Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy

2018 ◽  
Vol 25 (7) ◽  
pp. 719-727 ◽  
Author(s):  
Signe H Nielsen ◽  
Naja D Mygind ◽  
Marie M Michelsen ◽  
Daria F Bechsgaard ◽  
Hannah E Suhrs ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Angina Pectoris ◽  
Myocardial Fibrosis ◽  
Volume Fraction ◽  
Extracellular Volume ◽  
Diffuse Myocardial Fibrosis ◽  
Collagen Turnover ◽  
Collagen Formation ◽  
Artery Disease

Aim Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patients with diffuse myocardial fibrosis from asymptomatic controls. Methods and results Seventy-one women with angina pectoris without significant coronary artery disease assessed by invasive coronary angiogram were included. Competitive enzyme-linked immunosorbent assays (ELISAs) measuring circulating protein fragments in serum assessed the formation and degradation of collagen type III (Pro-C3, C3M and C3C), IV (P4NP7S and C4M), V (Pro-C5 and C5M) and VI (Pro-C6 and C6M), and degradation of collagen type I (C1M). Serum samples from 32 age-matched asymptomatic women were included as controls. Symptomatic women presented significantly elevated levels of Pro-C6, C3C, C3M, C4M and C8-C ( p < 0.0001–0.0058) and significantly decreased levels of Pro-C3, C5M and C6M ( p < 0.0001–0.041), reflecting accelerated collagen turnover and an imbalanced collagen formation and degradation compared to controls. Cardiac magnetic resonance T1 mapping was performed to determine extracellular volume fraction and thus diffuse myocardial fibrosis. A significant association was identified between C5M and extracellular volume fraction by cardiac magnetic resonance ( p = 0.01). Conclusion Women with angina pectoris, but without significant obstructive coronary artery disease, showed an imbalanced collagen turnover compared to asymptomatic controls. The examined biomarkers are tools to monitor active collagen remodelling in patients with angina pectoris, in risk of developing myocardial fibrosis.

scholarly journals Proteoglycan remodeling is accelerated in women with angina pectoris and diffuse myocardial fibrosis: the iPOWER Study

2020 ◽  
Author(s):  
Naja Dam Mygind ◽  
Signe Holm Nielsen ◽  
Marie Mide Michelsen ◽  
Adam Pena ◽  
Daria Frestad Bechsgaard ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Extracellular Matrix ◽  
Cardiac Magnetic Resonance ◽  
Coronary Artery ◽  
Myocardial Fibrosis ◽  
T1 Mapping ◽  
Obstructive Coronary Artery Disease ◽  
Extracellular Volume ◽  
Diffuse Myocardial Fibrosis ◽  
Artery Disease

Abstract Background Women with angina and no obstructive coronary artery disease have an unfavourable prognosis, possibly due to coronary microvascular disease and diffuse myocardial fibrosis. In diffuse myocardial fibrosis myocardial extracellular matrix proteins, including the proteoglycans biglycan and versican are actively remodeled by matrix metalloproteinase. We investigated MMP-mediated degradation of biglycan and versican in women with possible DMF assessed by cardiac magnetic resonance T1 mapping. Methods Seventy-one women with angina pectoris and a coronary angiogram with no significant obstructive coronary artery disease (< 50% stenosis) were included. Asymptomatic age-matched women served as controls (n = 32). Matrix metalloproteinase 12 generated neo-epitope fragment of versican (VCANM) and MMP-9 generated fragment of biglycan (BGM) were measured in serum by specific competitive enzyme-linked immunosorbent assays (ELISAs). T1 mapping was performed by cardiac magnetic resonance with gadolinium (0.1 mmol/kg) using a look-locker pulse sequencing measuring T1 and extracellular volume. Results Both BGM and VCANM levels were higher in symptomatic women compared with controls; 31.4 ng/mL vs. 16.4 ng/mL (p < 0.001) and 2.1 ng/mL vs. 1.8 ng/mL (p < 0.001), respectively. Both BGM and VCANM were moderately correlated to global extracellular volume (r2 = 0.38, p < 0.001 and r2 = 0.26, p = 0.015 respectively). Conclusion Turnover of BGM and VCANM was increased in symptomatic women compared to asymptomatic women and associated to extracellular volume, supporting a link between angina with no obstructive coronary artery disease and fibrotic cardiac remodeling. The examined biomarkers may prove to be suitable for monitoring active extracellular matrix remodeling.

Biomarkers of Myocardial Fibrosis are Associated with Diabetes but not with Coronary Microvascular Dysfunction in Women with Angina and No Obstructive Coronary Artery Disease

2020 ◽  
Author(s):  
Kira Bang Bove ◽  
Naja Dam Mygind ◽  
Signe Holm Nielsen ◽  
Marie Mide Michelsen ◽  
Daria Frestad Bechsgaard ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Angina Pectoris ◽  
Myocardial Fibrosis ◽  
Obstructive Coronary Artery Disease ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Transthoracic Doppler Echocardiography ◽  
Type Iv ◽  
Artery Disease

Abstract Background Coronary microvascular dysfunction (CMD) is highly prevalent in women with no obstructive coronary artery disease and possibly related to myocardial fibrosis caused by excessive extracellular matrix (ECM) remodeling. ECM turnover can be measured in blood indicating fibrotic activity. We hypothesized that women with DM, angina and no obstructive coronary artery disease have increased ECM turnover and that this is associated with CMD.Methods We included 344 women with angina pectoris and no obstructive coronary artery disease (187 with DM, predominantly type II) and 76 asymptomatic women without DM as controls. Biomarkers reflecting formation of type IV and VI collagen (PRO-C4 and PRO-C6) and degradation of type IV, V and VI collagen (C4M, C5M, C6M), mimecan (MIM) and titin (TIM) were measured in all participants. CMD was defined as coronary flow velocity reserve (CFVR) <2.0 assessed by transthoracic Doppler echocardiography.Results Median age was 64.2 (IQR 57.0-70.0), slightly higher in symptomatic women with DM. Median CFVR was 2.21 (1.89-2.55) in symptomatic women with DM, 2.35 (1.96-2.77) in symptomatic women without DM and 2.63 (2.19-2.95) in controls (age-adjusted p for trend<0.001). With exception of CM5, women with DM had significantly higher levels of all ECM biomarkers than women without DM (age-adjusted p<0.01), whereas biomarkers did not differ between symptomatic women without DM and controls. High ECM biomarker levels were associated with HbA1c, high BMI, low HDL and high triglycerides (p=0.003-0.0001). There was no correlation between ECM biomarkers and CFVR.Conclusion Women with angina pectoris and DM had increased levels of myocardial fibrosis biomarkers compared with women without DM. There was no association between CMD and biomarkers of myocardial fibrosis.

Abdominal Aortic Intima-Media Thickness Predicts Coronary Artery Disease Severity in Patients With Stable Angina Pectoris: A Prospective Study

Angiology ◽  
2021 ◽  
pp. 000331972199885
Author(s):  
Omer Faruk Cirakoglu ◽  
Ayşe Gül Karadeniz ◽  
Ali Riza Akyüz ◽  
Cihan Aydın ◽  
Sinan Şahin ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Angina Pectoris ◽  
Predictive Value ◽  
Intima Media Thickness ◽  
Stable Angina Pectoris ◽  
Coronary Artery Disease Severity ◽  
Abdominal Aortic ◽  
Artery Disease ◽  
Aortic Intima

Accurately identifying coronary artery disease (CAD) is the key element in guiding the work-up of patients with suspected angina. Thickening of the arterial wall is a hallmark of atherosclerosis. Therefore, the main purpose of this study was to determine whether abdominal aortic intima-media thickness (AAIMT), which is the earliest zone of atherosclerotic manifestations, has a predictive value in CAD severity. A total of 255 consecutive patients who were referred for invasive coronary angiography due to suspected stable angina pectoris were prospectively included in the study. B-mode ultrasonography was used to determine AAIMT before coronary angiography. Coronary artery disease severity was assessed with the SYNTAX score (SS). A history of hypertension, age, dyslipidemia, and higher AAIMT (odds ratio: 2.570; 95%CI 1.831-3.608; P < .001) were independent predictors of intermediate or high SS. An AAIMT <1.3 mm had a negative predictive value of 98% for the presence of intermediate or high SS and 83% for obstructive CAD. In conclusion, AAIMT showed a significant and independent predictive value for intermediate or high SS. Therefore, AAIMT may be a noninvasive and useful tool for decision-making by cardiologists (eg, to use a more invasive approach).

scholarly journals The link between left ventricular extracellular volume determined by T1 myocardial mapping and gut microbiota composition in individuals with heart failure and preserved ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.N Kaburova ◽  
O.M Drapkina ◽  
S.M Uydin ◽  
M.V Vishnyakova ◽  
M.S Pokrovskaya ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Gut Microbiota ◽  
Myocardial Fibrosis ◽  
Volume Fraction ◽  
Extracellular Volume ◽  
Left Ventricular ◽  
Diffuse Myocardial Fibrosis ◽  
Rrna Gene ◽  
Preserved Ejection Fraction

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) represents a major challenge in modern cardiology. As described previously, in HFpEF comorbidities promote a systemic inflammatory state, leading to diffuse myocardial fibrosis resulting in myocardial stiffening. Gut dysbiosis which is considered as the novel source of chronic systemic inflammation has been actively investigated as the risk factor for the development and aggravation of cardiovascular diseases including heart failure. Cardiac magnetic resonance T1-mapping is a novel tool, which allows noninvasive quantification of the extracellular space and diffuse myocardial fibrosis. Moreover, the extracellular volume (ECV) fraction can be calculated, providing information on the relative expansion of the extracellular matrix, thus being a noninvasive alternative to myocardial biopsy studies. Purpose The research was aimed at investigating the correlation between the left ventricular ECV and gut microbial genera in patients with HFpEF. Methods 42 patients with confirmed HF-pEF (mediana and interquartile range of age 67 [64; 72] years, 47% men, body mass index &lt;35 kg/m2 with no history of myocardial infarction or diabetes mellitus) were enrolled in the study. The patients underwent transthoracic echocardiography with Doppler study, HF-pEF was confirmed according to the recent ESC guidelines (based on E/e' ratio, N-terminal pro-B type natriuretic peptide &gt;125 pg/ml and symptoms of heart failure). The intestinal microbiome was investigated using high-throughput sequencing of bacterial 16S rRNA gene. As the last step of research T1-myocardial mapping with the modified look-locker inversion-recovery protocol (MOLLI) sequence at 1.5 Tesla was performed to assess left ventricular extracellular volume fraction. Results The mean±std in ECV was 31.02±4.4%. The relative abundance (%) of the most prevalent phyla in gut microbiota was 48±22.5 for Firmicutes, 47.4±22.8 for Bacteroidetes and 1.5 [1.5; 2.5] for Proteobacteria. The analysis showed significant negative correlations between ECV and the following bacterial genera: Faecalibacterium (r=−0.35), Blautia (r=−0.43), Lachnoclostridium (r=−0.32). Moreover ECV positively correlated with Holdemania (r=0.4), Victivallis (r=0.38), Dehalobacterium (r=0.38), Enterococcus (r=0.33) and Catabacter (r=0.32). All correlation values with p&lt;0.05. Conclusion We discovered both negative and positive significant correlations between ECV – the non-invasive marker of myocardial fibrosis and several bacterial genera, which may have negative impact on myocardial remodeling in HF-pEF. Funding Acknowledgement Type of funding source: None

scholarly journals Myocardial Fibrosis as a Predictor of Sudden Death in Patients With Coronary Artery Disease

2021 ◽  
Vol 77 (1) ◽  
pp. 29-41
Author(s):  
Abbasin Zegard ◽  
Osita Okafor ◽  
Joseph de Bono ◽  
Manish Kalla ◽  
Mauro Lencioni ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Sudden Death ◽  
Myocardial Fibrosis ◽  
Artery Disease
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