T2DM was the most powerful predictor of incident CRS (any type, HR: 2.182, 95% CI 2.150–2.214) among all baseline characteristics. The incidence of all-type CRS was higher in matched patients with T2DM (1.30%/year, 95% CI 1.29–1.32) than in those with no T2DM (0.65%/year, 95% CI 0.64–0.66): sHR 1.905 (95% CI 1.867–1.943). The risk of CRS associated with diabetes (vs no diabetes) was higher for type 4 (sHR 2.182, 95% CI 2.098–2.269) than for type 2 (sHR 1.834, 95% CI 1.783–1.887) and for acute (sHR 1.707, 95% CI 1.637–1.780) CRS.
Among the 451,942 patients with HF or CKD at baseline, 26,396 patients had CRS at baseline, among whom 11,355 (43.0%) had diabetes: 8,314 of them were matched 1:1 with 8,314 with CRS and no T2DM. Compared to CRS patients with no diabetes, matched patients with CRS and T2DM had a greater incidence of all-cause death (sHR 1.085, 95% CI 1.048–1.123), cardiovascular death (sHR 1.145, 95% CI 1.080–1.214), ESKD (sHR 1.319, 95% CI 1.223–1.422), hospitalization for HF (sHR 1.119, 95% CI 1.078–1.162) and MI (sHR 1.294, 95% CI 1.139–1.470) during follow-up.

Conclusions
T2DM is a major risk factor for all CRS subtypes, may differently affect the incidence of type 2, type 4 and acute CRS and aggravates the risk of deleterious outcomes after CRS.

Funding Acknowledgement
Type of funding sources: None.