Alcohol, health loss, and mortality: can wine really save the good name of moderate alcohol consumption?

It is estimated that one­third of the world's population consumes alcohol. At the same time, it is well­known that excessive alcohol consumption in one of the leading causes of premature mortality. The history of production of alcoholic beverages, especially wine, dates back as long as 8000 years. However, people soon realized adverse effects of alcohol abuse and tried to limit its consumption. Higher alcohol consumption is associated with health loss and increased risk of all­cause mortality. It is linearly associated with a greater risk of many types of cancers, liver disease, incidence of atrial fibrillation, hemorrhagic stroke, or heart failure. Although many scientific societies recommend reduction of alcohol intake and specify the recommended limits of consumption, there is no proven safe amount of alcohol for the general population. There are conflicting data on the effect of low­to­moderate alcohol consumption on mortality, with most of the studies indicating a J­shaped curve related mostly to a reduction of coronary artery disease complications, including cardiovascular death. Among different types of alcohol, red wine consumption may have different health effects, due to its high content of antioxidative polyphenols. Wine, together with abundance of plant­based foods, olive oil, and fish, is an important part of the Mediterranean diet. There are both observational and randomized studies documenting a wide spectrum of health­promoting effects of such a diet, especially a reduction in major adverse cardiovascular events. People who want to drink alcohol should be advised to limit their consumption to a minimum, and should consider choosing red wine.

Position paper of the Polish Expert Group on the use of pitavastatin in the treatment of lipid disorders in Poland endorsed by the Polish Lipid Association.

Lipid disorders, primarily hypercholesterolemia, are the most common cardiovascular (CV) risk factor in Poland (this applies even 3/4 of people). The low-density lipoprotein cholesterol (LDL-C) serum level is the basic lipid parameter that should be measured to determine CV risk and determines the aim and target of lipid-lowering treatment (LLT). Lipid-lowering treatment improves cardiovascular prognosis and prolongs life in both primary and secondary cardiovascular prevention. Despite the availability of effective lipid-lowering drugs and solid data on their beneficial effects, the level of LDL-C control is highly insufficient. This is related, among other things, to physician inertia and patients' fear of side effects. The development of lipidology has made drugs available with a good safety profile and enabling personalisation of therapy. Pitavastatin, the third most potent lipid-lowering statin, is characterised by a lower risk of muscle complications and new cases of diabetes due to its being metabolised differently. Thus, pitavastatin is a very good therapeutic option in patients at high risk of diabetes or with existing diabetes, and in patients at cardiovascular risk. This expert opinion paper attempts at recommendation on the place and possibility of using pitavastatin in the treatment of lipid disorders.

Whether and Why Do We Need a Vaccine Against Atherosclerosis? Can We Expect It Anytime Soon?

PURPOSE OF REVIEW: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of premature death. Lipid disorders, particularly elevated serum low-density lipoprotein cholesterol (LDL-C), contribute significantly to ASCVD. The risk of developing ASCVD is influenced by the duration of exposure to elevated LDL-C concentrations (cholesterol-years concept). Implementing lipid-lowering treatments based on the principles of "the earlier the better," "the lower the better," and "the longer the better" has been shown to reduce cardiovascular risk and significantly extend lifespan. Despite the availability of numerous lipid-lowering drugs, achieving satisfactory control of lipid disorders remains very challenging. Therefore, there is a need for novel approaches to improve treatment adherence. RECENT FINDINGS: One promising solution under investigation is the development of an anti-PCSK9 vaccine, which could be administered annually to provide long-term control over LDL-C concentrations. Experimental studies and the sole clinical trial conducted thus far have demonstrated that the anti-PCSK9 vaccine induces a durable immune response associated with lipid-lowering and anti-atherosclerotic effects. Furthermore, it has exhibited good tolerability and a satisfactory safety profile. However, we still need data from phase 2, 3, and cardiovascular outcome trial to confirm its safety and efficacy and add value in the armamentarium of available and perspective lipid-lowering drugs. This article highlights the significance of developing an anti-PCSK9 vaccine and provides an overview of the current knowledge on various anti-PCSK9 vaccines.

Hyponatremia in patients with arterial hypertension: pathophysiology and management.

Sodium is the main cation in the extracellular space. In physiological conditions, sodium concentration in plasma is 135-145 mmol/l. The kidneys play the most important role in the regulation of sodium homeostasis. In recent years, a significant role of glycosaminoglycans, localized mainly in the subcutaneous tissue, and the role of glycocalyx on the surface of vascular endothelial cells, have been documented in the regulation of sodium metabolism. Hyponatremia is defined by a plasma sodium concentration lower than 135 mmol/l. Hyponatremia significantly worsens the prognosis of patients with different chronic diseases. In patients with arterial hypertension, the risk of hyponatremia is 1.5 times higher than in the general population. One of the causes of hyponatremia in patients with arterial hypertension is the use of thiazide or thiazide-like diuretics. The symptoms of hyponatremia are caused mainly by the swelling of cells in the central nervous system. Treatment of hyponatremia depends on the degree and duration (acute or chronic) of hyponatremia as well as presence of clinical symptoms. Too rapid correction of hyponatremia might result in a potentially fatal osmotic demyelinating syndrome. In the present review paper, pathophysiology and management of hyponatremia in patients with arterial hypertension are discussed.

2023: The year in cardiovascular disease - the year of new and prospective lipid lowering therapies. Can we render dyslipidemia a rare disease by 2024?

In 2023 there are still even 75% of patients over the target of low-density lipoprotein cholesterol (LDL-C), and hypercholesterolemia is the most common and the worst monitored cardiovascular risk factor. How it is possible, considering the knowledge we have on the role of cholesterol in the process of atherosclerosis, atherosclerotic cardiovascular disease (ASCVD) and its complications, on the methods of lipid disorders diagnosis, prevention, and treatment. Nowadays, almost 4 million deaths per year are attributed to LDL-C, and even 2/3 of all CVD deaths to ASCVD, therefore hypothetically we should easily prevent few to several million of deaths with early diagnosis, and early and intensive non-pharmacological and pharmacological therapies. Moreover, lipidology is now, besides oncology, the area with the highest number of new and ongoing trials with new effective and safe medications that have already appeared and will soon be available. Therefore, we have no doubt that year 2023 should be called the year of new and prospective lipid lowering therapies (LLTs). In this State-of-the-Art paper we summarized the most important trials, studies, and recommendations on the new and prospective LLTs, with suitable graphical summaries that might be helpful for the physicians in their practice with a look to the nearest future with prospective therapies being still under investigation. Let's hope all those medications helps to render dyslipidemia a rare disease in next few years.

The Ketogenic Effect of SGLT-2 Inhibitors-Beneficial or Harmful?

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, also called gliflozins or flozins, are a class of drugs that have been increasingly used in the management of type 2 diabetes mellitus (T2DM) due to their glucose-lowering, cardiovascular (CV), and renal positive effects. However, recent studies suggest that SGLT-2 inhibitors might also have a ketogenic effect, increasing ketone body production. While this can be beneficial for some patients, it may also result in several potential unfavorable effects, such as decreased bone mineral density, infections, and ketoacidosis, among others. Due to the intricate and multifaceted impact caused by SGLT-2 inhibitors, this initially anti-diabetic class of medications has been effectively used to treat both patients with chronic kidney disease (CKD) and those with heart failure (HF). Additionally, their therapeutic potential appears to extend beyond the currently investigated conditions. The objective of this review article is to present a thorough summary of the latest research on the mechanism of action of SGLT-2 inhibitors, their ketogenesis, and their potential synergy with the ketogenic diet for managing diabetes. The article particularly discusses the benefits and risks of combining SGLT-2 inhibitors with the ketogenic diet and their clinical applications and compares them with other anti-diabetic agents in terms of ketogenic effects. It also explores future directions regarding the ketogenic effects of SGLT-2 inhibitors.

Potential Therapeutic Strategies in the Treatment of Metabolic-Associated Fatty Liver Disease.

Metabolic-associated Fatty Liver Disease is one of the outstanding challenges in gastroenterology. The increasing incidence of the disease is undoubtedly connected with the ongoing obesity pandemic. The lack of specific symptoms in the early phases and the grave complications of the disease require an active approach to prompt diagnosis and treatment. Therapeutic lifestyle changes should be introduced in a great majority of patients; but, in many cases, the adherence is not satisfactory. There is a great need for an effective pharmacological therapy for Metabolic-Associated Fatty Liver Disease, especially before the onset of steatohepatitis. Currently, there are no specific recommendations on the selection of drugs to treat liver steatosis and prevent patients from progression toward more advanced stages (steatohepatitis, cirrhosis, and cancer). Therefore, in this Review, we provide data on the clinical efficacy of therapeutic interventions that might improve the course of Metabolic-Associated Fatty Liver Disease. These include the drugs used in the treatment of obesity and hyperlipidemias, as well as affecting the gut microbiota and endocrine system, and other experimental approaches, including functional foods. Finally, we provide advice on the selection of drugs for patients with concomitant Metabolic-Associated Fatty Liver Disease.

The association between daily step count and all-cause and cardiovascular mortality: a meta-analysis.

AIMS: There is good evidence showing that inactivity and walking minimal steps/day increase the risk of cardiovascular (CV) disease and general ill-health. The optimal number of steps and their role in health is, however, still unclear. Therefore, in this meta-analysis, we aimed to evaluate the relationship between step count and all-cause mortality and CV mortality. METHODS AND RESULTS: We systematically searched relevant electronic databases from inception until 12 June 2022. The main endpoints were all-cause mortality and CV mortality. An inverse-variance weighted random-effects model was used to calculate the number of steps/day and mortality. Seventeen cohort studies with a total of 226 889 participants (generally healthy or patients at CV risk) with a median follow-up 7.1 years were included in the meta-analysis. A 1000-step increment was associated with a 15% decreased risk of all-cause mortality [hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.81-0.91; P < 0.001], while a 500-step increment was associated with a 7% decrease in CV mortality (HR 0.93; 95% CI 0.91-0.95; P < 0.001). Compared with the reference quartile with median steps/day 3867 (2500-6675), the Quartile 1 (Q1, median steps: 5537), Quartile 2 (Q2, median steps 7370), and Quartile 3 (Q3, median steps 11 529) were associated with lower risk for all-cause mortality (48, 55, and 67%, respectively; P < 0.05, for all). Similarly, compared with the lowest quartile of steps/day used as reference [median steps 2337, interquartile range 1596-4000), higher quartiles of steps/day (Q1 = 3982, Q2 = 6661, and Q3 = 10 413) were linearly associated with a reduced risk of CV mortality (16, 49, and 77%; P < 0.05, for all). Using a restricted cubic splines model, we observed a nonlinear dose-response association between step count and all-cause and CV mortality (Pnonlineraly < 0.001, for both) with a progressively lower risk of mortality with an increased step count. CONCLUSION: This meta-analysis demonstrates a significant inverse association between daily step count and all-cause mortality and CV mortality with more the better over the cut-off point of 3867 steps/day for all-cause mortality and only 2337 steps for CV mortality.

There is strong evidence showing that sedentary life may significantly increase the risk of cardiovascular (CV) disease and shorten the lifespan. However, the optimal number of steps, both the cut-off points over which we can see health benefits, and the upper limit (if any), and their role in health are still unclear. In this meta-analysis of 17 studies with almost 227 000 participants that assessed the health effects of physical activity expressed by walking measured in the number of steps, we showed that a 1000-step increment correlated with a significant reduction of all-cause mortality of 15%, and similarly, a 500-step increment correlated with a reduced risk of CV mortality of 7%. In addition, using the dose­response model, we observed a strong inverse nonlinear association between step count and all-cause mortality with significant differences between younger and older groups. It is the first analysis that not only looked at age and sex but also regional differences based on the weather zones, and for the first time, it assesses the effect of up to 20 000 steps/day on outcomes (confirming the more the better), which was missed in previous analyses. The analysis also revealed that depending on the outcomes, we do not need so many steps to have health benefits starting with even 2500/4000 steps/day, which, in fact, undermines the hitherto definition of a sedentary life.

Regional differences in physicians' behavior and factors influencing the intensity of PCSK9 inhibitor therapy with alirocumab: a subanalysis of the ODYSSEY APPRISE study.

Background: Despite better accessibility of the effective lipid-lowering therapies, only about 20% of patients at very high cardiovascular risk achieve the low-density lipoprotein cholesterol (LDL-C) goals. There is a large disparity between European countries with worse results observed for the Central and Eastern Europe (CEE) patients. One of the main reasons for this ineffectiveness is therapeutic inertia related to the limited access to appropriate therapy and suitable dosage intensity. Thus, we aimed to compare the differences in physicians' therapeutic decisions on alirocumab dose selection, and factors affecting these in CEE countries vs. other countries included in the ODYSSEY APPRISE study. Methods: ODYSSEY APPRISE was a prospective, single-arm, phase 3b open-label (≥12 weeks to ≤30 months) study with alirocumab. Patients received 75 or 150 mg of alirocumab every 2 weeks, with dose adjustment during the study based on physician's judgment. The CEE group in the study included Czechia, Greece, Hungary, Poland, Romania, Slovakia, and Slovenia, which we compared with the other nine European countries (Austria, Belgium, Denmark, Finland, France, Germany, Italy, Spain, and Switzerland) plus Canada. Results: A total of 921 patients on alirocumab were involved [modified intention-to-treat (mITT) analysis], including 114 (12.4%) subjects from CEE countries. Therapy in CEE vs. other countries was numerically more frequently started with lower alirocumab dose (75 mg) at the first visit (74.6 vs. 68%, p = 0.16). Since week 36, the higher dose was predominantly used in CEE patients (150 mg dose in 51.6% patients), which was maintained by the end of the study. Altogether, alirocumab dose was significantly more often increased by CEE physicians (54.1 vs. 39.9%, p = 0.013). Therefore, more patients achieved LDL-C goal at the end of the study (<55 mg/dl/1.4 mmol/L and 50% reduction of LDL-C: 32.5% vs. 28.8%). The only factor significantly influencing the decision on dose of alirocumab was LDL-C level for both countries' groups (CEE: 199.2 vs. 175.3 mg/dl; p = 0.019; other: 205.9 vs. 171.6 mg/dl; p < 0.001, for 150 and 75 mg of alirocumab, respectively) which was also confirmed in multivariable analysis (OR = 1.10; 95% CI: 1.07-1.13). Conclusions: Despite larger unmet needs and regional disparities in LDL-C targets achievement in CEE countries, more physicians in this region tend to use the higher dose of alirocumab, they are more prone to increase the dose, which is associated with a higher proportion of patients reaching LDL-C goals. The only factor that significantly influences decision whether to increase or decrease the dose of alirocumab is LDL-C level.

Sodium-Glucose Cotransporter 2 Inhibitors to Decrease the Uric Acid Concentration-A Novel Mechanism of Action.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are glucose-lowering agents whose positive impact on cardiovascular risk has been described extensively. Not only do they influence lipid profile, blood pressure, atherosclerosis risk, hemoglobin level, and insulin resistance, but they also reduce cardiovascular events, all-cause mortality, and hospitalization rates. Some of these effects may be due to their impact on serum uric acid (SUA) concentration. Findings from nine meta-analyses showed that, indeed, SGLT2is significantly reduce SUA. The data on the drug- and dose-dependency of this effect were inconclusive. Several factors alternating the beneficial effects of SGLT2is on SUA, such as glycated hemoglobin concentration (HbA1c), presence of diabetes, and baseline SUA level, were described. Even though there is a consensus that the lowering of SUA by SGLT2is might be due to the increased urinary excretion rate of uric acid (UEUA) rather than its altered metabolism, the exact mechanism remains unknown. The influence of SGLT2is on SUA may not only be used in gout treatment but may also be of huge importance in explaining the observed pleiotropic effects of SGLT2is.

Nutrition, Nutraceuticals and Bioactive Compounds in the Prevention and Fight against Inflammation.

Chronic low-grade systemic inflammation is a key factor involved in the pathogenesis of many diseases and their complications (Figure 1) [...].

Assessment the awareness toward hypertension and diabetes mellitus: Syrian cross sectional study.

BACKGROUND: Diabetes and arterial hypertension are the two most common types of non-communicable diseases (NCDs) impacting people globally. There is no prior research on the Syrian population's knowledge and treatment of hypertension and diabetes. It is crucial to investigate how the Syrian public understands and perceives these disorders in order to address the increased incidence and prevalence of hypertension and diabetes. This research intends to assess the level of hypertension and diabetes-related awareness, knowledge, attitude, and practices among Syrian individuals. METHODS: A cross-sectional survey was conducted online between 1 August and 25 August 2022. The questionnaire for the study was developed based on previous research, and the inclusion criteria for the sample were Syrian residents older than 18 who presently live in Syria. The survey consisted four sections: sociodemographics information, WHO STEPS survey instrument on knowledge of and lifestyle determinants for hypertension and diabetes, respondents' knowledge of and comprehension of hypertension and diabetes, and respondents' awareness of these disorders. RESULTS: Among 976 participants, 65.8% were females. the most common causes for hypertension from the perspective of participants were (90.1%) for stress, (87%) High salt consumption, (82.1%) genetics, (78.2%) old age, (78%) obesity (69%) anxiety, and (38.6%) for drug usage. Primary and middle school educational status participants had greater hypertension knowledge (92.3%) than other educational levels. There was a statistical significant difference between the knowledge toward the hypertension and the drinking alcohol, which the nonalcoholic knowledgeable persons were the most common (819 / 976)(P < 0.05). Participants whose lifestyles did not include alcohol use had a higher hypertension knowledge level (90.3%). Participants who do not consume alcohol have shown better hypertension knowledge (90.3%) than those who do (81.9%). Almost age groups have shown good knowledge of diabetes, especially participants aged above 55 (93.8%). However, most individuals have examined blood pressure (82.3%), whereas fewer than half had screened for blood sugar (64.4%). About 82.2% of individuals check their blood pressure frequently, whereas 6.2% monitor their blood sugar. There were significant associations between hypertension knowledge and gender, education, employment, and economic position (P value < 0.05). Men (mean = 8.39, SD = 2.02, P-value < 0.05) have a higher hypertension knowledge than females, and knowledge of hypertension among participants was shown to be higher among those in good income status than other economic levels (mean = 8.34, SD = 1.98). Age, gender, education, employment, and marital status were all associated with diabetes knowledge. Participants between the ages of 40 and 55 showed better knowledge of diabetes compared to other age groups (mean = 11.32, SD = 2.54); also, men demonstrated greater knowledge of diabetes than females (mean = 10.76, SD = 2.79). CONCLUSION: We indicated that the Syrian population has a good to moderate understanding of hypertension and diabetes. However, there is still a shortage of standardized, regular screening practices. Since individuals remain involved in unhealthy lifestyle habits, it is vital to provide accurate information about hypertension and diabetes to encourage them to make healthy changes.