Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels.

Lipoprotein(a) [Lp(a)] is made up of a low-density lipoprotein (LDL) particle and a specific apolipoprotein(a). The blood concentration of Lp(a) is approximately 90% genetically determined, and the main genetic factor determining Lp(a) levels is the size of the apo(a) isoform, which is determined by the number of KIV2 domain repeats. The size of the apo(a) isoform is inversely proportional to the blood concentration of Lp(a). Lp(a) is a strong and independent cardiovascular risk factor. Elevated Lp(a) levels ≥ 50 mg/dl (≥ 125 nmol/l) are estimated to occur in more than 1.5 billion people worldwide. However, determination of Lp(a) levels is performed far too rarely, including Poland, where, in fact, it is only since the 2021 guidelines of the Polish Lipid Association (PoLA) and five other scientific societies that Lp(a) measurements have begun to be performed. Determination of Lp(a) concentrations is not easy due to, among other things, the different sizes of the apo(a) isoforms; however, the currently available certified tests make it possible to distinguish between people with low and high cardiovascular risk with a high degree of precision. In 2022, the first guidelines for the management of patients with elevated lipoprotein(a) levels were published by the European Atherosclerosis Society (EAS) and the American Heart Association (AHA). The first Polish guidelines are the result of the work of experts from the two scientific societies and their aim is to provide clear, practical recommendations for the determination and management of elevated Lp(a) levels.

Health-Promoting Properties of Anthocyanins from Cornelian Cherry (Cornus mas L.) Fruits.

The cornelian cherry is a plant that annually provides fruits, drupe-type, ranging in color from yellow through pink, red, carmine, and almost black. Cornelian cherry bears abundant fruit in temperate climate conditions, which means that its dark-colored fruits can be treated as an excellent source of anthocyanins. After consuming, anthocyanins have a protective function in the human body. Raw fruit extracts and their pure isolates, rich in anthocyanins, have a wide spectrum of health-promoting properties. This review focuses on the health-promoting properties of anthocyanins from fruits of cornelian cherry, documented in research conducted in vitro, in vivo, and in humans. The results obtained so far confirm the beneficial effects of anthocyanins on the blood parameters, whose values are important in predicting and assessing the risk and progression of cardiovascular and metabolic diseases. A beneficial effect on molecular and histopathological changes in target organs such as the heart, brain, kidneys, and liver has also been demonstrated. Anthocyanins from cornelian cherry have a strong antioxidant effect, which explains their protective effects on organs and anticancer effects. Moreover, they have antiglycemic, antihyperlipidemic, anti-inflammatory, and antimicrobial properties. The work highlights the perspectives and directions of necessary research.

Effect of Inhibiting Butyrylcholinesterase Activity Using Fractionated Coffee Extracts Digested In Vitro in Gastrointestinal Tract: Docking Simulation and Calorimetric and Studies.

Butyrylcholinesterase (BChE) is a major enzyme from the alpha-glycoprotein family that catalyzes the hydrolysis of neurotransmitter acetylcholine (ACh), lowering the concentration of ACh in the nervous system, which could cause aggravation of Alzheimer's disease (AD). In select pathological conditions, it is beneficial to reduce the activity of this enzyme. The aim of this study was to evaluate the degree of BChE inhibition by coffee extracts fractionated into mono- and diesters of caffeic acid/caffeine, digested in vitro in the gastrointestinal tract. The bioactive compounds from coffee showed high affinity for BchE, -30.23--15.28 kJ/mol, and was the highest for the caffeine fraction from the green Arabica extract. The isolated fractions were highly effective in inhibiting BChE activity at all in vitro digestion phases. It has been shown that the fractionation of coffee extracts could be potentially used to obtain high prophylactic or even therapeutic effectiveness against AD.

Targeted Treatment against Lipoprotein (a): The Coming Breakthrough in Lipid Lowering Therapy.

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.

Bioaccessibility of coffee bean hydroxycinnamic acids during in vitro digestion influenced by the degree of roasting and activity of intestinal probiotic bacteria, and their activity in Caco-2 and HT29 cells.

In coffee beans, especially roasted, a significant part of hydroxycinnamic acid (HCAs) and their esters chlorogenic acids (CHAs) is attached to melanoidins through both covalent and non-covalent bonds. Bound and, to a greater extent, unbound HCAs, including those released from the polymerized material during digestion, can be pivotal in preventing of many chronic civilization diseases. The aim of the study was to determine the amount of free CHAs and those released from coffee extracts during in vitro digestion in various sections of the gastrointestinal tract, in the presence and absence of probiotic bacteria. The concentration of free CHAs was the lowest in the stomach and achieved the highest levels in the large intestine. Probiotic bacteria caused significant release of CHAs, and in the colon their concentration was the highest. The studies with Caco-2 and HT-29 cell lines showed that digested coffee extracts had cytoprotective potential against tert-BOOH induced oxidative stress.

Evinacumab, an ANGPTL3 Inhibitor, in the Treatment of Dyslipidemia.

Familial hypercholesterolemia (FH) is an inherited disorder. The level of low-density lipoprotein cholesterol (LDL-C) in patients with homozygous FH can be twice as high as that in patients with heterozygous FH. The inhibition of ANGPTL3 shows an important therapeutic approach in reducing LDL-C and triglycerides (TG) levels and, thus, is a potentially effective strategy in the treatment of FH. Evinacumab is a monoclonal antibody inhibiting circulating ANGPTL3, available under the trade name Evkeeza® for the treatment of homozygous FH. It was reported that evinacumab is effective and safe in patients with homozygous and heterozygous FH, as well as resistant hypercholesterolemia and hypertriglyceridemia. This paper summarizes existing knowledge on the role of ANGPTL3, 4, and 8 proteins in lipoprotein metabolism, the findings from clinical trials with evinacumab, a fully human ANGPTL3 mAb, and the place for this new agent in lipid-lowering therapy.

Bioactive Substances, Heavy Metals, and Antioxidant Activity in Whole Fruit, Peel, and Pulp of Citrus Fruits.

The use of whole citrus fruits in the food industry means that the valuable peel is used, but this may raise palatability or health concerns among consumers. The content of sugars, dietary fibre, redox compounds, lead, and cadmium was compared in citrus fruits (orange; pomelo; mandarin; lemon; key lime; and red, yellow, and green grapefruit). The pulp of all fruits contained significantly less fibre, tannins, and phenolic compounds than the peel. Whole citrus fruits had significantly lower content of sugars and higher content of dietary fibre and phenolic compounds, including ferulic acid, than their pulps. Whole grapefruits had higher concentrations of ascorbic acid. Whole lemons, limes, and mandarins had higher antioxidant potential than their pulp, due to their higher content of ascorbic acid, tannins, and phenolic compounds. Lead and cadmium content in whole fruits, while higher than in the pulps, was well below the acceptable daily intake.

The potential role of inflammation in cryptogenic stroke.

PURPOSE: The study aimed to identify biomarkers predictive of cryptogenic stroke in patients aged <65. MATERIALS AND METHODS: We investigated 520 patients with ischemic stroke. Out of them we assigned 65 patients to the cryptogenic stroke group (age 54 (47-58), 42% male) and 36 without stroke to the control group (age 53 (47-58), 61% male). In all patients we assessed carotid intima-media thickness (cIMT) and the levels of biomarkers which might be involved in the underlying biological mechanism of ischemic stroke. RESULTS: There were no differences between stroke and control groups in the levels of syndecan 4, resistin, leptin, low-density lipoprotein cholesterol, triglycerides, prothrombin time, or activated partial thromboplastin time. There was no statistically significant difference in cIMT between groups. The level of high-density lipoprotein cholesterol was statistically significantly lower in the cryptogenic stroke group than in the controls (1.1 mmol/L (0.95-1.46) vs 1.37 (1.19-1.6) p = 0.02). Patients in the stroke group had higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) (391 pg/ml (107-1249) vs 109 (46-236); p = 0.003), interleukin 6 (2.6 pg/ml (0.8-8.1) vs 0.7 (0.4-1.2) p = 0.002) and asymmetric dimethylarginine (ADMA) (0.44 µmol/L (0.39-0.55) vs 0.36 (0.32-0.4); p = 0.0002) than the control group. In the multivariate analysis Il-6 was the only biomarker statistically significant associated with the occurrence of cryptogenic stroke (odds ratio 1.918, 95% confidence interval 1.029-3.575; p = 0.04). CONCLUSIONS: Endothelial dysfunction assessed by increased level of ADMA affects the inflammatory state in patients with cryptogenic stroke. Increase in the inflammatory cytokine IL-6 by 1 pg/ml almost doubles the risk of stroke.

The sirtuin family members SIRT1, SIRT3 and SIRT6: Their role in vascular biology and atherogenesis.

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.

The role of nutraceuticals in the prevention of cardiovascular disease.

Cardiovascular disease (CVD) ranks among the most common health-related and economic issues worldwide. Dietary factors are important contributors to cardiovascular risk, either directly, or through their effects on other cardiovascular risk factors including hypertension, dyslipidemia and diabetes mellitus. Nutraceuticals are natural nutritional compounds, which have been shown to be efficacious in preventative medicine or in the treatment of disease. Several foods and dietary supplements have been shown to protect against the development of CVD. 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.

Oxidative stress in human erythrocytes treated with bromfenvinphos and its impurities.

Bromfenvinphos (BFVF) is an organophosphorus (OP) pesticide which was widely used in agriculture and veterinary practice. During synthesis of this insecticide five main impurities are formed: dihydro-bromfenvinphos, dibromo-bromfenvinphos, 2,4-dichlorophenacyl bromide, 2,4-dichlorophenacylidene bromide and 2,4-dichlorophenacylidyne bromide, which can be present in technical grade bromfenvinphos in amounts from 0.1 to 4%. The aim of this study was to examine the influence of bromfenvinphos and its manufacturing impurities on parameters of oxidative stress, the activity of antioxidative enzymes and the level of reduced glutathione. Human erythrocytes were incubated with bromfenvinphos and its impurities in the concentrations range from 0.5 to 500 µM for 1 h. This study indicated that 2,4-dichlorophenacyl derivatives more strongly oxidized analyzed parameters in human erythrocytes than bromfenvinphos. Investigated compounds caused an increase in lipid peroxidation and oxidation of fluorescent probe DCFH2 - the strongest pro-oxidative changes were provoked by 2,4-dichlorophenacyl bromide. None of the compounds studied in the concentrations from 0.5 to 500 µM changed the activity of SOD and only 2,4-dichlorophenacyl decreased activity of CAT. The level of GSH was only altered by 2,4-dichlorophenacyl derivatives. It was observed that increasing number of bromine atoms in the side chain of those derivatives was associated with decreased GSH level.

The effect of bromfenvinphos, its impurities and chlorfenvinphos on acetylcholinesterase activity.

The aim of this work was to examine the effect of two organophosphorous compounds i.e. bromfenvinphos (BFVF) and chlorfenvinphos (CFVF) possessing acaricidal and insecticidal properties, on the activity of human erythrocytes acetylcholinesterase (AChE, EC 3.1.1.7). Moreover, the effect of five bromfenvinphos production impurities on AChE activity was studied. The erythrocytes were incubated with the compounds studied in the concentrations range from 0.05 to 250 µM for 1h. The organophosphorous compounds studied in low concentrations increased Km value but they did not change Vmax value (competitive inhibition). Higher concentrations of the compounds studied decreased Vmax value and increased Km value, what revealed a mixed type of AChE inhibition by these xenobiotics. Basic significance in AChE activity inhibition has the type of halogen in vinyl group. Chlorfenvinphos (insecticide) exhibited stronger enzyme inhibition than bromfenvinphos. CFVF and dibromo-bromfenvinphos possessed the lowest Ki and Ki' values among all the compounds studied. The presence of Cl atom (chlorfenvinphos) instead of Br atom (bromfenvinphos) considerably increases antiesterase activity of the individual compound. Three impurities like 2,4-dichlorophenacyl bromide, 2,4-dichlorophenacylidene bromide and 2,4-dichlorophenacylidyne bromide did not induce any statistically changes in AChE activity. Two impurities of bromfenvinphos such as: dihydro-bromfenvinphos and dibromo-bromfenvinphos revealed significant effect on the AChE activity, which may be connected with the presence a phosphate group in these substances. It was proven that an increase in antiesterase activitiy of the compounds studied corresponded with the increase in the number of Br atoms at carbon of their vinyl group: dibromo-bromfenvinphos>bromfenvinphos>dihydro-bromfenvinphos.