Long-term influence of diet and/or omega-3 fatty acids on matrix metalloproteinase-9 and pregnancy-associated plasma protein-A in men at high risk of coronary heart disease

Background. Matrix metalloproteinases (MMPs) are important in the atherosclerotic process. The relationship between MMPs and traditional risk factors for cardiovascular disease (CVD) and any influence of lifestyle changes are largely unknown. Objectives. In a factorial design, we studied the effects of 3 years of dietary counselling and/or n-3 PUFA supplementation (2.4 g/d) on the levels of MMP-9, tissue inhibitor of metalloproteinase (TIMP-1) and pregnancy-associated plasma protein (PAPP-A) in a population of elderly men at high risk of CVD (n=563, age 70 +/- 6 years). We further explored the association between these markers and different disease entities, carotid intima media thickness (IMT) and traditional risk factors for CVD. Results. Smokers had significantly higher levels of MMP-9 (p < 0.0001), and TIMP-1 levels were lower in subjects with previous AMI (p = 0.021). MMP-9 was significantly correlated with LDL-C and inversely with HDL-C (both p < 0.0001). There were no significant correlations between the measured variables and IMT. Significant reductions in MMP- 9 and PAPP-A levels after 36 months were found in all study groups, however, with no between-group differences. Conclusions. The elevated levels of MMP- 9 in smokers and the reduced levels of TIMP-1 in patients with previous AMI reflect an importance of MMPs in the development of CVD. Intervention with diet and/or n-3 PUFA supplementation did not influence the levels of MMP- 9, TIMP-1 or PAPP-A in the present population.