High Risk Of Cardiovascular Disease Research Articles

Life’s Essential 8 and risks of mortality and cardiovascular morbidity in individuals with PRISm and its associations with transition trajectories of PRISm

BackgroundAlthough morbidity and mortality are reportedly increased in individuals with preserved ratio impaired spirometry (PRISm), little is known about how to optimise PRISm-related health.AimsIs Life’s Essential 8 (LE8) associated with...

Cardiovascular risk and allostatic load in PTSD: The role of cumulative trauma and resilience in affected and trauma-exposed adults.

The pathophysiology of posttraumatic stress disorder (PTSD) involves dysregulation of stress-sensitive biological systems due to repeated trauma exposure, predisposing individuals to the development of cardiovascular disease (CVD). Allostatic load (AL), an indicator of maladaptive stress responses, could shed light on the underlying biological mechanisms. We determined whether CVD risk and AL were associated with trauma load and resilience in women with PTSD and trauma-exposed controls (TEC). Adults with PTSD N=114 and TEC N=95 were administered the Clinician Administered Posttraumatic Stress Disorder Scale for DSM-5, to assess for current PTSD diagnosis and severity, the Life Events Checklist for DSM-5 for lifetime exposure to potentially traumatic events (cumulative trauma) and the Connor-Davidson Resilience Scale. An AL score was calculated as a sum of dichotomous variables from four physiological systems (neuroendocrine, metabolic, cardiovascular, and inflammatory). CVD risk was assessed with the South African Framingham risk score. In patients with PTSD, cumulative trauma was associated with higher AL (p=0.04) and CVD risk (p=0.02). In TEC, AL was inversely associated with resilience (p=0.04). There was a significant interaction between cumulative trauma and resilience on AL (p=0.009) in PTSD cases, with a stronger association between cumulative trauma and AL in those with higher resilience. Resilience may have differential detrimental and protective effects on AL in individuals with PTSD and TEC. Cumulative trauma exposure may, independently, increase the likelihood of high AL and CVD risk in PTSD, with resilience moderating this effect. Remaining resilient while experiencing PTSD symptoms may impose a biological strain that could have long-term harmful effects.

Opposite outcomes of triglyceride-glucose index and associated cardiovascular mortality risk in type 2 diabetes mellitus participants by different obesity criteria

We investigated the correlation between Triglyceride-glucose (TyG) index and cardiovascular disease (CVD) mortality in type 2 diabetes mellitus (T2DM) population across different obesity classications using a cohort study. We analyzed 7867 T2DM participants from the National Health and Nutrition Examination Survey 1999–2018, categorizing them into obese or non-obese group by body mass index (BMI) and waist circumference (WC). Cox regression models were used to estimate the correlation between TyG index and CVD mortality risk, comparing the results across the two obesity classifications. Over a 9.1-year follow-up, 691 CVD deaths occurred. Among non-obese T2DM participants (BMI-defined), the hazard ration for CVD mortality was 1.73 in the fourth quartile group of TyG index compared with the first quartile group. Conversely, among obese T2DM participants (WC-defined), the fourth quartile group of TyG index held a 1.51-fold risk of CVD mortality compared with the first quartile group. The association between obesity and higher CVD risk was observed in WC-defined obesity but not in BMI-defined obesity. A totally opposite relationship appeared between TyG index and CVD mortality based on how obesity was defined using BMI or WC in the T2DM participants, suggesting a reevaluation of BMI’s accuracy in predicting mortality risk.

Visit-to-visit lipid variability on long-term major adverse cardiovascular events: a prospective multicentre cohort from the CORE-Thailand registry

Lipid variability (LV) has been studied and proposed as a potential predictor for cardiovascular disease (CVD), and increased LV may contribute to adverse clinical outcomes. This study aimed to investigate the association of various LV parameters with the risk of long-term major adverse cardiovascular events (MACE) among the Thai population. The study used data from the CORE-Thailand Registry, a prospective multicentre study of adults with high cardiovascular risk or established CVD. The primary outcome was 4-point MACE, including non-fatal myocardial infarction, non-fatal stroke, heart failure hospitalisation, and all-cause mortality. LV was defined as visit-to-visit variability in individual and combined lipid parameters using the coefficient of variation (CV), and patients were stratified into four groups according to CV quartiles. The hazard ratio (HR) and 95% confidence interval (CI), adjusted for potential confounders, were calculated using the Cox proportional hazards model. In a total of 9,390 patients, 6,041 patients with data of intra-individual LV were included. After adjusting covariates in the Cox proportional hazards model, higher LV was independently associated with an increased risk of 4-point MACE (HR for quartiles 2, 3, and 4 of the CV of total cholesterol, compared to first quartile, were 3.63 (95% CI 3.20–4.06, P < 0.001), 6.85 (95% CI 6.23–7.47, P < 0.001), and 8.91 (95% CI 8.18–9.64, P < 0.001), respectively). The present study demonstrated that higher visit-to-visit LV, particularly in the higher quartiles, was independently associated with MACE, MI, and all-cause mortality in the Thai population at high cardiovascular risk or established atherosclerotic CVD, indicating that LV might be useful as a potential risk indicator.

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

Unlocking the mysteries of n-oxPTH: implications for CKD patients.

Parathyroid hormone (PTH) is a pivotal hormone that regulates serum calcium and phosphate and is closely associated with higher risk of cardiovascular disease and mortality in patients with chronic kidney disease (CKD). PTH can undergo oxidation at methionine 8 and methionine 18 of the molecule. This oxidation process leads to a lower binding affinity to the PTH receptor due to molecular refolding, particularly for PTH oxidized at methionine 8. Although, the oxidation of PTH has been reported for several decades, it is only recently that a method has been developed to detect non-oxidized PTH (n-oxPTH) levels. The utilization of this assay enables the precise detection of n-oxPTH levels and facilitates the evaluation of their correlation with poor prognosis in patients with CKD. However, the current available clinical research findings indicate that n-oxPTH does not demonstrate clinical superiority over iPTH. Here, we provide a comprehensive review on the mechanism of PTH oxidation, the n-oxPTH assay method, and its correlation with iPTH and clinical outcomes.

Association of socioeconomic inequality in cardiovascular disease risk with economic development across 57 low- and middle-income countries: cross-sectional analysis of nationally representative individual-level data

BackgroundAccording to epidemiological transition theory, cardiovascular disease (CVD) risk shifts down the socioeconomic distribution with economic development. MethodsWe tested this hypothesis using nationally representative data on 88,559 individuals aged 40-80 years from 57 low- and middle-income countries (LMICs). We used measured risk factors to estimate the 10-year probability of a CVD event (CVD risk) and proxied socioeconomic status (SES) by years of education. We used a concentration index to measure socioeconomic inequality in CVD risk and decomposed it into risk factor contributions. We estimated associations CVD risk and inequality in that risk with gross national income (GNI) per capita (pc). ResultsWe estimated that a 1% higher GNI pc was associated with higher mean CVD risk of 0.0265 percentage points (pp) (95% CI: 0.0169 – 0.0361) among females and 0.0150 pp (0.0082 – 0.0219) among males. All risk factors, except systolic blood pressure (SBP) and smoking among females, were positively associated with GNI pc. In most countries, lower SES was associated with higher CVD risk. Age, SBP, diabetes (females only) and smoking (males particularly) contributed most to this inequality, while inequality in total cholesterol was mostly in the opposite direction. Lower SES individuals tended to have relatively higher CVD risk at higher GNI pc, particularly among females. This was due to differences in the distributions of SBP and, for females, age and diabetes. ConclusionsEconomic development was associated with higher and more unequal CVD risk, which may warrant shifting targeting of CVD primary prevention to socially disadvantaged groups.

Pay Attention to Hypertension (PAtH): Findings from a cardiovascular health promotion intervention for adults with intellectual disabilities participating in Special Olympics programming.

Cardiovascular disease (CVD) affects adults globally. People with intellectual disabilities (PWID) may be at higher risk of CVD and associated risk factors (e.g. obesity, hypertension, and diabetes). We developed Pay Attention to Hypertension (PAtH), a cardiovascular health promotion intervention, and tested its impact on changes in blood pressure (BP), lifestyle behaviours and health-related empowerment among PWID. PAtH was developed with a Special Olympics community organisation that supports PWID in developing self-confidence and social skills through participation in sports. The 6-month intervention consisted of 1-h individualised virtual sessions delivered monthly by nursing students/novice nurses. Sessions covered specific themes, including monitoring BP, adopting healthy lifestyles and managing stress, and were individually tailored to the capacities and needs of participants. A single group pre-post-intervention design was used to assess the intervention's effects among participants who completed the intervention and data collection. Data included baseline and follow-up BP measurements from 7-day logbooks and questionnaires assessing lifestyle behaviours [physical activity (PA), screen time and diet], and health-related empowerment. Seventy-four participants were included in the analyses. Between baseline and follow-up, there were no changes in systolic and diastolic BP, PA or leisure screen time. The proportion of participants who reported adding salt when cooking decreased from baseline to follow-up (19.7% vs. 12.7%, P=0.034), and we found improvements for several items measuring health-related empowerment (P≤0.003). Improvements in health-related empowerment were found following PAtH. More intensive interventions may be needed to result in changes in lifestyle behaviours and BP. The integration of adapted cardiovascular health promotion initiatives within well-established community organisations such as Special Olympics is a promising avenue to contribute to cardiovascular health promotion among PWID.

Increased atherogenicity in mood disorders: a systematic review, meta-analysis and meta-regression.

Major depressive disorder (MDD) and bipolar disorder (BD) often coexist with metabolic syndrome. Both are linked to increased atherogenicity and a higher risk of cardiovascular diseases. Nevertheless, a comprehensive analysis of key atherogenic biomarkers in MDD/BD is still lacking. This meta-analysis evaluates the relationship between atherogenic indices and MDD/BD, while identifying the most effective atherogenic biomarker. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched electronic databases, including PubMed, Google Scholar, and Web of Science, for articles published up to August 1, 2024. We included 85 eligible studies (14 on BD and 71 on MDD), covering 70,856 participants: 18,738 patients and 52,118 healthy controls. MDD/BD patients showed significant increases (p < 0.001) in the Castelli Risk Index 2 (CRI2), Atherogenic Index of Plasma (AIP), and (triglyceride or TG + low-density lipoprotein + very low-density lipoprotein)/(high-density lipoprotein cholesterol or HDL + Apolipoprotein A or ApoA) ratio, but not CRI1 and ApoB/ApoA ratio. Significant lower HDL and lecithin: cholesterol acyltransferase activity, and higher TG levels were observed in MDD/BD patients compared with controls. There were no significant differences between MDD and BD patients. Most included studies lacked the most essential information on the inclusion and exclusion of important confounders. AIP is the most effective atherogenicity index for mood disorders. Regular lipid profiling and metabolic syndrome screening are crucial in MDD/BD. Early intervention with lipid-lowering therapies is recommended to prevent the worsening of atherogenicity and disease progression.

Assessing cardiovascular disease risk and social determinants of health: A comparative analysis of five risk estimation instruments using data from the Eastern Caribbean Health Outcomes Research Network.

Accurate assessment of cardiovascular disease (CVD) risk is crucial for effective prevention and resource allocation. However, few CVD risk estimation tools consider social determinants of health (SDoH), despite their known impact on CVD risk. We aimed to estimate 10-year CVD risk in the Eastern Caribbean Health Outcomes Research Network Cohort Study (ECS) across multiple risk estimation instruments and assess the association between SDoH and CVD risk. Five widely used CVD risk estimation tools (Framingham and WHO laboratory, both laboratory and non-laboratory-based, and ASCVD) were applied using data from ECS participants aged 40-74 without a history of CVD. SDoH variables included educational attainment, occupational status, household food security, and perceived social status. Multivariable logistic regression models were used to compare differences in the association between selected SDoH and high CVD risk according to the five instruments. Among 1,777 adult participants, estimated 10-year CVD risk varied substantially across tools. Framingham non-lab and ASCVD demonstrated strong agreement in categorizing participants as high risk. Framingham non-lab categorized the greatest percentage as high risk, followed by Framingham lab, ASCVD, WHO lab, and WHO non-lab. Fifteen times more people were classified as high risk by Framingham non-lab compared with WHO non-lab (31% vs 2%). Mean estimated 10-year risk in the sample was over 2.5 times higher using Framingham non-lab vs WHO non-lab (17.3% vs 6.6%). We found associations between food insecurity, those with the lowest level compared to the highest level of education, and non-professional occupation and increased estimated CVD risk. Our findings highlight significant discrepancies in CVD risk estimation across tools and underscore the potential impact of incorporating SDoH into risk assessment. Further research is needed to validate and refine existing risk tools, particularly in ethnically diverse populations and resource-constrained settings, and to develop race- and ethnicity-free risk estimation models that consider SDoH.

Association of cardiovascular disease risk with liver steatosis and fibrosis in people with HIV in low- and middle-income countries.

The aim of this study was to understand the relationship between cardiovascular disease (CVD) risk and liver steatosis and fibrosis among people with HIV (PLWH) at least 40 years of age on antiretroviral therapy (ART) in low and middle-income countries (LMIC). We used cross-sectional behavioral and clinical data collected during study enrollment visits in 2020-2022 for the Sentinel Research Network of International epidemiology Databases to Evaluate AIDS (SRN of IeDEA). Ten-year CVD risk was calculated using 2019 WHO nonlaboratory and laboratory models. Transient elastography was used to assess liver disease. Presence of steatosis and significant fibrosis were defined by controlled attenuation parameter (CAP) at least 248 dB/m and liver stiffness measurement (LSM) at least 7.1 kPa, respectively. Participants with viral hepatitis, hazardous alcohol consumption, and unsuppressed HIV viral load were excluded from the analysis. Logistic regression was used to estimate odds ratios, adjusting for study site, CD4 + T cell count, stavudine and didanosine exposure, and in models stratified by sex and geographic region. There were 1750 participants from nine LMIC. Median CVD risk was 3% for both nonlaboratory and laboratory-based models. Adjusted odds ratios (ORs) for steatosis and significant fibrosis associated with laboratory CVD risk (≥10 vs. <5%) were OR = 1.83 [95% confidence interval (95% CI) = 1.21-2.76; P = 0.004] and OR = 1.62 (95% CI = 0.85-3.07; P = 0.14), respectively. Associations of CVD risk with steatosis were stronger in men and among participants at study sites outside Africa. Higher CVD risk was associated with steatosis but not with significant fibrosis in PWH in our LMIC cohort.

Association between descending aorta wall thickness or wall area and cardiovascular disease risk factors in cardiovascular disease-free patients: a study based on water-calcium material decomposition and subtraction-based computed tomography dark-blood imaging.

Due to the low contrast between the vascular lumen and vessel wall, conventional computed tomography (CT) is not an effective method for visualizing the vessel wall. The purpose of this study was to assess the feasibility of vessel wall visualization using contrast-enhanced dual-energy CT (DECT)-derived water-calcium material decomposition (WMD) and subtraction-based dark-blood imaging (DBI). An additional objective of this study was to determine the association of descending aorta wall thickness (WT) and wall area (WA) with cardiovascular disease (CVD) risk factors and to ascertain the potential of DECT-derived WT and WA as image markers for identifying individuals at high risk for future CVD. In this cross-sectional study, virtual noncontrast (VNC), subtraction-based DBI, and WMD images of 106 patients were generated from the arterial-phase DECT data files. To assess the vessel wall visualization, the contrast-to-noise ratios (CNRs) of the descending aorta between the vessel wall and lumen or periaortic fat ( ) were calculated and compared in VNC, subtraction-based DBI, and WMD images. Subsequently, two radiologists independently assessed the vessel wall visualization of these three kinds of images using a four-point scale. To evaluate the association between WT or WA and CVD risk factors, descending aortic WT and WA were measured in the subtraction-based DBI and WMD images, while interobserver agreement was assessed through intraclass correlation coefficients (ICCs). The relationship between the WT or WA and CVD risk factors was determined using univariate and multiple regression analyses. Both WMD and subtraction-based DBI images demonstrated superior and qualitative scores as compared to VNC images ( : 0.59±0.47, 4.36±2.14, and 4.81±3.28, respectively; qualitative scores: 1.04±0.71, 2.53±0.50, and 2.92±0.27, respectively; for virtual non-contrast, subtraction-based DBI and WMD images respectively, all P values <0.05), which indicated better image qualities for vessel wall imaging. The mean descending aorta WT values were 2.18±0.27 and 2.17±0.27 mm for observer 1 and 2.14±0.27 and 2.15±0.26 mm for observer 2 in the subtraction-based DBI and WMD images, respectively. Age and smoking status were predictors for both WT and WA, while males had higher WA values than did females. Blood pressure was only significant for WA measured in subtraction-based DBI. Both subtraction-based DBI and WMD images in DECT can be used to effectively visualize vessel walls and measure WT and WA, with both measurements demonstrating a positive correlation with CVD risk factors of age and smoking.

Danggui Liuhuang Decoction Ameliorates Endothelial Dysfunction by Inhibiting the JAK2/STAT3 Mediated Inflammation

Ethnopharmacological relevanceVascular endothelial dysfunction (VED) is recognized as a key triggering diabetic vascular complications. Danggui Liuhuang Decoction (DGLHD) has shown potential in mitigating these complications. However, the clinical efficacy of DGLHD in enhancing endothelial function, as well as the molecular mechanisms underlying its alleviation of Type 2 Diabetes-Related Vascular Endothelial Dysfunction (T2DM-VED), remains insufficiently understood. Aim of the studyThis study aims to validate the therapeutic efficacy of DGLHD in ameliorating T2DM-VED through clinical research. Furthermore it seeks to analyze the pharmacodynamic basis and molecular mechanisms of DGLHD, elucidating the biological processes through which DGLHD alleviates VED in type 2 diabetes mellitus (T2DM). Materials and methodsPatients diagnosed with "Yin deficiency with hyperactive fire syndrome", who are at a high risk for atherosclerotic cardiovascular disease (ASCVD) associated with T2DM, were recruited for this study. The effect of DGLHD on vascular endothelial function in T2DM was assessed by measuring the levels of pro-inflammatory factors through enzyme-linked immunosorbent assay (ELISA) and flow-mediated dilation (FMD). The primary components of DGLHD were analyzed using the UHPLC-Q-Exactive Orbitrap system. Potential therapeutic targets of DGLHD were predicted using network pharmacology and molecular docking analysis. To validate the mechanism of DGLHD on T2DM-VED, endothelial injury and inflammation cell models were established using human umbilical vein endothelial cells (HUVECs). A mouse model of diabetic endothelial injury was also developed to observe the effects of DGLHD on pro-inflammatory factors and vascular endothelial factors were observed through immunohistochemistry. Additionally, the effects on the JAK2/STAT3 signaling pathway were observed through Western blot experiments. ResultsDGLHD was found to contain 201 active components. Network pharmacology analysis indicated that the treatment of T2DM-VED with DGLHD is associated with modulation of the JAK2/STAT3 signaling pathway. Molecular docking analysis demonstrated that small molecules in DGLHD interact with JAK2 and STAT3. Our clinical study demonstrated that DGLHD significantly reduces the levels of pro-inflammatory factors and improves FMD readings in diabetic patients, thereby alleviating T2DM-VED. DGLHD was shown to inhibit the phosphorylation of JAK2 and STAT3, which blocks the JAK2/STAT3 signaling pathway transmission, reducing the release of pro-inflammatory and vascular endothelial growth factors, and preventing the inflammatory response in vivo and in vitro. ConclusionThis study demonstrates the potential efficacy of DGLHD in improving endothelial function in T2DM patients at high risk for ASCVD. By inhibiting the JAK2/STAT3 signaling pathway, DGLHD effectively reduces the release of pro-inflammatory factors and vascular endothelial growth factors, alleviating VED.

Hepatic Steatosis and Fibrosis, Cardiorespiratory Fitness, and Metabolic Mediators in the Community.

Individuals with steatotic liver disease (SLD) are at high cardiovascular disease (CVD) risk, but approaches to characterise and mitigate this risk are limited. By investigating relations, and shared metabolic pathways, of hepatic steatosis/fibrosis and cardiorespiratory fitness (CRF), we sought to identify new avenues for CVD risk reduction in SLD. In Framingham Heart Study (FHS) participants (N = 2722, age 54 ± 9 years, 53% women), vibration-controlled transient elastography (VCTE) was performed between 2016-2019 to assess hepatic steatosis (continuous attenuation parameter [CAP]) and fibrosis (liver fibrosis measure [LSM]). Concurrently, participants underwent maximum effort cardiopulmonary exercise testing (CPET), and metabolomic profiling (201 circulating metabolites) was performed in a subsample (N = 1268). Mean BMI was 28.0 ± 5.3, 27% had hepatic steatosis, 7.6% had fibrosis, and peak oxygen uptake (VO2) was 26.2 ± 6.8 mL/kg/min in men and 20.7 ± 6.0 mL/kg/min in women (95% predicted overall). In linear models adjusted for cardiometabolic risk factors, greater CAP and LSM were associated with lower peak VO2 (p ≤ 0.002 for all), and the CAP association remained significant after BMI adjustment (p < 0.0001). We observed shared metabolic architecture of CAP, LSM, and peak VO2, with metabolites mediating up to 35% (for CAP) and 74% (for LSM) of the association with peak VO2. Metabolite mediators included amino acids and derivatives implicated in cardiometabolic risk and both protective and deleterious lipid species. Hepatic steatosis and fibrosis are associated with CRF impairment in the community, and these relations are partly mediated by pathways of altered lipid metabolism and general cardiometabolic risk.

Cardiovascular Risk from Metabolic Dysfunction-Associated Steatotic Liver Disease, Cardiometabolic Risk Factor Count, and Their Longitudinal Changes: A Nationwide Cohort Study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with incident cardiovascular disease (CVD). However, CVD risk could vary across and within individuals with MASLD. We investigated the cardiovascular implications of MASLD, cardiometabolic risk factor count, and their longitudinal changes. From nationwide health screening data, we included adults aged 20-79 without increased/excessive alcohol intake, concomitant liver diseases, and prior CVD at baseline examination in 2009 (N=7,292,497). Participants were classified according to MASLD status; those with MASLD were further categorized by their count of qualifying cardiometabolic risk factors (1-5). Individuals who underwent follow-up examinations in 2011 (N=4,198,672) were additionally classified according to their baseline and follow-up MASLD status; those with persistent MASLD were further categorized by combination of baseline and follow-up cardiometabolic risk factor counts. The risk of incident CVD was assessed using multivariable-adjusted Cox model. Over a median follow-up of 12.3 years, 220,088 new CVD events occurred. The presence of MASLD was associated with higher incidence of CVD. Among participants with MASLD, the risk of CVD increased gradually with higher cardiometabolic risk factor count (per 1-higher; HR, 1.18 [95% CI, 1.18-1.19]). The development of MASLD during follow-up was associated with higher risk of CVD (HR, 1.28 [95% CI, 1.25-1.31]), whereas the regression of MASLD was associated with lower risk of CVD (HR, 0.84 [95% CI, 0.82-0.86]). Among individuals with persistent MASLD, gaining and losing cardiometabolic risk factor count during follow-up were associated with elevated and reduced risk of CVD, respectively. MASLD status, cardiometabolic risk factor count, and their longitudinal changes were all associated with the risk of incident CVD. Accurate identification of these markers may facilitate personalized management of MASLD-related CVD risk.

Exploring the interplay: aspirin therapy, genetic polymorphisms, and homocysteine levels in cardiovascular disease patients

Cardiovascular disease (CVD) is a significant worldwide health threat expected to cause 23.6 million deaths annually by 2030. Homocysteine is an amino acid that is generated during the breakdown of methionine. Elevated levels of homocysteine are recognised as a standalone risk factor for cardiovascular disease, such as coronary artery disease and stroke. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) play essential roles in regulating homocysteine levels and maintaining cardiovascular health. The C677T (rs1801133) mutation of the MTHFR gene is closely linked to coronary artery disease due to decreased enzyme activity while the A2756G mutation (rs1805087) in the MS gene disrupts the remethylation process and is linked to elevated homocysteine levels and a higher risk of cardiovascular disease. Aspirin is a key treatment for cardiovascular disease by preventing platelet activation and aggregation, reducing the likelihood of blood clot formation. In addition, aspirin usage seems to be connected to homocysteine levels in persons dealing with CVD. The precise interplay between aspirin therapy, genetic polymorphisms, and their collective impact on homocysteine levels in CVD patients remains unclear. Therefore, this investigation aims to explore the effects of genetic polymorphisms (MTHFR and MS genes) and aspirin therapy on homocysteine levels in CVD patients from two hospitals in Selangor, Malaysia. Blood samples from 52 patients were collected and analysed, with homocysteine levels quantified using LCMS-QQQ, aspirin abundance determined through LCMS-QTOF, and genetic polymorphisms of MTHFR and MS genes identified using RT-PCR. Interestingly, individuals with CVD exhibiting elevated homocysteine levels did not show the mutant genotype for neither MTHFR nor MS genes. Furthermore, the potential influence of aspirin therapy emerged as a plausible explanation for the observed lower homocysteine levels in these patients. Other variables than genetic predisposition may play a role in causing elevated homocysteine levels in people with CVD. Our findings suggest that aspirin therapy may have a potential impact on reducing homocysteine levels in these patients. However, more research is needed to understand the underlying mechanisms.

Association of GUCY1A3 (rs7692387), CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893) gene polymorphism with antiplatelet drug metabolism and prognosis of cardiovascular complications

Introduction: The identification of predictors for resistance to antiplatelet drugs including the search for new gene polymorphisms responsible for the development of the pathological process is an important direction to reduce the risk of complications after cardiac surgery and improve postoperative prognosis. Objective: The study was aimed at investigating the available data on the molecular genetic markers GUCY1A3 (rs7692387), CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893) and their association with antiplatelet drug metabolism and adverse outcome after cardiac surgery.Methods: The systematic review was conducted in accordance with the PRISMA criteria. The search was performed in databases Medline (PubMed), Google Scholar and the Russian Science Citation Index using queries and keywords. During the first selection, 3,210 results were obtained. The final analysis included 21 studies conducted between 2004 and 2024.Results: Since 2017 a number of studies have revealed the association of GUCY1A3 gene polymorphism with a high risk of cardiovascular diseases, as well as with an abnormal reaction to acetylsalicylic acid. The mechanism of the pathological process was related to the impact of gene polymorphism on vasoreactivity, platelet aggregation and, as a consequence, on the risk of thrombotic complications.Polymorphisms of CYP2C19*2 and CYP2C19*3 were the most common variants of alleles that reduced clopidogrel metabolism and increased the risk of cardiovascular events. However, therapy based on CYP2C19 genotyping requires a more detailed investigation with the inclusion of ethnic, demographic and socio-economic factors in the analysis.Conclusion: Resistance to acetylsalicylic acid, clopidogrel and other antiplatelet drugs depends on many genetic factors. Further investigation of the GUCY1A3 and CYP2C19 gene polymorphisms is promising for the development of algorithms for genotype-oriented antiplatelet therapy, the introduction of which into medical practice will reduce the number of complications after cardiac surgery and improve the quality of medical care. Received 16 September 2024. Revised 2 November 2024. Accepted 5 November 2024. FundingThe study did not have sponsorship. Conflict of interestThe authors declare no conflict of interest. Contribution of the authorsConception and study design: A.V. Kurguzov, O.V. KamenskayaData collection and analysis: I.Yu. Loginova, A.S. Isaev, D.V. DoroninDrafting the article: I.Yu. Loginova, A.S. KlinkovaCritical revision of the article: O.V. Kamenskaya, A.M. ChernyavskiyFinal approval of the version to be published: I.Yu. Loginova, A.V. Kurguzov, A.S. Isaev, O.V. Kamenskaya, D.V. Doronin, A.S. Klinkova, A.M. Chernyavskiy

Cognitive function status and its correlation with blood pressure control in patients with hypertension in China

Objective: To investigate the global cognitive function and the function of specific cognitive domains in hypertensive patients at high risk of cardiovascular disease in China, and to explore the impact of cognition function on blood pressure control. Methods: This is a cross-sectional survey. Data were obtained from the ESPRIT study. Patients with a history of hypertension who participated in the ESPRIT study from September 2019 to July 2020 were selected. Mini-mental state examination (MMSE) was used to evaluate patients' overall cognition and the function of each cognitive domain. According to the total MMSE score, patients were divided into the cognitive-intact group (MMSE total score=30 points), cognitive-declined group (MMSE total score<30 points, but did not reach the dementia screening threshold) and cognitive-impaired group (MMSE total score reached the dementia screening threshold). A multivariable logistic regression model was used to explore the effects of cognitive function and MMSE score on blood pressure control. The years of education were removed from the adjustment variables for sensitivity analysis. The interaction effect modeling of stratified variables and exposed variables was used for hierarchical analysis. Results: A total of 10 834 patients with hypertension at high risk of cardiovascular disease were enrolled, aged 65 (60, 69) years and 4 476 (41.3%) patients were female. There were 989 patients in cognitive-intact group, 8 676 patients in cognitive-declined group and 1 169 patients in cognitive-impaired group. The MMSE score of all included patients was (25.6±3.8) points. In the overall study population, 10.8% (1 169/10 834) of hypertensive patients had cognitive impairment, with an MMSE total score of (18.6±4.1) points. The cognitive domains with obvious impairment were recall memory (-80%), visuospatial function (-64%), attention and computation (-60%); 80.1% (8 676/10 834) of hypertensive patients did not meet the criteria for cognitive dysfunction, but had cognitive decline, and the cognitive domains with significant impairment were recall memory (-51%) and visuospatial structure (-23%). Multivariate logistic regression analysis showed that cognitive dysfunction (OR=0.88, 95%CI: 0.72-1.08, P=0.212) and cognitive decline (OR=0.96, 95%CI: 0.83-1.12,P=0.629) was not correlated with blood pressure control. MMSE total score and scores in each cognitive domain were not correlated with blood pressure control (P>0.05). Sensitivity analysis showed that cognitive function was not related to blood pressure control (all P>0.05). Stratified analysis according to different frequency of medication showed that cognitive function and MMSE score were not correlated with blood pressure control (P>0.05). Conclusion: One in ten hypertensive patients who were at high risk of cardiovascular disease have comorbid cognitive impairment. In patients with high risk of cardiovascular disease, the most affected cognitive domains were recall memory, visuospatial function, attention and calculation. Part of hypertensive patients have not reached the level of cognitive dysfunction, but have begun to show cognitive decline. Cognitive function is not an independent influencing factor on blood pressure control.

Type 2 diabetes and chronic kidney disease as long-term predictors of cardiovascular events in patients with coronary artery disease.

Both chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) confer a high risk of cardiovascular disease and mortality. These entities frequently coincide. The separate and joint impact of CKD and T2DM on the risk of major cardiovascular events (MACE) and survival is unclear. In this prospective cohort study, patients with angiographically proven coronary artery disease were investigated according to their CKD and T2DM status (T2DM-/CKD-, T2DM+/CKD-, T2DM-/CKD+, T2DM+/CKD+) and followed for up to 18 years. A total of 1441 patients were included in the study of whom 39% experienced MACE (T2DM-/CKD-: 31%, T2DM+/CKD-: 43%, T2DM-/CKD+: 53%, T2DM+/CKD+: 61%) and 53% died. A log-rank test revealed significant differences between the event-free time period of the four groups (χ2 (3) = 112.57, p < 0.001). The presence of T2DM and CKD was associated with a 2.72-fold increase [1.98-3.73] in MACE compared to patients who suffered from neither condition (p < 0.001). T2DM alone led to a 1.37-fold increase [1.1-1.7], (p = 0.004), CKD alone to a 1.71-fold increase [1.31-2.25], (p < 0.001). T2DM and CKD in patients with coronary artery disease are mutually independent predictors of cardiovascular events. Patients with both CKD and T2DM are at an extremely high risk for cardiovascular events.

Cardiovascular mortality trends and disparities in U.S. breast cancer patients, 1999–2020: a population-based retrospective study

BackgroundBreast cancer survivors face a higher risk of cardiovascular disease (CVD) compared to non-breast cancer patients, yet contemporary data on CVD-related mortality within this group remains scarce.ObjectiveTo investigate trends and disparities in CVD mortality among breast cancer patients.MethodsWe queried the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC Wonder) and conducted serial cross-sectional analyses on national death certificate data for CVD mortality in breast cancer patients aged 25 and above from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals and analyzed trends over time using the Joinpoint Regression Program, with further analyses stratified by age, race, census region, and urbanization level.ResultsA total of 74,733 CVDs with comorbid breast cancer in the United States were identified between 1999 and 2020. The AAMR from CVDs with comorbid breast cancer decreased from 2.57 (95% CI [2.50–2.65]) in 1999 to 1.20 (95% CI [1.15–1.24]) in 2020, with an average annual percent change (AAPC) of − 4.3. The three most common causes of CVDs were ischemic heart disease (47.8%), cerebrovascular disease (17.1%), and hypertensive disease (10.6%). Our analysis revealed a significant decrease in AAMR for all CVD subtypes, except for hypertensive diseases and arrhythmias. The decrease in annual percent change (APC) was more pronounced in individuals aged ≥ 65 years compared to those < 65 years (-4.4, 95%CI [-4.9, -3.9] vs. -2.9, 95%CI [-4.1, -1.7], respectively. Notably, non-Hispanic Blacks consistently exhibited the highest AAMR (1.95, 95%CI [1.90–1.99]), whereas Hispanic or Latina patients had the lowest AAMR (0.75, 95% CI [0.72–0.78]). The AAMR was also higher in rural regions than in urban areas (1.64, 95%CI [1.62–1.67] vs. 1.55, 95%CI [1.53–1.56]).ConclusionThe study highlights a significant decline in CVD mortality among breast cancer patients over two decades, with persistent disparities by race and region. Exceptionally, hypertensive diseases and arrhythmias did not follow this declining trend.