1,721,162 research outputs found
2013 ESC/EASD guidelines on the management of diabetes and cardiovascular disease: Established knowledge and evidence gaps.
No full textp66 Shc as the engine of vascular aging.
No full textThe present work is addressing the latest advances made in understanding the molecular mechanisms of vascular aging. Increased production of reactive oxygen species (ROS) is the common denominator of vascular aging, endothelial dysfunction and atherosclerosis. ROS are generated by different intracellular molecular pathways. In view of its role in determining the redox state of the cells and their responses to free radicals, mitochondrial p66Shc protein has been regarded as part of a putative transduction pathway relevant to endothelial integrity. Future efforts should translate our knowledge of the mechanisms of aging and its interaction with risk factors into the development of new therapeutic strategies to prevent age-associated cardiovascular disease
A 'once-and-done' approach to the lifelong reduction of elevated cholesterol
Full text linkndividuals with spontaneous loss-of-function PCSK9 mutations experience a significant reduction of both LDL-C levels (30–40%) as well as
CHD risk (88%), and appear free from adverse clinical consequences.2
Gene-editing technologies, which include the CRISPR–Cas nucleases
and CRISPR base editor, have the potential to permanently modify
disease-causing genes
The challenge of polypharmacy in cardiovascular medicine
No full textAlbeit great efforts in reducing the burden of cardiovascular diseases (CVD), their prevalence continues to grow worldwide. Among the causes for this rising burden, the upcoming pandemic of obesity and diabetes further enhances the estimates of CV mortality and healthcare costs over the next decades. Nevertheless, advances in CVD treatment has increased life-expectancy, and future perspectives announce a growing aging population, with increasing comorbid conditions predisposing to CVD. Despite the emphasis on primary prevention, CV risk factors are still poorly controlled and a further need for CV drugs is upcoming. In chronic CVD such as hypertension, ischemic heart disease (IHD) and heart failure, the progressive use of multiple drugs is common and is recommended by international guidelines. However, the chronic use of five or more medications, defined as polypharmacy, has shown to be neither always efficacious nor safe. Polypharmacy is associated with an increased morbidity and costs. The use of multiple medications often leads to inappropriate drug use, underprescription, low adherence and side effects. In order to overcome these issues, a fixed-dose combination pill ('polypill') for the prevention of CVD has been recently proposed. A hypothetical meta-analysis estimated for this strategy a reduction of IHD and stroke by 88 and 80% respectively in people aged 55 or over. Such polypill can be cost effective and increase patient adherence. However, large randomized trials are required to define its impact on clinical outcomes. This review will focus on challenges of polypharmacy in CV medicine, illustrating potential options to face this emerging crisis
Advanced glycation endproducts and plaque instability: A link beyond diabetes
Full text link[No abstract available
[Polytherapy in cardiovascular prevention: open issues].
No full textDespite the considerable advances in preventive treatment achieved over the last two decades, the increasing burden of cardiovascular disease represents an urgent need for new therapeutic strategies to reduce cardiovascular mortality and morbidity. The current pandemic of obesity, hypertension and diabetes, as a result of unhealthy lifestyle and dietary habits together with predisposing genetic backgrounds, is the main cause of increased cardiovascular mortality and raised overall health expenditure. Despite the growing number of cardiovascular prevention campaigns, the control of cardiovascular risk factors remains largely unsatisfactory worldwide. Unhealthy lifestyles lead to an increased consumption of drugs to achieve target levels of cardiovascular risk factors, namely blood pressure and low-density lipoprotein cholesterol. This phenomenon results in a disproportionate increase in the number of cardiovascular drugs, already in the early stages of disease. Despite current guidelines encourage combination therapies in cardiovascular prevention, the adoption of polytherapy, commonly defined as the use of 5 or more drugs, is extremely frequent and is often paradoxically unsuccessful due to poor patient education and adherence, increased adverse effects and inappropriate drug prescribing. Moreover, increased life-expectancy resulting from early treatment of myocardial infarction and improved heart failure management has led to an older population characterized by an increased prevalence of comorbid conditions. This is a further reason for increased prescription of drugs leading to an impairment of patient adherence and increased adverse effects. In order to overcome the emerging problem of polytherapy, the use of a single "polypill" containing a combination of drugs for cardiovascular prevention has been postulated. Such an approach is providing promising results in the management of hypertension and dyslipidemia. However, available evidence is still preliminary and prospective data on cardiovascular outcomes are still lacking. This present article proposes a critical analysis of some open issues related to polytherapy in cardiovascular prevention
[Metformin and left ventricular remodeling after acute myocardial infarction: molecular mechanisms and clinical implications]
No full textDespite clear advances in reperfusion therapy and pharmacological treatment, a large proportion of patients with an acute myocardial infarction will die of its consequences. In this regard, it is very important to understand the molecular processes underpinning ischemia-reperfusion injury and occurrence of left ventricular dysfunction, with the aim to develop mechanism-based therapeutic strategies. Experimental evidence indicates that metformin, a biguanide often used in the treatment of diabetes, has favorable effects on left ventricular function. This effect is largely mediated by activation of AMP-activated protein kinase (AMPK), a key molecule orchestrating many biochemical processes such as glucose uptake, glycolysis, oxidation of free fatty acids and mitochondrial biogenesis. These processes significantly contribute to raise ATP levels and restore myocardial contractile efficiency. AMPK also activates endothelial nitric oxide synthase and promotes autophagy, thus preventing inflammation and cellular death. These basic studies prompted many researchers to test the cardioprotective effects of metformin in the clinical setting. In diabetic patients with ST-elevation myocardial infarction (STEMI), retrospective analyses showed that metformin is associated with reduced infarct size as compared to non-metformin-based strategies, implicating beneficial effects beyond glucose control. A recent randomized trial, the GIPS-III study, has postulated that metformin may improve left ventricular function following STEMI even in patients without diabetes. Metformin (500 mg twice/day), administered 3h after percutaneous coronary intervention, did not result in improved left ventricular ejection fraction after 4-month follow-up. Based on these results, it remains unclear whether metformin exerts a cardioprotective effect regardless of glycemic control. Further randomized studies in diabetic and nondiabetic patients are required to address these important questions. The present review critically discusses established knowledge and evidence gaps on the effects of metformin on left ventricular function in diabetic and nondiabetic patients with myocardial infarction
Obesity-induced impairment of pluripotent stem cells: novel insights into vascular repair strategies
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