Tissue inhibitor of matrix metalloproteinases 4 (TIMP4) in a population of young adults: Relations to cardiovascular risk markers and carotid artery intima-media thickness. The Cardiovascular Risk in Young Finns Study

Abstract

Objectives. The tissue inhibitor of metalloproteinases 4 (TIMP4) is present in significant amounts in human atherosclerotic coronary artery lesions, but its relations with the early pathogenesis of atherosclerotic changes have not been clarified. We studied the associations of circulating TIMP4 with pre-clinical markers of atherosclerosis and traditional cardiovascular risk factors by using longitudinal data on carotid artery intima-media (cIMT) thickness in a population-based cohort of asymptomatic young adult Finns. Methods. Data on cIMT, plasma TIMP4, lipids, CRP, blood pressure, BMI, smoking status and daily alcohol intake were obtained from 980 24–39 year-old participants in 2001. The 6-year follow-up in cIMT measurements were performed in 2007 for 769 participants. Results. Plasma TIMP4 concentrations (mean ± SD) were 2.3 ± 1.7 ng/mL in men and 2.5 ± 1.8 ng/mL in women. Age, LDL-cholesterol, BMI and systolic blood pressure were directly associated with TIMP4 concentration. In a multivariable model, the independent determinants of TIMP4 included systolic blood pressure (p = 0.008) and daily smoking (p = 0.009), both being inversely associated with TIMP4. These two baseline variables explained 1.5% of the variation in TIMP4. TIMP4 was significantly and inversely associated with cIMT measured 6 years later (beta =− 0.0135, p = 0.01) explaining 0.7% of the variability of cIMT. Conclusion. In young apparently healthy adults, circulating TIMP4 concentration was independently and inversely associated with cIMT, a marker of vascular structure and function.

Key Words::

• Tissue inhibitor of metalloproteinases
• carotid intima-media thickness
• atherosclerosis
• cohort
• studies
• risk factors
• epidemiology

Acknowledgements

The Young Finns Study has been financially supported by the Academy of Finland grants 126925, 121584, 124282, 129378, 117787 and 41071, the Social Insurance Institution of Finland, Kuopio, Tampere and Turku University Hospital Medical Funds, Turku University Foundation, Juho Vainio Foundation, Paavo Nurmi Foundation, Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of paper.