Type 2 diabetes and chronic kidney disease combinations in heart failure across the ejection fraction spectrum: clinical associations, medication use, and cause-specific outcomes
G Ferrannini, T Pol, C Ljugman, U Dahlstrom, A Merolla, L H LundAbstract
Background
Heart failure (HF) often coexists with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), which increase the risk of mortality and hospitalization due to HF (HHF). Several drug classes recommended in HF have been shown to reduce cardiorenal morbidity and mortality in CKD and/or T2DM, but real-world studies report low use and frequent discontinuation.
Purpose
In a real-world HF population, to report: i) the prevalence of T2DM and CKD and their combination across ejection fraction (EF) categories; ii) HF medication use, in particular mineralocorticoid receptor antagonists (MRA); iii) estimated cause-specific event rates and multivariable-adjusted risks for death, HHF, and end-stage renal disease (ESRD).
Methods
Adult patients enrolled in the Swedish HF registry 2017-2023, not on dialysis and with no missing data for EF or renal function, were divided into no CKD/no T2DM, CKD only, T2DM only, both CKD/T2DM. HF medication use and cardiovascular (CV) death, first HHF, their composite, all-cause death, and ESRD event rates and risks were assessed overall and by EF.
Results
Among 54,341 patients (34% females, mean age 73 years; 52% had HFrEF, 26% HFmrEF and 21% HFpEF), 51% had no CKD/no T2DM, 24% CKD only, 14% T2DM only, and 11% both CKD/T2DM. CKD alone or with T2DM was more prevalent in HF with preserved EF (HFpEF; 29% and 15%) than with mildly reduced EF (HFmrEF; 23% and 11%) and reduced EF (HFrEF 22% and 10%; p<0.001) and in older, female patients with worse HF symptoms, but added less incremental risk in HFpEF. Relevant medication use according to EF and to the presence of CKD/T2DM is shown in Figure 1.MRA use ranged 48%-64% in HFrEF, 36%-46% in HFmrEF, and 25%-42% in HFpEF, and in HFrEF it was lower in the presence of CKD. Event rates for each outcome according to EF are shown in Table 1. Unadjusted and adjusted (HR) ratios for HHF/CV death were for CKD 2.35 and 1.40 respectively, and for both CKD/T2DM they were 3.07 and 1.72 respectively. For the mortality and HHF outcomes the HR for T2DM alone (compared to the reference no CKD or T2DM) ranged 1.45-1.53 crude and 1.26-1.33 adjusted; for CKD alone 2.25-3.13 crude and 1.40-1.56 adjusted; and for both CKD/T2DM 3.07-3.37 crude and 1.70-1.80 adjusted. For ESRD, T2DM alone did not significantly increase risk, but the HR for CKD alone was 2.94 crude and 3.04 adjusted and for both CKD/T2DM 7.66 crude and 5.74 adjusted.
Conclusion
T2DM, CKD and their combination were highly prevalent in HF, especially in HFpEF. CKD was a strong and T2DM a moderate independent risk factor for all outcomes. In particular, CKD added considerably and T2DM only modestly to the independent risks of death, CV death, and ESRD, whereas both added considerably to the risk of HHF. CKD added more to risk in HFrEF and was associated with lower MRA use in HFrEF. Our findings inform both MRA implementation strategies and future trials of drugs targeting aldosterone.Figure 1For image description, please refer to the figure legend and surrounding text.Table 1For image description, please refer to the figure legend and surrounding text.