Lower Mortality Risk Research Articles

Time in target range for systolic blood pressure and glucose with cardiovascular disease and all-cause mortality risks.

Evidence on the combined effect of time in the target range (TTR) for systolic blood pressure (SBP) and fasting blood glucose (FBG) in real-world settings was scarce. We aimed to evaluate the separate and combined effects of SBP TTR and FBG TTR on cardiovascular disease (CVD) and all-cause mortality risks among participants with comorbidity of hypertension and diabetes. The data was derived from the Kailuan study. The target ranges for SBP and FBG were set as 110-140 mmHg and 3.9-7.0 mmol/L, and linear interpolation to calculate TTR. Cox proportional hazard regression models were used to estimate the separate and combined effects of SBP TTR and FBG TTR on CVD and all-cause mortality risks. We included 11,899 participants with hypertension and diabetes comorbidity whose mean age was 54.52 ± 10.36 years, and 9,873 (83.00%) were male. After a follow-up of 6.67 years, 1,381 cases of CVD and 2,148 cases of all-cause mortality were documented. In the fully adjusted model, compared with the participants with both SBP TTR and FBG TTR lower than 25%, participants with both greater SBP TTR and FBG TTR had the lowest risks of CVD (HR: 0.53; 95%CI: 0.57-0.78) and mortality (HR: 0.59; 95%CI: 0.47-0.74). Per 1 SD increase in SBP TTR was associated with a 14% reduction in CVD risk (HR, 0.86; 95% CI, 0.80-0.92) and a 10% reduction in mortality risk (HR, 0.90; 95% CI, 0.85-0.95), all significant results were maintained in the FBG TTR analyses. Both higher SBP TTR and FBG TTR were associated with lower risks of CVD and all-cause mortality in participants with comorbidity of hypertension and diabetes. Simultaneous control of SBP and FBG within the target ranges is a beneficial strategy for CVD prevention.

Exploring the impact of polychlorinated biphenyls on comorbidity and potential mitigation strategies.

Polychlorinated Biphenyls (PCBs) persist in the environment and accumulate in humans. Currently, there is a lack of understanding about the overall impact of PCBs on human health, and effective interventions for exposed populations are insufficient. Our study aimed to assess the impact of PCBs on various diseases and mortality risks using data from the National Health and Nutrition Examination Survey, while proposing lifestyle adjustments, particularly dietary modifications, to mitigate mortality risk. Statistical analyses employed principal component analysis, multifactorial logistic regression, multifactorial Cox regression, comorbidity network analysis, and machine learning prediction models. Results indicated significant associations between 7 types of PCBs and 12 diseases (p < 0.05), with 6 diseases showing significant positive correlations (OR > 1, p < 0.05), along with listing the 25 most relevant diseases, such as asthma and chronic bronchitis (OR [95% CI] = 5.85 [4.37, 7.83], p < 0.0001), arthritis and osteoporosis (OR [95% CI] = 6.27 [5.23, 7.55], p < 0.0001). This suggested that PCBs may be intimately involved in the development and progression of multiple diseases. By constructing multidimensional machine learning models and conducting multiple iterations for precision and error measurement, PCBs may have the potential to become specific biomarkers for certain diseases in the future. Building upon this, we further suggested that controlling dietary intake to reduce dietary inflammatory index (DII) could lower mortality and disease risks. While PCBs were independent risk factors for mortality, substantial evidence suggested that adjusting DII might mitigate the adverse effects of PCBs to some extent. Further physiological mechanisms require deeper exploration through additional research.

Association of postoperative opioid type with mortality and readmission rates: multicentre retrospective cohort study.

Opioid treatment in postoperative pain management is crucial, but the impact of administration practices on outcomes is unclear. The hypothesis was that prescription trends remained stable over recent years, and that no difference in mortality and readmission risks is associated with prescription strategies. Electronic health records of surgical episodes in the Capital and Zealand Regions of Denmark from 2017 to 2021 were analysed. All opioids administered during postoperative admission were converted to oral morphine equivalents (OMEQs) and an average daily dose per patient was calculated. The opioid administered in the highest OMEQ dosages is considered the primary opioid strategy for the surgical case. Administration trends were analysed through linear regression, and Cox regression was used to calculate hazard ratios to assess dominant opioid strategies' association with 90-day mortality and readmission rates while controlling for confounders. A total of 183 317 patients met the inclusion criteria. Prescription trends remained steady during the study period. Multivariable analysis revealed increased readmission risk (HR 1.18, P < 0.001) of tramadol and tapentadol compared to morphine. They exhibited decreased 90-day mortality risk (HR 0.63, P < 0.001). Oxycodone had similar readmission risk (HR 1.009, P = 0.24) but lower 90-day mortality risk (HR 0.68, P < 0.001). Postoperative in-hospital opioid administration remained stable from 2017 to 2021. Tramadol/tapentadol had a higher risk of readmission but lower mortality risk. Oxycodone had comparable readmission but reduced mortality risk. This study provides a framework for future clinical trials assessing this potential impact of opioids in a targeted manner.

Impact of skilled nursing facility quality on Medicare beneficiaries with dementia: Evidence from vacancies.

People living with dementia are less likely to be admitted to high-rated nursing homes than people without dementia, despite their increased care needs. We investigated the effect of admission to nursing homes with higher staffing ratings on adverse outcomes for individuals with and without dementia post-hospitalization. Among Traditional Medicare beneficiaries discharged to nursing homes between 2011 and 2017, we examined the relationship between facility staffing star-ratings and short-term readmission and mortality using an instrumental variables approach to account for selection bias. The instrumental variables were the number of nearby vacant beds in high-rated facilities. Admission to a higher-rated nursing home lowered post-discharge mortality risk at 90 days and reduced 30- and 90-day readmission. Point estimates were larger for people with dementia. Findings underscore the need for enhancing direct care staffing in nursing homes and addressing access disparities, particularly for individuals with dementia who benefit significantly from high-quality care. We assessed how admission to nursing homes with higher staffing ratings impacted outcomes for individuals with and without dementia by exploiting variation in local bed vacancies as a source of quasi-random assignment. For both persons with and without dementia, adjusted short-term mortality and readmission rates were lower among those discharged to nursing homes with higher staffing ratings. Effects were larger for persons with dementia, indicating welfare loss from inequitable access to higher-rated nursing homes. Increasing staffing in nursing homes and reducing disparities for persons with dementia is essential for enhancing both equity and value.

Utility of venoarterial extracorporeal membrane oxygenation in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Background Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) continues to portend poor clinical prognosis and remains a major cause of morbidity and mortality. Although venoarterial (VA) extracorporeal membrane oxygenation (ECMO) is frequently used in the treatment of AMI-CS, studies evaluating its benefit compared to percutaneous ventricular assist devices (pVAD) or standard medical therapy in this patient population have yielded conflicting results. Purpose The goal of this meta-analysis is to evaluate the use of ECMO compared to either pVAD or medical therapy with or without intra-aortic balloon counterpulsation (IABP) in patients presenting with AMI-CS. Methods A database search was performed for studies reporting on the association of ECMO compared to pVAD or medical therapy with or without IABP with clinical outcomes in patients with AMI-CS. The endpoints of interest were 30-day all-cause mortality and long term all-cause mortality. The databases searched included Pubmed, Web of Science, and Embase. The search was not restricted by time or publication status. Registry studies were excluded from this analysis. Results A total of 8 studies with 937 participants (447 treated with ECMO, 243 treated with pVAD, 247 treated with medical therapy with or without IABP) met inclusion criteria. Mean age was 63 years old, 80.5% were men, mean left ventricular ejection fraction was 26%, mean follow-up was 6.3 months (ranging 1-12 months). Treatment of AMI-CS patients with ECMO was not associated with lower risk of 30-day all-cause mortality compared to pVAD or standard medical therapy with or without IABP placement (OR 1.29, 95% CI 0.87-1.90; p=0.21; OR 0.58, 95% CI 0.25-1.35; p=0.13). Heterogenetic was low to moderate for each subgroup. Test for subgroup differences did not demonstrate statistically significant differences in the results for pVAD and for standard medical therapy with or without IABP (p=0.10, I2=64.1%). Compared to pVAD, ECMO was not associated lower risk of long-term mortality (OR 1.27, 95% CI 0.85-1.90; p=0.24). The heterogeneity for this analysis was low (I2=0%). Conclusion In patients presenting with AMI-CS, use of VA-ECMO is not associated with lower risk of mortality compared to pVAD or standard medical therapy with or without IABP placement. The risks and benefits of ECMO should be carefully considered compared to other forms of temporary mechanical circulatory support.Figure 1

Percutaneous mechanical circulatory support versus intraaortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Background Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is a disease process associated with significantly poor clinical prognosis, placing patients at increased risk for morbidity and mortality. Currently, the optimal choice for temporary mechanical circulatory support remains unclear, with studies evaluating use of percutaneous ventricular assist devices (pVAD) yielding conflicting results. Purpose The goal of this meta-analysis is to evaluate the efficacy of pVAD compared to intra-aortic balloon counterpulsation (IABP) in patients presenting with AMI-CS. Methods A database search was performed for studies reporting on the association of pVAD compared to IABP with clinical outcomes in patients with AMI-CS. The primary endpoint of interest was 30-day all-cause mortality. Secondary endpoints included cardiovascular (CV) mortality, and recurrence of AMI. The databases searched included Pubmed, Web of Science, and Embase. The search was not restricted by time or publication status. Registry studies were excluded from this analysis. Subgroup analysis was performed separating randomized controlled trials from retrospective cohort studies. Results A total of 8 studies with 651 participants (322 treated with pVAD, 329 treated with IABP) met inclusion criteria. Mean age was 65 years old, 73.9% were men, mean left ventricular ejection fraction was 28%, mean follow-up was 9.8 months (ranging 1-66 months). Treatment of AMI-CS patients with pVAD was not associated with lower risk of 30-day all-cause mortality compared to IABP (OR 0.90, 95% CI 0.63-1.27; p=0.55). Heterogeneity was low for the RCT subgroup and moderate for the cohort study subgroup (I2=0%; I2=48%). Use of pVAD in patients with AMI-CS was associated with a non-statistically significant trend toward lower CV mortality compared to IABP (OR 0.53, 95% CI 0.29-0.99; p=0.05). The heterogeneity was low (I2=0%). Use of pVAD was not associated with significantly lower risk of recurrent AMI (OR 0.62, 95% CI 0.22-1.74; p=0.37). Heterogeneity was low for this analysis (I2=0%). Test for subgroup differences was not statistically significant for any of the above analyses. Conclusion In patients presenting with AMI-CS, use of pVAD compared to IABP is not associated with lower risk of all-cause mortality or recurrent AMI. However given the apparent trend toward lower risk of CV mortality in patients treated with pVAD, additional high-quality prospective studies are required.Figure 1

Independent associations of educational attainment and its joint associations with LE8 score for risk of cardiovascular disease incidence and mortality among Chinese people

Abstract Background/Introduction Educational attainment is a social determinant of health. Quantifying its associations with risk of cardiovascular disease (CVD) incidence and mortality has public health importance. Recently, the American Heart Association introduced the Life’s Essential 8 (LE8) score to evaluate CVD risk. However, it remains unclear how educational attainment and the LE8 score interact in their joint associations with CVD and mortality. Purpose To examine the associations of educational level with the incidence of CVD, including coronary heart disease (CHD) and stroke, and total mortality. Also, we examined the joint associations of educational level and the LE8 score with CVD incidence and total mortality. Methods We prospectively followed 91,744 Chinese adults from the Kailuan Study (2006-2021), who were free of CVD at baseline. Information on educational level, diet, lifestyle, and health conditions was collected every 2 years. LE8 score was calculated based on eight components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. We used time-dependent Cox models to assess the associations of educational level with the outcomes as well as the joint associations of educational level and LE8 score, with adjustments for demographics, dietary and lifestyle factors, and medical history. Results During a mean follow-up of 13.1 years, there were 12,916 incident CVD cases and 13,090 deaths. Compared with the participants who only received illiteracy or elementary education, those who received high school education and above had a lower risk of CVD incidence (HR = 0.82, 95% CI = 0.76, 0.88), stroke incidence (0.72, (0.66, 0.79)), and total mortality (0.73, (0.68, 0.77)). Educational level was not associated with risk of CHD. Furthermore, significant additive interactions between educational attainment and LE8 score on the risk of CVD and mortality were observed (all p values for additive interactions &amp;lt;0.01). Compared with the participants who only received illiteracy or elementary education and had a low LE8 score, those who only received illiteracy or elementary education but had a high LE8 score still had a 27%-47% lower risk of CVD and total mortality, while those who received high school education and above and had a high LE8 score had a 51%-74% lower risk of CVD and total mortality. Conclusions Higher educational level was associated with a lower risk of CVD and mortality. These inverse associations were most apparent among participants with both a high educational level and a high LE8 score, while the participants with a low educational level but with a high LE8 score still had a significantly lower risk. These findings highlight the importance of improvement in educational attainment in preventing CVD events and deaths, and suggest that CVD events and deaths attributable to lower levels of education may be reduced by improving LE8 score.

Association between PCSK9 inhibitor with cause-specific morality amongst cancer survivors

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor has emerged as a novel pharmacotherapy for dyslipidemia and been shown to be effective in reducing the risks of atherosclerotic cardiovascular diseases. PCSK9 is aberrantly expressed in a broad spectrum of cancers and has been demonstrated to contribute to cancer prognosis. However, no prior study has investigated the associations between PCSK9 inhibitors (PCSK9i) with cardiovascular and cancer mortality amongst cancer survivors. Purpose This study investigated the effects of PCSK9i on cause-specific mortality amongst cancer survivors. Methods This retrospective study used data from the Tianjin Coronary Artery Disease Cohort, which included medical data from 71 secondary or tertiary hospitals in Tianjin, China. Adult patients with coronary artery disease (CAD) diagnosed with incident cancer between 2017 and 2023 were enrolled in this study. Propensity score matching with a 1:3 ratio for PCSK9i users versus non-users was performed. The primary outcomes included all-cause mortality, cardiovascular mortality, and cancer mortality. Multivariable Cox regression was used to test associations between PCSK9i with outcomes, adjusting for age, gender, cardiovascular and non-cardiovascular comorbidities, lipid-lowing agents and other medication use, lipid level, as well as cancer characteristics. Multivariable competing risk analysis was used as sensitivity analysis. Results A total of 62,341 incident cancer patients were identified. After matching, 424 PCSK9i users and 1,272 non-users were included in this study. During a median follow-up of 1,009 days, 315 patients died, among which 98 died due to cardiovascular cause, 146 died due to cancer cause. Compared to non-users, cancer patients treated with PCSK9i presented with significantly lower risk of all-cause mortality (hazard ratio [HR], 0.33; 95% confidence interval [CI] 0.23-0.47; p &amp;lt;0.001), after adjusting for potential confounders. In addition, PCSK9i therapy was associated with a 63% lower risk of cardiovascular mortality (HR, 0.37; 95%CI 0.20-0.69; p=0.002) and a 75% lower risk of cancer-related mortality (HR, 0.25; 95%CI 0.14-0.45; p&amp;lt;0.001), in relation to non-PCSK9i group. Sensitivity analysis using multivariable competing risk model also suggested a significant association between PCSK9i treatment with reduced risk of cardiovascular mortality (HR, 0.41; 95%CI 0.22-0.76; p=0.005) and cancer mortality (HR, 0.26; 95%CI 0.15-0.48; p&amp;lt;0.001) among cancer survivors. Conclusion The use of PCSK9i was associated lower risks of all-cause, cardiovascular-related, and cancer-related mortality amongst cancer survivors. These findings potentially indicate benefits of PCSK9i beyond adverse cardiovascular events related to atherosclerosis.

LE8 score in relation to cardiovascular disease and mortality in individuals with diabetes

Abstract Background Evidence regarding the potential health effects of Life’s Essential 8 (LE8) score among individuals with type 2 diabetes (T2D) is limited. Purpose We aimed to examine the associations of LE8 score with risk of cardiovascular disease (CVD) and mortality, among individuals with T2D. Methods We prospectively followed 19,915 Chinese participants with T2D at baseline or diagnosed during follow-up (Kailuan Study: 2006-2020), who were free of CVD at diagnosis of diabetes. Diet, lifestyle, and health conditions were repeatedly assessed every 2 years. The LE8 score (range, 0-100), was calculated based on 8 components: diet quality, physical activity, smoking status, sleep health, BMI, blood lipids, blood glucose, and blood pressure. We used time-varying cox models to model the associations. Results During a median follow-up of 11.5 years in participants with T2D, there were 3,295 incident CVD cases and 3,123 deaths. Higher LE8 score was associated with lower risk of CVD incidence and total mortality among participants with diabetes. The multivariate-adjusted hazard ratios and 95%CIs for the highest quintile of LE8 score compared with the lowest quintile were 0.56 (0.53, 0.59) for CVD incidence, 0.57 (0.53, 0.62) for heart disease incidence, 0.53 (0.49, 0.57) for stroke incidence, and 0.73 (0.69, 0.78) for total mortality (all p trend&amp;lt;0.001). Furthermore, compared with participants with stable or decreased LE8 score after diabetes diagnosis, those with increased LE8 score had 17%-42% lower risk of CVD incidence, heart disease incidence, stroke incidence, and total mortality. These associations persisted in subgroup analysis stratified by age, sex, BMI, smoking status, alcohol intake, family history of diabetes and CVD, and follow-up time. Conclusions Higher LE8 score was associated with a substantially lower risk of CVD incidence and total mortality among adults with T2D. These findings further support the tremendous benefit of adhering to a high CVH, defined as the LE8 in reducing the subsequent burden of cardiovascular complications and improving overall health in individuals with T2D.Main TableMain Figure

Relative effectiveness of high-dose versus standard-dose quadrivalent influenza vaccine against hospitalizations and mortality according to frailty score: a post-hoc analysis of the DANFLU-1 trial

Abstract Background Frailty is a major risk factor for adverse cardiovascular events. Influenza vaccination has been shown to protect against cardiovascular fatal and nonfatal events. However, limited data exist on the added benefit of high-dose versus standard-dose influenza vaccination according to frailty status. Purpose We sought to assess the relative effectiveness of high-dose (QIV-HD) versus standard-dose (QIV-SD) quadrivalent influenza vaccination according to frailty status in elderly individuals. Methods This is a post-hoc analysis of the randomized controlled feasibility trial of QIV-HD versus QIV-SD conducted during the 2021–2022 influenza season in adults aged 65–79 years. We assessed the following prespecified outcomes: hospitalizations for pneumonia or influenza, cardio-respiratory hospitalizations, cardiovascular hospitalizations, all-cause hospitalizations and all-cause mortality. Level of frailty was defined according to the Hospital Frailty Risk Score based on ICD-10 codes for relevant comorbidities any time prior to vaccination. We divided the participants into two categories according to Frailty Score (FS): low frailty (0-4 points) and intermediate or high frailty (≥5 points). We analyzed outcomes as time to first event using Cox proportional hazards regression. Results Among 12,473 randomly assigned participants to QIV-HD versus QIV-SD (mean age 71.7 years, 47.1% female), 10,711 (85.9%) were categorized as having low frailty and 1,762 (14.1%) had intermediate or high frailty. In total, 38 individuals were hospitalized for pneumonia or influenza during follow-up, 219 were hospitalized for cardiorespiratory illness, 1055 were hospitalized due to any cause and 62 died during follow-up. FS significantly modified the effect of QIV-HD versus QIV-SD for all-cause mortality (P for interaction 0.02). In participants with low frailty, QIV-HD was associated with a lower risk of all-cause mortality (Figure 1: HR 0.26, 95% CI 0.13 to 0.55), whereas there was no evidence of effect among those with intermediate or high frailty (HR 1.68, 95% CI 0.66 to 4.26). QIV-HD versus QIV-SD was associated with a lower incidence of hospitalizations for pneumonia and influenza, this effect was consistent regardless of frailty status (P for interaction 0.88). QIV-HD was not associated with a significantly lower incidence of hospitalizations due to cardiovascular, cardiorespiratory or respiratory disease or any cause regardless of frailty status. Conclusions In this post-hoc analysis of a large-scale pragmatic trial, QIV-HD was similarly associated with a lower incidence of hospitalizations for pneumonia and influenza among older adults irrespective of frailty status. The potential benefit of QIV-HD versus QIV-SD may therefore be applicable regardless of frailty status. However, our results suggest that QIV-HD is associated with a lower risk of all-cause mortality among adults with low frailty only.Figure 1.

The effect of Glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in type 2 diabetes mellitus patients with coronary artery disease

Abstract Background Cardiovascular disease is the primary cause of mortality in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials (RCT) have shown that Glucagon-like peptide-1 receptor agonists (GLP-1RA) improve cardiovascular outcomes in T2DM patients, with greater therapeutic benefits observed in patients with established atherosclerotic cardiovascular disease. However, the effect of GLP1-RA therapy on cardiovascular outcomes has been inconsistent and the RCT have not been sufficiently powered to examine the effect of GLP1-RA on mortality or their therapeutic effect in different subgroups of T2DM patients. Purpose This study aimed to examine the effect of GLP1-RA therapy on cardiovascular outcomes and mortality in a real-world cohort of T2DM patients with coronary artery disease (CAD). Methods This study included T2DM patients with CAD who were treated with metformin at a daily dose of ≥ 1g for a period of ≥ 180 days. CAD was defined as ≥ 50% luminal stenosis in any coronary artery segment according to a nationwide angiography and angioplasty registry. We performed sequential emulated target trials at monthly intervals between January 1, 2013 and December 31, 2020 to examine the effect of GLP1-RA therapy on major adverse cardiovascular outcomes (MACE), a composite of myocardial infarction, ischemic stroke and all-cause mortality. Secondary outcomes included the individual components of MACE. Marginal structural models were used to compute pooled effect estimates. This was an intention-to-treat analysis with 5 years of follow-up for each emulated target trial. Inverse probability of treatment weighting was used to adjust for confounding due to differences in patient demographics at baseline. Results This study consisted of 26,746 individuals who were treated with GLP1-RA and 74,638 controls. The 5-year cumulative risk of MACE was 27.7 % in the GLP1-RA group and 32.7 % in the control group (risk ratio 0.85 [95% confidence interval 0.82 – 0.88]). GLP1-RA therapy was associated with a lower risk of all-cause mortality (risk ratio 0.76 [95% confidence interval 0.72 – 0.79]) and myocardial infarction (risk ratio 0.95 [95% confidence interval 0.89 – 1.00]). We found little or no effect of GLP1-RA therapy on the risk of ischemic stroke (risk ratio 1.13 [95% confidence interval 0.97 – 1.27]). Conclusions In this large real-world cohort of T2DM patients with established CAD, we observed that GLP1-RA therapy was associated with a lower risk of MACE, myocardial infarction and all-cause mortality.

A larger reduction of spatial mean QRS-T angle during cardiac resynchronisation therapy is associated with a lower risk of mortality and heart failure hospitalisation

Abstract Background Predicting clinical outcome in heart failure patients undergoing cardiac resynchronization therapy (CRT) remains challenging, necessitating improved risk stratification for CRT recipients. Previous studies have shown an association between large spatial peak and mean QRS-T angles and cardiovascular disease. Little is known, however, about their relation to clinical outcome following CRT. Purpose To investigate the association between spatial peak and mean QRS-T angles and long-term clinical outcome following CRT initiation. Methods All patients with native LBBB receiving CRT at a large-volume tertiary care center between 2015 and 2020 were retrospectively evaluated. Spatial peak and mean QRS-T angles were derived from digital pre- and post-CRT 12-lead ECGs that were processed using Glasgow algorithm and Kors’ regression transformation. The QRS-T angles and their change after CRT were analyzed in relation to the primary composite endpoint of heart failure hospitalisation or all-cause mortality using Cox regression analysis adjusted for clinical covariates (age, gender, CRT-P or CRT-D, secondary ICD indication, ischemic etiology, NYHA class, LVEF, diabetes, atrial fibrillation, baseline QRS duration, NT-proBNP, and eGFR). Results The study group comprised 250 patients (a median age [Q1–Q3] of 72.2 years [64.5–76.3]; 22% female; 58% New York Heart Association (NYHA) class III-IV; LVEF 27% [22–30]) who were followed over a median follow-up time of 4.5 years [3.2–5.8] after CRT implantation. The median post-CRT spatial peak and mean QRS-angles were 142° [116–160] and 152° [127–166], and the median angle was decreased by 16° [-0.6–41] and 14° [-0.4–38], respectively. Both a larger post-CRT mean QRS-T angle (HR 1.20, 95%CI 1.08-1.33, p=&amp;lt;.001) and peak QRS-T angle (HR 1.08, 95%CI 1.01-1.17, p=0.046) were associated with the primary endpoint. A larger reduction of mean QRS-T angle, but not peak QRS-T angle, was associated with a risk reduction (HR 0.87, 95%CI 0.79-0.95, p&amp;lt;0.003). In Kaplan-Meier analysis, patients with a post-CRT mean QRS-T angle above median had a higher risk of reaching the endpoint (log-rank p=0.002, Figure 1). Conclusion Our results show that a larger magnitude of the post-CRT spatial peak and mean QRS-T angles, and a larger reduction of the latter, are associated with long-term heart failure hospitalisation and death. These findings suggest that spatial QRS-T angle may have a potential role in refined risk stratification of CRT patients.Figure 1.K-M curve spatial mean QRS-T

Heart failure burden among adults with congenital heart disease

Abstract Background Adult congenital heart disease (ACHD) is associated with high rates of healthcare utilization and mortality. Data on Heart failure (HF) burden among ACHD patients are limited. Purpose To study the association between HF and healthcare utilization and mortality among ACHD patients in the community. Methods The retrospective cohort study comprised 11,653≥ 18 year old ACHD patients insured by two large Israeli healthcare providers between January 2007 and December 2011. We used multivariable Cox proportional hazard and negative binomial models to study the associations of HF with mortality and healthcare utilization, respectively. Inverse treatment probability weighting accounted for drug indication. Results ACHD-HF patients (N=908; 7.8%) were older (median: 69 vs. 45 years), more likely men (53% vs. 45%), with complex congenital heart disease (14% vs. 4%), and higher comorbidity rates than ACHD patients without HF. HF was associated with higher healthcare utilization. Compared to patients without HF, ACHD-HF patients had higher adjusted relative rates (RR) of primary care (1.26, 95% confidence interval [CI]: 1.17-1.3), and cardiology clinic visits (1.9, 95% CI: 1.7-2.0), higher hospitalization rates (RR=2.0, 95% CI: 1.7-2.1), and higher risk of death (mortality hazard ratio [HR]: 1.9, 95% CI: 1.5-20.) over the study period. Among ACHD-HF patients, Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and diuretics were associated with a lower mortality risk (treated vs. untreated HR=0.56, 95% CI: 0.48-0.65; HR=0.7, 95% CI: 0.6-0.8; HR=0.84, 95% CI: 0.73-0.97; respectively). Conclusions HF presents a major burden on ACHD patients and health care systems. Drugs recommended to the general HF patient population are also associated with lower risk of hospitalization and mortality in ACHD patients. Clinical trials are needed to establish the benefit of HF pharmacotherapy in ACHD patients.Age adjusted ACHD patient survival by HF

Sex differences in clinical characteristics, phenotypes, management, and long-term outcomes of myocardial injury: an international cohort study

Abstract Background Several studies have demonstrated sex differences in patients presenting to the emergency department (ED) with myocardial infarction, heart failure or syncope. Whether sex-specific differences in chest pain patients with myocardial injury exist is unknown. Purpose To determine whether sex-specific differences in the clinical characteristics, phenotypes, management, and long-term outcomes of patients with myocardial injury exist. Methods Patients presenting to the ED with chest pain suggestive of MI were consecutively enrolled into a prospective multicenter international diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists, applying the fourth universal definition of myocardial infarction, using all available medical records, including serial hs-cTn and cardiac imaging. Follow-ups were performed at 3 months, 1-, 2- and 5-years. The primary outcome was 5-year all-cause mortality. Secondary outcomes included 5-year cardiovascular mortality and non-cardiovascular mortality. Multivariable flexible parametric (Royston-Parmar) models assuming proportional hazards were fitted. Models were adjusted for age, history of coronary artery disease, history of malignancy, diabetes, hypertension, smoking status, history of liver disease, and renal function. Results Among 8046 chest pain patients presenting to the ED, 1158 (14.4%) had myocardial injury, of which 358 (31%) were females and 800 (69%) males. Women were older (79 years, vs. 73 years), had fewer cardiovascular risk factors and comparable non-cardiovascular comorbidities except for lung disease which was more commonly found in men. Myocardial injury phenotypes varied between sexes (Figure). The most common phenotype in both sexes was heart failure, yet it was more common in men (37.2%) than in women (22.3%). The second most common phenotype in women was hypertension (15.4%) and arrhythmia (15.4 %), while in men was myocarditis (17.8 %), followed by arrhythmia (15.8%). Women underwent less invasive coronary angiography (19.8% vs 26.9%) or stress testing (12% vs 21.5%). In the angiographic findings, women presented more often with normal findings (30.4% vs. 19.6%) or mild CAD (20.3% vs. 11.2%) whereas men displayed more frequently 3-vessel disease (14.5% vs. 36.4%), Table. After adjusting for known confounders, women were associated with a lower 5-years risk for all-cause mortality (HR 0.69; 95%CI: 0.56–0.83) and cardiovascular mortality (HR 0.61; 95%CI: 0.46–0.79). No statistically significant difference in non-cardiovascular mortality risk was found (HR 0.79; 95%CI: 0.59-1.04). Conclusions Women presenting with chest pain to the ED and having myocardial injury were less likely than men to undergo coronary angiography or non-invasive cardiac imaging. Long-term risk for all-cause or cardiovascular mortality was lower for women compared to men.Myocardial Injury phenotypesPatient management

Low levels of apolipoprotein M are associated with increased risk of ventricular arrhythmias

Abstract Background Ventricular arrhythmia (VA) is a frequent cause of sudden cardiac death (SCD). Treatment to prevent SCD includes device therapy with implantable cardioverter defibrillator (ICD). Although the electrophysiology underlying VA have been described, the molecular understanding of VA risk remains unclear. Purpose To identify proteins that are associated with higher and lower risk of VA. Methods SMASH 1 Study was a prospective observational study of 490 patients treated with ICD. The plasma proteome was analyzed with the Olink Explore 384 Cardiometabolic platform at study inclusion, and patients were followed for mean 3.1± 0.7 years. VA events were defined as adjudicated ventricular fibrillation or sustained ventricular tachycardia registered from ICD recordings and clinical events were recorded from electronic health records. Protein concentrations were quantified relatively as normalized protein expression on a log2-transformed concentrations where a large number represents higher protein level in the sample. Results The mean age was 66±12 years, 83% were male and 51% had a primary prevention ICD-indication. Episode(s) of VA occurred in 137 patients (28%) during follow-up. In total, 353 distinct proteins were successfully analyzed in all patients. Among these, high B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels were associated with a higher risk of VA, while Apolipoprotein M (APOM) was the only protein significantly associated with a lower risk of VA after multiple testing using Benjamini-Hochberg correction (Figure, Panel A). After adjusting for age, sex, body mass index, coronary artery disease, heart failure, renal function, left ventricular ejection fraction and antiarrhythmic medication, only low APOM levels remained significantly associated with VA: HR 0.51 (95%CI 0.32-0.79] per log unit increase, p=0.003. Patients in the lowest quartile of APOM had a particularly high risk of incident VA: HR 2.26 (95%CI 1.60-3.19), p=3.61x10-6, compared to quartile 2-4 (Figure, Panel B). High APOM levels were also associated with a lower risk of HF hospitalizations (HR 0.25 [95%CI 0.16-0.40], p&amp;lt;0.001) and all-cause mortality (HR 0.36 [95%CI 0.22-0.60], p&amp;lt;0.001), and these associations remained significant in adjusted models. Conclusions Low levels of APOM are associated with a greater risk of incident VA, independently of established risk factors. Low APOM also predicted risk of HF hospitalizations and mortality in our cohort, which suggest protective cardiovascular effects of APOM. Figure: Association of individual proteomic measures with risk of ventricular arrhythmias (VA).A:Volcano plots of the associations of individual plasma proteins with incident VA. The dotted line represents the significance level at false discovery rate &amp;lt;0.05 and the red dots are significant proteins after multiple testing using Benjamini-Hochberg correction.B: Risk of VA by quartile of Apolipoprotein M.

Strike early-strike strong lipid-lowering strategy with PCSK9i in ACS patients. Real-world evidence from AT-TARGET-IT registry

Abstract Background/Introduction No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in real-world. Purpose This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. Methods The lipid control outcome was the percentage of patients reaching the LDL-C target of &amp;lt; 55 mg/dL at first lipid control. The clinical outcome was the incidence of composite major CV events (all cause death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization) during follow-up in relation to quartiles of LDL-C at first lipid control. Results We included 771 patients with ACS from AT-TARGET-IT registry, receiving PCSK9i prescription during hospitalization or at discharge. Median LDL-C was 137 mg/dL and decreased to 43 mg/dL at first lipid control. 527 (68.3%) patients achieved LDL-C target at the first lipid control at a median time of 37 days from hospitalization; of them, 404 (76.8%) were discharged on statin plus ezetimibe background therapy. Event curves through a median follow-up of 11 months across quartiles of LDL-C showed a stepwise lower risk of 4P-MACE, 3P-MACE, all-cause mortality, and ischemia-driven revascularization in lower quartile of LDL-C values at first lipid control (&amp;lt;23 mg/dL) and in patients reaching LDL-C &amp;lt;55 mg/dL. Conclusions Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk.

Infective endocarditis - characteristics and long-term outcomes in patients with congenital heart disease are distinct from those without congenital heart disease

Abstract Background Patients with congenital heart disease (CHD) form a high-risk niche among patients considered at high-risk of infective endocarditis (IE). Their life-long exposure to the risk of IE, starting from birth, necessitates a nuanced approach to both prevention and treatment strategies. However, comprehensive data from an unselected nationwide cohort, including children, are lacking. Purpose This study sets out to compare characteristics and associated outcomes among patients with IE with and without CHD. Methods Using nationwide registries, all Danish patients diagnosed with IE from 1977-2021 were identified and stratified on whether they had a diagnosis of CHD, regardless of its complexity. Characteristics prior to and during admission as well as associated outcomes (i.e., in-hospital mortality, 1-year mortality, and 10-year mortality, and IE recurrence) were compared between groups. Results In total, 14,040 patients were diagnosed with IE from 1977-2021 including 895 (6.4%) with a diagnosis of CHD. Patients with versus without CHD were significantly younger at time of IE diagnosis (median age 38.8 years [IQR 21.2-56.4 years] versus 70.7 years [IQR 58.8-78.9 years], Figure 1) and less comorbid. Patients with versus without CHD were hospitalized due to IE for a similar period of time but more often underwent cardiac surgery during admission (44.9% versus 21.3%). The IE-related bacteremia was significantly different between groups: the most common bacteriemia in relation to IE was Streptococci (29.9%) in patients with CHD and Staphylococcus Aureus (29.9%) in patients without CHD. Patients with CHD were associated with a significantly lower risk of in-hospital mortality (6.4% versus 19.8%), 1-year mortality (10.5% versus 32.4%) and 10-year mortality (21.3% versus 58.7%) compared with those without CHD. The 10-year incidence of IE recurrence was similar among groups (p-value 0.5). Conclusions Patients with CHD who develop IE are distinctive from patients with IE without CHD in terms of characteristics as well as long-term outcomes. Notably, our findings stress a key point: the majority of children and adolescents with IE have a CHD. These unselected findings should help guide future preventive strategies, diagnosis, and management.

Are migrant workers at greater risk of workplace deaths? A systematic review and meta-analysis

Abstract Background Globally, 170 million individuals migrate for work. Yet, evidence on their mortality risk remains unclear. Our aim was to synthesize global evidence on migrant worker mortality risk compared to local workers and to identify the multiple intersecting social determinants of mortality. Methods We conducted a systematic review of peer-reviewed literature which reported on mortality outcome of migrant workers. Studies published between 1 Jan 2000 to 17 Jan 2023 in English were searched in MEDLINE, Embase, PsycINFO, and Ovid Global Health. Meta-analysis using random effects model was used to calculate pooled estimates and narrative synthesis was used to develop a data-driven framework on intersectional social determinants. Results Out of 11,495 identified records, 44 were included, of which 11 were pooled in meta-analyses. The combined migrant worker death count was 44,338, with data from 16 countries, including migrants from agriculture, construction, and service industries. Compared to local workers, migrant workers had a higher risk of fatal occupational injury (pooled RR = 1.71, 95%CI: 1.22-2.38, I² = 99.4%), and a lower risk of all-cause mortality (pooled RR = 0.94, 95%CI: 0.88-0.99, I² = 90.7%). Key social determinants associated with increased mortality risk were either migration-related (e.g. lower language proficiency, undocumented status) or labour-related (e.g. precarious employment, labour migration policies) interacting over migrant workers’ life course. Conclusions As the largest evidence synthesis to date, these findings indicate that migrant workers have higher fatal occupational injury rates than local workers, indicating the need for tailored protections for migrant workers. These data confirm that the all-cause mortality advantage observed in migrant populations applies to the working population. Future interventions should be designed to address both migration- and labour-related determinants of migrant worker health. Key messages • Migrant workers have a higher risk of workplace fatality despite being generally healthier than local workers, explained by structural determinants such as precarious employment. • Future interventions must address migration- and labour-related social determinants of health at structural levels, such as extending labour protection laws to migrant workers.

Correlation between short-term quality of life improvement and clinical outcomes - a post-hoc ISCHEMIA trial analysis

Abstract Background Patients with symptomatic coronary artery disease (CAD) exhibit improvement in quality of life (QoL) after invasive management (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]). However, it is not clear how QoL improvements after intervention are related to clinical outcomes. Purpose Using the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) population, we sought to assess the relationship between short-term QoL improvement and long-term clinical outcomes. Methods All participants in the ISCHEMIA trial who were randomized to the invasive arm and who had QoL scores available were included in the analysis. QoL improvement was calculated using the difference between the Seattle Angina Questionnaire (SAQ) score at baseline and at six months regarding randomization. The primary outcome was the trial-defined composite outcome (cardiovascular death, myocardial infarction, cardiac arrest or hospitalization for unstable angina/heart failure) and all-cause death. The secondary outcome was all-cause mortality. Median follow-up was 3.3 years. Cox proportional hazards models included clinically relevant demographic and angiographic covariates. Results After the exclusion of the conservative treatment arm and patients without QoL follow-up or covariate data, 1,577 patients were selected for the final analysis (Fig.1). The median baseline SAQ score was 74 (interquartile range, IQR: 60-88), the change in score at six months was 14 (IQR: 2-26), and 76.1% of patients experienced improvement in QoL. Six-month QoL improvement was not associated with a lower risk of the primary outcome (hazard ratio [HR]: 0.961, 95% confidence interval [CI], 0.920-1.005, p=0.081 – Table 1), but was associated with all-cause mortality (HR: 0.919, 95% CI, 0.859-0.982, p=0.013 – Table 1). In this population, increased age (HR: 2.370, 95% CI, 1.710-3.287, p&amp;lt;0.001, per 10 years) was also associated with higher risk of all-cause mortality. Conclusions Among invasive treated patients in ISCHEMIA trial, six-month QoL improvement was associated with a lower risk of long-term all-cause mortality, but not with a lower risk of major adverse events.Figure 1.Study population.

Free fatty acids and mortality among adults in the United States: a report from US National Health and Nutrition Examination Survey (NHANES)

Abstract Introduction Free fatty acids (FFAs) serve as vital energy sources in multiple body tissues and they have been associated with elevated cardiovascular disease risk and mortality. There is a scarcity of prospective studies examining the associations between specific FFAs and long-term health outcomes. Purpose To examine the correlation between different FFAs types and all-cause or cardiovascular mortality in a large, nationally representative sample of adults in the United States (US), and examine how different concentrations and types of FFAs may mediate this association. Methods This cohort study included 3719 and 3900 participants in the unsaturated fatty acids (USFAs) and saturated fatty acids (SFAs) populations, respectively, who participated in the US National Health and Nutrition Examination Survey (NHANES) from 2011-2014. Multiple model calibration was performed using univariate and multivariate cox regression analysis to explore the associations between circulating FFAs and all-cause or cardiovascular mortality. Results The UFAs (myristoleic acid (14:1 n-5), palmitoleic acid (16:1 n-7), cis-vaccenic acid (18:1 n-7), nervonic acid (24:1 n-9), eicosatrienoic acid (20:3 n-9), docosatetraenoic acid (22:4 n-6), and docosapentaenoic acid (22:5 n-6)) were associated with an elevated risk of all-cause mortality ((hazard ratio (HR) 1.02 [1.006-1.034]; P=0.004), (HR 1.001 [1.001–1.002]; P＜ 0.001), (HR 1.006 [1.003–1.009]; P＜ 0.001), (HR 1.007 [1.002–1.012]; P = 0.003), (HR 1.027 [1.009–1.046]; P= 0.003), (HR 1.024 [1.012–1.036]; P＜ 0.001) and (HR 1.019 [1.006–1.032]; P = 0.005), respectively), whereas docosahexaenoic acid (22:6 n-3) was linked to a lower risk (HR 0.998 [0.996–0.999]; P = 0.007). Among SFAs, palmitic acid 16:0 was associated with a higher all-cause risk (HR 1.00 [1.00–1.00]; P = 0.022), while tricosanoic acid (23:0) and lignoceric acid (24:0) were associated with lower risks (HR 0.975 [0.959–0.991]; P = 0.002) and (HR 0.992 [0.984–0.999]; P = 0.036). Kaplan–Meier survival curves according to FFAs quartiles shown the highest risk for all-cause mortality was observed in the group with the highest concentration, except serum 23:0. The association between FFAs concentration and cardiovascular mortality in the multivariate analysis indicated that only 22:6 n-3 (HR 0.997 [0.994-1.000]; P=0.035) had a lower risk of cardiovascular mortality in the USFAs group, while none of the SFAs was found to be associated with cardiovascular mortality. While, the relationship between 22:6 n-3, and cardiovascular mortality was characterized by neither a linear nor nonlinear association (P-linear = 0.215; P-nonlinear = 0.260). Conclusion In this cohort of US adults, the types and concentrations of FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs effectively lowered this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality.FFA and all-cause mortality