The association of novel inflammatory marker GlycA and incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Background: Emerging evidence has implicated that inflammation contributes to the pathogenesis of atrial fibrillation (AF). GlycA is a novel marker of systemic inflammation with low intra-individual variability and high analytic precision. GlycA has been associated with incident cardiovascular disease (CVD) independent of other inflammatory markers. However, whether GlycA is associated with AF, specifically, has yet to be established. We examined the association between GlycA and AF in a multi-ethnic cohort.

Methods: We studied 6,602 MESA participants aged 45-85, with no clinical CVD at baseline, with data on GlycA and incident AF. We used multivariable-adjusted Cox models to evaluate the association between GlycA and incident AF. We also examined other inflammatory markers [high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6) and fibrinogen] and incident AF for comparison.

Results: The mean (SD) age was 62 (10) years, 53% women. The mean plasma GlycA was 381 (62) μmol/L. Over median follow-up of 12.9 years, 869 participants experienced AF. There was no statistically significant association between GlycA and incident AF after adjusting for sociodemographics, CVD risk factors, and other inflammatory markers [Hazard Ratio (95% CI) per 1 SD increment in GlycA: 0.97 (0.88-1.06)]. Neither hsCRP nor fibrinogen was associated with incident AF in same model. In contrast, IL-6 was independently associated with incident AF [HR 1.12 per 1 SD increment (1.05-1.19)].

Conclusions: Although GlycA has been associated with other CVD types, we found that GlycA was not associated with AF. More research will be required to understand why IL-6 was associated with AF but not GlycA.

Clinical trial registration: MESA is not a clinical trial. However, the cohort is registered at: URL: https://ichgcp.net/clinical-trials-registry/NCT00005487 Unique identifier: NCT00005487.

Conflict of interest statement

The authors have read the journal’s policy and have the following competing interests: JDO is a paid employee of Laboratory Corporation of America Holdings (LabCorp). There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Flow diagram illustrating study sample inclusion and exclusion criteria as well as the number of participants with and without AF during follow-up.

Fig 2. Kaplan-Meier survival estimates for the association between GlycA and atrial fibrillation.

Log-rank test: P = 0.64.

Fig 3. Restricted cubic spline of the association between GlycA and atrial fibrillation adjusted for age, sex, race/ethnicity, MESA field site, education, health insurance, BMI, smoking status, pack-years of smoking, physical activity, systolic blood pressure, use of antihypertensive medication, total cholesterol, HDL-cholesterol, use of lipid-lowering medication, diabetes, eGFR, ln(CRP), ln(IL-6) and ln(fibrinogen).

The black curve represents hazard ratios for atrial fibrillation by proportion of population with the respective GlycA concentration. Grey boundaries represent the 95% CI of the hazard ratios. Knots were at the 5th, 35th, 66.5th, and 95th percentiles which correlates to GlycA levels of 289.8, 353.1, 400.2, and 488.8 μmol/L, respectively.