Plasma matrix metalloproteinases are associated with incident cardiovascular disease and all-cause mortality in patients with type 1 diabetes: a 12-year follow-up study

Cardiovascular Diabetology

Original Investigation

A. Jorsal¹  C. G. Schalkwijk²  C. D. A. Stehouwer²  L. Engelen²  S. A. Peeters³  J. Buijs⁴  H.-H. Parving⁵  P. Rossing⁶  L. Tarnow⁷ 

[1] Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark;Steno Diabetes Center, Gentofte, Denmark;Department of Internal Medicine, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands;CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands;Department of Internal Medicine, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands;Department of Internal Medicine, Zuyderland hospital, Heerlen, The Netherlands;Department of Internal Medicine, Zuyderland hospital, Heerlen, The Netherlands;Department of Medical Endocrinology, Rigshospitalet, Copenhagen, Denmark;Faculty of Health Science, Aarhus University, Aarhus, Denmark;Faculty of Health, University of Copenhagen, Copenhagen, Denmark;Steno Diabetes Center, Gentofte, Denmark;Faculty of Health Science, Aarhus University, Aarhus, Denmark;Faculty of Health, University of Copenhagen, Copenhagen, Denmark;Steno Diabetes Center, Gentofte, Denmark;Faculty of Health Science, Aarhus University, Aarhus, Denmark;Nordsjaellands Hospital, Hilleroed, Denmark;

关键词: Type 1 diabetes;    Cardiovascular disease;    All-cause mortality;    Matrix metalloproteinase;    Tissue inhibitor of metalloproteinase;    Estimated glomerular filtration rate;   

DOI  :  10.1186/s12933-017-0539-1

 received in 2017-01-24, accepted in 2017-04-20,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAltered regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular events and all-cause mortality in type 1 diabetic patients.MethodsWe prospectively followed 337 type 1 diabetic patients [mean age 41.4 years (9.6), 39% female], 170 with and 167 without diabetic nephropathy, with median follow-up of 12.3 years. Survival analyses were applied to investigate differences in plasma MMP-1, -2, -3, -9, -10, and TIMP-1-levels in patients with and without a cardiovascular event and in those who died vs survivors. All analyses were adjusted for age, sex, duration of diabetes, HbA1c, nephropathy and for other conventional cardiovascular risk factors.ResultsAfter adjustment for potential confounders, higher MMP-2 plasma levels were significantly associated with higher incidence of cardiovascular events [HR 1.49 (95% CI 1.11; 1.99)], and higher plasma levels of MMP-1 [1.38 (1.07; 1.78)], MMP-2 [1.60 (1.19; 2.15)] and MMP-3 [1.39 (1.05; 1.85)] were associated with all-cause mortality. All associations were independent of low-grade inflammation and endothelial dysfunction as estimated by plasma markers. Associations between MMP-2 and cardiovascular events and between MMP-3 and mortality were attenuated after further adjustment for eGFR and changes in eGFR.ConclusionsHigher levels of MMP-2 are associated with CVD and higher MMP-1, -2 and -3 with all-cause mortality. In addition, associations between MMP-2 and CVD, and MMP-3 and mortality were attenuated after adjustment for eGFR while both MMPs were associated with eGFR decline, indicating a possible mediating role of eGFR.

【 授权许可】

CC BY   
© The Author(s) 2017