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Coronary artery disease (CAD) is a complex, multifactorial disease caused, in particular, by inflammation and cholesterol metabolism. At the molecular level, the role of tissue-specific signaling pathways leading to CAD is still largely unexplored. This study relied on two main resources: (1) genes with impact on atherosclerosis/CAD, and (2) liver-specific transcriptome analyses from human and mouse studies. The transcription factor activating transcription factor 3 (ATF3) was identified as a key regulator of a liver network relevant to atherosclerosis and linked to inflammation and cholesterol metabolism. ATF3 was predicted to be a direct and indirect (via MAF BZIP Transcription Factor F (MAFF)) regulator of low-density lipoprotein receptor (LDLR). Chromatin immunoprecipitation DNA sequencing (ChIP-seq) data from human liver cells revealed an ATF3 binding motif in the promoter regions of MAFF and LDLR. siRNA knockdown of ATF3 in human Hep3B liver cells significantly upregulated LDLR expression (p < 0.01). Inflammation induced by lipopolysaccharide (LPS) stimulation resulted in significant upregulation of ATF3 (p < 0.01) and subsequent downregulation of LDLR (p < 0.001). Liver-specific expression data from human CAD patients undergoing coronary artery bypass grafting (CABG) surgery (STARNET) and mouse models (HMDP) confirmed the regulatory role of ATF3 in the homeostasis of cholesterol metabolism. This study suggests that ATF3 might be a promising treatment candidate for lowering LDL cholesterol and reducing cardiovascular risk.

Cardiovascular diseases (CVDs) are some of the major causes of death worldwide. The modern lifestyle elevates the risk of CVDs. CVDs have several risk factors such as obesity, dyslipidemia, atherosclerosis, hypertension, and diabetes. Using herbal and natural products plays a pivotal role in the treatment of different diseases such as CVDs, diabetes, and metabolic syndrome. Propolis, a natural resinous mixture, is made by honey bees. Its main components are phenolics and terpenoid compounds such as caffeic acid phenethyl ester, chrysin, and quercetin. In this review, multiple studies regarding the pharmacological impacts of propolis and its constituents with their related mechanisms of action against mentioned CVD risk factors have been discussed in detail. Here, we used electronic databases or search engines such as Scopus, Web of Science, Pubmed, and Google Scholar without time limitations. The primary components of propolis are phenolics and terpenoid compounds such as caffeic acid phenethyl ester, chrysin and quercetin. Propolis and its constituents have been found to exhibit anti-obesity, anti-hypertension, anti-dyslipidemic, anti-atherosclerosis, and anti-diabetic effects. The vast majority of studies discussed in this review demonstrate that propolis and its constituents could have therapeutic effects against mentioned CVD risk factors via several mechanisms such as antioxidant, anti-inflammatory, reducing adipogenesis, HMG-CoA reductase inhibitory effect, inhibition of the ACE, increasing insulin secretion, NO level, etc.

Atherosclerosis is a progressive inflammatory disease leading to mortality and morbidity in the civilized world. Atherosclerosis manifests as an accumulation of plaques in the intimal layer of the arterial wall that, by its subsequent erosion or rupture, triggers cardiovascular diseases. Diabetes mellitus is a well-known risk factor for atherosclerosis. Indeed, Type 2 diabetes mellitus patients have an increased risk of atherosclerosis and its associated-cardiovascular complications than non-diabetic patients. Sodium-glucose co-transport 2 inhibitors (SGLT2i), a novel anti-diabetic drugs, have a surprising advantage in cardiovascular effects, such as reducing cardiovascular death in a patient with or without diabetes. Numerous studies have shown that atherosclerosis is due to a significant inflammatory burden and that SGLT2i may play a role in inflammation. In fact, several experiment results have demonstrated that SGLT2i, with suppression of inflammatory mechanism, slows the progression of atherosclerosis. Therefore, SGLT2i may have a double benefit in terms of glycemic control and control of the atherosclerotic process at a myocardial and vascular level. This review elaborates on the anti-inflammatory effects of sodium-glucose co-transporter 2 inhibitors on atherosclerosis.

Purpose Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality worldwide. Statins, which are effective in preventing ASCVD, are underused, particularly for primary prevention. This study examined trends in statin use for primary ASCVD prevention from 1999 to 2020, focusing on demographic variations. Methods Utilizing data from the National Health and Nutrition Examination Survey, the present study includes individuals aged 18 years and older who had a greater than 10% risk of ASCVD over 10 years, and excluded patients with existing ASCVD. Subgroup analyses by demographic categories were performed. We calculated the changes in statin usage and used linear and quadratic tests to assess the linear and nonlinear trends in those changes. Results A total of 10,037 participants were included. Statin usage increased from 16.16% in 1999 to 36.24% in 2010, and 41.74% in 2020 (quadratic P -value < 0.001). In the 18–44 years age group, statin usage increased from 2.52% in 1999 to 8.14% in 2020 (linear P -value = 0.322), showing no significant linear trend. In the “never-married” group, statin usage increased from 19.16% in 1999 to 30.05% in 2020 (linear P -value = 0.256). Conclusion Statin usage has shown a positive trend among populations requiring primary prevention for ASCVD. Currently, health policies are proving effective. However, the overall statin usage rate remains less than 50%. Additionally, young and never-married individuals should also receive special attention regarding statin usage as primary treatment for ASCVD.

Background Research on the association between atherosclerosis cardiovascular diseases (ASCVDs) and hearing loss (HL) in older people has yielded mixed findings in recent years. Understanding this relationship is crucial for developing early strategies that address both cardiovascular health and auditory function in older adults. Methods To examine the potential association between common ASCVDs (heart attack, coronary heart disease, and stroke) and HL, assessing the mediating effect of the frailty index (FI) and Life’s essential 8 (LE8) metrics. The degree of HL was measured by pure tone average (PTA). This cross-sectional analysis utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2003 to 2018, including 4,441 adults aged 60 or older with comprehensive cardiovascular and hearing measurement data. Statistical analysis was conducted from February 16, 2024, to July 7, 2024. Results The study identified significant correlations between all three ASCVDs and HL in older participants aged 60 or older, particularly noting that heart attacks were notably associated with HL at higher frequencies (2 and 4 kHz). Older participants, especially those aged 75 and above, were more susceptible to stroke-related HL, with a delayed impact observed in females. FI and LE8 mediated the heart attack-HL association in adults aged 75 and above, with FI demonstrating a stronger role than LE8. Conclusion The findings elucidate a complex interplay between cardiovascular health and auditory function, emphasizing that heart attacks may exacerbate HL through the frailty pathway in certain older populations. These results highlight the need for tailored cardiovascular interventions and proactive measures to mitigate HL risks. Future research should focus on defining these pathophysiological associations more clearly to develop targeted interventions for vulnerable older people. Graphical abstract

Cardiovascular disease (CVD) is causing high mortality worldwide (World Health Organization-WHO, 2015). Atherosclerosis, the hardening and narrowing of arteries caused by the accumulation of fatty acids and lipids (cholesterol plaques), is a main reason of stroke, myocardial infarction, and angina. Present therapies for cardiovascular disease basically use statins such as β-Hydroxy β-methylglutaryl-CoA, with <70% efficacy and multiple side effects. An in vitro investigation was conducted to evaluate the impact of kaempferol, a natural medication, in an atherosclerotic cell model. We used cytotoxicity assays, Boyden chamber invasion assays, and quantitative PCR. Affymetrix microarrays were used to profile the entire transcriptome of kaempferol-treated cell lines, and Partek Genomic Suite was used to interpret the results. Kaempferol was not cytotoxic to THP-1 macrophages. In comparison to the control, kaempferol reduced monocyte migration mediated by monocyte chemotactic protein 1 (MCP-1) by 80%. The qPCR results showed a 73.7-fold reduction in MCP-1 and a 2.5-fold reduction in intercellular adhesion molecule 1 (ICAM-1) expression in kaempferol-treated cells. In interferon gamma (IFN-γ) without kaempferol and IFN-γ with kaempferol treated cells, we found 295 and 168 differentially expressed genes (DEGs), respectively. According to DEG pathway analysis, kaempferol exhibits anti-atherosclerosis and anti-inflammatory characteristics. Kaempferol is an effective and safe therapy for atherosclerosis.

Brain metastases (BM) constitute the most common intracranial tumor in adults. Prior literature indicates the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score is associated with increased risk of cancer, potentially attributable to shared risk factors. Understanding the role of ASCVD risk scores in BM may help optimize their care and inform clinical decision-making. Our aim was to explore associations between ASCVD risk score in BM patients and their overall survival, hospital charges, and non-routine discharge disposition. Electronic medical records were reviewed to collect clinical data for BM patients undergoing surgery at a single institution (2017–2021). Regression analyses were performed accordingly and maximally selected rank statistics were employed to identify an optimal cutoff for ASCVD risk scores. The random survival forest (RSF) machine learning technique identified the most important variable associated with survival outcomes in BM patients. A total of 139 patients were included with average age 62.93±9.29 years, 48.2 % male, 25.2 % with high hospital charges, and 23.7 % experiencing non-routine discharge. Among these patients, 32.3 % had prior history of an ASCVD event, while 67.7 % did not. Overall, this cohort had an average 10-year ASCVD risk score of 12.51±12.98, indicating intermediate risk of ASCVD among all BM patients. On multivariate logistic regression, prior history of ASCVD was associated with higher odds of high hospital charges (OR=3.670, p=0.018), and higher ASCVD risk scores were associated with greater odds of non-routine discharge (OR=1.059, p=0.012). On the multivariate Cox regression model, higher ASCVD risk scores correlated with worse overall survival (HR=1.031, p=0.014). A threshold of 25.1 was identified for high-risk ASCVD scores. Patients with ASCVD scores >25.1 exhibited reduced overall survival in Kaplan-Meier analysis (p=0.015) and multivariate Cox regression (HR: 2.811, p=0.016). Notably, ASCVD risk scores were found to be the most important variable in predicting worse survival outcomes in BM patients compared to other established frailty indices. This study indicates higher ASCVD risk scores in BM patients are associated with worse overall survival. Integrating ASCVD assessment into clinical workflow may facilitate more informed risk-based decision-making. •10-year ASCVD risk score predicts worse survival in brain metastasis patients.•Prior ASCVD events increase the odds of higher hospital charges.•Elevated 10-year ASCVD risk scores associated with non-routine discharge.•ASCVD scores outperform traditional frailty indices in predicting BM survival.•Incorporating ASCVD risk scores can optimize risk-based decision-making for BM care.

Several risk prediction models exist to predict atherosclerotic cardiovascular disease in asymptomatic individuals, but systematic reviews have generally found these models to be of limited utility. The coronary artery calcium score (CACS) offers an improvement in risk prediction, yet its role remains contentious. Notably, its negative predictive value has a high ability to rule out clinically relevant atherosclerotic cardiovascular disease. Nonetheless, CACS 0 does not permanently reclassify to a lower cardiovascular risk and periodic reassessment every 5 to 10 years remains necessary. Conversely, elevated CACS (> 100 or > 75th percentile adjusted for age, sex and ethnicity) can reclassify intermediate-risk individuals to a high risk, benefiting from preventive medication. The forthcoming update to the Dutch cardiovascular risk management guideline intends to re-position CACS for cardiovascular risk assessment as such in asymptomatic individuals. Beyond CACS as a single number, several guidelines recommend coronary CT angiography (CCTA), which provides additional information about luminal stenosis and (high-risk) plaque composition, as the first choice of test in symptomatic patients and high-risk patients. Ongoing randomised studies will have to determine the value of atherosclerosis evaluation with CCTA for primary prevention in asymptomatic individuals.

Purpose of Review Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of premature death. Lipid disorders, particularly elevated serum low-density lipoprotein cholesterol (LDL-C), contribute significantly to ASCVD. The risk of developing ASCVD is influenced by the duration of exposure to elevated LDL-C concentrations (cholesterol-years concept). Implementing lipid-lowering treatments based on the principles of “the earlier the better,” “the lower the better,” and “the longer the better” has been shown to reduce cardiovascular risk and significantly extend lifespan. Despite the availability of numerous lipid-lowering drugs, achieving satisfactory control of lipid disorders remains very challenging. Therefore, there is a need for novel approaches to improve treatment adherence. Recent Findings One promising solution under investigation is the development of an anti-PCSK9 vaccine, which could be administered annually to provide long-term control over LDL-C concentrations. Experimental studies and the sole clinical trial conducted thus far have demonstrated that the anti-PCSK9 vaccine induces a durable immune response associated with lipid-lowering and anti-atherosclerotic effects. Furthermore, it has exhibited good tolerability and a satisfactory safety profile. However, we still need data from phase 2, 3, and cardiovascular outcome trial to confirm its safety and efficacy and add value in the armamentarium of available and perspective lipid-lowering drugs. Summary This article highlights the significance of developing an anti-PCSK9 vaccine and provides an overview of the current knowledge on various anti-PCSK9 vaccines.

Cardiovascular disease （CVD） is the leading cause of death worldwide and contributes considerably to morbidity The underlying cause is atherosclerosisThe development of new preventive therapies is one of the steps to control the CVD epidemic. It is increasingly demanded that promising therapies be evaluated in trials using cardiovascular （CV） morbidity and mortality （M and M） as a primary outcome.