Worsening Kidney Function and Cardiovascular Outcomes in Type 2 Diabetes and Atherosclerotic Disease.

BACKGROUND

The bidirectional association between worsening kidney function (WKF) and cardiovascular outcomes in type 2 diabetes (T2D) patients with atherosclerotic cardiovascular disease (ASCVD) is unclear.

OBJECTIVES

This study aimed to evaluate the bidirectional association between: 1) nonfatal cardiovascular events and WKF; and 2) severe hypoglycemia and WKF.

METHODS

We analyzed data from TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin), enrolling 14,671 patients with T2D and ASCVD randomized to sitagliptin or placebo. The primary outcome was a 4-component major adverse cardiovascular event (MACE4) comprising nonfatal myocardial infarction, stroke, cardiovascular death, or unstable angina hospitalization. We also examined hospitalization for heart failure (hHF). WKF was defined as a glomerular filtration rate decline of ≥40% (per the Modification of Diet in Renal Disease formula) or initiation of renal replacement therapy. Cox proportional hazards models assessed associations between WKF and subsequent MACE4 and hHF.

RESULTS

Over a median 3-year follow-up, 1,030 (7.0%) experienced WKF. Overall, WKF risk increased after nonfatal myocardial infarction, stroke, or unstable angina (adjusted HR [HRadj]: 2.0; 95% CI: 1.6-2.5) and was higher after hHF (HRadj: 6.1; 95% CI: 4.8-7.9). Median estimated glomerular filtration rate declines before MACE4 and hHF were -3.8% (IQR: -17.4, 9.4) and -9.2% (IQR: -22.7, 6.6), respectively. WKF was associated with increased risks of MACE4 (HRadj: 1.9; 95% CI: 1.5-2.4), hHF (HRadj: 3.2; 95% CI: 2.2-4.6), and severe hypoglycemia (HRadj: 2.8; 95% CI: 1.8-4.4).

CONCLUSIONS

In patients with T2D and ASCVD, WKF is common and linked to adverse cardiovascular outcomes and severe hypoglycemia, highlighting the need for early cardiorenal therapies.