Prevention Of Cardiovascular Disease Research Articles

Risk factors for major bleeding among patients with chronic kidney disease treated with acetylsalicylic acid

Introduction: Individuals with chronic kidney disease (CKD) are at increased risk for thrombotic events and bleeding. Acetylsalicylic acid (ASA), an effective antiplatelet agent, is one of the most frequently used medications for both primary and secondary prevention of cardiovascular disease (CVD). However, it can also contribute to bleeding events due to its inherent antiplatelet effect. The objective of this study was to determine the characteristics of CKD patients at increased risk for bleeding under ASA therapy. Methods: This retrospective analysis included patients with non-dialysis dependent CKD who were treated with ASA for primary prevention of CVD for at least 3 consecutive months and did not receive anti-coagulants or anti-platelets. Data were collected from electronic medical records from January 2014 to December 2018. CKD diagnosis was based on an estimated glomerular filtration rate of <60 ml/min/1.73 m2. CKD patients who experienced major bleeding events during ASA therapy (bleeding group) vs. all others (control group) were compared. Additional outcomes included first documented non-fatal cardiovascular event and all-cause mortality. Results: Of the 900 adult CKD patients included in this analysis, 82 (9.1%) had a major bleeding event during 31.6±25.9 months of follow-up. The most common bleeding site was gastrointestinal (52 cases, 63.4% of major bleeding events). Patients who had a major bleeding event were older (76.5±10 vs. 74±10.3 years, P=0.038). On multivariate analysis, age was the most important predictor of major bleeding event (odds ratio 1.029, 95% confidence interval 1.004–1.056). Conclusions: Given its controversial efficacy in primary prevention of CVD in CKD patients, characterizing those at increased risk for bleeding under ASA therapy is important in the era of tailored medicine. Age, CKD stage and cardiovascular risk are key factors to consider regarding the safety and effectiveness of ASA for CKD patients.

Changes in the estimated glucose disposal rate and incident cardiovascular disease: two large prospective cohorts in Europe and Asia

Background and aimsPrevious study found that estimated glucose disposal rate (eGDR) was significantly associated with cardiovascular disease (CVD). However, little is known about the change in eGDR over time and its association with the development of CVD. The aim of this study was to investigate the association of change in eGDR with CVD risk.MethodsThis study used data of two prospective cohorts: UK Biobank and China Health and Retirement Longitudinal Study (CHARLS) with two measurements of eGDR. Changes in the eGDR were classified using K‑means clustering analysis, and the cumulative eGDR was also calculated. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders.ResultsA total of 11,682 individuals from the UK Biobank, and 4,974 individuals from the CHARLS were included. The median follow-up periods were 9.7 years in the UK Biobank and 3.0 years in the CHARLS. Compared with persistently high level of eGDR (class 1), individuals with low level increasing (class 3) and persistently low level of eGDR (class 4) showed elevated risks of incident CVD in both UK Biobank (HR = 2.79, 95% 2.15–3.62 for class 3; HR = 3.19, 95% 2.50–4.08 for class 4) and CHARLS (HR = 1.66, 95% 1.29–2.13 for class 3; HR = 1.69, 95% 1.34–2.14 for class 4). In addition, lower level of cumulative eGDR were associated with elevated risks of incident CVD. The dose-response curve between cumulative eGDR and CVD risk showed a negative linear relationship.ConclusionDifferent changes in eGDR level are associated with different risks of incident CVD. Dynamic monitoring of eGDR level is of significant importance for the CVD prevention and treatment.

Risk Factors, Comorbidities, and Prevention of Cardiovascular Diseases: Don’t Forget the Primary Cause!

Cardiovascular diseases (CVDs) remain a leading cause of mortality worldwide. Despiteinnovative treatments, both pharmacological and interventional, CVDs continue toprogress. This is largely due to the increased incidence of diseases such as diabetes andother well-established cardiovascular risk factors, as well as cumulative comorbidities andemerging risk factors.

Statin prescription disparities in patients with breast cancer and diabetes for primary cardiovascular disease prevention

BackgroundThis brief report examines statin prescription trends for primary cardiovascular disease (CVD) prevention in breast cancer (BC) survivors with diabetes, a large population at particularly high CVD risk.MethodsA population-based, retrospective cohort study was conducted using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to Medicare claims. We identified women with preexisting diabetes who were diagnosed with stage 0–III primary BC between 2008 and 2017 without preexisting CVD. We assessed statin prescription rates over time and also examined differences in statin prescription rates according to patient sociodemographic characteristics. Using a multivariate logistic regression adjusted for sociodemographic and clinical variables, independent predictors of statin prescription were identified.ResultsOf 8,423 BC patients with diabetes without preexisting CVD, 5,698 (68%) had a statin prescription. Statin prescriptions increased over time (BC diagnosis year 2008–2009: 65%, 2010–2011: 67%, 2012–2013: 66%, 2014–2015: 69%, 2016–2017: 70%; p = 0.01) and differed by age (66–69: 66%, 70–74: 70%, 75–79: 69%, ≥80: 65%; p < 0.01) and race (White: 68%, Black: 62%, Latina: 66%, Other: 72%; p < 0.01). In a multivariate analysis, race (Black vs. White: OR 0.80, 95% CI: 0.68–0.95) remained a predictor of statin prescription.ConclusionIn older early-stage BC survivors, statin prescriptions increased over time and varied by age, race, and BC stage. These findings can potentially inform strategies to improve guideline-concordant statin prescriptions in a group at high risk for CVD and reduce disparities.

Gene-Based Targeting for Treatment of Hypercholesterolemia and Prevention of Atherosclerotic Cardiovascular Disease

Familial hypercholesterolemia, characterized by high levels of LDL cholesterol is a monogenic metabolic disorder linked to atherosclerotic cardiovascular disease. Several genetic mutations in genes such as LDLR and PSK9 are thought to cause familial hypercholesterolemia. This ultimately causes dysfunction of the LDLR pathway, increasing circulating LDL levels. Current treatment revolves around decreasing LDL cholesterol levels in the blood. Statins are the current gold standard while sterol absorption inhibitors (ezetimibe) and PCSK9 inhibitors (evolocumab) are either used as primary treatment in individuals with statin intolerance, or supplementary treatment otherwise. However, CRISPR-Cas9 offers an upstream therapeutic intervention, inducing mutations in pathogenic genes (such as LDLR) to upregulate or downregulate gene expression and subsequently reduce LDL cholesterol levels. This technology thus has great potential as a two-fold treatment option, offering an effective solution for familial hypercholesterolemia, while simultaneously diminishing the risk of atherosclerotic cardiovascular disease. A limitation to current research exists in the sole analysis of monogenic factors in genetic screening, thus polygenic, multifactorial analyses are required to assess more holistic treatment plans. Furthermore, there exist current limitations to CRISPR-Cas9 including ethical limitations and social considerations revolving around the perpetuation of social inequities through technology necessitating future research on global health policies.

Effects of aspirin and omega-3 fatty acids on composite and subdomain scores from the NEI-VFQ-25 questionnaire: the ASCEND-Eye randomized controlled trial

BackgroundThe double-blind, 2 × 2 factorial design, placebo-controlled ASCEND randomized trial compared the effects of 100 mg aspirin daily and, separately, 1 g omega-3 fatty acids (FAs) daily on the primary prevention of cardiovascular disease in 15,480 UK adults with diabetes. We report the effects of these randomized treatment allocations on scores derived from the National Eye Institute’s Visual Function Questionnaire-25 (NEI-VFQ-25) in a subset of participants involved in the ASCEND-Eye sub-study.MethodsOrdinal data from the NEI-VFQ-25 were analyzed using proportional odds regression methods. A common odds ratio with a 95% confidence interval was used to interpret the average effect size of randomization to each study treatment on composite and subdomain scores from the questionnaire.ResultsNeither randomization to aspirin nor omega-3 FAs for 7.5 years significantly affected composite or subdomain scores from the NEI-VFQ-25.ConclusionApplying the NEI-VFQ-25 in ASCEND-Eye represents one of the largest surveys of vision-targeted health-related quality of life in people with diabetes. Further observational analyses of these data are planned, to identify the clinical and demographic characteristics associated with lower composite and subdomain scores in a diabetic population.Trial registrationEudract No. 2004–000991-15; Multicentre Research Ethics Committee Ref No. 03/8/087 (29th December 2003); ClinicalTrials.gov No. NCT00135226 (24th August 2005); ISRCTN No. ISRCTN60635500 (1st September 2005).

Potential Cardiovascular Disease Treatment by Natural Drugs Targeting the HIF-1α Factor and its Pathway.

Cardiovascular diseases (CVDs) remain a key contributor to global morbidity and mortality. Being a vital regulator of hypoxia, hypoxia-inducible factor-1α (HIF-1α) is a crucial player in CVD treatment. Recently, increasing attention has been paid to the effect of natural drugs on CVDs. According to some studies, HIF-1α is a potential target for CVD treatment in traditional Chinese medicine. In this study, we describe the mechanism underlying the regulatory role of HIF-1α in CVDs and summarize 30 natural drugs and 3 formulations for CVD treatment through HIF-1α and its signaling pathway. The study provides new ideas for CVD prevention and treatment.

Gut Microbiome and Carotid Artery Intima-Media Thickness: A Narrative Review of the Current Scenario

Up to the last update, the gut microbiome (GM) had been associated with a different physiologic host process, including those affecting cardiovascular health. The carotid intima-media thickness (IMT) is an indicator of atherosclerosis and cardiovascular risk. The GM influence on atherosclerosis progression has garnered growing attention in recent years but the consensus in subclinical atherosclerosis remains elusive. The aim of this narrative review is to investigate the connection between the GM and carotid IMT, encompassing mechanisms like the microbiome impact on metabolite production, and systemic inflammation, and its effects on endothelial function. The literature analysis revealed that the GM appears to exert an influence on carotid IMT development, likely through mechanisms involving metabolites’ production, systemic inflammation, and endothelial function modulation. Additional research, however, is needed to finely elucidate the relationship between the GM and atherosclerosis. Specifically, more extensive studies are required to pinpoint individuals at the highest risk of developing atherosclerosis based on their GM composition. This will facilitate the enhancement and optimization of cardiovascular disease prevention strategies and enable the treatments’ customization for each patient. Further investigations are required to refine patient outcomes in the context of probiotics and other interventions aimed at improving microbiome composition and function.

Impact of Genetic Risk Information for Cardiovascular Disease on Behavioural, Psychological Responses, and Risk Factor Modification: A Systematic Review.

Cardiovascular disease (CVD) remains a significant public health concern, influenced by both genetic susceptibility and lifestyle factors. Integrating genetic risk information into clinical practice shows promise but has yielded mixed results regarding its impact on CVD prevention and management. This systematic review aimed to assess the impact of providing genetic CVD risk information on health behaviours, psychological outcomes, and risk factors. Following JBI methodology and PRISMA 2020 guidelines, four electronic databases and two trial registries were searched for randomised controlled trials evaluating the impact of genetic risk information on the CVD risk profile. Data was synthesised using a narrative synthesis approach. Of the 3,596 articles retrieved, 11 studies were eligible. Genetic risk information showed modest improvements in dietary behaviour but had inconclusive effects on physical activity and medication adherence. Minimal changes in psychological outcomes were noted, including a slight decrease in depression. The impact on traditional risk factors, such as systolic blood pressure and total cholesterol was also limited. Bias across all studies was noted. Genetic CVD risk information has limited effects on clinical outcomes and psychological factors, despite its potential to encourage some health behaviour changes. These findings suggest that genetic risk information alone may not be sufficient to significantly reduce cardiovascular risk, highlighting the need for further research to better understand its long-term effects.

Biomarkers of glucose-insulin homeostasis and incident type 2 diabetes and cardiovascular disease: results from the Vitamin D and Omega-3 trial

BackgroundDysglycemia and insulin resistance increase type 2 diabetes (T2D) and cardiovascular disease (CVD) risk, yet associations with specific glucose-insulin homeostatic biomarkers have been inconsistent. Vitamin D and marine omega-3 fatty acids (n-3 FA) may improve insulin resistance. We sought to examine the association between baseline levels of insulin, C-peptide, HbA1c, and a novel insulin resistance score (IRS) with incident cardiometabolic diseases, and whether randomized vitamin D or n-3 FA modify these associations.MethodsVITamin D and OmegA-3 TriaL (NCT01169259) was a randomized clinical trial testing vitamin D and n-3 FA for the prevention of CVD and cancer over a median of 5.3 years. Incident cases of T2D and CVD (including cardiovascular death, myocardial infarction, stroke, and coronary revascularization) were matched 1:1 on age, sex, and fasting status to controls. Conditional logistic regressions adjusted for demographic, clinical, and adiposity-related factors were used to assess the adjusted odds ratio (aOR) per-standard deviation (SD) and 95%CI of baseline insulin, C-peptide, HbA1c, and IRS (Insulin×0.0295 + C-peptide×0.00372) with risk of T2D, CVD, and coronary heart disease (CHD).ResultsWe identified 218 T2D case-control pairs and 715 CVD case-control pairs including 423 with incident CHD. Each of the four biomarkers at baseline was separately associated with incident T2D, aOR (95%CI) per SD increment: insulin 1.46 (1.03, 2.06), C-peptide 2.04 (1.35, 3.09), IRS 1.72 (1.28, 2.31) and HbA1c 7.00 (3.76, 13.02), though only HbA1c remained statistically significant with mutual adjustments. For cardiovascular diseases, we only observed significant associations of HbA1c with CVD (1.19 [1.02, 1.39]), and IRS with CHD (1.25 [1.04, 1.50]), which persisted after mutual adjustment. Randomization to vitamin D and/or n-3 FA did not modify the association of these biomarkers with the endpoints.ConclusionsEach of insulin, C-peptide, IRS, and HbA1c were associated with incident T2D with the strongest association noted for HbA1c. While HbA1c was significantly associated with CVD risk, a novel IRS appears to be associated with CHD risk. Neither vitamin D nor n-3 FA modified the associations between these biomarkers and cardiometabolic outcomes.

Rivaroxaban as a protector of Oxidative Stress-induced Vascular Endothelial Glycocalyx Damage via The IQGAP1/PAR1-2/PI3K/Akt Pathway.

The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a FXa inhibitor, on the glycocalyx under oxidative stress condition. We examined the impact of rivaroxaban on human umbilical vein endothelial cells (HUVECs) exposed to acute and chronic H₂O₂-induced oxidative stress. Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/ phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx. We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.

Antihypertensive Medication Category Prescriptions and Blood Pressure Control in African Surinamese and Ghanaian Migrants with Hypertension in Amsterdam, The Netherlands: The HELIUS Study.

West African (WA) migrants in Europe have higher hypertension rates than the host populations. For African migrants, guidelines recommend diuretics and/or calcium channel blockers (CCB) for primary cardiovascular disease prevention, but data on antihypertensive medication (AHM) prescription patterns or related hypertension control rates are lacking. We assessed AHM prescription patterns and its relation to hypertension control among hypertensive WA migrants in the Netherlands compared to the host population. Cross-sectional data from WA or Dutch origin participants from the HELIUS study were used. Participants with treated hypertension and without diabetes, cardiovascular disease, or microalbuminuria were selected. We used logistic and linear regression analyses to assess the association between AHM categories and hypertension control rates (systolic blood pressure (BP) ≤ 140 mmHg and diastolic BP ≤ 90 mmHg) and the systolic BP levels. We compared 999 WA participants and 314 Dutch participants. Hypertension control rates were lower in the WA origin compared to Dutch origin participants (44.3% versus 58.0%, p < 0.001). For WA participants, prescription rates for any AHM category were: CCB (54.8%), diuretics (18.5%) beta-blocking agents (27.3%) and renin-angiotensin system blockers (52.6%). Prescription rates were higher for CCB and similar for diuretics compared to the Dutch participants. Neither CCB nor diuretics were associated with better control rates. Compared to Dutch participants, West African participants had similar diuretic prescriptions but significantly higher prescriptions for CCB. However, neither medications was associated with better hypertension control. Future research should explore physician and patient factors to improve hypertension control.

'A potentially ticking time bomb' - barriers for prevention, diagnosis, and treatment of cardiovascular disease in people with intellectual disabilities.

Research suggests that people with intellectual disabilities have a higher risk for cardiovascular disease than the general population. The aim of this study was to identify barriers for the prevention, diagnosis, and treatment of cardiovascular disease for people with intellectual disabilities. We conducted individual interviews with relatives and general practitioners and focus group interviews with staff working at an assisted home facility, a cardiac ward, an obesity clinic and two rehabilitation centres (n = 33) in Norway. Inductive approach and thematic analysis were used to analyse the data. We identified barriers on an individual and a structural level. The underlying reason for these barriers is that health problems, such as cardiovascular disease, are regularly overlooked as the condition of intellectual disability overshadows other possible diagnoses. This focus on intellectual disability rather than other explanations leads to shortcomings in the prevention, diagnoses, and treatment of cardiovascular disease in this group.

Effects of light compression on chronic venous disease, edema and comfort in women during pregnancy and postpartum period: a prospective randomized study.

Lower limb edema associated with venous disorders is an increasingly common problem in pregnant women. The study aimed to assess the use of compression class 1 (ccl1=18-21 mmHg) in lower limb edema and CVD prevention in pregnant and postpartum women. 51 pregnant women (second trimester) were randomly recruited into either a study group CG with compression ccl1 or a control group NCG, both with physical activity (PA) recommendation. The assessment concerned venous system condition, limb size, and compression comfort. Edema was diagnosed as ≥10% measurement increase. Venous reflux (8/22 CG, 1/16 NCG) and an onset of CVD (6/22 CG, 1/16 NCG) were diagnosed in the first measurement. After postpartum, a significant reduction of the great saphenous vein (GSV) diameter in the proximal part of the left lower limb in CG (P=0.014) and expansion of the small saphenous vein (SSV) in the proximal part of the left lower limb in NCG (P=0.028) were observed. An analysis of the limb sizes in the second measurement revealed a significant increase of all circumferences and volumes in the NCG, and of lower leg volumes in the CG. Edema was diagnosed in five women in the NCG in the second measurement. Consequently, compression was recommended for the new group (NCG+C), and a significant edema reduction (P=0.026) occurred in the third measurement. Compression ccl1 reduces the risk of edema, venous insufficiency, and improves women's quality of life during pregnancy and postpartum.

Qihuang Zhuyu Formula Modulates Mitochondrial Function to Inhibit Platelet Activation via Endocannabinoid Signaling Mediated by the SIRT1/PPARα Pathway

Ethnopharmacological relevanceDeveloping effective drugs is urgent for preventing platelet activation and atherosclerotic disease. Qihuang Zhuyu Formula (QHZYF) is a curative medical plants formula in clinic while its molecular mechanism remains to be further elucidated. Aim of the studyTo investigate how QHZYF, via the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor alpha (PPARα) pathway, mediates the endocannabinoid system, regulates mitochondrial function, and inhibits platelet activation, thereby offering novel strategies for the prevention and treatment of cardiovascular diseases. MethodsThe chemical constituents of QHZYF were characterized by ultra-performance liquid chromatography tandem with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). For the in vivo experiments, an atherosclerosis rat model was developed. Platelet activation and endocannabinoid levels were assessed by ELISA, while the expression of PPARα was evaluated by immunofluorescence. Additionally, the expression of endocannabinoid-degrading enzymes was analyzed by Western blotting. In the in vitro studies, the protein-protein interaction between SIRT1 and PPARα was initially investigated using co-immunoprecipitation (Co-IP). Thereafter, platelets were co-cultured with human umbilical vein endothelial cells (HUVECs) stimulated by oxidized low-density lipoprotein (ox-LDL). The mitochondrial function of platelets was examined by flow cytometry. Platelet activation and endocannabinoid levels were quantified using ELISA, and the expression of PPARα and endocannabinoid-degrading enzymes was determined by Western blotting. Subsequently, QHZYF was incorporated into the aforementioned system, and the entire experimental protocol was replicated to explore how QHZYF influences platelet activation through the SIRT1/PPARα pathway-mediated endocannabinoid system. ResultsIn the in vivo experiments, it was observed that QHZYF significantly augmented the levels of SIRT1 and PPARα, concurrently with a decrease in the expression of endocannabinoid-degrading enzymes. This was paralleled by a rise in endogenous cannabinoid levels and a reduction in platelet activation, a process that was found to be regulated by SIRT1. The co-immunoprecipitation (Co-IP) analysis substantiated the cooperative interaction between SIRT1 and PPARα, underscoring their role in mediating the endocannabinoid system, regulating mitochondrial function, and consequently influencing platelet activation. In the in vitro studies, a co-culture system involving platelets and HUVECs stimulated with ox-LDL was employed. It was noted that the SIRT1/PPARα pathway mediates the endocannabinoid system in regulating mitochondrial function, which in turn affects platelet activation. The incorporation of QHZYF-containing serum into this system produced outcomes consistent with those observed in the in vivo experiments. These findings suggest that QHZYF operates by modulating the endocannabinoid system via the SIRT1/PPARα pathway, thereby controlling mitochondrial function and inhibiting platelet activation. ConclusionSIRT1 may mediate endogenous cannabinoid signaling through its interaction with PPARα, regulating mitochondrial function and subsequently influencing platelet activation. QHZYF effectively modulates the endocannabinoid system via the SIRT1/PPARα pathway, thereby inhibiting platelet activation.

Assessment of Lifetime Risk for Cardiovascular Disease: Time to Move Forward.

Over the past decades, there has been a notable increase in the risk of Cardiovascular Disease (CVD), even among younger individuals. Policymakers and the health community have revised CVD prevention programs to include younger people in order to take these new circumstances into account. A variety of CVD risk assessment tools have been developed in the past years with the aim of identifying potential CVD candidates at the population level; however, they can hardly discriminate against younger individuals at high risk of CVD.Therefore, in addition to the traditional 10-year CVD risk assessment, lifetime CVD risk assessment has recently been recommended by the American Heart Association/American College of Cardiology and the European Society of Cardiology prevention guidelines, particularly for young individuals. Methodologically, the benefits of these lifetime prediction models are the incorporation of left truncation observed in survival curves and the risk of competing events which are not considered equivalent in the common survival analysis. Thus, lifetime risk data are easily understandable and can be utilized as a risk communication tool for Public Health surveillance. However, given the peculiarities behind these estimates, structural harmonization should be conducted in order to create a sex-, race-specific tool that is sensitive to accurately identifying individuals who are at high risk of CVD. In this review manuscript, we present the most commonly used lifetime CVD risk tools, elucidate several methodological and critical points, their limitations, and the rationale behind their integration into everyday clinical practice.

Mediterranean Diet Pattern: Potential Impact on the Different Altered Pathways Related to Cardiovascular Risk in Advanced Chronic Kidney Disease

Background: Cardiovascular disease (CVD) remains the most common cause of mortality in chronic kidney disease (CKD) patients. Several studies suggest that the Mediterranean diet reduces the risk of CVD due to its influence on endothelial function, inflammation, lipid profile, and blood pressure. Integrating metabolomic and proteomic analyses of CKD could provide insights into the pathways involved in uremia-induced CVD and those pathways modifiable by the Mediterranean diet. Methods: We performed metabolomic and proteomic analyses on serum samples from 19 patients with advanced CKD (aCKD) and 27 healthy volunteers. The metabolites were quantified using four different approaches, based on their properties. Proteomic analysis was performed after depletion of seven abundant serum proteins (Albumin, IgG, antitrypsin, IgA, transferrin, haptoglobin, and fibrinogen). Integrative analysis was performed using MetaboAnalyst 4.0 and STRING 11.0 software to identify the dysregulated pathways and biomarkers. Results: A total of 135 metabolites and 75 proteins were differentially expressed in aCKD patients, compared to the controls. Pathway enrichment analysis showed significant alterations in the innate immune system pathways, including complement, coagulation, and neutrophil degranulation, along with disrupted linoleic acid and cholesterol metabolism. Additionally, certain key metabolites and proteins were altered in aCKD patients, such as glutathione peroxidase 3, carnitine, homocitrulline, 3-methylhistidine, and several amino acids and derivatives. Conclusions: Our findings reveal significant dysregulation of the serum metabolome and proteome in aCKD, particularly in those pathways associated with endothelial dysfunction and CVD. These results suggest that CVD prevention in CKD may benefit from a multifaceted approach, including dietary interventions such as the Mediterranean diet.

Sodium-glucose cotransporter 2 inhibitors in cardiocerebrovascular disease

Cardiovascular disease is a leading cause of global mortality, necessitating effective strategies for prevention and treatment. The cardiovascular disease continuum concept highlights the progression from risk factors such as hypertension and diabetes mellitus to advanced stages, including heart failure (HF) and death. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed to manage diabetes, have emerged as effective therapies across all stages of the cardiovascular disease continuum. Numerous cardiovascular outcome trials demonstrate that SGLT2 inhibitors significantly reduce major adverse cardiovascular events and hospitalizations for HF in patients with and without established atherosclerotic cardiovascular disease. Notably, SGLT2 inhibitors have shown remarkable benefits in reducing HF risk, even in patients without diabetes, including those with HF and preserved ejection fraction. Furthermore, recent studies in post–myocardial infarction patients suggest potential benefits in reducing hospitalizations for HF. Despite their widespread use, the precise mechanisms by which SGLT2 inhibitors confer cardiovascular protection remain unclear, suggesting the need for further investigation. In conclusion, SGLT2 inhibitors have revolutionized cardiovascular disease management, offering significant therapeutic potential across a broad spectrum of patients, and are expected to play an increasingly prominent role in both the prevention and treatment of cardiovascular disease.

Preventing ischemic heart disease in women: a systematic review of global directives and policies

Cardiovascular disease is the leading cause of mortality in women worldwide. Yet cardiovascular disease in women remains underdiagnosed and undertreated, especially among vulnerable populations such as older women, low-income populations, and ethnic minorities. Resultantly, reduction in cardiovascular mortality among women has stagnated. To examine, consolidate current research findings and policies to identify gaps in women’s heart health practice, this review screened 21476 records and synthesized results from 124 English language publications worldwide. Using a life course approach, we assessed the connection between clinical recommendations and policy, and documented global recommendations and policies addressing prevention of cardiovascular disease in women. Key recommendations include fostering environments that encourage sustainable health behaviors for young women, advocating for national surveillance systems and guidelines for monitoring and increasing the understanding of cardiovascular health in high-risk pregnancy/postpartum groups, developing community prevention programs for midlife/menopause, and implementing direct population health management initiatives for elderly women, with an emphasis on higher risk groups. Inequalities still exist among women with varying socioeconomic status and race between countries, and even within countries.

Adding traditional and emerging biomarkers for risk assessment in secondary prevention: A prospective cohort study of 20,656 patients with cardiovascular disease.

This study aims to explore whether conventional and emerging biomarkers could improve risk discrimination and calibration in secondary prevention of recurrent atherosclerotic cardiovascular disease (ASCVD), based on a model using predictors from SMART2. In a cohort of 20,658 UK Biobank participants with medical history of ASCVD, we analysed any improvement in C indices and net reclassification index (NRI) for future ASCVD events, following addition of LP-a, ApoB, cystatin C, HbA1c, GGT, AST, ALT, and ALP, to a model with predictors used in SMART2 for the outcome of recurrent major cardiovascular event. We also examined any improvement in C indices and NRIs replacing creatinine based estimated glomerular filtration rate (eGFR) with cystatin C based estimates. Calibration plots between different models were also compared. Compared with the baseline model (C index=0.663), modest increment in C indices were observed when adding HbA1c (ΔC=0.0064, p<0.001), cystatin C (ΔC=0.0037, p<0.001), GGT (ΔC=0.0023, p<0.001), AST (ΔC= 0.0007, p<0.005) or ALP (ΔC=0.0010, p<0.001) or replacing eGFRCr with eGFRCysC (ΔC=0.0036, p<0.001) or eGFRCr-CysC (ΔC=0.00336, p<0.001). Similarly, the strongest improvements in NRI were observed with the addition of HbA1c (NRI=0.014), or cystatin C (NRI= 0.006) or replacing eGFRCr with eGFRCr-CysC (NRI=0.001) or eGFRCysC (NRI=0.002). There was no evidence that adding biomarkers modify calibration. Adding several biomarkers, most notably cystatin C and HbA1c, but not LP-a, in a model using SMART2 predictors modestly improved discrimination.