Progress in cardiovascular diseases · 2026
Cardio-metabolic biomarkers including circulating ketone bodies and risk of incident atrial fibrillation in the multi-ethnic study of atherosclerosis (MESA).
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Chevli Parag Anilkumar, McParland James, Masrouri Soroush, Gokul Kaushik, Connelly Margery A, DeFilippi Christopher R, Bradford Natalie, Raina Anvi, Heckbert Susan R, Szklo Moyses, Suzuki Takeki, Shapiro Michael D, Bhave Prashant D
Аннотация
BACKGROUND: Atrial fibrillation (AF) reflects systemic cardio-metabolic dysfunction. While myocardial stress and injury biomarkers are associated with incident AF, the role of ketone bodies (KB) remains incompletely defined.
OBJECTIVES: To evaluate a multi-biomarker risk score integrating KB with NT-proBNP and hs-cTnT for incident AF prediction and its incremental value beyond established clinical models.
METHODS: We studied 6429 MESA participants free of AF and clinical CVD at baseline. A multi-biomarker risk score using total KB >252 μmol/L, NT-proBNP ≥125 pg/mL, and hs-cTnT ≥14 ng/L was categorized as Very Low Risk Score = 0, Low Risk Score = 1-3, Intermediate Risk Score = 4-5, and High Risk Score > 5. Associations with incident AF were evaluated using Cox proportional hazards and Fine-Gray competing risk models.
RESULTS: Over 16.4 years, 1269 participants developed AF before death. Higher risk score categories were associated with a strong, graded increase in AF risk independent of demographic, socioeconomic, and clinical covariates. High Risk Score > 5 had nearly threefold greater AF risk versus Very Low Risk Score = 0 (HR 2.72; 95% CI, 2.11-3.49; P < 0.001). At 5 years, AUC was 0.768 for CHARGE-AF, 0.784 after adding NT-proBNP, and 0.787 after adding hs-cTnT. Adding KB after NT-proBNP and hs-cTnT did not materially change the AUC; 10-year findings were similar. Decision curves showed no clear additional net benefit.
CONCLUSIONS: A multi-biomarker risk score integrating KB with NT-proBNP and hs-cTnT was strongly associated with incident AF and provided modest incremental predictive value beyond CHARGE-AF. External validation is warranted before clinical application.
OBJECTIVES: To evaluate a multi-biomarker risk score integrating KB with NT-proBNP and hs-cTnT for incident AF prediction and its incremental value beyond established clinical models.
METHODS: We studied 6429 MESA participants free of AF and clinical CVD at baseline. A multi-biomarker risk score using total KB >252 μmol/L, NT-proBNP ≥125 pg/mL, and hs-cTnT ≥14 ng/L was categorized as Very Low Risk Score = 0, Low Risk Score = 1-3, Intermediate Risk Score = 4-5, and High Risk Score > 5. Associations with incident AF were evaluated using Cox proportional hazards and Fine-Gray competing risk models.
RESULTS: Over 16.4 years, 1269 participants developed AF before death. Higher risk score categories were associated with a strong, graded increase in AF risk independent of demographic, socioeconomic, and clinical covariates. High Risk Score > 5 had nearly threefold greater AF risk versus Very Low Risk Score = 0 (HR 2.72; 95% CI, 2.11-3.49; P < 0.001). At 5 years, AUC was 0.768 for CHARGE-AF, 0.784 after adding NT-proBNP, and 0.787 after adding hs-cTnT. Adding KB after NT-proBNP and hs-cTnT did not materially change the AUC; 10-year findings were similar. Decision curves showed no clear additional net benefit.
CONCLUSIONS: A multi-biomarker risk score integrating KB with NT-proBNP and hs-cTnT was strongly associated with incident AF and provided modest incremental predictive value beyond CHARGE-AF. External validation is warranted before clinical application.