Prevention Of Atherosclerosis Research Articles

Role of the screening with coronary computed tomography angiography on lipid management and risk factors control in an asymptomatic Chinese population: a community-based, parallel-group, open-label, randomized clinical trial (RESPECT2).

Lipid management based on cardiovascular risk level is the cornerstone of primary prevention of coronary artery disease (CAD), while the accuracy and adherence of traditional cardiovascular risk stratification have been questioned. Prevention strategies based on imaging screening for atherosclerotic plaques are found to be more objective and adherent in recent studies. This trial aims to investigate the role of coronary computed tomography angiography (CCTA) in guiding the primary prevention of CAD in a randomized controlled design. Approximately 3400 middle-aged asymptomatic community participants will be recruited and randomized in a 1:1 ratio to a traditional cardiovascular risk score-guided (usual care group) or CCTA-guided (CCTA group) strategy. Participants with cardiovascular disease, prior lipid-lowering therapy, CCTA contraindication, or serious diseases that affect life span will be excluded. The intervention strategy includes blood pressure, blood glucose, and lipid management and lifestyle modifications. Blood pressure and glucose targets and lifestyle modification recommendations keep the same in both strategies, while lipid management is personalized based on traditional risk level or CCTA results, respectively. The primary outcome is the proportion of participants taking lipid-lowering medication regularly at both 6 and 12months. The secondary outcomes include the proportion of participants achieving low-density lipoprotein cholesterol lowering targets at 12months, mean changes in lipid levels from baseline to 12months, barriers to adherence, adverse reactions related to CCTA examination, and cardiovascular events. The study is the first randomized clinical trial to examine the effectiveness of a CCTA-guided versus a traditional risk score-guided primary prevention strategy in an asymptomatic community-based population. ClinicalTrials.gov NCT05725096. Registered on 2 February 2023.

Research Progress in Prevention and Treatment of Atherosclerosis by Regulating Endothelial Cells with Traditional Chinese Medicine

Atherosclerosis (AS)is an important pathological basis of cardiovascular and cerebrovascular diseases. Its pathogenesis is complex and involves many factors. Traditional Chinese medicine (TCM) has the advantage of multi-link and multi-target intervention in the prevention and treatment of AS, in which the regulation of endothelial progenitor cells (EPCs) is an important research direction. This article will review the research progress of TCM in preventing and treating AS by regulating EPCs.

Long-Term Effects of Low-Dose Aspirin on Gastrointestinal Symptoms and Bleeding Complications in Patients with Type 2 Diabetes.

Low-dose aspirin for primary prevention is determined by the balance of risks of cardiovascular events and adverse effects. We assessed the long-term gastrointestinal symptoms or bleeding with low-dose aspirin in diabetic patients. The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a randomized clinical trial to evaluate the efficacy and safety of low-dose aspirin in patients with type 2 diabetes. As a posthoc analysis, we investigated the incidence of upper gastrointestinal symptoms or bleeding in aspirin (100 mg enteric-coated aspirin or 81 mg buffered aspirin daily) and no-aspirin groups within and beyond 3 years. Of 2535 patients (mean age 65 years, 55% male) followed for a median of 11.2 years, 1258 were included in the aspirin group (951 enteric-coated, 208 buffered, 99 unknown) and 1277 were included in the no-aspirin group. The cumulative incidence of upper gastrointestinal symptoms or bleeding was higher in the aspirin group than the no-aspirin group (8.8% vs. 5.7% at 18 years; p<0.0001). The increased risk in the aspirin group was prominent within 3 years, and thehazard ratio (HR) [95% confidence interval (CI)] of the aspirin group was 7.10 [3.21-15.7], but attenuated beyond 3years (HR 1.20 [0.76-1.89]). In 1159 patients in the aspirin group, the cumulative incidence was lower in the enteric-coated than in the buffered aspirin groups (2.9% vs. 7.3%; p=0.003) within 3 years, and the adjusted HR of enteric-coated aspirin was 0.38 [0.20-0.72] compared with the buffered aspirin group. The upper gastrointestinal symptoms or bleeding of low-dose aspirin within 3 years, and the aspirin formulations, were relevant for decision making of initiation and continuation of low-dose aspirin for primary prevention.

Chungtaejeon (CTJ) inhibits adhesion and migration of VSMC through cytoskeletal remodeling pathway

IntroductionVascular remodeling is crucial for the progression of vascular disease such as atherosclerosis. We utilize the in vitro experimental model of atherosclerosis to elucidate the activity of Chungtaejeon (CTJ), a Korean fermented tea on adhesion and migration of human aortic vascular smooth muscle cells (HASMC). Materials and methodsVarious in vitro assays such as cell viability, cell adhesion, Western blot, immunofluorescence, were carried out on HASMC to explore pathway associated with cytoskeletal remodeling during the progression of atherosclerosis. ResultsIn result, CTJ significantly inhibited adhesion of HASMC as revealed by collagen assay. Similarly, CTJ inhibited the β1-integrin protein expression as well as FAK phosphorylation. Treatment of CTJ also inhibited stress fiber formation. Likewise, adherence of cells on collagen optimally increased the expression of both RhoA and Cdc42, however, treatment of CTJ dose dependently decreased their expression. The lysophosphatidic acid stimulation of HASMC rapidly increased the level of phosphorylated forms of MLC20 within 15 min, followed by an extended level of MLC20 phosphorylation. The treatment of CTJ at a dose of 50, 100 and 250 μg/ml remarkably reduced the diphosphorylated form while decreased the level of monophosphorylated form of MLC20. ConclusionsOur results suggests that, with further validation CTJ could be a promising herbal resource for prevention of atherosclerosis.

Capsaicin Improves Systemic Inflammation, Atherosclerosis, and Macrophage-Derived Foam Cells by Stimulating PPAR Gamma and TRPV1 Receptors.

Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. Apolipoprotein E knockout mice and their C57BL/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPARγ signaling pathways in bone marrow-derived macrophages. Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses.

Whole Food Plant-Based Dietary Education for Frontline RNs

Background: Coronary artery disease (CAD) is the leading cause of death for men and women in the United States, with myocardial infarction (MI) being a serious outcome. Plant-based diets are associated with a reduced incidence of CAD. Registered nurses (RNs) are highly trusted members of the healthcare team and are ethically responsible for providing reliable information based on scientific sources and guideline-directed recommendations. Registered nurses are optimally positioned to provide education on adopting whole foods plant-based (WFPB) diets to patients experiencing CAD inside and outside the hospital setting. It is unknown the degree to which nurses have adopted WFPB eating patterns and incorporated WFPB patient education into routine nursing care. The purpose of this study is to describe RN perceptions (susceptibility, severity, benefits and barriers, self-efficacy) related to the effect of a WFPB meal pattern for prevention and management of CAD, and RN intention to apply this dietary knowledge to their own health behaviors and nursing practices. Methods: This descriptive quasi-experimental pretest-posttest study measured concepts from the health belief model including RN perceptions of susceptibility, severity, benefits, and barriers, as well as self-efficacy and meal behaviors. The participating RNs completed these measures before and after they participated in any of the educational interventions designed using experiential learning theory. Registered nurses had the option of attending one or all three educational interventions on WFPB nutrition and CAD. Results: Eighty-six RNs working in cardiology specialties on three inpatient or one outpatient cardiac units at a large southeastern hospital system participated. The nurses believed CAD is a serious diagnosis (72/72) and that WFPB dietary patterns are cardioprotective for the prevention and management of CAD (63/72). However, nurse dietary behaviors were incongruent with their beliefs as some RNs (14/72) indicated they did not consume any vegetarian or fully plant-based meals. The most common barrier (36/72) to nurses adopting a WFPB dietary pattern was a taste preference for meat and animal products. Half of the eight nurses who completed at least one of the educational interventions and the postsurvey reported increased confidence to advise patients with CAD on the WFPB dietary pattern. Combined, participants self-reported their vegetarian or fully plant-based meal frequency increased slightly. Discussion: Registered nurses lack a working knowledge of WFPB eating patterns in their personal and professional lives, which may impact the quality of dietary education they provide to people with CAD or MI. Overcoming barriers to education on WFPB dietary patterns is important for increasing nurse confidence in teaching people with CAD about this evidence-based dietary health behavior. Conclusion: Registered nurses’ knowledge and perceptions of WFPB eating patterns may be enhanced through professional development activities. RNs may be more likely to engage with education that is frequent, brief, asynchronous, and online or part of existing onboarding such as lunch and learn events to sample WFPB foods. Future research is needed on strategies to engage and empower RNs to educate people with CAD on WFPB nutrition.

Cardiac rehabilitation for patients with coronary artery disease

Background: Coronary artery disease (CAD) is the leading cause of death in Korea, with high rates of recurrence and mortality associated with relapse. Therefore, various strategies are required to prevent recurrent CAD. Cardiac rehabilitation (CR) is proven to be safe and highly effective and is therefore considered essential treatment for secondary prevention of CAD. CR is reimbursed in Korea since February 2017.Current Concepts: CR comprises the following main components: education, evaluation, and treatment. CR education includes increasing awareness regarding the chronic risk factors associated with CAD and motivating patients to manage these factors independently. Such management includes smoking cessation, moderation in alcohol consumption, weight management, maintenance of physical activity, medication adherence, and psychosocial interventions. CR evaluation through cardiopulmonary exercise tests is useful to predict prognosis and provides basic information for exercise prescriptions. CR treatment includes prescription of a personalized exercise program, with aerobic exercise as the main component supported by resistance training.Discussion and Conclusion: CR is an important treatment modality that significantly improves exercise capacity while reducing readmission rates and mortality in patients with CAD . Therefore, it is essential to understand CR methods and concepts and encourage patients with CAD to participate in CR programs.

Monocytes Reprogrammed by 4-PBA Potently Contribute to the Resolution of Inflammation and Atherosclerosis.

Chronic inflammation initiated by inflammatory monocytes underlies the pathogenesis of atherosclerosis. However, approaches that can effectively resolve chronic low-grade inflammation targeting monocytes are not readily available. The small chemical compound 4-phenylbutyric acid (4-PBA) exhibits broad anti-inflammatory effects in reducing atherosclerosis. Selective delivery of 4-PBA reprogrammed monocytes may hold novel potential in providing targeted and precision therapeutics for the treatment of atherosclerosis. Systems analyses integrating single-cell RNA sequencing and complementary immunologic approaches characterized key resolving characteristics as well as defining markers of reprogrammed monocytes trained by 4-PBA. Molecular mechanisms responsible for monocyte reprogramming were assessed by integrated biochemical and genetic approaches. The intercellular propagation of homeostasis resolution was evaluated by coculture assays with donor monocytes trained by 4-PBA and recipient naive monocytes. The in vivo effects of monocyte resolution and atherosclerosis prevention by 4-PBA were assessed with the high-fat diet-fed ApoE-/- mouse model with IP 4-PBA administration. Furthermore, the selective efficacy of 4-PBA-trained monocytes was examined by IV transfusion of ex vivo trained monocytes by 4-PBA into recipient high-fat diet-fed ApoE-/- mice. In this study, we found that monocytes can be potently reprogrammed by 4-PBA into an immune-resolving state characterized by reduced adhesion and enhanced expression of anti-inflammatory mediator CD24. Mechanistically, 4-PBA reduced the expression of ICAM-1 (intercellular adhesion molecule 1) via reducing peroxisome stress and attenuating SYK (spleen tyrosine kinase)-mTOR (mammalian target of rapamycin) signaling. Concurrently, 4-PBA enhanced the expression of resolving mediator CD24 through promoting PPARγ (peroxisome proliferator-activated receptor γ) neddylation mediated by TOLLIP (toll-interacting protein). 4-PBA-trained monocytes can effectively propagate anti-inflammation activity to neighboring monocytes through CD24. Our data further demonstrated that 4-PBA-trained monocytes effectively reduce atherosclerosis pathogenesis when administered in vivo. Our study describes a robust and effective approach to generate resolving monocytes, characterizes novel mechanisms for targeted monocyte reprogramming, and offers a precision therapeutics for atherosclerosis based on delivering reprogrammed resolving monocytes.

Comparative Prognostic Value of Coronary Calcium Score and Perivascular Fat Attenuation Index in Coronary Artery Disease.

Coronary artery disease (CAD) is the leading global cause of mortality, accounting for approximately 30% of all deaths. It is primarily characterized by the accumulation of atherosclerotic plaques within the coronary arteries, leading to reduced blood flow to the heart muscle. Early detection of atherosclerotic plaques is crucial to prevent major adverse cardiac events. Notably, recent studies have shown that 15% of myocardial infarctions occur in patients with non-obstructive CAD, underscoring the importance of comprehensive plaque assessment beyond merely identifying obstructive lesions. Cardiac Computed Tomography Angiography (CCTA) has emerged as a cost-effective and efficient technique for excluding obstructive CAD, particularly in patients with a low-to-intermediate clinical likelihood of the disease. Recent advancements in CCTA technology, such as improved resolution and reduced scan times, have mitigated many technical challenges, allowing for precise quantification and characterization of both calcified and non-calcified atherosclerotic plaques. This review focuses on two critical physiological aspects of atherosclerotic plaques: the burden of calcifications, assessed via the coronary artery calcium score (CACs), and perivascular fat attenuation index (pFAI), an emerging marker of vascular inflammation. The CACs, obtained through non-contrast CT scans, quantifies calcified plaque burden and is widely used to stratify cardiovascular risk, particularly in asymptomatic patients. Despite its prognostic value, the CACs does not provide information on non-calcified plaques or inflammatory status. In contrast, the pFAI, derived from CCTA, serves as an indirect marker of coronary inflammation and has shown potential in predicting adverse cardiac events. Combining both CACs and pFAI assessment could offer a comprehensive risk stratification approach, integrating the established calcification burden with novel inflammatory markers to enhance CAD prevention and management strategies.

Challenging the efficacy and safety of clopidogrel versus aspirin monotherapy in secondary prevention of coronary artery disease: a comprehensive review

Challenging the efficacy and safety of clopidogrel versus aspirin monotherapy in secondary prevention of coronary artery disease: a comprehensive review

Time-Restricted Feeding Reduces Atherosclerosis in LDLR KO Mice but Not in ApoE Knockout Mice.

Dyslipidemia increases cardiovascular disease risk, the leading cause of death worldwide. Under time-restricted feeding (TRF), wherein food intake is restricted to a consistent window of <12 hours, weight gain, glucose intolerance, inflammation, dyslipidemia, and hypercholesterolemia are all reduced in mice fed an obesogenic diet. LDLR (low-density lipoprotein receptor) mutations are a major cause of familial hypercholesterolemia and early-onset cardiovascular disease. We subjected benchmark preclinical models, mice lacking LDLR-knockout or ApoE knockout to ad libitum feeding of an isocaloric atherogenic diet either ad libitum or 9 hours TRF for up to 13 weeks and assessed disease development, mechanism, and global changes in hepatic gene expression and plasma lipids. In a regression model, a subset of LDLR-knockout mice were ad libitum fed and then subject to TRF. TRF could significantly attenuate weight gain, hypercholesterolemia, and atherosclerosis in mice lacking the LDLR-knockout mice under experimental conditions of both prevention and regression. In LDLR-knockout mice, increased hepatic expression of genes mediating β-oxidation during fasting is associated with reduced VLDL (very-low-density lipoprotein) secretion and lipid accumulation. Additionally, increased sterol catabolism coupled with fecal loss of cholesterol and bile acids contributes to the atheroprotective effect of TRF. Finally, TRF alone or combined with a cholesterol-free diet can reduce atherosclerosis in LDLR-knockout mice. However, mice lacking ApoE, which is an important protein for hepatic lipoprotein reuptake do not respond to TRF. In a preclinical animal model, TRF is effective in both the prevention and regression of atherosclerosis in LDLR knockout mice. The results suggest TRF alone or in combination with a low-cholesterol diet can be a lifestyle intervention for reducing cardiovascular disease risk in humans.

Association of Physical Activity Levels with Coronary Artery Disease Risk Factors in Middle aged (40-55) Bangladeshi Women

Background: A sedentary lifestyle is associated with increased risk of Coronary Artery Disease (CAD) in women. At least 150min/wk of moderate activity or 75min/wk of vigorous activity or combination is recommended by American Heart Association (AHA) for primary prevention of CAD. The purpose of this study was to assess the physical activity levels of middle aged women and to find out the association of CAD risk factors with physical activity level. Methods: This cross-sectional analytical study was conducted in Dhaka Medical College Hospital (DMCH) cardiology OPD from May 2019 to April 2020. We interviewed 249 middle aged women (40-55) who attended our OPD during the study period and fulfilled the exclusion and inclusion criteria. Global Physical Activity Questionnaire (GPAQ) was used to assess physical activity level. Blood pressure and BMI was measured. OGTT and fasting lipid profile was done. Subjects with low physical activity was assigned in Group I (n=152), moderate activity in group II (n= 93) and high activity in group III (n= 4). Association between the physical activity levels and presence of CAD risk factors like DM, HTN, dyslipidemia and obesity was evaluated. Results: In this study we found that most of the study subjects (61.0%) were in low active group. Overall 70.2% women were menopausal and premature menopause (≤50 years) was found in 47.8% of subjects. Mean age of menopause was 47±3.8; (44-53) years and mean duration of menopause was 3.1±0.5 years. Overall prevalence of DM, HTN, obesity and dyslipidemia was 62.2%, 50.6%, 39.8% and 53.4% accordingly. Women in low active group were having significant higher proportion of DM (52.6%), HTN (65.8%), obesity (57.9%) and dyslipidemia (75.7%) in comparison to moderate active group. Only 4 women were in highly active group and none of the CAD risk factors was present among them. Bangladesh Heart Journal 2024; 39(2): 127-137

Achieving Successful Prevention of Coronary Artery Disease: A Worldwide Call to Action.

Achieving Successful Prevention of Coronary Artery Disease: A Worldwide Call to Action.

ОСТЕОПОРОЗ КАК ФАКТОР РИСКА СЕРДЕЧНО-СОСУДИСТЫХ ЗАБОЛЕВАНИЙ

Cardiovascular disease and bone fractures caused by osteoporosis are the leading causes of death in older adults. The purpose of this study was to demonstrate the correlation between overall risk of cardiovascular events and low bone density in postmenopausal women, and its impact on the incidence of major cardiovascular events. Our prospective study included 300 postmenopausal women. All those examined were divided into three groups depending on the measured bone tissue density: Group I – 84 examined with osteoporosis; Group II – 115 patients with osteopenia; and group III – 101 subjects with normal bone density. For all subjects, the overall ten-year risk of a fatal cardiovascular event was calculated using the SCORE system tables. Results. After 36 months of observation, cardiovascular diseases occurred in 19 (6.3%) subjects. Significant differences in the incidence of cardiovascular events were demonstrated between patients with osteoporosis, osteopenia and normal bone density (x2=28.7; p&lt;0.001), as well as between patients with high and low cardiovascular risk (x2=22, 6; p). &lt;0.001). Multivariate logistic regression analysis showed that smoking (2.23; 95% CI: 1.02–6.19; p=0.035) and an increase in total cardiovascular score (1.36; 95% CI: 1.17–1 .58; p&lt;0.001) are related. with an increased risk of cardiovascular events, while an increase in T-score was associated with a decreased risk of cardiovascular events (0.42; 95% CI: 0.25 to 0.73; p=0.002). Measurement of bone density with a standardized assessment of overall cardiovascular risk may be useful in selecting women in need of intensive prevention and treatment of atherosclerosis.

Behavioral, Clinical, and Coronary Artery Calcium Screening for Prevention and Treatment of Subclinical Atherosclerosis: Implications for Health Education

ABSTRACT Background In the USA, heart disease is the leading cause of death for women and men. Coronary artery disease (CAD) is the most common type of heart disease. Purpose To investigate the association between behavioral and non-behavioral risk factors associated with subclinical atherosclerosis. Methods Patients referred for a CT angiography completed a demographic/behavioral questionnaire and medical history interview for CAD risk factors. Risk factor data were correlated with CAD subclinical atherosclerosis scores for 521 participants. Results Frequency among four levels of CAD revealed: no disease 38%, mild atherosclerotic 20%, moderate atherosclerotic 30%, and severe atherosclerosis 12%. Significant (p ≤ .05) demographic variables were as follows: age, race, marital status, and employment status. Significant predictive behavioral variables were as follows: tobacco use, daily water intake, sodium consumption, exercise days per week, and junk food consumption. Risk factors significantly associated with subclinical CAD included hypertension, diabetes, sleep apnea, and abnormal coronary calcium score. Discussion Multi-slice CT angiography allows early reliable evaluation of subclinical atherosclerosis and correlation with behavioral/non-behavioral risk factors with level of CAD, instrumental to primary and secondary CAD prevention, limiting tertiary CAD treatment. Translation to Health Education Practice Study results have implications for Health Educators with regard to intervention research planning, implementation, and evaluation.

Assessing the causal relationship between metabolic biomarkers and coronary artery disease by Mendelian randomization studies

The development of coronary artery disease (CAD) is significantly affected by impaired endocrine and metabolic status. Under this circumstance, improved prevention and treatment of CAD may result from knowing the connection between metabolites and CAD. This study aims to delve into the causal relationship between human metabolic biomarkers and CAD by using two-sample Mendelian randomization (MR). Utilizing two-sample bidirectional MR analysis, we assessed the correlation between 1400 blood metabolites and CAD, and the metabolites data from the CLSA, encompassing 8299 participants. Metabolite analysis identified 1091 plasma metabolites and 309 ratios as instrumental variables. To evaluate the causal link between metabolites and CAD, we analyzed three datasets: ebi-a-GCST005195 (547,261 European & East Asian samples), bbj-a-159 (29,319 East Asian CAD cases & 183,134 East Asian controls), and ebi-a-GCST005194 (296,525 European & East Asian samples). To estimate causal links, we utilized the IVW method. To conduct sensitivity analysis, we used MR-Egger, Weighted Median, and MR-PRESSO. Additionally, we employed MR-Egger interception and Cochran’s Q statistic to assess potential heterogeneity and pleiotropy. What’s more, replication and reverse analyses were performed to verify the reliability of the results and the causal order between metabolites and disease. Furthermore, we conducted a pathway analysis to identify potential metabolic pathways. 59 blood metabolites and 27 metabolite ratios nominally associated with CAD (P < 0.05) were identified by IVW analysis method. A total of four known blood metabolites, namely beta-hydroxyisovaleroylcarnitine (OR 1.06, 95% CI 1.027–1.094, FDR 0.07), 1-palmitoyl-2-arachidonoyl (OR 1.07, 95% CI 1.029–1.110, FDR 0.09), 1-stearoyl-2- docosahexaenoyl (OR 1.07, 95% CI 1.034–1.113, FDR 0.07) and Linoleoyl-arachidonoyl-glycerol, (OR 1.07, 95% CI 1.036–1.105, FDR 0.05), and two metabolite ratios, namely spermidine to N-acetylputrescine ratio (OR 0.94, 95% CI 0.903–0.972, FDR 0.09) and benzoate to linoleoyl-arachidonoyl-glycerol ratio (OR 0.87, 95% CI 0.879–0.962, FDR 0.07), were confirmed as having a significant causal relationship with CAD, after correcting for the FDR method (p < 0. 1). A causal relationship was found to be established between beta -hydroxyisovalerylcarnitine and CAD with the validation in other two datasets. Moreover, multiple metabolic pathways were discovered to be associated with CAD. Our study supports the hypothesis that metabolites have an impact on CAD by demonstrating a causal relationship between human metabolites and CAD. This study is important for new strategies for the prevention and treatment of CAD.

Abstract Tu033: CXCL5: The Next Guardian of the Galaxy to challenge Atherosclerosis

Atherosclerosis is a persistent inflammatory disease characterized by the buildup of lipid-laden macrophages (foam cells) in arterial walls and has been linked to several cardiovascular ailments. Despite advances in understanding its pathogenesis, the underlying mechanisms of atherogenesis, particularly regarding chemokine influence, has yet to be investigated. Our laboratory has previously identified CXCL5, a chemokine known for its involvement in inflammatory responses, as a potential mediator of atherosclerosis. We found that patients with elevated CXCL5 levels were less likely to have experienced a previous heart attack or develop coronary artery disease, suggesting that CXCL5 may be atheroprotective. To further investigate the role of CXCL5 in atherosclerosis, we conducted a study using mice on an apolipoprotein E (apoE) knockout background, to promote the formation of plaque, with varying alleles (0, 1, or 2) of CXCL5. Mice were placed on a high-fat diet regimen starting at approximately 10 weeks of age and continued until 26 weeks of age. Aortas, echocardiograms, and blood plasma were obtained to assess the development of atherosclerosis and its impact on cardiac function and metabolic parameters. Our en face oil red o staining results showed that the aortas of mice lacking one (p=.0314) or both alleles (p=.0783) of CXCL5 exhibited elevated plaque formation compared to that of wild-type mice. Echocardiographic data revealed that left ventricular mass (corrected) was highest in CXCL5 knockout mice and increased significantly over time (p=.0170) in these animals. Additionally, a significant increase in heart rate (p=.0095) and glucose (p=.0274) levels was only observed in CXCL5 heterozygous mice over the 16-week period, while triglyceride levels increased in both CXCL5 heterozygous (p=.0010) and knockout (p=.0241) mice. Interestingly, high-density lipoprotein (HDL) levels, which is often considered as "good cholesterol," increased significantly only in wild-type (p=.0031) mice, where CXCL5 was present, over the 16-week period. These findings suggest that CXCL5 may play a protective role against atherosclerosis and its associated cardiac complications. In conclusion, our study provides novel insights into the complex interplay between inflammation, lipid metabolism, and cardiovascular disease, highlighting the potential therapeutic value of CXCL5 in the prevention and treatment of atherosclerosis.

Lipid-lowering effects of gefarnate in statin-treated patients with residual hypertriglyceridemia: a randomized controlled study.

The prevention of coronary artery disease (CAD) faces dual challenges: the aspirin-induced gastrointestinal injury, and the residual cardiovascular risk after statin treatment. Geraniol acetate (Gefarnate) is an anti-ulcer drug. It was reported that geraniol might participate in lipid metabolism through a variety of pathways. The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia. In this prospective, open-label, randomized, controlled trial, 69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group, received gefarnate (100 mg/3 times a day) combined with statin and statin alone, respectively. At baseline and after one-month treatment, the levels of plasma triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol were tested. After one-month gefarnate treatment, triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L (P = 0.0018), LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L (P = 0.0004), HDL-C level increased from 0.97 mmol/L to 1.17 mmol/L (P = 0.0228). Based on statin therapy, gefarnate could significantly reduce the plasma triglyceride level (P = 0.0148) and increase the plasma HDL-C level (P = 0.0307). Although the LDL-C and total cholesterol levels tended to decrease, there was no statistically significant difference. The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia. This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.

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.

Association between Interleukin-6 and Multiple Acute Infarctions in Symptomatic Intracranial Atherosclerotic Disease.

Interleukin-6 (IL-6) plays an important role in the pathophysiology of atherosclerosis. This study aimed to determine whether IL-6 is a crucial biomarker associated with Multiple Acute Infarctions (MAIs), which indicate an important stroke mechanism of artery-- to-artery embolism with a high risk of stroke recurrence in symptomatic Intracranial Atherosclerotic Disease (sICAD). We tested the association between circulating IL-6 levels and the presence of MAIs in a prospective population-based registry. We included 1,919 patients with sICAD and baseline IL-6 levels from the Third China National Stroke Registry for the current analysis, The baseline IL-6 was centrally measured at Beijing Tiantan Hospital, Images of the brain parenchyma and vascular structures were digitized and then blindly and independently read by two groups of trained readers, The recruited patients were divided into 3 groups according to IL-6 tertiles, The relationship between baseline IL-6 tertile levels and the presence of MAIs was modeled using multivariate logistic regression. Compared to patients in the first IL-6 tertile those in the second and third tertiles demonstrated a significantly higher proportion of MAIs. The odds ratios were 1.81 [95% Confidence Interval (CI), 1.42-2.30] for the second versus first tertile and 2.15 (95% CI 1.66-2.79) for the third versus first tertile, The proportion of patients with MAIs increased with rising IL-6 tertiles observed at 59.3%, 71.6% and 76.4% for the first, second and third tertiles, respectively (P for trend < 0.001). The association between higher IL-6 tertiles and increased proportion of MAIs was also present in subgroups defined by age < 65 years, age ≥ 65 years, male, and high-sensitivity C-reactive Protein (hs-CRP) ≥ 2 mg/L. Furthermore, a significant interaction was detected for the hs- CRP subgroup (P = 0.038). In sensitivity analyses, the positive correlation between IL-6 levels and the proportion of MAIs remained consistent. In patients with sICAD, higher IL-6 levels were associated with an increased proportion of MAIs. IL-6 could be used as a biomarker and a potential therapeutic target for future atherosclerosis treatment and prevention in patients with sICAD.