Prediabetes, Subclinical Myocardial Injury or Stress, and Heart Failure Risk for Adults With Hypertension

Importance It is unclear whether and the extent to which subclinical myocardial injury or stress coexisting with prediabetes is associated with the risk of heart failure (HF). Objective To evaluate the joint associations of prediabetes and subclinical myocardial injury or stress with incident HF risk. Design, Setting, and Participants This post hoc prospective cohort study analyzed data from the Systolic Blood Pressure Intervention Trial (SPRINT). Two analytic samples were used: (1) adults with hypertension without diabetes or prior HF for the baseline biomarkers analysis and (2) participants with biomarker measurements at both baseline and 12 months for the longitudinal biomarkers’ change. Prediabetes was defined as a fasting plasma glucose level of 100 to 125 mg/dL. Subclinical myocardial injury was defined as a high-sensitivity cardiac troponin I (hs-cTnI) level of 6 ng/L or higher in men and 4 ng/L or higher in women and subclinical myocardial stress defined as an N-terminal pro–B-type natriuretic peptide (NT-proBNP) level of 125 pg/mL or higher. A 25% or greater increase in any biomarker concentration from baseline to 12 months defined longitudinal change. Data were analyzed between January 1 and May 31, 2025. Main Outcomes and Measures The primary outcome was adjudicated incident HF. Cox proportional hazards models were used to estimate hazard ratios (HRs) for HF across joint categories of prediabetes and biomarker elevation. Results Of 8234 participants (mean [SD] age, 68 [9] years; 37.1% women), 3271 (39.7%) had prediabetes, 2942 (35.7%) had subclinical myocardial injury, and 3593 (43.6%) had subclinical myocardial stress. Over a median follow-up of 3.2 years (IQR, 2.8-3.8 years), 122 participants developed HF. Compared with normoglycemia and no myocardial injury, those with both prediabetes and injury had the highest HF risk (HR, 4.20; 95% CI, 2.31-7.63); similar findings were observed for myocardial stress (HR, 5.20; 95% CI, 2.52-10.70). In the longitudinal analysis (median follow-up, 2.3 years [IQR, 1.9-2-8 years]), 7449 participants with both prediabetes and a 25% or greater increase in hs-cTnI or NT-proBNP level had the highest risk of HF (for hs-cTnI: HR, 3.05; 95% CI, 1.58-5.88; for NT-proBNP: HR, 2.39; 95% CI, 1.28-4.46). Conclusions and Relevance These findings suggest that among adults with hypertension, prediabetes in combination with subclinical myocardial injury or stress is associated with a significantly elevated risk for HF. These findings support the integration of glycemic status and cardiac biomarkers profiling to improve HF risk stratification and guide prevention.