Cardiovascular Disease Prevention Strategies Research Articles

A novel classification of dyslipidaemia through the analysis of five million lipid profiles: an unsupervised machine learning approach

Abstract Background Dyslipidemia encompasses a wide range of lipoprotein disorders categorised through two classifications (Fredrickson-Levy [FL] or Sniderman).(1,2) However, both classifications are criticised for relying on incomplete knowledge of lipoprotein metabolism, especially with the emergence of novel treatment options and variations in individual treatment responses.(3) Clustering, an unsupervised machine learning (ML) algorithm that can process a wide range of variables, has the potential to unmask patient groups with distinct molecular profiles and unique therapeutic targets that can inform more effective prevention strategies for cardiovascular disease (CVD).(4) Aim We aimed to use unsupervised ML algorithms to discover intrinsic dyslipidaemia categories from lipoprotein measurements, recognise the necessary components of lipid panels for classification, and analyse the similarities between the newly formed clusters, FL and Sniderman classifications. Methods Lipid profiles of 5,080,248 patients were obtained from the ‘Very Large Database of Lipids’ database. This yielded up to 78 blood components per patient, including at least 31 lipoprotein variables. The analysis involved unsupervised K-means clustering with optimised values for K and the subset of variables, determined in an unsupervised manner using a suitable measure of complexity. We then interpreted our clusters using probabilistic decision trees to provide compact and interpretable representations. Finally, we compared the clusters with Sniderman and FL categories. Results In a completely unsupervised fashion, we identified 14 clusters that could be matched to Sniderman categories. The confusion matrix showed total agreement of 76% (see Figure 1, left panel), relative Cohen’s kappa of 0.78 (the relative version captures accuracy on categories containing smaller numbers of patient profiles) and an accuracy of 96% on the small Type III class. Similar results were observed when matching to FL types. We accurately represented our clusters using probabilistic decision trees of small depth (see Figure 2). We discovered that the data had low intrinsic dimension and a manifold-like structure in which the different clusters could be illustrated (see Figure 1, right panel). Specifically, only 3 variables were needed to obtain our classification: apolipoprotein b, total cholesterol and triglycerides. Conclusion We showed that completely unsupervised ML techniques can uncover dyslipidaemia categories in lipoprotein profiles from a large patient population. The categories largely align with existing classifications based on prior knowledge of lipoprotein metabolism. Furthermore, few lipoprotein variables were required for categorisation (low-dimension data), which could aid in determining which lipoproteins should be measured in a clinical setting. Further analysis of the differences between ML clusters and traditional classifications is needed, which may enhance CVD risk management.

Association of COVID-19 and influenza vaccinations and cardiovascular drugs with hospitalisation and mortality in COVID-19 and Long COVID: 2-year follow-up of 17 million individuals in England

Abstract Introduction For COVID-19 and Long COVID, determining the highest-risk subgroups, particularly in the context of compound pressures such as influenza and cardiovascular disease (CVD), may identify effective interventions to prevent adverse health outcomes, and inform public health and policy decisions. Methods Using national, linked electronic health records for England (NHS England Secure Data Environment: via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals with COVID-19 and Long COVID from January 2020 to February 2023. We compared all-cause hospitalisation and mortality in unmatched and matched cohort analyses, by prior CVD, high CVD risk (by QRISK2), COVID-19 and influenza vaccination status, and prescription of CVD preventive therapies. We investigated potential impact of targeted vaccination and CVD prevention strategies on mortality and hospitalisations by calculating population preventable fractions. Results We identified 17,373,850 individuals with COVID-19 [54.4% female; mean age 38.8 years; COVID-19 vaccination ≥2 doses:50.0%, influenza vaccination (≥1 dose):27.8%; mean follow-up 1.28 years] and 301,115 with Long Covid [61.8% female; mean age 46.0 years; COVID-19 vaccination ≥2 doses:66.4%, influenza vaccination:33.1%; mean follow-up 1.1 years]. Hospitalisation and mortality rates were 15.3% and 2.0% in COVID-19 (Long COVID rate 1.3%) and 16.8% and 1.4% in Long COVID, respectively. Adjusted risk of mortality and hospitalisation were reduced with COVID-19 vaccination ≥2 doses (COVID-19:HR 0.36, 95% CI 0.34-0.38 and 0.69, 0.68-0.69; Long COVID:0.44, 0.42-0.47 and 0.90, 0.89-0.91). With influenza vaccination, mortality was reduced, but not hospitalisation (COVID-19: 0.86, 0.85-0.86 and HR 1.01, 1.01-1.01, and Long COVID: 0.72, 0.67-0.76, and 1.05, 1.03-1.07), with greatest effect in those with prior CVD and high CVD risk. Mortality and hospitalisation were also reduced by CVD prevention in those with CVD, e.g. anticoagulants- COVID-19: 0.69, 0.69-0.70 and 0.92, 0.91-0.93; Long Covid: 0.59, 0.54-0.64, and 0.88, 0.84-0.92. COVID-19 vaccination, influenza vaccination and CVD drugs (Anticoagulants) averted 101117 of 193598, 2138 of 4017 and 16573 of 36847 preventable deaths among individuals after COVID-19, and 875 of 1189, 65 of 127 and 507 of 1007 preventable deaths among those with Long COVID, particularly in people with CVD. Conclusions Prior CVD and high CVD risk are associated with increased hospitalisation and mortality risk in people with COVID-19 and Long COVID. Targeted improvement in COVID-19 vaccination and CVD prevention, especially in those with CVD are priority interventions in pandemics to avoid excess hospitalisation and mortality.Baseline Characteristics and OutcomesHospitalisation/mortality by COVID vaccn

Investigating lifestyle determinants of carotid intima-media thickness: cross-sectional insights from the UK biobank cohort

Abstract Background/Introduction Carotid intima-media thickness (CIMT) is recognised as a crucial marker for cardiovascular disease (CVD) risk, inherently associated with vascular ageing and influenced by biomarkers such as elevated levels of HbA1c, dyslipidaemia, and hypertension. The significance of CIMT lies in its potential to act as a surrogate marker for CVD risk, bridging a gap in understanding the progression of vascular health. Purpose This study aims to investigate the correlation between CIMT and a composite biomarker score to enhance risk assessment and guide the prevention and treatment strategies for CVD. By examining this relationship, the study seeks to underline the importance of CIMT progression as an indicative marker for cardiovascular health. Methods A subset of participants from the UK Biobank, with valid CIMT measurements taken in 2014, was selected for this analysis. CIMT was measured through ultrasound techniques and considered the primary outcome variable, treated as continuous in the analysis. A linear regression model was used to examine the correlation between CIMT and lifestyle risk factors, with a focus on the moderating effects of sex. Results The study included 29,292 UK Biobank participants (48% female, mean age 64 years), with a mean CIMT of 687.11µm (SD 124.28). Significant predictors of CIMT were age (β=6.05) and male gender (β=13.02). Lifestyle factors such as body weight (β=0.84) and high physical activity (β=10.66) were positively correlated with CIMT. Current smokers showed a stronger association with CIMT (β=14.47) compared to former smokers (β=9.21). In females, age (β=6.07), body weight (β=0.71), CRBI score (β=9.95), and previous smoking (β=6.64) positively correlated with CIMT, while high CRP levels were negatively associated (β=-0.61). In males, significant factors included age (β=6.04), body weight (β=0.95), CRBI score (β=10.79), and smoking history, with previous smokers showing a stronger effect (β=11.67) and high physical activity notably associated with increased CIMT (β=18.73). Conclusion(s) The study's findings highlight the impact of lifestyle choices on vascular health, demonstrating that active living, maintaining a healthy weight, and abstaining from smoking can positively affect CIMT and thereby reduce CVD risk. The results confirm the importance of weight management for arterial health across all demographics and highlight the role of abnormal biomarker levels in increasing CIMT. This study contributes to a deeper understanding of the factors affecting CIMT and, by extension, cardiovascular health, advocating for targeted lifestyle interventions to mitigate CVD risk.

Increased prevalence of coronary atherosclerosis in cancer survivors: a matched cross-sectional study with coronary CT angiography

Abstract Background Cancer and atherosclerosis share many risk factors. Although cardiovascular disease is highly prevalent among cancer survivors, it is unknown whether coronary atherosclerosis is present at a younger age in patients with a history of cancer. Purpose The purpose of this study is to evaluate the prevalence of coronary atherosclerosis in different age groups of patients with a history of cancer compared to matched controls. Methods Consecutive patients with a history of cancer aged >30 years who underwent evaluation for coronary artery disease with coronary computed tomography angiography (CCTA) between 2010 and 2023 were included in this cross-sectional study. Patients with a history of cancer were matched 1:2 to a control population without oncological history using propensity score matching. Patients were matched on age, gender, body mass index, hypercholesterolemia, hypertension, diabetes, use of statins and smoking status. The presence of atherosclerosis in the main coronary arteries was compared between the groups. Results The study population consisted of 313 patients with an oncological history and 626 matched control patients. The median age during CCTA scan was 59.4 [50.4-67.5] years and 66.1% of the patients were female. Coronary atherosclerosis was observed in 258 (82.4%) patients with a history of cancer compared to 461 (73.6%) control patients with a risk ratio of 1.12 [95% CI: 1.04-1.20], p<0.01. Mainly younger patients with a history of cancer aged between 30-59 years had a significant increased prevalence of coronary atherosclerosis with a risk ratio of 1.18 [1.04-1.33] compared to healthy controls (p=0.02). In our study population, thoracic radiotherapy was not associated with an increased prevalence of coronary atherosclerosis. Calcified plaques were observed more frequently in patients with a history of cancer (14.4% vs. 9.3% respectively, p=0.018). Conclusion Patients with a history cancer have a higher prevalence of coronary atherosclerosis as observed on CCTA compared to matched patients without cancer. This effect was most pronounced in younger patients aged 30-59 years. There is an unmet need to define strategies for cardiovascular disease monitoring and prevention in this growing patient population of patients with a history of cancer.Presence of coronary atherosclerosisRadiotherapy and atherosclerosis

Association between the triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular diseases in people living with HIV: Evidence from a retrospectively cohort study 2005-2022.

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with HIV (PLWH) remain underexplored. We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People's Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects. At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) [95% confidence intervals (95% CI)] for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively (P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95%CI 3.35%-29.52, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence (P for non-linear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58, 21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88, 1.15, P = 0.880). Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Myeloproliferative Neoplasms and Cardiovascular Disease: A Review.

Myeloproliferative neoplasms (MPN) are a heterogenous group of disorders of clonal hematopoiesis characterized by constitutive activation of the JAK/STAT signaling pathway leading to proliferation of blood cells. Cardiovascular disease (CVD) contributes significantly to the morbidity and mortality of patients with MPN. Particularly well-known CVD complications of MPNs are arterial and venous thrombotic events. However, MPNs are also associated with other forms of CVD including atrial fibrillation, heart failure, and pulmonary hypertension. Recent studies have characterized outcomes of patients with MPN and CVD, including acute myocardial infarction (AMI), heart failure, atrial fibrillation, and pulmonary hypertension. Additionally, optimal cardiovascular disease prevention strategies in patients with MPN are not yet clear. Further investigation is warranted to improve CVD outcomes in patients with MPN. Clinicians should be aware of cardiovascular complications of MPN, including thrombotic as well as non-thrombotic complications (heart failure, arrhythmias, pulmonary hypertension).

From a Cup of Tea to Cardiovascular Care: Vascular Mechanisms of Action.

Tea consumption is increasingly recognized for its potential benefits to cardiovascular health. This study reviews the available research, concentrating on the major components of tea and their mechanisms of action in the cardiovascular system. Tea is abundant in bioactive compounds, such as flavonoids and polysaccharides, which possess significant antioxidant and anti-inflammatory properties. These compounds play a crucial role in mitigating oxidative stress and inflammation, thereby supporting cardiovascular health. They enhance endothelial function, leading to improved vascular relaxation and reduced arterial stiffness, and exhibit antithrombotic effects. Additionally, regular tea consumption is potentially associated with better regulation of blood pressure, improved cholesterol profiles, and effective blood sugar control. It has been suggested that incorporating tea into daily dietary habits could be a practical strategy for cardiovascular disease prevention and management. Despite the promising evidence, more rigorous clinical trials are needed to establish standardized consumption recommendations and fully understand long-term effects. This review offers a more comprehensive analysis of the current evidence based on endothelium function and identifies the gaps that future research should address.

Pathophysiology and clinical implications of coronary artery calcifications.

To provide a summary of current understanding of coronary artery calcifications (CACs), outlining the role of calcium in atherosclerosis to comprehend the clinical implications of CAC. CAC serves as a reliable indicator of coronary artery disease (CAD) and it is associated with cardiovascular events. In recognition of its significance, recent global guidelines have integrated CAC assessment into risk evaluation protocols, highlighting its role as a noninvasive tool for evaluating and stratifying patients' risk for cardiovascular events. Beyond the amount of CAC values, also, calcium morphology had been linked to cardiovascular events.By leveraging CAC assessment, healthcare providers can effectively up or down reclassify patients' risk and tailor preventive strategies accordingly. This comprehensive approach may involve lifestyle modifications, meticulous management of risk factors, and judicious use of preventive medications to mitigate the likelihood of future cardiovascular events, or withhold treatments in those without signs of CAC, to optimize resource use. The identification of CAC burden and morphology through noninvasive imaging modalities can reclassify the prediction of future cardiovascular risk and serve as a risk modifier for atherosclerosis. These data underscore the utility of selectively using CAC assessment in both primary and secondary prevention strategies for atherosclerotic cardiovascular disease.

Value of Glycemic Dispersion Index in Predicting Major Adverse Cardiovascular Events in Diabetic Patients with Concomitant Acute Coronary Syndrome.

This investigation aims to assess the predictive value of the glycemic dispersion index (GDI), calculated by incorporating glycated hemoglobin, fasting plasma glucose, and 2-hour postprandial plasma glucose, in predicting major adverse cardiovascular events (MACE) within a 12-month timeframe for diabetic patients with concomitant acute coronary syndrome (ACS). A retrospective study was conducted on 3261 diabetic patients with ACS who were hospitalized in the Department of Cardiology, the Sixth Affiliated Hospital of Kunming Medical University, from January 2016 to July 2022. Based on the inclusion and exclusion criteria, 512 patients were ultimately enrolled in the study. Their general information and laboratory test indicators were collected, and the occurrence of MACE within 12 months after admission was followed up and recorded for the enrolled patients, With the last follow-up having been concluded on July 31, 2023. The enrolled patients were stratified into four groups (Q1, Q2, Q3, Q4) based on their GDI values, from the lowest to the highest. Cox proportional hazards regression analysis and Kaplan-Meier survival analysis were employed to investigate the risk factors associated with MACE occurrence across these groups and to assess the cumulative risk of MACE over time within each group. The percentages of enrolled patients experiencing MACE in groups Q1 to Q4 were 10.16%, 12.50%, 15.63%, and 16.41%, respectively. GDI independently predicted the hazards for MACE in enrolled patients. The cumulative risk of MACE over time was considerably more significant in those with a GDI>4.21 than those with a GDI≤4.21. The elevated GDI is correlated with an augmented risk of MACE in diabetic patients with concomitant ACS, thereby serving as an early indicator for assessing the unfavorable clinical prognosis of patients. This study offers novel insights into glycemic variability monitoring, enhancing prevention and treatment strategies for cardiovascular disease in people with diabetes.

The Prevalence of Different Genotypic Forms of Familial Hypercholesterolemia in Relation to Race and Ethnicity

In the present study, a systematic literature review was conducted to examine the prevalence of homo- and heterozygous forms of Familial hypercholesterolemia among different racial and ethnic groups. Familial hypercholesterolemia (FH) is an inherited disorder characterised by elevated blood levels of cholesterol and low-density lipoprotein (LDL), which increases the risk of cardiovascular disease. Databases PubMed, Web of Science, and Elsiever were searched and only peer-reviewed articles with a large number of contributors and sufficient prevalence and ethnicity data were included. Diagnosis of FH was based on genetic testing or clinical criteria. The results of the study indicate inadequate and untimely diagnosis of FH, resulting in inadequate treatment. To date, only 9% of countries have statistical data on the prevalence of FH in the general population. In order to develop effective prevention strategies for cardiovascular diseases associated with FH, further research is needed to obtain accurate epidemiological data, including the race and ethnicity of patients. This will allow optimisation of strategies to reduce the burden of preventable cardiovascular disease associated with FH.&lt;br /&gt; &amp;nbsp;

Optimizing Cardiovascular Health: A Comprehensive Review of Risk Assessment Strategies for Primary Prevention.

Cardiovascular disease (CVD) is a leading global health concern, and effective primary prevention strategies are essential to mitigate its impact. This comprehensive review examines current risk assessment strategies for primary prevention of CVD, emphasizing the importance of early identification and intervention to reduce disease incidence. Traditional risk factors such as hypertension, hyperlipidemia, smoking, and lifestyle choices are discussed alongside emerging factors, including genetic predispositions and biomarkers. The review evaluates various risk assessment tools and models, such as the Framingham risk score, atherosclerotic CVD risk calculator, QRISK, and Reynolds risk score, highlighting their methodologies, strengths, and limitations. Additionally, the review explores lifestyle modifications, including dietary changes, physical activity, weight management, smoking cessation, and pharmacological interventions like statins and antihypertensives. Special considerations for different populations, including the elderly, women, and those with a family history of CVD, are addressed. Future directions in cardiovascular risk assessment are also discussed, focusing on technological advancements and personalized medicine. This review aims to enhance the implementation of effective primary prevention measures and improve cardiovascular health outcomes by providing a thorough analysis of risk assessment strategies.

The role of estrogen in Alzheimer's disease pathogenesis and therapeutic potential in women.

Estrogens are pivotal regulators of brain function throughout the lifespan, exerting profound effects from early embryonic development to aging. Extensive experimental evidence underscores the multifaceted protective roles of estrogens on neurons and neurotransmitter systems, particularly in the context of Alzheimer's disease (AD) pathogenesis. Studies have consistently revealed a greater risk of AD development in women compared to men, with postmenopausal women exhibiting heightened susceptibility. This connection between sex factors and long-term estrogen deprivation highlights the significance of estrogen signaling in AD progression. Estrogen's influence extends to key processes implicated in AD, including amyloid precursor protein (APP) processing and neuronal health maintenance mediated by brain-derived neurotrophic factor (BDNF). Reduced BDNF expression, often observed in AD, underscores estrogen's role in preserving neuronal integrity. Notably, hormone replacement therapy (HRT) has emerged as a sex-specific and time-dependent strategy for primary cardiovascular disease (CVD) prevention, offering an excellent risk profile against aging-related disorders like AD. Evidence suggests that HRT may mitigate AD onset and progression in postmenopausal women, further emphasizing the importance of estrogen signaling in AD pathophysiology. This review comprehensively examines the physiological and pathological changes associated with estrogen in AD, elucidating the therapeutic potential of estrogen-based interventions such as HRT. By synthesizing current knowledge, it aims to provide insights into the intricate interplay between estrogen signaling and AD pathogenesis, thereby informing future research directions and therapeutic strategies for this debilitating neurodegenerative disorder.

Dietary strategies for cardiovascular disease prevention

The present review aims to provide specific dietary guidelines based on scientific evidence to prevent the onset of cardiovascular disease (CVD). In general, a high daily consumption of foods of plant origin (whole grains, vegetables, fruits, legumes, and nuts) is recommended compared to foods of animal origin, especially red and processed meats, moderate use of extra virgin olive oil as a culinary fat compared to other types of fats and oils, and low salt intake, especially from processed foods. Despite the scientific evidence and the nutritional education carried out in primary care, CVD continues to be the leading cause of death worldwide, which highlights the need to develop attractive and motivating approaches that enable the population to adhere definitively to healthy habits.

Cardiovascular risk and the COVID-19 pandemic: a population-based and case‒control studies

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is associated with increases in morbidity and mortality worldwide. The mechanisms of how SARS-CoV-2 may cause cardiovascular (CV) complications are under investigation. The aim of the study was to assess the impact of the COVID-19 pandemic on CV risk.MethodsThese are single-centre Bialystok PLUS (Poland) population-based and case‒control studies. The survey was conducted between 2018 and 2022 on a sample of residents (n = 1507) of a large city in central Europe and patients 6–9 months post-COVID-19 infection (n = 126). The Systematic Coronary Risk Estimation 2 (SCORE2), the Systematic Coronary Risk Estimation 2-Older Persons (SCORE2-OP), the Cardiovascular Disease Framingham Heart Study and the LIFEtime-perspective model for individualizing CardioVascular Disease prevention strategies in apparently healthy people (LIFE-CVD) were used. Subsequently, the study populations were divided into CV risk classes according to the 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice.ResultsThe study population consisted of 4 groups: a general population examined before (I, n = 691) and during the COVID-19 pandemic (II, n = 816); a group of 126 patients post-COVID-19 infection (III); and a control group matched subjects chosen from the pre-COVID-19 pandemic (IV). Group II was characterized by lower blood pressure, low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) values than group I. Group III differed from the control group in terms of lower LDL-c level. There was no effect on CV risk in the general population, but in the population post-COVID-19 infection, CV risk was lower using FS-lipids, FS-BMI and LIFE-CVD 10-year risk scores compared to the prepandemic population. In all subgroups analysed, no statistically significant difference was found in the frequency of CV risk classes.ConclusionsThe COVID-19 pandemic did not increase the CV risk calculated for primary prevention. Instead, it prompted people to pay attention to their health status, as evidenced by better control of some CV risk factors. As the COVID-19 pandemic has drawn people’s attention to health, it is worth exploiting this opportunity to improve public health knowledge through the design of wide-ranging information campaigns.

One-size-fits-all versus risk-category-based screening interval strategies for cardiovascular disease prevention in Chinese adults: a prospective cohort study

In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%-21.9%), thus preventing an estimated 113 thousand (95% CI: 83-138) hard ASCVD events for Chinese adults aged 30-79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Safety, Tolerability, and Pharmacodynamics of AZD3366 (Optimized Human CD39L3 Apyrase) Alone and in Combination With Ticagrelor and Acetylsalicylic Acid: A Phase 1, Randomized, Placebo-Controlled Study.

ADP and ATP are importantly involved in vascular and thrombotic homeostasis, via multiple receptor pathways. Blockade of ADP P2Y12 receptors inhibits platelet aggregation and represents an effective cardiovascular disease prevention strategy. AZD3366 (APT102), a long-acting recombinant form of an optimized CD39L3 human apyrase, has effectively reduced ATP, ADP, and platelet aggregation and provided tissue protection in preclinical models, features that could be very beneficial in treating patients with cardiovascular disease. We conducted this phase 1, first-in-human study of single ascending doses of intravenous AZD3366 or placebo, including doses added to dual antiplatelet therapy with ticagrelor and acetylsalicylic acid. The primary objective was safety and tolerability; secondary and exploratory objectives included pharmacokinetics, pharmacodynamics (measured as inhibition of platelet aggregation), adenosine diphosphatase (ADPase) activity, and ATP/ADP metabolism. In total, 104 participants were randomized. AZD3366 was generally well tolerated, with no major safety concerns observed. ADPase activity increased in a dose-dependent manner with a strong correlation to AZD3366 exposure. Inhibition of ADP-stimulated platelet aggregation was immediate, substantial, and durable. In addition, there was a prompt decrease in systemic ATP concentration and an increase in adenosine monophosphate concentrations, whereas ADP concentration appeared generally unaltered. At higher doses, there was a prolongation of capillary bleeding time without detectable changes in the exvivo thromboelastometric parameters. AZD3366 was well tolerated in healthy participants and demonstrated substantial and durable inhibition of platelet aggregation after single dosing. Higher doses prolonged capillary bleeding time without detectable changes in exvivo thromboelastometric parameters. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04588727.

Towards Optimal Cardiovascular Health: A Comprehensive Review of Preventive Strategies.

Heart disease remains a prominent global health concern, with cardiovascular disease (CVD) standing as a leading cause of death worldwide. Preventing heart disease not only decreases the risk of premature death but also mitigates complications like heart attacks, strokes, and arrhythmias, thereby enhancing overall health and quality of life. The economic burden of heart disease treatment highlights the importance of implementing preventive measures, such as lifestyle changes and early interventions, which can alleviate healthcare costs. These strategies, targeting risk factors like hypertension (HTN), diabetes mellitus (DM), dyslipidemia, and obesity, not only prevent heart disease but also reduce the risk of other health issues. Herein, this review covers various preventive measures, including dietary interventions, exercise, controlling HTN, DM, cholesterol, and weight, smoking cessation, and pharmacological interventions. By critically analyzing the guidelines and leveraging robust data alongside variations in recommendations, this review aims to elucidate effective primary prevention strategies for CVD.

Maternal Injection with Dexamethasone Results in Female-Biased Autonomic Dysregulation in Rat Offspring

Autonomic dysfunction is an underlying risk factor for cardiovascular disease (CVD). Maternal injection of the synthetic GC dexamethasone (DEX) during the last 4 days of gestation results in female-biased increases in stress-responsive pressor (MAP), heart rate (HR) and altered heart rate variability (HRV) in adult rat offspring, suggesting a role for GC-mediated programming of autonomic function. The present study used pharmacological antagonists for adrenergic (SYM) or cholinergic (PS) receptors to investigate the degree to which changes in SYM or PS activity underlie the autonomic dysfunction in offspring of dams injected with DEX during late gestation. Naïve breeders were injected with DEX (0.4mg/kg/day, s.c.) or vehicle (hydroxypropyl beta cyclodextrin; Veh) on gestation days 18-21. Radiotelemetry was used in adult offspring for recording HR, MAP, and HRV (root mean square of successive differences: RMSSD). At 10-11 weeks rats were randomly assigned to receive SYM antagonists, α-adrenoceptor (prazosin; 0.5mg/kg, i.p.) + β-adrenoceptor (atenolol; 1mg/kg, i.p.), a PS antagonist (homatropine methylbromide; 0.2mg/kg, i.p), or saline (SAL, i.p.). Evaluations were made over 20 min following injection and then during a 20 min restraint. Females were tested on diestrus. In utero DEX exposure resulted in significantly lower RMSSD, an index of vagal tone, in DEX-exposed females and males. PS blockade significantly reduced RMSSD in Veh-, but not DEX-exposed female offspring. SYM blockade did not influence RMSSD in females. In males, PS blockade reduced in RMSSD in both DEX- and Veh-exposed offspring. SYM blockade only reduced RMSSD in males exposed to DEX. Area under the curve (AUC) analysis revealed that in female offspring, SYM blockade resulted in a greater reduction in HR in DEX-exposed offspring, compared to Veh (DEX-SYM: −220 bpm vs. DEX-SAL; Veh-SYM: −197 bpm vs. VEH-SAL) and during restraint (DEX-SYM: −535 bpm vs. DEX-SAL; Veh-SYM: −342 bpm vs. VEH-SAL). PS blockade resulted in a greater increase in HR in Veh-exposed females both following the injection (Veh-PS: −187 bpm vs. VEH-SAL; DEX-PS: −101 bpm vs. DEX-SAL) and during restraint (Veh-PS: −161 bpm vs. VEH-SAL; DEX-PS: −61 bpm vs. DEX-SAL). AUC analysis for MAP showed similar responses to those for HR with SYM blockade having a greater impact in DEX-exposed females and PS blockade having a greater effect in Veh-exposed females. By contrast, in male offspring in utero DEX exposure did not influence HR or MAP responses to SYM or PS blockade. Overall, these findings suggest that maternal DEX injections alter autonomic development primarily in in female offspring and is characterized by a shift from PS to SYM predominance. Better understanding of the mechanisms involved in this programming are important for identifying individuals at risk for CVD and development of interventional strategies for prevention of CVD. Funding: NIH U54 MH118919. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Subclinical Atherosclerosis to Guide Treatment in Dyslipidemia and Diabetes Mellitus.

Dyslipidemia and type 2 diabetes mellitus are two common conditions that are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In this review, we aimed to provide an in-depth and contemporary review of non-invasive approaches to assess subclinical atherosclerotic burden, predict cardiovascular risk, and guide appropriate treatment strategies. We focused this paper on two main imaging modalities: coronary artery calcium (CAC) score and computed tomography coronary angiography. Recent longitudinal studies have provided stronger evidence on the relationship between increased CAC, thoracic aorta calcification, and risk of cardiovascular events among those with primary hypercholesterolemia, highlighting the beneficial role of statin therapy. Interestingly, resilient profiles of individuals not exhibiting atherosclerosis despite dyslipidemia have been described. Non-conventional markers of dyslipidemia have also been associated with increased subclinical atherosclerosis presence and burden, highlighting the contribution of apolipoprotein B-100 (apoB)-rich lipoprotein particles, such as remnant cholesterol and lipoprotein(a), to the residual risk of individuals on-target for low-density lipoprotein cholesterol (LDL-C) goals. Regarding type 2 diabetes mellitus, variability in atherosclerotic burden has also been found, and CAC testing has shown significant predictive value in stratifying cardiovascular risk. Non-invasive assessment of subclinical atherosclerosis can help reveal the continuum of ASCVD risk in those with dyslipidemia and diabetes mellitus and can inform personalized strategies for cardiovascular disease prevention in the primary prevention setting.

Area deprivation and premature cardiovascular mortality: a nationwide population-based study in South Korea

BackgroundRegional disparities in cardiovascular disease (CVD) burden exist. The effect of area deprivation, one of the possible explanations, still needs to be fully understood. This population-based study investigated the association...