Matrix metalloproteinase-3 predicts clinical cardiovascular outcomes in patients with coronary artery disease: a 5 years cohort study

Guizani, Imen; Zidi, Wiem; Zayani, Y.; Boudiche, Sélim; Hadj-Taieb, Sameh; Sanhaji, Haïfa; Zaroui, Amira; Mechmèche, Rachid; Mourali, Mohamed Sami; Feki, Moncef; Allal-Elasmi, Monia

doi:10.1007/s11033-019-04914-4

Cited by 19 publications

(14 citation statements)

References 45 publications

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“…Non-MBDA-based CVD risk score refers to the first four scores in the first column. in model building, they were positively associated with CVD risk independently of the MBDA score and other variables, which is consistent with previous reports of their role in cardiovascular risk [53][54][55].…”

Section: Discussionsupporting

confidence: 91%

Derivation and internal validation of a multi-biomarker-based cardiovascular disease risk prediction score for rheumatoid arthritis patients

et al. 2020

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Background Rheumatoid arthritis (RA) patients have increased risk for cardiovascular disease (CVD). Accurate CVD risk prediction could improve care for RA patients. Our goal is to develop and validate a biomarker-based model for predicting CVD risk in RA patients. Methods Medicare claims data were linked to multi-biomarker disease activity (MBDA) test results to create an RA patient cohort with age ≥ 40 years that was split 2:1 for training and internal validation. Clinical and RA-related variables, MBDA score, and its 12 biomarkers were evaluated as predictors of a composite CVD outcome: myocardial infarction (MI), stroke, or fatal CVD within 3 years. Model building used Cox proportional hazard regression with backward elimination. The final MBDA-based CVD risk score was internally validated and compared to four clinical CVD risk prediction models. Results 30,751 RA patients (904 CVD events) were analyzed. Covariates in the final MBDA-based CVD risk score were age, diabetes, hypertension, tobacco use, history of CVD (excluding MI/stroke), MBDA score, leptin, MMP-3 and TNF-R1. In internal validation, the MBDA-based CVD risk score was a strong predictor of 3-year risk for a CVD event, with hazard ratio (95% CI) of 2.89 (2.46–3.41). The predicted 3-year CVD risk was low for 9.4% of patients, borderline for 10.2%, intermediate for 52.2%, and high for 28.2%. Model fit was good, with mean predicted versus observed 3-year CVD risks of 4.5% versus 4.4%. The MBDA-based CVD risk score significantly improved risk discrimination by the likelihood ratio test, compared to four clinical models. The risk score also improved prediction, reclassifying 42% of patients versus the simplest clinical model (age + sex), with a net reclassification index (NRI) (95% CI) of 0.19 (0.10–0.27); and 28% of patients versus the most comprehensive clinical model (age + sex + diabetes + hypertension + tobacco use + history of CVD + CRP), with an NRI of 0.07 (0.001–0.13). C-index was 0.715 versus 0.661 to 0.696 for the four clinical models. Conclusion A prognostic score has been developed to predict 3-year CVD risk for RA patients by using clinical data, three serum biomarkers and the MBDA score. In internal validation, it had good accuracy and outperformed clinical models with and without CRP. The MBDA-based CVD risk prediction score may improve RA patient care by offering a risk stratification tool that incorporates the effect of RA inflammation.

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Section: Discussionsupporting

confidence: 91%

Derivation and internal validation of a multi-biomarker-based cardiovascular disease risk prediction score for rheumatoid arthritis patients

et al. 2020

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“…Significantly elevated MMP-9 levels were measured in the sera of patients with coronary artery disease, and it may contribute to the pathogenesis of that illness [ 29 ]. MMPs could be used as valuable diagnostic biomarkers of stable coronary artery disease [ 29 , 30 ].…”

Section: Discussion Limitations and Strengthsmentioning

confidence: 99%

Vitamin D Deficiency Induces Elevated Oxidative and Biomechanical Damage in Coronary Arterioles in Male Rats

et al. 2020

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Background: Several reports prove interconnection between vitamin D (VD) deficiency and increased cardiovascular risk. Our aim was to investigate the effects of VD status on biomechanical and oxidative–nitrative (O–N) stress parameters of coronary arterioles in rats. Methods: 4-week-old male Wistar rats were divided into a control group (11 animals) with optimal VD supply (300 IU/kgbw/day) and a VD-deficient group (11 animals, <5 IU/kg/day). After 8 weeks, coronary arteriole segments were prepared. Geometrical, elastic, and biomechanical characteristics were measured by in vitro arteriography. O–N stress markers were investigated by immunohistochemistry. Results: Inner radius decreased; wall thickness and wall-thickness/lumen diameter ratio increased; tangential wall stress and elastic modulus were reduced in VD-deficient group. No difference could be found in wall-cross-sectional area, intima-media area %. While the elastic elements of the vessel wall decreased, the α-smooth muscle actin (α-SMA) immunostaining intensity showed no changes. Significant elevation was found in the lipid peroxidation marker of 4-hidroxy-2-nonenal (HNE), while other O–N stress markers staining intensity (poly(ADP)ribose, 3-nitrotyrosine) did not change. Conclusions: Inward eutrophic remodeling has developed. The potential background of these impairments may involve the initial change in oxidative damage markers (HNE). These mechanisms can contribute to the increased incidence of the cardiovascular diseases in VD deficiency.

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“…Most of these authors suggested that MMP‐9 is a functional biomarker in CAD. A similar Tunisian study found only MMP‐3 which could be used as a cardiovascular events predictor due to mostly for their endpoint study, the smaller population study (patients/controls), patient group subdivision and the difference of cities sampling 27 . MMP‐3 regulates vascular smooth muscle cell migration via MMP‐9 activation and the MMP‐3 expression and secretion may precede MMP‐9 expression and secretion 28 .…”

Section: Discussionmentioning

confidence: 99%

“…A similar Tunisian study found only MMP-3 which could be used as a cardiovascular events predictor due to mostly for their endpoint study, the smaller population study (patients/ controls), patient group subdivision and the difference of cities sampling. 27 MMP-3 regulates vascular smooth muscle cell migration via MMP-9 activation and the MMP-3 expression and secretion may precede MMP-9 expression and secretion. 28 As shown in previous studies, MMP-9 would be related to the stability of atherosclerotic plaques, so a higher level may indicate that plaques are vulnerable or have ruptured.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarker panels as predictors of severity in coronary artery disease

Braiek

Chahed

Dumont

et al. 2020

J Cellular Molecular Medi

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Matrix metalloproteinases (MMPs) are implicated in atherosclerotic plaque rupture and recondition. Specific tissue inhibitors (TIMPs) control MMP functions. Both MMPs and TIMPs are potential biomarkers of plaque instability. Elevated Apo‐CII and CIII and Apo‐E levels are recognized as cardiovascular disease risk factors. We aimed to establish the best blood biomarker panel to evaluate the coronary artery disease (CAD) severity. Plasma levels of MMP‐3 and MMP‐9, TIMP‐1 and TIMP‐2, Apo‐CII, Apo‐CIII and Apo‐E were measured in 472 patients with CAD evaluated by coronary angiography and electrocardiography, and in 285 healthy controls. MMP‐3 and MMP‐9 plasma levels in CAD patients were significantly increased ( P < 0.001) compared to controls (3.54‐ and 3.81‐fold, respectively). Furthermore, these increments are modulated by CAD severity as well as for Apo‐CII and Apo‐CIII levels ( P < 0.001). TIMPs levels were decreased in CAD versus controls ( P < 0.001) and in inverse correlation to MMPs. Standard ROC curve approach showed the importance of panels of biomarkers, including MMP‐3, MMP‐9, TIMP‐1, TIMP‐2, Apo‐CII and Apo‐CIII, for disease aggravation diagnosis. A high area under curve (AUC) value (0.995) was reached for the association of MMP‐9, TIMP‐2 and Apo‐CIII. The unbalance between MMPs and TIMPs in vascular wall and dyslipidaemia creates favourable conditions for plaque disruption. Our study suggests that the combination of MMP‐9, TIMP‐2 and Apo‐CIII values (‘CAD aggravation panel’) characterizes the severity of CAD, that is electrophysiological state, number of involved vessels, stent disposal and type of stent.

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Matrix metalloproteinase-3 predicts clinical cardiovascular outcomes in patients with coronary artery disease: a 5 years cohort study

Cited by 19 publications

References 45 publications

Derivation and internal validation of a multi-biomarker-based cardiovascular disease risk prediction score for rheumatoid arthritis patients

Derivation and internal validation of a multi-biomarker-based cardiovascular disease risk prediction score for rheumatoid arthritis patients

Vitamin D Deficiency Induces Elevated Oxidative and Biomechanical Damage in Coronary Arterioles in Male Rats

Identification of biomarker panels as predictors of severity in coronary artery disease

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