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Plasma Levels of Matrix Metalloproteinase-9 are Independently Associated With Psychosocial Factors in a Middle-Aged Normal Population

From the Department of Medical and Health Sciences (P.G., M.K.), Division of Community Medicine, Linköping University, Sweden.; Department of Medical and Health Sciences (L.N., L.J.), Division of Cardiology, Linköping University, Sweden.; Department of Medical and Health Sciences (J.C.), Division of Health and Society Linköping University, Linköping, Sweden.

Address correspondence and reprint requests to Garvin, Department of Medical and Health Sciences (IMH), Division of Community Medicine, Linköping University, 581 83 Linköping, Sweden. E-mail: peter.garvin{at}liu.se

Objective: To test the association between psychosocial factors and circulating levels of matrix metalloproteinase-9 (MMP-9) in a normal population sample. Psychosocial factors have been associated with inflammatory markers and are of prognostic significance for coronary artery disease (CAD). The degrading enzyme MMP-9 is upregulated in inflammatory processes and hypothesized to play a role in the rupture of atherosclerotic plaques.

Methods: A total of 402 participants (50% women), aged 45 to 69 years, were drawn randomly from a normal population. Psychosocial instruments covered depression (Center for Epidemiological Studies Depression Questionnaire, CES-D), vital exhaustion, hostile affect, cynicism, mastery, self-esteem, sense of coherence (SOC), emotional support, and social integration. Plasma MMP-9 was measured by an enzyme-linked immunosorbent assay method. Linear regression models were adjusted for age, sex, known CAD, rheumatoid arthritis, cancer, cardiovascular risk factors including C-reactive protein and ongoing medication.

Results: After full adjustment, there were independent associations of elevated MMP-9 levels with CES-D (+2.9 ng/ml per SD, p = .02), hostile affect (+3.0 ng/ml per SD, p = .02), cynicism (+3.5 ng/ml per SD, p = .006), and SOC (–2.5 ng/ml per SD, p = .046). A principal component analysis extracted three components. The first was mainly extracted from CES-D, vital exhaustion, self-esteem, mastery, and SOC; the second was mainly extracted from hostile affect and cynicism. Both were independently associated with MMP-9 (p = .02, p = .04) when run in the same model.

Conclusions: MMP-9 levels were associated with psychosocial factors in a middle-aged normal population sample, independently of traditional risk factors. The findings may constitute a possible link between psychosocial factors and cardiovascular risk.

Key Words: depression • hostile affect • cynicism • sense of coherence • metalloproteinases • cardiovascular

Abbreviations: CAD = coronary artery disease; CES-D = Center for Epidemiological Studies Depression Questionnaire; CRP = C-reactive protein; HDL = high-density lipoprotein; IL = interleukin; IQR = interquartile range; LDL = low-density lipoprotein; LSH = Life conditions, Stress and Health; MMP-9 = matrix metalloproteinase-9; PHCC = Primary Health Care Centre; SOC = sense of coherence; SBP = systolic blood pressure; SD = standard deviation.