Educational and social inequalities and cause-specific mortality in Mexico City: a prospective study.

BACKGROUND: Social inequalities in adult mortality have been reported across diverse populations, but there is no large-scale prospective evidence from Mexico. We aimed to quantify social, including educational, inequalities in mortality among adults in Mexico City. METHODS: The Mexico City Prospective Study recruited 150 000 adults aged 35 years and older from two districts of Mexico City between 1998 and 2004. Participants were followed up until Jan 1, 2021 for cause-specific mortality. Cox regression analysis yielded rate ratios (RRs) for death at ages 35-74 years associated with education and examined, in exploratory analyses, the mediating effects of lifestyle and related risk factors. FINDINGS: Among 143 478 participants aged 35-74 years, there was a strong inverse association of education with premature death. Compared with participants with tertiary education, after adjustment for age and sex, those with no education had about twice the mortality rate (RR 1·84; 95% CI 1·71-1·98), equivalent to approximately 6 years lower life expectancy, with an RR of 1·78 (1·67-1·90) among participants with incomplete primary, 1·62 (1·53-1·72) with complete primary, and 1·34 (1·25-1·42) with secondary education. Education was most strongly associated with death from renal disease and acute diabetic crises (RR 3·65; 95% CI 3·05-4·38 for no education vs tertiary education) and from infectious diseases (2·67; 2·00-3·56), but there was an apparent higher rate of death from all specific causes studied with lower education, with the exception of cancer for which there was little association. Lifestyle factors (ie, smoking, alcohol drinking, and leisure time physical activity) and related physiological correlates (ie, adiposity, diabetes, and blood pressure) accounted for about four-fifths of the association of education with premature mortality. INTERPRETATION: In this Mexican population there were marked educational inequalities in premature adult mortality, which appeared to largely be accounted for by lifestyle and related risk factors. Effective interventions to reduce these risk factors could reduce inequalities and have a major impact on premature mortality. FUNDING: Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, and the UK Medical Research Council Population Health Research Unit.

Detection rates of asymptomatic carotid artery stenosis and atrial fibrillation by selective screening of patients without cardiovascular disease.

BACKGROUND: Individuals with significant asymptomatic carotid artery stenosis (ACAS) and atrial fibrillation (AF) could benefit from specific interventions to prevent heart attack and stroke, but are often clinically 'silent'. We aimed to determine detection rate of ACAS and AF by screening, targeting a population at increased cardiovascular risk. METHODS: Data on adults who attended voluntary and self-funded commercial screening clinics in the United States or the United Kingdom between 2008 and 2013 were used. The Atherosclerotic Cardiovascular Disease (ASCVD) risk equation was applied to each participants and detection rates of targeted screening for ≥50% ACAS and AF to those at highest risk of CVD was assessed. RESULTS: Among 0.4 million individuals between 40 and 80 years, without CVD, 6191 (1.6%) had ACAS and 1026 (0.3%) had AF. Selective screening of participants with a predicted 10-year CVD risk of ≥20% identified 40% of ACAS cases, a prevalence of 3.7%, leading to a number needed to screen (NNS) of 27, as well as 39% of AF cases, a prevalence of 0.6%, with a NNS of 170. Selective screening of those with a predicted 10-year CVD risk of ≥15% identified 54% of ACAS cases, a prevalence of 3.3%, and an NNS of 31, as well as 51% of AF cases, a prevalence of 0.5%, with an NNS of 195. CONCLUSIONS: Selective screening for ACAS and AF implemented in ASCVD risk assessment greatly reduces the NNS when compared with population-level screening with detection rates of ACAS and AF substantially greater in people at higher predicted CVD risk.

Cigarette smoking and risk of severe infectious respiratory diseases in UK adults: 12-year follow-up of UK biobank.

BACKGROUND: The relevance of tobacco smoking for infectious respiratory diseases (IRD) is uncertain. We investigated the associations of cigarette smoking with severe IRD resulting in hospitalization or death in UK adults. METHODS: We conducted a prospective study of cigarette smoking and risk of severe IRD in UK Biobank. The outcomes included pneumonia, other acute lower respiratory tract infections (OA-LRTI) and influenza. Multivariable Cox regression analyses were used to estimate hazard ratios (HRs) of severe IRD associated with smoking habits after adjusting for confounding factors. RESULTS: Among 341 352 participants with no prior history of major chronic diseases, there were 12 384 incident cases with pneumonia, 7054 with OA-LRTI and 795 with influenza during a 12-year follow-up. Compared with non-smokers, current smoking was associated with ⁓2-fold higher rates of severe IRD (HR 2.40 [2.27-2.53] for pneumonia, 1.99 [1.84-2.14] for OA-LRTI and 1.82 [95% confidence interval: 1.47-2.24] for influenza). Incidence of all severe IRDs were positively associated with amount of cigarettes smoked. The HRs for each IRD (except influenza) also declined with increasing duration since quitting. CONCLUSIONS: Current cigarette smoking was positively associated with higher rates of IRD and the findings extend indications for tobacco control measures and vaccination of current smokers for prevention of severe IRD.

Educational inequalities and premature mortality: the Cuba Prospective Study.

BACKGROUND: Although socioeconomic status is a major determinant of premature mortality in many populations, the impact of social inequalities on premature mortality in Cuba, a country with universal education and health care, remains unclear. We aimed to assess the association between educational level and premature adult mortality in Cuba. METHODS: The Cuba Prospective Study (a cohort study) enrolled 146 556 adults aged 30 years and older from the general population in five provinces from Jan 1, 1996, to Nov 24, 2002. Participants were followed up until Jan 1, 2017, for cause-specific mortality. Deaths were identified through linkage to the Cuban Public Health Ministry's national mortality records. Cox regression models yielded rate ratios (RRs) for the effect of educational level (a commonly used measure for social status) on mortality at ages 35-74 years, with assessment for the mediating effects of smoking, alcohol consumption, and BMI. FINDINGS: A total of 127 273 participants aged 35-74 years were included in the analyses. There was a strong inverse association between educational level and premature mortality. Compared with a university education, men who did not complete primary education had an approximately 60% higher risk of premature mortality (RR 1·55, 95% CI 1·40-1·72), while the risk was approximately doubled in women (1·96, 1·81-2·13). Overall, 28% of premature deaths could be attributed to lower education levels. Excess mortality in women was primarily due to vascular disease, while vascular disease and cancer were equally important in men. 31% of the association with education in men and 18% in women could be explained by common modifiable risk factors, with smoking having the largest effect. INTERPRETATION: This study highlights the value of understanding the determinants of health inequalities in different populations. Although many major determinants lie outside the health system in Cuba, this study has identified the diseases and risk factors that require targeted public health interventions, particularly smoking. FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen).

Association Between Smoking, Smoking Cessation, and Mortality by Race, Ethnicity, and Sex Among US Adults.

Importance: Patterns of cigarette smoking and smoking cessation vary considerably across demographic groups in the US, but there is limited evidence on whether the hazards of smoking and benefits of quitting vary across these groups. Population-specific evidence on the benefits of quitting smoking may motivate cessation among groups historically underrepresented in medical research. Objective: To quantify the association between smoking, smoking cessation, and mortality by race, ethnicity, and sex. Design, Setting, and Participants: This nationally representative, prospective cohort study used data from the US National Health Interview Survey collected via questionnaire between January 1997 and December 2018 among adults aged 25 to 84 years at recruitment. Participants were followed up for cause-specific mortality through December 31, 2019. Exposures: Self-reported smoking status at recruitment, age at quitting smoking, and years since quitting smoking. Main Outcomes and Measures: The main outcomes were all-cause mortality and mortality from cancer, cardiovascular disease, and lower respiratory disease. Adjusted mortality rate ratios comparing never, former, and current smokers were calculated using Cox proportional hazards regression. Weighted analyses were conducted by race, ethnicity, and sex as reported by participants. Results: Among the 551 388 participants in the main analyses, the mean (SD) age at recruitment was 48.9 (15.3) years; 307 601 (55.8%) were women, 87 207 (15.8%) were Hispanic, 75 545 (13.7%) were non-Hispanic Black, 355 782 (64.5%) were non-Hispanic White, and 32 854 (6.0%) identified as other non-Hispanic race and ethnicity. There were 74 870 deaths among participants aged 25 to 89 years during follow-up (36 792 [49.1%] among men; 38 078 [50.9%] among women). The all-cause mortality rate ratio (RR) for current vs never smoking was 2.80 (95% CI, 2.73-2.88) overall. The RRs were similar by sex but varied by race and ethnicity: Hispanic, 2.01 (95% CI, 1.84-2.18); non-Hispanic Black, 2.19 (95% CI, 2.06-2.33); non-Hispanic White, 3.00 (95% CI, 2.91-3.10); and other non-Hispanic race and ethnicity, 2.16 (95% CI, 1.88-2.47). When comparing those who quit smoking before age 45 years with never smokers, all-cause mortality RRs were 1.15 (95% CI, 1.03-1.28) among Hispanic individuals, 1.16 (95% CI, 1.07-1.25) among non-Hispanic Black individuals, 1.11 (95% CI, 1.08-1.15) among non-Hispanic White individuals, and 1.17 (95% CI, 0.99-1.39) among other non-Hispanic individuals. Conclusions and Relevance: In this prospective cohort study, among men and women from diverse racial and ethnic groups, current smoking was associated with at least twice the all-cause mortality rate of never smoking. Quitting smoking, particularly at younger ages, was associated with substantial reductions in the relative excess mortality associated with continued smoking.

Reproductive factors and gall-bladder cancer, and the effect of common genetic variants on these associations: a case-control study in India.

BACKGROUND: In India, as elsewhere, the incidence of gall-bladder cancer (GBC) is substantially higher in women than in men. Yet, the relevance of reproductive factors to GBC remains poorly understood. METHODS: We used logistic regression adjusted for age, education and area to examine associations between reproductive factors and GBC risk, using 790 cases of histologically confirmed GBC and group-matched 1726 visitor controls. We tested the interaction of these associations by genetic variants known to increase the risk of GBC. RESULTS: Parity was strongly positively associated with GBC risk: each additional pregnancy was associated with an ∼25% higher risk {odds ratio [OR] 1.26 [95% confidence interval (95% CI) 1.17-1.37]}. After controlling for parity, GBC risk was weakly positively associated with later age of menarche [postmenopausal women, OR 1.11 (95% CI 1.00-1.22) per year], earlier menopause [OR 1.03 (95% CI 1.00-1.06) per year] and shorter reproductive lifespan [OR 1.04 (95% CI 1.01-1.07) per year], but there was little evidence of an association with breastfeeding duration or years since last pregnancy. Risk alleles of single-nucleotide polymorphisms in the ABCB4 and ABCB1 genetic regions had a multiplicative effect on the association with parity, but did not interact with other reproductive factors. CONCLUSIONS: We observed higher GBC risk with higher parity and shorter reproductive lifespan, suggesting an important role for reproductive and hormonal factors.

Random plasma glucose levels and cause-specific mortality among Chinese adults without known diabetes: an 11-year prospective study of 450,000 people.

INTRODUCTION: We examined the associations between long-term usual random plasma glucose (RPG) levels and cause-specific mortality risks among adults without known diabetes in China. RESEARCH DESIGN AND METHODS: The China Kadoorie Biobank recruited 512,891 adults (59% women) aged 30-79 from 10 regions of China during 2004-2008. At baseline survey, and subsequent resurveys of a random subset of survivors, participants were interviewed and measurements collected, including on-site RPG testing. Cause of death was ascertained via linkage to local mortality registries. Cox regression yielded adjusted HR for all-cause and cause-specific mortality associated with usual levels of RPG. RESULTS: During median 11 years' follow-up, 37,214 deaths occurred among 452,993 participants without prior diagnosed diabetes or other chronic diseases. There were positive log-linear relationships between RPG and all-cause, cardiovascular disease (CVD) (n=14,209) and chronic kidney disease (CKD) (n=432) mortality down to usual RPG levels of at least 5.1 mmol/L. At RPG <11.1 mmol/L, each 1.0 mmol/L higher usual RPG was associated with adjusted HRs of 1.14 (95% CI 1.12 to 1.16), 1.16 (1.12 to 1.19) and 1.44 (1.22 to 1.70) for all-cause, CVD and CKD mortality, respectively. Usual RPG was positively associated with chronic liver disease (n=547; 1.45 (1.26 to 1.66)) and cancer (n=12,680; 1.12 (1.09 to 1.16)) mortality, but with comparably lower risks at baseline RPG ≥11.1 mmol/L. These associations persisted after excluding participants who developed diabetes during follow-up. CONCLUSIONS: Among Chinese adults without diabetes, higher RPG levels were associated with higher mortality risks from several major diseases, with no evidence of apparent thresholds below the cut-points for diabetes diagnosis.

Body-mass index, blood pressure, diabetes and cardiovascular mortality in Cuba: prospective study of 146,556 participants.

BACKGROUND: Cardiovascular disease accounts for about one-third of all premature deaths (ie, age < 70) in Cuba. Yet, the relevance of major risk factors, including systolic blood pressure (SBP), diabetes, and body-mass index (BMI), to cardiovascular mortality in this population remains unclear. METHODS: In 1996-2002, 146,556 adults were recruited from the general population in five areas of Cuba. Participants were interviewed, measured (height, weight and blood pressure) and followed up by electronic linkage to national death registries until Jan 1, 2017; in 2006-08, 24,345 participants were resurveyed. After excluding all with missing data, cardiovascular disease at recruitment, and those who died in the first 5 years, Cox regression (adjusted for age, sex, education, smoking, alcohol and, where appropriate, BMI) was used to relate cardiovascular mortality rate ratios (RRs) at ages 35-79 years to SBP, diabetes and BMI; RR were corrected for regression dilution to give associations with long-term average (ie, 'usual') levels of SBP and BMI. RESULTS: After exclusions, there were 125,939 participants (mean age 53 [SD12]; 55% women). Mean SBP was 124 mmHg (SD15), 5% had diabetes, and mean BMI was 24.2 kg/m2 (SD3.6); mean SBP and diabetes prevalence at recruitment were both strongly related to BMI. During follow-up, there were 4112 cardiovascular deaths (2032 ischaemic heart disease, 832 stroke, and 1248 other). Cardiovascular mortality was positively associated with SBP (>=120 mmHg), diabetes, and BMI (>=22.5 kg/m2): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88-2.18]), as did diabetes (2.15, 1.95-2.37), and 10 kg/m2 higher usual BMI (1.92, 1.64-2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m2) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively. CONCLUSIONS: This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.

Alcohol consumption and cause-specific mortality in Cuba: prospective study of 120 623 adults.

BACKGROUND: The associations of cause-specific mortality with alcohol consumption have been studied mainly in higher-income countries. We relate alcohol consumption to mortality in Cuba. METHODS: In 1996-2002, 146 556 adults were recruited into a prospective study from the general population in five areas of Cuba. Participants were interviewed, measured and followed up by electronic linkage to national death registries until January 1, 2017. After excluding all with missing data or chronic disease at recruitment, Cox regression (adjusted for age, sex, province, education, and smoking) was used to relate mortality rate ratios (RRs) at ages 35-79 years to alcohol consumption. RRs were corrected for long-term variability in alcohol consumption using repeat measures among 20 593 participants resurveyed in 2006-08. FINDINGS: After exclusions, there were 120 623 participants aged 35-79 years (mean age 52 [SD 12]; 67 694 [56%] women). At recruitment, 22 670 (43%) men and 9490 (14%) women were current alcohol drinkers, with 15 433 (29%) men and 3054 (5%) women drinking at least weekly; most alcohol consumption was from rum. All-cause mortality was positively and continuously associated with weekly alcohol consumption: each additional 35cl bottle of rum per week (110g of pure alcohol) was associated with ∼10% higher risk of all-cause mortality (RR 1.08 [95%CI 1.05-1.11]). The major causes of excess mortality in weekly drinkers were cancer, vascular disease, and external causes. Non-drinkers had ∼10% higher risk (RR 1.11 [1.09-1.14]) of all-cause mortality than those in the lowest category of weekly alcohol consumption (<1 bottle/week), but this association was almost completely attenuated on exclusion of early follow-up. INTERPRETATION: In this large prospective study in Cuba, weekly alcohol consumption was continuously related to premature mortality. Reverse causality is likely to account for much of the apparent excess risk among non-drinkers. The findings support limits to alcohol consumption that are lower than present recommendations in Cuba. FUNDING: Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen).

Low-intensity daily smoking and cause-specific mortality in Mexico: prospective study of 150 000 adults.

BACKGROUND: Research is needed to determine the relevance of low-intensity daily smoking to mortality in countries such as Mexico, where such smoking habits are common. METHODS: Prospective study of 159 755 Mexican adults recruited from 1998-2004 and followed for cause-specific mortality to 1 January 2018. Participants were categorized according to baseline self-reported smoking status. Confounder-adjusted mortality rate ratios (RRs) at ages 35-89 were estimated using Cox regression, after excluding those with previous chronic disease (to avoid reverse causality). RESULTS: Among 42 416 men and 86 735 women aged 35-89 and without previous disease, 18 985 men (45%) and 18 072 women (21%) reported current smoking and 8866 men (21%) and 53 912 women (62%) reported never smoking. Smoking less than daily was common: 33% of male current smokers and 39% of female current smokers. During follow-up, the all-cause mortality RRs associated with the baseline smoking categories of <10 cigarettes per day (average during follow-up 4 per day) or ≥10 cigarettes per day (average during follow-up 10 per day), compared with never smoking, were 1.17 (95% confidence interval 1.10-1.25) and 1.54 (1.42-1.67), respectively. RRs were similar irrespective of age or sex. The diseases most strongly associated with daily smoking were respiratory cancers, chronic obstructive pulmonary disease and gastrointestinal and vascular diseases. Ex-daily smokers had substantially lower mortality rates than those who were current daily smokers at recruitment. CONCLUSIONS: In this Mexican population, low-intensity daily smoking was associated with increased mortality. Of those smoking 10 cigarettes per day on average, about one-third were killed by their habit. Quitting substantially reduced these risks.

Development and Internal Validation of a Risk Score to Detect Asymptomatic Carotid Stenosis.

OBJECTIVE: Asymptomatic carotid stenosis (ACS) is associated with an increased risk of ischaemic stroke and myocardial infarction. Risk scores have been developed to detect individuals at high risk of ACS, thereby enabling targeted screening, but previous external validation showed scope for refinement of prediction by adding additional predictors. The aim of this study was to develop a novel risk score in a large contemporary screened population. METHODS: A prediction model was developed for moderate (≥50%) and severe (≥70%) ACS using data from 596 469 individuals who attended screening clinics. Variables that predicted the presence of ≥50% and ≥70% ACS independently were determined using multivariable logistic regression. Internal validation was performed using bootstrapping techniques. Discrimination was assessed using area under the receiver operating characteristic curves (AUROCs) and agreement between predicted and observed cases using calibration plots. RESULTS: Predictors of ≥50% and ≥70% ACS were age, sex, current smoking, diabetes mellitus, prior stroke/transient ischaemic attack, coronary artery disease, peripheral arterial disease, blood pressure, and blood lipids. Models discriminated between participants with and without ACS reliably, with an AUROC of 0.78 (95% confidence interval [CI] 0.77-0.78) for ≥ 50% ACS and 0.82 (95% CI 0.81-0.82) for ≥ 70% ACS. The number needed to screen in the highest decile of predicted risk to detect one case with ≥50% ACS was 13 and that of ≥70% ACS was 58. Targeted screening of the highest decile identified 41% of cases with ≥50% ACS and 51% with ≥70% ACS. CONCLUSION: The novel risk model predicted the prevalence of ACS reliably and performed better than previous models. Targeted screening among the highest decile of predicted risk identified around 40% of all cases with ≥50% ACS. Initiation or intensification of cardiovascular risk management in detected cases might help to reduce both carotid related ischaemic strokes and myocardial infarctions.

Association of Blood Pressure With Cause-Specific Mortality in Mexican Adults.

Importance: Elevated blood pressure is a major cause of premature death, but there is little direct evidence demonstrating this association in studies of Hispanic populations. Objective: To assess the association between blood pressure and cause-specific mortality in a large cohort of Mexican adults with a high prevalence of uncontrolled diabetes. Design, Setting, and Participants: A total of 159 755 adults aged 35 years or older from 2 districts in Mexico City were recruited to this cohort study between April 1998 and September 2004 and followed up until January 2018. The present analyses focused on 133 613 participants who were aged 35 to 74 years and had no history of chronic disease besides diabetes. Exposure: Blood pressure. Main Outcomes and Measures: Cox regression, adjusted for confounders, yielded mortality rate ratios (RRs) for deaths of participants occurring between ages 35 and 74 years. Results: Of the 133 613 participants (43 263 [32.4%] men; mean [SD] age, 50 [11] years), 16 911 (12.7%) had self-reported previously diagnosed diabetes (including 8435 [6.3%] with uncontrolled diabetes, defined as hemoglobin A1c ≥9%) and 6548 (4.9%) had undiagnosed diabetes. Systolic blood pressure (SBP) was associated with vascular mortality between ages 35 to 74 years, with each 20 mm Hg lower usual SBP associated with 35% lower vascular mortality (RR, 0.65; 95% CI, 0.61-0.68), including 48% lower stroke mortality (RR, 0.52; 95% CI, 0.47-0.59) and 32% lower ischemic heart disease mortality (RR, 0.68; 95% CI, 0.63-0.74). These RRs were broadly similar in those with and without diabetes. Compared with those without diabetes and SBP less than 135 mm Hg at recruitment, the vascular mortality RR was 2.8 (95% CI, 2.4-3.3) for those without diabetes and SBP of 155 mm Hg or greater, 4.7 (95% CI, 4.1-5.4) for those with uncontrolled diabetes and SBP less than 135 mm Hg, and 8.9 (95% CI, 7.2-11.1) for those with uncontrolled diabetes and SBP of 155 mm Hg or greater. Lower SBP was also associated with decreased kidney-related mortality (RR per 20 mm Hg lower usual SBP, 0.69; 95% CI, 0.64-0.74), decreased mortality from infection (RR, 0.81; 95% CI, 0.71-0.91), and decreased mortality from hepatobiliary disease (RR, 0.87; 95% CI, 0.78-0.98), but not decreased neoplastic or respiratory mortality. SBP was more informative for vascular mortality than other blood pressure measures (eg, compared with SBP, diastolic blood pressure was only two-thirds as informative). Conclusions and Relevance: Blood pressure was most strongly associated with vascular and kidney-related mortality in this Mexican population, with particularly high absolute excess mortality rates among individuals with diabetes. The findings reinforce the need for more widespread use of blood pressure-lowering medication in Mexico, particularly among those with diabetes.

Tobacco smoking and the risk of Parkinson disease: A 65-year follow-up of 30,000 male British doctors.

OBJECTIVE: To investigate the causal relevance of current tobacco smoking for the risk of Parkinson disease (PD). METHODS: We compared the risks of death from PD with smoking habits in 30,000 male doctors in the British Doctors cohort study in 1951 and in survivors who had been resurveyed periodically for 5 decades. Cause-specific mortality was monitored for 65 years and included 283 deaths from PD. The relative risks (RRs) of PD (and 95% confidence intervals [CIs]) were estimated using Cox models for smoking habits (smoking status, amount smoked, and years since quitting) at baseline or updated habits at resurvey. RESULTS: The prevalence of current smoking declined progressively during follow-up from 67% to 8% between 1951 and 1998. The crude rates of PD death were lower in current smokers than in never smokers at baseline (30 vs 46/100,000 persons-years). After adjustment for age at risk, current smokers at baseline had a 30% lower risk of PD (RR 0.71; 95% CI 0.60-0.84), and continuing smokers classified using updated smoking habits at resurvey had a 40% lower risk (RR 0.60; 95% CI 0.46-0.77) of PD compared with never smokers. The risks of PD were inversely associated with the amount of tobacco smoked. The protective effect of current smoking vs never smoking for PD was attenuated by increasing duration since quitting smoking. CONCLUSIONS: In contrast to previous suggestions, the present report demonstrates a causally protective effect of current smoking on the risk of PD, which may provide insights into the etiology of PD.

Association of childhood smoking and adult mortality: prospective study of 120 000 Cuban adults.

BACKGROUND: The average age at which people start smoking has been decreasing in many countries, but insufficient evidence exists on the adult hazards of having started smoking in childhood and, especially, in early childhood. We aimed to investigate the association between smoking habits (focusing on the age when smokers started) and cause-specific premature mortality in a cohort of adults in Cuba. METHODS: For this prospective study, adults were recruited from five provinces in Cuba. Participants were interviewed (data collected included socioeconomic status, medical history, alcohol consumption, and smoking habits) and had their height, weight, and blood pressure measured. Participants were followed up until Jan 1, 2017 for cause-specific mortality; a subset was resurveyed in 2006-08. We used Cox regression to calculate adjusted rate ratios (RRs) for mortality at ages 30-69 years, comparing never-smokers with current smokers by age they started smoking and number of cigarettes smoked per day and with ex-smokers by the age at which they had quit. FINDINGS: Between Jan 1, 1996, and Nov 24, 2002, 146 556 adults were recruited into the study, of whom 118 840 participants aged 30-69 years at recruitment contributed to the main analyses. 27 264 (52%) of 52 524 men and 19 313 (29%) of 66 316 women were current smokers. Most participants reported smoking cigarettes; few smoked only cigars. About a third of current cigarette smokers had started before age 15 years. Compared with never-smokers, the all-cause mortality RR was highest in participants who had started smoking at ages 5-9 years (RR 2·51, 95% CI 2·21-2·85), followed by ages 10-14 years (1·83, 1·72-1·95), 15-19 years (1·56, 1·46-1·65), and ages 20 years or older (1·50, 1·39-1·62). Smoking accounted for a quarter of all premature deaths in this population, but quitting before about age 40 years avoided almost all of the excess mortality due to smoking. INTERPRETATION: In this cohort of adults in Cuba, starting to smoke in childhood was common and quitting was not. Starting in childhood approximately doubled the rate of premature death (ie, before age 70 years). If this 2-fold mortality RR continues into old age, about half of participants who start smoking before age 15 years and do not stop will eventually die of complications from their habit. The greatest risks were found among adults who began smoking before age 10 years. FUNDING: UK Medical Research Council, Cancer Research UK, British Heart Foundation, US Centers for Disease Control and Prevention (CDC) Foundation (with support from Amgen).

Validation of Risk Prediction Models to Detect Asymptomatic Carotid Stenosis.

Background Significant asymptomatic carotid stenosis (ACS) is associated with higher risk of strokes. While the prevalence of moderate and severe ACS is low in the general population, prediction models may allow identification of individuals at increased risk, thereby enabling targeted screening. We identified established prediction models for ACS and externally validated them in a large screening population. Methods and Results Prediction models for prevalent cases with ≥50% ACS were identified in a systematic review (975 studies reviewed and 6 prediction models identified [3 for moderate and 3 for severe ACS]) and then validated using data from 596 469 individuals who attended commercial vascular screening clinics in the United States and United Kingdom. We assessed discrimination and calibration. In the validation cohort, 11 178 (1.87%) participants had ≥50% ACS and 2033 (0.34%) had ≥70% ACS. The best model included age, sex, smoking, hypertension, hypercholesterolemia, diabetes mellitus, vascular and cerebrovascular disease, measured blood pressure, and blood lipids. The area under the receiver operating characteristic curve for this model was 0.75 (95% CI, 0.74-0.75) for ≥50% ACS and 0.78 (95% CI, 0.77-0.79) for ≥70% ACS. The prevalence of ≥50% ACS in the highest decile of risk was 6.51%, and 1.42% for ≥70% ACS. Targeted screening of the 10% highest risk identified 35% of cases with ≥50% ACS and 42% of cases with ≥70% ACS. Conclusions Individuals at high risk of significant ACS can be selected reliably using a prediction model. The best-performing prediction models identified over one third of all cases by targeted screening of individuals in the highest decile of risk only.

Sex-Specific Associations of Vascular Risk Factors With Abdominal Aortic Aneurysm: Findings From 1.5 Million Women and 0.8 Million Men in the United States and United Kingdom.

Background Large studies are required for reliable estimates of important risk factors for abdominal aortic aneurysm (AAA). This could guide targeted AAA screening programs, particularly in subgroups like women who are currently excluded from such programs. Method and Results In a cross-sectional study, 1.5 million women and 0.8 million men without known vascular disease attended commercial screening clinics in the United Kingdom or United States from 2008 to 2013. Measurements of vascular risk factors were related to AAA using logistic regression with correction for regression dilution bias. Screening detected 12 729 new AAA cases (0.6%). Compared with never smoking, current smoking was associated with 15 times the risk of AAA among women (risk ratio 15.0, 95% CI 13.2-17.0) and 7 times among men (7.3, 6.4-8.2). In women aged <75 years, the risk of AAA was nearly 30 times greater in current smokers (26.4, 20.3-34.2). In every age group, the prevalence of AAA in female smokers was greater than in male never-smokers. Positive log-linear associations with AAA for women and men were also observed for usual body mass index, usual systolic blood pressure, height, usual low-density lipoprotein cholesterol, and usual triglycerides. Conclusions Log-linear increases in the risks of AAA with traditional vascular risk factors should be considered when evaluating populations that may be at-risk for the development of AAA, and when considering potential treatments. However, at any given age, female smokers are at higher risk of AAA than male never-smokers, and a policy of screening male never-smokers but not higher-risk female smokers is questionable.

General and Abdominal Adiposity and Mortality in Mexico City: A Prospective Study of 150 000 Adults.

Background: Some reports suggest that body mass index (BMI) is not strongly associated with mortality in Hispanic populations. Objective: To assess the causal relevance of adiposity to mortality in Mexican adults, avoiding reverse causality biases. Design: Prospective study. Setting: 2 Mexico City districts. Participants: 159 755 adults aged 35 years and older at recruitment, followed for up to 14 years. Participants with a hemoglobin A1c level of 7% or greater, diabetes, or other chronic diseases were excluded. Measurements: BMI, waist-to-hip ratio, waist circumference, and cause-specific mortality. Cox regression, adjusted for confounders, yielded mortality hazard ratios (HRs) after at least 5 years of follow-up and before age 75 years. Results: Among 115 400 participants aged 35 to <75 years at recruitment, mean BMI was 28.0 kg/m2 (SD, 4.1 kg/m2) in men and 29.6 kg/m2 (SD, 5.1 kg/m2) in women. The association of BMI at recruitment with all-cause mortality was J-shaped, with the minimum at 25 to <27.5 kg/m2. Above 25 kg/m2, each 5-kg/m2 increase in BMI was associated with a 30% increase in all-cause mortality (HR, 1.30 [95% CI, 1.24 to 1.36]). This association was stronger at ages 40 to <60 years (HR, 1.40 [CI, 1.30 to 1.49]) than at ages 60 to <75 years (HR, 1.24 [CI, 1.17 to 1.31]) but was not materially affected by sex, smoking, or other confounders. The associations of mortality with BMI and waist-to-hip ratio were similarly strong, and each was weakened only slightly by adjustment for the other. Waist circumference was strongly related to mortality and remained so even after adjustment for BMI and hip circumference. Limitation: Analyses were limited to mortality. Conclusion: General, and particularly abdominal, adiposity were strongly associated with mortality in this Mexican population. Primary Funding Source: Mexican Health Ministry, Mexican National Council of Science and Technology, Wellcome Trust, Medical Research Council, and Kidney Research UK.

Tobacco smoking and risk of 36 cardiovascular disease subtypes: fatal and non-fatal outcomes in a large prospective Australian study.

BACKGROUND: Tobacco smoking is a leading cause of cardiovascular disease (CVD) morbidity and mortality. Evidence on the relation of smoking to different subtypes of CVD, across fatal and non-fatal outcomes, is limited. METHODS: A prospective study of 188,167 CVD- and cancer-free individuals aged ≥ 45 years from the Australian general population joining the 45 and Up Study from 2006 to 2009, with linked questionnaire, hospitalisation and death data up to the end of 2015. Hazard ratios (HRs) for hospitalisation with or mortality from CVD among current and past versus never smokers were estimated, including according to intensity and recency of smoking, using Cox regression, adjusting for age, sex, urban/rural residence, alcohol consumption, income and education. Population-attributable fractions were estimated. RESULTS: During a mean 7.2 years follow-up (1.35 million person-years), 27,511 (crude rate 20.4/1000 person-years) incident fatal and non-fatal major CVD events occurred, including 4548 (3.2) acute myocardial infarction (AMI), 3991 (2.8) cerebrovascular disease, 3874 (2.7) heart failure and 2311 (1.6) peripheral arterial disease (PAD) events. At baseline, 8% of participants were current and 34% were past smokers. Of the 36 most common specific CVD subtypes, event rates for 29 were increased significantly in current smokers. Adjusted HRs in current versus never smokers were as follows: 1.63 (95%CI 1.56-1.71) for any major CVD, 2.45 (2.22-2.70) for AMI, 2.16 (1.93-2.42) for cerebrovascular disease, 2.23 (1.96-2.53) for heart failure, 5.06 (4.47-5.74) for PAD, 1.50 (1.24-1.80) for paroxysmal tachycardia, 1.31 (1.20-1.44) for atrial fibrillation/flutter, 1.41 (1.17-1.70) for pulmonary embolism, 2.79 (2.04-3.80) for AMI mortality, 2.26 (1.65-3.10) for cerebrovascular disease mortality and 2.75 (2.37-3.19) for total CVD mortality. CVD risks were elevated at almost all levels of current smoking intensity examined and increased with smoking intensity, with HRs for total CVD mortality in current versus never smokers of 1.92 (1.11-3.32) and 4.90 (3.79-6.34) for 4-6 and ≥ 25 cigarettes/day, respectively. Risks diminished with quitting, with excess risks largely avoided by quitting before age 45. Over one third of CVD deaths and one quarter of acute coronary syndrome hospitalisations in Australia aged < 65 can be attributed to smoking. CONCLUSIONS: Current smoking increases the risk of virtually all CVD subtypes, at least doubling the risk of many, including AMI, cerebrovascular disease and heart failure. Paroxysmal tachycardia is a newly identified smoking-related risk. Where comparisons are possible, smoking-associated relative risks for fatal and non-fatal outcomes are similar. Quitting reduces the risk substantially. In an established smoking epidemic, with declining and low current smoking prevalence, smoking accounts for a substantial proportion of premature CVD events.