Bempedoic acid: new evidence and recommendations on use.

PURPOSES OF REVIEW: Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide. Recognizing the importance of dyslipidemia treatment in the prevention of cardiovascular events has become a part of standard clinical practice. Desired values of LDL cholesterol (LDL-C) have become lower and lower in the last few decades, as evidenced by the most recent guidelines. Therefore, efforts to lower LDL cholesterol concentrations with conventional therapies and combinations of lipid-lowering therapy may not be successful in a high proportion of patients. RECENT FINDINGS: Bempedoic acid is a novel agent, first in-class ATP Citrate Lyase (ACL) inhibitor, which targets biosynthesis of the cholesterol in the liver. Considering the results of phase 3 studies, it has been approved for sole use for dyslipidemia treatment for patients who are statin-intolerant or in combination with statin-ezetimibe for those suffering from familial hypercholesterolemia or ASCVD and unable to reach targeted LDL-C values. SUMMARY: Bempedoic acid has proven beneficial for further reduction of LDL cholesterol for targeted groups of patients. It is not only efficient but also a well tolerated, affordable, and available agent whose place in lipid-lowering management is yet to be fully understood with new data collected from ongoing clinical research. In this review we suggest the place of bempedoic acid in lipid-lowering management.

Obicetrapib on top of maximally tolerated lipid-modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN.

BACKGROUND: Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events. METHODS AND RESULTS: BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a), and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2,532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024. CONCLUSION: These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.

Phenotypes of Polish primary care patients using hierarchical clustering: Exploring the risk of mortality in the LIPIDOGEN2015 study cohort.

BACKGROUND: Comorbidities in primary care do not occur in isolation but tend to cluster together causing various clinically complex phenotypes. This study aimed to distinguish phenotype clusters and identify the risks of all-cause mortality in primary care. METHODS: The baseline cohort of the LIPIDOGEN2015 sub-study involved 1779 patients recruited by 438 primary care physicians. To identify different phenotype clusters, we used hierarchical clustering and investigated differences between clinical characteristics and mortality between clusters. We then performed causal analyses using causal mediation analysis to explore potential mediators between different clusters and all-cause mortality. RESULTS: A total of 1756 patients were included (mean age 51.2, SD 13.0; 60.3% female), with a median follow-up of 5.7 years. Three clusters were identified: Cluster 1 (n = 543) was characterised by overweight/obesity (body mass index ≥ 25 kg/m2), older (age ≥ 65 years), more comorbidities; Cluster 2 (n = 459) was characterised by non-overweight/obesity, younger, fewer comorbidities; Cluster 3 (n = 754) was characterised by overweight/obesity, younger, fewer comorbidities. Adjusted Cox regression showed that compared with Cluster 2, Cluster 1 had a significantly higher risk of all-cause mortality (HR 3.87, 95% CI: 1.24-15.91), whereas this was insignificantly different for Cluster 3. Causal mediation analyses showed that decreased protein thiol groups mediated the hazard effect of all-cause mortality in Cluster 1 compared with Cluster 2, but not between Clusters 1 and 3. CONCLUSION: Overweight/obesity older patients with more comorbidities had the highest risk of long-term all-cause mortality, and in the young group population overweight/obesity insignificantly increased the risk in the long-term follow-up, providing a basis for stratified phenotypic risk management.

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.

The Influence of Hybrid Comprehensive Telerehabilitation on Anxiety in Heart Failure Patients: The TELEREH-HF Randomized Clinical Trial.

Telerehabilitation for heart failure (HF) patients is beneficial for physical functioning, prognosis, and psychological status. The study aimed at evaluating the influence of hybrid comprehensive telerehabilitation (HCTR) on the level of anxiety in comparison to usual care (UC). The TELEREH-HF study was a multicenter prospective RCT in 850 clinically stable HF participants. Patients underwent clinical examinations, including the assessment of anxiety, at entry and after the 9-week training program (HCTR) or observation (UC). The State-Trait Anxiety Inventory (STAI) was used. 20.3% HCTR and 20.1% UC patients reported high level of anxiety as a state at baseline, with higher STAI results in younger participants (< 63 y.o.) (p = .048 for HCTR; p = .026 for UC). At both stages of the study, patients with lower level of physical capacity (measured by a peak VO2) had shown significantly higher level of anxiety. There were no significant changes in anxiety levels during the 9-week observation for the entire study population, although there were different patterns of change in anxiety (both trait and state) in younger and older groups,with the decrease in younger patients, and the increase-in the older group.Trial registry number NCT02523560 (Clinical Trials.gov), date of registration: August 14, 2015.

The interaction of Helicobacter pylori with cancer immunomodulatory stromal cells: New insight into gastric cancer pathogenesis.

Gastric cancer is the fourth most common cause of cancer-linked deaths in the world. Gastric tumor cells have biological characteristics such as rapid proliferation, high invasiveness, and drug resistance, which result in recurrence and poor survival. Helicobacter pylori (H. pylori) has been proposed as a first-class carcinogen for gastric cancer according to the 1994 world health organization (WHO) classification. One of the important mechanisms by which H. pylori affects the gastric environment and promotes carcinogenesis is triggering inflammation. H. pylori induces an inflammatory response and a plethora of different signal transduction processes, leading to gastric mucosal disturbance, chronic gastritis, and a multi-step complex pathway that initiates carcinogenesis. It seems undeniable that the interaction between various cell types, including immune cells, gastric epithelium, glands, and stem cells, is vital for the progression and development of carcinogenesis concerning H. pylori. The interactions of H. pylori with surrounding cells play a key role in cancer progression. In this review, we discuss the interplay between H. pylori and tumor-supportive cells, including mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid derived-suppressor cells (MDSCs) in gastric cancer. It is hoped that clarifying the specific mechanisms for 'cross-talk' between H. pylori and these cells will provide promising strategies for developing new treatments.

Association of body mass index and long-term mortality in patients from nationwide LIPIDOGRAM 2004-2015 cohort studies: no obesity paradox?

BACKGROUND: An obesity paradox has been described in relation to adverse clinical outcomes (e.g., mortality) with lower body mass index (BMI). AIMS: We sought to evaluate the association between BMI and weight loss with long-term all-cause mortality in adult populations under the care of family physicians. METHODS: LIPIDOGRAM studies were conducted in primary care in Poland in 2004, 2006, and 2015 and enrolled a total of 45,615 patients. The LIPIDOGRAM Plus study included 1627 patients recruited in the LIPIDOGRAM 2004 and repeated measurements in 2006 edition. Patients were classified by BMI categories as underweight, normal weight, overweight and class I, II, or III (obesity). Follow-up data up to December 2021 were obtained from the Central Statistical Office. Differences in all-cause mortality were analyzed using Kaplan‒Meier and Cox regression analyses. RESULTS: Of 45,615 patients, 10,987 (24.1%) were normal weight, 320 (0.7%) were underweight, 19,134 (41.9%) were overweight, and 15,174 (33.2%) lived with obesity. Follow-up was available for 44,620 patients (97.8%, median duration 15.3 years, 61.7% females). In the crude analysis, long-term all-cause mortality was lowest for the normal-weight group (14%) compared with other categories. After adjusting for comorbidities, the highest risk of death was observed for the class III obesity and underweight categories (hazard ratio, HR 1.79, 95% CI [1.55-2.05] and HR 1.57, 95% CI [1.22-2.04]), respectively. The LIPIDOGRAM Plus analysis revealed that a decrease in body weight (by 5 and 10%) over 2 years was associated with a significantly increased risk of death during long-term follow-up-HR 1.45 (95% CI 1.05-2.02, p = 0.03) and HR 1.67 (95% CI 1.02-2.74, p < 0.001). Patients who experienced weight loss were older and more burdened with comorbidities. CONCLUSIONS: Being underweight, overweight or obese is associated with a higher mortality risk in a population of patients in primary care. Patients who lost weight were older and more burdened with cardiometabolic diseases, which may suggest unintentional weight loss, and were at higher risk of death in the long-term follow-up. In nonsmoking patients without comorbidities, the lowest mortality was observed in those with a BMI < 25 kg/m2, and no U-curve relationship was observed.

Impact of vitamin D receptor polymorphisms in selected metabolic disorders.

PURPOSE OF REVIEW: Vitamin D (vitD) can regulate metabolic pathways in adipose tissue and pancreatic ß cells by interacting with its vitamin D receptor (VDR). The aim of this study was to review original publications published in the last months and verify the relationship between genetic variants in the VDR gene and type 2 diabetes (T2D), metabolic syndrome (MetS), overweight, and obesity. RECENT FINDINGS: The recent studies concern genetic variants located in the coding and noncoding regions of the VDR gene. Some of the described genetic variants may affect VDR expression or posttranslational processing altered functionality or vitD binding capacity of VDR. Nevertheless, the data collected in recent months on the assessment of the relationship between VDR genetic variants and the risk of T2D, MetS, overweight, and obesity still do not give a clear answer to whether they have a direct impact on these metabolic disorders. SUMMARY: Analysis of the potential association between VDR genetic variants and parameters such as glycemia, body mass index, body fat, and lipid levels improves the current understanding of the pathogenesis of T2D, MetS, overweight, and obesity. A thorough understanding of this relationship may provide important information for individuals with pathogenic variants and enable the implementation of appropriate prevention against the development of these disorders.

Rhabdomyolysis or Severe Acute Hepatitis Associated with the Use of Red Yeast Rice Extracts: an Update from the Adverse Event Reporting Systems.

PURPOSE OF REVIEW: Elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for atherosclerotic cardiovascular disease (ASCVD), and lowering LDL-C reduces the risk of cardiovascular adverse events. Among natural approaches known for their lipid-lowering properties, red yeast rice (RYR) has a cholesterol-lowering effect due to the presence of bioactive components (monacolins) that act by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. In August 2018, the European Food Safety Authority (EFSA) concluded in its assessment of the use of RYR (further amended in June 2022) that monacolins from RYR raise significant safety concerns when used as a food supplement at a dose of 10 mg/day. In particular, individual cases of serious adverse effects of monacolins from RYR have been reported at intakes as low as 3 mg/day. The EFSA Panel pointed out several uncertainties regarding the available data. RECENT FINDINGS: We conducted an in-depth and updated analysis of the serious adverse events, with a focus on rhabdomyolysis and acute hepatitis, associated with the consumption of RYR. An analysis of the Food and Drug Administration reporting systems revealed a very small number of cases of rhabdomyolysis or severe acute hepatitis associated with RYR use. In addition, only a few case reports of these serious adverse events associated with RYR use have been published. Based on data from adverse event reporting systems and available case reports, the occurrence of rhabdomyolysis or severe acute hepatitis that could be associated with the use of RYR appears to be extremely rare compared to the occurrence with statins, which is rare to common.

Coffee or tea: Anti-inflammatory properties in the context of atherosclerotic cardiovascular disease prevention.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of premature death worldwide. Inflammation and its biomarkers, like C-reactive protein (CRP), among the risk factors, such as hypertension, lipid disorders, and diabetes, may be also responsible for the residual cardiovascular disease (CVD) risk. Modern lipid-lowering treatment with statins, ezetimibe, PCSK9 inhibitors, or bempedoic acid does not fully protect against inflammation. The recommendations of the International Lipid Expert Panel (ILEP) indicate selected nutraceuticals with anti-inflammatory properties. Diet may have a significant impact on inflammation. Especially interesting in the context of inflammation is the consumption of coffee and tea. These drinks in many observational studies significantly reduced cardiovascular risk and mortality. The question is whether the anti-inflammatory effects of these drinks contribute significantly to the observed clinical effects. Thus, in this narrative review, we primarily discuss the anti-inflammatory properties of consuming tea and coffee. Based on a comprehensive analysis of the studies and their meta-analyses, inconsistent results were obtained, which makes it impossible to conclusively state how clinically significant the potential anti-inflammatory properties of black and green tea and coffee are. A number of confounding factors can cause the inconsistency of the available results. Consumption of tea and coffee appears to increase adiponectin concentrations, decrease reactive oxygen species, decrease low density lipoprotein (LDL) cholesterol concentrations (effect of green tea, etc.). Despite the still uncertain anti-inflammatory effect of tea and coffee, we recommend their consumption as a part of the healthy diet.

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP).

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Harnessing polyphenol power by targeting eNOS for vascular diseases.

Vascular diseases arise due to vascular endothelium dysfunction in response to several pro-inflammatory stimuli and invading pathogens. Thickening of the vessel wall, formation of atherosclerotic plaques consisting of proliferating smooth muscle cells, macrophages and lymphocytes are the major consequences of impaired endothelium resulting in atherosclerosis, hypercholesterolemia, hypertension, type 2 diabetes mellitus, chronic renal failure and many others. Decreased nitric oxide (NO) bioavailability was found to be associated with anomalous endothelial function because of either its reduced production level by endothelial NO synthase (eNOS) which synthesize this potent endogenous vasodilator from L-arginine or its enhanced breakdown due to severe oxidative stress and eNOS uncoupling. Polyphenols are a group of bioactive compounds having more than 7000 chemical entities present in different cereals, fruits and vegetables. These natural compounds possess many OH groups which are largely responsible for their strong antioxidative, anti-inflammatory antithrombotic and anti-hypersensitive properties. Several flavonoid-derived polyphenols like flavones, isoflavones, flavanones, flavonols and anthocyanidins and non-flavonoid polyphenols like tannins, curcumins and resveratrol have attracted scientific interest for their beneficial effects in preventing endothelial dysfunction. This article will focus on in vitro as well as in vivo and clinical studies evidences of the polyphenols with eNOS modulating activity against vascular disease condition while their molecular mechanism will also be discussed.

Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study From DA VINCI.

PURPOSE: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated. METHODS: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated. RESULTS: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively. CONCLUSION: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach.

Prevalence of statin intolerance: a meta-analysis.

AIMS: Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI. METHODS AND RESULTS: We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0-6.0%) vs. 17% (14-19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%)]. Age [odds ratio (OR) 1.33, P = 0.04], female gender (OR 1.47, P = 0.007), Asian and Black race (P < 0.05 for both), obesity (OR 1.30, P = 0.02), diabetes mellitus (OR 1.26, P = 0.02), hypothyroidism (OR 1.37, P = 0.01), chronic liver, and renal failure (P < 0.05 for both) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI. CONCLUSION: Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.

A Critical View over the Newest Antidiabetic Molecules in Light of Efficacy-A Systematic Review and Meta-Analysis.

The increase in life expectancy without a decrease in the years lived without disability leads to the rise of the population aged over 65 years prone to polypharmacy. The novel antidiabetic drugs can improve this global therapeutic and health problem in patients with diabetes mellitus (DM). We aimed to establish the efficacy (A1c hemoglobin reduction) and safety of the newest antidiabetic drugs (considered so due to their novelty in medical practice use), specifically DPP-4i, SGLT-2i, GLP-1 Ra, and tirzepatide. The present meta-analysis followed the protocol registered at Prospero with the CRD42022330442 registration number. The reduction in HbA1c in the DPP4-i class for tenegliptin was 95% CI -0.54 [-1.1, 0.01], p = 0.06; in the SGLT2-iclass for ipragliflozin 95% CI -0.2 [-0.87, 0.47], p = 0.55; and for tofogliflozin 95% CI 3.13 [-12.02, 18.28], p = 0.69, while for tirzepatide it was 0.15, 95% CI [-0.50, 0.80] (p = 0.65). The guidelines for treatment in type 2 DM are provided from cardiovascular outcome trials that report mainly major adverse cardiovascular events and data about efficacy. The newest antidiabetic non-insulinic drugs are reported to be efficient in lowering HbA1c, but this effect depends between classes, molecules, or patients' age. The newest antidiabetic drugs are proven to be efficient molecules in terms of HbA1c decrease, weight reduction, and safety, but more studies are needed in order to characterize exactly their efficacy and safety profiles.

HDL and cancer - causality still needs to be confirmed? Update 2020.

An inverse correlation between high-density lipoprotein cholesterol (HDL-C) and cancer risk has been shown by several epidemiological studies. Some studies have even suggested that HDL-C can be used as a prognostic marker in patients with certain types of cancer. However, whether reduced HDL-C level is a consequential or causal factor in the development and progression of cancer remains a controversial issue. In this review, we update and summarize recent advances that highlight the role of HDL and some of its components in prognosis, diagnosis and treatment of cancer.

The effect of caloric restriction and fasting on cancer.

Cancer is one of the most frequent causes of worldwide death and morbidity and is a major public health problem. Although, there are several widely used treatment methods including chemo-, immune- and radiotherapies, these mostly lack sufficient efficiency and induce toxicities in normal surrounding tissues. Thus, finding new approaches to mitigate side effects and potentially accelerate treatment is paramount. In line with this, increasing preclinical evidence indicates that caloric restriction (CR) and fasting might have anticancer effects by reducing tumor progression, enhancing death of cancer cells, and elevating the effectiveness and tolerability of chemo- and radiotherapies. Nonetheless, clinical studies assessing the potential of CR and fasting in cancer are scarce and inconsistent, and more investigations are still required to clarify their effect in different aspects of cancer treatment. In this review, we have summarized the findings of preclinical and clinical studies of CR and fasting with respect to efficacy and on the adverse effects of standard cancer treatments.

A close-up view of dynamic biomarkers in the setting of COVID-19: Striking focus on cardiovascular system.

Based on the recent reports, cardiovascular events encompass a large portion of the mortality caused by the COVID-19 pandemic, which drawn cardiologists into the management of the admitted ill patients. Given that common laboratory values may provide key insights into the illness caused by the life-threatening SARS-CoV-2 virus, it would be more helpful for screening, clinical management and on-time therapeutic strategies. Commensurate with these issues, this review article aimed to discuss the dynamic changes of the common laboratory parameters during COVID-19 and their association with cardiovascular diseases. Besides, the values that changed in the early stage of the disease were considered and monitored during the recovery process. The time required for returning biomarkers to basal levels was also discussed. Finally, of particular interest, we tended to abridge the latest updates regarding the cardiovascular biomarkers as prognostic and diagnostic criteria to determine the severity of COVID-19.

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000-2018.

BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA. METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

Proprotein Convertase Subtilisin/Kexin Type 9: A View beyond the Canonical Cholesterol-Lowering Impact.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), mainly synthetized and released by the liver, represents one of the key regulators of low-density lipoprotein cholesterol. Although genetic and interventional studies have demonstrated that lowering PCSK9 levels corresponds to a cardiovascular benefit, identification of non-cholesterol-related processes has emerged since its discovery. Besides liver, PCSK9 is also expressed in many tissues (eg, intestine, endocrine pancreas, and brain). The aim of the present review is to describe and discuss PCSK9 pathophysiology and possible non-lipid-lowering effects whether already extensively characterized (eg, inflammatory burden of atherosclerosis, triglyceride-rich lipoprotein metabolism, and platelet activation), or to be unraveled (eg, in adipose tissue). The identification of novel transcriptional factors in the promoter region of human PCSK9 (eg, ChREBP) characterizes new mechanisms explaining how controlling intrahepatic glucose may be a therapeutic strategy to reduce cardiovascular risk in type 2 diabetes. Finally, the evidence describing PCSK9 as involved in cell proliferation and apoptosis raises the possibility of this protein being involved in cancer risk.