Cumulative Burden of Prediabetes, Subclinical Myocardial Injury, and Myocardial Stress and Risk of Incident Atrial Fibrillation in Adults With Hypertension

Background: Metabolic dysfunction, subclinical myocardial injury, and myocardial stress may contribute to atrial fibrillation (AF), but ther independent and cumulative associations with incident AF are unclear. Methods: We analyzed 7,261 Systolic Blood Pressure Intervention Trial (SPRINT) participants without prevalent AF, who had baseline fasting glucose, high-sensitivity cardiac troponin I (hs-cTnI), and N-terminal pro?B-type natriuretic peptide (NT-proBNP) measurements. By trial design, SPRINT excluded individuals with diabetes, prior stroke or recent symptomatic heart failure or left ventricular ejection fraction <35%. Prediabetes represented metabolic dysfunction, elevated hs-cTnI myocardial injury, and elevated NT-proBNP myocardial stress. Cox models assessed associations of individual domains and the number of abnormal domains (0?3) with incident AF. Secondary analyses examined the 8 mutually exclusive domain combinations. Results: During a median 3.76-year follow-up, 174 participants developed AF. In multivariable adjusted model, prediabetes, elevated hs-cTnI, and elevated NT-proBNP were associated with incident AF (HR, 1.48 [95% CI, 1.07?2.05], 1.84 [95% CI, 1.30?2.60], and 2.35 [95% CI, 1.56?3.55], respectively). AF risk increased progressively with increasing domain burden (P for trend <0.001); each additional abnormal domain was associated with an 82% higher AF risk (HR, 1.82 [95% CI, 1.50?2.22]). Participants with abnormalities in all 3 domains had the highest risk (HR, 6.11 [95% CI, 2.82?13.24]). Conclusions: Prediabetes, subclinical myocardial injury, and myocardial stress were independently associated with incident AF, with progressively greater risk as abnormalities accumulated. These findings support a multidomain framework in which complementary metabolic and cardiac abnormalities collectively characterize susceptibility to AF.