Tissue Inhibitor of Matrix Metalloproteinase 1 Increases With Ageing and Can Be Associated With Stroke　― Nested Case-Control Study ―

Background: Increase of collagen in the extracellular matrix occurs with ageing. We investigated whether a collagen marker, tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), was associated with risk of stroke. Methods and Results: In a nested case-control study of 953 subjects from the general population, we evaluated determinants of TIMP-1 level and stroke risk. Mean subject age was 65.7±8.6 years (53.0% men); TIMP-1 was 72.4±28.2 pg/mL in the control group and 75.3±30.9 pg/mL in the stroke group. The relationship between TIMP-1 quartile and stroke was J-curved. Subjects in the highest TIMP-1 quartile (≥89 ng/mL) had a significantly higher OR of stroke (59–72 ng/mL; OR, 1.90; 95% CI: 1.09–3.31, P=0.023) than those in the second TIMP-1 quartile, and this tended toward significance even after adjusting for confounding factors (P=0.059). Elevation of serum TIMP-1 became more marked after age 65 years. On multiple linear regression analysis, significant determinants of TIMP-1 were older age (B=0.21 per 1 year; 95% CI: 0.52–1.07, P<0.001) and higher systolic blood pressure (SBP; B=0.19 per 1 mmHg, 95% CI: 0.08–0.42, P=0.004). Conclusions: TIMP-1 increased with ageing and with SBP, and can be associated with stroke.