YKL-40 is elevated in patients with peripheral arterial disease and diabetes or pre-diabetes

ObjectiveYKL-40 is secreted by macrophages in atherosclerotic lesions and involved in plaque rupture. YKL-40 is elevated in coronary artery disease, and predicts cardiovascular mortality. Experimental in vivo and in vitro data suggest a role of YKL-40 in tissue remodeling. A disease modulating potency of YKL-40 was not investigated in peripheral arterial disease (PAD).MethodsWe measured YKL-40 in 460 subjects: 316 PAD: 71 normal glucose metabolism (PAD-NGM), 90 pre-diabetes (PAD-PREDM) and 155 diabetes (PAD-DM); 20 diabetes with atherosclerosis but without PAD (AS-DM); 85 diabetes without macro-vascular complications (DM) and 39 healthy controls (CO).ResultsYKL-40 is higher in PAD vs. CO (median [25-75 percentile]: 103 [69-159] vs. 43 [30-80] ng/ml; p < 0.001). In addition, YKL-40 is elevated in DM (p < 0.001), PAD-NGM (p = 0.001), PAD-PREDM (p < 0.001), PAD-DM (p < 0.001) and AS-DM (p = 0.002) compared to CO. Among PAD, YKL-40 is increased in PAD-PREDM (p = 0.001) and PAD-DM (p = 0.01) vs. PAD-NGM. By multivariate regression YKL-40 is significantly associated with age (beta = 0.272), triglycerides (beta = 0.216), aspartate-amino-transferase (beta = 0.177) and c-reactive-protein (beta = 0.178). Underpinning its role YKL-40 was found to be associated with micro-/macroalbuminuria (p = 0.014/p = 008) - a strong remodeling inducer. In addition, YKL-40 was elevated in existence of mediasclerosis (p = 0.008), a remodeling process.ConclusionWe are first to show that YKL-40 is higher in subjects with peripheral arterial disease. YKL-40 was higher in PAD patients with pre-/diabetes. In addition, YKL-40 was associated with the “severity” of generalized atherosclerosis estimated by affected vascular beds. All our findings point towards a role of YKL-40 in the progression/prognosis of patients with PAD and concomitant diabetes.

► The role of YKL-40 in atherosclerosis was investigated in a cohort study. ► YKL-40 was higher in patients with peripheral arterial disease and/or diabetes. ► YKL-40 is associated with age, metabolism, liver function and inflammation. ► YKL-40 is associated with albuminuria and mediasclerosis. ► Thus, YKL-40 may be involved in the specific diabetic form of atherosclerosis.