Clinical InvestigationElectrophysiologyRelation between soluble ST2, growth differentiation factor–15, and high-sensitivity troponin I and incident atrial fibrillation
Section snippets
Sample
The community-based Framingham Heart Study was founded in 1948 by enrolling 5,209 participants in the original cohort. Starting in 1971, the offspring of the original cohort and their spouses were enrolled in the Framingham Offspring Study (n = 5,124) and were followed up every 4 to 8 years. We evaluated participants of the Framingham Heart Study Offspring Cohort who attended the sixth examination cycle (1995-1998; n = 3,532). Enrollment and follow-up details have been described elsewhere.14
Results
Our study sample consisted of 3,217 participants with a mean age of 59 ± 10 years, and 54% were women. During a 10-year follow-up, 242 participants developed AF. Characteristics of the participants are reported in Table I. Pearson correlation coefficients varied from 0.03 (BNP and soluble ST2) to 0.31 (BNP and GDF-15), as shown in online Appendix Supplementary Table I.
Discussion
In the present study, hsTnI was significantly related with incident AF, even after adjustment for well-known clinical risk factors, BNP, and CRP. The base model including AF risk factors, BNP, and CRP, performed reasonably well (c statistic of 0.803) and was not further improved by adding soluble ST2, GDF-15, and hsTnI, individually or together.
Despite the great interest in soluble ST2, GDF-15, and hsTnI in coronary heart disease,23, 24 heart failure,25, 26, 27, 28 and ischemic stroke,29, 30
Strengths and limitations
The Framingham Heart Study is a well-characterized, community-based sample with extensive routine ascertainment of clinical risk factors for AF and other cardiovascular conditions, rigorous clinical ascertainment of incident AF, and long-term follow-up. However, our analysis has some limitations that merit consideration. First, we had excellent power for modest but clinically meaning effects, but low power to detect small effects (80% power for HR of 1.16 and 90% power to detect a HR >1.17 at P
Conclusion
Of the 3 novel biomarkers we investigated in a large community-based cohort, hsTnI was associated with incident AF, although with modest effect size. None of the 3 biomarkers substantively increased risk prediction of AF beyond known AF risk factors and markers.
Sources of funding
The Framingham Heart Study is supported by N01-HC 25195. Dr Rienstra is supported by a grant from the Netherlands Organization for Scientific Research (Veni Grant No. 016.136.055). This work was supported by grants from the National Institutes of Health to Drs Benjamin and Ellinor (1R01HL092577), Dr Benjamin (1RC1HL101056, 1R01HL102214, and support via 6R01-NS 17950), and Dr Ellinor (5RO1HL104156, 1K24HL105780). Dr Ellinor is supported by an Established Investigator Award from the American
Disclosures
Dr Januzzi reports receiving grant support from Roche Diagnostics, Critical Diagnostics, Singulex, BG Medicine, Siemens, and Thermo-Fisher.
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