Summary 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.
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Summary Background Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about possible cancer risks. We aimed to assess any ...effects on site-specific cancer rates in the randomised trials of folic acid supplementation, at doses higher than those from fortification. Methods In these meta-analyses, we sought all trials completed before 2011 that compared folic acid versus placebo, had scheduled treatment duration at least 1 year, included at least 500 participants, and recorded data on cancer incidence. We obtained individual participant datasets that included 49 621 participants in all 13 such trials (ten trials of folic acid for prevention of cardiovascular disease n=46 969 and three trials in patients with colorectal adenoma n=2652). All these trials were evenly randomised. The main outcome was incident cancer (ignoring non-melanoma skin cancer) during the scheduled treatment period (among participants who were still free of cancer). We compared those allocated folic acid with those allocated placebo, and used log-rank analyses to calculate the cancer incidence rate ratio (RR). Findings During a weighted average scheduled treatment duration of 5·2 years, allocation to folic acid quadrupled plasma concentrations of folic acid (57·3 nmol/L for the folic acid groups vs 13·5 nmol/L for the placebo groups), but had no significant effect on overall cancer incidence (1904 cancers in the folic acid groups vs 1809 cancers in the placebo groups, RR 1·06, 95% CI 0·99–1·13, p=0·10). There was no trend towards greater effect with longer treatment. There was no significant heterogeneity between the results of the 13 individual trials (p=0·23), or between the two overall results in the cadiovascular prevention trials and the adenoma trials (p=0·13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast, or any other specific site. Interpretation Folic acid supplementation does not substantially increase or decrease incidence of site-specific cancer during the first 5 years of treatment. Fortification of flour and other cereal products involves doses of folic acid that are, on average, an order of magnitude smaller than the doses used in these trials. Funding British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency.
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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.
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.
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.
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.
UK Medical Research Council, British Heart Foundation, Cancer Research UK.
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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.
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.
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.
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.
Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Adherence to a combination of healthy lifestyle factors has been related to a considerable reduction of cardiovascular risk in white populations; however, little is known whether ...such associations persist in nonwhite populations like the Asian population. Objectives This study aimed to examine the associations of a combination of modifiable, healthy lifestyle factors with the risks of ischemic cardiovascular diseases and estimate the proportion of diseases that could potentially be prevented by adherence to these healthy lifestyle patterns. Methods This study examined the associations of 6 lifestyle factors with ischemic heart disease and ischemic stroke (IS) in the China Kadoorie Biobank of 461,211 participants 30 to 79 years of age who did not have cardiovascular diseases, cancer, or diabetes at baseline. Low-risk lifestyle factors were defined as nonsmoking status or having stopped smoking for reasons other than illness, alcohol consumption of <30 g/day, a median or higher level of physical activity, a diet rich in vegetables and fruits and limited in red meat, a body mass index of 18.5 to 23.9 kg/m2 , and a waist-to-hip ratio <0.90 for men and <0.85 for women. Results During a median of 7.2 years (3.3 million person-years) of follow-up, this study documented 3,331 incident major coronary events (MCE) and 19,348 incident ISs. In multivariable-adjusted analyses, current nonsmoking status, light to moderate alcohol consumption, high physical activity, a diet rich in vegetables and fruits and limited in red meat, and low adiposity were independently associated with reduced risks of MCE and IS. Compared with participants without any low-risk factors, the hazard ratio for participants with ≥4 low-risk factors was 0.42 (95% confidence interval: 0.34 to 0.52) for MCE and 0.61 (95% confidence interval: 0.56 to 0.66) for IS. Approximately 67.9% (95% confidence interval: 46.5% to 81.9%) of the MCE and 39.1% (95% confidence interval: 26.4% to 50.4%) of the IS cases were attributable to poor adherence to healthy lifestyle. Conclusions Adherence to healthy lifestyle may substantially lower the burden of cardiovascular diseases in Chinese.
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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.
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.
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.
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.
UK Medical Research Council, Cancer Research UK, British Heart Foundation, US Centers for Disease Control and Prevention (CDC) Foundation (with support from Amgen).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main ...stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China.
512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure.
During a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years SD 9), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 95% CI 1·28–1·34) and ischaemic stroke (1·30 1·29–1·31), but the association with intracerebral haemorrhage was about twice as steep (1·68 1·65–1·71). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 1·35–1·44) and diabetes (1·14 1·12–1·15). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (<80 years of age) annually.
Among adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality.
UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China.
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