Elsevier

American Heart Journal

Volume 167, Issue 1, January 2014, Pages 109-115.e2
American Heart Journal

Clinical Investigation
Electrophysiology
Relation between soluble ST2, growth differentiation factor–15, and high-sensitivity troponin I and incident atrial fibrillation

https://doi.org/10.1016/j.ahj.2013.10.003Get rights and content

Background

We investigated whether circulating concentrations of soluble ST2, growth differentiation factor–15 (GDF-15), and high-sensitivity troponin I (hsTnI) are associated with incident atrial fibrillation (AF) and whether these biomarkers improve current risk prediction models including AF risk factors, B-type natriuretic peptide (BNP), and C-reactive protein (CRP).

Methods

We studied the relation between soluble ST2, GDF-15, and hsTnI and development of AF in Framingham Heart Study participants without prevalent AF. We used Cox proportional hazard regression analysis to examine the relation of incident AF during a 10-year follow-up period with each biomarker. We adjusted for standard AF clinical risk factors, BNP, and CRP.

Results

The mean age of the 3,217 participants was 59 ± 10 years, and 54% were women. During a 10-year follow-up, 242 participants developed AF. In age- and sex-adjusted models, GDF-15 and hsTnI were associated with risk of incident AF; however, after including the AF risk factors and BNP and CRP, only hsTnI was significantly associated with AF (hazard ratio per 1 SD of loge hsTnI, 1.12, 95% CI 1.00-1.26, P = .045). The c statistic of the base model including AF risk factors, BNP, and CRP was 0.803 (95% CI 0.777-0.830) and did not improve by adding individual or all 3 biomarkers. None of the discrimination and reclassification statistics were significant compared with the base model.

Conclusion

In a community-based cohort, circulating hsTnI concentrations were associated with incident AF. None of the novel biomarkers evaluated improved AF risk discrimination or reclassification beyond standard clinical AF risk factors and biomarkers.

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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