Abstract
To evaluate the contribution of baseline and longitudinal changes in cardiometabolic health (CMH) towards heart failure (HF) risk among adults with type 2 diabetes (T2D). Participants of the Look AHEAD trial with T2D and without prevalent HF were included. Adjusted Cox models were used to create a CMH score incorporating target levels of parameters weighted based on relative risk for HF. The associations of baseline and changes in the CMH score with risk of overall HF, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF) were assessed using Cox models. Among the 5080 participants, 257 incident HF events occurred over 12.4 years of follow-up. The CMH score included 2 points each for target levels of waist circumference, glomerular filtration rate, urine albumin-to-creatinine ratio, and 1 point each for blood pressure and glycated haemoglobin at target. High baseline CMH score (6-8) was significantly associated with lower overall HF risk (adjusted hazard ratio [HR], ref=low score (0-3): 0.31, 95% confidence interval [CI] 0.21-0.47) with similar associations observed for HFpEF and HFrEF. Improvement in CMH was significantly associated with lower risk of overall HF (adjusted HR per 1-unit increase in score at 4 years: 0.80, 95% CI 0.70-0.91). In the ACCORD validation cohort, the baseline CMH score performed well for predicting HF risk with adequate discrimination (C-index 0.70), calibration (chi-square 5.53, p=0.70), and risk stratification (adjusted HR [high (6-8) vs. low score (0-3)]: 0.35, 95% CI 0.26-0.46). In the Look AHEAD subgroup with available biomarker data, incorporating N-terminal pro-B-type natriuretic peptide to the baseline CMH score improved model discrimination (C-index 0.79) and risk stratification (adjusted HR [high (8-10) vs. low score (0-4)]: 0.18, 95% CI 0.09-0.35). Achieving target levels of more CMH parameters at baseline and sustained improvements were associated with lower HF risk in T2D.
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