Prediabetes Plus Subclinical Myocardial Injury, Stress Significantly Increases HF Risk

Among adults with hypertension, the coexistence of prediabetes and subclinical myocardial injury or stress is strongly linked to future heart failure (HF) risk, a study finds.¹

Participants with elevated high-sensitivity cardiac troponin I (hs-cTnI) or N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels alongside prediabetes were up to 5 times more likely to develop HF than those with normal glucose and biomarker levels, highlighting the importance of integrating glycemic and cardiac biomarker assessment in preventive cardiology.

This post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) is published in JAMA Cardiology.

“The synergistic association of prediabetes with subclinical myocardial dysfunction likely reflects shared and interacting pathophysiologic mechanisms,” wrote the researchers of the study. “Prediabetes is characterized by insulin resistance, low-grade inflammation, endothelial dysfunction, and neurohormonal activation, all of which can contribute to cardiomyocyte injury and adverse ventricular remodeling.”

SPRINT investigated whether more intensive blood pressure lowering improves cardiovascular outcomes in adults without diabetes.² The trial randomly assigned 9361 participants with elevated systolic blood pressure greater than or equal to 130 mm Hg and increased cardiovascular risk to an intensive target less than 120 mm Hg or a standard target less than 140 mm Hg.

Over a median follow-up of 3.26 years, intensive treatment significantly reduced the risk of major cardiovascular events—including heart attack, stroke, and HF—and all-cause mortality compared with standard treatment. However, participants in the intensive group experienced higher rates of some adverse events, such as hypotension, syncope, electrolyte abnormalities, and acute kidney injury, highlighting the need to balance benefits and risks when implementing aggressive blood pressure control strategies.

In this study, researchers looked at 2 groups: those with biomarker measurements at the start of the study and those with measurements at both baseline and 12 months to track changes over time.¹ Prediabetes was defined as a fasting blood sugar of 100–125 mg/dL. Subclinical heart injury was identified using hs-cTnI, and heart stress was measured with NT-proBNP. A 25% or greater increase in these biomarkers over 12 months was considered significant. The study’s main outcome was the development of HF, and statistical models were used to determine how prediabetes and biomarker changes together influenced risk.

Among 8234 participants (mean age [SD] 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 (IQR) follow-up of 3.2 (2.8-3.8) years, 122 participants developed HF. Compared with participants who had normal glucose and no biomarker elevation, those with both prediabetes and myocardial injury had more than four times the risk of HF (HR, 4.20; 95% CI, 2.31-7.63), while those with prediabetes and myocardial stress had a more than 5-fold increased risk (HR, 5.20; 95% CI, 2.52-10.70).

In the longitudinal analysis of 7449 participants, a 25% or greater increase in hs-cTnI or NT-proBNP combined with prediabetes was also associated with the highest risk of heart failure (hs-cTnI: HR, 3.05; 95% CI, 1.58-5.88; NT-proBNP: HR, 2.39; 95% CI, 1.28-4.46).

However, the researchers noted several study limitations. This was an observational analysis, in which causal relationships could not be established. Prediabetes was defined using a single fasting glucose measurement, which may have misclassified some participants. Additionally, echocardiographic data were not available, preventing assessment of cardiac structure or heart failure subtypes.

Despite these limitations, the researchers believe these findings suggest that the combination of prediabetes and subclinical myocardial stress or injury significantly amplifies the risk of future HF.

“In conclusion, among adults with hypertension without diabetes in this cohort study, the presence of prediabetes in combination with subclinical myocardial injury or stress—whether defined at baseline or by longitudinal increases—was associated with a substantially increased risk of incident HF,” wrote the researchers.

References

1. Kaze AD, Juraschek SP, Cohen JB, et al. Prediabetes, subclinical myocardial injury or stress, and heart failure risk for adults with hypertension. JAMA Cardiol. doi:10.1001/jamacardio.2025.4927

2. The SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2116. doi:10.1056/NEHMoa1511939