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In this analysis of current data from a nationally representative U.S. survey, smoking was associated with a reduction in life expectancy of 10 years, and the excess risk was reduced by about 90% among smokers who quit by 40 years of age. Smoking is a major cause of premature death worldwide. 1 – 3 Despite substantial declines in the prevalence of smoking by adults, estimates based on extrapolation from studies in the 1980s suggest that for those between 35 and 69 years of age, smoking currently accounts for almost 200,000 deaths annually in the United States, or about one fourth of all deaths in this age group. 4 – 6 The prevalence of smoking peaked around 1960 among U.S. men and about two decades later among U.S. women. 7 , 8 Rates of death from vascular disease have decreased substantially since the 1980s owing to reductions in smoking . . .

Angiotensin-converting enzyme 2 (ACE2) is an endogenous counter-regulator of the renin–angiotensin hormonal cascade. We assessed whether plasma ACE2 concentrations were associated with greater risk of death or cardiovascular disease events. We used data from the Prospective Urban Rural Epidemiology (PURE) prospective study to conduct a case-cohort analysis within a subset of PURE participants (from 14 countries across five continents: Africa, Asia, Europe, North America, and South America). We measured plasma concentrations of ACE2 and assessed potential determinants of plasma ACE2 levels as well as the association of ACE2 with cardiovascular events. We included 10 753 PURE participants in our study. Increased concentration of plasma ACE2 was associated with increased risk of total deaths (hazard ratio [HR] 1·35 per 1 SD increase [95% CI 1·29–1·43]) with similar increases in cardiovascular and non-cardiovascular deaths. Plasma ACE2 concentration was also associated with higher risk of incident heart failure (HR 1·27 per 1 SD increase [1·10–1·46]), myocardial infarction (HR 1·23 per 1 SD increase [1·13–1·33]), stroke (HR 1·21 per 1 SD increase [1·10–1·32]) and diabetes (HR 1·44 per 1 SD increase [1·36–1·52]). These findings were independent of age, sex, ancestry, and traditional cardiac risk factors. With the exception of incident heart failure events, the independent relationship of ACE2 with the clinical endpoints, including death, remained robust after adjustment for BNP. The highest-ranked determinants of ACE2 concentrations were sex, geographic ancestry, and body-mass index (BMI). When compared with clinical risk factors (smoking, diabetes, blood pressure, lipids, and BMI), ACE2 was the highest ranked predictor of death, and superseded several risk factors as a predictor of heart failure, stroke, and myocardial infarction. Increased plasma ACE2 concentration was associated with increased risk of major cardiovascular events in a global study. Canadian Institute of Health Research, Heart & Stroke Foundation of Canada, and Bayer.

WHO estimates that about 170 000 deaths by suicide occur in India every year, but few epidemiological studies of suicide have been done in the country. We aimed to quantify suicide mortality in India in 2010. The Registrar General of India implemented a nationally representative mortality survey to determine the cause of deaths occurring between 2001 and 2003 in 1·1 million homes in 6671 small areas chosen randomly from all parts of India. As part of this survey, fieldworkers obtained information about cause of death and risk factors for suicide from close associates or relatives of the deceased individual. Two of 140 trained physicians were randomly allocated (stratified only by their ability to read the local language in which each survey was done) to independently and anonymously assign a cause to each death on the basis of electronic field reports. We then applied the age-specific and sex-specific proportion of suicide deaths in this survey to the 2010 UN estimates of absolute numbers of deaths in India to estimate the number of suicide deaths in India in 2010. About 3% of the surveyed deaths (2684 of 95 335) in individuals aged 15 years or older were due to suicide, corresponding to about 187 000 suicide deaths in India in 2010 at these ages (115 000 men and 72 000 women; age-standardised rates per 100 000 people aged 15 years or older of 26·3 for men and 17·5 for women). For suicide deaths at ages 15 years or older, 40% of suicide deaths in men (45 100 of 114 800) and 56% of suicide deaths in women (40 500 of 72 100) occurred at ages 15–29 years. A 15-year-old individual in India had a cumulative risk of about 1·3% of dying before the age of 80 years by suicide; men had a higher risk (1·7%) than did women (1·0%), with especially high risks in south India (3·5% in men and 1·8% in women). About half of suicide deaths were due to poisoning (mainly ingestions of pesticides). Suicide death rates in India are among the highest in the world. A large proportion of adult suicide deaths occur between the ages of 15 years and 29 years, especially in women. Public health interventions such as restrictions in access to pesticides might prevent many suicide deaths in India. US National Institutes of Health.

The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001–03 in homes in small areas that were chosen to be representative of all the parts of India. At least 130 trained physicians independently assigned causes to 122 429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. 7137 of 122 429 study deaths were due to cancer, corresponding to 556 400 national cancer deaths in India in 2010. 395 400 (71%) cancer deaths occurred in people aged 30–69 years (200 100 men and 195 300 women). At 30–69 years, the three most common fatal cancers were oral (including lip and pharynx, 45 800 [22·9%]), stomach (25 200 [12·6%]), and lung (including trachea and larynx, 22 900 [11·4%]) in men, and cervical (33 400 [17·1%]), stomach (27 500 [14·1%]), and breast (19 900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84 000) of male and 18·3% (35 700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100 000 were similar in rural (men 95·6 [99% CI 89·6–101·7] and women 96·6 [90·7–102·6]) and urban areas (men 102·4 [92·7–112·1] and women 91·2 [81·9–100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4–115·7] vs most educated 45·7 [37·8–53·6]; women, illiterate 106·7 [99·9–113·6] vs most educated 43·4 [30·7–56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64–0·71] vs 340, 1·06 [1·05–1·08]). Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. Bill & Melinda Gates Foundation and US National Institutes of Health.

In patients presenting with acute coronary syndromes and multivessel coronary artery disease, the question of whether to undertake a strategy of complete revascularisation in cases in which percutaneous coronary intervention (PCI) is performed routinely on non-culprit lesions (in addition to the culprit lesion) or whether to restrict PCI only to the culprit lesion is a common dilemma. The Complete Revascularisation Trialists' Collaboration aimed to determine, based on the totality of data from randomised trials, the effect of a complete revascularisation strategy on major cardiovascular events and whether it reduces cardiovascular death. In this individual patient data meta-analysis, trials were included if they enrolled at least 250 patients, compared a complete revascularisation strategy (with PCI) to a culprit lesion-only PCI strategy, and enrolled patients presenting with acute ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction. To ensure that no trials were overlooked, we searched Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomised controlled trials published between 1996 and Sept 15, 2025. The primary outcomes were the composite of cardiovascular death or new myocardial infarction and cardiovascular death alone. Hierarchical testing of cardiovascular death alone was planned contingent on reduction in cardiovascular death or new myocardial infarction based on the prespecified alpha level of 0·04. A one-stage individual patient data meta-analysis was performed using a Cox frailty model. All-cause death was the secondary outcome; non-cardiovascular death and new myocardial infarction were additional outcomes. All analyses included all randomly assigned patients. The meta-analysis was registered in PROSPERO, CRD420251124098. Six randomised controlled trials involving 8836 individuals were included. The median age was 65·8 years (IQR 57·0–76·0), and 2088 (23·6%) patients were female and 6748 (76·4%) were male. Overall, 7768 (87·9%) patients presented with ST-segment elevation myocardial infarction and 1068 (12·1%) with non-ST-segment elevation myocardial infarction. At a median follow-up of 36·0 months (IQR 30·6–48·0), cardiovascular death or new myocardial infarction occurred in 382 (9·0%) of 4259 patients in the complete revascularisation group compared with 528 (11·5%) of 4577 patients in the culprit lesion-only group (hazard ratio [HR] 0·76 [95% CI 0·67–0·87], p<0·0001). There were 155 (3·6%) cardiovascular deaths in the complete revascularisation group compared with 209 (4·6%) in the culprit lesion-only group (HR 0·76 [95% CI 0·62–0·93], p=0·0091). All-cause death occurred in 308 (7·2%) patients in the complete revascularisation group compared with 370 (8·1%) patients in the culprit lesion-only group (HR 0·85 [95% CI 0·73–0·99], p=0·039). Non-cardiovascular death was similar between the groups (153 [3·6%] in the complete revascularisation group vs 161 [3·5%] in the culprit lesion-only group; HR 0·98 [95% CI 0·78–1·22], p=0·85). Complete revascularisation reduced new myocardial infarctions compared with culprit lesion-only PCI (255 [6·0%] vs 357 [7·8%]; HR 0·76 [95% CI 0·65–0·90], p=0·0011). In patients presenting with acute myocardial infarction and multivessel disease, complete revascularisation reduced the composite of cardiovascular death or new myocardial infarction as well as cardiovascular death alone compared with a culprit lesion-only PCI strategy. In addition, all-cause death was lower with complete revascularisation. These data provide the strongest and most robust evidence to date that complete revascularisation improves important cardiovascular clinical outcomes. None.

There is considerable variability in how older adults with cancer tolerate and recover from surgery and systemic treatments. A greater understanding of individual trajectories is crucial in guiding personalized treatment decisions. Frailty may explain these inter-individual differences. Despite emerging evidence on the association between perioperative frailty assessment and outcomes after noncardiac surgery, there is limited data in gynecologic oncology. A perioperative cardiovascular risk assessment, recommended by scientific guidelines, is widely adopted in noncardiac surgery, often as the only standardized perioperative risk stratification approach. While based on robust evidence on the association with cardiovascular complications and overall mortality, it might be insufficient to predict other essential surgical, oncologic and patient-important outcomes. The FARGO study is a multi-centre prospective cohort study targeting 280 patients aged 55 or older undergoing surgery, with or without chemotherapy, for a suspected or confirmed gynecologic malignancy. The primary objective is to evaluate the predictive value of the Frailty Phenotype measured preoperatively, compared with the currently used perioperative risk assessment (cardiovascular risk assessment based on the Revised Cardiac Risk Index, age, and occurrence of myocardial injury after non-cardiac surgery) in predicting the composite outcome of all-cause death or new disability at six months after surgery. Secondary objectives include comparing the predictive value of the Frailty Phenotype with that of the Clinical Frailty Scale; evaluating the performance of a preoperative frailty assessments on other postoperative complications, chemotherapy tolerance, and 1-year recurrence-free survival; exploring the added predictive value of a dynamic perioperative frailty assessment repeated 28 days after surgery; assessing the acceptability of frailty assessments by physicians and patients; and establishing a biobank to investigate frailty biomarkers. The findings could have important implications for risk stratification, planning and tailoring surgical and oncologic care for older adults with gynecologic malignancies. Our study emphasizes patient-centered outcomes and stakeholders' perspectives. Trial registration: Clinicaltrials.gov Identifier: NCT05738252.

Despite the growing utility of cardiovascular magnetic resonance (CMR) for cardiac morphology and function, sex and age-specific normal reference values derived from large, multi-ethnic data sets are lacking. Furthermore, most available studies use a simplified tracing methodology. Using a large cohort of participants without history of cardiovascular disease (CVD) or risk factors from the Canadian Alliance for Healthy Heart and Minds, we sought to establish a robust set of reference values for ventricular and atrial parameters using an anatomically correct contouring method, and to determine the influence of age and sex on ventricular parameters. Participants (n = 3206, 65% females; age 55.2 ± 8.4 years for females and 55.1 ± 8.8 years for men) underwent CMR using standard methods for quantitative measurements of cardiac parameters. Normal ventricular and atrial reference values are provided: (1) for males and females, (2) stratified by four age categories, and (3) for different races/ethnicities. Values are reported as absolute, indexed to body surface area, or height. Ventricular volumes and mass were significantly larger for males than females (p < 0.001). Ventricular ejection fraction was significantly diminished in males as compared to females (p < 0.001). Indexed left ventricular (LV) end-systolic, end-diastolic volumes, mass and right ventricular (RV) parameters significantly decreased as age increased for both sexes (p < 0.001). For females, but not men, mean LV and RVEF significantly increased with age (p < 0.001). Using anatomically correct contouring methodology, we provide accurate sex and age-specific normal reference values for CMR parameters derived from the largest, multi-ethnic population free of CVD to date. ClinicalTrials.gov, NCT02220582. Registered 20 August 2014—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02220582.

Background In cardiovascular (CV) trials, analyzing the total number of events, rather than just time-to-first event, enhances understanding of participants' health. Adapting Cox models to account for between-subject heterogeneity in multiple events and understanding its impact plays crucial roles in total event analysis. Method This study compares effect sizes from first event and total event analyses in three cardiovascular trials: ORIGIN ( N  = 12,537, median follow-up of 6.2 years), COMPASS ( N  = 18,278, median follow-up of 1.8 years), TRANSCEND ( N  = 5,926, median follow-up of 1.1 years). It also examines the impact of heterogeneity, measured by the negative binomial overdispersion parameter. Treatment effects were assessed using the Cox model for first events and the negative binomial (NB), Andersen-Gill (AG), Prentice-Williams-Peterson (PWP), Wei-Lin-Weissfeld (WLW), and Lin-Wei-Yang-Ying (LWYY) models for total events. Hazard ratios (HRs) or risk ratios (RRs), 95% confidence intervals (CIs), and CI widths were reported. The risk ratio applies to negative binomial. The first composite was consisted of myocardial infarction (MI), stroke, cardiovascular death. Simulations assessed Type I error, power, and mean squared error across the different approaches. Results In ORIGIN, the incidence per 100 years increased from 2.9 to 3.8 for the first composite with a heterogeneity of 2.4. The HR or RR for the first composite was 1.03 (95% CI, 0.94–1.12, CI width = 0.18) using Cox, 1.01 (95% CI, 0.92–1.11, CI width = 0.19) for NB, 1.01 (95% CI, 0.94–1.09, CI width = 0.15) for AG, 1.02 (95% CI, 0.94–1.10, CI width = 0.16) for PWP total, 1.01 (95% CI, 0.94–1.09, CI width = 0.15) for PWP gap, 1.03 (95% CI, 0.94–1.12, CI width = 0.18) for WLW and 1.01 (95% CI, 0.92–1.11, CI width = 0.19) for LWYY. Similar trends were observed in other studies. Our simulation results showed that total event approaches had approximately 5% higher power than the Cox model, though power declined exponentially across all methods with increasing heterogeneity. Among the total event methods, AG, PWP gap, and LWYY demonstrated better power, with AG and LWYY also achieving the smallest mean squared error (MSE). Conclusions High heterogeneity arises when a small number of patients experience a disproportionately large number of events. This effect is more pronounced when the overall event incidence is low and few patients experience any events. The effect size and CI width stayed consistent with low heterogeneity across different approaches. Power decreased with high heterogeneity. The AG and LWYY approaches slightly outperformed the other approaches. Clinical trial registration ORIGIN (NCT00069784), COMPASS (NCT01776424), TRANSCEND (NCT00153101).

Aims To estimate the incidence of major adverse cardiovascular events (MACE), expanded MACE, and MACE or Death across Fibrosis- 4 score (FIB-4) categories in people with type 2 diabetes and to determine whether efpeglenatide’s effect varies with increasing FIB-4 severity. Materials and methods AMPLITUDE-O trial data were used to estimate the relationship of FIB-4 score categories to the hazard of MACE, expanded MACE, and MACE or death. Interactions on these outcomes between baseline FIB-4 score, and between FIB-4 score and efpeglenatide were also assessed. Results Baseline FIB-4 score was available for 4059 participants (99.6%) allowing subdivision of the population in tertiles. During a median follow-up of 1.8 years, numerical increases in the incidence of all 3 outcomes did not change significantly across tertiles of FIB-4 score (P for trend ≥ 0.25) with negligible relationship of the score to incident outcomes (MACE HR, per 1 SD higher score, 95% CI: 1.00, 0.89–1.13). Efpeglenatide’s effect on all MACE outcomes did not vary across FIB-4 tertiles (all interaction p values ≥ 0.64). Conclusions In high-risk people with type 2 diabetes, the degree of liver fibrosis, as estimated by FIB-4 score, was not related to incident cardiovascular outcomes. The beneficial effect of efpeglenatide on these outcomes is independent of FIB-4 category.

The global prevalence of childhood eczema has increased over the last few decades, with a marked increase in high-income countries. Differences in prevalence of childhood eczema between countries and ethnicities suggest that genetic and early modifiable environmental factors, such as dietary intake, may underlie this observation. To investigate the association between pregnancy diet and infant eczema in a consortium of prospective Canadian birth cohorts predominantly comprised of white Europeans and South Asians. We evaluated the association of maternal dietary patterns reported during pregnancy (assessed at 24-28 weeks gestation using a semi-quantitiative food-frequency questionnaire) with parent-reported physician-diagnosed infant eczema at 1-year from 2,160 mother-infant pairs. Using three dietary patterns (\"Western\", \"plant-based\", and \"Balanced\") previously derived in this cohort using principal component analysis, we used multivariable logistic regression to determine the association of these dietary patterns with infant eczema, adjusted for potential confounders. We observed a lower odds of eczema in the full sample combining white Europeans and South Asians with greater adherence to a plant-based (OR = 0.65; 95% CI: 0.55, 0.76; <0.001) and Western dietary pattern (OR = 0.73; 95% CI: 0.60, 0.89; P<0.01), after adjusting for other known predictors of eczema, including ethnicity, which was not significant. No associations were observed for the balanced diet. An interaction between the Western diet and ethnicity was observed (P<0.001). Following stratification by ethnicity, a protective association between the plant-based diet and infant eczema was confirmed in both white Europeans (OR = 0.59; 95% CI: 0.47, 0.74; P<0.001) and South Asians (OR = 0.77; 95% CI: 0.61, 0.97; P = 0.025). In white Europeans only, a Western diet was associated with a lower odds of infant eczema (OR = 0.69; 95% CI: 0.56, 0.87; P = 0.001) while a balanced diet increased the odds of infant eczema (OR = 1.23; 95% CI: 1.02, 1.49; P = 0.03). Beyond a plant-based diet, no significant associations with other dietary patterns were observed in South Asians. A plant-based diet during pregnancy is associated with a lowered odds of infant eczema at 1 year in all participants. Future studies of the components of plant-based diet which underlie the lower risk of eczema are needed.