Development Of Atherosclerotic Cardiovascular Disease Research Articles

The Effect of Retinoids in Vascular Smooth Muscle Cells: From Phenotyping Switching to Proliferation and Migration

Atherosclerosis, a term derived from the Greek “athero” (atheroma) and “sclerosis” (hardening), is a long-standing process that leads to the formation of atheromatous plaques in the arterial wall, contributing to the development of atherosclerotic cardiovascular disease. The proliferation and migration of vascular smooth muscle cells (VSMCs) and the switching of their phenotype play a crucial role in the whole process. Retinoic acid (RA), a natural derivative of vitamin A, has been used in the treatment of various inflammatory diseases and cell proliferation disorders. Numerous studies have demonstrated that RA has an important inhibitory effect on the proliferation, migration, and dedifferentiation of vascular smooth muscle cells, leading to a significant reduction in atherosclerotic lesions. In this review article, we explore the effects of RA on the pathogenesis of atherosclerosis, focusing on its regulatory action in VSMCs and its role in the phenotypic switching, proliferation, and migration of VSMCs. Despite the potential impact that RA may have on the process of atherosclerosis, further studies are required to examine its safety and efficacy in clinical practice.

Prevalence Of Metabolic Syndrome in Peri and Postmenopausal Women Aged 40- 65 Years in a Tertiary Care Centre

Metabolic syndrome (MetS) is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors—that appear to directly promote the development of atherosclerotic cardio-vascular disease (ASCVD). Menopausal transition with its incidental hormonal changes is considered to contribute to the development of MetS. This was a hospital based cross sectional descriptive study conducted in the Obstetrics and Gynaecology department of Nepal Medical College Teaching Hospital, Attarkhel, Gokarneshwor-8, Kathmandu, from the 1st of September 2023 till the 29th of February 2024 after clearance from the IRC (Ref. No: 56-080/081). Convenience sampling was used among women who fulfilled the inclusion criteria. The aim of the study was to determine the prevalence of MetS among the peri and postmenopausal women and to determine which component of the diagnostic criteria of MetS was more strongly associated with MetS in our population. Women were evaluated to have MetS using both the International Diabetes Federation (IDF) and the National Cholesterol Education Program- Adult Treatment Panel III (NCEP-ATPIII criteria). The prevalence of MetS by the IDF criteria was 54% among the perimenopausal women and 61% among the postmenopausal women. Similarly, the prevalence of MetS according to NCEP-ATPIII was 53.5% among the perimenopausal and 65% among the postmenopausal women. All the MetS diagnostic markers showed a strong correlation with MetS (p<0.001). The prevalence of MetS is high in our population by both the IDF and NCEP-ATP III criteria, being higher in the postmenopausal population, though not statistically significant.

Long-Term Evaluation of Lipid Profile Changes in Olympic Athletes.

Dyslipidemia is a major contributor to the development of atherosclerotic cardiovascular disease. Despite high level of physical activity, athletes are not immune from dyslipidemia, but longitudinal data on the variation of lipids are currently lacking. We sought to assess lipid profile changes over time in Olympic athletes practicing different sports disciplines (power, skills, endurance, and mixed). We enrolled 957 consecutive athletes evaluated from London 2012 to Beijing 2022 Olympic Games. Dyslipidemia was defined as low-density lipoprotein (LDL) ≥115mg/dl, high-density lipoprotein (HDL) <40mg/dl for males, or HDL <50mg/dl for females. Hypertriglyceridemia was defined as triglycerides >150mg/dl. At the follow-up, a variation of ±40mg/dl for LDL, ±6mg/dl for HDL, and ±50mg/dl for triglycerides was considered relevant. Athletes with follow-up <10months or taking lower lipid agents were excluded. Follow-up was completed in 717 athletes (74.9%), with a mean duration of 55.6months. Mean age was 27.2 ± 4.8years old, 54.6% were male (n = 392). Overall, 19.8% (n = 142) athletes were dyslipidemic at both blood tests, being older, practicing nonendurance sports, and predominantly male. In 69.3% (n = 129) of those with elevated LDL at t0, altered values were confirmed at follow-up, while the same occurred in 36.5% (n = 15) with hypo-HDL and 5.3% (n = 1) in those with elevated triglycerides. Weight and fat mass percentage modifications did not affect lipid profile variation. LDL hypercholesterolemia tends to persist over time especially among male, older, and nonendurance athletes. LDL hypercholesterolemia detection in athletes should prompt early preventive intervention to reduce the risk of future development of atherosclerotic disease.

The Association of the Cholesterol Efflux Capacity with the Paraoxonase 1 Q192R Genotype and the Paraoxonase Activity.

Paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and protects against atherosclerosis. However, the relationship between functional PON1 Q192R polymorphism, which is associated with the hydrolysis of paraoxon (POXase activity) and atherosclerotic cardiovascular disease (ASCVD), remains controversial. As the effect of PON1 Q192R polymorphism on the HDL function is unclear, we investigated the relationship between this polymorphism and the cholesterol efflux capacity (CEC), one of the biological functions of HDL, in association with the PON1 activity. The relationship between PON1 Q192R polymorphisms and CEC was investigated retrospectively in 150 subjects without ASCVD (50 with the PON1 Q/Q genotype, 50 with the Q/R genotype, and 50 with the R/R genotype) who participated in a health screening program. The POXase and arylesterase (AREase: hydrolysis of aromatic esters) activities were used as measures of the PON1 activity. The AREase activity was positively correlated with CEC independent of the HDL cholesterol levels. When stratified by the PON1 Q192R genotype, the POXase activity was also positively correlated with CEC independent of HDL cholesterol. PON1 Q192R R/R genotype carriers had a lower CEC than Q/Q or Q/R genotype carriers, despite having a higher POXase activity. Moreover, in a multiple regression analysis, the PON1 Q192R genotype was associated with the degree of CEC, independent of the HDL cholesterol and POXase activity. The PON1 Q192R R allele is associated with reduced CEC in Japanese people without ASCVD. Further studies on the impact of this association on the severity of atherosclerosis and ASCVD development are thus called for.

The prognostic role of remnant cholesterol in Asian menopausal women received percutaneous coronary intervention with acute coronary syndrome

BackgroundRemnant cholesterol (RC) exert a significant influence on atherosclerotic cardiovascular disease development. However, the prognostic implications of RC in menopausal women received percutaneous coronary intervention (PCI) who experiencing acute coronary syndrome (ACS) remain uncertain.MethodsRC was derived by subtracting the sum of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol from the total cholesterol. Kaplan-Meier survival and Cox regression analysis were employed for assessing the correlation between continuous RC levels and composite and individual adverse events in Q1-Q4 quartiles. Receiver operator characteristic (ROC) curves, derived from Cox regression, were employed for analyzing the relationship between RC and both composite and individual adverse events.Results1505 consecutive menopausal women who underwent PCI and diagnosed with ACS were included. Kaplan-Meier survival analysis demonstrated a progressive reduction in composite adverse event survival rates across the four groups, observed in both the general population and among diabetic individuals, as RC values increased (Log-rank P < 0.001). The analysis of multivariate Cox regression indicated RC remained independently associated with both composite and individual adverse events. ROC analysis showed that RC enhanced the area under the curve both in total and diabetic populations for composite adverse events.ConclusionAmong menopausal women diagnosed with ACS who underwent PCI, heightened levels of RC were found to be independently correlated with an increased occurrence of adverse events.

Atherosclerotic cardiovascular disease following a diagnosis of idiopathic inflammatory myopathy: analysis from a retrospective cohort in the TriNetX registry.

Idiopathic inflammatory myopathies (IIM) confer an increased risk of morbidity from atherosclerotic cardiovascular disease (ASCVD). While ASCVD risk has been studied in other countries, these results may not be applicable to patients with dermatomyositis (DM) and polymyositis (PM) in the United States. This retrospective analysis of a cohort of patients identified by ICD code from TriNetX investigated the incidence of ASCVD after International Classification of Disease (ICD) codes of DM, PM, dermatopolymyositis (DPM) or juvenile dermatomyositis (JDM). Patients were identified by entry of two ICD codes separated by at least 6months, according to their first diagnosis code; ASCVD was defined as first ICD code for myocardial infarction, ischemic stroke, transient ischemic attack, or peripheral arterial disease. Cox proportional hazards regression modeled time from first IIM ICD code to ASCVD event. A total of 35,554 patients were identified with the mean age at first IIM code of 54 and 26.1% were male. The most common comorbidity for all groups except JDM was hyperlipidemia (39.9%) though 79.2% of patients were on no cholesterol lowering medication. ASCVD occurred in 30.4% of patients with PM, 24.3% of patients with DM and 0.9% of patients with JDM. Patients with PM had a median time to event of 9.7years (95% Confidence interval (CI) 9.1, 10.7) and 14.3years (95% CI 12.6, 14.8) for DM. This study demonstrates that ASCVD is a comorbidity occurring after a median of 12.5years (95% CI 11.9, 13.6) in patients with IIM. ASCVD appears to be a long-term complication for IIM patients occurring in nearly a quarter of US patients without prior ASCVD with at least two ICD codes for IIM, with a median time to event of 12.5years. There appears to be a practice gap in the recognition and treatment of hyperlipidemia in these patients. Key Points • Hyperlipidemia was a common comorbidity identified in patients with IIM though most patients were not on cholesterol lowering medication. • Development of ASCVD appears to be a long-term complication for patients with IIM in the United States.

The Significance of Endothelial Dysfunction in Long COVID-19 for the Possible Future Pandemic of Chronic Kidney Disease and Cardiovascular Disease.

Various symptoms have been reported to persist beyond the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred to as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 are largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction is a strong candidate explaining the induction of long COVID-19. The angiotensin-converting enzyme 2 (ACE2), the entry receptor for SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for atherosclerotic cardiovascular disease (ASCVD) and a history of ASCVD raise the risk of severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with the development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in the development of ASCVD. We consider the influence of long COVID-19 on the development of chronic kidney disease (CKD) and ASCVD. Future assessments of the outcomes of long COVID-19 in patients resulting from therapeutic interventions that improve endothelial function may imply the significance of endothelial dysfunction in the development of long COVID-19.

HDL cholesterol efflux capacity and cholesterol loading capacity in long-term fasting: Evidence from a prospective, single-arm interventional study in healthy individuals

Background and aimsLong-term fasting (LF) is increasingly emerging as a non-pharmacological approach to modulate risk factors associated with the development of atherosclerotic cardiovascular diseases (ASCVD). However, protection from ASCVD is more tied to the functionality of high-density lipoprotein (HDL) than its plasma levels. Our prospective interventional study focuses on the functional properties of lipoproteins in modulating cholesterol homeostasis on peripheral cells and examines how LF may influence this and lipoprotein subclass composition. For that purpose, we investigated its impact on HDL-cholesterol efflux capacity (CEC), and on serum cholesterol loading capacity (CLC). MethodsForty healthy subjects (50 % females) underwent medically supervised 9-day fasting (250 kcal/day) in a specialised facility. Thirty-two subjects had a follow-up examination after one month of food reintroduction. ResultsLF was well tolerated and increased self-reported energy levels. Fasting reduced triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C). Very-low-density lipoprotein cholesterol (VLDL-C) and LDL3-C showed sustained reductions at follow-up. Only HDL-C, specifically HDL2-C levels, increased at follow-up. Total HDL-CEC decreased during LF and increased above baseline at follow-up. Fasting decreased ATP binding cassette (ABC)A1-mediated HDL-CEC whereas ABCG1-mediated HDL-CEC remained unaffected. Aqueous diffusion increased at follow up. LF decreased serum CLC and then returned to baseline levels. ConclusionsLF not only maintains lipoprotein functionality but also contributes to a favorable shift in the atherogenic risk profile, which persists even after food reintroduction. This further emphasizes the importance of considering HDL functionality alongside traditional lipid measurements to understand the potential for non-pharmacological interventions like LF to promote cardiovascular prevention and health. Trial registration numberNCT05031598.

Frequency of lipoprotein(a) testing and its levels in Pakistani population.

Lipoprotein(a) [Lp(a)] is a highly atherogenic particle identified as an independent risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). This study aimed to investigate the frequency of Lp(a) testing and the incidence of elevated Lp(a) levels in the Pakistani population. For this observational study, Lp(a) and lipid profile data from five years (June 2015 to October 2020) were acquired from the electronic patient records of a diagnostic laboratory with a countrywide network. The association of age and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL, and triglyceride (TG) levels with two thresholds for Lp(a), that is, <30 mg/dL and ≥30 mg/dL, was calculated using the Kruskal-Wallis test, while the association between Lp(a) levels and lipid variables was calculated using Spearman correlation. For five years, 1060 tests were conducted, averaging 212 tests per year. Of these, 37.2% showed Lp(a) levels above 30 mg/dL. No significant differences were observed in the results between males and females. However, younger individuals displayed significantly higher Lp(a) levels. Additionally, there was only a weak correlation between the Lp(a) levels and other lipid variables. Despite being recognized as a risk factor for ASCVD in the Pakistani population, only a small proportion of the large population underwent Lp(a) testing. Moreover, a significant proportion of the population exceeded this threshold.

DEFICIENCY OF VITAMIN D IN PATIENT WITH PRIMARY HYPOTHYROIDISM AND AS RELATED RISK FACTOR FOR CARDIOVASCULAR DISEASES

Hypothyroidism is believed to be associated with dyslipidemia and is considered a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD). Vitamin D, due to its steroid hormone action, retains cell function and controls the metabolism of lipids. Therefore, the present study was carried out to show the association of the risk factors of ASCVD. Cardiovascular disease (CVD) is caused by both clinical and subclinical hypothyroidism by disrupting healthy endothelial function by various mechanisms such as inflam- mation, triggering lipid disorders and oxidative stress. In the present study, a strong correlation was observed between increasing TSH and the parameters of lipid profile Hypothyroidism and hypovitaminosis D are known as inde-pendent risk factors for the development of cardiovascular diseases. Hypothyroidism and hypovitaminosis D are associated and correlated with total cholesterol, triglycerides, and low-density lipoprotein in Saudi patients. It is also recom- mended that vitamin D deficiency be checked in hypothyroid patients and that appropriate supplementation may be given if needed. Furthermore, for early detection and/or prediction of cardiovascular disease, screening of thyroid hormone and vitamin D levels should be undertaken at an early stage.

Associations of retinal microvascular alterations with diabetes mellitus: an OCTA-based cross-sectional study

BackgroundDiabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes.MethodsThe Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed.ResultsThis study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P < 0.001), longer axial length (AL, mm) (Beta = -0.13, 95%CI = -0.48 to -0.25, P = 0.002), and elevated heart rate (Beta = -0.10, 95%CI = -0.14 to -0.19, P = 0.014), after adjusting for younger age (Beta = -0.18, 95%CI = -0.24 to -0.35, P < 0.001), consistent with VD of the whole macular region. A higher FPG level was significantly correlated with lower SCP density of both PD and VD in the macular and parafoveal region (P < 0.05 for all), as well as increased systolic blood pressure and low-density lipoprotein cholesterol concentration (P < 0.01 for all).ConclusionsIn this large-sample cross-sectional study, OCTA evaluation revealed that high prevalence of diabetes and elevated FPG levels were correlated with reduced retinal VD and PD. Hypertension and hyperlipidemia are important risk factors for the development of atherosclerotic cardiovascular disease but have no significant effect on retinal microvascular abnormalities.

Gender-related and PUFA-related differences in lipoprotein-associated phospholipase A2 levels in patients with type 2 diabetes and atherosclerotic cardiovascular disease.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) may play an important role in the development of atherosclerotic cardiovascular disease (ASCVD). Increased plasma levels of Lp-PLA2 may predict future cardiovascular (CV) events in type 2 diabetes (T2D). The potential beneficial effects of polyunsaturated fatty acids (PUFA) on ASCVD have been widely investigated. However, the impact of different PUFA concentrations on Lp-PLA2 remains uncertain. We sought to determine the intergender differences in a population of patients with both T2D and ASCVD regarding Lp-PLA2 mass and the association between Lp-PLA2 mass and plasma levels of PUFA. In this cross-sectional study, we measured the Lp-PLA2 mass, PUFA concentrations and inflammatory markers in 74 patients (49 males and 25 females) with T2D and ASCVD. In this very high-risk population, males had, on average, 33.6% higher levels of Lp-PLA2 than females. The Lp-PLA2 mass was positively associated with interleukin 6 (IL-6) (r = 0.27, p = 0.019), creatinine (r = 0.29, p = 0.03) and triglyceride levels (r = 0.41, p = 0.002). Additionally, male gender and higher levels of triglycerides, leptin, oxidized low-density lipoprotein (oxLDL), and intercellular adhesion molecule 1 (ICAM-1) were independent predictors for an increased Lp-PLA2. Moreover, arachidonic acid (AA) negatively correlated with Lp-PLA2 (r = -0.26, p = 0.024), which was especially apparent in the female subgroup. In the population of patients with ASCVD and T2D, males present with higher plasma levels of Lp-PLA2 than females. Additionally, higher plasma levels of AA were associated with lower Lp-PLA2 levels. Our findings support the utilization of Lp-PLA2 as a novel biomarker in ASCVD risk assessment in a very high CV risk population.

Diagnosis and treatment of dyslipidemia in children and adolescents

Background: Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality worldwide, including in South Korea. Dyslipidemia is an independent risk factor for the development of atherosclerotic cardiovascular diseases. There is strong evidence that atherosclerosis begins early in life and that elevated lipid levels in childhood predict elevated lipid levels into adulthood.Current Concepts: A universal approach for cholesterol screening in all children is recommended. Lipid profiles should be studied for all children aged 9 to 11 years and then for those aged 17 to 21 years, as cholesterol levels may vary after puberty. The non-fasting lipid profile can be as useful in detecting severe genetic dyslipidemias as the fasting lipid profile and thus can be used as a first-line screening in children. The initial treatment for dyslipidemia in a child always begins with a 6-month trial of lifestyle modifications, such as improvements in dietary and physical activity patterns. Statins are as effective in children as in adults and can lower low-density lipoprotein cholesterol levels by up to 50%. Therefore, they are considered first-line therapy for children who meet the criteria for pharmacological therapy.Discussion and Conclusion: Statins and non-statin lipid-lowering agents can lower cholesterol levels with minimal adverse effects in children and adolescents with hypercholesterolemia. However, limited data is currently available on the long-term safety and efficacy of lipid-lowering agents in the pediatric population. Furthermore, non-statin lipid-lowering agents are used far less frequently in children. Therefore, further long-term safety and efficacy studies on lipid-lowering agents in pediatric populations and clinical trials with non-statin lipid-lowering agents are required.

Exosomes in Atherosclerosis: Role in the Pathogenesis and Targets for Therapy.

Atherosclerotic cardiovascular disease (ASCVD) is an advanced chronic inflammatory disease and the leading cause of death worldwide. The pathological development of ASCVD begins with atherosclerosis, characterised by a pathological remodelling of the arterial wall, lipid accumulation and build-up of atheromatous plaque. As the disease advances, it narrows the vascular lumen and limits the blood, leading to ischaemic necrosis in coronary arteries. Exosomes are nano-sized lipid vesicles of different origins that can carry many bioactive molecules from their parental cells, thus playing an important role in intercellular communication. The roles of exosomes in atherosclerosis have recently been intensively studied, advancing our understanding of the underlying molecular mechanisms. In this review, we briefly introduce exosome biology and then focus on the roles of exosomes of different cellular origins in atherosclerosis development and progression, functional significance of their cargoes and physiological impact on recipient cells. Studies have demonstrated that exosomes originating from endothelial cells, vascular smooth muscle cells, macrophages, dendritic cells, platelets, stem cells, adipose tissue and other sources play an important role in the atherosclerosis development and progression by affecting cholesterol transport, inflammatory, apoptotic and other aspects of the recipient cells' metabolism. MicroRNAs are considered the most significant type of bioactive molecules transported by exosomes and involved in ASCVD development. Finally, we review the current achievements and limitations associated with the use of exosomes for the diagnosis and treatment of ASCVD.

Статеві та клініко-інструментальні паралелі рівнів ліпопротеїн(а) в пацієнтів з дуже високим серцево-судинним ризиком

In recent years it has been established that elevated levels of Lp(a) are an independent genetic risk factor for the development of atherosclerotic cardiovascular diseases and aortic stenosis, however, issues of gender and age characteristics remain controversial.The aim of study was to analyze the gender characteristics of the relationship between Lp(a) levels and atherogenic changes in the lipid spectrum of the blood, clinical and instrumental characteristics, taking into account damage to the aortic valve and the results of coronary angiography in patients with stable coronary heart disease. Materials and methods. The 106 patients with chronic coronary heart disease (CAD) were examined. The average age of the subjects was 55.00±1.0 years (95% CI 51.11-58.89), among them: 78 men and 28 women.The entire cohort of patients was divided depending on the Lp(a) levels: 1group (n=58) with a Lp(a) level less than 50 mg/dl; 2 group (n=20) with Lp(a) level 50-100 mg/dl; 3 group (n=8) with Lp(a) level 101-150 mg/dl and 4 group (n=20) with Lp(a) level more than 150 mg/dl.Research methods included: 1. General clinical examination; 2. Laboratory characteristics of lipid (with determination of Lp(a)) and carbohydrate metabolism, as well as standard biochemical parameters; 3. Instrumental examination (electrocardiography, echocardiography, ultrasound peripheral vessels examination, coronary angiography); 4. Mathematical and statistical processing of the results obtained.Results and conclusions. In patients with CAD verified by clinical-instrumental and coronary angiographic criteria, it is noted that Lp(a) levels in women are on average significantly higher (P&lt; 0.05) than in men and increase with the onset of menopause.Close correlations have not been recorded between Lp(a) in mg/dL and total cholesterol, LDL cholesterol and non-HDL cholesterol, as well as the concentrations of glucose, glycosylated hemoglobin, serum creatinine, and the concentration of thyroid-stimulating hormone (TSH).Determined that in patients with documented atherosclerotic lesions of the coronary arteries against the Lp(a) levels above 100 mg/dl, there is a greater need for coronary revascularization. A close relationship is observed between the increase in Lp(a) levels and the percentage of detection of aortic stenosis, which confirms the pathogenetic role of this lipoprotein in the formation of this acquired aortic valve disease.

The Impact of the Apolipoprotein E Genotype on Cardiovascular Disease and Cognitive Disorders.

Apolipoprotein E (ApoE) plays a critical role in cholesterol transport and protection against the development of atherosclerotic cardiovascular disease (ASCVD). Humans have 3 prevalent isoforms of ApoE: apolipoprotein E2 (ApoE2), apolipoprotein E3 (ApoE3), and apolipoprotein E4 (ApoE4). The E4 allele has been associated with higher ASCVD risk. While E4 patients do have higher cholesterol levels, they do not have enough to account for the substantially elevated ASCVD risk relative to E2 and E3 patients. ASCVD risk calculators would underestimate the true effect of E4 if the difference was caused entirely by a difference in cholesterol level. This article reviews the function of ApoE in atherosclerosis, and how each isoform functions differently. We review what is known about the molecular mechanisms through which ApoE prevents endothelial dysfunction and damage, how ApoE stimulates macrophage efflux of cholesterol from atherogenic lesions, and the ways in which ApoE decreases inflammation throughout atherosclerosis. The impact of ApoE on Alzheimer's disease and a discussion of why it is possibly unrelated to ASCVD prevention are included. Clinical applications to hyperlipidemia management and ASCVD prevention in specific patient populations are discussed.

C-reactive protein, cardiovascular issues of an acute-phase protein: an update for theclinician

Inflammation is an important pathogenic factor for the development of atherosclerotic cardiovascular disease. Currently, the most frequently used biomarker reflecting systemic inflammation is C-reactive protein (CRP), an acute-phase protein produced primarily by hepatocytes under the influence of interleukin-6, interleukin-1 beta, and tumor necrosis factor. Growing evidence from epidemiological studies has shown a robust association between elevated serum or plasma CRP concentrations and the incidence of a first cardiovascular adverse event (including acute myocardial infarction, ischemic stroke, and sudden cardiac death) in the general population, as well as recurrence of major adverse cardiovascular events among patients with established disease. The additive value that CRP measurement gives to traditional risk factors is reflected in novel cardiovascular risk calculators and in current intervention regimens, which already consider CRP as a target therapeutic. However, the variations in CRP levels, that depend on sex, ethnicity, hormonal status, and some peculiarities of the measurement assays, must be taken into consideration when deciding to implement CRP as a useful biomarker in the study and treatment of atherosclerotic cardiovascular disease. This review aims to offer an updated vision of the importance of measuring CRP levels as a biomarker of cardiovascular risk beyond the traditional factors that estimate the risk of atherosclerotic disease.

Obesity in the 21st Century. Prevalence, Phenotypes, Course Variants and Consequences

The review article examines the issues of obesity regarding its prevalence, phenotypes, course and consequences. The anatomical, physiological and functional features of adipose tissue are discussed. The “Discussion” section presents the authors’ own clinical observations on therapeutic and surgical issues in the treatment of obesity. Currently, adipose tissue is divided into white, brown and beige. White and brown adipose tissue can turn into each other through the beige adipose tissue stage. The volume and activity of brown adipose tissue require greater expenditure in the metabolism of oxygen molecules and are more pronounced in women. The components of the extracellular matrix of adipose tissue are collagen types I, III, V, VI. The collagen structure of adipose tissue varies depending on the location, volume and size of fat, age, gender, functional state of the kidneys, thyroid gland, nature of food, energy expenditure and sleep patterns. With intense work and cold exposure, the hormone irisin is formed in skeletal muscles, which promotes the transformation of white adipose tissue into brown or beige, helps reduce body weight in obesity, and has a beneficial effect on the course of type 2 diabetes mellitus and associated diseases. Traditionally, obese individuals are divided into metabolically healthy obesity and metabolically unhealthy obesity based on the degree of metabolic disorders. In visceral fat, lipolysis occurs with high intensity, which supports the development of inflammation. In obesity, decreased expression of adiponectin accelerates the development of atherosclerotic cardiovascular diseases. As body weight increases, visceral adipose tissue acquires an inflammatory phenotype, manifested by increased expression of cytokines (interleukin-6, interleukin-1, interleukin-17, tumor necrosis factor-alpha), hyperactivation of the tissue renin-angiotensin-aldosterone system, as well as excessive cell infiltration immune system (leukocytes, neutrophils, T-lymphocytes, monocytes, macrophages). During inflammation in adipose tissue, inflammatory (M1) and atherogenic (M4) phenotypes of macrophages dominate. In morbid obesity, the number of macrophages in adipose tissue can reach up to 50% of all cells.

EXPRESS: Effectiveness of HMG-CoA reductase inhibitors on inflammation and metabolic markers in the US-Mexico border Hispanic population.

HMG-CoA reductase inhibitors (statins) are commonly used for dyslipidemia management to reduce the risk of cardiovascular disease (CVD). High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical exam at a family medicine clinic between January 1, 2021, and December 31, 2021. Effect size with a 95% confidence interval (CI) was estimated using adjusted regression analyses. Among 150 patients, 52 (34.67%) received statins. Patients who received statins had significantly reduced median hs-CRP (1.9 vs. 3.2, p=0.007), mean low-density lipoprotein (LDL-C) (101.18 vs. 124.6, p<0.001), and total cholesterol (172.6 vs. 194.5, p<0.001) concentrations compared to those who did not receive statins. In the propensity-scores matched analysis, lower concentrations of log-transformed hs-CRP (regression coefficient [RC], -0.48; 95%CI: -0.89, -0.07), LDL-C (RC, -19.57; 95%CI: -33.04, -6.1), and total cholesterol (RC, -23.47; 95%CI: -38.96, -7.98) were associated with statin use. In addition, hepatic steatosis (adjusted relative risk [aRR]=0.25; 95%CI: 0.08, 0.78, p= 0.017) was significantly lower among patients with the use of statins. Our study suggests that HMG-CoA reductase inhibitors may help reduce inflammation among Hispanic patients with dyslipidemia and hypertension. These findings have useful implications for preventing risk and disparities associated with cardiovascular and other inflammatory-induced diseases among the fastest-growing US Hispanic minorities.

Cardiovascular prevention in diabetes mellitus. Is it appropriate to speak of moderate or intermediate risk?

Diabetes, especially type 2 (DM2), is considered a risk situation for atherosclerotic cardiovascular disease (ASCVD). Subjects with DM2 have a mortality rate due to ASCVD three times higher than that found in the general population, attributed to hyperglycemia and the frequent association of other cardiovascular risk factors, such as atherogenic dyslipidemia.Numerous scientific societies have established a risk classification for ASCVD in diabetes based on 3 degrees (moderate, high and very high). The objectives of dyslipidemia control are clearly defined and accepted, and vary depending on the previously established cardiovascular risk.In moderate or intermediate risk, the guidelines propose a less aggressive intervention, maintaining LDL-C levels <100mg/dL and NO-HDL-C levels <130mg/dL, and waiting 10 years until reaching the high-risk category to initiate more aggressive treatment. However, during the decade of follow-up recommended in the guidelines, cholesterol deposition in the arterial wall increases, facilitating the development of an unstable and inflammatory atheromatous plaque, and the development of ASCVD. Alternatively, diabetes could be considered from the outset to be a high-risk situation and the goal should be LDL-C <70mg/dL. Furthermore, maintaining LDL-C levels <70mg/dL contributes to reducing and stabilizing atheromatous plaque, avoiding or reducing mortality episodes due to ASCVD during those years of diabetes evolution.Should we maintain the proposed objectives in subjects with diabetes and moderate risk for a decade until reaching the high cardiovascular risk phase or, on the contrary, should we adopt a more aggressive stance from the beginning seeking to reduce cardiovascular risk in the majority of patients with diabetes? Is it better to wait or prevent with effective therapeutic measures from the first moment?