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Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role of inflammation in the residual risk of ASCVD, emphasizing its impact on atherosclerosis progression and plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD. [ABSTRACT FROM AUTHOR]

Rest-activity rhythm is an essential behavior for human health. However, the association between rest-activity rhythm and atherosclerotic cardiovascular disease (ASCVD) risk remains unclear. Therefore, this study aimed to elucidate the association. This study included 87,039 participants from the UK Biobank who had 7-day accelerometry data and were free of ASCVD at baseline. Relative amplitude was calculated as the difference between the most active continuous 10-h period (M10) and the least active continuous 5-h period (L5) in 24 h, and lower relative amplitude indicated the disruption of rest-activity rhythm. Cox proportional hazard model was used to examine the association of relative amplitude with ASCVD. Further, the linear association between relative amplitude and arterial stiffness measurements, including arterial stiffness index (ASI) and carotid intima-media thickness (cIMT), was examined. During a mean follow-up period of 6.80 ± 1.10 years, 2798 ASCVD cases were identified. A dose-response relationship was observed between relative amplitude and ASCVD risk (P for trend<0.001). The adjusted hazard ratio, for the highest vs the lowest quintile of relative amplitude, was 1.54 (95 % confidence interval: 1.31, 1.79). Further, we found significant association of lower relative amplitude with ASI and cIMT. The onset timing of M10 at ≤06:00, 09:00, 10:00, or ≥11:00, as opposed to the reference time of 07:00, was associated with higher ASCVD risk. Low rest-activity rhythm amplitude was associated with a higher risk of ASCVD. Rest-activity rhythm amplitude may provide a method to identify individuals at risk of ASCVD in public health and clinical practice. • Rest-activity rhythm is an essential behavior for human health. • Low rest-activity rhythm amplitude was associated with higher ASCVD risk. • Early or late onset timing of 10h activity was associated with higher ASCVD risk. • Low rest-activity rhythm amplitude was associated with increased arterial stiffness. • Rest-activity rhythm amplitude could be a novel risk factor for ASCVD. [ABSTRACT FROM AUTHOR]

Olpasiran, a small interfering RNA (siRNA), blocks lipoprotein(a) (Lp(a)) production by preventing translation of apolipoprotein(a) mRNA. In phase 2, higher doses of olpasiran every 12 weeks (Q12W) reduced circulating Lp(a) by >95%. This study sought to assess the timing of return of Lp(a) to baseline after discontinuation of olpasiran, as well as longer-term safety. OCEAN(a)-DOSE (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction–DOSE Finding Study) was a phase 2, dose-finding trial that enrolled 281 participants with atherosclerotic cardiovascular disease and Lp(a) >150 nmol/L to 1 of 4 active doses of olpasiran vs placebo (10 mg, 75 mg, 225 mg Q12W, or an exploratory dose of 225 mg Q24W given subcutaneously). The last dose of olpasiran was administered at week 36; after week 48, there was an extended off-treatment follow-up period for a minimum of 24 weeks. A total of 276 (98.2%) participants entered the off-treatment follow-up period. The median study exposure (treatment combined with off-treatment phases) was 86 weeks (Q1-Q3: 79-99 weeks). For the 75 mg Q12W dose, the off-treatment placebo-adjusted mean percent change from baseline in Lp(a) was −76.2%, −53.0%, −44.0%, and −27.9% at 60, 72, 84, and 96 weeks, respectively (all P < 0.001). The respective off-treatment changes in Lp(a) for the 225 mg Q12W dose were −84.4%, −61.6%, −52.2%, and −36.4% (all P < 0.001). During the extension follow-up phase, no new safety concerns were identified. Olpasiran is a potent siRNA with prolonged effects on Lp(a) lowering. Participants receiving doses ≥75 mg Q12W sustained a ∼40% to 50% reduction in Lp(a) levels close to 1 year after the last dose. (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction–DOSE Finding Study [OCEAN(a)-DOSE]; NCT04270760) [ABSTRACT FROM AUTHOR]

In recent years, the prevalence and fatality rates of atherosclerotic cardiovascular disease have not only shown a consistent rise that cannot be ignored, but have also become a pressing social health problem that requires urgent attention. While interventional surgery and drug therapy offer significant therapeutic results, they often come with common side effects. Geniposide, an active component extracted from the Chinese medicine Gardenia jasminoides Ellis, shows promise in the management of cardiac conditions. This review comprehensively outlines the underlying pharmacological mechanisms by which geniposide exerts its effects on atherosclerosis. Geniposide exhibits a range of beneficial effects including alleviating inflammation, inhibiting the development of macrophage foam cells, improving lipid metabolism, and preventing platelet aggregation and thrombosis. It also demonstrates mitochondrial preservation, anti-apoptotic effects, and modulation of autophagy. Moreover, geniposide shows potential in improving oxidative stress and endoplasmic reticulum stress by maintaining the body's antioxidant and oxidative balance. Additionally, this review comprehensively details the biological properties of geniposide, including methods of extraction and purification, as well as its pharmacokinetics and toxicological characteristics. It further discusses the clinical applications of related biopharmaceuticals, emphasizing the potential of geniposide in the prevention and treatment of atherosclerotic cardiovascular diseases. Furthermore, it highlights the limitations of current research, aiming to provide insights for future studies. Highlights: Geniposide is an active iridoid glycoside compound extracted from the Chinese medicine Gardenia jasminoides Ellis. Geniposide can combat atherosclerosis through various mechanisms. Geniposide modulates immune cells and the reverse cholesterol transport, thereby limiting the formation of macrophage foam cells and improving lipid metabolism. The effects of geniposide on autophagy and apoptosis in VSMCs may be the emphasis of additional research. Whether geniposide can regulate the interaction between apoptosis and autophagy in CVD needs further investigation. Whether geniposide can target intestinal flora to inhibit atherosclerosis development needs further investigation. By selecting an appropriate route of administration and dosage regimen for geniposide, potential safety concerns can be effectively addressed. [ABSTRACT FROM AUTHOR]

Background: Studies assessing equity in the prevention of atherosclerotic cardiovascular disease (ASCVD) for Latinos living in the USA collectively yield mixed results. Latino persons are diverse in many ways that may influence cardiovascular health. The intersection of Latino nativity and ASCVD prevention is understudied. Objective: To determine whether disparities in ASCVD screening, detection, and prescribing differ for US Latinos by country of birth. Design: A retrospective cohort design utilizing 2014–2020 electronic health record data from a network of 320 community health centers across 12 states. Analyses occurred October 1, 2022, to September 30, 2023. Participants: Non-Hispanic White and Latino adults age 20–75 years, born in Cuba, Dominican Republic, El Salvador, Guatemala, Honduras, Mexico, and the USA. Exposures: Ethnicity and country of birth. Main Measures: Outcome measures included prevalence of statin eligibility, of having insufficient data to establish eligibility, odds of having a documented statin prescription, and rates of statin prescriptions and refills. We used covariate-adjusted logistic and generalized estimating equations logistic and negative binomial regressions to generate absolute and relative measures. Key Results: Among 108,672 adults, 23% (n = 25,422) were statin eligible for primary or secondary prevention of ASCVD using American College of Cardiology/American Heart Association guidelines. Latinos, born in and outside the USA were more likely eligible than Non-Hispanic White patients were (US-born Latino OR = 1.55 (95% CI = 1.37–1.75); non-US-born Latino OR = 1.63 (95% CI = 1.34–1.98)). The eligibility criteria that was met differed by ethnicity and nativity. Latinos overall were less likely missing data to establish eligibility and differences were again observed by specific non-US country of origin. Among those eligible, we observed no statistical difference in statin prescribing between US-born Latinos and non-Hispanic White persons; however, disparities varied by specific non-US country of origin. Conclusion: Efforts to improve Latino health in the USA will require approaches for preventing and reversing cardiovascular risk factors, and statin initiation that are Latino subgroup specific. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the most common cause of death in women. Pregnancy is an exposure unique to women leading to significant changes in maternal cardiovascular function. However, studies of the relationship between the number of pregnancies and ASCVD are rare. We aimed to clarify the association between the number of pregnancies and ASCVD. Methods: In this cross-sectional study, we used publicly available data from the National Health and Nutrition Examination Survey from 1999 to 2018. The number of pregnancies was divided into 0 (reference), 1, 2–3, 4–5, or ≥6, to create more stable estimates. A multiple logistic regression approach was used to examine the correlation between pregnancy and ASCVD in women aged 45 years or older who reported no menstruation in the past 12 months due to menopause, as well as in those aged 55 years or older, encompassing various age groups. We also separately estimated the association between the exposure of pregnancy and individual components of ASCVD. Results: In this study, age-adjusted data showed that women with six or more pregnancies had a doubled risk (odds ratio [OR]: 2.07) of ASCVD. The risk remained elevated at 1.69 times in women with four to five pregnancies and further increased to 1.90 times in women with six or more pregnancies, after adjusting for social factors. Similar patterns were observed when considering reproductive health and cardiovascular risk factors. Across the full population, every model that accounted for these variables consistently indicated that with an increasing number of pregnancies, we observed higher ORs for ASCVD risk (all p values <0.05). Conclusions: A higher number of pregnancies was associated with a higher risk of ASCVD after menopause, especially among women aged 45–64 years. Moreover, this association is particularly significant in the risk of stroke, cardiovascular heart disease, and heart attack. [ABSTRACT FROM AUTHOR]

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a), and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses the diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk. [ABSTRACT FROM AUTHOR]

Introduction: Although the risk of CVD is increased in cancer survivors, few studies have investigated the CVD risk in survivors of gastrointestinal (GI) cancer. Therefore, we evaluated the CVD risk using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score for GI cancer survivors and associated physical activity factors. Methods: Using the 2014–2019 Korean National Health and Nutrition Examination Surveys, data were collected for 262 GI cancer survivors and 1,310 cancer-free controls matched at a 1:5 ratio based on age and sex. The International Physical Activity Questionnaire Short-Form was used to assess physical activity, and the Euro QoL Questionnaire 5-Dimensional Classification (EQ-5D) was used to assess the health-related quality of life. Results: A multiple logistic regression analysis demonstrated a lower risk of ASCVD in GI cancer survivors than in controls (adjusted odds ratio [aOR] = 0.73, 95% confidence interval [CI] = 0.55-0.97). Moreover, the risk of having a high ASCVD score was significantly lower in individuals who performed sufficient aerobic physical activity (aOR = 0.59, 95% CI = 0.47-0.75) and those with an EQ-5D score 1 or 2 (aOR = 0.36, 95% CI = 0.20-0.65 and aOR = 0.31, 95% CI = 0.16-0.58, respectively). Conclusions: This population-based study demonstrated that engaging in sufficient physical activity can reduce the ASCVD risk among GI cancer survivors. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Faecal microbiota transplantation holds promise in mitigating fat accumulation and improving obesity. This study aimed to evaluate the long‐term efficacy of washed microbiota transplantation (WMT) among overweight patients.The clinical data pertaining to the treatment of patients with WMT were collected retrospectively. Compared alterations in body mass index (BMI), blood glucose, blood lipids and blood pressure prior to and following WMT treatment. Comprehensive efficacy evaluation and atherosclerosis cardiovascular disease (ASCVD) grading evaluation were carried out, with an analysis of gut microbiota composition before and after WMT.A total of 186 patients were included (80 overweight, 106 normal weight). WMT not only had the effect of improving overweight patients to the normal weight patients (p < .001), but also could significantly reduce BMI in the long term by restoring gut microbiota homeostasis (p < .001). In addition, the BMI improvement value of multi course was more significant than that of single course or double course. WMT had a significant ASCVD downgrade effect on the high‐risk and medium‐risk groups outside 1 year, while it did not increase the risk of upgrading ASCVD for low‐risk group.WMT could significantly reduce the BMI of overweight patients and still had an improvement effect in the long term. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a significant risk factor for developing cardiovascular disease and a leading cause of death worldwide. The occurrence of atherosclerosis is closely related to factors such as endothelial injury, lipid deposition, immunity, and inflammation. Conventional statins, currently used in atherosclerosis treatment, have numerous adverse side effects that limit their clinical utility, prompting the urgent need to identify safer and more effective therapeutic alternatives. Growing evidence indicates the significant potential of Chinese herbs in atherosclerosis treatment. Herbal monomer components, such as natural flavonoid compounds extracted from herbs like Coptis chinensis and Panax notoginseng, have been utilized for their lipid-lowering and inflammation-inhibiting effects in atherosclerosis treatment. These herbs can be used as single components in treating diseases and with other Chinese medicines to form herbal combinations. This approach targets the disease mechanism in multiple ways, enhancing the therapeutic effects. Thus, this review examines the roles of Chinese herbal medicine monomers and Chinese herbal compounds in inhibiting atherosclerosis, including regulating lipids, improving endothelial function, reducing oxidative stress, regulating inflammation and the immune response, and apoptosis. By highlighting these roles, our study offers new perspectives on atherosclerosis treatment with Chinese herbs and is anticipated to contribute to advancements in related research fields. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between serum uric acid (SUA) levels, thyroid hormones, and the occurrence of atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes mellitus (T2 DM), and to construct a risk prediction model for occurrence. Methods A retrospective study was conducted on 326 T2 DM patients treated in the Department of Endocrinology at Lishui People′s Hospital from May 2020 to May 2023. Patients were divided into the occurrence group (n=152) and non-occurrence group (n=174) based on whether ASCVD occurred. Clinical data and serum levels of SUA and thyroid hormones (TT3, TT4, FT3, FT4, TSH) were collected for all subjects. Univariate and multivariate logistic regression analyses were used to analyze the risk factors for ASCVD in T2DM patients, and a risk nomogram prediction model for ASCVD in T2DM patients was constructed based on these factors. Results There were statistically significant differences in age, fasting blood glucose, duration of diabetes, triglycerides, SUA, and TSH levels between the two groups (P＜0.05). However, there were no differences in other variables between the two groups (P＞0.05). Binary logistic regression analysis showed that older age, longer duration of diabetes, higher triglyceride levels, higher SUA levels, and higher TSH levels were independent risk factors for ASCVD in T2DM patients (P＜0.05). The ROC curve analysis results showed that the area under the ROC curve AUC of age, duration of diabetes, triglycerides, SUA, TSH, and the nomogram prediction model were 0.711, 0.702, 0.668, 0.755, 0.965, and 0.987, respectively, indicating good predictive value for ASCVD in T2DM patients. When the cut-off values were determined, the sensitivities were 0.638, 0.539, 0.638, 0.730, 0.941, and 0.960, respectively, and the specificities were 0.690, 0.799, 0.644, 0.661, 0.943, and 0.954, respectively. Bootstrap validation of the nomogram prediction model (B=1000) showed that the bias-corrected prediction curve overlapped well with the ideal curve, with a C-index of 0.975, indicating good predictive ability of the model. Decision curve analysis showed that the threshold probability range of the model was 0.01 to 0.98, with a net benefit rate ＞0. Conclusion Serum SUA and thyroid hormone levels are important indicators for predicting ASCVD in T2DM patients, and the constructed risk nomogram prediction model has good predictive performance and clinical application value. [ABSTRACT FROM AUTHOR]

Background: The role of diet choline in atherosclerotic cardiovascular disease (ASCVD) is uncertain. Findings from animal experiments are contradictory while there is a lack of clinical investigations. This study aimed to investigate the association between choline intake and ASCVD based on individuals from the National Health and Nutrition Examination Survey (NHANES) database. Methods: This cross-sectional study was conducted in 5525 individuals from the NHANES between 2011 and 2018. Participants were categorized into the ASCVD (n = 5015) and non-ASCVD (n = 510) groups. Univariable and multivariable-adjusted regression analyses were employed to investigate the relationship between diet choline and pertinent covariates. Logistic regression analysis and restricted cubic spline analysis were used to evaluate the association between choline intake and ASCVD. Results: ASCVD participants had higher choline intake compared to those without ASCVD. In the higher tertiles of choline intake, there was a greater proportion of males, married individuals, highly educated individuals, and those with increased physical activity, but a lower proportion of smokers and drinkers. In the higher tertiles of choline intake, a lower proportion of individuals had a history of congestive heart failure and stroke. After adjusting for age, gender, race, ethnicity, and physical activity, an inverse association between choline intake and heart disease, stroke, and ASCVD was found. A restricted cubic spline analysis showed a mirrored J-shaped relationship between choline and ASCVD, stroke and congestive heart failure in males. There was no association between dietary choline and metabolic syndrome. Conclusion: An inverse association was observed between choline intake and ASVCD among U.S. adults. Further large longitudinal studies are needed to test the causal relationship of choline and ASVCD. [ABSTRACT FROM AUTHOR]

Background: People with type 2 diabetes (T2D) are at elevated risk of cardiovascular disease (CVD) including stroke, yet existing real-world evidence (RWE) on the clinical and economic burden of stroke in this population is limited. The aim of this cohort study was to evaluate the clinical and economic burden of stroke among people with T2D in France. Methods: We conducted a retrospective RWE study using data from the nationally representative subset of the French Système National des Données de Santé (SNDS) database. We assessed the incidence of stroke requiring hospitalization between 2012 and 2018 among T2D patients. Subsequent clinical outcomes including CVD, stroke recurrence, and mortality were estimated overall and according to stroke subtype (ischemic versus hemorrhagic). We also examined the treatment patterns for glucose-lowering agents and CVD agents, health care resource utilization and medical costs. Results: Among 45,331 people with T2D without baseline history of stroke, 2090 (4.6%) had an incident stroke requiring hospitalization. The incidence of ischemic stroke per 1000 person-years was 4.9-times higher than hemorrhagic stroke (6.80 [95% confidence interval (CI) 6.47–7.15] versus 1.38 [1.24–1.54]). During a median follow-up of 2.4 years (interquartile range 0.6; 4.4) from date of index stroke, the rate of CVD, stroke recurrence and mortality per 1000 person-years was higher among hemorrhagic stroke patients than ischemic stroke patients (CVD 130.9 [107.7–159.0] versus 126.4 [117.2–136.4]; stroke recurrence: 86.7 [66.4–113.4] versus 66.5 [59.2–74.6]; mortality 291.5 [259.1–327.9] versus 144.1 [134.3–154.6]). These differences were not statistically significant, except for mortality (adjusted hazard ratio 1.95 [95% CI 1.66–2.92]). The proportion of patients prescribed glucagon-like peptide-1 receptor agonists increased from 4.2% at baseline to 6.6% during follow-up. The proportion of patients prescribed antihypertensives and statins only increased slightly following incident stroke (antihypertensives: 70.9% pre-stroke versus 76.7% post-stroke; statins: 24.1% pre-stroke versus 30.0% post-stroke). Overall, 68.8% of patients had a subsequent hospitalization. Median total medical costs were €12,199 (6846; 22,378). Conclusions: The high burden of stroke among people with T2D, along with the low proportion of patients receiving recommended treatments as per clinical guidelines, necessitates a strengthened and multidisciplinary approach to the CVD prevention and management in people with T2D. [ABSTRACT FROM AUTHOR]

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Most patients with atherosclerotic cardiovascular disease fail to achieve guideline-directed low-density lipoprotein cholesterol (LDL-C) goals. Twice-yearly inclisiran lowers LDL-C by ∼50% when added to statins. This study evaluated the effectiveness of an "inclisiran first" implementation strategy (adding inclisiran immediately upon failure to reach LDL-C <70 mg/dL despite receiving maximally tolerated statins) vs representative usual care in U.S. patients with atherosclerotic cardiovascular disease. VICTORION-INITIATE, a prospective, pragmatically designed trial, randomized patients 1:1 to inclisiran (284 mg at days 0, 90, and 270) plus usual care (lipid management at treating physician's discretion) vs usual care alone. Primary endpoints were percentage change in LDL-C from baseline and statin discontinuation rates. We randomized 450 patients (30.9% women, 12.4% Black, 15.3% Hispanic); mean baseline LDL-C was 97.4 mg/dL. The "inclisiran first" strategy led to significantly greater reductions in LDL-C from baseline to day 330 vs usual care (60.0% vs 7.0%; P < 0.001). Statin discontinuation rates with "inclisiran first" (6.0%) were noninferior vs usual care (16.7%). More "inclisiran first" patients achieved LDL-C goals vs usual care (<70 mg/dL: 81.8% vs 22.2%; <55 mg/dL: 71.6% vs 8.9%; P < 0.001). Treatment-emergent adverse event (TEAE) and serious TEAE rates compared similarly between treatment strategies (62.8% vs 53.7% and 11.5% vs 13.4%, respectively). Injection-site TEAEs and TEAEs causing treatment withdrawal occurred more commonly with "inclisiran first" than usual care (10.3% vs 0.0% and 2.6% vs 0.0%, respectively). An "inclisiran first" implementation strategy led to greater LDL-C lowering compared with usual care without discouraging statin use or raising new safety concerns. (A Randomized, Multicenter, Open-label Trial Comparing the Effectiveness of an "Inclisiran First" Implementation Strategy to Usual Care on LDL Cholesterol [LDL-C] in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C [≥70 mg/dL] Despite Receiving Maximally Tolerated Statin Therapy [VICTORION-INITIATE]; NCT04929249) [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: To enhance the predictive risk model for all-cause mortality in individuals with Type 2 Diabetes (T2DM) and prolonged Atherosclerotic Cardiovascular Disease (ASCVD) risk factors. Despite the utility of the Coronary Artery Calcium (CAC) score in assessing cardiovascular risk, its capacity to predict all-cause mortality remains limited. Methods: A retrospective cohort study included 1929 asymptomatic T2DM patients with ASCVD risk factors, aged 40–80. Variables encompassed demographic attributes, clinical parameters, CAC scores, comorbidities, and medication usage. Factors predicting all-cause mortality were selected to create a predictive scoring system. By using stepwise selection in a multivariate Cox proportional hazards model, we divided the patients into three risk groups. Results: In our analysis of all-cause mortality in T2DM patients with extended ASCVD risk factors over 5 years, we identified significant risk factors, their adjusted hazard ratios (aHR), and scores: e.g., CAC score > 1000 (aHR: 1.57, score: 2), CAC score 401–1000 (aHR: 2.05, score: 2), and more. These factors strongly predict all-cause mortality, with varying risk groups (e.g., very low-risk: 2.0%, very high-risk: 24.0%). Significant differences in 5-year overall survival rates were observed among these groups (log-rank test < 0.001). Conclusion: The Poh-Ai Predictive Scoring System excels in forecasting mortality and cardiovascular events in individuals with Type 2 Diabetes Mellitus and extended ASCVD risk factors. [ABSTRACT FROM AUTHOR]

To examine the association between depression, the use of antidepressants, and atherosclerotic cardiovascular disease (ASCVD). The South Korean national claims data was used. Among a nationally representative population, 273,656 subjects who had been diagnosed with depression and prescribed antidepressants ("DEP with antidepressants") and 78,851 subjects who had been diagnosed with depression but not prescribed antidepressants ("DEP without antidepressants") were identified to be eligible. Healthy controls (HCs) were 1:1 matched with DEP with antidepressants group for age and sex. We followed up on the occurrence of ASCVD including ischemic heart diseases and ischemic stroke. The risk of ASCVD was increased in the DEP with antidepressants group and decreased in the DEP without antidepressants group compared to HCs. Among those under antidepressants, tricyclic antidepressant users showed the highest risk of ASCVD compared to HCs. Among young adults, the risk of ASCVD was increased in both groups. The risk of ASCVD increased in depression patients taking antidepressants, while it decreased in depression patients not taking antidepressants. However, the relationship showed differences according to drug class and age group. • Depression is a well-known risk factor for atherosclerotic cardiovascular disease. • We examined the risk of ASCVD in depression patients with/without antidepressants. • Depression patients with antidepressants showed an increased risk of ASCVD. • Depression patients without antidepressants showed a decreased risk of ASCVD. • The use of antidepressants, rather than depression, is the risk factor for ASCVD. [ABSTRACT FROM AUTHOR]

Diabetes is a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia playing a critical role in the initiation and progression of ASCVD in diabetic patients. Currently in China, the prevalence of dyslipidemia in diabetes is high, while the control rate remains low. Therefore, to enhance lipid management in patients with diabetes, the Endocrinology and Metabolism Physician Branch of Chinese Medical Doctor Association, in collaboration with the Experts′ Committee of National Society of Cardiometabolic Medicine, has convened experts to develop a consensus on the management of dyslipidemia in patients with type 1 or type 2 diabetes. The development of this consensus is informed by the existing practices in lipid management among Chinese diabetic patients, incorporating contemporary evidence‑based findings and guidelines from national and international sources. The consensus encompasses the lipid profile characteristics, the current epidemiological status of dyslipidemia, ASCVD risk stratification, and lipid management procedures in diabetic patients. For the first time, both low‑density lipoprotein‑cholesterol (LDL‑C) and non‑high‑density lipoprotein‑cholesterol (non‑HDL‑C) have been recommended as primary targets for lipid intervention in diabetic patients. The consensus also includes a summary and recommendations for lipid management strategies in special diabetic populations, including children and adolescents, individuals aged 75 years and older, patients with chronic kidney disease, metabolic‑associated fatty liver disease, as well as those who are pregnant. This comprehensive consensus will contribute to the dissemination of key clinical advancements and guide clinical practice, aiming to improve cardiovascular outcomes in diabetic patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

[Display omitted] • In this nationwide primary prevention cohort study, about two-thirds of the subjects had a 10-year ASCVD risk of <5 %. • J-shaped associations were observed between MI risk, IS risk, and LDL cholesterol levels. • Associations between MI and IS risks and LDL cholesterol levels were influenced by ASCVD risk and obesity. • A J-shaped association was observed between hs-CRP level and LDL cholesterol level. • Therefore, low LDL cholesterol levels with no statin medication do not warrant safety from ASCVD. Low-density lipoprotein (LDL) cholesterol-lowering treatment is beneficial for the secondary or primary prevention of high-risk atherosclerotic cardiovascular disease (ASCVD). However, the prognostic implications of low LDL cholesterol levels in patients without previous ASCVD and without statin use remain elusive. From a nationwide cohort, 2,432,471 participants without previous ASCVD or statin use were included. For myocardial infarction (MI) and ischemic stroke (IS), participants were followed-up from 2009 to 2018. They were stratified according to 10-year ASCVD risk (<5 %, 5 %–<7.5 %, 7.5 %–<20 %, and ≥20 %) and LDL cholesterol level (<70, 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL). The relationship between LDL cholesterol levels and ASCVD events exhibited a J-shaped curve for both MI and IS. After classification according to the ASCVD risk, this J-shaped relationship was consistently observed for the composite of MI and IS. Participants with an LDL cholesterol level <70 mg/dL showed a higher MI risk than those with a level of 70–99 mg/dL or 100–129 mg/dL in the low-ASCVD risk group. The J-shaped curve between LDL cholesterol levels and MI risk was attenuated across ASCVD risk groups. For IS, participants with an LDL cholesterol level <70 mg/dL demonstrated increased risks compared with those with a level of 70–99 mg/dL, 100–129 mg/dL, or 130–159 mg/dL in the borderline, intermediate, and high ASCVD risk groups, respectively. In contrast, a linear association was observed in participants taking statins. Interestingly, a J-shaped association was observed between LDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) levels; the mean hs-CRP level and the proportion of individuals with increased hs-CRP levels were relatively high among individuals with an LDL cholesterol level <70 mg/dL. Although high LDL cholesterol levels increase the risk of ASCVD, low LDL cholesterol levels do not warrant safety from ASCVD. Therefore, individuals with low LDL cholesterol levels should be carefully monitored. [ABSTRACT FROM AUTHOR]

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Introduction: The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels. Methods: Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8 mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up. Results: The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively). Conclusion: This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk. [ABSTRACT FROM AUTHOR]

Background: Contemporary evidence supports the cardiovascular and renal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2is) in patients with diabetes. While metformin has traditionally been recommended as a first-line treatment, its exact role in improving cardiovascular outcomes remains uncertain. This study aims to evaluate the impact of combination therapy with metformin on the cardiovascular and renal outcomes in high-risk, treatment-naïve diabetic patients who have undergone SGLT2i therapy. Methods: Using the National Health Insurance Research Database in Taiwan, a retrospective cohort study was conducted. Treatment-naïve patients with diabetes and established atherosclerotic cardiovascular disease (ASCVD) undertaking SGLT2i therapy from 1 January 2016 to 31 December 2021 were included. Patients were categorized based on the concomitant use of metformin. Propensity score matching was employed to minimize confounding factors. The primary outcome was major adverse cardiovascular events (MACEs), with secondary outcomes including cardiovascular death, hospitalization for heart failure, and renal outcomes. Results: In total, 10,151 treatment-naïve diabetic patients with ASCVD were identified, with 2570 in the only SGLT2i therapy group and 7581 in the SGLT2i plus metformin group. In total, 2262 pairs were analyzed after propensity score adjustment. The risk of MACEs (36.6 vs. 42.1 events per 1000 person-years; hazard ratio 0.87, 95% confidence interval 0.70–1.09) and other outcomes did not significantly differ between the two treatment groups. Conclusions: In high-risk, treatment-naïve diabetic patients, initiating SGLT2i therapy alone or in combination with metformin resulted in comparable cardiovascular and renal outcomes. These findings suggest that metformin might not be mandatory as a first-line treatment for achieving cardiovascular benefits in such patients. [ABSTRACT FROM AUTHOR]

Aim: This study evaluated the safety and efficacy of a moderate‐intensity statin with ezetimibe combination therapy versus high‐intensity statin monotherapy in patients with metabolic syndrome (MetS) and atherosclerotic cardiovascular disease. Materials and Methods: In this post‐hoc subgroup analysis of the RACING trial, patients were analysed based on the presence of MetS. MetS was defined as meeting at least three of the five following criteria: (a) elevated waist circumference; (b) elevated triglycerides; (c) reduced high‐density lipoprotein cholesterol; (d) elevated blood pressure; and (e) elevated fasting glucose. The primary outcome was a 3‐year composite of cardiovascular death, major cardiovascular events, or non‐fatal stroke. Results: Of the 3780 patients enrolled in the RACING trial, 1703 (45.1%) had MetS at baseline. The primary outcome rate was 10.1% and 10.3% in patients with MetS receiving ezetimibe combination therapy versus high‐intensity statin monotherapy (hazard ratio = 0.97; 95% confidence interval = 0.72‐1.32; p =.868). Lower rates of intolerance‐related drug discontinuation or dose reduction (3.9% vs. 8.0%; p <.001) and lower low‐density lipoprotein cholesterol levels (57 vs. 65 mg/dl; p <.001) were observed with ezetimibe combination therapy versus high‐intensity statin monotherapy. Furthermore, the rate of new‐onset diabetes was 18.5% and 19.1% in each group (p =.822). There were no significant interactions between MetS and therapy regarding study outcomes in the total population. Conclusions: In patients with MetS and atherosclerotic cardiovascular disease, a moderate‐intensity statin with ezetimibe combination therapy had comparable cardiovascular benefits with those of high‐intensity statin monotherapy. Meanwhile, ezetimibe combination therapy was associated with lower drug intolerance and low‐density lipoprotein cholesterol levels, but there was no apparent between‐group difference in new‐onset diabetes. [ABSTRACT FROM AUTHOR]

The article discusses the use of gene editing as a potential therapy for reducing cholesterol levels in individuals with atherosclerotic cardiovascular disease (ASCVD). The current standard treatment for ASCVD involves the use of statins, but low adherence to these medications has led to the need for alternative therapies. The article explores different approaches to targeting PCSK9, a protein that plays a role in cholesterol regulation, including monoclonal antibodies, RNA interference, and gene editing using CRISPR/Cas9. The authors present the results of a phase 1b clinical trial evaluating the safety and tolerability of a gene editing therapy called VERVE-101 in patients with hypercholesterolemia. While the therapy showed promising results in reducing PCSK9 protein levels and LDL cholesterol, there were also some serious adverse events reported. The authors emphasize the need for further research to determine the long-term safety and efficacy of gene editing therapies for lipid-lowering. [Extracted from the article]

Familial hypercholesterolemia (FH) is a common inherited metabolic disorder with an elevated risk of atherosclerotic cardiovascular disease (ASCVD). The effects of coffee on FH individuals remain unclear. The aim of this study is to examine the association between coffee consumption and ASCVD and mortality in adults with clinical diagnosed FH. Cross-sectional and prospective (up to December 31st, 2019) analysis of National Health and Nutrition Examination Survey (NHANES) 1999–2018. Coffee consumption was calculated by 24-hour dietary recalls. Multivariable-adjusted logistic regression and Cox analysis were performed to evaluated the relationship between coffee consumption and ASCVD and all-cause mortality. A total of 1008 FH individuals with coffee information were included and were categorized into four groups: 357 (35.42%) did not consume coffee on a regular basis, 390 (38.69%) consumed 0.5–3 cups per day, 141 (13.99%) consumed 3–5 cups per day and 120 (11.90%) ≥5 cups per day. Higher coffee or caffeine consumption was associated with elevated risk of ASCVD and heart attack. Compared to non-coffee drinkers, ≥5 cups coffee drinking was associated with higher risk of all-cause mortality (multivariate HR: 1.67, 95%CI: 1.02–2.73, P = 0.04). The risk of all-cause death increased dose-dependently along with the higher coffee or caffeine intake (P < 0.05). The results remained similar among those who excluded non-coffee drinkers. Coffee consumption of up to five cups per day was associated with unfavorable ASCVD and all-cause mortality, suggesting that high coffee consumption should be avoided among patients with FH. [ABSTRACT FROM AUTHOR]

Introduction: N-3 polyunsaturated fatty acids (n-3 PUFAs), abundant in oily fish, exert anti-inflammatory cardiovascular protective effects. We aimed to investigate the association between fish-derived n-3 PUFAs, lifestyle habits, and neutrophil-to-lymphocyte ratio (NLR), an atherosclerotic cardiovascular disease (ASCVD) marker. Methods: This cross-sectional study included 6,950 participants with no history of ASCVD, who underwent annual health check-ups (average age, 46.3 ± 13.0 years; male:female ratio, 58.8%) between April 2019 and March 2020 at the Health Planning Center, Nihon University Hospital. We calculated n-3 PUFA consumption using a questionnaire and the Japan National Health and Nutrition Survey. Results: The average fish consumption frequency and fish-derived n-3 PUFA consumption were 2.20 ± 1.28 days/week and 5.20 ± 3.11 g/week, respectively. A higher fish-derived n-3 PUFA consumption was associated with a lower NLR. Multiple-stepwise regression analysis revealed that higher fish-derived n-3 PUFA consumption and more aerobic exercise habits were significant independent determinants of lower NLR. Furthermore, higher fish-derived n-3 PUFA consumption was associated with habitual aerobic exercise habits. Conclusion: Thus, higher fish-derived n-3 PUFA consumption and more aerobic exercise habits may be synergistically associated with lower NLR. This association may explain the preventive effects of fish consumption on the ASCVD risk. [ABSTRACT FROM AUTHOR]

Although statins have served as the cornerstone for pharmacological lowering of lipid levels in atherosclerotic cardiovascular disease (ASCVD) risk reduction, many patients are unable to achieve target doses of statin medication due to side effects or target levels of cholesterol reduction on statin monotherapy. The landscape of lipid-lowering strategies has expanded in recent years, with the emergence of therapies that make use of small interfering RNA (siRNA) and antisense oligonucleotides, in addition to traditional small-molecule agents. Non-statin therapies that have shown promising results in randomized controlled trials include adenosine triphosphate-citrate lyase inhibitors, proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibiting antibodies and siRNA, omega-3 polyunsaturated fatty acids, and lipoprotein(a) gene-inhibiting siRNA and ASOs, in addition to older therapies such as ezetimibe. In contrast, cholesteryl ester transfer protein (CETP) inhibitors have shown less promising results in randomized trials. The purpose of this narrative review is to summarize the evidence for these medications, with a focus on phase III randomized trials. [ABSTRACT FROM AUTHOR]

Objective To investigate the baseline and six-month follow-up data of the main lipid indices as well as low-density lipoprotein cholesterol (LDL-C) target goal attainment in accordance with the current guidelines among patients with acute cerebral infarction (ACI). Methods One thousand ninety-nine patients were consecutively enrolled from January 2021 to December 2022 and divided into ACI, old cerebral infarction (OCI), and control groups. General data [sex, age, body mass index (BMI), medications, smoking status, disease history, etc.], baseline data, and six-month follow-up main laboratory data were collected and analyzed. ACI patients were grouped into dyslipidemia and normal groups according to the lipid management guidelines of the European, American, and Chinese populations. Statistical methods were used to screen for possible predictors of dyslipidemia. Results Patients with ACI or OCI had higher total cholesterol (TC) and LDL-C levels than did the control group (all P<0.05). According to European (94.7%, 89.0% and 13.4%, P<0.01), American (94.7% vs. 67.7% vs. 45.9%, P<0.001) and Chinese (85.1% vs. 59.1% vs. 18.6%, P<0.001) standards, the proportion of dyslipidemia in the ACI group was greater than that in the OCI and control groups. According to European and American standards, increases in BMI and the estimated glomerular filtration rate (eGFR) are predictors of dyslipidemia in ACI patients. According to Chinese standards, increases in BMI, glycated hemoglobin (HbA1c) levels, and eGFRs are independent predictors of dyslipidemia in ACI patients. The 6-month follow-up of the main lipid levels revealed that among the ACI group, TC, LDL-C and triglyceride(TG) levels (4.86 vs. 3.79, P<0.001; 2.98 vs. 2.01, P<0.001; 1.46 vs. 1.20, P<0.001) and the proportion of dyslipidemia decreased significantly in accordance with European/American and Chinese standards (86.8% vs. 64.6%, P=0.015; 97.2% vs. 84.7%, P=0.012). Conclusion These results revealed that lipid management is still not optimal for patients with ACI. More attention should be given to ACI patients with elevated BMI, eGFR, and HbA1c values, which could lead to more individualized lipid management. Although the main lipid levels decreased significantly 6 months after discharge with lipid-lowering therapy, there is still a long way to go to enable more ACI patients to meet the guideline-recommended LDL-C target goal. [ABSTRACT FROM AUTHOR]

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American College of Cardiology/American Heart Association guidelines recommend distinct risk classification systems for primary and secondary cardiovascular disease prevention. However, both systems rely on similar predictors (eg, age and diabetes), indicating the possibility of a universal risk prediction approach for major adverse cardiovascular events (MACEs). The authors examined the performance of predictors in persons with and without atherosclerotic cardiovascular disease (ASCVD) and developed and validated a universal risk prediction model. Among 9,138 ARIC (Atherosclerosis Risk In Communities) participants with (n = 609) and without (n = 8,529) ASCVD at baseline (1996-1998), we examined established predictors in the risk classification systems and other predictors, such as body mass index and cardiac biomarkers (troponin and natriuretic peptide), using Cox models with MACEs (myocardial infarction, stroke, and heart failure). We also evaluated model performance. Over a follow-up of approximately 20 years, there were 3,209 MACEs (2,797 for no prior ASCVD). Most predictors showed similar associations with MACE regardless of baseline ASCVD status. A universal risk prediction model with the predictors (eg, established predictors, cardiac biomarkers) identified by least absolute shrinkage and selection operator regression and bootstrapping showed good discrimination for both groups (c-statistics of 0.747 and 0.691, respectively), and risk classification and showed excellent calibration, irrespective of ASCVD status. This universal prediction approach identified individuals without ASCVD who had a higher risk than some individuals with ASCVD and was validated externally in 5,322 participants in the MESA (Multi-Ethnic Study of Atherosclerosis). A universal risk prediction approach performed well in persons with and without ASCVD. This approach could facilitate the transition from primary to secondary prevention by streamlining risk classification and discussion between clinicians and patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Individual risk assessment for atherosclerotic cardiovascular disease is important for safe menopausal hormone prescription. Besides the traditional risk factors, female-specific risk variables related to pregnancy and gynecologic conditions importantly contribute to a more tailored risk assessment in women at middle age. Of these, prior pre-eclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome and early spontaneous menopause (<40 years) seem to be the strongest adverse risk variables. Concomitant inflammatory disorders should also be taken into account. Adding a coronary artery calcium score with a computed tomography scan to risk assessment has a high predictive value for future cardiovascular events. This should be considered to discriminate between low-risk and high-risk women when uncertainty exists. In women at intermediate risk, menopausal hormone therapy can be easily combined with preventive medication if cardiovascular risk factors are present. In women at higher risk who have severe disabling vasomotor symptoms, a lower dosage of hormone therapy can be considered in good collaboration between the gynecologist and the cardiologist/vascular specialist. [ABSTRACT FROM AUTHOR]

Background: The multimorbidity of Atherosclerotic cardiovascular disease (ASCVD) and many other chronic conditions is becoming common. This study aimed to assess multimorbidity distribution in ASCVD among adults in the United States from 1999 to 2018. Methods: This cross-sectional survey from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 using stratified multistage probability design. Among the 53,083 survey respondents during the study period, 5,729 US adults aged ≥ 20 years with ASCVD. Joinpoint regression was used to assess the statistical significance of prevalence trends in the prevalence of ASCVD stratified by multimorbidity. The Apriori association rule mining algorithm was used to identify common multimorbidity association patterns in ASCVD patients. Results: Overall, 5,729 of 53,083 individuals had ASCVD, and the prevalence showed a slow declining trend (biannual percentage change = -0.81%, p = 0.035, average 7.71%). The prevalence of ASCVD significantly decreased in populations without dyslipidemia, diabetes mellitus (DM), hypertension, asthma, chronic obstructive pulmonary disease (COPD), and arthritis (all groups, p < 0.05). Additionally, 65.6% of ASCVD patients had at least four of the 12 selected chronic conditions, with four and five being the most common numbers of conditions (17.9% and 17.7%, respectively). The five most common chronic conditions were (in order) dyslipidemia, hypertension, arthritis, chronic kidney disease, and DM. The coexistence of hypertension and dyslipidemia had the highest support in association rules (support = 0.63), while the coexistence of dyslipidemia, hypertension, metabolic syndrome, and DM had the highest lift (lift = 1.82). Conclusions: During the 20-year survey period, there was a significant decrease in the overall prevalence of ASCVD. However, this reduction was primarily observed in individuals without dyslipidemia, DM, hypertension, asthma, COPD, and arthritis. Among populations with any of the evaluated chronic conditions, the prevalence of ASCVD remained unchanged. Most of ASCVD patients had four or more concurrent chronic conditions. [ABSTRACT FROM AUTHOR]

Reducing circulating lipid levels is the centerpiece of strategies for preventing and treating atherosclerotic cardiovascular disease (ASCVD). Despite many available lipid-lowering medications, a substantial residual cardiovascular risk remains. Current clinical guidelines focus on plasma levels of low-density lipoprotein (LDL). Recent attention has been given to very low-density lipoprotein (VLDL), the precursor to LDL, and its role in the development of coronary atherosclerosis. Preclinical investigations have revealed that interventions targeting VLDL production or promoting VLDL metabolism, independent of the LDL receptor, can potentially decrease cholesterol levels and provide therapeutic benefits. Currently, methods, such as mipomersen, lomitapide, and ANGPTL3 inhibitors, are used to reduce plasma cholesterol and triglyceride levels by regulating the lipidation, secretion, and metabolism of VLDL. Targeting VLDL represents an avenue for new lipid-lowering strategies. Interventions aimed at reducing VLDL production or enhancing VLDL metabolism, independent of the LDL receptor, hold promise for lowering cholesterol levels and providing therapeutic benefits beyond LDL in the management of ASCVD. [ABSTRACT FROM AUTHOR]

There is growing evidence of prescribing sodium glucose co-transporters-2 inhibitor (SGLT-2) to patients with/at high risk of atherosclerotic cardiovascular disease as first-line (instead of metformin). This is the first meta-analysis to compare SGLT-2 inhibitors regarding the same. We aimed to compare SGLT-2 inhibitors and metformin regarding heart failure, acute coronary syndrome, and ischemic stroke. We systematically searched PubMed and Cochrane Library for relevant articles from the first article up to August 2022. The following keywords were used: Metformin, Salt glucose co-transporters inhibitors, SGLT-2 inhibitors, empagliflozin, dapagliflozin, canagliflozin, and first-line. The retrieved data were exported to an excel sheet detailing the author’s names, the country of origin of the study, the number of patients and control subjects, the study duration, and the total number of events in the interventional and exercise groups. Out of 108 articles screened, only three studies fulfilled the inclusion criteria, a databased study, and two cohorts with 10309 events and 86487 patients. The present meta-analysis showed that SGLT-2 inhibitors had lower rates of heart failure (odd ratio, 1.51, 95% CI, 1.10-2.08) and myocardial infarction (odd ratio, 1.45, 95% CI, 1.08-1.96) than metformin with a similar rate of stroke (odd ratio, 1.03, 95% CI, 0.66-1.61). Significant heterogeneity was observed. Sodium-glucose co-transporter inhibitors-2 as first-line therapy showed a lower heart failure and myocardial infarction compared to metformin. No significant difference was found between the two drugs regarding ischemic stroke. Further larger studies comparing the adverse event are needed. [ABSTRACT FROM AUTHOR]

Background: To estimate the contemporary prevalence of established cardiovascular disease (CVD) in adults with type 2 diabetes (T2D) in Mexico. Methods: CAPTURE was a multinational, non-interventional, cross-sectional study across 13 countries from five continents. Standardized demographic and clinical data were collected from adults with T2D attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data from Mexico are analyzed in this study. Results: Of the 9,823 patients included in the CAPTURE study, 820 (8.3%) participants were from Mexico, mainly attended in private centers (29.3% in 6 specialized diabetes treatment centers and 70.7% in 26 primary care centers). The median age was 63.0 years, 52.6% were women, the duration of diabetes was 11.8 years and the average HbA1c 7.5%. The weighted prevalence [95% CI] of CVD and atherosclerotic CVD was 36.9% [34.1–39.6] and 29.5% [26.7–32.3], respectively. Additionally, the prevalence of coronary heart disease, heart failure, peripheral arterial disease and cerebrovascular disease was 23.1% [20.6–25-7], 8.4% [6.8–10.0], 5.0% [3.5–6.5] and 3.9% [2.6–5.2], respectively. Glucose lowering drugs were used in 88.5% of patients, being metformin the most commonly drug used (79.4%), followed by sulfonylureas (26.3%). SGLT-2 inhibitors and GLP1 receptor agonists were used in 15.5% and 3.9%, respectively. Conclusions: In Mexico, nearly four out of ten patients with T2D mainly attended in private centers have CVD, particularly atherosclerotic CVD. Most patients were not taking glucose lowering drugs with proven CV benefit. [ABSTRACT FROM AUTHOR]

Multiomics approaches are pivotal in understanding atherosclerotic cardiovascular disease (ASCVD) and offer promising preventive and therapeutic strategies beyond traditional risk factors. Integrating genomics, epigenomics, transcriptomics, proteomics, and metabolomics data enhances risk stratification quality. Artificial intelligence (AI) and machine learning (ML) models provide advanced tools for accurate ASCVD risk prediction by integrating multiomics and clinical data. Large-scale collaborative efforts are essential for gathering comprehensive data sets to train AI/ML models effectively. Standardized data, interdisciplinary collaboration, and regulatory approval are crucial for successful implementation. Multiomics studies offer accurate preventive and therapeutic strategies for atherosclerotic cardiovascular disease (ASCVD) beyond traditional risk factors. By using artificial intelligence (AI) and machine learning (ML) approaches, it is possible to integrate multiple 'omics and clinical data sets into tools that can be utilized for the development of personalized diagnostic and therapeutic approaches. However, currently multiple challenges in data quality, integration, and privacy still need to be addressed. In this opinion, we emphasize that joined efforts, exemplified by the AtheroNET COST Action, have a pivotal role in overcoming the challenges to advance multiomics approaches in ASCVD research, with the aim to foster more precise and effective patient care. [ABSTRACT FROM AUTHOR]

Objective To investigate the correlation between serum levels of small dense low density lipoprotein-cholesterol （sdLDL-C） and chemokine CXC motifligand12（CXCL12） and diabetes mellitus with car⁃ diovascular disease（CVD). Methods A total of 256 diabetic patients treated in our hospital between June 2021 and September 2022 were selected as the diabetic group. The patients were grouped according to whether they had combined CVD or not. And the serum sdLDL-C as well as CXCL12 levels of each group were compared with healthy volunteers. Risk factors for the complication of CVD in diabetic patients were analyzed. To analyze the diag⁃ nostic value of sdLDL-C, CXCL12 and combined test for diabetic patients with complicated CVD. Results Serum sdLDL-C and CXCL12 levels were higher in the diabetes group than in the control group （P < 0.05). The duration of disease, BMI, LDL-C, and serum sdLDL-C and CXCL12 levels were higher in the cardiovascular disease group than in the non-cardiovascular disease group （P < 0.05). A multifactorial logistic regression analysis showed that sdLDL-C and CXCL12 were independent risk factors for the complication of CVD in diabetic patients （P < 0.05). The sensitivity and specificity of serum sdLDL-C and CXCL12 combined test were higher than that of single test. Conclusion Elevated serum sdLDL-C and CXCL12 levels in patients with diabetes mellitus are independent risk factors for the complication of CVD, and the combination of these two tests has a high diagnostic value for diabetes mellitus with CVD. [ABSTRACT FROM AUTHOR]

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which have proven cardiovascular benefits, are recommended in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). However, there is limited real-world evidence comparing the effects of once-weekly (OW) GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP-4is). This observational cohort study (1/1/2017–9/30/2021) used data from the Optum Clinformatics® Data Mart to compare time to incident clinical cardiovascular outcomes, health care resource utilization (HCRU), and medical costs in new adult users of OW GLP-1 RAs and DPP-4is with T2D and ASCVD. Methods: Time to occurrence of ischemic stroke, myocardial infarction (MI), or their composite and ASCVD-related and all-cause HCRU and medical costs were investigated. Baseline characteristics were balanced using inverse probability of treatment weighting. Survival analyses were conducted to compare risks during exposure. Results: OW GLP-1 RA users (weighted N = 25,287) had 26%, 22%, and 24% lower risk of ischemic stroke, MI, and their composite, respectively, compared with DPP-4i users (weighted N = 39,684; all P < 0.01). Compared with DPP-4i users, OW GLP-1 RA users had 25% and 26% lower ASCVD-related and all-cause hospitalization costs, 19% and 23% lower ASCVD-related and all-cause medical costs, 23% and 27% fewer ASCVD-related and all-cause hospitalizations, 13% and 8% fewer ASCVD-related and all-cause outpatient visits, and 8% fewer all-cause ER visits (all P < 0.01). Conclusions: In adults with T2D and ASCVD, OW GLP-1 RAs are associated with reduced stroke and MI risks and ASCVD-related and all-cause HCRU and costs vs DPP-4is. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Clinical guidelines for the management of individuals with type 2 diabetes mellitus endorse the systematic assessment of atherosclerotic cardiovascular disease risk for early interventions. In this study, we aimed to develop machine learning models to predict 3‐year atherosclerotic cardiovascular disease risk in Chinese type 2 diabetes mellitus patients. Materials and Methods: Clinical records of 4,722 individuals with type 2 diabetes mellitus admitted to 94 hospitals were used. The features included demographic information, disease histories, laboratory tests and physical examinations. Logistic regression, support vector machine, gradient boosting decision tree, random forest and adaptive boosting were applied for model construction. The performance of these models was evaluated using the area under the receiver operating characteristic curve. Additionally, we applied SHapley Additive exPlanation values to explain the prediction model. Results: All five models achieved good performance in both internal and external test sets (area under the receiver operating characteristic curve >0.8). Random forest showed the highest discrimination ability, with sensitivity and specificity being 0.838 and 0.814, respectively. The SHapley Additive exPlanation analyses showed that previous history of diabetic peripheral vascular disease, older populations and longer diabetes duration were the three most influential predictors. Conclusions: The prediction models offer opportunities to personalize treatment and maximize the benefits of these medical interventions. [ABSTRACT FROM AUTHOR]

High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood. Our goal was to identify and define key HDL-associated proteins that modulate CEC in humans. The proteomic signature of plasma HDL was quantified in 36 individuals in the multi-ethnic population-based Dallas Heart Study (DHS) cohort that exhibited persistent extremely high (>=90th%) or extremely low CEC (<=10th%) over 15 years. Levels of apolipoprotein (Apo)A-I associated ApoC-II, ApoC-III, and ApoA-IV were differentially correlated with CEC in high (r = 0.49, 0.41, and −0.21 respectively) and low (r = −0.46, −0.41, and 0.66 respectively) CEC groups (p for heterogeneity (pHet) = 0.03, 0.04, and 0.003 respectively). Further, we observed that levels of ApoA-I with ApoC-III, complement C3 (CO3), ApoE, and plasminogen (PLMG) were inversely associated with CEC in individuals within the low CEC group (r = −0.11 to −0.25 for subspecies with these proteins vs. r = 0.58 to 0.65 for subspecies lacking these proteins; p < 0.05 for heterogeneity). These findings suggest that enrichment of specific proteins on HDLs and, thus, different subspecies of HDLs, differentially modulate the removal of cholesterol from the vasculature. [ABSTRACT FROM AUTHOR]

In 2023 there are still even 75% of patients over the target of low-density lipoprotein cholesterol (LDL-C), and hypercholesterolemia is the most common and the worst monitored cardiovascular risk factor. How it is possible, considering the knowledge we have on the role of cholesterol in the process of atherosclerosis, atherosclerotic cardiovascular disease (ASCVD) and its complications, on the methods of lipid disorders diagnosis, prevention, and treatment. Nowadays, almost 4 million deaths per year are attributed to LDL-C, and even 2/3 of all CVD deaths to ASCVD, therefore hypothetically we should easily prevent few to several million of deaths with early diagnosis, and early and intensive non-pharmacological and pharmacological therapies. Moreover, lipidology is now, besides oncology, the area with the highest number of new and ongoing trials with new effective and safe medications that have already appeared and will soon be available. Therefore, we have no doubt that year 2023 should be called the year of new and prospective lipid lowering therapies (LLTs). In this State-of-the-Art paper we summarized the most important trials, studies, and recommendations on the new and prospective LLTs, with suitable graphical summaries that might be helpful for the physicians in their practice with a look to the nearest future with prospective therapies being still under investigation. Let's hope all those medications helps to render dyslipidemia a rare disease in next few years. [ABSTRACT FROM AUTHOR]

Artery stenosis due to atherosclerosis is the most common cause of cardiovascular disease. In addition to known risk factors, researchers have found that intestinal flora can influence the pathogenesis of atherosclerosis through its metabolites (short-chain fatty acids, trimethylamine oxide, indoles), the metabolism of bile acids, and the inflammatory response, and the relevant evidence has been supported experimentally. This article presents a systematic review of the relationship between intestinal flora and atherosclerotic cardiovascular disease, the microscopic mechanisms by which intestinal flora affect the pathogenesis of atherosclerotic cardiovascular disease, and recent advances in the treatment of atherosclerotic cardiovascular disease using intestinal flora as a target. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular diseases (ASCVD) present a global public health challenge with potentially fatal consequences. The key factor in the prevention of ASCVD is the control of LDL cholesterol (LDL-C) levels. Herein we present two important agents for the reduction of elevated LDL-C levels: rosuvastatin and ezetimibe. Rosuvastatin is a potent HMG-CoA reductase inhibitor that considerably lowers LDL-C, increases HDL cholesterol, and reduces triglyceride levels. Ezetimibe, on the other hand, inhibits the intestinal absorption of cholesterol. The combination of these drugs enables achieving target cholesterol levels. Although statins are the cornerstone therapy for LDL-C reduction, they often need to be combined with ezetimibe, especially in high-risk patients. Research shows that this combination can significantly reduce the risk of cardiovascular events. Despite the guidelines, achieving target LDL-C levels is often challenging in practice. A statin/ezetimibe combination may be key to achieving set targets and improving cardiac health. Control of LDL-C levels is key in the prevention of ASCVD. An integrated approach, including healthy diet, exercise, and pharmacotherapy, is crucial in fighting this global public health challenge. [ABSTRACT FROM AUTHOR]

The performance of the American College of Cardiology/American Heart Association pooled cohort equation (PCE) for atherosclerotic cardiovascular disease (ASCVD) in real-world clinical practice has not been evaluated extensively. The goal of this study was to test the performance of PCE to predict ASCVD risk in the community, and determine if including individuals with values outside the PCE range (ie, age, blood pressure, cholesterol) or statin therapy initiation over follow-up would significantly affect PCE predictive capabilities. The PCE was validated in a community-based cohort of consecutive patients who sought primary care in Olmsted County, Minnesota, between 1997 and 2000, followed-up through 2016. Inclusion criteria were similar to those of PCE derivation. Patient information was ascertained by using the record linkage system of the Rochester Epidemiology Project. ASCVD events (nonfatal and fatal myocardial infarction and ischemic stroke) were validated in duplicate. Calculated and observed ASCVD risk and c-statistics were compared across predefined groups. This study included 30,042 adults, with a mean age of 48.5 ± 12.2 years; 46% were male. Median follow-up was 16.5 years, truncated at 10 years for this analysis. Mean ASCVD risk was 5.6% ± 8.73%. There were 1,555 ASCVD events (5.2%). The PCE revealed good performance overall (c-statistic 0.78) and in sex and race subgroups; it was highest among non-White female subjects (c-statistic 0.81) and lowest in White male subjects (c-statistic 0.77). Out-of-range values and initiation of statin medication did not affect model performance. The PCE performed well in a community cohort representing real-world clinical practice. Values outside PCE ranges and initiation of statin medication did not affect performance. These results have implications for the applicability of current strategies for the prevention of ASCVD. [Display omitted] [ABSTRACT FROM AUTHOR]