Aortic wall stiffness as a side-effect of anti-cancer medication

Solomou, E; Aznaouridis, Konstantinos; Masoura, Constantina; Cutajar, Iosif; Toutouzas, Konstantinos; Vlachopoulos, Charalambos; Tousoulis, Dimitris

doi:10.1080/14779072.2019.1691528

Cited by 15 publications

(13 citation statements)

References 54 publications

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“…It is also important to acknowledge the potential in uence of a systemic reparative response after ACC treatment on the levels of serum PICP, with activation of brotic processes in organs other than the heart. In this regard, it has been shown that anti-cancer therapies may cause arterial stiffness, with increased collagen production suggested as a potential mechanism, among others, underlying this vascular alteration [34,35]. Since arterial stiffness contributes to LVD, we cannot discard that the association found between PICP with LVD in ACC-treated patients is re ecting the combined interaction of cardiac and vascular brosis.…”

Section: Discussionmentioning

confidence: 89%

Increased Serum Procollagen Type I C-terminal Propeptide Levels are Associated with Subclinical Left Ventricular Dysfunction in Patients with Breast Cancer Treated with Anthracycline-Based Cancer Chemotherapy

Adl

Santisteban

Lupón

et al. 2020

Preprint

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Background Anthracycline-based cancer chemotherapy (ACC) has been related to myocardial interstitial fibrosis (MIF), a lesion contributing to left ventricular dysfunction (LVD). We investigated whether biomarker-assessed MIF was associated with LVD in patients with breast cancer receiving ACC and in patients with ACC-induced heart failure (ACC-HF). Moreover, chemotherapy agent’s pro-fibrotic activity was evaluated in human cardiac fibroblasts (HCFs). Methods Echocardiography, serum biomarkers of collagen deposition (procollagen type-I C-terminal-propeptide [PICP]) and crosslinking (collagen type-I C-terminal-telopeptide/matrix metalloproteinase-1 ratio), and biomarkers of myocardial and vascular stress (galectin-3, sST2, amino-terminal pro-brain natriuretic peptide [NT-proBNP], hs-troponin-T and vascular cell adhesion molecule-1 [VCAM-1]) were assessed in 70 breast cancer patients at baseline, and during ACC at 3 and 6 months. Subclinical cardiotoxicity was defined as global longitudinal strain (GLS) relative reduction>15%. In addition, PICP and NT-proBNP were determined in 347 patients with different HF etiologies, 37 with ACC-HF (of whom 65% had been diagnosed with breast cancer) and 12-month-follow-up LVEF assessment. HCFs activation was examined after incubation with doxorubicin, cyclophosphamide, paclitaxel and trastuzumab for 24 hours. Results In patients with breast cancer, six-months-ACC reduced GLS and upregulated PICP, hs-troponin-T, NT-proBNP and VCAM-1 (P<0.01) versus baseline. At 6 months, elevation of PICP was higher in patients with subclinical cardiotoxicity versus the remaining patients (P for interaction<0.001). PICP levels were directly and independently associated with a relative reduction in GLS (P<0.001). In ACC-HF patients, baseline LVEF was inversely associated with PICP and NT-proBNP (P<0.01). After 12 months, LVEF did not change in patients with higher basal PICP (3rd tertile) but improved in the remaining patients (P<0.001). Doxorubicin, cyclophosphamide and trastuzumab stimulated collagen synthesis in HCFs. Conclusion These results indicate that biomarker-assessed MIF associates with early LVD in ACC-treated patients with breast cancer. In addition, these findings suggest that MIF may be associated with established LVD in ACC-HF patients, hindering LV functional improvement after 12 months. Finally, chemotherapy can directly activate collagen metabolism in HCFs.

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Section: Discussionmentioning

confidence: 89%

Increased Serum Procollagen Type I C-terminal Propeptide Levels are Associated with Subclinical Left Ventricular Dysfunction in Patients with Breast Cancer Treated with Anthracycline-Based Cancer Chemotherapy

Adl

Santisteban

Lupón

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In this regard, it has been shown that anti-cancer therapies may cause arterial stiffness, with increased collagen production suggested as a potential mechanism, among others, underlying this vascular alteration. 41,42 Since arterial stiffness contributes to LVD, we cannot discard that the association found between PICP with LVD in ACC-treated patients is re ecting the combined interaction of cardiac and vascular brosis.…”

Section: Discussionmentioning

confidence: 98%

Increased Serum Procollagen type I C-terminal Propeptide Levels are Associated with Left Ventricular Dysfunction in Patients Treated with Anthracycline-based Cancer Chemotherapy

Fuente

Santisteban

Lupón

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Anthracycline-based cancer chemotherapy (ACC) has been related to myocardial interstitial fibrosis (MIF), a lesion contributing to left ventricular dysfunction (LVD). We investigated whether biomarker-assessed MIF was associated with LVD in patients with breast cancer receiving ACC and in patients with ACC-induced heart failure (ACC-HF). Moreover, chemotherapy agent’s pro-fibrotic activity was evaluated in human cardiac fibroblasts (HCFs). Methods Echocardiography, serum biomarkers of collagen deposition (procollagen type-I C-terminal-propeptide [PICP]) and crosslinking (collagen type-I C-terminal-telopeptide/matrix metalloproteinase-1 ratio), and biomarkers of myocardial and vascular stress (galectin-3, sST2, amino-terminal pro-brain natriuretic peptide [NT-proBNP], hs-troponin-T and vascular cell adhesion molecule-1 [VCAM-1]) were assessed in 70 breast cancer patients at baseline, and during ACC at 3 and 6 months. Subclinical cardiotoxicity was defined as a global longitudinal strain (GLS) relative reduction>15%. In addition, PICP and NT-proBNP were determined in 347 patients with different HF etiologies, 37 with ACC-HF of whom 33 had 12-month-follow-up LVEF assessment. HCF activation was examined after incubation with chemotherapy agents for 24 hours. Results In breast cancer patients, six-months-ACC reduced GLS and upregulated PICP, hs-troponin-T, NT-proBNP and VCAM-1 (P<0.01) versus baseline. At 6 months, elevation of PICP was higher in patients with subclinical cardiotoxicity versus the remaining patients (P for interaction<0.001). PICP levels were directly associated with a relative reduction in GLS (P<0.001). In ACC-HF patients, baseline LVEF was inversely associated with PICP and NT-proBNP (P<0.01). After 12 months, LVEF did not change in patients with higher basal PICP (3rd tertile) but improved in the remaining patients (P<0.001). Doxorubicin, cyclophosphamide and trastuzumab stimulated collagen synthesis in HCFs, including PICP extracellular cleavage. Conclusion These results indicate that increased levels of PICP, a biomarker related to MIF, are associated with early LVD in ACC-treated patients with breast cancer and with established LVD in ACC-HF patients, hindering LV functional improvement after 12 months. Chemotherapy can directly activate collagen metabolism and increase PICP extracellular presence in HCFs. Therefore, PICP emerges as a promising biomarker of ACC-induced cardiotoxicity.

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“…Vascular damage results in an increase in the level of arterial stiffness defined as a decrease in the elastic property of the wall structure of the arteries. Arterial stiffness is a vascular biomarker describing the alterations of arterial properties which result in a reduction of the arterial wall elasticity, and therefore in a decrease of the buffering capacity of arteries to pulsatile cardiac ejection (3). Cancer patients and survivors have increased arterial stiffness more than the levels expected with aging (4,5).…”

Section: Introductionmentioning

confidence: 99%

“…Anthracyclines cause overexpression of inflammatory cytokines in endothelial cells and reduce production of endothelin and nitric oxide (NO) resulting in endothelial cells being more susceptible to apoptosis and the functional integrity of endothelium being compromised (7). All these mechanisms lead to a loss of the ability of endothelial cells to regulate the vascular smooth muscle tone and therefore arterial stiffness increases (3).…”

Section: Introductionmentioning

confidence: 99%

Çocukluk Çağı Kanser Sağ Kalanlarında Antrasiklin İlişkili Arteriyel Sertliğin Değerlendirilmesi

Köşger¹,

Caliskan²,

Özdemir³

et al. 2021

Osmangazi̇ Journal of Medicine

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Childhood cancer survivors have a significantly increased risk of cardiovascular morbidity and mortality. Improved screening methods are needed for early detection of cardiotoxicity. The aim of the study is to evaluate arterial stiffness as an indicator of vascular damage by oscillometric pulse wave analysis in childhood cancer survivors. A total of 38 patients and 25 age and gender matched healthy volunteers were included in this cross-sectional single centre study. All participants, underwent evaluation of arterial stiffness through non-invasive measurement of hemodynamic parameters such as pulse wave velocity (PWV) and central systolic blood pressure (c-SBP) with the Mobil-O-Graph® pulse wave analysis device. Left ventricular ejection fraction (LVEF) and left ventricular mass index (LVMI) were obtained by M-mode echocardiography. The median age of the childhood cancer survivors was 12.5 (4.25-18) and the median duration time after end of chemotherapy was 36 (12-116) months. Both groups were statistically similar in age, body mass index, LVEF and LVMI. Childhood cancer survivors had significantly lower peripheral systolic blood pressure compared to controls. Average c-SBP and PWV were similar between groups. Childhood cancer survivors > 15 years old also had similar PWV value with those < 15 years old. There were no signs of arterial stiffness in childhood cancer survivors late after chemotherapy according to the ambulatory oscillometric PWA. Longer follow-up duration may be required to determination of subclinical vascular damage

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Aortic wall stiffness as a side-effect of anti-cancer medication

Cited by 15 publications

References 54 publications

Increased Serum Procollagen Type I C-terminal Propeptide Levels are Associated with Subclinical Left Ventricular Dysfunction in Patients with Breast Cancer Treated with Anthracycline-Based Cancer Chemotherapy

Increased Serum Procollagen Type I C-terminal Propeptide Levels are Associated with Subclinical Left Ventricular Dysfunction in Patients with Breast Cancer Treated with Anthracycline-Based Cancer Chemotherapy

Increased Serum Procollagen type I C-terminal Propeptide Levels are Associated with Left Ventricular Dysfunction in Patients Treated with Anthracycline-based Cancer Chemotherapy

Çocukluk Çağı Kanser Sağ Kalanlarında Antrasiklin İlişkili Arteriyel Sertliğin Değerlendirilmesi

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