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.

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).

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.

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).

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.

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.

Burden of hypertension and associated risks for cardiovascular mortality in Cuba: a prospective cohort study.

BACKGROUND: In Cuba, hypertension control in primary care has been prioritised as a cost-effective means of addressing premature death from cardiovascular disease. However, there is little evidence from large-scale studies on the prevalence and management of hypertension in Cuba, and no direct evidence of the expected benefit of such efforts on cardiovascular mortality. METHODS: In a prospective cohort study, adults in the general population identified via local family medical practices were interviewed between Jan 1, 1996, and Nov 24, 2002, in five areas of Cuba, and a subset of participants were resurveyed between July 14, 2006, and Oct 19, 2008, in one area. During household visits, blood pressure was measured and information obtained on diagnosis and treatment of hypertension. We calculated the prevalence of hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or receiving treatment for hypertension) and the proportion of people with hypertension in whom it was diagnosed, treated, and controlled (systolic blood pressure <140 mm Hg, diastolic blood pressure <90 mm Hg). Deaths were identified through linkage by national identification numbers to the Cuban Public Health Ministry records, to Dec 31, 2016. We used Cox regression analysis to compare cardiovascular mortality between participants with versus without uncontrolled hypertension. Rate ratios (RRs) were used to estimate the fraction of cardiovascular deaths attributable to hypertension. FINDINGS: 146 556 participants were interviewed in the baseline survey in 1996-2002 and 24 345 were interviewed in the resurvey in 2006-08. After exclusion for incomplete data and age outside the range of interest, 136 111 respondents aged 35-79 years (mean age 54 [SD 12] years; 75 947 [56%] women, 60 164 [44%] men) were eligible for inclusion in the analyses. 34% of participants had hypertension. Among these, 67% had a diagnosis of hypertension. 76% of participants with diagnosed hypertension were receiving treatment and blood pressure was controlled in 36% of those people. During 1·7 million person-years of follow-up there were 5707 cardiovascular deaths. In the age groups 35-59, 60-69, and 70-79 years, uncontrolled hypertension at baseline was associated with RRs of 2·15 (95% CI 1·88-2·46), 1·86 (1·69-2·05), and 1·41 (1·32-1·52), respectively, and accounted for around 20% of premature cardiovascular deaths. INTERPRETATION: In this Cuban population, a third of people had hypertension. Although levels of hypertension diagnosis and treatment were commensurate with those in some high-income countries, the proportion of participants whose blood pressure was controlled was low. As well as reducing hypertension prevalence, improvement in blood pressure control among people with diagnosed hypertension is required to prevent premature cardiovascular deaths in Cuba. FUNDING: Medical Research Council, British Heart Foundation, Cancer Research UK.

Body-mass index, blood pressure, and cause-specific mortality in India: a prospective cohort study of 500 810 adults.

BACKGROUND: The association between cause-specific mortality and body-mass index (BMI) has been studied mainly in high-income countries. We investigated the relations between BMI, systolic blood pressure, and mortality in India. METHODS: Men and women aged 35 years or older were recruited into a prospective study from the general population in Chennai, India between Jan 1, 1998, and Dec 31, 2001. Participants were interviewed (data collected included age, sex, education, socioeconomic status, medical history, tobacco smoking, and alcohol intake) and measured (height, weight, and blood pressure). Deaths were identified by linkage to Chennai city mortality records and through active surveillance by household visits from trained graduate non-medical fieldworkers. After the baseline survey, households were visited once in 2002-05, then biennially until 2015. During these repeat visits, structured narratives of any deaths that took place before March 31, 2015, were recorded for physician coding. During 2013-14, a random sample of participants was also resurveyed as per baseline to assess long-term variability in systolic blood pressure and BMI. Cox regression (standardised for tobacco, alcohol, and social factors) was used to relate mortality rate ratios (RRs) at ages 35-69 years to systolic blood pressure, BMI, or BMI adjusted for usual systolic blood pressure. FINDINGS: 500 810 participants were recruited. After exclusion of those with chronic disease or incomplete data, 414 746 participants aged 35-69 years (mean 46 [SD 9]; 45% women) remained. At recruitment, mean systolic blood pressure was 127 mm Hg (SD 15), and mean BMI was 23·2 kg/m2 (SD 3·8). Correlations of resurvey and baseline measurements were 0·50 for systolic blood pressure and 0·88 for BMI. Low BMI was strongly associated with poverty, tobacco, and alcohol. Of the 29 519 deaths at ages 35-69 years, the cause was vascular for 14 935 deaths (12 504 cardiac, 1881 stroke, and 550 other). Vascular mortality was strongly associated with systolic blood pressure: RRs per 20 mm Hg increase in usual systolic blood pressure were 2·45 (95% CI 2·16-2·78) for stroke mortality, 1·74 (1·64-1·84) for cardiac mortality, and 1·84 (1·75-1·94) for all vascular mortality. Although BMI strongly affected systolic blood pressure (an increase of about 1 mm Hg per kg/m2) and diabetes prevalence, BMI was little related to cardiac or stroke mortality, with only small excesses even for grade 1 obesity (ie, BMIs of 30·0-35·0 kg/m2). After additional adjustment for usual systolic blood pressure, BMI was inversely related to cardiac and stroke mortality throughout the range 15·0-30·0 kg/m2: when underweight participants (ie, BMI 15·0-18·5 kg/m2) were compared with overweight participants (ie, BMI 25·0-30·0 kg/m2), the blood-pressure-adjusted RR was 1·28 (95% CI 1·20-1·38) for cardiac mortality and 1·46 (1·22-1·73) for stroke mortality. INTERPRETATION: In this South Asian population, BMI was little associated with vascular mortality, even though increased BMI is associated with increased systolic blood pressure, which in turn is associated with increased vascular mortality. Hence, some close correlates of below-average BMI must have important adverse effects, which could be of relevance in all populations. FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research UK.

Age at Menarche and Incidence of Diabetes: A Prospective Study of 300,000 Women in China.

Previous studies of predominantly Western populations have reported inconsistent associations between age at menarche and risk of diabetes. We examined this relationship among Chinese women, who generally experience menarche at a later age than Western women. In 2004-2008, China Kadoorie Biobank recruited 302,632 women aged 30-79 years from 10 areas across China, and recorded 5,391 incident cases of diabetes during 7 years of follow-up among 270,345 women without baseline diabetes, cardiovascular disease or cancer. Cox regression models yielded adjusted hazard ratios for incident diabetes associated with age at menarche. Overall, the mean age at menarche was 15.4 years, and decreased across successive generations. Age at menarche was linearly and inversely associated with incident diabetes, with adjusted hazard ratio of 0.96 (95% confidence interval (CI): 0.94, 0.97) per year delay. Hazard ratios were greater in younger generations (for women born in the 1960s-1970s, hazard ratio (HR) = 0.93, 95% CI: 0.90, 0.97; for women born in the 1950s, HR = 0.95, 95% CI: 0.93, 0.98; and for women born in the 1920s-1940s, HR = 0.97, 95% CI: 0.95, 0.99). Further adjustment for adulthood body mass index significantly attenuated the association (HR = 0.99, 95% CI: 0.97, 1.00), especially among those born before 1950 (HR = 1.00, 95% CI: 0.97, 1.02). Much of the inverse association between age at menarche and incident diabetes was mediated through increased adiposity associated with early menarche, especially in older generations.

Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease.

Atherosclerosis is a leading cause of vascular disease worldwide. Its major clinical manifestations include ischemic heart disease, ischemic stroke, and peripheral arterial disease. In high-income countries, there have been dramatic declines in the incidence and mortality from ischemic heart disease and ischemic stroke since the middle of the 20th century. For example, in the United Kingdom, the probability of death from vascular disease in middle-aged men (35-69 years) has decreased from 22% in 1950 to 6% in 2010. Most low- and middle-income countries have also reported declines in mortality from stroke over the last few decades, but mortality trends from ischemic heart disease have been more varied, with some countries reporting declines and others reporting increases (particularly those in Eastern Europe and Asia). Many major modifiable risk factors for atherosclerosis have been identified, and the causal relevance of several risk factors is now well established (including, but not limited to, smoking, adiposity, blood pressure, blood cholesterol, and diabetes mellitus). Widespread changes in health behaviors and use of treatments for these risk factors are responsible for some of the dramatic declines in vascular mortality in high-income countries. In order that these declines continue and are mirrored in less wealthy nations, increased efforts are needed to tackle these major risk factors, particularly smoking and the emerging obesity epidemic.

Contrasting male and female trends in tobacco-attributed mortality in China: evidence from successive nationwide prospective cohort studies.

BACKGROUND: Chinese men now smoke more than a third of the world's cigarettes, following a large increase in urban then rural usage. Conversely, Chinese women now smoke far less than in previous generations. We assess the oppositely changing effects of tobacco on male and female mortality. METHODS: Two nationwide prospective studies 15 years apart recruited 220,000 men in about 1991 at ages 40-79 years (first study) and 210,000 men and 300,000 women in about 2006 at ages 35-74 years (second study), with follow-up during 1991-99 (mid-year 1995) and 2006-14 (mid-year 2010), respectively. Cox regression yielded sex-specific adjusted mortality rate ratios (RRs) comparing smokers (including any who had stopped because of illness, but not the other ex-smokers, who are described as having stopped by choice) versus never-smokers. FINDINGS: Two-thirds of the men smoked; there was little dependence of male smoking prevalence on age, but many smokers had not smoked cigarettes throughout adult life. Comparing men born before and since 1950, in the older generation, the age at which smoking had started was later and, particularly in rural areas, lifelong exclusive cigarette use was less common than in the younger generation. Comparing male mortality RRs in the first study (mid-year 1995) versus those in the second study (mid-year 2010), the proportional excess risk among smokers (RR-1) approximately doubled over this 15-year period (urban: RR 1·32 [95% CI 1·24-1·41] vs 1·65 [1·53-1·79]; rural: RR 1·13 [1·09-1·17] vs 1·22 [1·16-1·29]), as did the smoking-attributed fraction of deaths at ages 40-79 years (urban: 17% vs 26%; rural: 9% vs 14%). In the second study, urban male smokers who had started before age 20 years (which is now typical among both urban and rural young men) had twice the never-smoker mortality rate (RR 1·98, 1·79-2·19, approaching Western RRs), with substantial excess mortality from chronic obstructive pulmonary disease (COPD RR 9·09, 5·11-16·15), lung cancer (RR 3·78, 2·78-5·14), and ischaemic stroke or ischaemic heart disease (combined RR 2·03, 1·66-2·47). Ex-smokers who had stopped by choice (only 3% of ever-smokers in 1991, but 9% in 2006) had little smoking-attributed risk more than 10 years after stopping. Among Chinese women, however, there has been a tenfold intergenerational reduction in smoking uptake rates. In the second study, among women born in the 1930s, 1940s, 1950s, and since 1960 the proportions who had smoked were, respectively, 10%, 5%, 2%, and 1% (3097/30,943, 3265/62,246, 2339/97,344, and 1068/111,933). The smoker versus non-smoker RR of 1·51 (1·40-1·63) for all female mortality at ages 40-79 years accounted for 5%, 3%, 1%, and <1%, respectively, of all the female deaths in these four successive birth cohorts. In 2010, smoking caused about 1 million (840,000 male, 130,000 female) deaths in China. INTERPRETATION: Smoking will cause about 20% of all adult male deaths in China during the 2010s. The tobacco-attributed proportion is increasing in men, but low, and decreasing, in women. Although overall adult mortality rates are falling, as the adult population of China grows and the proportion of male deaths due to smoking increases, the annual number of deaths in China that are caused by tobacco will rise from about 1 million in 2010 to 2 million in 2030 and 3 million in 2050, unless there is widespread cessation. FUNDING: Wellcome Trust, MRC, BHF, CR-UK, Kadoorie Charitable Foundation, Chinese MoST and NSFC.

Alcohol consumption and mortality: the Khon Kaen Cohort Study, Thailand.

BACKGROUND: The prevalence of alcohol consumption among Thais is high, around 30%. We quantified the relationship between alcohol drinking and mortality in a rural population in the most populous region of Thailand. METHODS: The data were from the Khon Kaen Cohort Study. About 24 000 Thai adults were enrolled between 1990 and 2001, and follow-up for vital status continued until March 16, 2012. Mortality data were obtained from the Bureau of Policy and Strategy, Ministry of the Interior, Thailand. A Cox proportional hazards model was used to analyze the association between alcohol drinking and death, controlling for age, education level, and smoking, and floating absolute risk was used to estimate the 95% confidence intervals of hazard ratios. RESULTS: In total, 18 457 participants (5829 men and 12 628 women) were recruited, of whom 3155 died (1375 men and 1780 women) during a median follow-up period of 13.6 years. Although alcohol drinking was common (64% of men and 25% of women), the amounts consumed were very low (average, 4.3 g/day in men and 0.8 g/day in women). As compared with never drinkers, mortality risk was lower among current drinkers and higher among ex-drinkers. Current drinking was not associated with mortality from cancer or diseases of the circulatory system, although ex-drinkers appeared to have a higher risk of death from the latter. CONCLUSIONS: The leading causes of mortality were not associated with current alcohol drinking at the low consumption levels observed in this population.

Alcohol and mortality in Russia: prospective observational study of 151,000 adults.

BACKGROUND: Russian adults have extraordinarily high rates of premature death. Retrospective enquiries to the families of about 50,000 deceased Russians had found excess vodka use among those dying from external causes (accident, suicide, violence) and eight particular disease groupings. We now seek prospective evidence of these associations. METHODS: In three Russian cities (Barnaul, Byisk, and Tomsk), we interviewed 200,000 adults during 1999-2008 (with 12,000 re-interviewed some years later) and followed them until 2010 for cause-specific mortality. In 151,000 with no previous disease and some follow-up at ages 35-74 years, Poisson regression (adjusted for age at risk, amount smoked, education, and city) was used to calculate the relative risks associating vodka consumption with mortality. We have combined these relative risks with age-specific death rates to get 20-year absolute risks. FINDINGS: Among 57,361 male smokers with no previous disease, the estimated 20-year risks of death at ages 35-54 years were 16% (95% CI 15-17) for those who reported consuming less than a bottle of vodka per week at baseline, 20% (18-22) for those consuming 1-2·9 bottles per week, and 35% (31-39) for those consuming three or more bottles per week; trend p<0·0001. The corresponding risks of death at ages 55-74 years were 50% (48-52) for those who reported consuming less than a bottle of vodka per week at baseline, 54% (51-57) for those consuming 1-2·9 bottles per week, and 64% (59-69) for those consuming three or more bottles per week; trend p<0·0001. In both age ranges most of the excess mortality in heavier drinkers was from external causes or the eight disease groupings strongly associated with alcohol in the retrospective enquiries. Self-reported drinking fluctuated; of the men who reported drinking three or more bottles of vodka per week who were reinterviewed a few years later, about half (185 of 321) then reported drinking less than one bottle per week. Such fluctuations must have substantially attenuated the apparent hazards of heavy drinking in this study, yet self-reported vodka use at baseline still strongly predicted risk. Among male non-smokers and among females, self-reported heavy drinking was uncommon, but seemed to involve similar absolute excess risks. INTERPRETATION: This large prospective study strongly reinforces other evidence that vodka is a major cause of the high risk of premature death in Russian adults. FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union, WHO International Agency for Research on Cancer.

Alcohol consumption in 0.5 million people from 10 diverse regions of China: prevalence, patterns and socio-demographic and health-related correlates.

BACKGROUND: Drinking alcohol has a long tradition in Chinese culture. However, data on the prevalence and patterns of alcohol consumption in China, and its main correlates, are limited. METHODS: During 2004-08 the China Kadoorie Biobank recruited 512,891 men and women aged 30-79 years from 10 urban and rural areas of China. Detailed information on alcohol consumption was collected using a standardized questionnaire, and related to socio-demographic, physical and behavioural characteristics in men and women separately. RESULTS: Overall, 76% of men and 36% of women reported drinking some alcohol during the past 12 months, with 33% of men and 2% of women drinking at least weekly; the prevalence of weekly drinking in men varied from 7% to 51% across the 10 study areas. Mean consumption was 286 g/week and was higher in those with less education. Most weekly drinkers habitually drank spirits, although this varied by area, and beer consumption was highest among younger drinkers; 37% of male weekly drinkers (12% of all men) reported weekly heavy drinking episodes, with the prevalence highest in younger men. Drinking alcohol was positively correlated with regular smoking, blood pressure and heart rate. Among male weekly drinkers, each 20 g/day alcohol consumed was associated with 2 mmHg higher systolic blood pressure. Potential indicators of problem drinking were reported by 24% of male weekly drinkers. CONCLUSION: The prevalence and patterns of drinking in China differ greatly by age, sex and geographical region. Alcohol consumption is associated with a number of unfavourable health behaviours and characteristics.

Association between smoking and mortality: Khon Kaen cohort study, Thailand.

BACKGROUND: Despite anti-smoking campaigns, smoking prevalence among Thai males aged 30 or older is high, at around 50%. The purpose of this study was to determine the relationship between smoking and mortality in a rural Thai community. MATERIALS AND METHODS: Subjects enrolled into the Khon Kaen cohort study between 1990 and 2001 were followed up for their vital status until 16th March 2012. The death resource was from the Bureau of Policy and Strategy, Ministry of Interior, Thailand. A Cox proportional hazards model was used to analyse the association between smoking and death, controlling for age, education level and alcohol drinking, and confidence intervals were calculated using the floating risk method. RESULTS: The study recruited 5,962 male subjects, of whom 1,396 died during a median 13.5 years of follow-up. Current smokers were more likely to die than never smokers after controlling for age, education level and alcohol drinking (HR, 95%CI: 1.41, 1.32- 1.51), and the excess mortality was greatest for lung cancer (HR, 95%CI: 3.51, 2.65-4.66). However, there was no increased risk with increasing dose of tobacco, and no difference in risk between smokers of yamuan (hand- rolled cigarettes) and manufactured tobacco. CONCLUSION: Mortality from cancer, particularly lung cancer, and from all causes combined is dependent on smoking status among men in rural Thailand, but the relative risks are lower than have been reported from studies in high income countries, where the tobacco epidemic is more established.

Alcohol drinking and overall and cause-specific mortality in China: nationally representative prospective study of 220,000 men with 15 years of follow-up.

BACKGROUND: Regular alcohol drinking contributes both favourably and adversely to health in the Western populations, but its effects on overall and cause-specific mortality in China are still poorly understood. METHODS: A nationally representative prospective cohort study included 220,000 men aged 40-79 years from 45 areas in China in 1990-91, and >40,000 deaths occurred during 15 years of follow-up. Cox regression was used to relate alcohol drinking to overall and cause-specific mortality, adjusting for age, area, smoking and education. RESULTS: Overall, 33% of the participants reported drinking alcohol regularly at baseline, consuming mainly distilled spirits, with an estimated mean amount consumed of 372 g/week (46.5 units per week). After excluding all men with prior disease at baseline and the first 3 years of follow-up, there was a 5% [95% confidence interval (CI) 2-8] excess risk of overall mortality among regular drinkers. Compared with non-drinkers, the adjusted hazard ratios among men who drank <140, 140-279, 280-419, 420-699 and ≥ 700 g/week were 0.97, 1.00, 1.02, 1.12 and 1.27, respectively (P < 0.0001 for trend). The strength of the relationship appeared to be greater in smokers than in non-smokers. There was a strong positive association of alcohol drinking with mortality from stroke, oesophageal cancer, liver cirrhosis or accidental causes, a weak J-shaped association with mortality from ischaemic heart disease, stomach cancer and lung cancer and no apparent relationship with respiratory disease mortality. CONCLUSION: Among Chinese men aged 40-79 years, regular alcohol drinking was associated with a small but definite excess risk of overall mortality, especially among smokers.