GlycA, a Novel Inflammatory Marker and Its Association With Peripheral Arterial Disease and Carotid Plaque: The Multi-Ethnic Study of Atherosclerosis

Abstract

GlycA, a composite biomarker of systemic inflammation, is associated with cardiovascular disease (CVD) and mortality, but its relationship with peripheral artery disease (PAD) is unknown. We assessed whether plasma GlycA is associated with ankle-brachial index (ABI), carotid plaque (CP), and incident clinical PAD among 6466 Multi-Ethnic Study of Atherosclerosis participants without CVD at baseline. GlycA, ABI, and CP were measured at baseline. Both ABI and CP were remeasured at 10 years. Incident clinical PAD was ascertained from hospital records. We used logistic, Cox, and linear mixed regression models adjusted for demographic and lifestyle factors. Mean (standard deviation, SD) was 62 (10) years for age and 381 (61) µmol/L for GlycA; 53% were women. GlycA was associated with both prevalent low ABI ≤0.8 (prevalence odds ratio [95% confidence interval, CI] per SD increment in GlycA, 1.65 [1.39-1.97]) and CP (1.19 [1.11-1.27]) at baseline. There were no significant associations of GlycA with incident low ABI, incident CP, or 10-year change in ABI or CP score. We identified 110 incident cases of PAD after 79 590 person-years. The hazard ratio (95% CI) of incident PAD per SD increment in GlycA was 1.38 (1.14-1.66). In conclusion, GlycA was associated with prevalent low ABI, prevalent CP, and incident PAD after a median of 14 years.

Trial registration: ClinicalTrials.gov NCT00005487.

Keywords: GlycA; ankle–branchial index; carotid plaque; inflammation; peripheral artery disease.

Conflict of interest statement

Declaration of Conflicts of Interest

Dr. Otvos is employed by LabCorp (formerly LipoScience). Dr. Mora received research grants from Atherotech, consulting fees from Quest and has a patent application on the use of GlycA for predicting risk of colorectal cancer. Dr. Stein receives royalties from the Wisconsin Alumni Research Foundation for patent related to carotid artery wall thickness and arterial age (technology not used in this paper). The other authors do not report any disclosures.

Figures

Figure 1.

Participant flow chart of inclusions and exclusions.

Figure 2.

Restricted cubic spline* of GlycA with incident peripheral artery disease, the Multi-Ethnic Study of Atherosclerosis, 2000‐2015 * The median (374.9 μmol/L) was used as reference in a Cox proportional hazards model adjusted for age, sex, race/center, education, BMI, smoking status, ln pack-years, and ln physical activity. Knots were placed at the 5th, 27.5th, 50th, 72.5th, and 95th percentiles. High extreme values (GlycA levels > 600 μmol/L) were excluded (n=17) from analysis.