Cardiovascular Death Research Articles

Sex differences in the efficacy of angiotensin receptor blockers on kidney and cardiovascular outcomes among individuals with type 2 diabetes and diabetic kidney disease: post hoc analyses of the RENAAL and IDNT trials.

Our aim was to assess sex differences in the efficacy of angiotensin receptor blockers (i.e. losartan and irbesartan) on kidney and cardiovascular outcomes in individuals with type 2 diabetes and diabetic kidney disease. Data from the Angiotensin II Antagonist Losartan Study (RENAAL) and Irbesartan type II Diabetic Nephropathy Trial (IDNT) were used. The kidney outcome was time to first event of end-stage kidney disease or doubling of serum creatinine. The cardiovascular outcome was time to first event of a composite of stroke, myocardial infarction, cardiovascular death or hospitalisation for heart failure. Sex differences were assessed by a sex × treatment interaction term in Cox proportional hazards models. Included were 1737 male participants and 924 female participants. The beneficial effect of angiotensin receptor blockers on the kidney outcome was similar between male and female participants (HR in male participants 0.72 [95% CI 0.59, 0.86] vs HR in female participants 0.86 [95% CI 0.69, 1.06]; sex × treatment interaction HR 1.19 [95% CI 0.89, 1.59]). For the cardiovascular outcome, angiotensin receptor blockers lowered the risk in male but not in female participants (HR in male participants 0.81 [95% CI 0.69, 0.95] vs HR in female participants 1.11 [95% CI 0.88, 1.40]; sex × treatment interaction HR 1.37 [95% CI 1.03, 1.82]). This study in individuals with type 2 diabetes and diabetic kidney disease suggests that the beneficial effects of angiotensin receptor blockers are similar in male and female participants for the kidney outcome but not for the cardiovascular outcome. More attention to sex differences in angiotensin receptor blockers' efficacy and underlying mechanisms of differences in response is needed. ClinialTrials.gov NCT00308347.

Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study.

Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA. A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%. Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5-14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%; P=0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%-0.62%]) were not significantly different from those without CAV (30%; P=0.94; median, 0.31% [IQR, 0.17%-0.71%]; P=0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%-1.11%]) compared with normal MBF patients (27%; P<0.001; median, 0.25% [IQR, 0.15%-0.52%]; P<0.001). HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.

Pre-interventional renal artery calcification and survival after transcatheter aortic valve implantation.

The prognostic significance of renal artery calcification (RAC) is unknown in patients with severe aortic stenosis (AS) eligible for transcatheter aortic valve implantation (TAVI). RAC can be assessed by computed tomography (CT) performed during pre-interventional planning for TAVI. This study aimed at investigating the utility of RAC for predicting survival after TAVI. In this longitudinal cohort study, RAC volume was measured by CT in 268 consecutive patients with severe AS undergoing TAVI. Association of RAC with mortality was assessed using Cox regression analysis. RAC was evaluated as a binary parameter and in a supplementary analysis as a logarithmically transformed continuous variable. Over a median follow-up time of 9.6 years, 237 (88.4%) patients died, with 174 (73.4%) deaths attributable to a cardiovascular cause. RAC was highly prevalent (N = 150 (86.2%)) among patients suffering cardiovascular death. Competing risk cumulative incidence curves revealed a higher occurrence of cardiovascular death in patients with RAC (P-value = 0.008), while this was not the case for non-cardiovascular death (P-value = 0.71). RAC was independently associated with cardiovascular death (HR 1.61 [95% CI: 1.01-2.57]; P = 0.047) after adjustment for age, sex, cardiovascular risk factors, impaired renal function, and aortic valve calcification. The presence or absence of RAC rather than its volume was important in all the analyses. RAC is a strong and independent predictor of cardiovascular death in patients with severe AS undergoing TAVI. Given its favourable properties for event prediction, RAC may be considered valuable for prognostic assessment of TAVI patients.

Expanding access to sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the Ministry of Health Malaysia - a multiple HTA approach.

Ministry of Health (MOH) Malaysia stakeholders seek primary care access to sodium-glucose cotransporter 2 inhibitor (SGLT2i). Addressing this required a complex decision, selecting among three SGLT2i for two different indications and two practice settings. The options include expanding the existing SGLT2i (empagliflozin) in the MOH Medicines Formulary to primary care and/or having dapagliflozin and/or luseogliflozin as alternatives. This study aimed to conduct a multiple health technology assessment (HTA) to determine the SGLT2i of choice for the MOH setting. The clinical benefits of SGLT2i were assessed through a systematic literature review and affordability was assessed through the development of three budget impact analysis models simulating seventy scenarios. Each model varied by prescribing indications, restrictions, and SGLT2i involved (M1: glycemic control, HbA1c between 6.5 percent and 10 percent, empagliflozin-dapagliflozin-luseogliflozin; M2: cardiovascular benefits, HbA1c less than 10 percent, empagliflozin-dapagliflozin; M3: a composite of M1 and M2). The outcome of the HTA was presented to the MOH decision-makers. Although there was no significant difference in glycemic control between the SGLT2i, differences exist in cardiovascular benefits conferred. Despite having scenarios with lower net budget impact (NBI) in the M1, M2, and M3 models, decision-makers decided to expand empagliflozin use to primary care setting and add dapagliflozin for hospital-only setting for both indications [NBI of $4.38 mil] due to empagliflozin's advantage in reducing risk for cardiovascular death and prior experience of its use in MOH. The multiple HTA approach guided the complex decision-making process by providing a holistic understanding of the decision's impact.

Effect of traditional Chinese medicine on cardiovascular death and all-cause death among patients with heart failure and/or atrial fibrillation.

We tried to define the association of adverse cardiovascular (CV) events, such as CV death and all-cause death among patients with heart failure (HF) and/or atrial fibrillation (AF) receiving traditional Chinese medicine (TCM) or not. We used data from the Taiwan National Health Insurance Research Database in a retrospective cohort study using propensity scoring (PS) matching. We matched 54,859 and 18,307 patients each to the treatment vs. non-treatment group and found a significantly decreased risk of adverse CV events after PS score matching, suggesting that TCM reduces the risk of these adverse outcomes. Compared to HF patients without AF in non-TCM user, HF patients without AF in TCM user and HF patients with AF in TCM user had decreased risk of CV death by 0.50 times (95% CI 0.49, 0.52) and 0.84 times (95% CI 0.49,0.52), respectively. HF patients without AF in TCM user and HF patients with AF in TCM user had decreased risk of all-cause death relative to HF patients without AF in non-TCM user by 0.53 times (95% CI 0.52, 0.54) and 0.74 times (95% CI 0.72,0.76), respectively. The results said that there is significant reduction of decrease in risk of CV death and all death among the patients receiving TCM, especially those without AF.

Impact of Angiographically Detected Residual Trabeculation After Left Atrial Appendage Closure Using the WATCHMAN Device: Insight From the OCEAN-LAAC Registry.

Research on the impact of angiographically detected residual trabeculation after left atrial appendage closure (LAAC) is limited. To investigate the incidence, characteristics, and clinical implications of angiographically detected residual trabeculation after LAAC using the WATCHMAN device. We analyzed 1350 consecutive patients with atrial fibrillation undergoing LAAC using the WATCHMAN device from the OCEAN-LAAC registry, which is a prospective ongoing, multicenter Japanese registry. The inclusion criteria comprised patients who successfully underwent LAAC and whose presence or absence of residual trabeculation can be confirmed using a contrast medium. The clinical outcomes were compared between patients with and without angiographically detected residual trabeculation. Residual trabeculation was angiographically detected in 5.6% (75/1350 patients). At the procedure, the proportion of peri-device leak (PDL) was significantly higher in the residual trabeculation group than in the non-residual trabeculation group (20% vs. 5.1%, p < 0.001). However, the PDL and device-related thrombosis at 45 days and 1 year were comparable between the two groups (37% vs. 23%, p = 0.24; 28% vs. 31%, p = 0.84; 2.1% vs. 1.4%, p = 0.50; 6.9% vs. 6.0%, p = 0.69, respectively). The 3-year cumulative incidence of ischemic stroke, all cardiovascular death, and all-cause death were comparable between the two groups (5.7% vs. 5.5%, log-rank p = 0.96; 7.7% vs. 8.9%, log-rank p = 0.34, 31.4% vs. 22.3%, log-rank p = 0.71, respectively). The angiographically detected residual trabeculation rate was 5.6%, and this population had a significantly higher prevalence of PDL at the procedure. However, the presence of residual trabeculation did not contribute to PDL or device-related thrombosis at follow-up or affect the clinical outcomes.

Genetic insights into the effect of trace elements on cardiovascular diseases: multi-omics Mendelian randomization combined with linkage disequilibrium score regression analysis

ObjectiveEpidemiological evidence indicates that trace elements are significantly associated with cardiovascular health. However, its causality and underlying mechanisms remain unclear. Therefore, this study aimed to investigate the causal relationship between trace elements and cardiovascular disease, as well as their potential mechanism of action.MethodTwo-sample Mendelian randomization (MR) analyses along with mediated and multivariate MR analyses were employed. These analyses utilized 13 trace elements as exposure variables and 20 cardiovascular diseases as outcome variables, with 4907 circulating plasma proteins, 1400 serum metabolites, 731 immune cell phenotypes, and 473 intestinal flora as potential mediators. The Bayesian weighted MR method was used to validate the MR results, and linkage disequilibrium score regression (LDSC) was applied to explore the genetic correlation between trace elements and cardiovascular disease.ResultOur findings indicated a positive or negative causal relationship between genetically predicted trace elements and cardiovascular disease. An analysis using the Bayesian weighted MR method demonstrated that our causal inference results were reliable. The results of the mediated MR analyses indicate that potassium may reduce the risk of ischemic heart disease by influencing the expression of the plasma proteins BDH2 and C1R. Vitamin B12 may increase the risk of coronary atherosclerosis and cardiovascular death by reducing the levels of VPS29 and PSME1 proteins, while vitamin C may mitigate the risk of cardiac arrest by inhibiting the expression of the TPST2 protein. In addition, potassium can reduce the risk of ischemic heart disease by lowering 4-methoxyphenyl sulfate levels. None of the instrumental variables exhibited pleiotropy in the MR analysis. A sensitivity analysis using the leave-one-out method further confirmed the robustness of our findings. LDSC results indicated a genetic correlation between multiple trace elements and various cardiovascular diseases.ConclusionThis study uncovered the true causal relationship between trace elements and cardiovascular disease risk using genetic methods, and revealed the significant mediating role of specific plasma proteins and metabolites in this relationship.

Traditional Chinese medicine for cardiovascular disease: efficacy and safety

In China and other Asian nations, traditional medicine has long been utilized in the treatment of cardiovascular diseases (CVD). While Chinese authorities have incorporated traditional Chinese medicine (TCM) treatment experiences as a supplementary guide for CVD, its international recognition remains limited due to a scarcity of high-quality and reliable randomized controlled trials (RCTs) evidence. The purpose of this study was to examine the clinical outcomes with TCM for CVD after the recent publication of large trials adding &amp;gt;20,000 individuals to the published data. Here, we systematically reviewed 55 published RCTs (modified Jadad scores &amp;gt; 4) in the past 20 years, involving a total of 36,261 patients. In most studies, TCM has been associated with significant improvements in alternative endpoints such as hypertension, coronary heart disease, stroke and heart failure. A total of 19 trials reported on primary outcomes such as cardiovascular events and death events. During the follow-up period, some Chinese patent medicines can effectively reduce the “hard” endpoints of coronary heart disease, stroke, and heart failure, the overall trend of cardiovascular outcomes is lower. The risk of adverse effects was not significantly increased compared to the control group, suggesting its potential as an alternative approach for primary and secondary prevention of CVD based on the available evidence.

Pitfalls of Choosing a Study End Point Including Cardiovascular Death in Comparative Clinical Trials

Pitfalls of Choosing a Study End Point Including Cardiovascular Death in Comparative Clinical Trials

Aortic pulse wave velocity predicts cardiovascular mortality among middle-aged metabolic syndrome subjects without overt cardiovascular disease

BackgroundThe objective of this cohort study was to assess the predictive value of main arterial markers for cardiovascular death in middle-aged subjects with metabolic syndrome (MetS).MethodsThis prospective longitudinal study analyzed data from 5829 metabolic syndrome subjects without overt cardiovascular disease aged between 40 and 64 years and enrolled in the Lithuanian High Cardiovascular Risk primary prevention program. Initial assessment comprised the evaluation of aortic pulse wave velocity (aPWV), carotid intima-media thickness (cIMT), carotid stiffness index, cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), aortic augmentation index adjusted for a heart rate of 75 bpm (AIXHR75), and endothelium-dependent flow-mediated dilatation (FMD).ResultsDuring the mean follow-up period of 6.35 ± 2.99 years, 170 subjects (2.9%) had died, with 41 out of these deaths (24.1%) related to cardiovascular causes. Cox proportional hazard regression analysis revealed associations between cardiovascular deaths and increases in aPWV (HR 1.34, 95% CI 1.14–1.58, p < 0.001), CAVI (HR 1.28, 95% CI 1.09–1.50, p = 0.002), and cIMT (HR 1.004, 95% CI 1.001–1.006, p = 0.003), as well as a decrease in ABI (HR 0.020, 95% CI 0.001–0.359, p = 0.008). However, after adjustment for age and gender, only aPWV remained a statistically significant predictor. Common survival tree analysis foregrounded the predictive significance of C-reactive protein (CRP), as the primary variable associated with an increased risk of cardiovascular death, followed by aPWV and smoking as secondary and tertiary variables. The analysis also demonstrated sex-related differences: in women, the primary predictive variable was aPWV, whereas in men, CRP was identified as the primary variable, followed by CAVI and cIMT.ConclusionsThe findings of this study suggest that, among the markers of subclinical arterial damage, an increase in both aPWV and CAVI has a statistically significant predictive value for cardiovascular mortality in the middle-aged subjects with MetS. However, only aPWV demonstrated predictive value that was independent of age and gender.

Left Anterior Descending Nonculprit Lesions and Clinical Outcomes in PatientsWith ST-Segment Elevation Myocardial Infarction.

In the COMPLETE (Complete vs Culprit-Only Revascularization to Treat Multi-Vessel Disease After Early PCI for STEMI) trial, complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) reduced important outcomes compared with culprit-only percutaneous coronary intervention. Whether clinical outcomes in STEMI patients with MVD are influenced by the presence of a left anterior descending (LAD) nonculprit lesion (NCL) remains unknown. This study sought to compare: 1) cardiovascular outcomes among patients with an NCL in the proximal/mid-LAD to patients with an NCL in other locations; and 2) the benefit of NCL revascularization in patients with and without a proximal/mid-LAD NCL. The COMPLETE trial enrolled patients presenting with STEMI and MVD to angiography-guided complete revascularization vs a culprit lesion-only strategy. All coronary angiograms were evaluated in a central core laboratory. In this prespecified subanalysis, treatment effect according to proximal/mid-NCL location was determined for the coprimary outcomes of: 1) cardiovascular death or new myocardial infarction; and 2) cardiovascular death, new myocardial infarction, or ischemia-driven revascularization. Cox proportional hazards models were performed with an interaction term for treatment allocation and NCL location. Of the 4,041 subjects in COMPLETE, 1,666 patients had a proximal/mid-LAD NCL (41.2%). The first coprimary outcome occurred in 8.5% (2.9%/y) of patients with a proximal/mid-LAD NCL vs 9.9% (3.4%/y) in those without (adjusted HR: 0.83; 95%CI: 0.67-1.03). Complete revascularization had a similar benefit in reducing the first coprimary outcome for patients with a proximal/mid-LAD NCL (7.7% vs 9.2%; HR: 0.85; 95%CI: 0.61-1.18) and those without (8.0% vs 11.9%; HR: 0.65; 95%CI: 0.50-0.86), with no differential treatment effect (interaction P = 0.235) CONCLUSIONS: Among patients presenting with STEMI and multivessel CAD, those with a proximal/mid-LAD NCL had similar event rates to those without. The benefit of complete revascularization between the groups was similar, with no evidence of heterogeneity.

Association of ACEI/ARB therapy with total and cardiovascular death in coronary artery disease patients with advanced chronic kidney disease: a large multi-center longitudinal study.

Advanced chronic kidney disease (CKD) is common among patients with coronary artery disease (CAD), and angiotensin‑converting enzyme inhibitors (ACEI) or angiotensin‑receptor blockers (ARB) can improve cardiac and renal function, but whether ACEI/ARB therapy improves long-term prognosis remains unclear among these high-risk patients. Therefore, this research aimed to investigate the relationship between ACEI/ARB therapy and long-term prognosis among CAD patients with advanced CKD. CAD patients with advanced CKD were included in five hospitals. Advanced CKD was defined as estimated glomerular filtration rate (eGFR)<30 ml/min per 1.73 m2. Cox regression models and competing risk Fine and Gray models were used to examine the relationship between ACEI/ARB therapy and all-cause and cardiovascular death, respectively. Of 2527 patients, 47.6% population of our cohort was discharged on ACEI/ARB. The overall all-cause and cardiovascular mortality were 38.6% and 24.7%, respectively. Multivariate Cox regression analyses indicated that ACEI/ARB therapy was found to be associated with lower rates of both all-cause mortality (hazard ratio (HR)=0.836, 95% confidence interval (CI): 0.738-0.948, p = 0.005) and cardiovascular mortality (HR = 0.817, 95%CI: 0.699-0.956, p = 0.011). In the propensity-matched cohort, the survival benefit was consistent, and significantly better survival was observed for all-cause mortality (HR = 0.856, 95%CI: 0.752-0.974, p = 0.019) and cardiovascular mortality (HR = 0.830, 95%CI: 0.707-0.974, p = 0.023) among patients treated with ACEI/ARB. ACEI/ARB therapy showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up, which manifested that strategies to maintain ACEI/ARB treatment may improve clinical outcomes among these high-risk populations.

Impact of Adherence to Beta-Blockers in Patients With All-Comers ST-Segment Elevation Myocardial Infarction and According to Left Ventricular Ejection Fraction at Discharge: Results From the Real-World Registry FAST-STEMI.

Beta-blockers are a crucial part of post-myocardial infarction (MI) pharmacological therapy. Recent studies have raised questions about their efficacy in patients without reduced left ventricular ejection fraction (LVEF). This study aims to assess adherence to beta-blockers after discharge for ST-segment elevation myocardial infarction (STEMI) and the impact of adherence on outcomes based on LVEF at discharge. The retrospective registry FAST-STEMI evaluated real-world adherence to main cardiovascular drugs in patients with STEMI between 2012 and 2017 by comparing purchased tablets with expected ones at 1 year through pharmacy registries. Optimal adherence was defined as ≥80%. Primary outcomes included all-cause and cardiovascular death while secondary outcomes were MI, major/minor bleeding events, and ischemic stroke. The study included 4688 patients discharged on beta-blockers. The mean age was 64 ± 12.3 years, 76% were male, and the mean LVEF was 49.2 ± 8.8%. The mean adherence at 1 year was 87.1%. Optimal adherence was associated with lower all-cause (adjusted hazard ratio, 0.62, 95% confidence interval, 0.41-0.92, P : 0.02) and cardiovascular (adjusted hazards ratio, 0.55, 95% confidence interval, 0.26-0.98, P : 0.043) mortality. In patients with LVEF ≤40%, optimal adherence was linked to reduced all-cause and cardiovascular mortality, but this was not found in patients with either preserved or mildly reduced LVEF. Predictors of cardiovascular mortality included older age, chronic kidney disease, male gender, and atrial fibrillation. Optimal adherence to beta-blocker therapy in patients with all-comers STEMI reduced all-cause and cardiovascular mortality at 1 year; once stratified by LVEF, this effect was confirmed only in patients with reduced LVEF (<40%) at hospital discharge. Impact of adherence to beta-blockers in all-comers STEMI patients and according to LVEF at discharge: results from the real-world registry FAST-STEMI.

Serum uric acid, renal function and prognosis in patients with chronic heart failure and reduced ejection fraction. Insights from the Italian network on heart failure.

The role of hyperuricemia on short-term clinical prognosis in outpatients with heart failure and reduced ejection fraction (HFrEF) has few investigations and inconclusive results. We evaluated the prognostic impact of serum uric acid (SUA) on short-term clinical outcome among ambulatory patients with chronic HFrEF enrolled in a nationwide cardiology registry, stratified by the presence of chronic renal dysfunction (CKD). 2246 outpatients with LVEF ≤40 %, vital status at 1-year follow-up known, and with SUA and creatinine available were stratified accordingly to SUA tertiles (≤5.6 5.7-7.3, >7.3 mg/dl) and by CKD as defined by an estimated glomerular filtration rate < 60 ml/min/1.73m2. Patients in the 2nd and 3rd SUA tertile were older, more symptomatic (NYHA class III-IV), with a lower EF, higher creatinine and heart rate. They had more commonly atrial fibrillation and CKD. At 1-year follow-up, patients in the 2nd and 3rd SUA levels tertile had an increased risk of cardiovascular death and/or HF hospitalization than those in the first tertile (HR 1.72 95 % CI 1.26-2.35, and HR 2.20 95 % CI 1.63-2.97, respectively). After multivariable adjustment, SUA was no longer associated with adverse outcome in the overall cohort. When the multivariable analysis was separately performed in patients with or without CKD, SUA was independently associated with cardiovascular death/HF hospitalization (p = 0.02) only in the latter group. Mildly to moderately elevated SUA levels are associated to one-year survival in outpatients with HFrEF, but hyperuricemia resulted an independent marker of outcome only in patients without CKD.

Blood Pressure Predicted From Artificial Intelligence Analysis of Retinal Images Correlates With Future Cardiovascular Events

BackgroundHigh systolic blood pressure (SBP) is one of the leading modifiable risk factors for premature cardiovascular death. The retinal vasculature exhibits well-documented adaptations to high SBP and these vascular changes are known to correlate with atherosclerotic cardiovascular disease (ASCVD) events. ObjectivesThe purpose of this study was to determine whether using artificial intelligence (AI) to predict an individual’s SBP from retinal images would more accurately correlate with future ASCVD events compared to measured SBP. Methods95,665 macula-centered retinal images drawn from the 51,778 individuals in the UK Biobank who had not experienced an ASCVD event prior to retinal imaging were used. A deep-learning model was trained to predict an individual’s SBP. The correlation of subsequent ASCVD events with the AI-predicted SBP and the mean of the measured SBP acquired at the time of retinal imaging was determined and compared. ResultsThe overall ASCVD event rate observed was 3.4%. The correlation between SBP and future ASCVD events was significantly higher if the AI-predicted SBP was used compared to the measured SBP: 0.067 v 0.049, P = 0.008. Variability in measured SBP in UK Biobank was present (mean absolute difference = 8.2 mm Hg), which impacted the 10-year ASCVD risk score in 6% of the participants. ConclusionsWith the variability and challenges of real-world SBP measurement, AI analysis of retinal images may provide a more reliable and accurate biomarker for predicting future ASCVD events than traditionally measured SBP.

Results of Five-Year Outpatient Follow-Up of Patients With Heart Failure in a Specialized Center.

Aim To evaluate the risks of all-cause death (ACD), cardiovascular death (CVD), death from recurrent acute decompensated heart failure (ADHF), and a composite index of CVD and death from recurrent ADHF in patients with chronic heart failure (CHF) after the first hospitalization for ADHF during a long-term, five-year follow-up in the conditions of specialized medical care and in real clinical practice.Material and methods This prospective cohort observational study included 942 patients after ADHF. Group 1 consisted of 510 patients who continued the outpatient follow-up at a specialized center for the treatment of CHF (cCHF); group 2 consisted of 432 patients followed up at outpatient and polyclinic institutions (OPI) at the place of residence. During the five-year follow-up, the causes of death were determined based on the medical records of inpatients, postmortem examinations, or the conclusion in the medical records of outpatients. Rates of ACD, CVD, death from recurrent ADHF, and the composite index (CVD and death from ADHF) were analyzed. Statistical analysis was performed with a R statistical package.Results ACD was 32.3% and 53.5% in groups 1 and 2, respectively (p&lt;0.001). Based on the results of Cox proportional hazards models, it was shown that the follow-up in group 1, regardless of other factors, was associated with a decrease in the ACD risk (HR 2.07; 95% CI 1.68-2.54; p&lt;0.001), CVD (HR 1.94; 95% CI 1.26-2.97; p=0.002), death from recurrent ADHF (HR 2.4; 95% CI 1.66-3.42; p&lt;0.001) and the composite mortality index (HR 2.2; 95% CI 1.65-2.85; p&lt;0.001) compared to group 2. The risks of death in CHF patients with moderately reduced left ventricular ejection fraction (LVEF) (HFmrEF) were consistent with the death rates in CHF patients with low LVEF (HFrEF) and were significantly higher than in CHF patients with preserved LVEF (HFpEF). The prognosis of life worsened with an increase in the Clinical Condition Assessment Scale score and age. The prognosis of life was better in women, as well as with higher values of systolic blood pressure (BP) and 6-minute walk test. In the structure of death in both groups, death from ADHF and sudden cardiac death (SCD) prevailed.Conclusion The absence of specialized follow-up at an outpatient CHF center increases the risks of ACD, CVD, death from recurrent ADHF, and the composite endpoint at a depth of five-year observation. The leading causes of death were recurrent ADHF and SCD.

Polygenic Prediction of Recurrent Events After Early-Onset Myocardial Infarction.

Myocardial infarction (MI) is a complex disease caused by both lifestyle and genetic factors. This study aims to investigate the predictive value of genetic risk, in addition to traditional cardiovascular risk factors, for recurrent events following early-onset MI. The Italian Genetic Study of Early-Onset Myocardial Infarction is a cohort study enrolling patients with MI before 45 years. Monogenic variants causing familial hypercholesterolemia were identified, and a coronary artery disease polygenic score (PGS) was calculated. Ten-fold cross-validated Cox proportional hazards models were fitted sequentially including all clinical variables, the PGS, and monogenic variants on the composite outcome of cardiovascular death, recurrent MI, stroke, or revascularization. During a 19.9-year follow-up, 847 (50.7%) patients experienced recurrent events. Each 1-SD higher PGS was associated with a 21% higher hazard of recurrent events (hazard ratio, 1.21 [95% CI, 1.13-1.31]; P=4.04×10-6). Except for secondary prevention, PGS was the strongest determinant of recurrent event risk (C index, 0.56 [95% CI, 0.54-0.58]) compared with clinical risk factors. Overall, predictive performance of clinical risk factors (C index, 0.69 [95% CI, 0.67-0.71]) improved after adding the PGS (C index, 0.69 [95% CI, 0.68-0.71]; P=0.006). When dividing the population by PGS quintiles, the highest fifth had a 57% higher hazard of recurrent events than the lowest fifth (hazard ratio, 1.57 [95% CI, 1.26-1.96]; P=5.57×10-5). When compared with other clinical risk factors, PGS was the strongest predictor of event recurrence among patients with an early-onset MI. Though the discriminative power of recurrent event prediction in this cohort was modest, the addition of PGS significantly improved discrimination.

Global, regional, and national mortality burden attributable to air pollution from landscape fires: a health impact assessment study

Landscape fire-sourced (LFS) air pollution is an increasing public health concern in the context of climate change. However, little is known about the attributable global, regional, and national mortality burden related to LFS air pollution. We calculated country-specific population-weighted average daily and annual LFS fine particulate matter (PM2·5) and surface ozone (O3) during 2000-19 from a validated dataset. We obtained the relative risks (RRs) for both short-term and long-term impact of LFS PM2·5 and O3 on all-cause, cardiovascular, and respiratory mortality. The short-term RRs were pooled from community-specific standard time-series regressions in 2267 communities across 59 countries or territories. The long-term RRs were obtained from published meta-analyses of cohort studies on all-source PM2·5 and O3. Annual mortality, population, and socio-demographic data for each country or territory were extracted from the Global Burden of Diseases Study 2019. These data were used to estimate country-specific annual deaths attributable to LFS air pollution using standard algorithms. Globally, 1·53 million all-cause deaths per year (95% empirical confidence interval [eCI] 1·24-1·82) were attributable to LFS air pollution during 2000-19, including 0·45 million (0·32-0·57) cardiovascular deaths and 0·22 million respiratory deaths (0·08-0·35). LFS PM2·5 and O3 contributed to 77·6% and 22·4% of the total attributable deaths, respectively. Over 90% of all attributable deaths were in low-income and middle-income countries, particularly in sub-Saharan Africa (606 769 million deaths per year), southeast Asia (206 817 million deaths), south Asia (170 762 million deaths), and east Asia (147 291 million deaths). The global cardiovascular attributable deaths saw an average 1·67% increase per year (ptrend <0·001), although the trends for all-cause and respiratory attributable deaths were not statistically significant. The five countries with the largest all-cause attributable deaths were China, the Democratic Republic of the Congo, India, Indonesia, and Nigeria, although the order changed in the second decade. The leading countries with the greatest attributable mortality rates (AMRs) were all in sub-Saharan Africa, despite decreasing trends from 2000 to 2019. North and central America, and countries surrounding the Mediterranean, showed increasing trends of all-cause, cardiovascular, and respiratory AMRs. Increasing cardiovascular AMR was also observed in southeast Asia, south Asia, and east Asia. In 2019, the AMRs in low-income countries remained four times those in high-income countries, though this had reduced from nine times in 2000. AMRs negatively correlated with a country-specific socio-demographic index (Spearman correlation coefficients r around -0·60). LFS air pollution induced a substantial global mortality burden, with notable geographical and socioeconomic disparities. Urgent actions are required to address such substantial health impact and the associated environmental injustice in a warming climate. Australian Research Council, Australian National Health and Medical Research Council.

Incidence, progression, and outcomes of heart failure with improved ejection fraction: The added value of longitudinally assessed ejection fraction

BackgroundThe revised universal definition of heart failure (HF) established a standardized definition for HF with improved ejection fraction (HFimpEF) and emphasized the importance of longitudinally assessing left ventricular EF (LVEF). We aim to investigate the incidence, disease progression, and clinical outcomes of HFimpEF in a longitudinal cohort of hospitalized HF patients. MethodsWe retrospectively included HF patients with baseline LVEF ≤40 % and satisfactory echocardiographic follow-ups. HFimpEF was defined as a ≥ 10-point increase in LVEF to >40 %. Transient HFimpEF was defined as a recurrent LVEF ≤40 % after achieving HFimpEF. Clinical outcomes were all-cause death, cardiovascular death, and HF rehospitalization. ResultsDuring a median follow-up of 47.9 months, 517 of 923 patients met HFimpEF criteria; 65.0 % HFimpEF cases occurred within 12 months. HFimpEF patients had lower risks of all-cause death (hazard ratio [HR] = 0.16, P < 0.001), cardiovascular death (HR = 0.19, P < 0.001), and HF rehospitalization (HR = 0.39, P < 0.001). However, 160 HFimpEF patients experienced LVEF worsening during follow-up; their risks for adverse events were higher (HR = 1.89 for all-cause death, HR = 2.13 for cardiovascular death, HR = 2.13 for HF rehospitalization, P < 0.05 for all) compared to persistent HFimpEF patients, and their capability of LVEF re-improvement was diminished. An inverted U-shaped LVEF profile for HFimpEF—characterized by a slow, modest increase followed by a decline—portended a higher mortality risk. ConclusionsHFimpEF was observed in 56.0 % of HF patients. Longitudinally assessing LVEF helps identify HFimpEF patients and facilitates disease progression monitoring and risk stratification.

Albiglutide and atrial fibrillation in patients with type 2 diabetes and established cardiovascular disease - insights from the Harmony Outcomes trial.

Atrial fibrillation and flutter (AF) are common in patients with type 2 diabetes and are associated with worse outcomes. Harmony Outcomes was a multicenter, event-driven, double-blind, placebo-controlled trial comparing the effects of albiglutide, a glucagon-like peptide-1 (GLP1) receptor agonist, with placebo on a composite of major adverse cardiac events (MACE; non-fatal myocardial infarction; non-fatal stroke and cardiovascular death) in 9,463 patients aged >40years with type-2 diabetes and established cardiovascular disease. Herein, the cardiovascular effects of albiglutide in patients with and without AF, as well as the effects on AF events during follow-up, were analyzed. Patients with a history of AF (8.9%) exhibited a higher event rate for the primary composite MACE endpoint during 1.6 years of follow-up (12.7 vs. 6.3 events/100 person-years, adjusted hazard ratio (aHR)1.41 (95% Confidence Interval (CI)1.14-1.74, p=0.001). Treatment with albiglutide reduced the occurrence of the primary endpoint irrespective of history of AF at baseline (history of AF: aHR0.83 (0.58-1.19), no history of AF: aHR0.77 (0.66-0.90); pinteraction=0.71). During follow-up, 239 patients (2.5%) experienced an AF event. Overall, Albiglutide was associated with numerically fewer AF events (108 vs 131; HR 0.82 (0.63-1.06, p=0.12), irrespective of baseline history of AF (pinteraction=0.92). In patients with type 2 diabetes, treatment with albiglutide, compared to placebo, reduced the risk of cardiovascular events irrespective of history of AF. Further, albiglutide treatment did not increase AF adverse events but was associated with a trend to a lower rate of AF events during follow-up without reaching statistical significance.