Cardiovascular Death Research Articles

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.

Effects of new hypoglycemic drugs on patients with heart failure: a systematic review and network meta-analysis.

Currently, there is no relevant study comparing sodium-dependent glucose transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase inhibitor (DPP4i) head to head to evaluate their comprehensive impact on heart failure patients. We conducted a comprehensive literature search across multiple databases. Utilizing the risk of bias tool from the Cochrane Collaboration, the methodological quality of included studies was critically assessed and potential publication bias was examined via funnel plots. All results are presented as mean difference; 95% confidence interval (MD; 95% CI). The network meta-analysis indicated that in regards to left ventricular function, there is a big difference in the left ventricular ejection fraction (LVEF) of Empagliflozin 25mg (13.64; 0.26, 27.01) compared to Canagliflozin 100mg; and significant differences in the left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) of Dapagliflozin 10mg (-0.76; -1.27, -0.25 and -0.95; -1.86, -0.05), Vildagliptin 50mg (-1.05; -1.47, -0.63 and -1.12; -2.19, -0.05), and Sitagliptin 100mg (-1.34; -2.31, -0.38 and -1.89; -3.50, -0.27) compared to Empagliflozin 10mg. In terms of the quality of life, there are significant differences in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the Quality of life score of Sitagliptin 100mg (408.08; 213.59, 602.57 and 3.74; 1.57, 5.92) compared to Dapagliflozin 5mg. In terms of the cardiovascular outcome events, there is a significant difference in the heart failure rehospitalization rate of Dapagliflozin 10mg (0.45; 0.25, 0.82) and Empagliflozin 10mg (0.48; 0.28, 0.81) compared to Liraglutide 1.8mg. Further significant differences are found in the all-cause mortality of Dapagliflozin 10mg (0.81; 0.66, 0.98) compared to Vildagliptin 50mg; the cardiovascular death of Albiglutide 30mg (0.49; 0.28, 0.86) compared to Exenatide 2mg; and the arrhythmic events of Liraglutide 1.8mg (0.49; 0.26, 0.90) compared to Empagliflozin 10mg. The network meta-analysis of SGLT2i, GLP-1RA, and DPP4i as a class of drugs showed that GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. Key message What is already known on this topic-It has been confirmed that three new hypoglycemic drugs have a protective effect on the cardiovascular system. Studies have shown that sodium-dependent glucose transporter 2 inhibitors (SGLT2i) can improve cardiovascular outcomes and enhance the quality of life of heart failure patients. Currently, SGLT2i is widely used in the clinical treatment of heart failure, and related studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase inhibitor (DPP4i) also play important roles in the treatment of heart failure. What this study adds-However, there is no relevant research on whether these drugs' clinical efficacy is dose-dependent. How this study might affect research, practice, or policy-This study included different doses of hypoglycemic drugs and used a network meta-analysis method to comprehensively evaluate the effects of three hypoglycemic drugs on heart function, quality of life, and prognosis in heart failure patients, providing a basis for clinical practice.

The contribution of cumulative blood pressure load to dementia, cognitive function and mortality in older adults.

Few studies evaluated the contribution of long-term elevated blood pressure (BP) towards dementia and deaths. We examined the association between cumulative BP (cBP) load and dementia, cognitive decline, all-cause and cardiovascular deaths in older Australians. We also explored whether seated versus standing BP were associated with these outcomes. The Sydney Memory and Aging Study included 1037 community-dwelling individuals aged 70-90 years, recruited from Sydney, Australia. Baseline data was collected in 2005-2007 and the cohort was followed for seven waves until 2021. cSBP load was calculated as the area under the curve (AUC) for SBP ≥140 mmHg divided by the AUC for all SBP values. Cumulative diastolic BP (cDBP) and pulse pressure (cPP) load were calculated using thresholds of 90 mmHg and 60 mmHg. Cox and mixed linear models were used to assess associations. Of 527 participants with both seated and standing BP data (47.7% men, median age 77), 152 (28.8%) developed dementia over a mean follow-up of 10.5 years. Higher cPP load was associated with a higher risk of all-cause deaths, and cSBP load was associated with a higher risk of cardiovascular deaths in multivariate models ( P for trend < 0.05). Associations between cPP load, dementia and cognitive decline lost statistical significance after adjustment for age. Differences between sitting and standing BP load were not associated with the outcomes. Long-term cPP load was associated with a higher risk of all-cause deaths and cSBP load associated with a higher risk of cardiovascular deaths in older Australians.

Heat and cause-specific cardiopulmonary mortality in Germany: a case-crossover study using small-area assessment

High temperatures have been associated with increased mortality, with evidence reported predominately in large cities and for total cardiovascular or respiratory deaths. This case-crossover study examined heat-related cause-specific cardiopulmonary mortality and vulnerability factors using small-area data from Germany. We analyzed daily counts of cause-specific cardiopulmonary deaths from 380 German districts (2000-2016) and daily mean temperatures estimated by spatial-temporal models. We applied conditional quasi-Poisson regression using distributed lag nonlinear models to examine heat effects during May-September in each district and random-effects meta-analysis to pool the district-specific estimates. Potential individual- and district-level vulnerability factors were examined by subgroup analyses and meta-regressions, respectively. Heat was associated with increased mortality risks for all cardiopulmonary sub-causes. The relative risk (RR) of total cardiovascular and respiratory mortality for a temperature increment from the 75th to the 99th percentile was 1.24 (95% confidence interval: 1.23, 1.26) and 1.34 (1.30, 1.38), respectively. The RRs of cardiovascular sub-causes ranged from 1.16 (1.13, 1.19) for myocardial infarction to 1.32 (1.29, 1.36) for heart failure. For respiratory sub-causes, the RR was 1.27 (1.22, 1.31) for COPD and 1.49 (1.42, 1.57) for pneumonia. We observed greater susceptibility related to several individual- and district-level characteristics, e.g., among females or in highly urbanized districts. Heat vulnerability factors remained consistent between urban and rural areas. Our study highlights heat-related increases in cause-specific cardiopulmonary mortality across Germany and identifies key vulnerability factors, offering insights for improving public health practices to mitigate heat-related health impacts. European Union's Horizon 2020 research and innovation program; Helmholtz Associations Initiative and Networking Fund.

Estimated health effect, cost, and cost-effectiveness of mandating sodium benchmarks in Australia's packaged foods: a modelling study.

Excess dietary sodium is a leading cause of death and disability globally. Because packaged foods are a major source of sodium in many countries, including Australia, mandatory limits for sodium might improve population health. We aimed to estimate the long-term health and economic effect of mandating such thresholds in Australia. We used a multiple cohort, proportional, multistate, life table model to simulate the effect of mandating either the WHO global sodium benchmarks or the currently non-mandatory Australian Healthy Food Partnership (HFP) sodium targets. We compared maintaining the current sodium intake status quo with intervention scenarios, using nationally representative data on dietary intake, sodium in packaged foods, and food sales volume. Blood pressure and disease burden data were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study. The effect of sodium reduction on blood pressure and disease risk was modelled on the basis of meta-analyses of randomised trials and cohort studies. Intervention and health-care costs were used to calculate the incremental cost per health-adjusted life-year (HALY) gained. Costs and HALYs were discounted annually at 3%. Compared with the status quo intervention, mandating the WHO benchmarks could be cost saving over the first 10 years (AUD$223 [95% uncertainty interval 82-433] million saved), with 2743 (1677-3976) cardiovascular disease deaths and 43 971 (26 892-63 748) incident cardiovascular disease events averted, and 11 174 (6800-16 205) HALYs gained. Over the population's lifetime, the intervention was cost effective (100·0% probability). Mandating the HFP sodium targets was also estimated to be cost effective (100·0% probability), but with 29% of the health benefits compared with the WHO benchmarks. Our modelling study supports mandating sodium thresholds for packaged foods as a cost-effective strategy to prevent death and disease in Australia. Although making Australia's voluntary reformulation targets mandatory might save thousands of lives, mandating the WHO global benchmarks could yield substantially greater health gains. None.

Bioadaptor implant versus contemporary drug-eluting stent in percutaneous coronary interventions in Sweden (INFINITY-SWEDEHEART): a single-blind, non-inferiority, registry-based, randomised controlled trial.

Persistent non-plateauing adverse event rates in patients who underwent percutaneous coronary intervention (PCI) remain a challenge. A bioadaptor is a novel implant that addresses this issue by restoring the haemodynamic modulation of the artery, allowing cyclic pulsatility, vasomotion, and adaptative remodelling, by unlocking and providing dynamic support to the artery. We aimed to assess outcomes with the device versus a contemporary drug-eluting stent (DES) in a representative PCI population. INFINITY-SWEDEHEART is a single-blind, non-inferiority, registry-based, randomised controlled study conducted in 20 hospitals in Sweden. Patients aged 18-85 years, with chronic or acute coronary syndrome ischaemic heart disease, with an indication for PCI, with up to three de novo lesions suitable for implantation with one single device per lesion, and successful pre-dilatation were identified via the Swedish Coronary Angiography and Angioplasty Registry and eligible for enrolment. Participants were randomly assigned (1:1), using block randomisation with random variation in block size and stratified by site, to either the DynamX bioadaptor (Elixir Medical, Milpitas, CA, USA) or a zotarolimus-eluting DES (Resolute Onyx and Onyx Trustar, Medtronic, Minneapolis, MN, USA). The primary endpoint was the device-oriented clinical endpoint of target lesion failure at 12 months (a composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation), assessed in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment, regardless of treatment received) who had either experienced an event up to 12 months or completed the trial up to 12 months. Non-inferiority was established if the upper limit of the two-sided 95% CI for the absolute risk difference was less than 4·2%. Powered secondary endpoints were landmark analyses from 6 months onwards for target lesion failure, target vessel failure (composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target vessel revascularisation), and target lesion failure for patients with acute coronary syndrome assessed in the ITT population). This study is registered with ClinicalTrials.gov, NCT04562805, and follow-up to 5 years is ongoing. Between Sept 30, 2020, and July 11, 2023, 2399 patients were randomly assigned to receive the bioadaptor (n=1201) or DES (n=1198; ITT population). Median age was 69·5 years (IQR 61·2-75·6), 575 (24·0%) of 2399 patients were female, and 1824 (76·0%) were male (data on race and ethnicity were not collected), and 1838 (76·6%) patients presented with acute coronary syndrome. The primary endpoint of 12-month target lesion failure occurred in 28 (2·4%) of 1189 assessable patients in the bioadaptor group versus 33 (2·8%) of 1192 assessable patients in the DES group, with a risk difference of -0·41% (95% CI -1·94 to 1·11; pnon-inferiority<0·0001). In the prespecified landmark analysis from 6 months to 12 months, the Kaplan-Meier estimates of target lesion failure were 0·3% (with events in three of 1170 patients) in the bioadaptor group versus 1·7% (with events in 16 of 1176 patients) in the DES group (hazard ratio 0·19 [95% CI 0·06 to 0·65]; p=0·0079), of target vessel failure were 0·8% (events in eight of 1167) versus 2·5% (events in 23 of 1174; 0·35 [0·16 to 0·79]; p=0·011), and of target lesion failure in patients with acute coronary syndrome were 0·3% (events in two of 906) versus 1·8% (events in 12 of 895; 0·17 [0·04 to 0·74]; p=0·018). The rate of definite or probable device thrombosis, which was recorded as a safety outcome, was low and did not differ between groups (eight [0·7%] of 1201 in the bioadaptor group vs six [0·5%] of 1198 in the DES group; difference in event rates of 0·16% [95% CI -0·50 to 0·83]). Among patients with coronary artery disease, including those with acute coronary syndrome, treatment with the bioadaptor was non-inferior to contemporary DES, showing potential to mitigate non-plateauing device-related events and improving outcomes in patients undergoing PCI. The additional planned follow-up will help to reinforce the clinical significance of the 1-year findings. Elixir Medical.

Smoking Cessation and Incident Cardiovascular Disease

The association between smoking cessation and cardiovascular disease (CVD) risk in relation to cumulative smoking exposure remains poorly understood. To evaluate the associations among smoking cessation, lifetime smoking burden, and CVD risk according to the number of years elapsed after smoking cessation. This retrospective cohort study of the Korean National Health Insurance Service database investigated smoking duration and intensity between January 2006 and December 2008. Participants were categorized by self-reported smoking habits as current, ex-, or never-smokers. Smoking records were updated every 2 years until December 2019, with participants whose smoking status changed or whose smoking status was unclear excluded. Data analysis was performed between June and December 2022. Time-updated self-reported smoking status, years since quitting, and cumulative smoking amount (pack-years [PY]). The primary outcome was incidence and hazard ratio of CVD (composite of cardiovascular death, myocardial infarction, stroke, and heart failure). Overall, 5 391 231 participants (39.9% male; mean [SD] age, 45.8 [14.7] years; 853 756 [15.8%] current smokers, 104 604 [1.9%] ex-smokers, and 4 432 871 [82.2%] never smokers) were followed up for a mean (SD) of 4.2 (4.4) years. The median (IQR) baseline cumulative smoking amounts were 14.0 (7.5-20.0) PY in current smokers and 10.5 (5.3-20.0) PY in ex-smokers. The median (IQR) duration of smoking cessation was 4 (2-8) years for ex-smokers. Regardless of continued smoking, a dose-dependent association was evident between smoking and incident CVD. Compared with current smokers, ex-smokers with a lifetime smoking burden of less than 8 PY (light ex-smokers) experienced a significant reduction in CVD risk within 10 years of cessation, with a CVD risk similar to that of never-smokers. Conversely, ex-smokers with at least 8 PY (heavy ex-smokers) exhibited a slower decline in CVD risk than light ex-smokers, requiring more than 25 years for the residual CVD risk to disappear. In this cohort study, smoking and CVD risk exhibited a dose-dependent association, with light ex-smokers having a CVD risk similar to that of never-smokers relatively soon after smoking cessation. For heavy ex-smokers, greater than 25 years might be required for the residual CVD risk to align with that of never-smokers.

Long-term cardiovascular outcomes of immune checkpoint inhibitor-related myocarditis: A large single-centre analysis.

Immune checkpoint inhibitors (ICI) are the cornerstone of modern oncology; however, side effects such as ICI-related myocarditis (irM) can be fatal. Recently, Bonaca proposed criteria for irM; however, it is unknown if they correlate well with cardiovascular (CV) ICI-related adverse events. Additionally, whether incident irM portends worse long-term CV outcomes remains unclear. We aimed to determine the incidence of long-term CV comorbidities and CV mortality among irM patients. The ICI-related adverse event (irAE) registry was queried to identify irM patients by using Bonaca criteria. Random controls were selected after excluding patients with other concomitant irAEs. Patients' demographics, comorbidities and myocarditis presenting features were gathered. Outcomes included 2-year freedom from CV comorbidities (composite of atrial fibrillation, stroke, myocardial infarction and heart failure) and freedom from CV death. IrM was treated as a time-varying covariate. Seventy-six patients developed irM at a median of 167days (mean age 69, 63.2% male, 47% lung cancer). Majority of patients had new wall motion abnormalities or EKG changes on presentation. Mean LVEF was 43%, median peak TnT was 0.81, and median NTproBNP was 2057 at irM onset. Two-year freedom from CV comorbidities (67% vs 86.8%, P<0.001) and death (93.4% vs 99.3%, P=0.003) was lower among irM patients. Incident irM was an independent predictor of CV death (HR 8.28, P=0.048), but not CV comorbidities (HR 2.21, P=0.080). This is the largest case-control study on irM highlighting worse long-term CV outcomes. Future studies are needed to establish appropriate therapeutic strategies and efficient screening strategies for irM survivors.

Carotid plaque thickness predicts cardiovascular events and death in patients with chronic kidney disease

BackgroundClassical risk scoring systems underestimate the risk of cardiovascular disease in chronic kidney disease (CKD). Coronary artery calcium score (CACS) has improved prediction of cardiovascular events in patients with CKD. The maximal carotid plaque thickness (cPTmax) measured in ultrasound scans of the carotid arteries has demonstrated similar predictive value as CACS in the general population. This is the first study to investigate whether cPTmax can predict cardiovascular events in CKD and to compare the predictive value of cPTmax and CACS in CKD.MethodTwo hundred patients with CKD stage 3 from the Copenhagen CKD Cohort underwent ultrasound scanning of the carotid arteries. The assessment consisted of locating plaque and measuring the thickest part of the plaque, cPTmax. Based on the distribution of cPTmax, the participants were divided into 3 groups: No plaques, cPTmax 1.0–1.9 mm and cPTmax > 1.9 mm (median cPTmax = 1.9 mm among patients with plaques). To measure CACS, 175 of the patients underwent a non-contrast CT scan of the coronary arteries. The follow-up time spanned between the ultrasound scan and a predefined end-date or the time of first event, defined as a composite of major cardiovascular events or death of any cause (MACE).ResultsThe median follow-up time was 5.4 years during which 45 patients (22.5%) developed MACE. In a Cox-regression adjusted for classical cardiovascular risk factors, patients with cPTmax > 1.9 mm had a significantly increased hazard ratio of MACE (HR 3.2, CI: 1.1–9.3), p = 0.031) compared to patients without plaques. C-statistics was used to evaluate models for predicting MACE. The improvement in C-statistics was similar for the two models including classical cardiovascular risk factors plus cPTmax (0.247, CI: 0.181–0.312) and CACS (0.243, CI: 0.172–0.315), respectively, when compared to a model only controlled for time since baseline (a Cox model with no covariates).ConclusionOur results indicate that cPTmax may be useful for predicting MACE in CKD. cPTmax and CACS showed similar ability to predict MACE.

Evaluating the budget impact of Empagliflozin in managing heart failure with reduced ejection fraction: Proposing strategic policies for Malaysian public healthcare.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors such as Empagliflozin, are increasingly recommended as part of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) in many developed nations. This recommendation is based on robust clinical evidence showing that adding Empagliflozin to GDMT improves heart failure symptoms, clinical outcomes, functional status, and overall quality of life. In Malaysia, where healthcare is predominantly public and heavily subsidized, the introduction of new treatments can significantly impact costs, requiring detailed economic assessments. This study evaluates the budget impact of incorporating Empagliflozin into GDMT for HFrEF from the perspective of the public healthcare system. A five-year budget impact model was developed, integrating local data such as population, drug use, costs, clinical outcomes, and healthcare expenses. In the current scenario (GDMT alone), the projected five-year expenditure is MYR 6.12 billion (USD 3.92 billion). With Empagliflozin, the total cost rises by 0.71% to MYR 6.16 billion (USD 3.95 billion), driven by drug acquisition costs of MYR 160.12 million (USD 102.64 million) and adverse event costs of MYR 211,543 (USD 135,604). However, these costs are offset by savings from reduced HF hospitalizations, fewer cardiovascular deaths, and improved renal outcomes. Sensitivity analysis identified hospitalization costs, the price of Empagliflozin, and cardiovascular deaths in diabetic patients as key factors influencing the budget impact. Policymakers can improve the affordability of Empagliflozin through strategies like price negotiations, cost-sharing, and focusing on high-risk groups to optimize healthcare expenditure while ensuring effective treatment access.

Cardiovascular effects of obstructive sleep apnoea and effects of continuous positive airway pressure therapy: evidence from different study models

INTRODUCTIONCardiovascular consequences of obstructive sleep apnoea (OSA) and the effects of continuous positive airway pressure (CPAP) therapy on blood pressure, endothelial dysfunction, and MACE (major adverse cardiovascular events) have been studied over decades using different study designs. However, clinical findings from different study models on cardiovascular outcomes are sometimes contradictory.METHODSA literature search was conducted in PubMed for randomised controlled trials, meta-analyses, population-based epidemiological studies and OSA cohort studies up to September 2023 investigating the cardiovascular effect of OSA and CPAP in adults with OSA on the following cardiovascular endpoints: blood pressure, arterial hypertension, endothelial function, and MACE (myocardial infarction, stroke, transient ischemic attack, cardiovascular death). The level of evidence for these outcomes was discussed on the basis of different study models.RESULTS AND CONCLUSIONSThere is high-level evidence of a causal relationship between OSA and arterial hypertension and endothelial dysfunction, as well as on higher MACE incidence among subgroups of patients with untreated OSA. The cardiovascular effects of OSA depend on the severity of OSA, symptoms, phenotype, and comorbidities. The blood pressure-lowering effect of CPAP is mainly observed in uncontrolled and treatment-resistant hypertension. The MACE risk reduction in OSA depends on good long-term CPAP adherence. Younger, sleepy patients with more severe OSA, higher hypoxaemic burden and without overt cardiovascular end-organ disease may particularly benefit from CPAP treatment in terms of cardiovascular risk reduction. Randomised controlled trials of CPAP or other effective OSA treatments in primary cardiovascular prevention and in patients at highest risk are lacking.

Vericiguat Global Study in Participants with Chronic Heart Failure: Design of the VICTOR trial.

In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, the soluble guanylate cyclase stimulator vericiguat reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death in patients with heart failure (HF) and reduced ejection fraction (HFrEF) with recent worsening HF. The effect of vericiguat in patients with HFrEF without recent worsening HF remains unknown. The VICTOR (Vericiguat Global Study in Participants with Chronic Heart Failure) trial was designed to assess the efficacy and safety of vericiguat in patients with ejection fraction ≤40% without recent worsening HF on a background of current foundational HFrEF therapy. The primary endpoint for VICTOR is time to first event for the composite of HHF or cardiovascular death. The trial will also assess the effect of vericiguat on time to cardiovascular death, time to HHF, total HHF, and all-cause death. As an event-driven trial, at least 1080 primary events are expected, but follow-up will continue until the targeted number of at least 590 cardiovascular deaths has been reached. Approximately 6000 participants will be randomized to vericiguat or placebo. VICTOR is the first large event-driven HFrEF trial performed in the contemporary era of quadruple foundational guideline-directed medical therapy, in a compensated ambulatory HF population. VICTOR will add important information to the evidence of the effects of vericiguat across the spectrum of patients with HFrEF.

Sodium-glucose cotransporter-2 inhibitors in acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

We aimed to assess the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus placebo, initiated within the hospitalization period, in addition to habitual treatment, for treating adult patients with confirmed acute myocardial infarction (AMI). We also conducted subgroup analysis by diabetes mellitus (DM) status and type of AMI. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcome was hospitalization for heart failure (HF). The secondary outcomes were all-cause death, cardiovascular death, and serious adverse events (AEs). We pooled risk ratios (RR) with a 95% confidence interval (CI) for binary outcomes. The between-study variance was assessed using tau2 statistics. We included five RCTs, encompassing 11,211 patients. SGLT2i significantly reduced the risk of hospitalization for HF compared to placebo (RR 0.73; 95% CI [0.61, 0.88]). However, the risk of all-cause death (RR 1.05; 95% CI [0.78, 1.41]) and cardiovascular death (RR 1.04; 95% CI [0.84, 1.29]) was similar between the groups, as well as the risk of serious AEs (RR 1.01; 95% CI [0.90, 1.14]). In the subgroup analysis by DM status and type of AMI, there were no significant subgroup differences for the outcomes of hospitalization for HF and all-cause death. In patients with AMI, treatment with SGLT2i is safe and significantly reduces the risk of hospitalization for HF, but it has no impact on all-cause death and cardiovascular death compared to placebo.

Association of prophylactic low-dose aspirin use with all-cause and cause-specific mortality in cancer patients

The long-term use of aspirin for preventing cardiovascular disease has been recommended for decades. However, there is currently uncertainty regarding the long-term effects of aspirin use on the risk of all-cause, cardiovascular, and cancer mortality in cancer patients. The aim of this work was to analyze the connection between the prophylactic use of low-dose aspirin and the risk of all-cause death, cardiovascular death, and carcinoma death in carcinoma patients in the United States. A cohort study was conducted using National Health and Nutrition Examination Survey (NHANES) data (2011–2012, 2013–2014, 2015–2016, and 2017–2018) and associated mortality data. The 95% confidence intervals (CIs) and hazard ratios (HRs) between non-aspirin use and prophylactic low-dose aspirin use and the risk of death were measured via Cox proportional hazard regression models. A total of 1819 participants were included in the present research, of whom 945 were nonaspirin users and 874 were prophylactic aspirin users. Compared with non-aspirin users, prophylactic low-dose aspirin users had a decreased risk of all-cause death (HR = 0.647, 95% CI = 0.489–0.857). There was no statistically significant difference in the risk of cardiovascular death (HR = 0.623, 95% CI = 0.362–1.074) or cancer death (HR = 0.709, 95% CI = 0.410–1.226). Prophylactic use of low-dose aspirin may lower all-cause mortality in individuals with cancer but does not have a substantial effect on cardiovascular risk or cancer-specific mortality in this patient population.

Effects of age, sex, daily dose, comorbidity and co-medication on venlafaxine-associated cardiovascular adverse events: A pharmacovigilance analysis of the FDA Adverse Event Reporting System database.

This study aimed to provide a comprehensive view of cardiovascular adverse events (AEs) associated with venlafaxine (VEN) therapy. Cardiovascular AE reports for patients receiving VEN therapy were retrieved from January 2004 to December 2023 from the FDA Adverse Event Reporting System database. Effects of age, sex and daily VEN dose on the occurrence of different types of cardiovascular AEs and the influence of demographics, VEN dose, comorbidity and co-medication on death in patients with cardiovascular AEs were analysed by multivariate logistic regression analysis. The study included 16 110 AE reports following VEN treatment (median age: 51 years, females: 69.78%, median VEN daily dose: 100 mg/day). VEN daily dose was associated with increased risks of cardiac arrhythmias, embolic and thrombotic events, torsade de pointes/QT prolongation, ischaemic heart disease, cardiac failure, cardiomyopathy and overall cardiovascular events. The elderly (≥ 75 years), male sex, comorbidity (infections and infestations, cardiac disorders, nervous system disorders) and co-medication (quetiapine and clozapine) were related to death following VEN-associated cardiovascular AEs; however, the risk of cardiovascular death did not increase with regular VEN doses. Our study confirmed the association of cardiovascular AEs with VEN therapy and revealed the influencing factors for the risk of VEN-related cardiovascular AEs and death due to these events. Based on the obtained evidence, the cardiovascular health of late-elderly patients with complex comorbidity and polytherapy should be closely monitored when they receive VEN therapy. As an exploratory study, prospective studies are needed to validate our findings in the future.

Contemporary outcomes of catheter ablation of the structural ventricular tachycardias in severe ischemic and non‐ischemic cardiomyopathies in Turkish population

AbstractIntroductionCurrently, there are no data regarding outcomes of the catheter ablation for structural ventricular tachycardia (VT) in Türkiye. In this observational study, we aim to investigate cardiac outcomes of patients undergoing catheter VT ablation at a tertiary center in Türkiye.MethodsThis was a retrospective observational study performed at a single university center. Patients with a confirmed ischemic or non‐ischemic cardiomyopathy, undergoing structural VT ablation were included. Procedural and mid‐term outcomes were analyzed.ResultsA total of 124 patients were enrolled in the study. 54(43.5%) patients presented with an electrical storm. During the mean follow‐up of 351 ± 232 days 10(8.1%) patients experienced a recurrence. There was only one peri‐procedural death and cardiac tamponade occurred in two patients.14(11.3%) patients died during the follow‐up, most commonly due to a cardiovascular death. In the multivariate analysis only age &gt;70 was found to be correlated with death during follow‐up, with p =.008, HR = 4.923.ConclusionA good acute success with low complications was observed in patients undergoing VT ablation for structural heart disease in a tertiary center in Türkiye. Mid‐term outcomes are comparable with international studies with no difference in VT recurrence in ischemic and non‐ischemic patients. Similar to international studies, significant mid‐term mortality was observed.

Impact of Triglyceride Levels on the Long-term Clinical Outcomes in Patients With Acute Myocardial Infarction.

Hypertriglyceridemia is a known cardiovascular risk factor. However, the relationship between serum triglyceride (TG) levels and the clinical outcomes in patients with acute myocardial infarction (AMI) is unclear. We conducted a single-center, retrospective observational study involving 538 consecutive patients with AMI who underwent emergent percutaneous coronary intervention within 12 hours of onset. Patients were categorized into three groups based on their serum TG levels at admission as follows: T1 group (TG <78 mg/dl, n=172), T2 group (78≤TG<141 mg/dl, n=177), and T3 group (141 mg/dl ≤TG, n=176). The primary endpoint was major adverse cardiovascular events (MACEs) defined as a composite of cardiovascular death, non-fatal MI, and non-fatal stroke. The median follow-up period was 2.4 (1.5-4.2) years. Patients in the T1 group were older, had a higher proportion of females, and had fewer cardiovascular risk factors. However, they also had a higher prevalence of multi-vessel coronary artery disease and severely calcified culprit lesions. The T1 group had a significantly higher rate of MACEs (20.4% in T1, 12.4% in T2 and 8.5% in T3, p<0.05 by Log-rank test, respectively). Multivariate analysis revealed that T1 was an independent predictor of MACEs (hazard ratio=2.19, 95% confidence interval=1.16-4.14, p<0.05). Although patients with AMI with low TG levels at admission had fewer coronary risk factors, they had more severe calcified culprit lesions and worse clinical outcomes.

Effect of body mass index on mortality for diabetic patients with aortic stenosis

Abstract Background Several studies suggest an "obesity paradox," associating obesity with better cardiovascular outcomes compared to normal or underweight individuals (1-3). Purpose This study explores the impact of body mass index (BMI) on mortality in patients with diabetic mellitus (DM) and aortic stenosis (AS). Methods This is a retrospective cohort study conducted at a tertiary centre. Between 2014 and 2019, patients with DM who underwent echocardiography were screened (4). Patients were enrolled if AS was diagnosed, according to established guidelines (5). Two echocardiography specialists independently reviewed the echocardiography in the cohort. The index date of the DM-AS cohort was the first AS diagnosis by echocardiography, and detailed data collection methods are described in previous studies (6,7). Patients were categorized as underweight, normal weight, or obese based on BMI (&amp;lt;18.5, 18.5 to 27, and &amp;gt;27 kg/m2, respectively). Outcomes included all-cause mortality, cardiovascular, and non-cardiovascular death, which were adjudicated by a central committee. The occurrence times of the outcomes of interest were determined using diagnosis codes from electronic health records, and medical records were reviewed until the last clinical visit or death. Results Among 74,835 DM patients, 734 had AS. Normal weight comprised 65.5% (n=481), underweight 4.1% (N=30), and 30.4% were obese. With a median follow-up time of 34 months, 285 patients (38.8%) experienced outcomes of death, comprising 93 patients (32.7%) with cardiovascular death and 192 patients (67.3%) with non- cardiovascular death. Underweight patients had significantly higher all-cause mortality (HR 1.96, 95% CI 1.22 – 3.14, p = 0.005), while obese patients had significantly lower mortality (HR 0.79, 95% CI 0.68 - 0.91, p=0.001) compared to the normal group. Regarding etiologies, underweight patients had a higher risk of non- cardiovascular death (HR 2.47, 95% CI 1.44-4.25, p = 0.001), while obese patients had a lower risk of cardiovascular death (HR 0.66, 95% CI 0.50-0.86, p=0.003). Subgroup analysis showed a consistent trend without significant interaction. To elucidate the interaction of BMI as a continuous variable with outcomes, restricted cubic spline analysis was applied. Cardiovascular death showed a negative association with BMI across available BMI levels, and non-cardiovascular death exhibited a U curve, with the lowest hazard ratio occurring when BMI was between 25 to 30. Conclusion Our study underscored the significance of both cardiovascular and non-cardiovascular deaths as crucial contributors to overall mortality in DM patients with AS. Being underweight is associated with increased non- cardiovascular death, while obesity is linked to less cardiovascular death. Proposed mechanisms include reduced frailty, enhanced tolerance to guideline-directed medical therapies (GDMTs), and heightened disease awareness in the obese group (8,9).Kaplan–Meier analysis for outcomesAssociation between BMI and outcomes

Left atrial reservoir strain measured by three-dimensional echocardiography is associated with major adverse cardiovascular events in the general population

Abstract Background Left atrial (LA) strain measured by three-dimensional (3D) echocardiography (3DE) is a novel way of evaluating LA function. The prognostic value of LA strain by 3DE in incident heart failure (HF) and cardiovascular (CV) death has not previously been documented. Purpose We south to investigate whether 3D LA strain measures were associated with incident heart failure (HF) and cardiovascular (CV) death in a population at low risk of CV events. Methods A total of 1,934 participants from a prospective longitudinal cohort study of the general population underwent a comprehensive transthoracic echocardiographic examination including 3DE where LA reservoir strain (LASr), conduit strain (LAScd) and contraction strain (LASct) were quantified. All participants were at sinus-rhythm during 3DE. The endpoint was a composite of HF and CV death. Cox proportional hazards regression was applied. Multivariable adjustments were made for the ARIC-HF risk score (age, gender, heart rate, systolic blood pressure, antihypertensive medication, diabetes, ischemic heart disease, smoking, and body mass index) and left atrial volume index. Results Mean age was 54±17 years, 43% were male. During a median follow-up time of 4.8 years (interquartile range 4.3-5.4 years), 89 participants (4.6%) either developed HF or died of a CV cause. In univariable analysis, LASr and LAScd, but not LASct were significantly associated with the outcome, but after multivariable adjustment only LASr remained significantly associated with outcome (HR 1.04 (95% CI: 1.01-1.08), p=0.016, per 1% decrease) while LAScd and LASct did not. LASr provided incremental prognostic information beyond the ARIC-HF risk score (continuous NRI 0.21±0.11, p=0.027). Compared to participants with a LASr in the 1st tertile (LASr&amp;gt;32%) Participants with an LASr in the in the 3rd tertile (LASr&amp;lt;26.5%) had an almost 7-fold increased risk of HF or CV-death (HR 6.93 (95% CI 3.29-14.58; p=0.001)(Figure). Conclusion LA reservoir strain assessed by 3DE was independently associated with incident HF and CV death, which was not the case for LA conduit and contraction strain. In addition, LA reservoir strain added incremental value beyond clinical risk scores.

Serum amyloid A-low-density-lipoprotein complex and cause-specific mortality in patients with suspected or known coronary artery disease: The ANOX Study

Abstract Background Serum amyloid A-low-density-lipoprotein (SAA-LDL) is a complex formed from the oxidative interaction between SAA and LDLs. A relatively small-scale study has shown that circulating SAA-LDL levels may serve as a prognostic marker in patients with stable coronary artery disease (CAD). However, the association between SAA-LDL and cause-specific mortality in patients with suspected or known CAD is unknown. Methods Serum SAA-LDL levels were measured in 2416 patients with suspected or known CAD undergoing elective coronary angiography. The outcomes were all-cause death, cardiovascular (CV) death, non-CV death, cancer death, and other non-CV death. Patients were followed up over a 3-year period. Results During the follow-up, 254 (10.5%) deaths occurred, including 88 (3.6%) CV deaths, 151 (6.3%) non-CV deaths, 66 (2.7%) cancer deaths, 85 (3.5%) other non-CV deaths, and 15 (0.6%) undetermined deaths. Stepwise regression analysis including baseline data on potential clinical confounders and established CV biomarkers (i.e., N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein [hs-CRP]) revealed that the strongest independent determinant of SAA-LDL levels was hs-CRP (partial regression coefficient, 0.248; standard error, 0.010; p&amp;lt;0.001). After adjusting for potential clinical confounders and established CV biomarkers, the highest quartile of SAA-LDL levels (vs. the lowest quartile) was significantly associated with all-cause death (adjusted hazard ratio [aHR], 1.56; 95% confidence interval [CI], 1.05–2.34) and non-CV death (aHR, 1.76; 95% CI, 1.02–3.11), but not with CV death (aHR, 1.16; 95% CI, 0.62–2.20), cancer death (aHR, 1.68; 95% CI, 0.71–4.34), or other non-CV death (aHR, 1.65; 95% CI, 0.82–3.45) in the entire cohort. In patients with low hs-CRP levels (≤1.0 mg/L, n=1253), the highest quartile of SAA-LDL levels was significantly associated with all-cause death (aHR, 2.19; 95% CI, 1.11–4.57), non-CV death (aHR, 2.78; 95% CI, 1.05–8.79), and cancer death (aHR, 4.65; 95% CI, 1.12–31.9), but not with CV death (aHR, 1.22; 95% CI, 0.39–3.92) or other non-CV death (aHR, 1.68; 95% CI, 0.42–8.35). In contrast, the highest quartile of SAA-LDL levels was not significantly associated with all-cause death (aHR, 1.18; 95% CI, 0.72–1.96), CV death (aHR, 1.02; 95% CI, 0.45–2.31), non-CV death (aHR, 1.46; 95% CI, 0.75–2.91), cancer death (aHR, 1.35; 95% CI, 0.43–4.58), or other non-CV death (aHR, 1.38; 95% CI, 0.60–3.25) in patients with high hs-CRP levels (&amp;gt;1.0 mg/L, n=1163). Conclusions Elevated SAA-LDL levels were independently associated with all-cause and non-CV mortality, but unexpectedly not with CV mortality, in patients with suspected or known CAD. These associations were pronounced in patients with low hs-CRP levels (≤1.0 mg/L). The association between the SAA-LDL level and cancer mortality suggests its predictive utility in patients with low hs-CRP levels (≤1.0 mg/L).