Among 7,261 hypertensive adults in the SPRINT trial followed for a median 3.76 years, 174 developed atrial fibrillation. Each of three biomarker domains independently predicted incident AF: prediabetes (HR 1.48), elevated high-sensitivity cardiac troponin I reflecting subclinical myocardial injury (HR 1.84), and elevated NT-proBNP reflecting myocardial stress (HR 2.35). Crucially, risk compounded with domain accumulation — each additional abnormal domain raised AF hazard by 82%, and participants with all three abnormalities faced a sixfold elevated risk (HR 6.11, 95% CI 2.82–13.24).
This preprint, not yet peer-reviewed, advances a clinically actionable multidomain framing of AF susceptibility that goes beyond traditional single-biomarker approaches. Both hs-cTnI and NT-proBNP are already widely available in clinical labs, and prediabetes is identifiable through routine fasting glucose — meaning this composite risk score requires no new technology. The finding aligns with growing evidence that AF emerges from converging metabolic, structural, and hemodynamic insults rather than any single pathway, reinforcing cardio-metabolic integration as central to arrhythmia risk. Key limitations include the relatively short median follow-up of under four years, an exclusively hypertensive cohort that excluded diabetes and severe heart failure (limiting generalizability), and the modest absolute AF event count of 174 cases. Whether intervening on prediabetes specifically reduces AF incidence in this population remains untested. Confirmatory prospective trials targeting multidomain burden are now warranted.
