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Tex Heart Inst J. 2008; 35(4): 388–394.
PMCID: PMC2607088
Matrix Metalloproteinase-1 and Tissue Inhibitors Do Not Predict Incident Coronary Artery Disease in the Atherosclerosis Risk in Communities (ARIC) Study
Vijay Nambi, MD, Alanna C. Morrison, PhD, Ron C. Hoogeveen, PhD, Josef Coresh, MD, PhD, Shawn Miles, MD, Charles Etta Rhodes, BS, A. Richey Sharrett, MD, B. Eric Boerwinkle, PhD, and Christie M. Ballantyne, MD
Section of Atherosclerosis and Vascular Medicine (Drs. Ballantyne, Hoogeveen, and Nambi; and Ms Rhodes), Department of Medicine, Baylor College of Medicine; Center for Cardiovascular Disease Prevention (Drs. Ballantyne and Nambi), Methodist DeBakey Heart Center; Human Genetics Center and Institute of Molecular Medicine (Drs. Boerwinkle and Morrison), University of Texas–Houston Health Science Center; Houston, Texas 77030; Departments of Epidemiology (Drs. Coresh and Sharrett) and Department of Biostatistics and Medicine (Dr. Coresh), Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205; and Division of Cardiovascular Medicine (Dr. Miles), Department of Medicine, Pennsylvania Hospital, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Abstract
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.

Key words: Biological markers/analysis, coronary artery disease/enzymology/physiopathology, matrix metalloproteinase-1, risk factors, tissue inhibitor of metalloproteinase-1