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
Abstract Background Altered 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, a...
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| Format: | Article |
| Language: | English |
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BMC
2017-04-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12933-017-0539-1 |
| _version_ | 1828518668994084864 |
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| author | S. A. Peeters L. Engelen J. Buijs A. Jorsal H.-H. Parving L. Tarnow P. Rossing C. G. Schalkwijk C. D. A. Stehouwer |
| author_facet | S. A. Peeters L. Engelen J. Buijs A. Jorsal H.-H. Parving L. Tarnow P. Rossing C. G. Schalkwijk C. D. A. Stehouwer |
| author_sort | S. A. Peeters |
| collection | DOAJ |
| description | Abstract Background Altered 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. Methods We 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. Results After 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. Conclusions Higher 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. |
| first_indexed | 2024-12-11T18:59:52Z |
| format | Article |
| id | doaj.art-5ba044e823f841c0bc711ec531ba2476 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-12-11T18:59:52Z |
| publishDate | 2017-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-5ba044e823f841c0bc711ec531ba24762022-12-22T00:54:03ZengBMCCardiovascular Diabetology1475-28402017-04-0116111210.1186/s12933-017-0539-1Plasma matrix metalloproteinases are associated with incident cardiovascular disease and all-cause mortality in patients with type 1 diabetes: a 12-year follow-up studyS. A. Peeters0L. Engelen1J. Buijs2A. Jorsal3H.-H. Parving4L. Tarnow5P. Rossing6C. G. Schalkwijk7C. D. A. Stehouwer8Department of Internal Medicine, Maastricht University Medical CentreDepartment of Internal Medicine, Maastricht University Medical CentreDepartment of Internal Medicine, Zuyderland hospitalDepartment of Cardiology, Aarhus University HospitalDepartment of Medical Endocrinology, RigshospitaletSteno Diabetes CenterSteno Diabetes CenterDepartment of Internal Medicine, Maastricht University Medical CentreDepartment of Internal Medicine, Maastricht University Medical CentreAbstract Background Altered 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. Methods We 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. Results After 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. Conclusions Higher 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.http://link.springer.com/article/10.1186/s12933-017-0539-1Type 1 diabetesCardiovascular diseaseAll-cause mortalityMatrix metalloproteinaseTissue inhibitor of metalloproteinaseEstimated glomerular filtration rate |
| spellingShingle | S. A. Peeters L. Engelen J. Buijs A. Jorsal H.-H. Parving L. Tarnow P. Rossing C. G. Schalkwijk C. D. A. Stehouwer 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 Type 1 diabetes Cardiovascular disease All-cause mortality Matrix metalloproteinase Tissue inhibitor of metalloproteinase Estimated glomerular filtration rate |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Type 1 diabetes Cardiovascular disease All-cause mortality Matrix metalloproteinase Tissue inhibitor of metalloproteinase Estimated glomerular filtration rate |
| url | http://link.springer.com/article/10.1186/s12933-017-0539-1 |
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