Development Of Atherosclerotic Disease Research Articles

Novel Plasma Biomarkers Associated with Future Peripheral Atherosclerotic Disease and Abdominal Aortic Aneurysm—Insights from Contemporary Prospective Studies from the Malmö Diet and Cancer Study

Introduction: The potential utility of inflammatory and hemodynamic plasma biomarkers for the prediction of incident lower extremity arterial disease (LEAD), carotid artery stenosis (CAS), isolated atherosclerotic disease without concomitant abdominal aortic aneurysm (AAA), and isolated AAA without concomitant atherosclerotic disease has not yet been integrated in clinical practice. The main objective of this prospective study was to find predictive plasma biomarkers for cardiovascular disease and to evaluate differences in plasma biomarker profiles between asymptomatic and symptomatic CAS, as well as between isolated atherosclerotic disease and isolated AAA. Methods: Blood samples collected at baseline from participants in the prospective Malmö Diet and Cancer study (MDCS) cardiovascular cohort (n = 5550 middle-aged individuals; baseline 1991–1994) were used for plasma biomarker analysis. Validation of each incident cardiovascular diagnosis was performed by random sampling. Cox regression analysis was used to calculate hazard ratios (HRs) per one standard deviation increment of each respective log-transformed plasma biomarker with 95% confidence intervals (CI). Results: Adjusted lipoprotein-associated phospholipase A2 (Lp-PLA2) activity (HR 1.33; CI 1.17–1.52) and mass (HR 1.20; CI 1.05–1.37), C-reactive protein (CRP) (HR 1.55; CI 1.36–1.76), copeptin (HR 1.46; CI 1.19–1.80), N-terminal pro-B-type natriuretic peptide (N-BNP) (HR 1.28; 1.11–1.48), and cystatin C (HR 1.19; 95% 1.10–1.29) were associated with incident symptomatic LEAD. Adjusted N-BNP (HR 1.59; CI 1.20–2.11), mid-regional proadrenomedullin (HR 1.40; CI 1.13–1.73), cystatin C (HR 1.21; CI 1.02–1.43), and CRP (HR 1.53; CI 1.13–1.73) were associated with incident symptomatic but not asymptomatic CAS. Adjusted HR was higher for Lp-PLA2 (mass) for incident isolated AAA compared to for isolated atherosclerotic disease. Conclusions: Plasma biomarker profile data support that subclinical vascular inflammation and cardiovascular stress seem to be relevant for the development of atherosclerotic disease and AAA.

Therapeutic Avenues to Modulate B-Cell Function in Patients With Cardiovascular Disease.

The adaptive immune system plays an important role in the development and progression of atherosclerotic cardiovascular disease. B cells can have both proatherogenic and atheroprotective roles, making treatments aimed at modulating B cells important therapeutic targets. The innate-like B-cell response is generally considered atheroprotective, while the adaptive response is associated with mixed consequences for atherosclerosis. Additionally, interactions of B cells with components of the adaptive and innate immune system, including T cells and complement, also represent key points for therapeutic regulation. In this review, we discuss therapeutic approaches based on B-cell depletion, modulation of B-cell survival, manipulation of both the antibody-dependent and antibody-independent B-cell response, and emerging immunization techniques.

The Impact of Dietary Carbohydrates on Inflammation-Related Cardiovascular Disease Risk: The ATTICA Study (2002-2022).

The aim of this study was to evaluate the potential interplay between a carbohydrate diet and inflammation in atherosclerotic cardiovascular disease (ASCVD) development. ATTICA is a prospective observational study of 3042 adults free of cardiovascular disease (CVD) who were recruited in 2002 and followed for 20 years. Baseline data on carbohydrate intake and inflammatory biomarker levels were collected. Participants were stratified by carbohydrate intake (low vs. high: </> 190 g/day) and carbohydrate quality. At the 20-year follow-up in 2022, 1988 participants had complete data for CVD assessment. The overall quantity and quality of carbohydrate intake did not show a significant association with CVD incidence; inflammatory markers were positively correlated with an increased risk of CVD (p-values < 0.05). Chronic systemic inflammation seems to affect the CVD risk of participants who had a higher carbohydrate intake more substantially, as compared to those with low intake. Additionally, individuals with higher high carbohydrate/low fiber intake experienced a higher risk of inflammation-related CVD, compared to those with high carbohydrate/high fiber intake. The presented findings revealed that the effect of inflammation markers on the CVD risk is influenced both by the amount and quality of carbohydrate intake, irrespective of overall dietary habits and clinical and lifestyle characteristics.

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.

Lipoprotein (a) concentration as a risk factor for ischaemic stroke and its subtypes.

To investigate the relationship between serum lipoprotein (a) [Lp(a)] concentration and the risk of ischaemic stroke (IS) and its subtypes. Lp(a) plays a role in atherogenic, pro-thrombotic, and antifibrinolytic processes. Elevated plasma Lp(a) is a strong independent risk factor for the development and progression of atherosclerotic disease. The association between lipoproteins and IS is more complex than that reported for cardiovascular diseases, with inconsistent and contradictory results from epidemiological studies. 231 patients with acute IS (defined as cases) and 163 age- and sex-matched control subjects were included in this prospective case-control study. Demographic and clinical variables (i.e. age, sex, smoking, presence of chronic diseases and concomitant medication) and laboratory data (i.e. concentrations of total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, Lp(a), apolipoprotein A1, apolipoprotein B) were recorded. The mean age and the percentage of men did not significantly differ between groups. Compared to controls, there was a significantly higher percentage of cases reported with concomitant diseases: diabetes mellitus, myocardial infarction, ischaemic heart disease, peripheral arterial disease, and atrial fibrillation. The study showed a significantly higher serum Lp(a) concentration in cases than in control subjects (81.81 nmol/L [c.32.7 mg/dL] vs. 59.75 nmol/L [c.23.9 mg/dL]; p = 0.036) and found an association between Lp(a) levels stratified by quartiles and the risk for ischaemic stroke (Q1 [Lp(a) < 13 nmol/L] vs. Q4 [Lp(a) > 117 nmol/L]: OR 2.23; 95% CI 1.23-4.03; p = 0.008). A subgroup analysis based on the TOAST classification of IS also showed a significant association between Lp(a) value of more than 75 nmol/L (30 mg/dL) and the risk of large-artery atherosclerosis stroke compared to the controls (OR 2.4; 95% CI 1.39-3.93; p = 0.001), as well as a statistically non-significant association with other subtypes of IS. The influence of Lp(a) remained significant even after adjusting for established risk factors for IS (OR 1.99; 95% CI 1.05-3.76; p = 0.04; respectively for the large-artery atherosclerotic subtype: OR 2.54; 95% CI 1.39-4.67; p = 0.003). We found that Lp(a) is an independent risk factor for ischaemic stroke, and for the large-artery atherosclerotic subtype of ischaemic stroke.

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.

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.

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.

The Pathophysiological Associations Between Obesity, NAFLD, and Atherosclerotic Cardiovascular Diseases.

Obesity, non-alcoholic fatty liver disease (NAFLD), and atherosclerotic cardiovascular diseases are common and growing public health concerns. Previous epidemiological studies unfolded the robust correlation between obesity, NAFLD, and atherosclerotic cardiovascular diseases. Obesity is a well-known risk factor for NAFLD, and both of them can markedly increase the odds of atherosclerotic cardiovascular diseases. On the other hand, significant weight loss achieved by lifestyle modification, bariatric surgery, or medications, such as semaglutide, can concomitantly improve NAFLD and atherosclerotic cardiovascular diseases. Therefore, certain pathophysiological links are involved in the development of NAFLD in obesity, and atherosclerotic cardiovascular diseases in obesity and NAFLD. Moreover, recent studies indicated that simultaneously targeting several mechanisms by tirzepatide and retatrutide leads to greater weight loss and markedly improves the complications of metabolic syndrome. These findings remind the importance of a mechanistic viewpoint for breaking the association between obesity, NAFLD, and atherosclerotic cardiovascular diseases. In this review article, we mainly focus on shared pathophysiological mechanisms, including insulin resistance, dyslipidemia, GLP1 signaling, inflammation, oxidative stress, mitochondrial dysfunction, gut dysbiosis, renin-angiotensin-aldosterone system (RAAS) overactivity, and endothelial dysfunction. Most of these pathophysiological alterations are primarily initiated by obesity. The development of NAFLD further exacerbates these molecular and cellular alterations, leading to atherosclerotic cardiovascular disease development or progression as the final manifestation of molecular perturbation. A better insight into these mechanisms makes it feasible to develop new multi-target approaches to simultaneously unhinge the deleterious chain of events linking obesity and NAFLD to atherosclerotic cardiovascular diseases.

Assessment of the Influence of Postdilution Online Hemodiafiltration on the Rate of Removal of Middle Molecular Weight Uremic Toxins

Abstract Hemodiafiltration is a method of treatment used to replace kidney function, which effectively removes uremic toxins of middle molecular weight from the blood of patients with the end-stage of chronic kidney disease. The aim of this study was to examine the effect of postdilution online hemodiafiltration on the degree of β2- microglobulin removal. Thirty patients treated with postdilution online hemodiafiltration were examined. The main parameter for assessing the removal efficiency of uremic toxins of middle molecular weight was the concentration of β2-microglobulin in the serum before and after a single session of postdilution online hemodiafiltration. The following tests were used for statistical analysis: Shapiro-Wilk test, Student’s T test for bound samples and Wilcoxon test. The average total convective volume is 21.38 ± 2.97 liters per session. The reduction index of β2-microglobulin during a single session of postdilution online hemodiafiltration is 70.86 ± 6.87%. The average loss of albumin during a single postdilution online hemodiafiltration is 2.50 ± 0.92 g/4h, and the albumin reduction index is 6.20 ± 2.12%. Postdilution online hemodiafiltration effectively removes β2-microglobulin from the blood of patients with end-stage chronic kidney disease. The reduction index of β2-microglobulin is ˜ 71.00% and the loss of albumin is less than 4.0 g/4h. This dialysis modality prevents the development of dialysis-related amyloidosis and atherosclerotic cardiovascular diseases in the population of patients treated with regular hemodiafiltration.

Spatial analysis of 10-year predicted risk and incident atherosclerotic cardiovascular disease: the CoLaus cohort.

Whether cardiovascular risk scores geographically aggregate and inform on spatial development of atherosclerotic cardiovascular diseases (ASCVD) remains unknown. Our aim is to determine the spatial distribution of 10-year predicted cardiovascular risk and ASCVD, and to compare the overlap of the resulting spatial distributions. Using prospective data from the CoLaus|PsyCoLaus cohort study (2003-2021) we computed SCORE2 in participants free from ASCVD. Geographical distributions of predicted risk and events were determined using the Gi* Getis-Ord autocorrelation statistic. 6203 individuals (54% women, mean age 52.5 ± SD 10.7, ASCVD incidence rate 5.7%) were included. We identified clusters of high versus low predicted risk (4%, 6%, respectively) and ASCVD (5%, 5% respectively) at baseline. They persisted at follow-up. Overlap of SCORE2 and ASCVD clusters was marginal. Body-mass index and alcohol consumption explained most of the predicted risk distribution. For ASCVD, high clusters persisted or were reinforced after multivariate adjustment, while low incidence clusters were reduced, multifactorial determinants. Incidence rate of ASCVD was 2.5% higher (IC 95%, 1.4-3.7) in clusters of higher incidence of ASCVD. To develop up-to-date, geographically targeted prevention strategies, there is a need to study novel geographically risk factors affecting ASCVD and to update commonly used prediction models for a population approach.

Fluoride promotes the secretion of inflammatory factors in microglia through NLRP3/Caspase-1/GSDMD pathway.

It is widespread of endemic fluorosis in China, and the exposure of excessive fluoride will cause nervous system disease and activate microglia. However, the mechanism of the damage is not clear. It is well-known that NLRP3/Caspase-1/GSDMD pathway, a classic pyroptosis pathway, is widely involved in the occurrence and development of nervous system-related diseases, infectious diseases, and atherosclerotic diseases. This research aimed to explore the molecular mechanism of sodium fluoride on inflammation and pyroptosis in BV2 microglia based on the NLRP3/Caspase-1/GSDMD signaling pathway. BV2 microglia was treated with sodium fluoride at the dose of 0.25, 1, and 2mmol/L for 24, 48, and 72h, respectively. Cell viability, cell morphology, lactate dehydrogenase content, and related proteins and genes were examined to investigate if sodium fluoride caused damage to BV2 microglia through the pyroptosis pathway. Dithiolam (5μmol/L), a pyroptosis inhibitor, was added for further verification. NaF could induced BV2 cells injury in a dose-dependent fashion through disrupting the integrity of cell membranes and increasing IL-1β via upregulating NLRP3, Caspase-1, and its downstream protein GSDMD. Disulfiram couldimprove these changes caused by NaF. In conclusion, our results suggested that NLRP3/Caspase-1/GSDMD-mediated classical pyroptosis pathway was involved in fluoride-induced BV2 microglia damage.

Arterial Adventitial Vasa Vasorum Density Reflects The Progression Of Unstable Plaques: A Retrospective Clinical Study

Arterial adventitial vasa vasorum (AVV) plays an important role in the occurrence and development of atherosclerotic (AS) disease. AS is a systemic disease, and plaque is not only a local vascular event, but also occurs at multiple sites throughout the vascular bed. Currently, effective anti-AVV therapies are lacking. Therefore, we posed the following scientific questions: "does human carotid adventitial vasa vasorum density reflect plaque neovascularization and intimal-media hyperplasia in carotid?"; and "is it possible to reduce human AVV density by sonodynamic therapy (SDT)?" A retrospective study was conducted on 160 patients with carotid atherosclerosis. Duplex ultrasound scanning (DUS), contrast-enhanced ultrasound (CEUS), coronary angiography, and coronary CT angiography (CTA) were used for diagnosis and screening. Pearson correlation tests and Receiver operating characteristic (ROC) curve were used to analyze the relationships between AVV hyperplasia, vasa vasorum (VV) hyperplasia and the intima-media thickness (IMT). SDT was developed for the treatment of arterial AVV hyperplasia and AS plaques. The presence of local AVV in carotid unstable plaques correlated with the echogenic properties of the carotid plaque and the extent of plaque progression; Furthermore local AVV hyperplasia in patients with carotid atherosclerotic plaques was associated with acute coronary syndrome (ACS) events; Local AVV hyperplasia in patients with carotid atherosclerotic plaques was associated with coronary artery stenosis. Notably, SDT reduced local AVV hyperplasia and shrank the plaques in human femoral and carotid atherosclerotic lesions. The presence of AVV in human carotid arteries reflects the severity of carotid and coronary artery AS. Further, SDT can reduce the hyperplasia of local AVV in human femoral and carotid plaques.

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.

Impact of clonal haematopoiesis on atherosclerotic cardiovascular disease according to low-density lipoprotein cholesterol levels in general population.

Clonal haematopoiesis of indeterminate potential (CHIP), defined as a clonal expansion of age-related recurrent somatic mutations, has recently emerged as a novel cardiovascular risk factor. However, the precise role of CHIP in the development of atherosclerotic cardiovascular disease (ASCVD) remains unclear. Among 4,300 asymptomatic Korean participants aged 40-79 years, we investigated the risk of ASCVD by CHIP and the interplay between CHIP and conventional risk factors in ASCVD development. Additionally, we assessed changes in coronary arteries based on the presence of CHIP using coronary computed tomography angiography (CCTA). CHIP was present in 363 participants (8.4%), and its prevalence increased with age. Commonly mutated genes were DNMT3A, TET2 and ASXL1, in order. During follow-up (median, 4.7 years), 18 ASCVD cases (5.0%) were observed in CHIP carriers vs. 62 (1.6%) in non-carriers (p < 0.001), indicating an elevated risk of ASCVD associated with CHIP (adjusted HR 2.49, 95% CI 1.45-4.29, p < 0.001). Notably, with high levels of low-density lipoprotein (LDL) cholesterol, CHIP enhanced the risk of ASCVD (adjusted HR 6.20, 95% CI 3.14-12.23, p < 0.001), demonstrating synergism between CHIP and LDL cholesterol levels (S-index, 4.94; 95% CI 1.08-22.53, p = 0.039). Serial CCTAs confirmed that CHIP, in conjunction with high LDL cholesterol levels, had significant early impact on coronary arteries, revealing new measurable coronary atherosclerosis, mainly with unstable plaque, in proximal lesions. The presence of CHIP was significantly associated with the risk of ASCVD, promoting the early stage of atherosclerosis through synergy with high LDL cholesterol in the general population.

Lipid Disorders Management Strategies (2024) in Prediabetic and Diabetic Patients.

Dyslipidaemia is a modifiable risk factor commonly associated with diabetes mellitus and prediabetes, with a major impact on the early development of atherosclerotic cardiovascular disease. Various studies have tried to identify the key treatment targets, their optimal values according to patients' CV risk, and the most efficient yet safe therapeutic agents which, alongside lifestyle changes, would improve lipid levels and reduce cardiovascular mortality and morbidity. Currently, there are multiple pharmacologic options that can be used in the management of dyslipidaemia, such as statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, n-3 polyunsaturated fatty acids or fibrates, to name only a few, while many other are under development. In the current setting of a continuously increasing population of patients with metabolic disorders, this review aims to summarise current knowledge regarding lipid disorders and the recommendations of recent guidelines in treating dyslipidaemia in patients with diabetes mellitus or prediabetes.

Awareness of smoking cessation amongst German vascular surgeons.

Background: Smoking represents the well-known enemy of vascular well-being. Numerous previous studies emphasised the important role of smoking on the development and progression of atherosclerotic cardiovascular disease. The current study aimed to identify hurdles and barriers for an insufficient implementation of secondary prevention in the treatment of lower extremity peripheral arterial disease (PAD). Methods: All members of the German Society for Vascular Surgery and Vascular Medicine (DGG) with valid email addresses were invited to participate in an electronic survey on smoking. Results are descriptively presented. Results: Amongst 2716 invited participants, 327 (12%) submitted complete responses, thereof 33% women and 80% between 30 and 59 years old (87% board certified specialists). 83% were employed by hospitals (56% teaching hospital, 14% university, 13% non-academic) and 16% by outpatient facilities. 6% are active smokers (63% never) while a mean of five medical education activities on smoking cessation were completed during the past five years of practice. Only 27% of the institutions offered smoking cessation programs and 28% of the respondents were aware of local programs while a mean of 46% of their patients were deemed eligible for participation. 63% of the respondents deemed outpatient physicians primarily responsible for smoking cessation, followed by medical insurance (26%). Conclusions: The current nationwide survey of one scientific medical society involved in the care of patients with vascular disease revealed that smoking cessation, although being commonly accepted as important pillar of comprehensive holistic care, is not sufficiently implemented in everyday clinical practice.

Prevalence of metabolic disorders among women in reproductive age group in hilly rural area of North India.

Metabolic syndrome consists of cardiometabolic risk factors that promote the development of atherosclerotic cardiovascular disease, type 2 'DM' and obesity. These are associated with increased cardiovascular mortality and morbidity. Metabolic disorders (MD) are becoming more prevalent both in developing countries and developed countries and are now considered as lifestyle diseases. In women of reproductive age group, especially pregnancy, the blood glucose level is increasing which adversely affects the health of mother and child. Similarly, high blood pressure also precipitates the problems. This study was carried out to find the prevalence of hypertension, diabetes mellitus, obesity and 'MD' among the women living in remote rural set-up. This cross-sectional study was done among women of reproductive age group in 15 villages from 5 panchayats of field practice area of Maharishi Markandeshwar Medical College and Hospital, Kumarhatti, Solan. They were screened for 'MD' through investigative procedures (weight, height, BMR, abdominal girth, blood pressure through sphygmomanometer, blood glucose through the glucometer method), serum HDL and triglycerides. Respondents from the family were asked about the common/general information of house. The tool used for collecting general and relevant information from the respondent was a questionnaire, which was pretested for validity before being used in the field. Four-hundred and sixty-seven women of reproductive age group participated in the study. Half of the participants were with qualification of matriculate and 9.2% participants were illiterate. Three-fourths of the participants were married women and 89% were vegetarian. Sixty-four per cent of participants were housewives. Half of the participants had a normal BMI, whereas 28.9% were overweight and 10% were obese. The prevalence of hypertension and diabetes among the participants were 12.5% and 9.8%, respectively. Forty-seven per cent participants had a waist circumference above 80 cm. The level of non-communicable diseases is related with the MD which has the adverse effect on the various systems and organs of the subjects. The MD can be controlled with the certain changes in the life style pattern. The GOI is also concerned with such scenarios in the country. It is recommended that women of reproductive age group undergo regular blood pressure and blood sugar screenings to detect hypertension and diabetes early and take appropriate measures to manage them.

Genetic Predisposition of Atherosclerotic Cardiovascular Disease in Ancient Human Remains.

Several computed tomographic studies have shown the presence of atherosclerosis in ancient human remains. However, while it is important to understand the development of atherosclerotic cardiovascular disease (ASCVD), genetic data concerning the prevalence of the disease-associated single nucleotide polymorphisms (SNPs) in our ancestors are scarce. For a better understanding of the role of genetics in the evolution of ASCVD, we applied an enrichment capture sequencing approach to mummified human remains from different geographic regions and time periods. Twenty-two mummified individuals were analyzed for their genetic predisposition of ASCVD. Next-generation sequencing methods were applied to ancient DNA (aDNA) samples, including a novel enrichment approach specifically designed to capture SNPs associated with ASCVD in genome-wide association studies of modern humans. Five out of 22 ancient individuals passed all filter steps for calculating a weighted polygenic risk score (PRS) based on 87 SNPs in 56 genes. PRSs were correlated to scores obtained from contemporary people from around the world and cover their complete range. The genetic results of the ancient individuals reflect their phenotypic results, given that the only two mummies showing calcified atherosclerotic arterial plaques on computed tomography scans are the ones exhibiting the highest calculated PRSs. These data show that alleles associated with ASCVD have been widespread for at least 5,000 years. Despite some limitations due to the nature of aDNA, our approach has the potential to lead to a better understanding of the interaction between environmental and genetic influences on the development of ASCVD.