Cardiovascular Disease Risk Research Articles

Longitudinal Measures of Cardiovascular Risk Factors Are Associated with Subfertility in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Previous reports have noted associations between subfertility in women and increased risk of cardiovascular disease (CVD) events in later life. However, reports conflict regarding the associations between subfertility and CVD risk factors. Using data from a population-based cohort of Black and White women, we examined the association between longitudinal assessments of CVD risk factors and subfertility. The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective cohort of Black and White women who have undergone repeated assessment of CVD risk factors beginning at study baseline (1985-1986). Risk factors included cigarette smoking, body mass index (BMI), blood pressure, lipid levels, glucose, and C-reactive protein. At approximately 40 years of age, an ancillary study assessed histories of subfertility. We used generalized estimating equations with a logit link model to examine associations between subfertility (dependent variable) and repeated CVD risk factors (independent variables), with adjustment for age, race, center, and education level in 1107 women. Cigarette use and higher levels of BMI, glucose, and triglycerides and lower levels of high-density lipoprotein cholesterol (HDL) were associated with subfertility after adjustment for age, race, and education. In multivariable models which included all of these risk factors, cigarette use (odds ratio [OR] 1.004, 95% confidence interval [CI] 1.002, 1.006, p<0.0001) and HDL (OR 0.99, 95% CI 0.99, 0.995, p=0.046) were still associated with subfertility, but associations with BMI, glucose, and triglycerides were no longer significant. Women with subfertility histories have adverse CVD risk factors across the reproductive lifespan. Cigarette use is a strong risk factor for infertility.

Oxidative Stress and Cardiovascular Complications in Type 2 Diabetes: From Pathophysiology to Lifestyle Modifications.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly increases the risk of cardiovascular disease, which is the leading cause of morbidity and mortality among diabetic patients. A central pathophysiological mechanism linking T2DM to cardiovascular complications is oxidative stress, defined as an imbalance between reactive oxygen species (ROS) production and the body's antioxidant defenses. Hyperglycemia in T2DM promotes oxidative stress through various pathways, including the formation of advanced glycation end products, the activation of protein kinase C, mitochondrial dysfunction, and the polyol pathway. These processes enhance ROS generation, leading to endothelial dysfunction, vascular inflammation, and the exacerbation of cardiovascular damage. Additionally, oxidative stress disrupts nitric oxide signaling, impairing vasodilation and promoting vasoconstriction, which contributes to vascular complications. This review explores the molecular mechanisms by which oxidative stress contributes to the pathogenesis of cardiovascular disease in T2DM. It also examines the potential of lifestyle modifications, such as dietary changes and physical activity, in reducing oxidative stress and mitigating cardiovascular risks in this high-risk population. Understanding these mechanisms is critical for developing targeted therapeutic strategies to improve cardiovascular outcomes in diabetic patients.

Exploring the Therapeutic Role of Flavonoids Through AMPK Activation in Metabolic Syndrome: A Narrative Review.

Metabolic syndrome (MetS) is a cluster of interrelated metabolic abnormalities that significantly elevate the risk of cardiovascular disease, obesity, and diabetes. Flavonoids, a diverse class of bioactive polyphenolic compounds found in plant-derived foods and beverages, have garnered increasing attention as potential therapeutic agents for improving metabolic health. This review provides a comprehensive analysis of the therapeutic effects of flavonoids in the context of the MetS, with a particular focus on their modulation of the AMP-activated protein kinase (AMPK) pathway. AMPK serves as a central regulator of cellular energy balance, glucose metabolism, and lipid homeostasis, making it a critical target for metabolic intervention. Through a systematic review of the literature up to April 2024, preclinical studies across various flavonoid subclasses, including flavonols, and flavan-3-ols, were analysed to elucidate their mechanistic roles in metabolic regulation. Many studies suggests that flavonoids enhance glycolipid metabolism by facilitating glucose transporter 4 (GLUT4) translocation and activating the AMPK pathway, thereby improving glycemic control in diabetes models. In obesity-related studies, flavonoids demonstrated significant inhibitory effects on lipid synthesis, reduced adipogenesis, and attenuated proinflammatory cytokine secretion via AMPK activation. These findings show the broad therapeutic potential of flavonoids in addressing the MetS and its associated disorders. While these preclinical insights highlight flavonoids as promising natural agents for metabolic health improvement, it is important to note that their excessive concentrations may disrupt these pathways, potentially leading to metabolic imbalance and cytotoxicity. Further studies and clinical trials are essential to determine optimal dosing regimens, formulations, and the long-term safety and efficacy of flavonoids. This review highlights the importance of flavonoids for natural interventions targeting MetS and its comorbidities, offering a foundation for future translational research.

Machine learning algorithms for predictive modeling of dyslipidemia-associated cardiovascular disease risk in pregnancy: a comparison of boosting, random forest, and decision tree regression

BackgroundCardiovascular diseases (CVD) are major contributors to maternal mortality and morbidity during pregnancy and increased atherogenic index of plasma levels is associated with a higher risk of CVD and obesity.MethodsIn this study, we utilized three different machine learning algorithms (boosting, random forest, and decision tree regression) to predict dyslipidemia-associated cardiovascular disease using atherogenic index and lipid profile parameters based on a cross-sectional study datasets of 112 pregnant women aged between 15 and 49 conducted at Aminu Kano Teaching Hospital.ResultsThe results showed that random forest regression outperformed both boosting and decision tree regression, recording the lowest error criteria (MSE = 0.071 and RMSE = 0.266) for evaluating the model. These findings indicated that all the three algorithms have the potential to effectively model the data from atherogenic indices and lipid profile parameters but random forest and boosting were found to outperform decision tree models with respective R2 values of 0.95 and 0.92.ConclusionsOverall, the study highlights the accuracy of machine learning models (random forest, boosting, and decision trees) in predicting dyslipidemia-associated cardiovascular diseases and the findings could contribute to the development of effective strategies for the prevention and treatment of dyslipidemia-associated cardiovascular diseases.

INACTIVITY—THE SLOW BUT CERTAIN PATH TO CARDIOVASCULAR DISEASE

Cardiovascular diseases (CVD) remain the leading cause of global mortality, with Romania classifiedas a high cardiovascular risk country. Sedentary behaviors and obesity, closely interrelated factors,significantly contribute to the increased CVD risk. This study analyzed 45 subjects aged between 18and 49 years, none of them being a professional athlete. Data collected included sex, age, BMI,metabolic equivalents (METs), and predictive values for the age and sex of the patient. The study aimedto evaluate the relationship between these variables and to assess the situation regarding the incidenceof sedentary lifestyle. Only 18% of the subjects demonstrated an increased exercise tolerance.Approximately 50% were overweight, and 26% were obese. Subjects with normal BMI showed greaterexercise tolerance compared to overweight and obese individuals. Overall, 82% of participants did notmeet the ESC guidelines for physical activity. The low levels of physical activity highlight the urgentneed for national educational and structural interventions to reduce cardiovascular risk and promotean active lifestyle, particularly among vulnerable groups such as young people and overweightindividuals.

Identify the underlying true model from other models for clinical practice using model performance measures

ObjectiveTo assess whether the outcome generation true model could be identified from other candidate models for clinical practice with current conventional model performance measures considering various simulation scenarios and a CVD risk prediction as exemplar.Study design and settingThousands of scenarios of true models were used to simulate clinical data, various candidate models and true models were trained on training datasets and then compared on testing datasets with 25 conventional use model performance measures. This consists of univariate simulation (179.2k simulated datasets and over 1.792 million models), multivariate simulation (728k simulated datasets and over 8.736 million models) and a CVD risk prediction case analysis.ResultsTrue models had overall C statistic and 95% range of 0.67 (0.51, 0.96) across all scenarios in univariate simulation, 0.81 (0.54, 0.98) in multivariate simulation, 0.85 (0.82, 0.88) in univariate case analysis and 0.85 (0.82, 0.88) in multivariate case analysis. Measures showed very clear differences between the true model and flip-coin model, little or none differences between the true model and candidate models with extra noises, relatively small differences between the true model and proxy models missing causal predictors.ConclusionThe study found the true model is not always identified as the “outperformed” model by current conventional measures for binary outcome, even though such true model is presented in the clinical data. New statistical approaches or measures should be established to identify the casual true model from proxy models, especially for those in proxy models with extra noises and/or missing causal predictors.

Inflammatory markers link triglyceride-glucose index and obesity indicators with adverse cardiovascular events in patients with hypertension: insights from three cohorts

BackgroundAmong hypertensive cohorts across different nations, the relationship between the triglyceride-glucose index (TyG) and its conjunction with obesity metrics in relation to cardiovascular disease (CVD) incidence and mortality remains to be elucidated.MethodsThis study enrolled 9,283, 164,357, and 5,334 hypertensives from the National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKBB), and Shanghai Pudong cohort. The related outcomes for CVD were defined by multivariate Cox proportional hazards models, Generalized Additive Models and Mendelian randomization analysis. Mediation analysis explored the mediating role of inflammatory markers in the above relationships.ResultsFive measures of insulin resistance were linked to CVD and related death in a U-shaped pattern, with the highest group having different risk increases. Higher glucose triglyceride-waist height ratio (TyG-WHTR) was linked to higher all-cause mortality (UKBB: HR 1.21, 95%CI 1.16–1.26, NHANES: HR 1.17, 95%CI 1.00–1.36), CVD mortality (UKBB: HR 1.36, 95%CI 1.23–1.49, NHANES: HR 1.32, 95%CI 1.00–1.72) risks. In the China Pudong cohort, higher triglyceride/high-density lipoprotein-cholesterol (TG/HDL_C) ratio was associated with higher risks of CVD and stroke (HR 1.31, 95%CI 1.00–1.73 and 1.67, 1.06–2.63). Inflammation markers like systemic inflammatory response index (SIRI) and C-reactive protein (CRP) partially explained these links, with CRP having a stronger effect. Genetically predicted TyG was also linked to stroke (OR 1.26, 95%CI 1.10–1.45) risk.ConclusionsAn elevated TyG index and its related indices are significantly correlated with an increased risk of CVD and related mortality across three national cohorts. These indices are anticipated to serve as valid predictors of incident CVD and mortality in individuals with hypertension.Graphical abstract

Long-term health benefit and economic return of time in range (TIR) improvement in individuals with type 2 diabetes.

Time in range (TIR) is an important metric to measure variability of blood glucose levels. The aim is to quantify the long-term health benefits and economic return associated with improved TIR for individuals with type 2 diabetes (T2D). A Markov model with three states (T2D, T2D with cardiovascular disease (CVD) and death) estimated 20-year medical costs, quality-adjusted life-years (QALY) gained and CVD risk under four TIR scenarios: >85%, 71%-85%, 51%-70% and ≤50%. The T2D population was identified using the National Health and Nutrition Examination Survey, and model parameters were sourced from literature. Costs were estimated from a healthcare sector perspective and standardized to 2021 US dollars. Cost ceilings were determined using three willingness-to-pay (WTP) thresholds: $100 000/QALY, $50 000/QALY and $0/QALY (cost-saving). Compared to TIR <50%, improving TIR to 51%-70% resulted in a 0.79 QALY increase and 4.91% CVD risk reduction; to 71%-85%, a 0.95 QALY increase and 6.24% CVD risk reduction; to >85%, a 1.18 QALY increase and 8.75% CVD risk reduction. To be cost-effective at $100 000/QALY, annual costs for TIR improvements from <50% to 51%-70%, 71%-85% and >85% should be <$1148, $4200 and $7252, respectively. To be cost-saving, these costs should be <$612, $2816 and $5021. Improving TIR yields significant health benefits. We calculated feasible medical cost allocations for TIR improvements, informing the implementation of interventions like continuous glucose monitoring devices.

Cost-Effectiveness of a Polypill for Cardiovascular Disease Prevention in an Underserved Population

The Southern Community Cohort Study (SCCS) Polypill Trial showed that a cardiovascular polypill (a single pill containing a statin and 3 half-standard dose antihypertensive medications) effectively controls cardiovascular disease (CVD) risk factors in a majority Black race and low-income population. The cost-effectiveness of polypill treatment in this population has not been previously studied. To determine the cost-effectiveness of the cardiovascular polypill. A discrete-event simulation version of the well-established CVD policy model simulated clinical and economic outcomes of the SCCS Polypill Trial from a health care sector perspective. A time horizon of 10 years was adopted. Polypill treatment was priced at $463 per year in the base-case analysis. Model input data were derived from the National Health and Nutrition Examination Survey, Medical Expenditure Panel Survey, pooled longitudinal cohort studies, the SCCS Polypill Trial, and published literature. Two cohorts were analyzed: an SCCS Polypill Trial-representative cohort of 100 000 individuals and all trial-eligible non-Hispanic Black US adults. Study parameters and model inputs were varied extensively in 1-way and probabilistic sensitivity analysis. Polypill treatment or usual care. Primary outcomes were direct health care costs (US dollar 2023) and quality-adjusted life-years (QALYs), both discounted 3% annually, and the incremental cost per QALY gained. In the trial-representative cohort of 100 000 individuals (mean [SD] age, 56.9 [5.9] years; 61 807 female [61.8%]), polypill treatment was projected to yield a mean of 1190 (95% uncertainty interval, 287-2159) additional QALYs compared with usual care, at a cost of approximately $10 152 000. Hence, polypill treatment was estimated to cost $8560 per QALY gained compared with usual care and was high value (<$50 000 per QALY gained) in 99% of simulations. Polypill treatment was estimated to be high value when priced at $559 or less per year and cost saving when priced at $443 or less per year. In almost all sensitivity analyses, polypill treatment remained high value. In a secondary analysis of 3 602 427 trial-eligible non-Hispanic Black US adults (mean [SD] age, 55.4 [7.6] years; 2 006 597 female [55.7%]), polypill treatment was high value, with an estimated cost of $13 400 per QALY gained. Results of this economic evaluation suggest that polypill treatment could be a high value intervention for a low-income, majority Black population with limited access to health care services. It could additionally reduce health disparities.

Impact of Time-Restricted Eating and High-Intensity Exercise on Nutrient Intake in Women with Overweight/Obesity: Secondary Analysis of a Randomized Controlled Trial.

Inadequate micronutrient intakes are common in individuals with overweight/obesityand can exacerbate cardiovascular and metabolic disease risk. Diet and exercise are primary strategies for managing overweight and may influence nutrient intakes. In this secondary analysis of dietary data collected in a randomized controlled trial (RCT, ClinicalTrials.gov (NCT04019860), 15 June 2019) of time-restricted eating (TRE), high-intensity interval training (HIIT), a combination (TREHIIT), or a control group (CON), we investigated intervention effects on energy and nutrient intakes in women with overweight/obesity. We randomized 131 women (body mass index (BMI) ≥ 27 kg/m2) to 7 weeks of TRE (≤10-h daily eating window with ad libitum energy intake), HIIT (3 sessions/week, performed at ≥90% maximal heart rate), TREHIIT, or CON. Participants recorded all energy intake in an online food diary during a baseline week (week 0) and at the end of the study (week 6 and week 7). We investigated between-group differences in changes in mean energy, macronutrient, and micronutrient intakes. TRE had reduced intakes of potassium, magnesium, and phosphorus compared with CON (p < 0.01). TREHIIT had non-significant reduced intakes of potassium, thiamine, magnesium, copper, and phosphorus (0.01< p < 0.05). HIIT alone did not negatively impact micronutrient intakes. TRE and TREHIIT induced suboptimal intakes for a greater number of micronutrients compared with HIIT and CON. A ≤10-h TRE window might increase the risk of micronutrient inadequacy in women with overweight/obesity. Future research is needed to investigate the effects of integrating nutritional guidelines with TRE interventions to mitigate the risk of micronutrient inadequacy in individuals with overweight/obesity.

The Exposome, Social Determinants, and Environmental Pollution: Comprehensive Cardiovascular Risk in Women.

Cardiovascular disease (CVD) remains a significant global health concern for women, influenced by a complex interplay of social, economic, and environmental factors. This article examines cardiovascular risk through the lens of the exposome, which encompasses all environmental exposures from conception onward, including pollution, diet, and chronic stress. Social determinants such as socioeconomic status (SES), education, and stress management play crucial roles in shaping women's cardiovascular health. Lower SES and education are associated with greater exposure to adverse living conditions, poor nutrition, and limited access to healthcare, increasing the risk of CVD. Environmental pollution, particularly air pollution and climate-related changes, further exacerbates cardiovascular risk by promoting oxidative stress and inflammation. Additionally, gender-specific factors, such as pregnancy and menopause, interact with the exposome, heightening the vulnerability of women to cardiovascular risks over their lifetime. Addressing these risk factors requires a comprehensive approach, incorporating public health strategies that focus on reducing pollution, improving food security, and mitigating social inequalities. By addressing the cumulative and interacting exposures that contribute to cardiovascular disease, especially in women, more effective prevention strategies can be developed to improve long-term health outcomes.

How to Use Imaging: Complex Cases of Atherosclerosis, Myocardial Inflammation, and Cardiomyopathy in Cardio-Oncology.

It is well understood that cancer therapies including chemotherapy, tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiation can increase the risk of cardiovascular disease in patients with cancer. This can manifest as a multitude of pathologies including left ventricular dysfunction, myocarditis, cardiomyopathy, accelerated atherosclerosis, and coronary vasospasm. Multimodal cardiac imaging plays a critical role in diagnosing such pathologies by relying on noninvasive tools including echocardiograms, cardiac magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and coronary computed tomography angiography. These methods have unique considerations and in recent years have made significant progress in their diagnostic capabilities in this patient population. As the field of cardio-oncology continues to expand rapidly, guidance on the management of such toxicities and the development of imaging technologies is crucial. In this review, we present 2 complex cases of atherosclerosis and myocarditis in patients with cancer, highlighting our rationale for management and discussing the nuances of various cardiac imaging modalities.

Astemizole Exacerbates 5-Fluorouracil-Triggered Cardiotoxicity by Enhancing Ptgs2.

5-fluorouracil (5-FU), a commonly utilized antitumor agent for the treatment of colon cancer, is linked to an increased risk of cardiovascular diseases. Antihistamines including astemizole (AST) have been reported to present cardiovascular toxicity; however, it remains unclear how 5-FU-mediated cardiotoxicity is affected by AST during the treatment of colon cancer. This study explored the role of AST in 5-FU-induced cardiotoxicity in colon cancer. 5-FU was used to induce cardiotoxicity in cardiomyocytes (HL-1 cells) and BALBc mice, creating in vitro and in vivo models of chemotherapeutic drug-induced cardiotoxicity. In the mice model, we found that the blocking of histamine signal by AST aggravated 5-FU-induced cardiac function injury and cardiac fibrosis. In HL-1 cardiomyocyte cells, the increases of apoptosis and generation of mitochondrial reactive oxygen species (mtROS) were evaluated after the combination treatment of AST and 5-FU. Proinflammatory M1-like-type macrophages were dominant in the AST and 5-FU combination group compared to control groups. The protein expression of prostaglandin-endoperoxide synthase 2 (Ptgs2) was assessed both in vitro and in vivo using Western blot analysis. Clinically, altered Ptgs2 was closely associated with adverse cardiovascular outcomes. Overall, the combination of AST and 5-FU significantly enhanced cardiotoxicity by inducing cardiomyocyte apoptosis, inflammation, and the expression of Ptgs2.

Predictive Value of Complete Blood Count (CBC)-Derived Indices-C-Reactive-Protein-Albumin-Lymphocyteindex (CALLY), Glucose-to-Lymphocyte Ratio (GLR), Prognostic Nutritional Index (PNI), Hemoglobin, Albumin, Lymphocyte, Platelet (HALP), and Controlling Nutritional Status (COUNT)-on Body Composition Changes After Bariatric Surgery.

Obesity is linked to increased risks of cardiovascular disease, diabetes, and certain cancers. Bariatric surgery (BS) aids in weight management, significantly altering body composition. This study evaluates the predictive value of five complete blood count (CBC)-derived indices[C-reactive-protein-albumin-lymphocyte (CALLY), glucose-to-lymphocyte ratio (GLR), prognostic nutritional index (PNI), hemoglobin, albumin, lymphocyte, platelet (HALP), and controlling nutritional status (COUNT)]on body composition changes post-BS. A retrospective study was conducted on 240 patients undergoing BS atSina Hospital,Tehran, Iran. Indices were calculated using routine laboratory tests, and body composition changes were measured using bioelectrical impedance analysis at 3 and 6months post-surgery. RESULTS: Higher pre-surgical GLR values positively correlated with increased fat-free mass (FFM) (p = 0.005 1, p = 0.003 2), muscle mass (MM) (p = 0.011 1, p = 0.008 2), and total body water (TBW) (p = 0.005 1, p = 0.005 2) post-surgery.In contrast, higher PNI was negatively associated with changes in FM (p = 0.029 1, p = 0.015 2), FFM (p = 0.002 1, p = 0.018 2), TBW (p = 0.002 1, p = 0.015 2) and MM (p = 0.003 2), particularly after laparoscopic sleeve gastrectomy (LSG). Furthermore, there was a significant correlation between pre-surgical HALP score and changes in FFM (p = 0.002 1, p = 0.042 2), TBW (p = 0.002 1) and MM (p = 0.011 1, p = 0.041 2). In addition, the modified HALP score showed a more significant correlation compared to the HALP score to predict the changes FM (p = 0.002 1, p = 0.002 2), FFM (p = 0.001 1, p = 0.006 2), TBW (p = 0.001 1, p = 0.003 2) and MM (p = 0.001 1, p = 0.023 2) particularly, after 6months. Our findings suggest that pre-surgical assessment of GLR, PNI, and HALP indices may provide valuable insights into predicting changes in body composition after bariatric surgery. Specifically, these indices could serve as tools for tailoring preoperative nutritional strategies and post-surgical interventions. However, as this study is retrospective, further prospective research with longer follow-ups is required to validate these findings and evaluate their utility in clinical practice. 1 3months after metabolic bariatric surgery. 2 6months after metabolic bariatric surgery.

Predicting cardiovascular disease in patients with mental illness using machine learning.

Cardiovascular disease (CVD) is twice as prevalent among individuals with mental illness compared to the general population. Prevention strategies exist but require accurate risk prediction. This study aimed to develop and validate a machine learning model for predicting incident CVD among patients with mental illness using routine clinical data from electronic health records. A cohort study was conducted using data from 74,880 patients with 1.6 million psychiatric service contacts in the Central Denmark Region from 2013 to 2021. Two machine learning models (XGBoost and regularised logistic regression) were trained on 85% of the data from six hospitals using 234 potential predictors. The best-performing model was externally validated on the remaining 15% of patients from another three hospitals. CVD was defined as myocardial infarction, stroke, or peripheral arterial disease. The best-performing model (hyperparameter-tuned XGBoost) demonstrated acceptable discrimination, with an area under the receiver operating characteristic curve of 0.84 on the training set and 0.74 on the validation set. It identified high-risk individuals 2.5 years before CVD events. For the psychiatric service contacts in the top 5% of predicted risk, the positive predictive value was 5%, and the negative predictive value was 99%. The model issued at least one positive prediction for 39% of patients who developed CVD. A machine learning model can accurately predict CVD risk among patients with mental illness using routinely collected electronic health record data. A decision support system building on this approach may aid primary CVD prevention in this high-risk population.

Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics.

Metabolic alterations are commonly associated with various cancers and are recognized as contributing factors to cancer progression, invasion, and metastasis. Drug repurposing, a strategy in drug discovery, utilizes existing knowledge to recommend established drugs for new indications based on clinical data or biological evidence. This approach is considered a less risky alternative to traditional drug development. Metformin, a biguanide, is a product of Galega officinalis (French lilac) primarily prescribed for managing type 2 diabetes, is recognized for its ability to reduce hepatic glucose production and enhance insulin sensitivity, particularly in peripheral tissues such as muscle. It also improves glucose uptake and utilization while decreasing intestinal glucose absorption. Statins, first isolated from the fungus Penicillium citrinum is another class of medication mainly used to lower cholesterol levels in individuals at risk for cardiovascular diseases, work by inhibiting the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is essential for cholesterol biosynthesis in the liver. Metformin is frequently used in conjunction with statins to investigate their potential synergistic effects. Combination of metformin and simvastatin has gathered much attention in cancer research because of its potential advantages for cancer prevention and treatment. In this review, we analyze the effects of metformin and simvastatin, both individually and in combination, on key cancer hallmarks, and how this combination affects the expression of biomolecules and associated signaling pathways. We also summarize preclinical research, including clinical trials, on the efficacy, safety, and potential applications of repurposing metformin and simvastatin for cancer therapy.

Time-restricted feeding reduces cardiovascular disease risk in obese mice.

Disrupted feeding and fasting cycles as well as chronic high fat diet (HFD)-induced obesity are associated with cardiovascular disease risk factors. We designed studies that determined whether two weeks of time-restricted feeding (TRF) intervention in mice fed a chronic HFD would reduce cardiovascular disease risk factors. Mice were fed a normal diet (ND; 10% fat) ad libitum or HFD (45% fat) for 18 weeks ad libitum to establish diet-induced obesity. ND or HFD mice were continued on ad libitum diet or subjected to TRF (limiting food availability to 12 hr only during the dark phase) during the final two weeks of the feeding protocol. TRF improved whole-body metabolic diurnal rhythms without a change in body weight. HFD mice showed reduced blood pressure dipping compared to ND, which was restored by TRF. Further, TRF reduced aortic wall thickness, decreased aortic stiffness, as well as increased kidney tubular brush border integrity, decreased renal medullary fibrosis, and reduced renal medullary T cell inflammation in HFD mice. These findings indicate that TRF may be an effective intervention for improving vascular and kidney health in a model of established diet-induced obesity.

Environmental burden of disease resulting from long-term nitrogen dioxide exposure in Germany

BackgroundExposure to nitrogen dioxide (NO2) is associated with an increased risk of cardiovascular, respiratory, and other diseases and health outcomes. Although NO2 emissions have decreased in Germany, concentrations currently observed still pose a threat to population health. The aim of this study is to estimate the environmental burden of disease (EBD) resulting from long-term NO2 exposure in Germany from 2010 to 2021.MethodsTo estimate the attributable disease burden, World Health Organization’s EBD approach was used. We first conducted a systematic literature review to identify exposure–response functions (ERFs) which mathematically represent the association between NO2 exposure and the health outcomes: asthma, chronic obstructive pulmonary disease (COPD), type 2 diabetes mellitus (T2DM), ischemic heart disease, lung cancer, stroke, and cardiovascular and respiratory mortality. Then, we estimated the years of life lost (YLL), years lived with disability (YLD) and, where possible, disability-adjusted life years (DALYs) due to these health outcomes in Germany, using mostly publicly available data. In a third step, using the ERFs and modelled ambient NO2 exposure data, the fraction of the disease burden attributable to NO2 exposure was estimated for each health outcome and year, stratified by sex.ResultsThe systematic review yielded recent ERFs for some exposure-outcome pairs, but not always for both mortality and morbidity outcomes. A full DALY calculation was possible for COPD and T2DM. For the other outcomes, either only YLL or YLD were calculated. Summing up the estimated YLD and YLL of all outcomes, the burden of disease due to NO2 exposure in Germany decreased from 261,503 (95% UI 69,290–489,273) lost healthy years in 2010 to 100,032 (95% UI 24,558–191,715) in 2021.ConclusionsAlthough the burden of disease attributable to NO2 exposure decreased from 2010 to 2021, NO2 still poses a threat to population health in Germany. While the current legal concentration limit was generally not exceeded in Germany in 2021, stricter new values proposed by WHO were frequently surpassed. When comparing the results to a previous assessment, it was obvious how strongly different input data impact the results. Transparent reporting of input data and discussing potential challenges when interpreting EBD results are critical.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health. Metabolic dysfunction and associated insulin resistance, together with the predilection for ectopic fat deposition in the liver and surrounding tissues, are associated with elevated risk of endothelial dysfunction, systemic inflammatory response, and ectopic fat deposition in the epicardium. This complex pathophysiology can accelerate atherogenic dyslipidemia, atherogenesis, diastolic dysfunction, valvular calcification, and cardiac arrhythmias. Despite the mounting evidence of mechanistic pathways underpinning MASLD and CVD, current recommendations have not clearly focused upon MASLD as a risk factor or target for intervention in CVD. We have brought together a diverse range of international experts committed to promoting cardiovascular-liver-metabolic health and related outcomes across the globe. The overarching goal of this document is to offer a construct for clinicians in the cardiovascular field with regards to (1) diagnosis and screening of MASLD through the use of noninvasive serum and imaging tests; (2) screening for CVD in all individuals with MASLD regardless of established atherosclerotic risk factors; and (3) the approach to management of MASLD with respect to prevention of CVD through lifestyle, as well as pharmacologic and surgical strategies. To achieve this, the modified Delphi method was applied and a series of evidence-based quality standard recommendations have been identified.

Life’s Essential 8 cardiovascular health metrics and long-term risk of cardiovascular disease at different stages: A multi-stage analysis

Life’s Essential 8 cardiovascular health metrics and long-term risk of cardiovascular disease at different stages: A multi-stage analysis