Matrix metalloproteinase-8 and tissue inhibitor of matrix metalloproteinase-1 predict incident cardiovascular disease events and all-cause mortality in a population-based cohort

TY - JOUR

T1 - Matrix metalloproteinase-8 and tissue inhibitor of matrix metalloproteinase-1 predict incident cardiovascular disease events and all-cause mortality in a population-based cohort

AU - Kormi, Immi

AU - Nieminen, Mikko T

AU - Havulinna, Aki S

AU - Zeller, Tanja

AU - Blankenberg, Stefan

AU - Tervahartiala, Taina

AU - Sorsa, Timo

AU - Salomaa, Veikko

AU - Pussinen, Pirkko J

PY - 2017/7

Y1 - 2017/7

N2 - Background Extracellular matrix degrading proteases and their regulators play an important role in atherogenesis and subsequent plaque rupture leading to acute cardiovascular manifestations. Design and methods In this prospective cohort study, we investigated the prognostic value of circulating matrix metalloproteinase-8, tissue inhibitor of matrix metalloproteinase-1 concentrations, the ratio of matrix metalloproteinase-8/ tissue inhibitor of matrix metalloproteinase-1 and, for comparison, myeloperoxidase and C-reactive protein concentrations for incident cardiovascular disease endpoints. The population-based FINRISK97 cohort comprised 7928 persons without cardiovascular disease at baseline. The baseline survey included a clinical examination and blood sampling. During a 13-year follow-up the endpoints were ascertained through national healthcare registers. The associations of measured biomarkers with the endpoints, including cardiovascular disease event, coronary artery disease, acute myocardial infarction, stroke and all-cause death, were analysed using Cox regression models. Discrimination and reclassification models were used to evaluate the clinical implications of the biomarkers. Results Serum tissue inhibitor of matrix metalloproteinase-1 and C-reactive protein concentrations were associated significantly with increased risk for all studied endpoints. Additionally, matrix metalloproteinase-8 concentration was associated with the risk for a coronary artery disease event, myocardial infarction and death, and myeloperoxidase concentration with the risk for cardiovascular disease events, stroke and death. The only significant association for the matrix metalloproteinase-8/ tissue inhibitor of matrix metalloproteinase-1 ratio was observed with the risk for myocardial infarction. Adding tissue inhibitor of matrix metalloproteinase-1 to the established risk profile improved risk discrimination of myocardial infarction ( p=0.039) and death (0.001). Both matrix metalloproteinase-8 (5.2%, p < 0.001) and tissue inhibitor of matrix metalloproteinase-1 (12.9%, p < 0.001) provided significant clinical net reclassification improvement for death. Conclusions Serum matrix metalloproteinase-8 and tissue inhibitor of matrix metalloproteinase-1 can be considered as biomarkers of incident cardiovascular disease events and death.

AB - Background Extracellular matrix degrading proteases and their regulators play an important role in atherogenesis and subsequent plaque rupture leading to acute cardiovascular manifestations. Design and methods In this prospective cohort study, we investigated the prognostic value of circulating matrix metalloproteinase-8, tissue inhibitor of matrix metalloproteinase-1 concentrations, the ratio of matrix metalloproteinase-8/ tissue inhibitor of matrix metalloproteinase-1 and, for comparison, myeloperoxidase and C-reactive protein concentrations for incident cardiovascular disease endpoints. The population-based FINRISK97 cohort comprised 7928 persons without cardiovascular disease at baseline. The baseline survey included a clinical examination and blood sampling. During a 13-year follow-up the endpoints were ascertained through national healthcare registers. The associations of measured biomarkers with the endpoints, including cardiovascular disease event, coronary artery disease, acute myocardial infarction, stroke and all-cause death, were analysed using Cox regression models. Discrimination and reclassification models were used to evaluate the clinical implications of the biomarkers. Results Serum tissue inhibitor of matrix metalloproteinase-1 and C-reactive protein concentrations were associated significantly with increased risk for all studied endpoints. Additionally, matrix metalloproteinase-8 concentration was associated with the risk for a coronary artery disease event, myocardial infarction and death, and myeloperoxidase concentration with the risk for cardiovascular disease events, stroke and death. The only significant association for the matrix metalloproteinase-8/ tissue inhibitor of matrix metalloproteinase-1 ratio was observed with the risk for myocardial infarction. Adding tissue inhibitor of matrix metalloproteinase-1 to the established risk profile improved risk discrimination of myocardial infarction ( p=0.039) and death (0.001). Both matrix metalloproteinase-8 (5.2%, p < 0.001) and tissue inhibitor of matrix metalloproteinase-1 (12.9%, p < 0.001) provided significant clinical net reclassification improvement for death. Conclusions Serum matrix metalloproteinase-8 and tissue inhibitor of matrix metalloproteinase-1 can be considered as biomarkers of incident cardiovascular disease events and death.

KW - Adult

KW - Aged

KW - Biomarkers/blood

KW - Cardiovascular Diseases/enzymology

KW - Cause of Death/trends

KW - Europe/epidemiology

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Incidence

KW - Luminescent Measurements

KW - Male

KW - Matrix Metalloproteinase 8/blood

KW - Middle Aged

KW - Population Surveillance/methods

KW - Predictive Value of Tests

KW - Prognosis

KW - Proportional Hazards Models

KW - Prospective Studies

KW - Risk Assessment

KW - Risk Factors

KW - Time Factors

KW - Tissue Inhibitor of Metalloproteinase-1/blood

U2 - 10.1177/2047487317706585

DO - 10.1177/2047487317706585

M3 - SCORING: Journal article

C2 - 28429955

VL - 24

SP - 1136

EP - 1144

JO - EUR J PREV CARDIOL

JF - EUR J PREV CARDIOL

SN - 2047-4873

IS - 11

ER -