Serum Chitotriosidase Activity, a Marker of Activated Macrophages, Predicts New Cardiovascular Events Independently of C-Reactive Protein

Abstract

Background: C-reactive protein (CRP) is a well-established inflammation marker associated with cardiovascular risk. However, its relationship with chitotriosidase activity, a novel marker of activated macrophages highly expressed in human atherosclerotic plaques, is unknown. Therefore, we sought to determine if serum chitotriosidase activity predicts the risk of new coronary events, and to analyze its relationship with CRP. Methods: Chitotriosidase activity and genotype, and high-sensitivity CRP were measured at baseline in 133 middle-aged men with stable coronary heart disease, who were followed for the occurrence of cardiovascular morbidity and mortality for a mean of 4 years. We studied the value of these proteins in predicting the risk of new cardiovascular events. Results: Serum chitotriosidase activity was higher in the group of subjects with a prespecified major event (nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization procedures and death from cardiovascular causes) than in the group of subjects without event, 116 ± 30.9 nmol/ml·h versus 74.2 ± 5.69 nmol/ml·h, respectively (p = 0.042). The baseline values of chitotriosidase activity and CRP did not correlate (R = 0.104, p = 0.266), but both parameters were related to a reduction of event-free survival in the Cox regression analysis, with relative risks of 2.61 (p = 0.060) and 2.56 (p = 0.019), respectively. Chitotriosidase activity seems to be a better marker for new events occurring after 2 years of follow-up than in the first 2 years. Both markers had similar predictive values, and their sensitivity (64%) and negative predictive value (84%) were improved when combined. Conclusions: Our results suggest that serum chitotriosidase activity predicts the risk of new cardiovascular events in the following 4 years. This new cardiovascular risk marker is independent of CRP and, when combined, the prediction of the risk of new cardiovascular events and the identification of a lower risk group seem to improve.

Serum Chitotriosidase Activity in Patients With Coronary Artery Disease

“…28,29 In a related study, Artieda et al also showed that chitotriosidase activity predicts the risk of new adverse cardiovascular events in a follow-up period of 4 years. 30 Canudas et al reported that serum chitotriosidase activity is not associated with lipid levels before and after treatment with statins, which suggests that plasma lipid level alteration does not affect macrophage chitotriosidase expression level in vivo 31 and is in accordance with our study, showing no correlation between blood lipid levels and chitotriosidase activity.…”

Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

“…[16][17] Chit activity seems to be related to the severity of atherosclerotic lesions, thereby suggesting a possible role for Chit as a marker of atherosclerotic extension. [18][19][20] In addition, it was reported that patients with atherothrombotic stroke (ATS) and ischemic disease (IHD) had significantly higher Chit activities than the control group. 19 However, ATS subjects had higher Chit activity than IHD subjects, whose atherosclerosis is localized more specifically in coronary vessels.…”

Serum Chitotriosidase Activity in Acute Coronary Syndrome

“…Serum CHIT activity was more prominent in stroke patients than in patients with ischemic heart disease, suggesting more widespread atherosclerosis. In a related study, Artieda et al (2007) also showed that CHIT activity predicts the risk of new adverse cardiovascular events within a follow-up period of four years 21) . Canudas et al (2001) reported that serum CHIT activity is not associated with lipid levels before and after treatment with statins, which suggests that plasma lipid level alteration does not affect the macrophage CHIT expression level in vivo and is in accordance with our study, showing no correlation between blood lipid levels and CHIT activity 22) .…”