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.

GlycA measured by NMR spectroscopy is associated with disease activity and cardiovascular disease risk in chronic inflammatory diseases

“…GlycA concentrations are associated with both prevalent and incident CVD events independent of traditional risk factors [ 32 ] ( Table 1 ). GlycA is associated with the presence and extent of coronary artery disease (CAD) and peripheral artery disease (PAD) [ [41] , [42] , [43] ], and in persons with clinical and subclinical CVD [ 44 , 45 ]. Independent of traditional CVD risk factors and clinical parameters, GlycA concentrations are associated with incident CVD events, as noted in the Women’s Health Study (WHS) [ 46 ], the Prevention of Renal and Vascular End-stage Disease (PREVEND) Study [ 47 ], the Multi-Ethnic Study of Atherosclerosis (MESA) [ 48 ], the Intermountain Health Collaborative Study [ 49 ], the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial [ 50 ], the Dallas Heart Study [ 51 ], and the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) [ 52 ].…”

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

“…BMI, physical activity, smoking, blood pressure, glucose, cholesterol)–health metrics which are also risk factors for AF [ 18 ]. Higher GlycA levels have been linked with subclinical atherosclerosis [ 30 , 33 , 34 ], incident CVD [ 19 – 22 ], and with heart failure with preserved ejection fraction [ 23 ]. In a prior MESA study comparing the predictive value of GlycA and other inflammatory biomarkers, GlycA had a significantly predictive value comparable to hsCRP, IL-6, and D-dimer, if not superior, for total death, CVD, chronic inflammatory-related severe hospitalization and death, and total cancer [ 21 ].…”

“…atherosclerosis [30,33,34], incident CVD [19][20][21][22], and with heart failure with preserved ejection fraction [23]. In a prior MESA study comparing the predictive value of GlycA and other inflammatory biomarkers, GlycA had a significantly predictive value comparable to hsCRP, IL-6, and D-dimer, if not superior, for total death, CVD, chronic inflammatory-related severe hospitalization and death, and total cancer [21].…”

Carotid Plaque Inflammation Assessed by18F-FDG PET/CT and Lp-PLA2Is Higher in Symptomatic Patients

“…Serum biomarkers of atherosclerosis have mainly been studied in CAD, and studies carried out in carotid stenosis patients are less common. 40,41 Given the different pathological mechanisms of these diseases, discoveries in the coronary arteries may not be transferable to carotid artery disease. Assessment of carotid artery plaque inflammation is important both to establish risk and to evaluate treatment responses in clinical trials.…”