The sirtuins, silent mating-type information regulation 2 (SIRTs), are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases with important roles in regulating energy metabolism and senescence. Activation of SIRTs appears to have beneficial effects on lipid metabolism and antioxidants, prompting investigation of the roles of these proteins in atherogenesis. Although clinical data are currently limited, the availability and safety of SIRT activators such as metformin and resveratrol provide an excellent opportunity to conduct research to better understand the role of SIRTs in human atherosclerosis. Encouraging observations from preclinical studies necessitate rigorous large, prospective, randomized clinical trials to determine the roles of SIRT activators on the progression of atherosclerosis and ultimately on cardiac outcomes, such as myocardial infarction and mortality.

IntroductionCardiovascular disease (CVD) is common, indeed the majority of adults above sixty years of age will experience some manifestation of CVD. Based on data from 2012 and 2013, it has been estimated that CVD is responsible for 17.3 million deaths annually worldwide (1). Morbidity is also high, and in Europe, 200 billion Euros of healthcare expenditure is attributable to CVD (2). Risk factors for CVD can be categorized as modifiable and non-modifiable. Modifiable risk factors include obesity, hypertension, hyperlipidemia, diabetes mellitus, metabolic syndrome and lifestyle risk factors such as unhealthy diet, smoking and physical inactivity. Dietary factors are also important contributors to cardiovascular risk, either directly, or through their effects on other risk factors including hypertension, dyslipidemia and diabetes mellitus (3). Reduction of risk factors in the population, especially blood pressure reduction and lipid-lowering can have important impacts upon mortality from CVD (4).Protective effects against CVD have been demonstrated for several foods and dietary supplements (5) thus presenting new possibilities for population-level reduction of CVD risk. Evidence suggests that this approach is very promising. For example, in the PREDIMED observational study, participants in the highest quintile of polyphenol consumption had a relative risk of CVD of 54% compared to those in the lowest quintile (6). The aim of this review is to present an update on the most recent evidence relating to the use of nutraceuticals in the context of the prevention and treatment of CVD. Unfortunately, few studies have measured the associations between nutraceutical consumptions and "hard" outcomes such as mortality. Large randomized controlled trials are particularly rare, and thus there is a paucity of evidence in this area. Thus, our discussion will be largely focused on the effects of NutraceuticalsThe term "nutraceuticals" was introduced by Stephen DeFelice, founder and chairman of the Foundation for Innovation in Medicine, in 1989. A nutraceutical is defined as a "food, or parts of a food, that provide medical or health benefits, including the prevention and treatment of disease" (7). The definition encompasses medicinal products made from natural ingredients. Several classes of nutraceuticals have been proposed to have potential benefits in the treatment of CVD and the ones with the strongest evidence are briefly summarized below. Sterols/stanolsPlant sterols/stanols are phytosterols, and have been identified in a range of plant products including various fruits and vegetables, cereals, seeds and nuts. Their biological activity results from their molecular structural similarity to cholesterol (8). PolyphenolsPolyphenols are phytochemicals with widespread distribution in foods of plant origin. They are found in fruits, vegetables, cereal and legumes. Additionally, they are found in beverages produced from plant products such as tea, coffee, wine and cocoa. Polyphenols are structurally diverse, and over 8,000 have...

Atherosclerotic cardiovascular diseases (ASCVD) are a very important cause of premature death. The most important risk factor for ASCVD is lipid disorders. The incidence of lipid disorders and ASCVD is constantly increasing, which means that new methods of prevention and treatment of these diseases are still being searched for. In the management of patients with lipid disorders, the primary goal of therapy is to lower the serum LDL-C concentration. Despite the available effective lipid-lowering therapies, the risk of ASCVD is still increased in some patients. A high level of serum lipoprotein (a) (Lp(a)) is a risk factor for ASCVD independent of serum LDL-C concentration. About 20% of Europeans have elevated serum Lp(a) levels, requiring treatment to reduce serum Lp(a) concentrations in addition to LDL-C. Currently available lipid lowering drugs do not sufficiently reduce serum Lp(a) levels. Hence, drugs based on RNA technology, such as pelacarsen, olpasiran, SLN360 and LY3819469, are undergoing clinical trials. These drugs are very effective in lowering the serum Lp(a) concentration and have a satisfactory safety profile, which means that in the near future they will fill an important gap in the armamentarium of lipid-lowering drugs.

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