Risk of acute myocardial infarction among new users of chondroitin sulfate: A nested case-control study.

Ramón Mazzucchelli,Antonio Rodríguez-Miguel,Francisco J De Abajo,Sara Rodríguez-Martín,Alberto García-Lledó,Miguel Gil,Diana Barreira-Hernández,Alberto García-Vadillo,Ping-Hsun Wu

doi:10.1371/journal.pone.0253932

Abstract

To test the hypothesis that the use of chondroitin sulfate (CS) or glucosamine reduces the risk of acute myocardial infarction (AMI). Case-control study nested in a primary cohort of patients aged 40 to 99 years, using the database BIFAP during the 2002-2015 study period. From this cohort, we identified incident cases of AMI and randomly selected five controls per case, matched by exact age, gender, and index date. Adjusted odds ratios (AOR) and 95% confidence interval (CI) were computed through a conditional logistic regression. Only new users of CS or glucosamine were considered. A total of 23,585 incident cases of AMI and 117,405 controls were included. Of them, 89 cases (0.38%) and 757 controls (0.64%) were current users of CS at index date, yielding an AOR of 0.57 (95%CI: 0.46-0.72). The reduced risk among current users was observed in both short-term (<365 days, AOR = 0.58; 95%CI: 0.45-0.75) and long-term users (>364 days AOR = 0.56; 95%CI:0.36-0.87), in both sexes (men, AOR = 0.52; 95%CI:0.38-0.70; women, AOR = 0.65; 95%CI:0.46-0.91), in individuals over or under 70 years of age (AOR = 0.54; 95%CI:0.38-0.77, and AOR = 0.61; 95%CI:0.45-0.82, respectively) and in individuals at intermediate (AOR = 0.65; 95%CI:0.48-0.91) and high cardiovascular risk (AOR = 0.48; 95%CI:0.27-0.83), but not in those at low risk (AOR = 1.11; 95%CI:0.48-2.56). In contrast, the current use of glucosamine was not associated with either increased or decreased risk of AMI (AOR = 0.86; 95%CI:0.66-1.08). Our results support a cardioprotective effect of CS, while glucosamine seems to be neutral. The protection was remarkable among subgroups at high cardiovascular risk.

Highlights

Osteoarthritis (OA) and cardiovascular (CV) diseases are epidemiologically associated
The reduced risk among current users was observed in both short-term (364 days AOR = 0.56; 95% confidence intervals (95%CI):0.36–0.87), in both sexes, in individuals over or under 70 years of age (AOR = 0.54; 95%CI:0.38–0.77, and AOR = 0.61; 95%CI:0.45–0.82, respectively) and in individuals at intermediate (AOR = 0.65; 95%CI:0.48–0.91) and high cardiovascular risk (AOR = 0.48; 95%CI:0.27–0.83), but not in those at low risk
Our results support a cardioprotective effect of chondroitin sulfate (CS), while glucosamine seems to be neutral

Summary

Introduction

Osteoarthritis (OA) and cardiovascular (CV) diseases are epidemiologically associated. In 2008, Hochberg [1], in a systematic review, reported a higher mortality risk in patients with OA as compared to the general population and suggested that it could be the result of a lowgrade systemic inflammation, lack of physical activity, or both These results were confirmed by Hawker et al [2] in a cohort of patients with symptomatic knee and/or hip OA and Barbour et al [3] analyzing the association between hip radiographic OA and mortality. Throughout the evolution of the process, and due to endothelium inflammation, monocytes migrate from the bloodstream, infiltrate in atherosclerotic lesions, differentiate into macrophages and foam cells [9,10] These cells produce proinflammatory mediators such as TNF-α and interleukin 1ß, which play a key role in the development and exacerbation of atherosclerosis [11,12]. Such inflammatory hypothesis has gained a strong support after the recent publication of two clinical trials [13,14]

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Conclusion