Cardiologists and primary care physicians treating hypertensive patients frequently encounter prediabetes alongside subtle heart biomarker elevations, but this post hoc analysis from the landmark SPRINT trial reveals that this combination dramatically amplifies heart failure risk to about four times, providing actionable data to refine risk stratification beyond blood pressure targets alone. 
In this study published in the JAMA Cardiology, the researchers analyzed two SPRINT samples: 8,234 adults with hypertension but without diabetes or prior heart failure for baseline biomarkers, and 7,449 participants with measurements at baseline and 12 months for dynamic changes. Prediabetes meant fasting glucose of 100-125 mg/dL, subclinical myocardial injury showed high-sensitivity cardiac troponin I at 6 ng/L or higher in men and 4 ng/L or higher in women, while subclinical myocardial stress indicated N-terminal pro-B-type natriuretic peptide above 125 pg/mL. 
Baseline Combination Creates Dangerous Synergy
Among participants averaging 68 years old with 37.1% women, 39.7% had prediabetes, 35.7% showed subclinical myocardial injury, and 43.6% had subclinical myocardial stress, reflecting common findings in routine cardiology practice. Over follow-up, 122 developed adjudicated heart failure events, with the highest risk appearing in those combining prediabetes and myocardial injury (HR 4.20, 95% CI 2.31-7.63) versus normoglycemia without injury, and similarly elevated risk with prediabetes plus myocardial stress (HR 5.20, 95% CI 2.52-10.70).
Rising Biomarkers Signal Imminent Threat
Longitudinal analysis confirmed that prediabetes patients experiencing 25% or greater increases in biomarkers faced sharply higher heart failure risk, with hs-cTnI elevation yielding HR 3.05 (95% CI 1.58-5.88) and NT-proBNP rise showing HR 2.39 (95% CI 1.28-4.46), demonstrating progressive subclinical damage drives clinical events even over short-term follow-up.
Hypertension Clinics Gain New Screening Tool
In prediabetic hypertensive patient with normal ejection fraction, the clinicians may order hs-cTnI and NT-proBNP alongside HbA1c and lipids, as SPRINT proves this quartet identifies four-to-five times higher heart failure odds warranting immediate SGLT2 inhibitor consideration regardless of ejection fraction.
Risk Stratification Evolves Immediately
These findings elevate simple biomarker plus glucose testing above traditional scores, enabling precise therapy escalation with ARNI, SGLT2i, or MRA agents before hospitalization occurs, particularly valuable in SPRINT-like older adults with controlled blood pressure.
Prevention Windows Still Exist
Early detection of this synergistic risk opens intervention opportunities through aggressive prediabetes reversal, weight management, and serial biomarker monitoring to track response and prevent progression to symptomatic heart failure.