Cohort Profile: the Cuba Prospective Study Nurys Armas Rojas, Ben Lacey, Sarah Lewington,* Patricia Varona Pérez, Julie Ann Burrett, José Manuel Morales Rigau, Paul Sherliker, Jillian Boreham, Osvaldo Jesús Hernández López, Blake Thomson, Fernando Achiong Estupi~ nan, Mayda Dı́az González, Noel Rosquete Mu~ noz, Marelis Cendra Asencio, Jonathan Emberson, Richard Peto and Alfredo Due~ nas Herrera National Institute of Cardiology and Cardiovascular Surgery, Havana, Cuba, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK, MRC Population Health Research Unit, University of Oxford, Oxford, UK, Institute of Hygiene, Epidemiology and Microbiology, Cuban Ministry of Public Health, Havana, Cuba, Provincial Centre of Hygiene, Epidemiology and Microbiology, Matanzas, Cuba, Municipal Centre of Hygiene, Epidemiology and Microbiology, Jagüey Grande, Matanzas, Cuba, Municipal Centre of Hygiene, Epidemiology and Microbiology, Colón, Matanzas, Cuba and Municipal Centre of Hygiene, Epidemiology and Microbiology, Camagüey, Camagüey, Cuba

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.

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.

The quantification of drug harms proposed by David Nutt and colleagues1 trivialises the large number of premature deaths still being caused by tobacco. In 2007, smoking caused about 28 000 UK deaths at ages 35–69 years (figure), and those killed by tobacco at these ages lost, on average, more than 20 years of non-smoker life expectancy.2,3 This is more than the number killed by any other single cause and, we suspect, more than the number killed by all the other drugs on Nutt and colleagues' list put together, including alcohol.

Abstract Background: Past studies have assessed trends in smoking prevalence among different social strata in developed countries. However, we know of no study that quantifies changes in social inequalities in smoking-attributable mortality rates over time. The aim of this study was to assess changes in social inequalities for smoking-attributable male mortality rates by educational level between two time periods in France and Poland. Methods: The contribution of smoking to adult male mortality in each population was estimated indirectly from disease-specific death rates in that population (using absolute lung cancer rates to indicate proportions due to smoking of mortality from certain other diseases). We applied these methods to male death rates at ages 35-69 years from three different social strata in France and Poland, based on a total of 202,779 deaths. The social strata were low, middle, and high based on completed years of education (less than 12 years, 12 years, and more than 12 years, respectively). For France, the comparison periods were 1990-94 and 1995-99; for Poland, 1995 was compared to 2002. Results: Smoking-attributable mortality rates were 3 to 6 times higher in the lowest education group as compared to the highest education group in both countries. In France, smoking-attributable mortality rates within each education group remained similar between 1990-94 and 1995-99. Between 1995 and 2002, Poland showed a reduction in smoking-attributable mortality rates by 15%, 4%, and 52% in the low, middle, and high education group, respectively. Conclusion: Although men in the lowest education group in France were around four times more likely to die from smoking as compared to those in the highest education group, there was little change between the periods studied for this country. While smoking-attributable mortality rates in the highest education group of Polish males decreased much more compared to the lower education groups; declines were seen in all education groups. Mortality rates from more recent years, when tobacco control efforts have accelerated in both countries, will be of interest to confirm these trends. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B86.

Background The changes in Russian mortality rates during the last two decades are unprecedented in a modern industrialized country. Although these fluctuations have attracted much interest, trends for major groups of causes of death have been analysed while trends in specific causes of death might shed light on the underlying determinants.Methods We analysed trends in total and cause-specific mortality in Russia for 1991-2006. The records of 24 836 forensic autopsies carried out during the period 1990-2004 in the city of Barnaul were analysed with respect to blood alcohol level.Results Diseases of the circulatory system (in the age group 35-69 years) and external causes (in the age group 15-34 years) were the main contributors to the fluctuations in Russian mortality rates observed in 1991-2006. The largest relative changes were for conditions directly related to alcohol intake. Among cardiovascular diseases, fluctuations were due to 'other forms' of acute and chronic ischaemia, and to atherosclerotic heart disease, while rates of myocardial infarction were low and relatively constant. In the autopsy series a very high proportion of decedents whose death was attributed to 'other' or 'not classified' cardiovascular diseases had lethal or potentially lethal concentrations of ethanol in blood.Conclusions The increases in mortality in 1991-94 and in 1998-2003 coincided with economic and societal crisis, while decreases in 1994-98 and 2003-06 correlate with improvement in the economic situation. Excessive alcohol intake is a major cause of premature male Russian mortality, although many alcohol-related deaths are wrongly attributed to diseases of the circulatory system.

The largest study ever undertaken to examine the health effects of tobacco finds that there are already a million deaths a year from smoking in China, and it predicts large increases in mortality over the next few decades. This pattern is likely to be repeated in other developing countries.

Low body mass index (BMI) has been associated with increased risk of lung cancer. However, the nature of the association, especially in populations with relatively low BMI, is less well characterized, as is the relevance to it of smoking. A nationally representative prospective cohort study included 217,180 Chinese men aged 40-79 years in 1990-91 who had no prior history of cancer and were followed up for 15 years. Standardized hazard ratios (HRs) were calculated for lung cancer mortality by baseline BMI. The mean baseline BMI was 21.7 kg/m(2), and 2,145 lung cancer deaths were recorded during 15 years of follow-up. The prevalence of smoking was strongly inversely associated with BMI, but no apparent relationship was seen between amount smoked (or other measures of smoking intensity) and BMI among smokers. Overall there was a strong inverse association between BMI and lung cancer mortality (p < 0.0001 for trend) after excluding the first 3 years of follow-up. This association appeared to be confined mainly to current smokers, with no apparent relationship in nonsmokers (p < 0.001 for difference between slopes). Among current smokers, the inverse association appeared to be log-linear, with each 5 kg/m(2) lower BMI associated with a 35% (95% confidence interval: 24-46%; p < 0.0001) higher lung cancer mortality, and it persisted after excluding those who had reported poor health status or history of any disease or respiratory symptoms at baseline. In this relatively lean Chinese male population, low BMI was strongly associated with increased risk of lung cancer only among current smokers.

We did, somewhat to our surprise, find in Russia fewer breast cancer deaths than expected among women who reportedly drank the equivalent of at least one 500 mL bottle of vodka per week. There were 28 breast cancer deaths (relative risk 0·54, 95% CI 0·43–0·69) among women who reportedly drank at least one but less than three bottles per week, and seven deaths (relative risk 0·26, 0·17–0·39) among those who usually drank more (among whom the average consumption was about one bottle of vodka per day).1Zaridze D Brennan P Boreham J et al.Alcohol and cause-specific mortality in Russia: a retrospective case-control study of 48 557 adult deaths.Lancet. 2009; 373: 2201-2214Summary Full Text Full Text PDF PubMed Scopus (259) Google Scholar Because these findings are already adjusted for age, they cannot be accounted for by competing causes of death. We could not adjust our results for any differences in bodyweight, but such adjustment would not have been appropriate because heavy drinking might directly or indirectly cause malnutrition or emaciation, which might in turn offer some protection against breast cancer. Even if extreme drinking does somewhat reduce breast cancer, however, this is of little relevance to public health, since overall mortality (from any cause) was greatly increased by alcohol among women who drank about one bottle of vodka per day. Of those, 503 (relative risk 8·17) died from the diseases that we had found in men to be closely associated with alcohol use, 351 (relative risk 9·26) died from accidents and violence, and another 277 such women died from alcohol poisoning. Moreover, alcohol caused even greater numbers of premature deaths among men than among women; the overall probability that a 15-year-old male will die before age 55 years is only 7% at current UK death rates, but it is 31% at current Russian death rates (figure, death rates for 2007). At these ages, alcohol is the main cause of the large difference in mortality between Russia and the UK, and is the main cause of the large temporal fluctuations in Russian mortality. Alcohol is even more important than tobacco as a cause of death in Russia, and alcohol and tobacco together account for most or all of the difference in premature mortality between Russia and western Europe. These findings recently led the Russian President to ask his Health Minister for a national anti-alcohol strategy.4Kilner J Say no to vodka, president tells Russians.http://www.reuters.com/article/lifestyleMolt/idUSTRE55T6LW20090630Google Scholar Whether or not the apparent shortfall in breast cancer mortality among heavy drinkers is real, it accounts for only about 0·1% of adult deaths in Russia. Careful interpretation of it is therefore of little relevance to the findings for alcohol and overall mortality. We declare that we have no conflicts of interest. Did alcohol protect against death from breast cancer in Russia?David Zaridze and colleagues (June 27, p 2201)1 investigated the effect of alcohol consumption on cause-specific mortality in Russia and observed that high alcohol intake had a protective effect on death from breast cancer, a finding that contrasts with current evidence of increased risk of breast cancer with alcohol consumption.2 Full-Text PDF

Background Alcohol is an important determinant of the high and fluctuating adult mortality rates in Russia, but cause-specific detail is lacking. Our case-control study investigated the effects of alcohol consumption on male and female cause-specific mortality.Methods In three Russian industrial cities with typical 1990s mortality patterns (Tomsk, Bamaul, Biysk), the addresses of 60416 residents who had died at ages 15-74 years in 1990-2001 were visited in 2001-05. Family members were present for 50 066 decedents; for 48 557 (97%), the family gave proxy information on the decedents' past alcohol use and on potentially confounding factors. Cases (n=43082) were those certified as dying from causes we judged beforehand might be substantially affected by alcohol or tobacco; controls were the other 5475 decedents. Case versus control relative risks (RRs; calculated as odds ratios by confounder-adjusted logistic regression) were calculated in ever-drinkers, defining the reference category by two criteria: usual weekly consumption always less than 0.5 half-litre bottles of vodka (or equivalent in total alcohol content) and maximum consumption of spirits in 1 day always less than 0.5 half-litre bottles. Other ever-drinkers were classified by usual weekly consumption into three categories: less than one, one to less than three, and three or more (mean 5.4 [SD 1.4]) bottles of vodka or equivalent.Findings In men, the three causes accounting for the most alcohol-associated deaths were accidents and violence (RR 5.94, 95% CI 5.35-6.59, in the highest consumption category), alcohol poisoning (21.68, 17.94-26.20), and acute ischaemic heart disease other than myocardial infarction (3.04, 2.73-3.39), which includes some misclassified alcohol poisoning. There were significant excesses of upper aerodigestive tract cancer (3.48, 2.84-4.27) and liver cancer (2.11, 1.64-2.70). Another five disease groups had RRs of more than 3.00 in the highest alcohol category: tuberculosis (4.14, 3.44-4.98), pneumonia (3.29, 2.83-3.83), liver disease (6.21, 5.16-7.47), pancreatic disease (6.69, 4.98-9.00), and ill-specified conditions (7.74, 6.48-9.25). Although drinking was less common in women, the RRs associated with it were generally more extreme. After correction for reporting errors, alcohol-associated excesses accounted for 52% of all study deaths at ages 15-54 years (men 8182 [59%] of 13968, women 1565 [33%] of 4751) and 18% of those at 55-74 years (men 3944 [22%] of 17 536, women 1493 [12%] of 12 302). Allowance for under-representation of extreme drinkers would further increase alcohol-associated proportions. Large fluctuations in mortality from these ten strongly alcohol-associated causes were the main determinants of recent fluctuations in overall mortality in the study region and in Russia as a whole.Interpretation Alcohol-attributable mortality varies by year; in several recent years, alcohol was a cause of more than half of all Russian deaths at ages 15-54 years. Alcohol accounts for most of the large fluctuations in Russian mortality, and alcohol and tobacco account for the large difference in adult mortality between Russia and western Europe.Funding UK Medical Research Council, Cancer Research UK, British Heart Foundation, International Agency for Research on Cancer, and European Commission Directorate-General for Research.

Background: The nationwide effects of smoking on mortality in India have not been assessed reliably.Methods: In a nationally representative sample of 1.1 million homes, we compared the prevalence of smoking among 33,000 deceased women and 41,000 deceased men (case subjects) with the prevalence of smoking among 35,000 living women and 43,000 living men (unmatched control subjects). Mortality risk ratios comparing smokers with nonsmokers were adjusted for age, educational level, and use of alcohol.Results: About 5% of female control subjects and 37% of male control subjects between the ages of 30 and 69 years were smokers. In this age group, smoking was associated with an increased risk of death from any medical cause among both women (risk ratio, 2.0; 99% confidence interval [CI], 1.8 to 2.3) and men (risk ratio, 1.7; 99% CI, 1.6 to 1.8). Daily smoking of even a small amount of tobacco was associated with increased mortality. Excess deaths among smokers, as compared with nonsmokers, were chiefly from tuberculosis among both women (risk ratio, 3.0; 99% CI, 2.4 to 3.9) and men (risk ratio, 2.3; 99% CI, 2.1 to 2.6) and from respiratory, vascular, or neoplastic disease. Smoking was associated with a reduction in median survival of 8 years for women (99% CI, 5 to 11) and 6 years for men (99% CI, 5 to 7). If these associations are mainly causal, smoking in persons between the ages of 30 and 69 years is responsible for about 1 in 20 deaths of women and 1 in 5 deaths of men. In 2010, smoking will cause about 930,000 adult deaths in India; of the dead, about 70% (90,000 women and 580,000 men) will be between the ages of 30 and 69 years. Because of population growth, the absolute number of deaths in this age group is rising by about 3% per year.Conclusions: Smoking causes a large and growing number of premature deaths in India.

Abstract In 1983, a survey of biochemistry, diet and lifestyle was undertaken in 65 of the 69 counties. In 1989, a more detailed survey was undertaken in all 69 of the counties, involving analyses of samples from adults aged 35 to 64 of plasma, of red blood cells, and, from men only, of urine; a three-day weighed household dietary survey, used to estimate average daily intakes of a wide variety of foods and nutrients per “reference man”; questionnaires (including some physical measurements) about dietary, lifestyle, anthropometric, social and economic factors, representing either the individuals being interviewed, their families, or their communities; and geographic characteristics of the county.

OBJECTIVE:To examine the relationship between smoking and risk of esophageal cancer (EC), and present a theoretical framework of control selection in population-based case-control study which was incorporated into a nationwide retrospective survey of mortality in China.METHODS:A large-scale population-based case-control study was incorporated into the nationwide retrospective survey of mortality conducted 1989 - 1991 in 24 urban cities selected by non-random sampling and 79 rural counties selected from 3000 counties included in the 1973 - 1975 cancer distribution survey by random sampling during. A questionnaire survey was conducted by home visit to investigate the death causes and smoking history of 19 734 deceased male adults who died of esophageal cancer during 1986 - 1988 at the age >or= 35. Two control groups were set up to undergo questionnaire survey by home visit to investigate the smoking history of the deceased persons and the informants. Control group I included the surviving spouses or other informants of 31 989 male adults who died of non-malignant digestive diseases during 1986 - 1988 at the age >or= 35, and control group II included 104 846 male spouses of the deceased female adults who died of different causes during 1986 - 1989 at the age >or= 35. The relative risks and population smoking attributable risks for EC were calculated using non-conditional logistic model, and the results were compared for consistency between the analyses using two different control groups.RESULTS:The EC absolute death rates were higher in the smokers than in the non-smokers in all urban and rural area groups. The total EC absolute death rate per 1000 among the non-smokers vs. smokers was 0.37:0.65 in the urban areas, 0.99:1.29 in the inland rural areas, and 1.09:1.62 in the coastal rural areas in the control group I, and there was a similar trend in the control group II. There was a significant dose-response relation between the period of smoking and the death risk of EC and between the daily cigarette consumption and the death risk of EC. The risk ratios, for example, for cigarette per day < 10, 10-, and 20- in the urban men were 1.42, 1.82, 2.22 in the control group I (trend test P < 0.01), and 1.57, 1.95, and 3.18 in the control group II (trend test P < 0.01).CONCLUSION:Smoking is an important risk factor for mortality from EC in China. Investigating the surviving spouses of the deceased patients is a creative, effective, and feasible trial, with the prerequisite of whole population-based survey, in study of the main types of death and the relevant risk factors.

Abstract Mortality rates for 1973-75 were taken from the nationwide survey that had been done during the mid-1970s for other purposes, and mortality rates for 1986-88 were from a special survey carried out in 1989-90 as part of the present study. Many of the causes assigned in the 1973-75 survey are less specific than those assigned in the later survey, although overall mortality and, in most counties, mortality rates from the main causes of death are reasonably reliable from both periods. Age-standardised mortality rates for particular age ranges were always calculated as the unweighted average of the component five-year mortality rates (e.g., 35-39, 40- 44,…,65-69 for the age range 35-69).

Abstract The 2,400 counties that comprise rural China, with an average population of a few hundred thousand per county, differ greatly from each other in the ways the local populations live and in the main diseases by which they die. Many of these differences in lifestyle and disease rates have persisted for centuries. Even though in recent decades there has been a nationwide reduction in death from infectious disease (particularly in childhood), there is still great heterogeneity among counties in childhood mortality rates, as well as in the age-standardised mortality rates from the main chronic diseases of middle age.

Abstract Local survey teams were trained to administer the questionnaires, make physical measurements, collect blood and urine samples and conduct the dietary survey. Aggregate information about the survey xiangs and villages was also gathered, through interviews with officials at the appropriate administrative levels. Two questionnaires focusing on mothers and children—although somewhat external to the main study design—were also included. Each of the six study questionnaires is described briefly below, and the questionnaires themselves are appended (pp787-801) in the original Chinese and in English translation.

Abstract A three-day household dietary survey was carried out in 60 households per county in mainland China (a total of 60 x 69 = 4140 households), split roughly equally between the two study xiangs in that county. These included the same households surveyed in 1983, to the extent possible, with replacements to compensate for attrition due to death or migration.

Abstract In the early 1980s, 69 counties were randomly chosen from the total of about 2400 largely rural counties in China to represent the full range of mortality rates (in the previous 1973-75 nationwide survey) for seven major types of cancer: nasopharynx, oesophagus, stomach, liver, lung, colorectal and leukaemia. These counties are distributed throughout China and are, in aggregate, reasonably representative of rural mainland China as a whole.

Abstract Fasting 10 ml venous blood samples were collected from 8,280 individuals in mainland China in trace-mineral-free heparinized vacutainers, which were placed on ice in light-free vacuum jars. Samples were transported to the county laboratory within about four hours of the last blood draw of the day. Upon arrival at the county laboratory, blood samples were immediately separated into three fractions: 1.3 ml of packed red blood cells (RBCs), washed three times with saline, haemolyzed with 3 ml preservative buffer, then mixed and frozen.