ABSTRACT
The global prevalence of diabetes mellitus (DM) has led to a pandemic, with significant microvascular and macrovascular complications including coronary artery disease (CAD), which worsen clinical outcomes and cardiovascular prognosis. Patients with both acute coronary syndrome (ACS) and DM have worse prognosis and several pathophysiologic mechanisms have been implicated including, insulin resistance, hyperglycemia, endothelial dysfunction, platelet activation and aggregations as well as plaque characteristics and extent of coronary lesions. Therefore, regarding reperfusion strategies in the more complex anatomies coronary artery bypass surgery may be the preferred therapeutic strategy over percutaneous coronary intervention while both hyperglycemia and hypoglycemia should be avoided with closed monitoring of glycemic status during the acute phase of myocardial infraction. However, the best treatment strategy remains undefined. Non-insulin therapies, due to the low risk of hypoglycemia concurrently with the multifactorial CV protective effects, may be proved to be the best treatment option in the future. Nevertheless, evidence for the beneficial effects of glucagon like peptide-1 receptor agonists, dipeptidyl-peptidase 4 inhibitors and sodium glycose cotransporter 2 inhibitors, despite accumulating, is not robust and future randomized control trials may provide more definitive data.
ABSTRACT
BACKGROUND: Cardiotoxicity restricts anthracycline and trastuzumab treatment of Human Epidermal Growth Factor Receptor 2 positive early breast cancer. Endothelial dysfunction and arteriosclerosis are significant cardiovascular risk factors. OBJECTIVES: We studied the effect of anthracycline-based chemotherapy, with or without trastuzumab, on endothelium and arteriosclerosis in patients with breast cancer. METHODS: In this case-control study, 52 women with breast cancer and 104 women without breast cancer were examined longitudinally up to 15 months following (in the breast cancer group) initiation of chemotherapy. Arterial stiffness was evaluated through pulse wave velocity (PWV), while endothelial function via flow-mediated dilatation (FMD) at baseline (T0), 3 (T1), 6 (T2), and 15 (T3) months later. RESULTS: There was no difference between subjects with breast cancer and control in PWV and FMD at baseline. Longitudinally, participants with breast cancer exhibited considerable impairment of PWV and FMD compared to the control group (p for interaction <0.001 for both parameters). In breast cancer patients, there was a significant increase from T0 to T3 in PWV (7.43 ± 1.68 m/s vs. 8.18 ± 2.00 m/s, p = 0.01) and decrease in FMD (6.95 ± 2.86% vs. 5.03 ± 2.83%, p = 0.006). The addition of trastuzumab in the treatment did not have any effect on PWV (p = 0.74) or FMD (p = 0.91). CONCLUSIONS: In patients with breast cancer, there is progression of endothelial dysfunction and arteriosclerosis up to 15 months following initiation of anthracycline-based chemotherapy. Trastuzumab has no additive effect on endothelial function or arterial stiffness.
