Ezetimibe, cardiovascular risk and atherogenic dyslipidaemia

Ezetimibe is a selective cholesterol absorption inhibitor with an excellent side-effect profile, able to reduce low-density lipoprotein (LDL) cholesterol by 15-25% from baseline in monotherapy and on top of statins and fibrates. Yet, it seems that ezetimibe produces quantitative rather than qualitative changes in LDL, with small net effects on atherogenic dyslipidaemia. This is supported by findings from the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) study on atherosclerosis progression, where the addition of ezetimibe to simvastatin in patients with heterozygous familial hypercholesterolaemia did not affect the mean change in carotid intima-media thickness, although a significant reduction in LDL cholesterol levels was observed. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study has further shown that combination treatment with simvastatin significantly reduced LDL cholesterol levels in patients with aortic stenosis, but did not affect the primary end point of aortic valve and cardiovascular events, although a significant reduction in the risk of ischaemic events was reported. Formal cardiovascular outcome trials are underway and these will provide additional insights into the long-term effects of ezetimibe on clinical events as well as on atherogenic dyslipidaemia, beyond LDL cholesterol levels

The Therapeutic Role of SGLT-2 Inhibitors in Acute Heart Failure: From Pathophysiologic Mechanisms to Clinical Evidence with Pooled Analysis of Relevant Studies across Safety and Efficacy Endpoints of Interest

(1) Background: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors constitute a novel drug class with remarkable cardiovascular benefits for patients with chronic heart failure (HF). Recently, this class has been utilized in acute HF as an additional treatment option to classic diuretics, which remain the cornerstone of treatment. (2) Methods: We attempted to identify those pathophysiologic mechanisms targeted by SGLT-2 inhibitors, which could be of benefit to patients with acute HF. We then conducted a comprehensive review of the literature within the PubMed database in order to identify relevant studies, both randomized controlled trials (RCTs) and observational studies, assessing the safety and efficacy of SGLT-2 inhibitors in acute HF. (3) Results: SGLT-2 inhibitors induce significant osmotic diuresis and natriuresis, decrease interstitial fluid volume and blood pressure, improve left ventricular (LV) function, ameliorate LV remodeling and prevent atrial arrhythmia occurrence, mechanisms that seem to be beneficial in acute HF. However, currently available studies, including six RCTs and two real-world studies, provide conflicting results concerning the true efficacy of SGLT-2 inhibitors, including "hard" surrogate endpoints. (4) Conclusions: Current evidence appears insufficient to substantiate the use of SGLT-2 inhibitors in acute HF. Further trials are required to shed more light on this issue

Metformin: Sex/Gender Differences in Its Uses and Effects-Narrative Review

Metformin (MTF) occupies a major and fundamental position in the therapeutic management of type 2 diabetes mellitus (T2DM). Gender differences in some effects and actions of MTF have been reported. Women are usually prescribed lower MTF doses compared to men and report more gastrointestinal side effects. The incidence of cardiovascular events in women on MTF has been found to be lower to that of men on MTF. Despite some promising results with MTF regarding pregnancy rates in women with PCOS, the management of gestational diabetes, cancer prevention or adjunctive cancer treatment and COVID-19, most robust meta-analyses have yet to confirm such beneficial effects

The effects of statins on blood pressure: current knowledge and future perspectives

Statin therapy has gained interest in the field of hypertension due to the potential role of different statin agents in blood pressure (BP) lowering [1-3]. The potential mechanisms involved include the downregulation of the angiotensin II-type 1 receptor, the decrease of vasoconstrictor endothelin-1 levels, and the increase in the endothelial production of nitric oxide (NO), an effect that is correlated with the upregulation of endothelial NO synthase expression [4-6]. Furthermore, we have recently reported the effects of statin treatment on endothelial function, oxidative stress and inflammation in patients with hypertension and normal cholesterol levels [7]. Yet, despite the beneficial effects shown by statins in hypertensive animal models as well as in small clinical studies, the results from meta-analyses and large clinical trials have been controversial. Indeed, the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA) [8] demonstrated that the combination of amlodipinebased therapy and atorvastatin was highly effective in preventing cardiovascula

Is subclinical cardiovascular disease linked with periodontal disease in diabetic and non-diabetic subjects?

: Periodontal disease leads to a systemic hyper-inflammatory state that might impair other co-morbidities including cardiovascular disease. Evidence-based findings showed that periodontitis may be linked with subclinical signs of cardiovascular diseases such as arterial stiffness. Nevertheless, some contrasting results have been reported over the years. A cross-sectional study regarding the relationship between periodontal disease and subclinical cardiovascular diseases, in non-diabetic and diabetic individuals, has been recently published. Therefore, the aim of this commentary is to give an in-depth on this topic

Effects of Dark Chocolate on Cardiovascular Risk

Cocoa is rich in polyphenols, a subgroup of dietary flavonoids, which seems to be able to reduce cardiovascular risk. Since dark chocolate is popular in Europe and the United States, and it is a potent source of polyphenols, there is increasing interest on its potential effects on cardiovascular risk. Evidence suggests that dark chocolate has some beneficial effects on cardiovascular risk factors, particularly on atherogenic dyslipidemia. Beneficial effects include the reduction of elevated blood pressure in hypertensive subjects, the increase in vasodilatation with improved endothelial function, as well as the inhibition of platelet activation and function. In addition, dark chocolate seems to reduce C-reactive protein concentrations and to modulate atherogenic dyslipidemia, reducing plasma total-cholesterol, LDL-cholesterol and triglyceride levels, with a concomitant increase in HDL-cholesterol concentrations. Yet, further studies are needed before recommending habitual dark chocolate consumption for the reduction of cardiovascular risk

The legacy effect in early-stage diabetes: Don't stay by me, cardiovascular disease!

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Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review

The approval of once daily liraglutide, 3.0 mg, and once weekly semaglutide, 2.4 mg, for chronic weight management provides a novel effective strategy against obesity. The reliable models that might predict weight reducing potential at the individual level have not been identified yet. However, the coexistence of diabetes has been consistently related with less effective response than in people without this comorbidity. We aimed to review the efficacy of GLP-1 RAs approved for weight management in individuals with and without diabetes and discuss some potential mechanisms for consistently observed differences in efficacy between these two populations. The mean weight loss difference between GLP-1 RAs and placebo as add-on to lifestyle intervention in patients with diabetes was 4% to 6.2% compared to 6.1 to 17.4% in people without diabetes. Semaglutide compared to liraglutide resulted in greater weight loss. Some hypothetical explanations for the weaker anti-obesity response for both GLP-1 RAs in people with diabetes include the background medications that promote weight gain, the fear of hypoglycaemia inherently related to the treatment of diabetes, a decrease in glycosuria and subsequently less weight loss in diabetics, an altered microbiota in patients with obesity and diabetes and a genetic background that predispose to weight gain in patients with diabetes. Moreover, people with diabetes may have had obesity for longer and may be less adherent to exercise, which seems to potentiate the effects of GLP-1 RA. Emerging multimodal approaches combining peptides targeting receptors at different levels might therefore be of additional benefit particularly in patients with diabetes