David A. Leon

Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29.

Abstract Objective: To establish whether fetal growth rate (as distinct from size at birth) is associated with mortality from ischaemic heart disease. Design: Cohort study based on uniquely detailed obstetric records with 97% follow up over the entire life course and linkage to census data in adult life. Subjects: All 14 611 babies delivered at the Uppsala Academic Hospital, Sweden, during 1915-29 followed up to end of 1995. Main outcome measures: Mortality from ischaemic heart disease and other causes. Results: Cardiovascular disease showed an inverse association with birth weight for both men and women, although this was significant only for men. In men a 1000 g increase in birth weight was associated with a proportional reduction in the rate of ischaemic heart disease of 0.77 (95% confidence interval 0.67 to 0.90). Adjustment for socioeconomic circumstances at birth and in adult life led to slight attenuation of this effect. Relative to the lowest fourth of birth weight for gestational age, mortality from ischaemic heart disease in men in the second, third, and fourth fourths was 0.81 (0.66 to 0.98), 0.63 (0.50 to 0.78), and 0.67 (0.54 to 0.82), respectively. The inclusion of birth weight per se and birth weight for gestational age in the same model strengthened the association with birth weight for gestational age but removed the association with birth weight. Conclusions: This study provides by far the most persuasive evidence of a real association between size at birth and mortality from ischaemic heart disease in men, which cannot be explained by methodological artefact or socioeconomic confounding. It strongly suggests that it is variation in fetal growth rate rather than size at birth that is aetiologically important.

Birth weight and risk of type 2 diabetes: A systematic review

CONTEXT Low birth weight is implicated as a risk factor for type 2 diabetes. However, the strength, consistency, independence, and shape of the association have not been systematically examined. OBJECTIVE To conduct a quantitative systematic review examining published evidence on the association of birth weight and type 2 diabetes in adults. DATA SOURCES AND STUDY SELECTION Relevant studies published by June 2008 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1950), and Web of Science (from 1980), with a combination of text words and Medical Subject Headings. Studies with either quantitative or qualitative estimates of the association between birth weight and type 2 diabetes were included. DATA EXTRACTION Estimates of association (odds ratio [OR] per kilogram of increase in birth weight) were obtained from authors or from published reports in models that allowed the effects of adjustment (for body mass index and socioeconomic status) and the effects of exclusion (for macrosomia and maternal diabetes) to be examined. Estimates were pooled using random-effects models, allowing for the possibility that true associations differed between populations. DATA SYNTHESIS Of 327 reports identified, 31 were found to be relevant. Data were obtained from 30 of these reports (31 populations; 6090 diabetes cases; 152 084 individuals). Inverse birth weight-type 2 diabetes associations were observed in 23 populations (9 of which were statistically significant) and positive associations were found in 8 (2 of which were statistically significant). Appreciable heterogeneity between populations (I(2) = 66%; 95% confidence interval [CI], 51%-77%) was largely explained by positive associations in 2 native North American populations with high prevalences of maternal diabetes and in 1 other population of young adults. In the remaining 28 populations, the pooled OR of type 2 diabetes, adjusted for age and sex, was 0.75 (95% CI, 0.70-0.81) per kilogram. The shape of the birth weight-type 2 diabetes association was strongly graded, particularly at birth weights of 3 kg or less. Adjustment for current body mass index slightly strengthened the association (OR, 0.76 [95% CI, 0.70-0.82] before adjustment and 0.70 [95% CI, 0.65-0.76] after adjustment). Adjustment for socioeconomic status did not materially affect the association (OR, 0.77 [95% CI, 0.70-0.84] before adjustment and 0.78 [95% CI, 0.72-0.84] after adjustment). There was no strong evidence of publication or small study bias. CONCLUSION In most populations studied, birth weight was inversely related to type 2 diabetes risk.

Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50-60 years

Abstract Objective: To establish whether the relation between size at birth and non-insulin dependent diabetes is mediated through impaired β cell function or insulin resistance. Design: Cohort study. Setting: Uppsala, Sweden. Subjects: 1333 men whose birth records were traced from a cohort of 2322 men born during 1920-4 and resident in Uppsala in 1970. Main outcome measures: Intravenous glucose tolerance test at age 50 years and non-insulin dependent diabetes at age 60 years. Results: There was a weak inverse correlation (r=-0.07, P=0.03) between ponderal index at birth and 60 minute insulin concentrations in the intravenous glucose tolerance test at age 50 years. This association was stronger (r=-0.19, P=0.001) in the highest third of the distribution of body mass index than in the other two thirds (P=0.01 for the interaction between ponderal index and body mass index). Prevalence of diabetes at age 60 years was 8% in men whose birth weight was less than 3250 g compared with 5% in men with birth weight 3250 g or more (P=0.08; 95% confidence interval for difference −0.3% to 6.8%). There was a stronger association between diabetes and ponderal index: prevalence of diabetes was 12% in the lowest fifth of ponderal index compared with 4% in the other four fifths (P=0.001; 3.0% to 12.6%). Conclusion: These results confirm that reduced fetal growth is associated with increased risk of diabetes and suggest a specific association with thinness at birth. This relation seems to be mediated through insulin resistance rather than through impaired β cell function and to depend on an interaction with obesity in adult life.

Huge variation in Russian mortality rates 1984–94: artefact, alcohol, or what?

BACKGROUND According to published data, between 1984 and 1994 mortality rates in Russia initially underwent a rapid decline followed by an even steeper increase. In 1994, male life expectancy at birth was 57.6 years, having fallen by 6.2 years since 1990. There has been concern that such striking fluctuations in mortality are an artefact, although, among other factors, alcohol consumption has been implicated. METHODS We analysed the age-specific and cause-specific patterns of mortality decrease and increase by use of data from a newly reconstructed mortality series for Russia so that we could examine the plausibility of various explanations for the mortality trends. FINDINGS All major causes of death, with the exception of neoplasms, showed declines in mortality between 1984 and 1987 and increases between 1987 and 1994. In relative terms, these tended to be largest for the age-group 40-50 years; surprisingly, they were of the same magnitude among women and men. The largest declines and subsequent increases in proportional terms were observed for alcohol-related deaths and accidents and violence. However, pronounced effects were also seen for deaths from infections, circulatory disease, and respiratory disease. No substantial variations were seen for neoplasms. INTERPRETATION The stability of mortality from neoplasms in contrast to other causes over the period 1984-94 largely precludes the possibility that the changes in life expectancy are mainly an artefact, particularly one due to underestimation of the population. Although factors such as nutrition and health services may be involved, the evidence is that substantial changes in alcohol consumption over the period could plausibly explain the main features of the mortality fluctuations observed. These results provide a major challenge to public health in Russia and to our understanding of the determinants of alcohol consumption and its role in explaining mortality patterns within and between many other countries.

Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults

Summary Background High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. Methods With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. Findings 5·24 million individuals were included; 166 955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m2 increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56–1·69; p<0·0001), gallbladder (1·31, 1·12–1·52; p<0·0001), kidney (1·25, 1·17–1·33; p<0·0001), cervix (1·10, 1·03–1·17; p=0·00035), thyroid (1·09, 1·00–1·19; p=0·0088), and leukaemia (1·09, 1·05–1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12–1·27), colon (1·10, 1·07–1·13), ovarian (1·09, 1.04–1.14), and postmenopausal breast cancers (1·05, 1·03–1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95–1·00; premenopausal breast cancer 0·89, 0·86–0·92) and in never-smokers (prostate 0·96, 0·93–0·99; premenopausal breast cancer 0·89, 0·85–0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93–1·05; oral cavity 1·07, 0·91–1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m2 population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. Interpretation BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. Funding National Institute for Health Research, Wellcome Trust, and Medical Research Council.

Failure to realise growth potential in utero and adult obesity in relation to blood pressure in 50 year old Swedish men

Abstract Objectives: To clarify the type of fetal growth impairment associated with increased blood pressure in adult life, and to establish whether this association is influenced by obesity and is mediated through impairment of insulin action. Design: Cross sectional survey with retrospective ascertainment of size at birth from obstetric archives. Subjects: 1333 men resident in Uppsala, Sweden, who took part in a 1970 study of coronary risk factors at age 50 and for whom birth weight was traced. Main outcome measures: Systolic and diastolic blood pressure at age 50. Results: In the full study population for a 1000 g increase in birth weight there was a small change in systolic blood pressure of −2.2 mm Hg (95% confidence interval −4.2 to −0.3 mm Hg) and in diastolic blood pressure of −1.0 mm Hg (−2.2 to 0.1 mm Hg). Much stronger effects were observed among men who were born at term and were in the top third of body mass index at age 50, for whom a 1000 g increase in birth weight was associated with a change of −9.1 mm Hg (−16.4 to −1.9 mm Hg) systolic and −4.2 mm Hg (−8.3 to −0.1 mm Hg) diastolic blood pressure. Men who were light at birth (<3250 g) but were of above median adult height had particularly high blood pressure. Adjustment for insulin concentrations reduced the associations of birth weight with systolic and diastolic blood pressure. Conclusions: A failure to realise growth potential in utero (as indicated by being light at birth but tall as an adult) is associated with raised adult blood pressure. Impaired fetal growth may lead to substantial increases in adult blood pressure among only those who become obese. Metabolic disturbances, possibly related to insulin resistance, may provide a pathway through which fetal growth affects blood pressure.

Liver cirrhosis mortality rates in Britain from 1950 to 2002: an analysis of routine data

BACKGROUND Rates of mortality due to cirrhosis of the liver are an important indicator of population levels of alcohol harm. Total recorded alcohol consumption in Britain doubled between 1960 and 2002, giving rise to a need to examine and assess cirrhosis mortality trends. METHODS Mortality rates were calculated for all ages and for specific age-groups (15-44 years and 45-64 years) for cirrhosis of the liver. Rates were directly age-standardised to the European standard population and compared with rates from 12 western European countries for the period 1955-2001. FINDINGS Cirrhosis mortality rates increased steeply in Britain during the 1990s. Between the periods 1987-1991, and 1997-2001, cirrhosis mortality in men in Scotland more than doubled (104% increase) and in England and Wales rose by over two-thirds (69%). Mortality in women increased by almost half (46% in Scotland and 44% in England and Wales). These relative increases are the steepest in western Europe, and contrast with the declines apparent in most other countries examined, particularly those of southern Europe. Cirrhosis mortality rates in Scotland are now one of the highest in western Europe, in 2002 being 45.2 per 100,000 in men and 19.9 in women. INTERPRETATION Current alcohol policies in Britain should be assessed by the extent to which they can successfully halt the adverse trends in liver cirrhosis mortality. The situation in Scotland warrants particular attention.

Hypertension In Sub-Saharan Africa A Systematic Review

Hypertension is an important public health challenge worldwide. Information on the burden of disease from hypertension is essential in developing effective prevention and control strategies. An up-to-date and comprehensive assessment of the evidence concerning hypertension in sub-Saharan Africa is lacking. A literature search of the PUBMED database was conducted and supplemented by a manual search of bibliographies of retrieved articles. The search was restricted to population based studies on hypertension in sub-Saharan Africa published between January 1975 and May 2006. Data were extracted after a standard protocol and using standard data collection forms. Thirty-seven publications met the inclusion criteria. The prevalence of hypertension varied extensively between and within studies. Prevalence of hypertension was higher in urban than rural studies in all studies that covered both types of area, and also increased with increasing age in most studies. In most studies less than 40% of people with blood pressure above the defined normal range had been previously detected as hypertensive. Of people with previously diagnosed hypertension, less than 30% were on drug treatment in most studies, and less than 20% had blood pressure within the defined normal range. Hypertension is of public health importance in sub-Saharan Africa, particularly in urban areas, with evidence of considerable under-diagnosis, treatment, and control. There is an urgent need to develop strategies to prevent, detect, treat, and control hypertension effectively in the African region.

Hazardous alcohol drinking and premature mortality in Russia: a population based case-control study

BACKGROUND The reason for the low life expectancy in Russian men and large fluctuations in mortality are unknown. We investigated the contribution of alcohol, and hazardous drinking in particular, to male mortality in a typical Russian city. METHODS Cases were all deaths in men aged 25-54 years living in Izhevsk occurring between Oct 20, 2003, to Oct 3, 2005. Controls were selected at random from the city population and were frequency matched to deaths by age. Interviews with proxy informants living in the same household as cases were done between Dec 11, 2003, and Nov, 16 2005, and were obtained for 62% (1750/2835) of cases and 57% (1750/3078) of controls. We ascertained frequency and usual amount of beer, wine, and spirits consumed and frequency of consumption of manufactured ethanol-based liquids not intended to be drunk (non-beverage alcohol), and markers of problem drinking. Complete information on markers of problem drinking, frequency of alcohol consumption, education, and smoking was available for 1468 cases and 1496 controls. FINDINGS 751 (51%) cases were classed as problem drinkers or drank non-beverage alcohol, compared with 192 (13%) controls. The mortality odds ratio (OR) for these men, compared with those who either abstained or were non-problematic beverage drinkers, was 6.0 (95% CI 5.0-7.3) after adjustment for smoking and education. The mortality ORs for drinking non-beverage alcohol in the past year (yes vs no) was 9.2 (7.2-11.7) after adjustment for age. Adjustment for volume of ethanol consumed from beverages lowered the OR to 8.3 (6.5-10.7), and further adjustment for education and smoking reduced it to 7.0 (5.5-9.0). A strong direct gradient with mortality was seen for frequency of non-beverage alcohol drinking independent of volume of beverage ethanol consumed. 43% of mortality was attributable to hazardous drinking (problem drinking or non-beverage alcohol consumption, or both) adjusted for smoking and education. INTERPRETATION Almost half of all deaths in working age men in a typical Russian city may be accounted for by hazardous drinking. Our analyses provide indirect support for the contention that the sharp fluctuations seen in Russian mortality in the early 1990s could be related to hazardous drinking as indicated by consumption of non-beverage alcohol.

Economic change, crime, and mortality crisis in Russia: regional analysis

Objective: To identify which aspects of socioeconomic change were associated with the steep decline in life expectancy in Russia between 1990 and 1994. Design: Regression analysis of regional data, with percentage fall in male life expectancy as dependent variable and a range of socioeconomic measures reflecting transition, change in income, inequity, and social cohesion as independent variables. Determination of contribution of deaths from major causes and in each age group to changes in both male and female life expectancy at birth in regions with the smallest and largest declines. Setting: Regions (oblasts) of European Russia(excluding Siberia and those in the Caucasus affected by the Chechen war). Subjects: The population of European Russia. Results: The fall in life expectancy at birth varied widely between regions, with declines for men and women highly correlated. The regions with the largest falls were predominantly urban, with high rates of labour turnover, large increases in recorded crime, and a higher average but unequal distribution of household income. For both men and women increasing rates of death between the ages of 30 and 60 years accounted for most of the fall in life expectancy, with the greatest contributions being from conditions directly or indirectly associated with heavy alcohol consumption. Conclusions: The decline in life expectancy in Russia in the 1990s cannot be attributed simply to impoverishment. Instead, the impact of social and economic transition, exacerbated by a lack of social cohesion, seems to have played a major part. The evidence that alcohol is an important proximate cause of premature death in Russia is strengthened.