Matrix metalloproteinase-1 and tissue inhibitors do not predict incident coronary artery disease in the Atherosclerosis Risk in Communities (ARIC) study

Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are thought to be associated with coronary artery disease. The association of these markers with incident coronary artery disease has not been well described. Using a case-cohort design, we selected 216 individuals who had incident coronary artery disease (case group) and 225 individuals from a cohort random sample (comparison group) from participants enrolled in the Atherosclerosis Risk in Communities study. We measured plasma levels of MMP-1 and TIMP-1, traditional risk factors, and other markers of inflammation. We found no significant difference in TIMP-1 levels between the case group (827.8 ± 23.8 ng/mL) and the comparison group (819.31 ± 16.1 ng/mL) (P=0.77), and no significant difference in the frequency of MMP-1 levels that were dichotomized at the minimum detectable value of 1.7 ng/mL (P=0.49). In models adjusted for age, sex, race, body mass index, hypertension, diabetes, total cholesterol, high-density lipoprotein cholesterol, triglycerides, fibrinogen, von Willebrand factor, and white blood cell count, the hazard-rate ratio for incident coronary artery disease was 1.14 (95% confidence interval, 0.63-2.04; P=0.67) for individuals whose TIMP-1 levels were above, versus at or below the mean, and 1.17 (95% confidence interval, 0.63-2.19; P=0.62) for individuals whose MMP-1 levels were above 1.7 ng/mL. We conclude that TIMP-1 and MMP-1 levels in plasma were not predictive of incident coronary artery disease in a case-cohort random sample of the Atherosclerosis Risk in Communities study, a population study of asymptomatic middle-aged adults who had no prevalent atherosclerosis upon enrollment.