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

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Abstract

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.

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