Incretins-Based Therapies and Their Cardiovascular Effects: New Game-Changers for the Management of Patients with Diabetes and Cardiovascular Disease.

Atherosclerosis is the leading cause of death worldwide, especially in patients with type 2 diabetes mellitus (T2D). GLP-1 receptor agonists and DPP-4 inhibitors were demonstrated to play a markedly protective role for the cardiovascular system beyond their glycemic control. Several cardiovascular outcome trials (CVOT) reported the association between using these agents and a significant reduction in cardiovascular events in patients with T2D and a high cardiovascular risk profile. Moreover, recent evidence highlights a favorable benefit/risk profile in myocardial infarction and percutaneous coronary revascularization settings. These clinical effects result from their actions on multiple molecular mechanisms involving the immune system, platelets, and endothelial and vascular smooth muscle cells. This comprehensive review specifically concentrates on these cellular and molecular processes mediating the cardiovascular effects of incretins-like molecules, aiming to improve clinicians' knowledge and stimulate a more extensive use of these drugs in clinical practice as helpful cardiovascular preventive strategies.

Effects of Lipid Lowering Therapies on Vulnerable Plaque Features: An Updated Narrative Review of the Literature.

The clinical evidence on the efficacy of lipid lowering therapy in patients with coronary artery disease (CAD) is unequivocally established. However, the effects of these therapies on plaque composition and stability are less clear. The use of intracoronary imaging (ICI) technologies has emerged as a complement to conventional angiography to further characterize plaque morphology and detect high-risk plaque features related to cardiovascular events. Along with clinical outcomes studies, parallel imaging trials employing serial evaluations with intravascular ultrasound (IVUS) have shown that pharmacological treatment has the capacity to either slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved. Subsequently, the introduction of high-intensity lipid lowering therapy led to much lower levels of low-density lipoprotein cholesterol (LDL-C) levels than achieved in the past, resulting in greater clinical benefit. However, the degree of atheroma regression showed in concomitant imaging trials appeared more modest as compared to the magnitude of clinical benefit accrued from high-intensity statin therapy. Recently, new randomized trials have investigated the additional effects of achieving very low levels of LDL-C on high-risk plaque features-such as fibrous cap thickness and large lipid accumulation-beyond its size. This paper provides an overview of the currently available evidence of the effects of moderate to high-intensity lipid lowering therapy on high-risk plaque features as assessed by different ICI modalities, reviews data supporting the use of these trials, and analyse the future perspectives in this field.

A sudden right-to-left shunt: the importance of evaluating patent foramen ovale during exercise.

A 55-year-old male affected by heart failure with reduced ejection fraction and a history of a transient cerebrovascular accident was accepted to the Cardiology Department for worsening dyspnea. A cardiopulmonary exercise test was performed after therapy optimization to further evaluate exercise intolerance. A rapid increase in the minute ventilation/carbon dioxide production slope, end-tidal oxygen pressure, and respiratory exchange ratio, with a concomitant decrease in end-tidal carbon dioxide pressure and oxygen saturation, were observed during the test. These findings indicate exercise-induced pulmonary hypertension leading to a right-to-left shunt. Subsequent echocardiography with a bubble test unveiled the presence of an unknown patent foramen ovale. It is, therefore, necessary to exclude a right-to-left shunt by cardiopulmonary exercise testing, particularly in patients predisposed to develop pulmonary hypertension during exercise. Indeed, this eventuality might potentially provoke severe cardiovascular embolisms. However, the patent foramen ovale closure in patients with heart failure with reduced ejection fraction is still debated because of its potential hemodynamic worsening.

Impact of baseline kidney function on the effects of sodium-glucose co-transporter-2 inhibitors on kidney and heart failure outcomes: A systematic review and meta-analysis of randomized controlled trials.

AIM: To determine whether the magnitude of the cardiorenal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2is) varies with baseline kidney function. METHODS: We searched randomized, placebo-controlled trials testing the effects of SGLT2is on renal and cardiovascular outcomes. Efficacy outcomes, stratified by baseline estimated glomerular filtration rate (eGFR) categories, included renal disease progression, a composite heart failure (HF) outcome and mortality. RESULTS: Thirteen trials testing SGLT2is in 90 402 participants with available eGFR data were included. The risk of bias was judged as low for all trials. SGLT2is reduced the relative risks of renal disease progression by 27% to 57% and of HF outcomes by 13% to 32% across different eGFR categories, with an overall low heterogeneity. Meta-regression analyses showed a significant direct relationship between baseline eGFR and the magnitude of SGLT2is' renal protection (P = .003). The greatest risk reduction was in participants with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.43, 95% CI: 0.32-0.58) and the smallest was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.73, 95% CI: 0.62-0.86, P < .001). Conversely, for HF, the greatest risk reduction was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.68, 95% CI: 0.48-0.96) and the smallest was in those with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.87, 95% CI: 0.56-1.34). CONCLUSIONS: SGLT2is reduce the risk of renal and HF outcomes for all eGFR categories. The greatest benefits in terms of kidney protection may be achieved by early initiation of SGLT2is in people with preserved eGFR. The greatest risk reduction for HF outcomes is observed in people with lower eGFR values.

[From regression to stabilization: new insights into the evolution of coronary atherosclerotic plaque]. / Dalla regressione alla stabilizzazione: l'evoluzione della placca aterosclerotica coronarica secondo le nuove evidenze.

Coronary artery atherosclerosis is a constantly evolving disease. Over the years, new drug therapies have been shown to reduce adverse cardiovascular events and improve the survival of patients with coronary artery disease. New intracoronary imaging modalities, including intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy, have been introduced to detect the anatomic changes which follow an effective lipid-lowering therapy in human coronary plaques. Particularly, the use of optical coherence tomography made it possible to evaluate plaque composition and showed how an intensive lipid-lowering therapy can stabilize atherosclerosis by improving vulnerable plaque features. Future non-invasive applications are required for large-scale use of these findings.