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Hyperlipidemia, commonly referred to as dyslipidemia, is characterized by elevated serum cholesterol and/or triglyceride levels. This condition contributes significantly to the high mortality rates associated with cardiovascular diseases, posing a serious threat to global health. Although statins remain the predominant pharmacological treatment for hyperlipidemia, their associated side effects have led to a growing interest in alternative therapeutic approaches. Traditional Chinese Medicine (TCM) is exploring these alternatives, with the Erchen Decoction (ECD) emerging as a promising candidate. This review aims to summarize current clinical research, elucidate the mechanisms of action, and assess the compatibility of ECD in the management of hyperlipidemia. By doing so, we hope to provide valuable insights and references for clinical practice and future research. [ABSTRACT FROM AUTHOR]

A decrease in the levels of low-density lipoprotein receptors (LDLRs) leads to the accumulation of LDL cholesterol (LDL-C) in the bloodstream, resulting in hypercholesterolemia and atherosclerotic cardiovascular diseases. Increasing the expression level or inducing the activity of LDLR in hepatocytes can effectively control hypercholesterolemia. Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, primarily produced in the liver, promotes the degradation of LDLR. Inhibiting the expression and/or function of PCSK9 can increase the levels of LDLR on the surface of hepatocytes and promote LDL-C clearance from the plasma. Thus, targeting PCSK9 represents a new strategy for developing preventive and therapeutic interventions for hypercholesterolemia. Currently, monoclonal antibodies are used as PCSK9 inhibitors in clinical practice. However, the need for oral and affordable anti-PCSK9 medications limits the perspective of choosing PCSK9 inhibitors for clinical usage. Emerging research reports have demonstrated that natural phytochemicals have efficacy in maintaining cholesterol stability and regulating lipid metabolism. Developing novel natural phytochemical PCSK9 inhibitors can serve as a starting point for developing small-molecule drugs to reduce plasma LDL-C levels in patients. In this review, we summarize the current literature on the critical role of PCSK9 in controlling LDLR degradation and hypercholesterolemia, and we discuss the results of studies attempting to develop PCSK9 inhibitors, with an emphasis on the inhibitory effects of natural phytochemicals on PCSK9. Furthermore, we provide insight into the mechanisms of action by which the reported phytochemicals exert their potential PCSK9 inhibitory effects against hypercholesterolemia.

This study evaluated the relationship of non-invasive arterial stiffness parameters with an individual 10-year risk of fatal and non-fatal atherosclerotic cardiovascular disease (ASCVD) events in the cohort post-coronavirus disease 2019 (COVID-19). The study group included 203 convalescents aged 60.0 (55.0–63.0) and 115 (56.7%) women. The ASCVD risk was assessed as low to moderate to very high based on medical history (for 62 participants with pre-existing ASCVD/diabetes/chronic kidney disease in the entire cohort) or calculated in percentages using the Systemic Coronary Risk Evaluation 2 (SCORE2) algorithm based on age, sex, smoking status, systolic blood pressure (BP), and non-high-density lipoprotein cholesterol (for 141 healthy participants). The stiffness index (SI) and reflection index (RI) measured by photoplethysmography, as well as pulse pressure (PP), calculated as the difference between systolic and diastolic BP, were markers of arterial stiffness. Stiffness parameters increased significantly with the increase in ASCVD risk in the entire cohort. In 30 (14.8%) patients in the low- to moderate-risk group, the median SI was 8.07 m/s (7.10–8.73), RI 51.40% (39.40–65.60), and PP 45.50 mmHg (40.00–57.00); in 111 (54.7%) patients in the high-risk group, the median SI was 8.70 m/s (7.40–10.03), RI 57.20% (43.65–68.40), and PP 54.00 mmHg (46.00–60.75); and in 62 (30.5%) patients in the very-high-risk group, the median was SI 9.27 m/s (7.57–10.44), RI 59.00% (50.40–72.40), and PP 60.00 mmHg (51.00–67.00). In healthy participants, the SI ≤ 9.0 m/s (sensitivity of 92.31%, area under the curve [AUC] 0.686, p < 0.001) based on the receiver operating characteristics was the most sensitive variable for discriminating low to moderate risk, and PP > 56.0 mmHg (sensitivity of 74.36%, AUC 0.736, p < 0.001) was used for discriminating very high risk. In multivariate logistic regression, younger age, female sex, PP ≤ 50 mmHg, SI ≤ 9.0 m/s, and triglycerides < 150 mg/dL had the best relationship with low to moderate SCORE2 risk. In turn, older age, currently smoking, PP > 56.0 mmHg, RI > 68.6%, and diastolic BP ≥ 90 mmHg were related to very high SCORE2 risk. In conclusion, arterial stiffness is significantly related to ASCVD risk in post-COVID-19 patients and can be helpful as a single risk marker in everyday practice. Cut-off points for arterial stiffness parameters determined based on SCORE2 may help make individual decisions about implementing lifestyle changes or pharmacological treatment of ASCVD risk factors [ABSTRACT FROM AUTHOR]

Hyperlipidemia, commonly referred to as dyslipidemia, is characterized by elevated serum cholesterol and/or triglyceride levels. This condition contributes significantly to the high mortality rates associated with cardiovascular diseases, posing a serious threat to global health. Although statins remain the predominant pharmacological treatment for hyperlipidemia, their associated side effects have led to a growing interest in alternative therapeutic approaches. Traditional Chinese Medicine (TCM) is exploring these alternatives, with the Erchen Decoction (ECD) emerging as a promising candidate. This review aims to summarize current clinical research, elucidate the mechanisms of action, and assess the compatibility of ECD in the management of hyperlipidemia. By doing so, we hope to provide valuable insights and references for clinical practice and future research.

An increased concentration of lipoprotein(a) (Lp(a)) is one of the main genetic residual risk factors for atherosclerotic cardiovascular diseases, as well as their complications. Lp(a) is a complex supramolecular complex in which the unique glycosylated apo(a) protein, which has a wide polymorphism, is linked by a disulfide bond to the apoB100 molecule (protein component of the low-density lipoprotein (LDL) particle). Therefore, Lp(a) is often called LDL-like particle. Unlike all other lipoproteins, Lp(a) concentration is determined genetically, almost constant throughout the life, and has wide individual and interethnic variability. As an independent risk factor, elevated Lp(a) concentrations can significantly increase global cardiovascular risk, especially in patients with other risk factors. Modern international and national guidelines recommend measuring Lp(a) concentration not only in certain categories of patients, but also in every person at least once in their life for a correct assessment of cardiovascular risk.

High lipoprotein(a) (LP(a)) level contributes as an independent risk factor to the development of cardiovascular diseases of atherosclerotic origin. The article contains data on the structural features of this particle, the genetic determination of its metabolism and content in blood plasma, and the pathogenic mechanisms of its proatherogenic, proinflammatory and prothrombotic effects. The authors analyzed epidemiological data on the frequency of elevated LP(a) levels in different population groups and its association with the risk of cardiovascular diseases. The data presented concern the indicators of LP(a) as a risk factor for the development of ischemic stroke (including recurrent stroke) and its individual pathogenetic subtypes, as well as the relationship between LP(a) levels and functional outcomes after cerebral accidents. Current recommendations for the treatment of patients with elevated LP(a) levels in the context of primary and secondary prevention of cardiovascular diseases are analyzed.

The role of cholesterol, mainly low-density lipoproteins (LDL-C), as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) is now established and accepted by the international scientific community. Based on this evidence, the European and American guidelines recommend early risk stratification and "rapid" achievement of the suggested target according to the risk estimation to reduce the number of major cardiovascular events. Prolonged exposure over the years to high levels of LDL-C is one of the determining factors in the development and progression of atherosclerotic plaque, on which the action of conventional risk factors (cigarette smoking, excess weight, sedentary lifestyle, arterial hypertension, diabetes mellitus) as well as non-conventional risk factors (gut microbiota, hyperuricemia, inflammation), alone or in combination, favors the destabilization of the atherosclerotic lesion with rupture/fissuration/ulceration and consequent formation of intravascular thrombosis, which leads to the acute clinical manifestations of acute coronary syndromes. In the current clinical practice, there is a growing number of cases that, although extremely common, are emblematic of the concept of long-term exposure to the risk factor (LDL hypercholesterolemia), which, not adequately controlled and in combination with other risk factors, has favored the onset of major cardiovascular events. The triple concept of "go lower, start earlier and keep longer!" should be applied in current clinical practice at any level of prevention. In the present manuscript, we will review the current evidence and documents supporting the causal role of LDL-C in determining ASCVD and whether it is time to remove it from any score. [ABSTRACT FROM AUTHOR]

Background/aim: Type 2 diabetes mellitus (T2DM) is closely associated with atherosclerotic cardiovascular diseases (ASCVD). The objective of this study was to describe the degree of ASCVD risk factor control and their association with carotid intima-media thickness (CIMT) in T2DM patients followed up at a diabetes clinic in Southern, Sri Lanka. Materials and methods: A crosssectional study was conducted to examine the association between CIMT and nonalcoholic fatty liver disease (NAFLD)in 300 T2DM patients. Both CIMT and its associations with modifiable cardiometabolic risk factors were examined using ultrasonography. The recommended optimal targets for risk factors were defined as glycated hemoglobin (HbA1C) < 7 %, absence of NAFLD, albumin-to-creatinine ratio (ACR) < 30 mg, triglyceride (TG) < 150 mg/dL, low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL, high-density lipoprotein cholesterol (HDL-C) in men > 40 and in women > 50 mg/dL, systolic blood pressure (SBP) < 130 mmHg, and diastolic blood pressure (DBP) < 80 mmHg. Results: SBP, DBP, LDL-C, TG, HDL-C, HbA1C, and ACR were optimally controlled in 59.3%, 75.0%, 46.7%, 84.3%, 46.0%, 33.0%, and 18.7% of patients, respectively. Notably, nearly half of the study subjects did not have NAFLD. Only three patients (1%) had achieved all therapeutic targets. There were statistically significant differences in CIMT between optimally controlled TG and suboptimally controlled TG group (p = 0.027) and between the groups with and without NAFLD (p = 0.045) when adjusted for age and duration of diabetes. CIMT showed significant and positive associations with LDL-C (p = 0.024), TG (p = 0.026), and NAFLD (p = 0.005). Among these, the presence of NAFLD had the highest odds of having higher CIMT when compared to LDL-C and TG. Conclusion: The majority of patients have not achieved the recommended targets for ASCVD risk factors and are at high risk of ASCVD. It is therefore necessary to identify the reasons for not achieving the treatment targets in order to reduce the ASCVD burden by controlling LDL-C, TG, and NAFLD. [ABSTRACT FROM AUTHOR]

Numerous studies have shown that a low level of high-density lipoprotein cholesterol (HDL-C) is an independent biomarker of cardiovascular disease. High-density lipoprotein (HDL) is considered to be a protective factor for atherosclerosis (AS). Therefore, raising HDL-C has been widely recognized as a promising strategy to treat atherosclerotic cardiovascular diseases (ASCVD). However, several studies have found that increasing HDL-C levels does not necessarily reduce the risk of ASCVD. HDL particles are highly heterogeneous in structure, composition, and biological function. Moreover, HDL particles from atherosclerotic patients exhibit impaired anti-atherogenic functions and these dysfunctional HDL particles might even promote ASCVD. This makes it uncertain that HDL-raising therapy will prevent and treat ASCVD. It is necessary to comprehensively analyze the structure and function of HDL subfractions. We review current advances related to HDL subfractions remodeling and highlight how current lipid-modifying drugs such as niacin, statins, fibrates, and cholesteryl ester transfer protein inhibitors regulate cholesterol concentration of HDL and specific HDL subfractions. [ABSTRACT FROM AUTHOR]

Objective: Several studies have illustrated that elevated RC levels are related to a heightened risk of acute ischemic stroke (AIS). Our research aimed to explore the correlation between RC levels and poor prognosis after a 90‐day interval in AIS patients. Methods: A total of 287 individuals were enrolled in the study, the primary outcome was defined as poor prognosis. RC was derived by the exclusion of low‐density lipoprotein cholesterol (LDL‐C) and high‐density lipoprotein cholesterol (HDL‐C) from total cholesterol (TC). Results: Following the screening process, 253 AIS patients were included in the study, presenting a median age of 66[57, 75] years. Upon stratifying RC levels into quartiles, those in the top quartile faced a greater likelihood of diabetes diagnosis (42.86%, p =.014) and experienced a higher rate of unfavorable outcomes after 90 days (36.51%, p =.001). After accounting for confounding factors, the correlation between the fourth quartile of RC levels and the amplified likelihood of poor prognosis remained significant (odds ratio (OR) 8.471, 95% confidence interval (CI) (1.841, 38.985); p =.006). Analysis of subgroups unveiled a notable correlation between higher RC levels and poor 90‐day prognosis, particularly in individuals with elevated NIHSS scores (p =.044). A progressively increasing 90‐day risk of poor prognosis after an RC greater than 0.38 mmol/L was visualized by restricted cubic spline plots (p‐overall =.011). Conclusions: Including RC as a contributing element may refine the prediction of poor 90‐day prognosis for AIS patients. Integrating RC with traditional risk factors can potentially enhance the predictive value for cerebrovascular disease. [ABSTRACT FROM AUTHOR]

Evidence from prospective cohort studies has revealed an inverse association between cheese consumption and the development of atherosclerosis (AS), atherosclerotic cardiovascular diseases (ASCVD), and their complications. However, it remains unclear whether this observed association is influenced by potential confounding factors that may arise during the long-term development process of AS, ASCVD, and its complications. Therefore, to further clarify the causal relationship between cheese consumption and AS, ASCVD, and its complications, we conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between cheese intake and the aforementioned health outcomes. We employed a two-sample MR analysis based on publicly available genome-wide association studies (GWAS) to infer the causal relationship, with no overlap between their participating populations. The effect estimates were calculated using the random-effects inverse-variance-weighted method. Sensitivity analyses were conducted using Cochran's Q statistic, funnel plot, leave-one-out analysis, and MR-Egger intercept tests. The genetically predicted cheese intake was found to be associated with lower risks of coronary AS (odds ratio [OR] = 0.72, 95 % confidence interval [CI] 0.59–0.88, P = 0.001), peripheral vascular AS (OR = 0.56, 95 % CI 0.37–0.84, P = 0.006), other vascular AS (OR = 0.66, 95 % CI 0.44–0.99, P = 0.043), coronary artery disease (OR = 0.64, 95 % CI 0.56–0.74, P = 1.57e-09), angina pectoris (OR = 0.70, 95 % CI 0.58–0.84, P = 4.92e-05), myocardial infarction (OR = 0.63, 95 % CI 0.52–0.77, P = 3.56e-06), heart failure (OR = 0.62, 0.49–0.79, P = 1.20e-04), total ischemic stroke (OR = 0.76, 95 % CI 0.63–0.91, P = 0.003), peripheral artery disease (OR = 0.64, 95 % CI 0.43–0.95, P = 0.028), and cognitive impairment (OR = 0.65, 95 % CI 0.56–0.74, P = 3.40e-10). However, no associations were observed for cerebrovascular AS, arrhythmia, cardiac death, ischemic stroke (large artery AS), ischemic stroke (small vessel), ischemic stroke (cardioembolic), and transient ischemic attack. This two-sample MR analysis reveals a causally inverse association between cheese intake and multi-vascular AS (including coronary AS, peripheral vascular AS, and other vascular AS), as well as multiple types of ASCVD and its complications (such as coronary artery disease, angina pectoris, myocardial infarction, heart failure, total ischemic stroke, and peripheral artery disease). The findings from this study may lay a stronger theoretical foundation and present new opportunities for the dietary management of future atherosclerotic cardiovascular diseases. • Genetically predicted cheese consumption lowered the risks of coronary atherosclerosis (AS), peripheral vascular AS, other vascular AS. • Genetically predicted cheese consumption lowered the risks of coronary heart disease, angina pectoris, myocardial infarction, heart failure, total ischemic stroke, peripheral artery disease, and cognitive impairment. • The findings from this study may lay a stronger theoretical foundation and present new opportunities for the dietary management of future atherosclerotic cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background and Aims RNA-based, antibody-based, and genome editing-based therapies are currently under investigation to determine if the inhibition of angiopoietin-like protein-3 (ANGPTL3) could reduce lipoprotein-lipid levels and atherosclerotic cardiovascular disease (ASCVD) risk. Mendelian randomisation (MR) was used to determine whether genetic variations influencing ANGPTL3 liver gene expression, blood levels, and protein structure could causally influence triglyceride and apolipoprotein B (apoB) levels as well as coronary artery disease (CAD), ischaemic stroke (IS), and other cardiometabolic diseases. Methods RNA sequencing of 246 explanted liver samples and genome-wide genotyping was performed to identify single-nucleotide polymorphisms (SNPs) associated with liver expression of ANGPTL3. Genome-wide summary statistics of plasma protein levels of ANGPTL3 from the deCODE study (n = 35 359) were used. A total of 647 carriers of ANGPTL3 protein-truncating variants (PTVs) associated with lower plasma triglyceride levels were identified in the UK Biobank. Two-sample MR using SNPs that influence ANGPTL3 liver expression or ANGPTL3 plasma protein levels as exposure and cardiometabolic diseases as outcomes was performed (CAD, IS, heart failure, non-alcoholic fatty liver disease, acute pancreatitis, and type 2 diabetes). The impact of rare PTVs influencing plasma triglyceride levels on apoB levels and CAD was also investigated in the UK Biobank. Results In two-sample MR studies, common genetic variants influencing ANGPTL3 hepatic or blood expression levels of ANGPTL3 had a very strong effect on plasma triglyceride levels, a more modest effect on low-density lipoprotein cholesterol, a weaker effect on apoB levels, and no effect on CAD or other cardiometabolic diseases. In the UK Biobank, the carriers of rare ANGPTL3 PTVs providing lifelong reductions in median plasma triglyceride levels [−0.37 (interquartile range 0.41) mmol/L] had slightly lower apoB levels (−0.06 ± 0.32 g/L) and similar CAD event rates compared with non-carriers (10.2% vs. 10.9% in carriers vs. non-carriers, P =.60). Conclusions PTVs influencing ANGPTL3 protein structure as well as common genetic variants influencing ANGPTL3 hepatic expression and/or blood protein levels exhibit a strong effect on circulating plasma triglyceride levels, a weak effect on circulating apoB levels, and no effect on ASCVD. Near-complete inhibition of ANGPTL3 function in patients with very elevated apoB levels may be required to reduce ASCVD risk. [ABSTRACT FROM AUTHOR]

To prospectively examine whether depressive symptoms were associated with higher risks of incident cardiovascular diseases (CVD) in individuals with type 2 diabetes. Included were 17,031 participants from UK Biobank with type 2 diabetes who were free of depression (identified by self-reported medical history, hospital record, and antidepressant use), and composite CVD, including atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). Cox proportional hazards models were applied to examine the association between depressive symptoms measured by Patient Health Questionaire-2 (PHQ-2) and incident composite CVD and its subtypes, adjusting for potential confounders. During a median follow-up of 12.3 years, we documented 2875 incident composite CVD cases (including 1303 coronary artery disease, 531 ischemic stroke, 530 peripheral arterial disease, and 1142 HF cases). The presence of depressive symptoms had higher risks of composite CVD (adjusted HR, 1.34; 95 % CI, 1.17–1.54) among individuals with type 2 diabetes. Dose-response relationships were observed between depressive symptoms and the composite CVD, ASCVD, and three individual CVD outcomes (P -trend <0.05 for all). Depressive symptoms were associated with a higher risk of CVD events across all degrees of metabolic control and diabetes severity. Dose-response associations were also found between depressive symptoms score and all incident CVD outcomes, except for ischemic stroke, after adjustment for cardiovascular and diabetes-related risk factors. Therefore, simple screening questions regarding depressive symptoms might be applied to people with type 2 diabetes to predict CVD outcomes. • Results identified dose-response relationships between depressive symptoms score and CVD, which was independent of lifestyle, metabolic conditions and diabetes severity. • Results supported American Diabetes Association's recommendations for routine screening for depressive symptoms in people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Brown and Goldstein are among the Nobel Prize-winning scientists whose experiments on the low-density lipoprotein (LDL] receptor in patients with familial hypercholesterolemia (FH) proved the prototype for receptor-mediated endocytosis. After the FH study, there is convincing evidence that LDL-cholesterol is at the root of atherosclerotic cardiovascular disease. In accordance with these facts, we conducted a study among a prospective and retrospective group of FH patients, with the main goal to perform cascade screening among their first-degree relatives. The launch of a FH screening program is a step forward in our efforts to reduce early atherosclerosis and its complications. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerotic cardiovascular diseases (ASCVD) are significant sources of mortality and morbidity with substantial economic implications and preventive measures play key roles in this regard. Metabolic syndrome (MetS) is a common condition, and its association with ASCVD and mortality has made it clinically important. However, controversies persist regarding the best definition for MetS. Here in, we investigated the ability of the International Diabetes Federation (IDF) and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) in the prediction of ASCVD incidence. Methods: We conducted an investigation on individuals diagnosed with MetS as part of the "Kerman Coronary Artery Diseases Risk Factor Study" (KERCADRS). This study was a cohort study conducted on a population aged 15–75 years residing in Kerman, Iran to assess the risk of ASCVD. We employed ACC/AHA ASCVD Risk Estimator for predicting ASCVD occurrence in the future and then compared the results with different definitions of MetS including IDF and NCEP ATP III. Results: Patients with MetS consistent with NCEP ATP III had higher ASCVD risk scores than those with IDF (10.63 ± 10.989 vs. 9.50 ± 9.357). NCEP ATP III had better overall performance in terms of specificity, accuracy, sensitivity and positive and negative predictive values especially in higher ASCVD risk score categories. The agreement between IDF and NCEP ATP III was none to slight (Cohen's Kappa <0.2) except for IDF in the group of ASCVD >30%, which revealed no agreement (Cohen's Kappa = 0). Conclusion: NCEP ATP III has better overall performance compared to IDF. The ability of NCEP ATP III increases as the ASCVD risk score goes higher. IDF may be useful in primary screening and patients with lower ASCVD risk scores. [ABSTRACT FROM AUTHOR]

Abstract Objective Several studies have illustrated that elevated RC levels are related to a heightened risk of acute ischemic stroke (AIS). Our research aimed to explore the correlation between RC levels and poor prognosis after a 90‐day interval in AIS patients. Methods A total of 287 individuals were enrolled in the study, the primary outcome was defined as poor prognosis. RC was derived by the exclusion of low‐density lipoprotein cholesterol (LDL‐C) and high‐density lipoprotein cholesterol (HDL‐C) from total cholesterol (TC). Results Following the screening process, 253 AIS patients were included in the study, presenting a median age of 66[57, 75] years. Upon stratifying RC levels into quartiles, those in the top quartile faced a greater likelihood of diabetes diagnosis (42.86%, p = .014) and experienced a higher rate of unfavorable outcomes after 90 days (36.51%, p = .001). After accounting for confounding factors, the correlation between the fourth quartile of RC levels and the amplified likelihood of poor prognosis remained significant (odds ratio (OR) 8.471, 95% confidence interval (CI) (1.841, 38.985); p = .006). Analysis of subgroups unveiled a notable correlation between higher RC levels and poor 90‐day prognosis, particularly in individuals with elevated NIHSS scores (p = .044). A progressively increasing 90‐day risk of poor prognosis after an RC greater than 0.38 mmol/L was visualized by restricted cubic spline plots (p‐overall = .011). Conclusions Including RC as a contributing element may refine the prediction of poor 90‐day prognosis for AIS patients. Integrating RC with traditional risk factors can potentially enhance the predictive value for cerebrovascular disease.

Background: Atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), and obesity are associated with increased morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Nonetheless, their prevalence among patients with T2DM in Saudi Arabia (SA) remains unknown. As current guidelines recommend, these comorbidities require adding certain antidiabetic agents with cardiorenal benefits. However, the prescribers' adherence to these recommendations remains unclear. Methods: A two-center retrospective cross-sectional study was conducted including adult patients (≥18 years) with T2DM admitted to hospital or seen at outpatient clinics between January and December 2020. Patients were classified into two groups based on the presence or absence of ASCVD. Patients with no prior ASCVD history were further classified based on the 10-year ASCVD risk estimation. Endpoints of interest included the prevalence of ASCVD, HF, CKD, and obesity in patients with T2DM. We also evaluated the characteristics of the utilized antidiabetic agents, statin, and aspirin therapies.. Results: Of the 1,218 included patients with T2DM, the majority were female (57.0 %), and aged 45–64 years (53.0 %) with a mean age of 59.3 ± 13.1 years. Hypertension and dyslipidemia were the most prevalent comorbidities (67.7 % and 69.0 %, respectively). Among all patients, 18.6 % had an established ASCVD and the prevalence of HF, CKD, and obesity were 5.1 %, 8.7 %, and 58.3 %, respectively. The most common types of ASCVD witnessed were revascularization (42.3 %), myocardial infarction (36.6 %), and stroke (33.9 %); with an increased prevalence of ASCVD as the age increases (52.8 % at age ≥ 65 years). In the non‐ASCVD group, the 10-year ASCVD risk was intermediate or high in 62.7 % of these patients. The rates of utilization of guidelines-recommended therapies were 83.6 % for metformin, 9.4 % for GLP-1 RA, 10.8 % for SGLT2i, 35.2 % for aspirin alone or in combination with clopidogrel, and 79.7 % for statin therapy. Conclusions: ASCVD, HF, CKD, and obesity are common complications in patients with T2DM in SA, with low overall utilization of the recommended guidelines-recommended medical therapies. Multimodal strategies should be utilized to assess T2DM and its complications, and to improve prescribers' adherence to guidelines-recommended therapies.

The close attention of researchers is riveted to the study of socially significant multifactorial diseases and syndromes with a hereditary predisposition, which include chronic heart failure, formed as a result of atherosclerosis of the coronary arteries. The promise of genomic studies in atherosclerosis and heart failure is associated with the possibility of determining the genetic risk of developing and predicting adverse cardiovascular events before the onset of clinical signs/symptoms. From the standpoint of understanding the pathogenesis of atherosclerosis as a variant of nonspecific inflammation, which has a wave-like character, it is assumed that genes encoding pro-inflammatory cytokines influence the pathological process. The aim of the review was to analyze the results of studies available in available publications on the rs1800629 polymorphism of the tumor necrosis factor (TNF) gene in patients with atherosclerotic cardiovascular diseases. Most data indicate the presence of an increased cardiovascular risk in carriers of the A allele of the rs1800629 polymorphism of the TNF gene. It was determined that carriage of the AA genotype is associated with essential arterial hypertension and remodeling of the left ventricular myocardium. In patients with chronic heart failure with preserved and moderately reduced left ventricular ejection fraction of the AA genotype, low blood pressure and frequent occurrence of atrial fibrillation were noted. A number of papers present the results of studies of the rs1800629 polymorphism of the TNF gene and the prognostic significance of the rs1800629 polymorphism of the TNF gene in heart failure.

This study evaluated the relationship of non-invasive arterial stiffness parameters with an individual 10-year risk of fatal and non-fatal atherosclerotic cardiovascular disease (ASCVD) events in the cohort post-coronavirus disease 2019 (COVID-19). The study group included 203 convalescents aged 60.0 (55.0–63.0) and 115 (56.7%) women. The ASCVD risk was assessed as low to moderate to very high based on medical history (for 62 participants with pre-existing ASCVD/diabetes/chronic kidney disease in the entire cohort) or calculated in percentages using the Systemic Coronary Risk Evaluation 2 (SCORE2) algorithm based on age, sex, smoking status, systolic blood pressure (BP), and non-high-density lipoprotein cholesterol (for 141 healthy participants). The stiffness index (SI) and reflection index (RI) measured by photoplethysmography, as well as pulse pressure (PP), calculated as the difference between systolic and diastolic BP, were markers of arterial stiffness. Stiffness parameters increased significantly with the increase in ASCVD risk in the entire cohort. In 30 (14.8%) patients in the low- to moderate-risk group, the median SI was 8.07 m/s (7.10–8.73), RI 51.40% (39.40–65.60), and PP 45.50 mmHg (40.00–57.00); in 111 (54.7%) patients in the high-risk group, the median SI was 8.70 m/s (7.40–10.03), RI 57.20% (43.65–68.40), and PP 54.00 mmHg (46.00–60.75); and in 62 (30.5%) patients in the very-high-risk group, the median was SI 9.27 m/s (7.57–10.44), RI 59.00% (50.40–72.40), and PP 60.00 mmHg (51.00–67.00). In healthy participants, the SI ≤ 9.0 m/s (sensitivity of 92.31%, area under the curve [AUC] 0.686, p < 0.001) based on the receiver operating characteristics was the most sensitive variable for discriminating low to moderate risk, and PP > 56.0 mmHg (sensitivity of 74.36%, AUC 0.736, p < 0.001) was used for discriminating very high risk. In multivariate logistic regression, younger age, female sex, PP ≤ 50 mmHg, SI ≤ 9.0 m/s, and triglycerides < 150 mg/dL had the best relationship with low to moderate SCORE2 risk. In turn, older age, currently smoking, PP > 56.0 mmHg, RI > 68.6%, and diastolic BP ≥ 90 mmHg were related to very high SCORE2 risk. In conclusion, arterial stiffness is significantly related to ASCVD risk in post-COVID-19 patients and can be helpful as a single risk marker in everyday practice. Cut-off points for arterial stiffness parameters determined based on SCORE2 may help make individual decisions about implementing lifestyle changes or pharmacological treatment of ASCVD risk factors

Abstract Introduction Atherosclerotic cardiovascular diseases (ASCVD) are significant sources of mortality and morbidity with substantial economic implications and preventive measures play key roles in this regard. Metabolic syndrome (MetS) is a common condition, and its association with ASCVD and mortality has made it clinically important. However, controversies persist regarding the best definition for MetS. Here in, we investigated the ability of the International Diabetes Federation (IDF) and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) in the prediction of ASCVD incidence. Methods We conducted an investigation on individuals diagnosed with MetS as part of the “Kerman Coronary Artery Diseases Risk Factor Study” (KERCADRS). This study was a cohort study conducted on a population aged 15–75 years residing in Kerman, Iran to assess the risk of ASCVD. We employed ACC/AHA ASCVD Risk Estimator for predicting ASCVD occurrence in the future and then compared the results with different definitions of MetS including IDF and NCEP ATP III. Results Patients with MetS consistent with NCEP ATP III had higher ASCVD risk scores than those with IDF (10.63 ± 10.989 vs. 9.50 ± 9.357). NCEP ATP III had better overall performance in terms of specificity, accuracy, sensitivity and positive and negative predictive values especially in higher ASCVD risk score categories. The agreement between IDF and NCEP ATP III was none to slight (Cohen's Kappa 30%, which revealed no agreement (Cohen's Kappa = 0). Conclusion NCEP ATP III has better overall performance compared to IDF. The ability of NCEP ATP III increases as the ASCVD risk score goes higher. IDF may be useful in primary screening and patients with lower ASCVD risk scores.

Large epidemiological studies show U-shaped relationships between high-density lipoprotein cholesterol (HDL-C) levels and all-cause mortality in individuals without atherosclerotic cardiovascular diseases (ASCVD). Association in those with ASCVD by sex is unclear. We examined the association between HDL-C levels and 10-year all-cause mortality in subjects (≥40 years of age) with ASCVD using the 2010 National Health Insurance Service and the National Death Registry of Korea. We categorized HDL-C levels into three groups (low: <40 mg/dL for males, <50 mg/dL for females; high: 40–90 mg/dL for males, 50–90 mg/dL for females; extremely high: >90 mg/dL) and 10 mg/dL intervals. We conducted a sex-stratified and adjusted Cox proportional hazards analysis. Out of 1,711,548 individuals (54% female, mean age 61.4 years), 10-year mortality was observed in 218,252 (12.8%). Males had a higher mortality rate than females (16.2% vs. 9.8%; p < 0.001). When adjusting for age, body mass index, LDL-cholesterol, triglycerides, hypertension, diabetes, smoking, and alcohol consumption, the low and extremely high HDL-C groups had significantly higher hazard ratios for 10-year mortality compared to the high HDL-C group in males [1.183 (1.166–1.199), 1.359 (1.288–1.434)] and in females [1.153 (1.138–1.169), 1.095 (1.029–1.167)]. The frequency distribution bars for the 10-year mortality rate showed sex-specific nadirs of 50–59 mg/dL in males and 70–79 mg/dL in females. In this ASCVD cohort, the extremely high HDL-C (>90 mg/dL) group had 35.9% and 9.5% higher 10-year mortality risks than the high HDL-C group for males and females, respectively. There was a slightly U-shaped relationship between baseline HDL-C levels and a 10-year mortality rate, with earlier inflection in males than in females. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular diseases (including myocardial infarction, stroke, and peripheral arterial disease) continue to be a leading cause of premature death, disability, and healthcare expenditures worldwide. Therefore, preventing the vascular accumulation of atherogenic cholesterol-containing lipoproteins is crucial in averting major cardiovascular events. The Colombian Cholesterol Roadmap update is the outcome of a meeting held during the 2023 National Cardiology Congress, with the support of the World Heart Federation and a panel of clinical and thematic experts, along with representatives from various institutions involved in the management of dyslipidaemias in Colombia. The present update of this Cholesterol Roadmap provides a conceptual framework to describe the findings and achievements derived from working groups focused on identifying barriers that hinder the appropriate treatment of hypercholesterolemia in Colombia. It also outlines proposed actions adjusted to the local context, aiming to develop national policies and approaches within our healthcare systems. Furthermore, it reaffirms the commitment to intersectoral collaboration to achieve the cardiovascular health goals set for the year 2030. [ABSTRACT FROM AUTHOR]

Bempedoic acid is a new cholesterol-lowering drug that recently received approval from the US Food and Drug Administration and the European Medicines Agency. This drug targets lipid and glucose metabolism as well as inflammation by downregulating the ATP citrate lyase and upregulating of AMP-activated protein kinase (AMPK). The main effect is to reduce cholesterol synthesis in the liver, and its use is generally not associated with undesirable muscle disorders. Bempedoic acid can reduce the processes of gluconeogenesis, which leads to an improvement in insulin sensitivity, glucose metabolism and features of the metabolic syndrome. The anti-inflammatory effect of bempedoic acid is mainly achieved by activating the AMPK pathway in immune cells, which helps reduce the level of C-reactive protein in plasma. The effects of bempedoic acid on the course of atherosclerotic cardiovascular disease, type 2 diabetes and chronic liver disease have been evaluated in randomi­zed clinical trials that require further research. Phase III clinical safety trial show that bempedoic acid is generally well tolerated in combination with statins, ezetimibe, or proprotein convertase subti­lisin/kexin type 9 inhibitors in achieving target levels of low-density lipoprotein cholesterol. The aim of this review is to analyze the main mechanisms of action, potential clinical targets of bempedoic acid and describe the existing evidence from clinical trials. The search was done in the Scopus, Science Direct (from Elsevier), and PubMed databases, including the Medline. The following keywords were used: bempedoic acid, low-density lipoprotein cholesterol, atherosclerotic cardiovascular diseases, diabetes. In order to identify research results that could not be found during the online search, a manual search of the bibliography of publications was used.

The role of cholesterol, mainly low-density lipoproteins (LDL-C), as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) is now established and accepted by the international scientific community. Based on this evidence, the European and American guidelines recommend early risk stratification and “rapid” achievement of the suggested target according to the risk estimation to reduce the number of major cardiovascular events. Prolonged exposure over the years to high levels of LDL-C is one of the determining factors in the development and progression of atherosclerotic plaque, on which the action of conventional risk factors (cigarette smoking, excess weight, sedentary lifestyle, arterial hypertension, diabetes mellitus) as well as non-conventional risk factors (gut microbiota, hyperuricemia, inflammation), alone or in combination, favors the destabilization of the atherosclerotic lesion with rupture/fissuration/ulceration and consequent formation of intravascular thrombosis, which leads to the acute clinical manifestations of acute coronary syndromes. In the current clinical practice, there is a growing number of cases that, although extremely common, are emblematic of the concept of long-term exposure to the risk factor (LDL hypercholesterolemia), which, not adequately controlled and in combination with other risk factors, has favored the onset of major cardiovascular events. The triple concept of “go lower, start earlier and keep longer!” should be applied in current clinical practice at any level of prevention. In the present manuscript, we will review the current evidence and documents supporting the causal role of LDL-C in determining ASCVD and whether it is time to remove it from any score.

Aim. To evaluate the effectiveness of acetylsalicylic acid (ASA) drugs for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in clinical practice and compare the effectiveness of the Cardiomagnyl with other ASA drugs.Material and methods. This observational, non-interventional, retrospective study included data from electronic medical records (>18 million) of 18199 patients with ASCVD who were divided into 2 following groups: patients who received ASA 75100 mg (n=9784) and patients who did not receive ASA (n=8325). The prescription rate of ASA, the choice of the first drug, the duration of ASA therapy, the frequency of switching ASA during treatment, and the choice of the second ASA drug when changing therapy were assessed. Due to the heterogeneity of patients in the above groups, to assess the clinical outcomes, propensity score matching was performed and comparable groups were selected to evaluate the effectiveness of ASA drugs 75-100 mg in patients with ASCVD (n= 427) in comparison with patients not receiving ASA (n=427) and to assess the effectiveness of Cardiomagnyl 75 mg (n=1308) in comparison with enterosoluble ASA 100 mg (CRA) (n=1308) taking into account 24 parameters.Results. The average proportion of patients with ASCVD taking ASA drugs was 58%. During treatment, 54% of patients underwent a change in drug therapy from one ASA drug to another. The prescription rate of Cardiomagnyl as a first-choice drug was 33%, and as a second drug when changing therapy — 21%. The duration of Cardiomagnyl therapy was the longest compared to other ASA drugs and amounted to 16,3 months. The incidence of ischemic stroke, myocardial infarction and major adverse cardiovascular events in the group of patients who received ACS 75-100 mg was significantly lower than in patients who did not take ASA drugs and amounted to 4,7% vs 8,7%, 0,9% vs 3,3%, 5,6% vs 11,9%, respectively. Significantly lower incidence of unstable angina (0,8% vs 2,0%), myocardial infarction (1,5% vs 3,9%) and major adverse cardiovascular events (5,4% vs 7,8%) in group of patients who received Cardiomagnyl 75 mg as opposed to enterosoluble ASA.Conclusion. Significant advantages of buffered ASA (Cardiomagnyl) were revealed in comparison with enterosoluble ASA in clinical practice.

Purpose: Statins are the cornerstone therapy for primary or secondary prevention of atherosclerotic cardiovascular disease (ASCVD). However, a significant portion of patients are intolerant to statin or show inadequate lipid-lowering. Bempedoic acid (BA) has been shown to decrease low-density lipoprotein cholesterol (LDL-C) in clinical trials. However, the evidence on the effect of BA on clinical cardiovascular outcomes was limited until the CLEAR Outcomes trial. Thus, to fully appraise the available data, we performed this meta-analysis. Methods: PubMed, Pubmed Central, Embase, and Scopus databases were searched for relevant articles published before May 1, 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4. Results: Out of 2209 studies evaluated, five randomized control trials with 17,384 patients with established ASCVD or at high risk of ASCVD were included for analysis. The BA therapy reduced major adverse cardiovascular events (OR 0.85, CI 0.77-0.93;

In recent years, there has been an increasing interest in understanding the systemic nature of COPD and its frequently associated comorbidities. COPD is characterized by chronic lung disease involving local and systemic inflammation and non-reversible airway obstruction. The disease course is marked by recurrent exacerbations and is often accompanied by various comorbidities. This study aimed to evaluate the prevalence of comorbidities among Iraqi patients with COPD and their association with disease severity. A case-control study was conducted at Al-Sader Hospital in Annajaf from October 2019 to October 2020, involving 200 participants. The study population comprised 100 patients with COPD (COPD group) and 100 individuals without COPD serving as the control group. Patients with COPD were divided into four groups according to the disease severity. The prevalence of type 2 diabetes mellitus (T2DM), atherosclerotic cardiovascular diseases (ASCVD), hypertension, and dyslipidemia was determined in all groups. Patients with COPD had a significantly higher prevalence of T2DM, ASCVD, hypertension, and dyslipidemia, and, except for T2DM, the prevalence was significantly higher in the more severe groups. It was concluded that T2DM, ASCVD, hypertension, and dyslipidemia were commonly associated with COPD. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) is the primary contributor to global mortality rates, which significantly escalates healthcare expenditures. Risk factors for ASCVD (including dyslipidemia) frequently present in clusters rather than separately. Addressing these risk factors is crucial in the early initiation of a comprehensive management plan that involves both lifestyle modifications and pharmacotherapy to reduce the impact of ASCVD. A team of Jordanian professionals from various medical organizations and institutes took the initiative to create a set of guidelines for dyslipidemia screening and therapy. A detailed, comprehensive literature review was undertaken utilizing several databases and keywords. This consensus statement provides recommendations for dyslipidemia management in Jordanians on several issues including cardiovascular risk estimation, screening eligibility, risk categories, treatment goals, lifestyle changes, and statin and non-statin therapies. It is recommended that all Jordanian individuals aged 20 years old or older undergo lipid profile testing. This should be followed by determining the level of cardiovascular risk depending on the presence or absence of ASCVD and cardiovascular risk factors, eligibility for lipid-lowering therapy, and the target low-density cholesterol serum level to be achieved. In conclusion, prioritizing the management of dyslipidemia is of the utmost importance in improving public health and reducing the burden of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Homozygous familial hypercholesterolemia (HoFH) is a rare, primarily an autosomal dominant genetic disorder that causes markedly elevated low-density lipoprotein (LDL) cholesterol levels predisposing patients to risk of developing premature atherosclerotic cardiovascular diseases. Disease manifestations usually develop in 1st or 2nd decade of life and severity depends on the duration of exposure to elevated LDL cholesterol levels. The mainstay in management is early recognition and treatment with various lipid-lowering agents including lipid-apheresis in severe cases not responding to drug therapy. We report three cases of HoFH presenting to our institute in their 2nd decade of life with different cutaneous and cardiovascular manifestations and discuss challenges in their management.

Bempedoic acid is a new cholesterol-lowering drug that recently received approval from the US Food and Drug Administration and the European Medicines Agency. This drug targets lipid and glucose metabolism as well as inflammation by downregulating the ATP citrate lyase and upregulating of AMP-activated protein kinase (AMPK). The main effect is to reduce cholesterol synthesis in the liver, and its use is generally not associated with undesirable muscle disorders. Bempedoic acid can reduce the processes of gluconeogenesis, which leads to an improvement in insulin sensitivity, glucose metabolism and features of the metabolic syndrome. The anti-inflammatory effect of bempedoic acid is mainly achieved by activating the AMPK pathway in immune cells, which helps reduce the level of C-reactive protein in plasma. The effects of bempedoic acid on the course of atherosclerotic cardiovascular disease, type 2 diabetes and chronic liver disease have been evaluated in randomized clinical trials that require further research. Phase III clinical safety trial show that bempedoic acid is generally well tolerated in combination with statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors in achieving target levels of low-density lipoprotein cholesterol. The aim of this review is to analyze the main mechanisms of action, potential clinical targets of bempedoic acid and describe the existing evidence from clinical trials. The search was done in the Scopus, Science Direct (from Elsevier), and PubMed databases, including the Medline. The following keywords were used: bempedoic acid, low-density lipoprotein cholesterol, atherosclerotic cardiovascular diseases, diabetes. In order to identify research results that could not be found during the online search, a manual search of the bibliography of publications was used. [ABSTRACT FROM AUTHOR]

Background The impact of an elevated body mass index (BMI) on atherosclerotic cardiovascular disease (ASCVD) risk in individuals who are metabolically healthy is debated. We investigated the respective contributions of BMI as well as lifestyle and cardiometabolic risk factors combined to ASCVD incidence in 319 866 UK Biobank participants. Methods and Results We developed a cardiovascular health score (CVHS) based on 4 lifestyle and 6 cardiometabolic parameters. The impact of the CVHS on incident ASCVD (15 699 events) alone and in BMI and waist‐to‐hip ratio categories was assessed using Cox proportional hazards in women and men separately. In participants with a high CVHS (8–10), those with a BMI ≥35.0 kg/m2 had a nonsignificantly higher ASCVD risk (hazard ratio [HR], 1.20 [95% CI, 0.84–1.70]; P=0.32) compared with those with a BMI of 18.5 to 24.9 kg/m2. In participants with a BMI of 18.5 to 24.9 kg/m2, those with a lower CVHS (0–2) had a higher ASCVD risk (HR, 4.06 [95% CI, 3.23–5.10]; P

The Russian Society of Cardiology (RKO)With the participation of: The National Society for the Study of Atherosclerosis (NOA), the Russian Association of Endocrinologists (RAE), the Russian Society of Cardiosomatic Rehabilitation and Secondary Prevention (RosOKR), the Russian Scientific Medical Society of Therapists (RNMOT), the Eurasian Association of Cardiologists, the Eurasian Association of Therapists (EAT), the Russian Association of Gerontologists and Geriatricians

OBJECTIVE: Aspirin is an essential drug in the prevention of atherosclerotic cardiovascular disease (ASCVD). It is ultimately indicated in a patient with ASCVD. However, its role is debated in primary prevention. We aimed to investigate the appropriateness of aspirin use in diabetic patients according to recommendations of recent guidelines. PATIENTS AND METHODS: ASSOS was a multicenter observational study investigating aspirin use in cardiology outpatient clinics. We evaluated aspirin use in diabetic patients in primary prevention from the ASSOS study. We also assessed the appropriate use of aspirin according to the European Society of Cardiology (ESC), American College of Cardiology/American Heart Association (ACC/AHA), American Diabetes Association (ADA), Consensus Statement of Endocrinology, Cardiology, and Nephrology (ENCARNE), and the United States Preventive Services Task Force (USPTF). RESULTS: A total of 5,007 patients of whom 1,537 had type 2 diabetes mellitus (DM) were included in the study. 1,132 of the total participants used aspirin for primary prevention; 313 of them had type 2 DM. Only 248 (76.7%), 132 (40.8%), and 128 (39.6%) diabetic patients indicated aspirin use according to the ESC/INCARNE, ACC/AHA, and ADA/USPTF guidelines, respectively. CONCLUSIONS: Inappropriate aspirin use was common among diabetic patients, according to clinical practice guideline recommendations. In addition, the differences between the indications for the use of aspirin in diabetic patients according to the guidelines were remarkable. Guidelines that minimize these differences are needed for clinicians, and compliance with these guidelines in clinical practice could reduce inappropriate aspirin use. [ABSTRACT FROM AUTHOR]

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Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Large epidemiological studies show U-shaped relationships between high-density lipoprotein cholesterol (HDL-C) levels and all-cause mortality in individuals without atherosclerotic cardiovascular diseases (ASCVD). Association in those with ASCVD by sex is unclear. We examined the association between HDL-C levels and 10-year all-cause mortality in subjects (≥40 years of age) with ASCVD using the 2010 National Health Insurance Service and the National Death Registry of Korea. We categorized HDL-C levels into three groups (low: 90 mg/dL) and 10 mg/dL intervals. We conducted a sex-stratified and adjusted Cox proportional hazards analysis. Out of 1,711,548 individuals (54% female, mean age 61.4 years), 10-year mortality was observed in 218,252 (12.8%). Males had a higher mortality rate than females (16.2% vs. 9.8%; p < 0.001). When adjusting for age, body mass index, LDL-cholesterol, triglycerides, hypertension, diabetes, smoking, and alcohol consumption, the low and extremely high HDL-C groups had significantly higher hazard ratios for 10-year mortality compared to the high HDL-C group in males [1.183 (1.166–1.199), 1.359 (1.288–1.434)] and in females [1.153 (1.138–1.169), 1.095 (1.029–1.167)]. The frequency distribution bars for the 10-year mortality rate showed sex-specific nadirs of 50–59 mg/dL in males and 70–79 mg/dL in females. In this ASCVD cohort, the extremely high HDL-C (>90 mg/dL) group had 35.9% and 9.5% higher 10-year mortality risks than the high HDL-C group for males and females, respectively. There was a slightly U-shaped relationship between baseline HDL-C levels and a 10-year mortality rate, with earlier inflection in males than in females.

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality. Life satisfaction is a measure of mental health with a potential cardioprotective role. This study aimed to investigate the association between life satisfaction and ASCVD risk in the general Japanese population. Method: We used data from 6,877 people (30–84 years) registered in the Suita Study, a Japanese population-based prospective cohort study. All participants were free from stroke and coronary heart disease (CHD) at baseline. Then, participants were followed up for incident ASCVD, including cerebral infarction and CHD. Cox proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of incident ASCVD according to life satisfaction. Results: Within 102,545 person-years (median follow-up = 16.6 years), 482 incident ASCVD events were identified. In the age- and sex-adjusted model, being very satisfied, rather satisfied, or not sure, compared to being dissatisfied with life, showed a lower risk of ASCVD: HR (95% CI) = 0.55 (0.41, 0.74), 0.67 (0.50, 0.89), and 0.57 (0.36, 0.88), respectively (p-trend < 0.001). The associations remained consistent after adjusting for stress and unfortunate events: HR (95% CI) = 0.57 (0.42, 0.77), 0.68 (0.50, 0.91), and 0.54 (0.35, 0.84), respectively (p-trend < 0.001). The results did not vary between cerebral infarction and CHD: HR (95% CI) for being very satisfied with life = 0.58 (0.37, 0.91) and 0.55 (0.36, 0.84), respectively. Conclusion: Life satisfaction was inversely associated with the risk of ASCVD in the investigated general Japanese population.

Atherosclerosis is a basic pathological characteristic of many cardiovascular diseases, and if not effectively treated, patients with such disease may progress to atherosclerotic cardiovascular diseases (ASCVDs) and even heart failure. The level of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) is significantly higher in patients with ASCVDs than in the healthy population, suggesting that it may be a promising new target for the treatment of ASCVDs. PCSK9 produced by the liver and released into circulation inhibits the clearance of plasma low-density lipoprotein-cholesterol (LDL-C), mainly by downregulating the level of LDL-C receptor (LDLR) on the surface of hepatocytes, leading to upregulated LDL-C in plasma. Numerous studies have revealed that PCSK9 may cause poor prognosis of ASCVDs by activating the inflammatory response and promoting the process of thrombosis and cell death independent of its lipid-regulatory function, yet the underlying mechanisms still need to be further clarified. In patients with ASCVDs who are intolerant to statins or whose plasma LDL-C levels fail to descend to the target value after treatment with high-dose statins, PCSK9 inhibitors often improve their clinical outcomes. Here, we summarize the biological characteristics and functional mechanisms of PCSK9, highlighting its immunoregulatory function. We also discuss the effects of PCSK9 on common ASCVDs.

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. [ABSTRACT FROM AUTHOR]

Background: Postoperative atrial fibrillation (POAF) is the most common complication after surgery for atherosclerotic cardiovascular disease (ASCVD) and leads to extended hospital stays and increased mortality. Myeloperoxidase (MPO) in postoperative pericardial drainage fluid is associated with an increased risk of POAF; however, the correlations between MPO in intraoperative pericardial fluid and POAF remain largely unknown. The aim of the study was to evaluate whether MPO is associated with POAF. Methods: A total of 97 patients with no history of atrial arrhythmia who had undergone coronary artery bypass surgery (CABG) were identified. We prospectively measured the levels of MPO in intraoperative pericardial fluid and blood using the human magnetic Luminex assay. Then, the occurrence of atrial fibrillation was continuously observed by postoperative ECG and telemetry strips until discharge. Results: Our data showed that POAF occurred in 24 of 97 patients (24.74%). MPO levels in blood were higher in the POAF group than the SR group (p = 0.064). Patients with POAF had significantly higher intraoperative pericardial fluid MPO levels than patients who remained in SR (p = 0.021). There was no significant correlation between pericardial fluid MPO levels and blood MPO levels (r = −0.47, p = 0.770). In a multivariable logistic regression model, pericardial fluid MPO levels were significantly associated with a higher risk of POAF (odds ratio = 1.016, 95% confidence interval, 1.001–1.031; p = 0.031). Conclusions: Higher intraoperative pericardial fluid MPO levels are linked with POAF in patients undergoing CABG. This finding provides insight into a possible mechanism of MPO in pericardial fluid increase susceptibility to developing POAF in patients undergoing CABG. [ABSTRACT FROM AUTHOR]

Choline has been shown to exert atherogenic effects in Apoe −/− and Ldlr −/− mice, related to its conversion by gut bacteria into trimethylamine (TMA) that is converted by the liver into the proinflammatory metabolite trimethylamine-N-oxide (TMAO). Since butyrate beneficially modulates the gut microbiota and has anti-inflammatory and antiatherogenic properties, the aim of the present study was to investigate whether butyrate can alleviate choline-induced atherosclerosis. To this end, we used APOE*3-Leiden.CETP mice, a well-established atherosclerosis-prone model with human-like lipoprotein metabolism. Female APOE*3-Leiden.CETP mice were fed an atherogenic diet alone or supplemented with choline, butyrate or their combination for 16 weeks. Interestingly, choline protected against fat mass gain, increased the abundance of anti-inflammatory gut microbes, and increased the expression of gut microbial genes involved in TMA and TMAO degradation. Butyrate similarly attenuated fat mass gain and beneficially modulated the gut microbiome, as shown by increased abundance of anti-inflammatory and short chain fatty acid-producing microbes, and inhibited expression of gut microbial genes involved in lipopolysaccharide synthesis. Both choline and butyrate upregulated hepatic expression of flavin-containing monooxygenases, and their combination resulted in highest circulating TMAO levels. Nonetheless, choline, butyrate and their combination did not influence atherosclerosis development, and TMAO levels were not associated with atherosclerotic lesion size. While choline and butyrate have been reported to oppositely modulate atherosclerosis development in Apoe −/− and Ldlr −/− mice as related to changes in the gut microbiota, both dietary constituents did not affect atherosclerosis development while beneficially modulating the gut microbiome in APOE*3-Leiden.CETP mice. [Display omitted] • Choline does not aggravate atherosclerosis development in APOE*3-Leiden.CETP mice. • Co-administration of choline and butyrate increases plasma trimethylamine-N-oxide (TMAO) levels. • Plasma TMAO levels do not associate with atherosclerotic lesion size. [ABSTRACT FROM AUTHOR]

Concerns regarding adverse events associated with the use of acid suppressants have increased. However, the impact of proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs) on the risk of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to estimate the risk of ASCVD in association with the use of PPIs and H2RAs. This prospective cohort study included participants without cardiovascular diseases or anti-hypertensive treatment at baseline (2006–2010) in the UK Biobank. The outcomes were ASCVD and each subtype (coronary artery disease, myocardial infarction, peripheral artery disease, and ischemic stroke). The association was estimated by Cox proportional-hazards models. Among 316,730 individuals (aged 50–88 years), during a median of 12.5 years of follow-up, we documented 13,503 (4.3%) incident ASCVD. Regular PPIs use was associated with a higher risk of ASCVD (HR: 1.16, 95% CI: 1.09–1.23) and every subtype of ASCVD. Among each type of PPIs, omeprazole (HR: 1.19, 95% CI: 1.11–1.28), lansoprazole (HR: 1.11, 95% CI: 1.02–1.22), and pantoprazole (HR: 1.40, 95% CI: 1.00–1.97) were associated with a higher risk of ASCVD. Stratification analysis showed that PPIs use was associated with a higher risk of ASCVD among individuals without indications of medications for PPIs. In addition, use of H2RAs was not related to the risk of ASCVD (HR: 0.97, 95% CI: 0.85–1.11). PPIs were associated with increased risk of ASCVD, particularly amongst participants without indications for medication. Our findings are of important practical significance and suggest that clinicians should be cautious in prophylactic use of PPIs. [Display omitted] • Evidence of association between proton pump inhibitors (PPIs) and atherosclerotic cardiovascular disease (ASCVD) is lacking. • PPI use was related to a higher risk of ASCVD. • Histamine‐2 receptor antagonists (H2RAs) use was not related to the risk of ASCVD. • Effect of different types of PPIs on the risk of ASCVD was various. • Higher ASCVD risks were observed among PPI users without indications for medication. [ABSTRACT FROM AUTHOR]

Chlamydia pneumoniae is the etiologic agent of respiratory tract infections in humans, including community-acquired pneumonia, and has been associated with atherosclerotic cardiovascular diseases. The present systematic review of reviews aimed at answering important questions on the involvement of C. pneumoniae in the pathogenesis of atherosclerosis, its cellular and molecular mechanisms, and whether there is evidence of a causal relationship. The databases PubMed/Medline, Scopus, and Web of Science were searched for all review articles published from 2003 to the end of 2023. A total of 27 reviews, systematic reviews, and systematic reviews with metanalysis were included. Overall, current evidence suggests that C. pneumoniae is a biologically plausible candidate for the causation of atherosclerosis, albeit not all the 4 Koch postulates are fulfilled; oxidative stress and inflammation are the most likely pathogenic mechanisms mediated by C. pneumoniae. However, it is still unclear how the persistent form, responsible for chronic inflammation, fits into this etiopathogenetic scenario. In the future, the newly-designed transformation systems for the genomic manipulation of C. pneumoniae will surely help expand our knowledge on the role of this pathogen in atherogenesis.

Abstract Background The treatment effects on hospitalization for heart failure (hHF) from sodium-glucose cotransporter 2 (SGLT2) inhibitors may vary among type 2 diabetes (T2D) patients depending on whether or not they have established atherosclerotic cardiovascular diseases (ASCVD). We aimed to examine differences in hHF outcomes after dapagliflozin or empagliflozin use between T2D patients with and without a history of established ASCVD. Methods We conducted a retrospective multi-institutional cohort study in Taiwan. We included T2D patients newly receiving dapagliflozin or empagliflozin during 2016–2019, and followed them up until December 31, 2020. We implemented 1:1 propensity score matching to create homogenous groups for comparisons. We generated Cox proportional hazard models to compare the risk of hHF between dapagliflozin and empagliflozin (reference group). We included interaction terms of SGLT2 inhibitor and ASCVD history in the regression models to examine effect modification by ASCVD. Results We included a total cohort of 9,586 dapagliflozin new users and 9,586 matched empagliflozin new users. The overall hHF risks were similar for dapagliflozin and empagliflozin (HR: 0.90, 95% CI 0.74–1.09). However, differential hHF risks between dapagliflozin and empagliflozin were observed only in the subgroup without ASCVD (HR: 0.67, 95% CI 0.49–0.90), while not in the subgroup with ASCVD (HR: 1.12, 95% 0.87–1.45), and the p-value for examining interaction was 0.0097. Conclusion In this study, history of established ASCVD was associated with different hHF risks among SGLT2 inhibitors. For T2D patients without ASCVD, dapagliflozin may offer a more favorable hHF reduction effect, compared to empagliflozin, in clinical practice. Future prospective studies should be conducted to validate our findings.

Dysferlin (DYSF) has drawn much attention due to its involvement in dysferlinopathy and was reported to affect monocyte functions in recent studies. However, the role of DYSF in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVD) and the regulation mechanism of DYSF expression have not been fully studied. In this study, Gene Expression Omnibus (GEO) database and epigenome-wide association study (EWAS) literatures were searched to find the DNA methylation-driven genes (including DYSF) of ASCVD. The hub genes related to DYSF were also identified through weighted correlation network analysis (WGCNA). Regulation of DYSF expression through its promoter methylation status was verified using peripheral blood leucocytes (PBLs) from ASCVD patients and normal controls, and experiments on THP1 cells and Apoe-/- mice. Similarly, the expressions of DYSF related hub genes, mainly contained SELL, STAT3 and TMX1, were also validated. DYSF functions were then evaluated by phagocytosis, transwell and adhesion assays in DYSF knock-down and overexpressed THP1 cells. The results showed that DYSF promoter hypermethylation up-regulated its expression in clinical samples, THP1 cells and Apoe-/- mice, confirming DYSF as a DNA methylation-driven gene. The combination of DYSF expression and methylation status in PBLs had a considerable prediction value for ASCVD. Besides, DYSF could enhance the phagocytosis, migration and adhesion ability of THP1 cells. Among DYSF related hub genes, SELL was proven to be the downstream target of DYSF by wet experiments. In conclusion, DYSF promoter hypermethylation upregulated its expression and promoted monocytes activation, which further participated in the pathogenesis of ASCVD. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) patients are at higher risk for nonalcoholic fatty liver disease (NAFLD), atherosclerotic cardiovascular diseases (ASCVD), and death. Given a lack of longitudinal data on patients with MetS in Southeast Asia, this study investigated the incidence of NAFLD and ASCVD and the all-cause mortality rate during a 10-year follow-up of Thai patients with MetS. Retrospective data were collected on 496 MetS patients with ultrasonography or transient elastography results. The patients had been followed up continuously by a university hospital between October 2011 and November 2021, and their mean age was 61.0 ± 10.9 years. Patients with secondary causes of hepatic steatosis were excluded. Cox proportional hazards regression models with time-varying covariates were adopted. During the 10-year follow-up, 17 patients (11.2%) developed NAFLD, and 27 (6.4%) developed ASCVD. The NAFLD and ASCVD incidence rates were 21.7 and 10.9 events per 1000 person years, respectively. The mortality rate was 14.2 deaths per 1000 person years. The prevalence of hypertension, dyslipidemia, ASCVD, NAFLD, advanced fibrosis, and cirrhosis at baseline was significantly higher in the nonsurvival group. The NAFLD incidence and mortality rate of patients with MetS were lower than those in previous studies. Intensive, holistic, and continuous care should be considered for better outcomes. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular diseases (ASCVD) are the leading cause of morbidity and mortality in Western societies. Statins are the first-choice therapy for dislipidemias and are considered the cornerstone of ASCVD. Statin-associated muscle symptoms are the main reason for dropout of this treatment. There is an urgent need to identify new biomarkers with discriminative precision for diagnosing intolerance to statins (SI) in patients. MicroRNAs (miRNAs) have emerged as evolutionarily conserved molecules that serve as reliable biomarkers and regulators of multiple cellular events in cardiovascular diseases. In the current study, we evaluated plasma miRNAs as potential biomarkers to discriminate between the SI vs. non-statin intolerant (NSI) population. It is a multicenter, prospective, case-control study. A total of 179 differentially expressed circulating miRNAs were screened in two cardiovascular risk patient cohorts (high and very high risk): (i) NSI (n = 10); (ii) SI (n = 10). Ten miRNAs were identified as being overexpressed in plasma and validated in the plasma of NSI (n = 45) and SI (n = 39). Let-7c-5p, let-7d-5p, let-7f-5p, miR-376a-3p and miR-376c-3p were overexpressed in the plasma of SI patients. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. We propose a three-miRNA predictive fingerprint (let-7f, miR-376a-3p and miR-376c-3p) and several clinical variables (non-HDLc and years of dyslipidemia) for SI discrimination; this model achieves sensitivity, specificity and area under the receiver operating characteristic curve (AUC) of 83.67%, 88.57 and 89.10, respectively. In clinical practice, this set of miRNAs combined with clinical variables may discriminate between SI vs. NSI subjects. This multiparametric model may arise as a potential diagnostic biomarker with clinical value. [ABSTRACT FROM AUTHOR]

Background: High-density lipoprotein cholesterol (HDL-C) is a well-known predictor of atherosclerotic cardiovascular diseases (ASCVD). We explored the relationships between HDL-C levels and 10-year major adverse cardiovascular events (MACE) and provided sexspecific upper reference limits for HDL-C levels. Methods: Based on the Korean National Health Insurance Sharing Service, we identified 5,703,897 subjects (women, 48%) with age =40 years, eligible HDL-C results, and no prior ASCVD in 2009. We investigated the distribution of 10-year MACE according to HDLC levels in 10 mg/dL (0.26 mmol/L) intervals and in three HDL-C groups (low: men <40 mg/dL [1.03 mmol/L], women <50 mg/dL [1.29 mmol/L]; high: between low and extremely high levels; and extremely high: >90 mg/dL [2.33 mmol/L]). Results: There were U-shaped relationships between HDL-C levels and 10-year MACE with later inflection in women than in men (nadir: 80-99 mg/dL [2.07-2.56 mmol/L] and 50-59 mg/dL [1.29-1.53 mmol/L], respectively). In men, the extremely high HDL-C group showed significantly higher 10-year MACE than the high group (28.1% vs. 24.6%, P < 0.0001). In women, the extremely high group showed the lowest 10-year MACE; if the extremely high starting point was raised to 130 mg/dL, it became similar to that in men and showed higher 10-year MACE than the high group (25.6% vs. 20.1%, P <0.0001). Conclusions: The 10-year MACE showed U-shaped relationships with HDL-C levels, and extremely high HDL-C level at 90 mg/dL (2.33 mmol/L) in men was corresponding in risk to 130 mg/dL (3.36 mmol/L) in women. [ABSTRACT FROM AUTHOR]

Defined as the total cholesterol minus high-density lipoprotein (HDL), non-HDL cholesterol has been increasingly acknowledged as a measure of risk estimation for developing atherosclerotic cardiovascular diseases (ASCVD). Comprising of apolipoprotein B100-containing cholesterols (very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL), and lipoprotein (a) (Lp(a))), and apolipoprotein B48-containing lipoproteins (chylomicrons and its remnants), elevated serum levels of non-HDL cholesterol in early adolescence has been strongly linked with the development of ASCVD in adulthood. This article reviews the evidence from longitudinal studies, which demonstrate the cumulative risk of ASCVD in relation to the elevated levels of non-HDL cholesterol earlier in life.