Risk Of Major Cardiovascular Events Research Articles

Incidence, Risk Factors, and Consequences of Acute Kidney Injury in Patients Undergoing Esophageal Cancer Surgery: A Historical Cohort

Background: Limited data exist on postoperative acute kidney injury (AKI) in patients who have undergone esophageal cancer surgery. The purpose of this study was to evaluate the incidence, risk factors, and consequences of postoperative acute kidney after esophagectomy. Methods: This was a retrospective cohort study. The study was conducted in a tertiary specialized cancer center in Italy. All patients undergoing elective esophageal cancer surgery between 2016 and 2021 were included in the study. AKI was defined according to Kidney Disease Improving Global Outcomes criteria (both serum creatinine and urine output), within 48 h after surgery. Preoperative and intraoperative data were registered. We also collected data concerning progression of AKI, need for renal replacement therapy, mortality, and medical (pulmonary, cardiovascular, septic) and surgical complications within 30 days from surgery, as well as length of hospital stay. Results: Incidence of postoperative AKI was 32%. The independent risk factors were body mass index and the use of an invasive surgical approach. Persistent AKI accounted for 15% of the cases and it was associated with increased risk of major cardiovascular events (odds ratio 4.14, 95% CI 1.05–15.8, p-value 0.036), pulmonary complications (OR 3.67, 95% CI 1.04–14.9, p-value 0.050), and increased length of hospital stay (AME 7.2, 0.5–13.9, p-value 0.035). Conclusions: Postoperative AKI is common after esophageal cancer surgery. BMI and a totally invasive surgical approach are independent risk factors. Persistent AKI lasting more than 48 h increased the risk for any cardiovascular or pulmonary complications, with prolonged length of hospital stay.

Salt Intake in Adults with Diabetes and Hypertension: The Longitudinal Study of Adult Health-Brasil Study.

Background and Objective: Hypertension and type-2 diabetes are strong risk factors for cardiovascular diseases, and their management requires lifestyle changes, including a shift in dietary habits. The consumption of salt has increased in the last decades in some countries, but its association with type-2 diabetes remains unknown. Thus, we aimed to estimate the amount of salt intake among adults with and without diabetes and to assess whether concomitant hypertension and diabetes are associated with higher salt intake. Methods: Data from 11,982 adults 35-74 years of age enrolled in the baseline of the Longitudinal Study of Adult Health-Brasil study (2008-2010) were studied. A clinical and anthropometric evaluation was performed, and their daily salt intake was estimated by the overnight 12-hr urine sodium excretion. Results: Salt intake (gram per day) was higher in participants with diabetes as compared with those without diabetes, regardless of sex (men: 14.2 ± 6.4 vs. 12.4 ± 5.6, P < 0.05; women: 10.5 ± 4.8 vs. 9.1 ± 4.1, P < 0.05). However, salt intake is high in participants with fasting glucose ≥126 mg/dL or HbA1c ≥6.5%, but not in participants with blood glucose 2 hr after the glucose tolerance test ≥200 mg/dL. When hypertension and diabetes coexisted, salt consumption was higher than among people without these conditions. The prevalence of hypertension increased with increasing salt intake in women with diabetes, but not in men with this condition. Conclusions: Our findings highlight the high consumption of salt in individuals with diabetes and/or hypertension, and the need for effective strategies to reduce salt consumption in these groups of increased risk for major cardiovascular events, especially in women.

Large-scale plasma proteomics in the UK Biobank modestly improves prediction of major cardiovascular events in a population without previous cardiovascular disease.

Improved identification of individuals at high risk of developing cardiovascular disease would enable targeted interventions and potentially lead to reductions in mortality and morbidity. Our aim was to determine whether use of large-scale proteomics improves prediction of cardiovascular events beyond traditional risk factors (TRFs). Using proximity extension assays, 2919 plasma proteins were measured in 38 380 participants of the UK Biobank. Both data- and literature-based feature selection and trained models using extreme gradient boosting machine learning were used to predict risk of major cardiovascular events (MACE: fatal and non-fatal myocardial infarction, stroke and coronary artery revascularisation) during a 10-year follow-up. Area under the curve (AUC) and net reclassification index (NRI) were used to evaluate the additive value of selected protein panels to MACE prediction by Systematic COronary Risk Evaluation 2 (SCORE2) or the 10 TRFs used in SCORE2. SCORE2 and SCORE2 refitted to UK Biobank data predicted MACE with AUCs of 0.740 and 0.749, respectively. data-driven selection identified 114 proteins of greatest relevance for prediction. Prediction of MACE was not improved by using these proteins alone (AUC of 0.758) but was significantly improved by combining these proteins with SCORE2 or the 10 TRFs (AUC=0.771, p<001, NRI=0.140, and AUC=0.767, p=0.03, NRI 0.053, respectively). Literature-based protein selection (113 proteins from five previous studies) also improved risk prediction beyond TRFs while a random selection of 114 proteins did not. Large-scale plasma proteomics with data-driven and literature-based protein selection modestly improves prediction of future MACE beyond TRFs.

De Novo Metabolic Syndrome 1 Year after Liver Transplantation and Its Association with Mid- and Long-Term Morbidity and Mortality in Liver Recipients.

Background: Metabolic syndrome (MS) constitutes an important source of cardiovascular- and cancer-related morbidity and mortality in the general population. Limited information is available on whether these findings can be directly extrapolated to liver recipients. This study aimed to investigate the impact of post-transplant MS present 1 year after liver transplantation on survival rates, risk of major cardiovascular events (CVEs), and de novo malignancies. Methods: Adult deceased-liver-donor recipients who underwent transplantation in our centre between 2010 and 2019 and reached at least 1 year of post-transplantation follow-up were eligible. Results: Of 259 enrolled patients, 20% developed post-transplant MS 1 year after the procedure. The presence of post-transplant MS at 1 year did not affect all-cause mortality (p = 0.144) and risk of de novo malignancies (p = 0.198) in liver recipients. However, it was associated with an overall and time-dependent increase in the risk of major CVEs (p < 0.001). MASH aetiology of liver disease, pre-existing major CVEs, and development of de novo malignancy were independent predictors of all-cause mortality in liver recipients. Conclusions: New onset MS exerts a wide-ranging effect on the post-transplant prognosis of liver recipients. Obtaining optimal control over all modifiable metabolic risk factors is central to improving long-term outcomes in this population.

Predischarge oxygen uptake efficiency slope has short and long-term value in the prognosis of patients after acute myocardial infarction.

Patients who survive an acute myocardial infarction (AMI) have a higher risk of having a major cardiovascular event (MACE). Cardiopulmonary exercise testing (CPET) could develop prognostic stratification and prescribing exercise prescription. Patients after AMI frequently terminate CPET early with submaximal testing results. We aimed to look at the characteristics of patients' predischarge CPET variables after AMI intervention and find potential CPET variables with prognostic value. Between July 2012 and August 2017, we recruited patients who survived first AMI after primary percutaneous coronary intervention and received predischarge CPET retrospectively in a tertiary medical center of Taiwan. Patients were followed-up on a MACE or administrative censoring occurred (up to 5 years). To identify significant predictors of a MACE, a Cox regression model was used. One hundred thirteen patients (103 men and 10 women) were studied, with an average age of 58.32 ± 12.49. MACE over 3 months, 2-years, and 5-years was 17.70%, 53.10%, and 62.83%, respectively. The oxygen uptake efficiency slope during the whole during of CPET (OUES 100) divided by body surface area (OUES 100/BSA) was found to be a significant event predictor for MACE at 3-month, 2- and 5-years. Cox regression analysis revealed that those with OUES 100/BSA <0.722 ( p = 0.004), OUES 100/BSA <0.859 ( p = 0.002), and OUES 100/BSA <0.829 ( p = 0.002) had a 7.14-fold, 3.47-fold, and 2.72-fold increased risk of 3-month, 2-year, and 5-year MACE, respectively. It is critical to identify a submaximal predictor during CPET for patients who survive AMI. Our findings suggested that OUES could be a significant prognostic indicator in patients after first AMI in both the short and long term.

Remission of Obesity-Related Sleep Apnea and Its Effect on Mortality and Cardiovascular Events After Metabolic and Bariatric Surgery: A Propensity Matched Cohort Study.

While obstructive sleep apnea (OSA) is common among patients with obesity and linked to cardiovascular disease, there is a lack of studies evaluating the effects of reaching remission from OSA after metabolic and bariatric surgery (MBS). A registry-based nationwide study including patients operated with sleeve gastrectomy or Roux-en-Y gastric bypass from 2007 until 2019 in Sweden. Patients who reached remission of OSA were compared to those who did not reach remission, and a propensity score matched control group of patients without OSA at the time of operation. Main outcome was overall mortality, secondary outcome was major cardiovascular events (MACE). In total, 5892 patients with OSA and 11,552 matched patients without OSA completed a 1-year follow-up and were followed for a median of 6.8 years. Remission of OSA was seen for 4334 patients (74%). Patients in remission had a lower risk for overall mortality (cumulative incidence 6.0% v. 9.1%;p<0.001) and MACE (cumulative incidence 3.4% vs 5.8%;p<0.001) at 10-years after operation compared to those who did not reach remission. The risk was similar to that of the control group without OSA at baseline (cumulative incidence for mortality 6.0%, p=0.493, for MACE 3.7%, p=0.251). The remission rate of OSA was high after MBS. This was in turn associated with reduced risk for death and MACE compared to patients who did not achieve remission reaching a similar risk seen among patients without OSA at baseline. A diligent follow-up of patients who do not reach remission remains important.

Glucagon-like Peptide 1 Receptor Agonists and Cardiovascular Outcomes in Solid Organ Transplant Recipients With Diabetes Mellitus.

Glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce cardiovascular events and mortality in type 2 diabetes. Limited data are available on diabetes treatment after solid organ transplantation. We aimed to explore the effect of GLP1-RAs on cardiovascular outcomes in transplanted recipients with diabetes. We extracted data on adult transplant recipients (kidney, lungs, liver, heart) insured in a large health maintenance organization. Death-censored patients with diabetes treated with GLP1-RAs were matched with nonusers. The primary outcome was a composite of major cardiovascular events (MACEs): a nonfatal cardiac event (myocardial infarction, stable/unstable angina, coronary bypass, and coronary angiography), ischemic stroke and all-cause mortality. Secondary outcomes were MACE or peripheral vascular disease (MACE-PVD), and all-cause mortality. Safety outcomes included biliopancreatic adverse events. We included 318 patients (69% males, average age 58.3 ± 11.0 y) with a 3.1-y median follow-up. The incidence of MACE was 101 of 1000 patient-years in GLP1-RAs users compared with 134 of 1000 in controls (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.27-0.78). GLP1-RAs similarly reduced the risk of MACE-PVD (HR 0.53; 95% CI, 0.33-0.88) and the risk of all-cause mortality (HR 0.39; 95% CI, 0.18-0.84). Biliopancreatic adverse events occurred less in GLP1-RA users. Transplant recipients with diabetes who used GLP1-RAs had lower risks for MACE and all-cause mortality. These results may profoundly implicate the daily management of posttransplant recipients with diabetes, a population with a high prevalence of cardiometabolic risk factors and cardiovascular death. Transplant patients are usually excluded from randomized controlled trials and, hence might be undertreated with disease-modifying drugs. Larger prospective studies are needed in this unique population.

Association of plasma angiogenin with risk of major cardiovascular events in type 2 diabetes

BackgroundAngiogenin, an enzyme belonging to the ribonucleases A superfamily, plays an important role in vascular biology. Here, we sought to study the association of plasma angiogenin and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes (T2D).MethodsThis prospective study included 1083 T2D individuals recruited from a secondary hospital and a primary care facility. The primary outcome was a composite of four-point MACE (nonfatal myocardial infarction, stroke, unstable angina pectoris leading to hospitalization and cardiovascular death). Circulating angiogenin was measured by a proximity extension assay. Cox regression models were used to evaluate the association of baseline plasma angiogenin with the risk of MACE.ResultsDuring a median follow-up of 9.3 years, 109 (10%) MACE were identified. Plasma angiogenin was significantly higher in participants with MACE than in those without MACE (P < 0.001). Doubling of plasma angiogenin concentration was associated with a 3.10-fold (95% CI 1.84–5.22) increased risk for MACE. The association was only moderately attenuated after adjustment for demographic and cardiometabolic risk factors (adjusted HR 2.38, 95% CI 1.34–4.23) and remained statistically significant after additional adjustment for estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (uACR) (adjusted HR 1.90, 95% CI 1.02–3.53). A consistent outcome was obtained when plasma angiogenin was analysed as a categorical variable in tertiles.ConclusionsPlasma angiogenin was associated with the risk of future cardiovascular events in patients with T2D and may be a promising novel biomarker for identifying high-risk T2D patients for early management.

Major cardiovascular events under biologic psoriasis therapies: a 19-year real-world analysis of FAERS data.

Over the years when biologic psoriasis therapies (TNF inhibitors, IL-12/23 inhibitors, IL-23 inhibitors, and IL-17 inhibitors) have been used in psoriasis patients, reports of major cardiovascular events (MACEs) have emerged. This study aims to investigate the association between MACEs and biologic psoriasis therapies by using information reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS). FAERS data (January 2004 to December 2022) were reviewed. For each drug-event pair, the proportional reporting ratio (PRR) and the multi-item gamma Poisson shrinker (MGPS) algorithms were used to identify drug-adverse event associations. We filtered the query for indication and identified 173,330 reports with psoriasis indication in FAERS throughout the analyzed time frame. MACEs occurred in 4,206 patients treated with biologics. All the four biological classes had an elevated and similar reporting rates for MACEs relative to other alternative psoriasis treatments (PRR from 2.10 to 4.26; EB05 from 1.15 to 2.45). The descending order of association was IL-12/23 inhibitors>IL-17 inhibitors>IL-23 inhibitors>TNF inhibitors. The signal strength for myocardial infarction (PRR, 2.86; χ2, 296.27; EBGM 05, 1.13) was stronger than that for stroke, cardiac fatality, and death. All the biological classes demonstrated a little higher EBGM 05 score≥1 for the MACEs in patients aged 45-64 years. The time-to-onset of MACEs was calculated with a median of 228 days. Analysis of adverse event reports in the FAERS reflects the potential risk of MACEs associated with the real-world use of biological therapies in comparison to other alternative psoriasis treatments. Future long-term and well-designed studies are needed to further our knowledge regarding the cardiovascular safety profile of these agents.

Update on sex specific risk factors in cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide and accounts for roughly 1 in 5 deaths in the United States. Women in particular face significant disparities in their cardiovascular care when compared to men, both in the diagnosis and treatment of CVD. Sex differences exist in the prevalence and effect of cardiovascular risk factors. For example, women with history of traditional cardiovascular risk factors including hypertension, tobacco use, and diabetes carry a higher risk of major cardiovascular events and mortality when compared to men. These discrepancies in terms of the relative risk of CVD when traditional risk factors are present appear to explain some, but not all, of the observed differences among men and women. Sex-specific cardiovascular disease research-from identification, risk stratification, and treatment-has received increasing recognition in recent years, highlighting the current underestimated association between CVD and a woman's obstetric and reproductive history. In this comprehensive review, sex-specific risk factors unique to women including adverse pregnancy outcomes (APO), such as hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus, preterm delivery, and newborn size for gestational age, as well as premature menarche, menopause and vasomotor symptoms, polycystic ovarian syndrome (PCOS), and infertility will be discussed in full detail and their association with CVD risk. Additional entities including spontaneous coronary artery dissection (SCAD), coronary microvascular disease (CMD), systemic autoimmune disorders, and mental and behavioral health will also be discussed in terms of their prevalence among women and their association with CVD. In this comprehensive review, we will also provide clinicians with a guide to address current knowledge gaps including implementation of a sex-specific patient questionnaire to allow for appropriate risk assessment, stratification, and prevention of CVD in women.

Abstract 135: Efficacy and Safety of PCSK9 Inhibitors for Stroke Prevention: Systematic Review and Meta-Analysis

Objective: Investigate the efficacy and safety of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on stroke prevention. Background: PCSK9i reduce low-density lipoprotein cholesterol (LDL-Chol) and lipoprotein a (LpA) levels. Their efficacy in reducing the risk of major cardiovascular events has been shown in multiple randomized clinical trials (RCT). However, clinical equipoise remains on the magnitude and mechanisms by which PCSK9i decrease the risk of stroke. Methods: We performed a systematic search of biomedical databases from inception to July 15, 2023, to identify RCTs that investigated the efficacy of PCSK9i versus placebo for major cardiovascular event prevention. The primary outcome was total stroke. The safety outcome was the risk of adverse neurological events, as defined by each trial. Effect size was represented by risk ratio (RR), and analysis was done using random-effects meta-analysis. Heterogeneity was assessed by I 2 and Cochrane Q statistics. Meta-regression analyses were performed to assess the association between LDL-Chol and LpA reduction and stroke risk. Results: Overall, 19 studies with 92,786 patients were included. The quality of the evidence was moderate and heterogeneity for all comparisons was low ( I 2 &lt;25%). The mean age was 60.1 years for the PCSK9i group and 59.6 years for the placebo group, with a mean follow-up time of 60.1 weeks. PCSK9i reduced the LDL-Chol levels by 11% and LpA levels by 8%. PCSK9i were associated with a significant reduction in stroke risk (RR 0.71, 95% CI 0.62-0.81, I 2 =0%), without an increase in mortality (RR 0.94, 95% CI 0.85-1.05, I 2 =0%). The risk of adverse neurological events was similar between groups (RR 1.02, 95% CI 0.88-1.18, I 2 =0%). In meta-regression analyses, the stroke risk was not associated with the magnitude of the effect of PCSK9i on LDL-Chol (LDL Chol β=-0.01, 95% CI=-0.03-0.01) and LpA (β=-0.01, 95% CI=-0.06-0.03) levels. Conclusions: PCSK9i significantly reduced the stroke risk, without increasing mortality or the risk of adverse neurological events. Our findings also suggest that the beneficial effect of PCSK9i on stroke risk is mediated by LDL-Chol- and LpA-independent mechanisms.

Knowledge, Attitudes and Practices Survey of Recombinant Zoster Vaccine among Cardiologists and Cardiac Nurses in Italy.

Background and Objectives: Cardiac patients are particularly at risk of herpes zoster (HZ), which is associated with a higher risk of major cardiovascular events. This research aimed to analyze the knowledge, attitudes and practices towards recombinant zoster vaccine (RZV) among cardiac healthcare professionals (HPs). Materials and Methods: A cross-sectional survey was conducted in a cardiological hospital in Italy. Multivariate regression models were built to identify factors associated with the outcomes of interest. Results: The response rate was 78.2% (154/197). Overall, age > 50 years and immunosuppression were recognized as risk factors for HZ by 38.3% and 75.3% of respondents, respectively. Regarding RZV, 29.1% of the HPs correctly responded about its schedule and 57.6% about the possibility of administration in immunocompromised individuals. This knowledge was significantly higher in HPs with a higher educational level (odds ratio (OR) = 4.42; 95%CI 1.70-11.47), in those who knew that HZ could cause postherpetic neuralgia (OR = 2.56; 95%CI 1.05-6.25) or major cardiovascular events (OR = 4.23; 95%CI 1.50-11.91), in those who had participated in professional updates on vaccinations (OR = 3.86; 95%CI 1.51-9.87) and in those who stated the need for further information about the RZV (OR = 6.43; 95%CI 1.42-29.98). Younger HPs (coefficient (β) = -0.02; 95%CI -0.04--0.01), those with a positive attitude toward RZV safety (β = 2.92; 95%CI 2.49-3.36) and those who had previously cared for patients with HZ (β = 0.45; 95%CI 0.03-0.88) reported a more positive attitude toward RZV effectiveness. The practice of recommending vaccination was more prevalent in younger HPs (OR = 0.94; 95%CI 0.89-0.99), in those who had a master's degree or higher education (OR = 7.21; 95%CI 1.44-36.08), in those with more positive attitudes toward RZV effectiveness (OR = 7.17; 95%CI 1.71-30.03) and in HPs who had already recommended the vaccine to patients in the past (OR = 4.03; 95%CI 1.08-14.96). Conclusions: Despite being a single-center study, our research brings attention to factors that currently impact cardiac HPs' approaches to RZV. The findings indicate potential measures to enhance HPs' awareness and practices, ultimately aiming to improve vaccination adherence and reduce the burden associated with HZ.

Effect of Intensive Blood Pressure Control on Cardiovascular Outcomes in Cancer Survivors.

To evaluate whether cancer modifies the effect of intensive blood pressure control on major cardiovascular outcomes. Using data of the SPRINT (Systolic Blood Pressure Intervention Trial), we compared the risk of the composite outcomes of myocardial infarction, other acute coronary syndromes, stroke, heart failure, and cardiovascular death in patients with and without a history of cancer. Using Cox proportional hazards regression, we tested interactions between history of cancer and intensive blood pressure control on major cardiovascular outcomes. The study included a total of 9336 patients, with a mean age of 67.9±9.4 years, among whom 2066 (22.2%) were cancer survivors. Over a median follow-up of 3.2 years, 561 primary cardiovascular outcomes were observed. Cancer survivors had a similar risk of experiencing the primary outcome compared with patients without cancer after multivariable adjustment (adjusted hazard ratio, 0.94 [95% CI, 0.77-1.15]). Intensive blood pressure control reduced risk of the primary cardiovascular outcome similarly for cancer survivors (hazard ratio, 0.70 [95% CI, 0.51-0.97]) and patients without cancer (HR, 0.76 [95% CI, 0.63-0.93]; P for interaction 0.74). In SPRINT study, intensive blood pressure treatment reduced the risk of major cardiovascular events in cancer survivors to a similar extent to that of patients without cancer. Cancer history not requiring active treatment in last 2 years should not be an obstacle to intensive treatment of hypertension. This post hoc analysis should be considered as hypothesis-generating and merit further clinical trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Comparative analysis of hemodialysis and peritoneal dialysis on the risk of new onset diabetes mellitus

BackgroundDiabetes mellitus is a significant risk factor for cardiovascular events and mortality in dialysis patients. The impact of different dialysis modalities on the risk of new onset diabetes mellitus (NODM) remains a subject of debate. Previous studies did not adequately account for critical confounding factors such as pre-dialysis glycemic status, medication use, and nutritional status, which may influence the association between dialysis modality and NODM risk. MethodsWe conducted a retrospective cohort study of 1426 non-diabetic end-stage renal disease (ESRD) patients who underwent either hemodialysis (HD) or peritoneal dialysis (PD) at a single medical center. We used different statistical methods, adjusting for potential confounding factors, and accounted for competing risk of death. ResultsOver 12 years, 331 patients (23 %) developed NODM. After adjusting for potential confounding factors and mortality, PD patients had a significantly higher risk of NODM compared to HD patients (adjusted HR 1.52, p = 0.001). A propensity-matched cohort sensitivity analysis yielded similar results. Among patients with prediabetes, those receiving PD had a 2.93 times higher risk of developing NODM than those receiving HD (p for interaction <0.001), whereas no significant difference was observed among euglycemic patients. NODM was also associated with a 1.78 times increased risk of major cardiovascular events. ConclusionOur study provides evidence that PD treatment may increase the risk of NODM in ESRD patients, particularly among those with preexisting prediabetes. These findings highlight the importance of personalized treatment approaches, and nephrologists should consider prediabetes when choosing the dialysis modality for their patients.

Rationale and design of the effect of evolocumab in patients at high cardiovascular risk without prior myocardial infarction or stroke (VESALIUS-CV) trial

The reduction of low-density lipoprotein cholesterol (LDL-C) with evolocumab, a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9i), reduces the risk of major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD) with a prior MI, prior stroke, or symptomatic peripheral artery disease, with no offsetting safety concerns. The effect of evolocumab on CV outcomes in lower risk patients without a history of MI or stroke has not been explored. VESALIUS-CV is a randomized, double-blind, placebo-controlled, global clinical trial designed to evaluate the effect of evolocumab on the risk of major cardiovascular events in patients at high cardiovascular risk but without a prior ischemic event. The study population consists of 12,301 patients with atherosclerosis or high-risk diabetes mellitus without a prior MI or stroke; an LDL-C ≥ 90 mg/dL, or non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 120 mg/dL, or apolipoprotein B ≥ 80 mg/dL; and treated with optimized lipid-lowering therapy. Patients were randomized in a 1:1 ratio to evolocumab 140 mg subcutaneously every 2 weeks or matching placebo. The primary efficacy objective is to assess whether evolocumab reduces the risk of the dual primary composite endpoints of coronary heart disease (CHD) death, myocardial infarction (MI), or ischemic stroke (triple primary endpoint) and of CHD death, MI, ischemic stroke, or ischemia-driven arterial revascularization (quadruple primary endpoint). Recruitment began in June 2019 and completed in November 2021. The trial is planned to continue until at least 751 patients experience an adjudicated triple endpoint, at least 1254 experience an adjudicated quadruple endpoint, and the median follow-up is ≥4.5 years. VESALIUS-CV will determine whether the addition of evolocumab to optimized lipid-lowering therapy reduces cardiovascular events in patients at high cardiovascular risk without a prior MI or stroke. NCT03872401.

Adherence to an integrated care pathway for stroke is associated with lower risk of major cardiovascular events: A report from the Athens Stroke Registry

BackgroundA recent European Society of Cardiology (ESC) Council on Stroke position paper proposed a holistic integrated care management approach for stroke patients, to improve cardiovascular outcomes. The impact of implementing the ABCstroke pathway ‘concept’ on clinical outcomes has never been estimated before. In order to investigate the potential effect of ABCstroke pathway adherence to cardiovascular outcomes post stroke, we performed a post-hoc analysis from the Athens Stroke Registry. Methods and resultsThis analysis was performed in the Athens Stroke Registry, which includes all consecutive patients with acute first-ever ischemic stroke. The Kaplan–Meier product limit was used to estimate the cumulative hazard of each outcome according to adherence with the ABCstroke pathway.We studied 2513 patients [median (IQR) age 71 (62–78) years; 37.7 % female] with ischemic stroke with median follow-up period of 30 (6–75) months. Full adherence to the ABC pathway was identified in 156 (6.2 %) of the patients, while 192 (7.6 %) did not adhere to any of the therapeutic pillars of ABCstroke. Full adherence to ABC treatment pathway was associated with significant reduction of stroke recurrence, compared to patients with no or partial adherence (aHR: 0.61; 95 %CI: 0.37–0.99), as well as a lower risk of MACE (HR: 0.59; 0.39–0.88) and death (aHR: 0.22; 95 %CI: 0.12–0.41). ConclusionFull adherence to the ABCstroke pathway based on the current guidelines was evident in only 6.2 % of our ischaemic stroke cohort but was independently associated with lower risks of stroke recurrence, major cardiovascular events and mortality. This highlights a potential opportunity to improve clinical outcomes post-stroke with a holistic or integrated care management approach.

Hospital and long-term periods of myocardial infarction in comorbid men and women under 60 years

Aim of the study was to assess the impact of comorbidity on the hospital and 2-year stage of treatment for myocardial infarction (MI) in men and women under 60 years of age.Material and methods. The analysis included 350 patients with MI younger than 60 years of age. The majority of patients (87.4 %) were men. For all patients, the risk was calculated according to the GRACE ASC Risk Model scale and an analysis was made of the severity of comorbidity according to the own model “K9” (patent RU2734993C1 from October 27, 2020), based on the summation of 9 diseases: diabetes mellitus, atrial fibrillation, stroke, arterial hypertension, obesity, peripheral atherosclerosis, thrombocytopenia, anemia, chronic kidney disease.Results. Comorbidity (the presence of 2 or more diseases) was recorded insignificantly more often in men (65.9 % versus 53.6 %, p = 0.12). In men, but not in women, comorbidity was associated with a 23.5 % reduction in percutaneous coronary intervention (p = 0.006). Both in-hospital mortality and the risk of major cardiovascular events (death/MI/stroke) 2 years after discharge were minimal (up to 0.7 % and up to 8.1 %, respectively) in the absence of comorbidity in both men and women, higher in comorbid women (3.4 and 12.5 %, respectively) and maximum in comorbid men (6.1 and 18.4 %, respectively). Comorbidity more significantly aggravated the 2-year prognosis in patients undergoing percutaneous coronary intervention than in receiving primary conservative treatment, increasing the risk of developing the death/MI/stroke end point by 3 times (16.7 and 5.8 %, respectively, p = 0.013). The addition of comorbidity data to the GRACE scale in the Cox regression analysis can significantly improve the prognosis of the onset of the 2-year endpoint, increasing the χ2 value from 64.08 to 79.86, and the value of the area under the ROC-curve (AUC) to 0.79 (95 % confidence interval (95 % CI) 0.71–0.88). At the same time, ROC analysis showed that the modified GRACE scale predicts the onset of the death/ MI/stroke endpoint in men much better than in women: AUC 0.81 (95 % CI 0.72–0.90) and AUC 0.67 (95 % CI 0.51–0.83), respectively.Conclusions. Comorbidity is comparable to the GRACE scale and effectively predicts the likelihood of hospital mortality. At the same time, the GRACE scale has an unsatisfactory predictive value for the 2-year endpoint “death/MI/stroke”. Modification of the GRACE scale with data on comorbidity has important clinical implications in men, but not in women, allowing more effective stratification of the risk of adverse events in the long term after myocardial infarction.

Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance

BackgroundClopidogrel resistance profoundly increases the risk of major cardiovascular events in coronary artery disease (CAD) patients. Here, we comprehensively analyse global m6A modification alterations in clopidogrel-resistant (CR) and non-CR patients.MethodsAfter RNA isolation, the RNA transcriptome expression (lncRNA, circRNA, and mRNA) was analysed via RNA-seq, and m6A peaks were identified by MeRIP-seq. The altered m6A methylation sites on mRNAs, lncRNAs, and circRNAs were identified, and then, GO and KEGG pathway analyses were performed. Through joint analysis with RNA-seq and MeRIP-seq data, differentially expressed mRNAs harbouring differentially methylated sites were identified. The changes in m6A regulator levels and the abundance of differentially methylated sites were measured by RT-PCR. The identification of m6A-modified RNAs was verified by m6A-IP-qPCR.ResultsThe expression of 2919 hypermethylated and 2519 hypomethylated mRNAs, 192 hypermethylated and 391 hypomethylated lncRNAs, and 375 hypermethylated and 546 hypomethylated circRNAs was shown to be altered in CR patients. The m6A peaks related to CR indicated lower mark density at the CDS region. Functional enrichment analysis revealed that inflammatory pathways and insulin signalling pathways might be involved in the pathological processes underlying CR. The expression of mRNAs (ST5, KDM6B, GLB1L2, and LSM14B), lncRNAs (MSTRG.13776.1 and ENST00000627981.1), and circRNAs (hsa_circ_0070675_CBC1, hsa-circRNA13011-5_CBC1, and hsa-circRNA6406-3_CBC1) was upregulated in CR patients, while the expression of mRNAs (RPS16 and CREG1), lncRNAs (MSTRG.9215.1), and circRNAs (hsa_circ_0082972_CBC1) was downregulated in CR patients. Moreover, m6A regulators (FTO, YTHDF3, and WTAP) were also differentially expressed. An additional combined analysis of gene expression and m6A peaks revealed that the expression of mRNAs (such as ST5, LYPD2, and RPS16 mRNAs) was significantly altered in the CR patients.ConclusionThe expression of m6A regulators, the RNA transcriptome, and the m6A landscape was altered in CR patients. These findings reveal epitranscriptomic regulation in CR patients, which might be novel therapeutic targets in future.

Adherence to the EAT-Lancet reference diet is associated with a reduced risk of incident cancer and all-cause mortality in UK adults

Food systems have been identified as significant contributors to the global environmental emergency. However, there is no universally agreed-upon definition of what constitutes a planetary healthy, sustainable diet. In our study, we investigated the association between the EAT-Lancet reference diet, a diet within the planetary boundaries, and incident cancer, incident major cardiovascular events, and all-cause mortality. Higher adherence to the EAT-Lancet reference diet was associated with lower incident cancer risk (hazard ratio [HR]continuous: 0.99; 95% confidence interval [CI]: 0.98-0.99]) and lower all-cause mortality (HR continuous: 0.98; 95% CI: 0.98-0.99), while mostly null associations were detected for major cardiovascular event risk (HR continuous: 1.00; 95% CI: 0.98-1.01). Stratified analyses using potentially modifiable risk factors led to similar results. Our findings, in conjunction with the existing literature, support that adoption of the EAT-Lancet reference diet could have a benefit for the prevention of non-communicable diseases.

Influenza vaccination and major cardiovascular risk: a systematic review and meta-analysis of clinical trials studies

Cardiovascular events remain a substantial global health concern, necessitating innovative strategies for prevention. This study aims to assess the potential impact of influenza vaccination on major cardiovascular events. A search of the medical English literature was conducted using PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL up to 1 August 2023. Meta-analysis and stratified analyses were performed to investigate specific outcomes, including myocardial infarction (MI), cardiovascular death, and stroke. Pooled relative risks (RR) along with their 95% confidence intervals (CI) were calculated to evaluate the associations. A comprehensive analysis was conducted on a total of 9059 patients, with 4529 patients receiving the influenza vaccine and 4530 patients receiving a placebo. Among patients who received the influenza vaccine, a notable reduction in the occurrence of major cardiovascular events was observed, with 517 cases compared to 621 cases in the placebo group (RR 0.70; 95% CI 0.55–0.91). The stratified analysis revealed a decreased risk of MI in vaccinated patients (RR 0.74; 95% CI 0.56–0.97) and a significant reduction in cardiovascular death events (RR 0.67; 95% CI 0.45–0.98). This study provides compelling evidence that influenza vaccination is associated with a decreased risk of major cardiovascular events, particularly myocardial infarction, and cardiovascular death. These findings highlight the potential of influenza vaccination as an adjunctive strategy in cardiovascular disease prevention. Further research and exploration of underlying mechanisms are warranted to elucidate the observed beneficial effects.