Natural phytochemicals as small-molecule proprotein convertase subtilisin/kexin type 9 inhibitors.

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.

Relationship of Non-Invasive Arterial Stiffness Parameters with 10-Year Atherosclerotic Cardiovascular Disease Risk Score in Post-COVID-19 Patients-The Results of a Cross-Sectional Study.

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.

Control of cardiometabolic risk factors and their association with carotid intima media thickness among patients with type 2 diabetes mellitus-single center experience in a developing country.

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.

Evolving Concepts of the SCORE System: Subtracting Cholesterol from Risk Estimation: A Way for a Healthy Longevity?

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.

Primary Prevention of Coronary and Other Cardiovascular Diseases: A Focused Review.

In 2022, the Japan Atherosclerosis Society (JAS) updated its prevention guidelines, the "Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2022" (JAS2022GL), expanding its scope from coronary artery disease (CAD) to atherosclerotic cardiovascular diseases (ASCVDs), including atherothrombotic stroke. The following year, the Japanese Circulation Society (JCS) updated its guidelines for primary prevention entitled "JCS 2023 Guideline on the Primary Prevention of Coronary Artery Disease" (JCS2023GL). Since those publications, scientific advancements in relevant fields have continued. This review article outlines the current recommendations provided by the guidelines, provides background information supporting these recommendations, introduces scientific findings subsequent to prior publications, and discusses future directions on select topics for the primary prevention of CVD. The topics covered in this review are traditional risk factors, including dyslipidemia and hypertension, the application of comprehensive risk stratification or risk scoring systems, patient-specific topics, salt and alcohol, and environmental factors. These topics were deliberate and selected by the authors, who were involved in the compilation of either or both JAS2022GL and JCS2023GL. This review not only emphasizes the pivotal role of continuously updated guidelines in shaping clinical practice but also stresses the urgent need for ongoing research to bridge existing knowledge and practice gaps.

Relationship between remnant cholesterol and short-term prognosis in acute ischemic stroke patients.

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.

The prevalence of cardiovascular diseases, chronic kidney disease, and obesity in patients with type 2 diabetes mellitus and the description of concurrent treatments: A two-center retrospective cross-sectional study in Saudi Arabia.

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.

Elevated remnant cholesterol and non-HDL cholesterol concentrations from real-world laboratory results: a cross-sectional study in Southeast Asians.

Introduction: Triglyceride-rich remnant lipoproteins (TRLs) are considered atherogenic due to the presence of remnant cholesterol, which is transported by apolipoprotein B. In clinical practice, the concentration of TRLs can be estimated by calculating remnant cholesterol or non-HDL cholesterol levels. Aim: This study aims to investigate the proportion of patients who have low LDL cholesterol (LDL-C) concentration but elevated remnant cholesterol concentration, stratified by the presence of hypertriglyceridaemia and ethnicity, using real-world hospital data. Our secondary aim is to investigate the proportion of patients with elevated non-HDL cholesterol levels using guideline-recommended goals. Methods: A 2-year retrospective study was conducted at a single centre, analyzing lipid blood tests of all patients, including directly measured LDL-C. Fasting for blood tests was not mandatory. Results: The study included a total of 21,605 consecutive patients with plasma lipid profiles analyzed in our hospital laboratory. The median age was 61 years. In patients with ASCVD (n = 14,704), 23.7% had an LDL-C level of <1.8 mmol/L, 11.3% had elevated remnant cholesterol concentrations at ≥0.65 mmol/L, and 48.8% were at the non-high-density lipoprotein cholesterol (non-HDL-C) goal (<2.6 mmol/L). Among patients diagnosed with atherosclerotic cardiovascular disease (ASCVD) with LDL-C levels of <1.8 mmol/L (n = 3,484), only 11.9% had high levels of remnant cholesterol, but 96% of the ASCVD patients also achieved the recommended non-HDL-C target of <2.6 mmol/L. When the LDL-C level was <1.8 mmol/L, the mean concentration of remnant cholesterol was 0.214 mmol/L when the triglyceride level was <1.7 mmol/L (n = 3,380), vs. 0.70 mmol/L when the triglyceride level was elevated (n = 724), p < 0.001. Among patients with a triglyceride level of ≥1.7 mmol/L and an LDL-C level of <.8 mmol/L, there were 254 patients with elevated remnant cholesterol concentration and 71 patients with suboptimal non-HDL levels. Malays had a higher mean remnant cholesterol concentration compared with both Chinese and Indians across all LDL-C levels, particularly in the presence of hypertriglyceridaemia. Conclusions: An elevated remnant cholesterol concentration of >0.65 mmol/L was present in 11% of all patients. The current guideline-recommended non-HDL-C goal, which uses a 0.8 mmol/L estimate of remnant cholesterol concentration, was achieved in >92% of patients, suggesting that it is unlikely to be clinically useful for the majority of our patient population except where there is concomitant hypertriglyceridaemia. Further studies are needed to establish the appropriate non-HDL-C goal or calculated remnant cholesterol concentration, paired with the LDL-C goal or otherwise, in a Southeast Asian population.

Comparing the association of two metabolic syndrome definitions, NCEP ATP III and IDF, with the risk of developing atherosclerotic cardiovascular disease: An analytical cross-sectional study.

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.

Genetic inhibition of angiopoietin-like protein-3, lipids, and cardiometabolic risk.

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.

High-Density Lipoprotein Subfractions Remodeling: A Critical Process for the Treatment of Atherosclerotic Cardiovascular Diseases.

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.

Cheese consumption on atherosclerosis, atherosclerotic cardiovascular diseases and its complications: A two-sample Mendelian randomization study.

BACKGROUND AND AIM: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

Sex-Specific Relationships between HDL-Cholesterol Levels and 10-Year Mortality in Individuals with Atherosclerotic Cardiovascular Disease: A Nationwide Cohort Study of South Koreans.

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.

Ruta colombiana del colesterol. Mesa redonda nacional sobre el colesterol en Colombia. Llamado a la acción / Colombian Cholesterol Roadmap. National roundtable on cholesterol in Colombia. Call to action

Resumen La enfermedad cardiovascular aterosclerótica (infarto de miocardio, accidente cerebrovascular y enfermedad arterial periférica) continúan siendo las causas más importantes de muerte prematura, discapacidad y gastos en atención médica en todo el mundo. Por lo tanto, evitar la acumulación vascular de lipoproteínas aterogénicas de colesterol es fundamental para prevenir los eventos cardiovasculares mayores. La actualización de la ruta colombiana del colesterol, Colombian Cholesterol Roadmap, es el resultado de la reunión realizada en el Congreso Nacional de Cardiología 2023, con el apoyo de la Federación Mundial del Corazón y una mesa de expertos clínicos, temáticos y representantes de diferentes instituciones relacionadas con el manejo de las dislipidemias en Colombia. Este documento tiene como objetivo ser un marco conceptual para describir los hallazgos y logros obtenidos a partir de las mesas de trabajo relacionadas con la identificación de barreras que limitan el tratamiento adecuado de la hipercolesterolemia en Colombia y las acciones que fueron propuestas ajustadas al contexto local que buscan desarrollar políticas nacionales y enfoques en nuestros sistemas de salud. Así mismo, confirma el compromiso del trabajo articulado intersectorial para lograr las metas en salud cardiovascular propuestas para el año 2030.

Abstract 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.

Life satisfaction and the risk of atherosclerotic cardiovascular disease in the general Japanese population: the Suita Study.

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.

Comorbidities in patients with chronic obstructive pulmonary disease: a comprehensive study.

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.

The Role of Neutrophil to Lymphocyte Ratio and its Common Clinical Outcomes Among Patients with Non-ST Elevation Acute Coronary Syndrome.

Objectives: To evaluate the admission neutrophil-to-lymphocyte ratio (NLR) for risk stratification for in-hospital outcomes and complications in non-ST-elevation acute coronary syndrome (non-ST-ACS) patients. Methods: We recruited consecutive patients with non-ST-ACS. The NLR was obtained and stratified as low, intermediate, and high-risk based on <3.0, 3.0-6.0, and >6.0, respectively. The new ST-T changes, arrhythmias, contrast-induced nephropathy (CIN), and mortality were recorded. Results: Median NLR was 3 [2.1-5.3] for 346 patients with 19.9% and 30.6% in high- and intermediate-risk group. New ST-T changes were observed in 3.5% (12) out of which 8, 3, and 1 patient in low, intermediate, and high-risk group (p = 0.424), respectively. Arrhythmias were observed in 5.8% (20) with 7, 5, and 8 patients in low, intermediate, and high-risk group (p = 0.067), respectively. CIN was observed in 4.9% (17) with 5, 5, and 7 in low, intermediate, and high-risk group (p = 0.064), respectively. In-hospital mortality was recorded in 1.4% (5) with 2 and 3 patients in high and low-risk group (p = 0.260), respectively. Conclusion: A significant number of non-ST-ACS patients fall in the high-risk category of NLR. Although, the association between NLR and in-hospital mortality and adverse events was not statistically significant but relatively higher rates of events were observed in high risk group.

A Jordanian Multidisciplinary Consensus Statement on the Management of Dyslipidemia.

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.

Apolipoprotein B compared with low-density lipoprotein cholesterol in the atherosclerotic cardiovascular diseases risk assessment.

The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and clinical evidence strongly supports the concept that the lipid content of the particles is secondary to the number of circulating atherogenic particles that are trapped within the arterial lumen. Since each low-density lipoproteins (LDL) particle contains one apoB molecule, as do intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, apoB level represents the total number of atherogenic lipoproteins, which is independent of particle density, and not affected by the heterogeneity of particle cholesterol content (clinically evaluated by LDL-cholesterol level). From this perspective, apoB is proposed as a better proxy to LDL-cholesterol for assessing atherosclerotic cardiovascular disease risk, especially in specific subgroups of patients, including subjects with diabetes mellitus, with multiple cardiometabolic risk factors (obesity, metabolic syndrome, insulin resistance, and hypertension) and with high triglyceride levels and very low LDL-cholesterol levels. Therefore, given the causal role of LDL-cholesterol in atherosclerotic cardiovascular disease (ASCVD) development, routine measurement of both LDL-cholesterol and apoB is of utmost importance to properly estimate global cardiovascular risk and to determine the 'residual' risk of ASCVD in patients receiving therapy, as well as to monitor therapeutic effectiveness.

[Acetylsalicylic acid in primary and secondary prevention of atherosclerotic cardiovascular disease]. / Primenenie atsetilsalitsilovoi kisloty pri pervichnoi i vtorichnoi profilaktike ateroskleroticheskikh serdechno-sosudistykh zabolevanii.

The article is devoted to an urgent problem - primary and secondary prevention of atherosclerotic cardiovascular diseases. Modern approaches to management tactics depending on age and the appointment of antiplatelet therapy with acetylsalicylic acid in low doses from 75 to 150 mg/day are presented. At the same time, the relatively high effectiveness of the use of ASA for primary prevention in men 40-69 years old without an increased risk of bleeding from the gastrointestinal tract is shown. Low doses of ASA provide little benefit in reducing the risk of CVD in people 40 years and older, when there is no history of CVD, but at the same time they are at increased risk of CVD.