Therapeutic potentials of allicin in cardiovascular disease: advances and future directions.

Cardiovascular disease (CVD) remains the predominant cause of mortality and disability worldwide. Against this backdrop, finding effective drugs for the pharmacological treatment of CVD has become one of the most urgent and challenging issues in medical research. Garlic (Allium sativum L.) is one of the oldest plants and is world-renowned for its dietary and medicinal values. Allicin (diallyl thiosulfinate) is one of the primary natural active ingredients in garlic, which has been proven to have powerful cardioprotective effects and mediate various pathological processes related to CVD, such as inflammatory factor secretion, myocardial cell apoptosis, oxidative stress, and more. Therefore, allicin holds a promising application prospect in the treatment of CVD. This review summarized the biological functions of allicin and its potential mechanisms in CVD, including antioxidation, anti-inflammation, and anti-apoptosis effects. Reckoning with these, we delved into recent studies on allicin's cardioprotective effects concerning various CVDs, such as atherosclerosis, hypertension, myocardial infarction, arrhythmia, cardiac hypertrophy, heart failure, and cardiotoxicity. Further, considering the tremendous advancement in nanomedicine, nanotechnology-based drug delivery systems show promise in addressing limitations of allicin's clinical applications, including improving its solubility, stability, and bioavailability. Through this review, we hope to provide a reference for further research on allicin in cardioprotection and drug development.

Growth differentiation factor 15 (GDF-15) as a biomarker of cardiovascular risk in chronic musculoskeletal pain.

BACKGROUND: It is unknown whether growth differentiation factor 15 (GDF-15) is associated with chronic musculoskeletal pain (CMP) and whether or not its association with incident cardiovascular disease (CVD) changes according to CMP status. METHODS: 1,957 randomly-selected adults aged ≥65 years without prior CVD were followed up between 2015-2023. CMP was classified according to its intensity, frequency, and interference with daily activities. The association between GDF-15 levels and CMP was assessed using linear models with progressive inclusion of potential confounders, whereas the association between GDF-15 and CVD risk was evaluated with Cox-proportional hazard models with similar adjustment and interaction terms between GDF-15 and CMP. The incremental predictive performance of GDF-15 over standard predictors was evaluated using discrimination and risk reclassification metrics. RESULTS: GDF-15 concentrations were 6.90% (95%CI:2.56;11.25) higher in individuals with CMP, and up to 8.89% (4.07;15.71) and 15.79% (8.43;23.16) higher in those with ≥3 CMP locations and interfering pain. These increased levels were influenced by a higher prevalence of cardiometabolic risk factors, functional impairments, depressive symptoms, and greater levels of inflammation in individuals with CMP. In fully-adjusted models, a two-fold increase in GDF-15 was associated with a with a 1.49 increased risk (95%CI: 1.08; 2.05) of a CVD event in individuals with CMP, but not among those without CMP [1.02 (0.77; 1.35)]; p-interaction 0.041. Adding GDF-15 to models including the Framingham Risk Score improved predictive performance among individuals with CMP. CONCLUSIONS: We provide evidence that GDF-15 could serve as a biomarker to assess CMP, as well as to predict CVD incidence in individuals with CMP.

Diabetic Heart Disease: An Intricate Interplay of a Widespread Metabolic Disorder with the Cardiovascular System.

Diabetes is a chronic medical condition that causes high glycaemic levels, leading to damage to vital organs over time. It is a common disease worldwide, affecting around 422 million individuals living in middle- and low-income countries, which make up most of the population. Unfortunately, diabetes results in 1.5 million deaths annually. Diabetic patients are at a higher risk for developing cardiovascular conditions. Diabetic heart disease constitutes multiple genres, including diabetic cardiomyopathy, coronary artery disease, and heart failure. Hypoglycaemic agents aim to prevent these metabolic issues however some of these are cardiotoxic in nature. In contrast, other hypoglycaemic agents work beyond controlling glycaemic levels with their cardioprotective properties. Given that there is an alarming increase in diabetic heart disease cases universally, we have attempted to review the existing data on the topic and the effects of hypoglycaemic drugs on heart diseases.

Analysis of Alterations in Intestinal Flora in Chinese Elderly with Cardiovascular Disease and Its Association with Trimethylamine.

To investigate the changes in the intestinal flora in the Chinese elderly with cardiovascular disease (CVD) and its correlation with the metabolism of trimethylamine (TMA), the intestinal flora composition of elderly individuals with CVD and healthy elderly individuals was analyzed using 16S rRNA sequencing, the TMA levels in the feces of elderly were detected using headspace-gas chromatography (HS-GC), and four kinds of characterized TMA-producing intestinal bacteria in the elderly were quantified using real-time fluorescence quantitative polymerase chain reaction (qPCR). The results showed that Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, and Verrucomicrobia are the dominant microorganisms of the intestinal flora in the Chinese elderly. And there were significant differences in the intestinal bacteria composition between healthy elderly individuals and those with CVD, accompanied by a notable difference in the TMA content. The richness and diversity of the intestinal flora in the elderly with CVD were higher than those in the healthy elderly. Correlation analysis indicated that certain significantly different intestinal flora were associated with the TMA levels. Our findings showed a significant difference in TMA-producing intestinal flora between healthy elderly individuals and those with CVD. The TMA levels were found to be positively and significantly correlated with Klebsiella pneumoniae, suggesting that this bacterium is closely linked to the production of TMA in the elderly gut. This may have implications for the development and progression of CVD in the elderly population.

Advancements in tissue engineering for cardiovascular health: a biomedical engineering perspective.

Myocardial infarction (MI) stands as a prominent contributor to global cardiovascular disease (CVD) mortality rates. Acute MI (AMI) can result in the loss of a large number of cardiomyocytes (CMs), which the adult heart struggles to replenish due to its limited regenerative capacity. Consequently, this deficit in CMs often precipitates severe complications such as heart failure (HF), with whole heart transplantation remaining the sole definitive treatment option, albeit constrained by inherent limitations. In response to these challenges, the integration of bio-functional materials within cardiac tissue engineering has emerged as a groundbreaking approach with significant potential for cardiac tissue replacement. Bioengineering strategies entail fortifying or substituting biological tissues through the orchestrated interplay of cells, engineering methodologies, and innovative materials. Biomaterial scaffolds, crucial in this paradigm, provide the essential microenvironment conducive to the assembly of functional cardiac tissue by encapsulating contracting cells. Indeed, the field of cardiac tissue engineering has witnessed remarkable strides, largely owing to the application of biomaterial scaffolds. However, inherent complexities persist, necessitating further exploration and innovation. This review delves into the pivotal role of biomaterial scaffolds in cardiac tissue engineering, shedding light on their utilization, challenges encountered, and promising avenues for future advancement. By critically examining the current landscape, we aim to catalyze progress toward more effective solutions for cardiac tissue regeneration and ultimately, improved outcomes for patients grappling with cardiovascular ailments.

The effects of cereal ß-glucans on cardiovascular risk factors and the role of the gut microbiome.

The human gut microbiome has emerged as a key influencer of human health and disease, particularly through interactions with dietary fiber. However, national dietary guidelines worldwide are only beginning to capitalize on the potential of microbiome research, which has established the vital role of host-microbe interactions in mediating the physiological effects of diet on overall health and disease. ß-glucans have been demonstrated to modulate the composition of the gut microbiota, leading to improved outcomes in cardiovascular disease (CVD). Raised serum cholesterol and blood pressure are important modifiable risk factors in the development of CVD and emerging evidence highlights the role of the gut microbiota in ameliorating such biomarkers and clinical characteristics of the disease. The proposed mechanism of action of ß-glucans on the pathophysiological mechanisms of disease have yet to be elucidated. Validating gaps in the literature may substantiate ß-glucans as a potential novel dietary therapy against modifiable risk factors for CVD and would further support the public health significance of including a habitual fiber-rich diet.

Adiposity trajectories and cardiovascular disease risk in women: a population-based cohort study with a focus on menopausal status.

Objectives: A single measurement of adiposity indices could predict the incidence of cardiovascular disease (CVD); nonetheless their long-term pattern and its association with incident CVD are rarely studied. This study aimed to determine distinct trajectories of adiposity indices among participants of Tehran Lipid and Glucose Study (TLGS) and their association with incident CVD. Furthermore, this study aimed to investigate whether this association differed among individuals according to their menopausal status. Method: A total of 6840 women participated in TLGS, aged 20 years and older were included in this study; they were followed for a median of 16 years. Body mass index (BMI), waist circumference (WC), conicity index (CI) and body roundness index (BRI) were included in the analysis as adiposity indices. The cohort outcome panel of medical specialists identified the CVD outcomes. Trajectory analyses were used to identify homogeneous distinct clusters of adiposity indices trajectories. The association between the trajectory group membership and incident CVD were explored by Cox proportional hazard models, with unadjusted and adjusted model for baseline age, physical activity, smoking status, menopause and family history of CVD. Results: Three BMI trajectory groups of low, medium, and high and two trajectories for WC, BRI and CI were identified. Adjusted cox proportional hazard models revealed significant associations between the hazard of CVD experience and the high trajectory group of the BMI (HR: 2.06, 95% CI: 1.38-3.07), WC (HR: 2.71, 95% CI: 1.98-3.70), CI (HR: 1.87, 95% CI: 1.26-2.77) and BRI (HR: 1.55-95% CI: 1.12-2.15), compared to the low trajectory group. Subgroup analysis based on the menopausal status of participants showed that the HR of CVD incidences for all of trajectories adiposity indices, except BMI, was statistically significant. Adjusted cox proportional hazard models, in those women not reached menopause during study, revealed that the HR (95% CI) of CVD incidences for high trajectory of BMI, WC, CI and BRI were 2.80 (1.86-7.05); 2.09 (1.40-6.16); 1.72 (1.42-5.61), and 3.09 (1.06-9.01), respectively. These values for those were menopause at the initiation of the study were 1.40 (1.11, 2.53); 1.65 (1.04-2.75); 1.69 (1.01-2.87), and 1.61 (0.98-2.65), respectively. Conclusion: Our findings suggest that adiposity trajectories, particularly central adiposity index of CI, could precisely predict the CVD risk. Consequently, preventive strategies should be tailored accordingly.

The Differential Impact of Medical Therapy and Lifestyle Modification on Cardiovascular Health and Risk of Adverse Cardiovascular Events: A Narrative Review.

Cardiovascular diseases (CVDs) continue to be a worldwide health concern, requiring effective strategies for risk reduction. This article explores the extensive collaboration between medical therapy and lifestyle modifications in the management of CVDs, aiming to interpret whether a single approach holds the key to reducing major cardiovascular events. In the realm of pharmaceutical therapy, statins, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors, and antiplatelet agents have shown significant effectiveness, as evidenced by landmark trials such as Scandinavian Simvastatin Survival Study (4S) and Heart Outcomes Prevention Evaluation (HOPE). Concurrently, lifestyle adjustments, encompassing physical activity, dietary changes, and management of stress, emerge as indispensable elements in cardiovascular care. The article discusses the pivotal role of patient adherence, tailored approaches, and the synergistic impact of combining medical therapy and lifestyle modifications. Challenges, such as socioeconomic disparities and uncertainties in lipid management, underscore the need for ongoing research and precision medicine. Digital health interventions offer novel avenues for personalized care. Despite advancements, uncertainties persist regarding the optimal balance between medical and lifestyle interventions in lowering major cardiovascular event risks. This article emphasizes the ongoing evolution of cardiovascular care, highlighting the imperative need for evidence-based guidelines tailored to individual patient needs.

Triglyceride levels and risk of cardiovascular disease and all-cause mortality in Chinese adults younger than 40 years old: a prospective cohort study.

Background: Data on the associations of triglyceride (TG) levels with cardiovascular disease (CVD) and all-cause mortality mainly focused on the middle-aged or elderly population, with limited information available for younger adults. This study aimed to identify such associations among Chinese young adults. Methods: This study included Chinese adults younger than 40 years free of CVD, cancer, and lipid-lowering agents at baseline in the Kailuan study who were enrolled during 2006 through 2016. All participants were biennially followed up till December 2020. The enzymatic colorimetric method was used to measure baseline fasting TG. Participants were categorized into four groups by quartiles of TG, with the lowest quartile (Q1) as the reference group. The primary outcomes were CVD [composite of myocardial infarction (MI) and ischemic stroke] and all-cause mortality. CVD and mortality risks were estimated with Cox regression models. Results: A total of 43,882 participants were included. Their mean age was 30.6±5.56 years, and 80.2% were males. During a median follow-up of 11.2 years, 298 CVD events and 345 deaths occurred. The incidences of CVD and all-cause mortality were 0.67 and 0.76 per 1,000 person-years, respectively. Compared with individuals in the lowest quartile (Q1), participants in the highest quartile (Q4) showed a 126% higher risk of developing CVD [adjusted hazard ratio (HR) 2.26; 95% confidence interval (CI): 1.56 to 3.29; P=0.001] and a 61% higher risk of all-cause mortality (adjusted HR 1.61; 95% CI: 1.14 to 2.28; P=0.007). In addition, analyses of CVD subtypes showed that adjusted HRs (Q4 vs. Q1) were 3.25 (95% CI: 1.33 to 7.97; P=0.01) for MI, and 1.88 (95% CI: 1.16 to 3.04; P=0.01) for ischemic stroke. Conclusions: Among Chinese young adults, elevated fasting TG levels were associated with increased CVD and all-cause mortality risks.

Navigating the Link Between Non-alcoholic Fatty Liver Disease/Non-alcoholic Steatohepatitis and Cardiometabolic Syndrome.

The global prevalence of non-alcoholic fatty liver disease (NAFLD) is nearly 25% and is increasing rapidly. The spectrum of liver damage in NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis, characterised by the presence of lobular inflammation and hepatocyte ballooning degeneration, with or without fibrosis, which can further develop into cirrhosis and hepatocellular carcinoma. Not only is NAFLD a progressive liver disease, but numerous pieces of evidence also point to extrahepatic consequences. Accumulating evidence suggests that patients with NAFLD are also at increased risk of cardiovascular disease (CVD); in fact, CVDs are the most common cause of mortality in patients with NAFLD. Obesity, type 2 diabetes and higher levels of LDL are common risk factors in both NAFLD and CVD; however, how NAFLD affects the development and progression of CVD remains elusive. In this review, we comprehensively summarise current data on the key extrahepatic manifestations of NAFLD, emphasising the possible link between NAFLD and CVD, including the role of proprotein convertase substilisin/kenin type 9, extracellular vesicles, microbiota, and genetic factors.

The effect of physical activity on cytokine levels in adults living with type 1 diabetes-a preliminary study.

The aim of this study is to investigate whether physical activity and the level of body fat are factors reducing the level of pro-inflammatory cytokines in people with T1DM. Twenty-five men (27.8 ± 9.4 years old; 178.9 ± 6.9 cm; 80.6 ± 12 kg) and 18 women (28.1 ± 12.5 years old; 162.4 ± 5.5; 63.1 ± 9.9 kg) were divided into four groups based on body fat percentage and level of physical activity (AN-active people with normal body fat; IAN-inactive people with normal body fat; AO-active people with excessive body fat, IAO-inactive people with excessive body fat). The level of cytokines in the blood serum was assessed. The level of IL-8 was higher (measurable) in inactive men, regardless of adiposity degree and in women, only in the inactive group with normal body fat. IL-6 was found only in active men with excessive adiposity. In conclusion, the findings from this study allow to indicate that moderate level of physical activity may contribute to a reduction in the development of systemic low-grade inflammation in patients with T1DM, and thus, may reduce the risk of CVD.

Chemokine ligand 18 predicts all-cause mortality in patients hospitalized with chest pain of suspected coronary origin.

Introduction: Chemokines mediate recruitment and activation of leucocytes. Chemokine ligand 18 (CCL18) is mainly expressed by monocytes/macrophages and dendritic cells. It is highly expressed in chronic inflammatory diseases, and locally in atherosclerotic plaques, particularly at sites of reduced stability, and systemically in acute coronary syndrome patients. Reports on its prognostic utility in the latter condition, including myocardial infarction (MI), are scarce. Aim: To assess the utility of CCL18 as a prognostic marker of recurrent cardiovascular events in patients hospitalized with chest pain of suspected coronary origin. Methods: The population consisted of 871 consecutive chest-pain patients, of whom 386 were diagnosed with acute myocardial infarction (AMI) based on Troponin-T (TnT) levels >50 ng/L. Stepwise Cox regression models, applying normalized continuous loge/SD values, were fitted for the biomarkers with cardiac mortality within 2 years and total mortality within 2 and 7 years as the dependent variables. Results: Plasma samples from 849 patients were available. By 2 years follow-up, 138 (15.8%) patients had died, of which 86 were cardiac deaths. Univariate analysis showed a positive, significant association between CCL18 and total death [HR 1.55 (95% 1.30-1.83), p < 0.001], and for cardiac death [HR 1.32 (95% 1.06-1.64), p = 0.013]. Associations after adjustment were non-significant. By 7 years follow-up, 332 (38.1%) patients had died. CLL18 was independently associated with all-cause mortality [HR 1.14 (95% CI, 1.01-1.29), p = 0.030], but not with MI (n = 203) or stroke (n = 55). Conclusion: CCL18 independently predicts long-term all-cause mortality but had no independent prognostic bearing on short-term cardiac death and CVD events.

Low income and education are associated with greater ASCVD risk scores among adults in the US.

Introduction: Social determinants of health (SDOH) are fundamental causes of poor cardiovascular health, yet cardiovascular disease (CVD) risk assessment tools exclude SDOH. Our objective was to determine whether SDOH are independently associated with CVD risk in US adults. Methods: Utilizing the National Health and Nutrition Examination Survey (NHANES), we combined years 1999-2018 and included participants aged 40-79 without history of CVD and with information to calculate CVD risk (n = 21,694). Ten-year risk of atherosclerotic CVD (ASCVD) was calculated using the American Heart Association/American College of Cardiology (AHA/ACC) pooled cohort equations. We used linear regression models to estimate the association between SDOH and ASCVD risk, after adjusting for demographic factors. All analyses accounted for the complex survey design. Results: Mean age was 54.7 years, with 52.7 % female, 73.8 % non-Hispanic White, 9.4 % non-Hispanic Black, and 10.7 % Hispanic. From adjusted models, compared with an income of ≥ $75 K, ASCVD risk was greater by 3.06 (95 % CI: 2.65, 3.47) among those with income < $25 K, by 1.55 (95 % CI: 1.21, 1.89) among those with income $25 K-<$55 K, and by 1.20 (95 % CI: 0.84, 1.56) among those with income $55 K-<$75 K. Compared to college graduates, ASCVD risk was greater by 3.09 (95 % CI: 2.56, 3.62) among those with less than a high school education, by 1.65 (95 % CI: 1.31, 200) among those who were high school graduates, and by 1.41 (95 % CI: 1.11, 1.72) among those with some college education. Conclusion: We found strong graded associations between lower income and lower educational attainment with greater CVD risk.

Cardiovascular disease and preventive care service utilization among midlife adults: The roles of diagnosis and depression.

Objectives: Secondary preventive care is important for monitoring the progression of cardiovascular disease (CVD). However, the factors that promote secondary prevention were not well understood. This study addressed this gap by investigating the impact of CVD diagnosis on preventive care utilization among midlife adults. Given the high prevalence of depression among this population, it further examined whether depression interacted with CVD diagnosis to affect preventive care utilization. Methods: The study sample included 6,222 midlife adults from six waves of the National Longitudinal Survey of Youth 1979 (NLSY79) collected between 2006 and 2016. Multiple logistic regressions were conducted to examine the relationship between a CVD diagnosis and each of the five types of preventive care utilization: influenza vaccinations, electrocardiography (EKG) and screening for high blood pressure, cholesterol, and blood sugar. Depression was then added to examine its possible moderation effect. Results: The results showed that midlife adults with a CVD diagnosis were more likely to utilize all five types of preventive care services. EKG, the most relevant preventive care type with CVD diagnosis, had the largest strength of likelihood. Depression strengthened the relationship between a CVD diagnosis and the utilization of blood pressure tests, but it showed no associations with other four types of preventive care utilization. Conclusions: The study findings indicate that a CVD diagnosis could serve as an opportunity for promoting secondary preventive care utilization. Future research needs to explore how a CVD diagnosis affects different population groups, and further explore the roles of depression.

Atherosclerosis and the Bidirectional Relationship between Cancer and Cardiovascular Disease: From Bench to Bedside-Part 1.

Atherosclerosis, a complex metabolic-immune disease characterized by chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis, while atherosclerosis, with its inflammatory microenvironment, can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review, we aim to summarize the state of the art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology and exert a positive impact on precision cardiology and cardio-oncology.

High lipoprotein(a): Actionable strategies for risk assessment and mitigation.

High levels of lipoprotein(a) [Lp(a)] are causal for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is the most prevalent inherited dyslipidemia and strongest genetic ASCVD risk factor. This risk persists in the presence of at target, guideline-recommended, LDL-C levels and adherence to lifestyle modifications. Epidemiological and genetic evidence supporting its causal role in ASCVD and calcific aortic stenosis continues to accumulate, although various facets regarding Lp(a) biology (genetics, pathophysiology, and expression across race/ethnic groups) are not yet fully understood. The evolving nature of clinical guidelines and consensus statements recommending universal measurements of Lp(a) and the scientific data supporting its role in multiple disease states reinforce the clinical merit to start population screening for Lp(a) now. There is a current gap in the implementation of recommendations for primary and secondary cardiovascular disease (CVD) prevention in those with high Lp(a), in part due to a lack of protocols for management strategies. Importantly, targeted apolipoprotein(a) [apo(a)]-lowering therapies that reduce Lp(a) levels in patients with high Lp(a) are in phase 3 clinical development. This review focuses on the identification and clinical management of patients with high Lp(a). Specifically, we highlight the clinical value of measuring Lp(a) and its use in determining Lp(a)-associated CVD risk by providing actionable guidance, based on scientific knowledge, that can be utilized now to mitigate risk caused by high Lp(a).

Predictive analytics for cardiovascular patient readmission and mortality: An explainable approach.

BACKGROUND: Cardiovascular patients experience high rates of adverse outcomes following discharge from hospital, which may be preventable through early identification and targeted action. This study aimed to investigate the effectiveness and explainability of machine learning algorithms in predicting unplanned readmission and death in cardiovascular patients at 30 days and 180 days from discharge. METHODS: Gradient boosting machines were trained and evaluated using data from hospital electronic medical records linked to hospital administrative and mortality data for 39,255 patients admitted to four hospitals in New South Wales, Australia between 2017 and 2021. Sociodemographic variables, admission history, and clinical information were used as potential predictors. The performance was compared to LASSO regression, as well as the HOSPITAL and LACE risk score indices. Important risk factors identified by the gradient-boosting machine model were explored using Shapley values. RESULTS: The models performed well, especially for the mortality outcomes. Area under the receiver operating characteristic curve values were 0.70 for readmission and 0.87-0.90 for mortality using the full gradient boosting machine algorithms. Among the top predictors for 30-day and 180-day readmission were increased red cell distribution width, old age (especially above 80 years), high measured troponin and urea levels, not being married or in a relationship, and low albumin levels. For mortality, these included increased red cell distribution width, old age (especially older than 70 years), high measured troponin and urea levels, high neutrophil and monocyte counts, and low eosinophil and lymphocyte counts. The Shapley values gave clear insight into the dynamics of decision-tree-based models. CONCLUSIONS: We demonstrated an explainable predictive algorithm to identify cardiovascular patients who are at high risk of readmission or death at discharge from the hospital and identified key risk factors.