Arrhythmias and conduction disturbance
Relation of Multiple Inflammatory Biomarkers to Incident Atrial Fibrillation

https://doi.org/10.1016/j.amjcard.2009.02.053Get rights and content

Basic and clinical studies have suggested that inflammation predisposes to atrial fibrillation (AF). We assessed the association of 12 circulating inflammatory biomarkers (i.e., C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II) with incident AF in 2863 Framingham Offspring Study participants (mean age 60.7 years, SD = 9.4, 55% women). During follow-up (median 6 years), 148 participants (43% women) developed incident AF. In the multivariable proportional hazards models, the inflammatory biomarker panel was associated with incident AF (p = 0.03). With stepwise selection (p <0.01 for entry and retention), log-transformed osteoprotegerin was associated with incident AF (hazard ratio per SD 1.30, 95% confidence interval 1.08 to 1.56, p = 0.006). Adjusting for interim myocardial infarction or heart failure attenuated the association between osteoprotegerin and incident AF (hazard ratio 1.18, 95% confidence interval 0.98 to 1.43, p = 0.09). In conclusion, circulating osteoprotegerin concentration was significantly associated with incident AF in our community-based sample, possibly mediated by interim cardiovascular events.

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Participants

For the Framingham Offspring cohort, 5,124 individuals were recruited in the early 1970s and were followed routinely.8 The seventh examination cycle (1998 to 2001) was attended by 3,539 participants who were eligible for analysis. For the present investigation, we excluded individuals with any missing inflammatory biomarker measurements (n = 483), incomplete or missing follow-up data (n = 22), prevalent AF (n = 132), or missing covariate data (n = 39), leaving 2,863 attendees for analysis. The

Results

During follow-up through 2007 (median 6.2 years, maximum 8.0 years), 148 incident AF cases (43% women) were identified. Table 1 lists the baseline characteristics of the study sample. In brief, the cohort was middle-age to elderly and about one half of the participants were women. At baseline, heart valve disease, myocardial infarction, and heart failure were uncommon and observed in <5% of participants. Of those with cardiovascular disease at baseline, 38 (11.8%) developed AF. In contrast, of

Discussion

We examined the association of 12 circulating inflammatory biomarkers with incident AF in a contemporary community-based middle-age to elderly cohort. The biomarker osteoprotegerin was significantly associated with incident AF. The relation between osteoprotegerin and incident AF was attenuated and no longer achieved statistical significance in models accounting for interim myocardial infarction and heart failure, suggesting that interim cardiovascular events might partially mediate the

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    This study was supported by National Institutes of Health/National Heart, Lung, Blood Institute Grants N01-HC-25195 and 6R01-NS 17950, and National Institutes of Health Grants HL064753. HL076784, and AG028321 (E. J. Benjamin), 1 RO1HL71039 (R. S. Vasan), Bethesda, Maryland; National Institutes of Health Research Career Award K24 HL04334 (R. S. Vasan), Bethesda, Maryland; Deutsche Forschungsgemeinschaft (German Research Foundation) Research Fellowship SCHN 1149/1-1 (R. B. Schnabel), Bonn, Germany; and Grant 1K23HL083102, Doris Duke Charitable Foundation Clinical Scientist Development Award (S. Kathiresan), New York, New York.

    Lipoprotein-associated phospholipase A2 activity and mass measurements were provided to the Heart Study by GlaxoSmithKline, Williamsburg, Delaware, at no cost.

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