Associations between serum high-density lipoprotein cholesterol levels and cause-specific mortality in a general population of 345 000 men and women aged 20-79 years.

BACKGROUND: Benefits of elevated high-density lipoprotein cholesterol (HDL-C) levels are challenged by reports demonstrating U-shaped relations between HDL-C levels and all-cause mortality; the association with cause-specific mortality is less studied. METHODS: A total of 344 556 individuals (20-79 years, 52 % women) recruited from population-based health screening during 1985-2003 were followed until the end of 2018 for all-cause and cause-specific mortality by serum HDL-C level at inclusion of <30, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, 90-99 and >99 mg/dl (< 0.78, 0.78-1.01, 1.04-1.27, 1.30-1.53, 1.55-1.79, 1.81-2.04, 2.07-2.31, 2.33-2.56, >2.56 mmol/L). Hazard ratios (HRs) were adjusted for sex, age, calendar period, smoking, total cholesterol, triglycerides, systolic blood pressure, physical activity, educational length, body mass index and ill health. RESULTS: During a mean follow-up of 22 years, 69 505 individuals died. There were U-shaped associations between HDL-C levels and all-cause, cancer and non-cardiovascular disease/non-cancer mortality (non-CVD/non-cancer), whereas for CVD there was increased risk of death only at lower levels. With HDL-C stratum 50-59 mg/dl (1.30-1.53 mmol/L) as reference, HRs [95% confidence intervals (CIs)] for levels >99 mg/dl (>2.56 mmol/L) were 1.32 (1.21-1.43), 1.05 (0.89-1.24), 1.26 (1.09-1.46) and 1.68 (1.48-1.90) for all-cause, CVD, cancer and non-CVD/non-cancer mortality, respectively. For HDL-C levels <30 mg/dl (0.78 mmol/L), the corresponding HRs (95% CIs) were 1.30 (1.24-1.36), 1.55 (1.44-1.67), 1.14 (1.05-1.23) and 1.19 (1.10-1.29). The mortality from alcoholic liver disease, cancers of mouth-oesophagus-liver, chronic liver diseases, chronic obstructive pulmonary disease, accidents and diabetes increased distinctly with increasing HDL-C above the reference level. HDL-C levels lower than the reference level were mainly associated with increased mortality of ischaemic heart disease (IHD), other CVDs, stomach cancer and diabetes. CONCLUSIONS: Higher HDL-C levels were associated with increased mortality risk of several diseases which also have been associated with heavy drinking, and lower HDL-C levels were associated with increased mortality from IHD, other CVDs, gastric cancer and diabetes.

Life history trade-offs associated with exposure to low maternal capital are different in sons compared to daughters: Evidence from a prospective Brazilian birth cohort.

Background: Environmental exposures in early life explain variability in many physiological and behavioural traits in adulthood. Recently, we showed that exposure to a composite marker of low maternal capital explained the clustering of adverse behavioural and physical traits in adult daughters in a Brazilian birth cohort. These associations were strongly mediated by whether or not the daughter had reproduced by the age of 18 years. Using evolutionary life history theory, we attributed these associations to trade-offs between competing outcomes, whereby daughters exposed to low maternal capital prioritised investment in reproduction and defence over maintenance and growth. However, little is known about such trade-offs in sons. Methods: We investigated 2,024 mother-son dyads from the same birth cohort. We combined data on maternal height, body mass index, income, and education into a composite "maternal capital" index. Son outcomes included reproductive status at the age of 18 years, growth trajectory, adult anthropometry, body composition, cardio-metabolic risk, educational attainment, work status, and risky behaviour (smoking, violent crime). We tested whether sons' early reproduction and exposure to low maternal capital were associated with adverse outcomes and whether this accounted for the clustering of adverse outcomes within individuals. Results: Sons reproducing early were shorter, less educated, and more likely to be earning a salary and showing risky behaviour compared to those not reproducing, but did not differ in foetal growth. Low maternal capital was associated with a greater likelihood of sons' reproducing early, leaving school, and smoking. High maternal capital was positively associated with sons' birth weight, adult size, and staying in school. However, the greater adiposity of high-capital sons was associated with an unhealthier cardio-metabolic profile. Conclusion: Exposure to low maternal investment is associated with trade-offs between life history functions, helping to explain the clustering of adverse outcomes in sons. The patterns indicated future discounting, with reduced maternal investment associated with early reproduction but less investment in growth, education, or healthy behaviour. However, we also found differences compared to our analyses of daughters, with fewer physical costs associated with early reproduction. Exposure to intergenerational "cycles of disadvantage" has different effects on sons vs. daughters, hence interventions may have sex-specific consequences.

Obesity Prevalence and Associated Socio-Demographic Characteristics and Health Behaviors in Russia and Norway.

Associations between obesity and socio-demographic and behavioral characteristics vary between populations. Exploring such differences should throw light on factors related to obesity. We examined associations between general obesity (GO, defined by body mass index) and abdominal obesity (AO, defined by waist-to-hip ratio) and sex, age, socio-economic characteristics (education, financial situation, marital status), smoking and alcohol consumption in women and men aged 40-69 years from the Know Your Heart study (KYH, Russia, N = 4121, 2015-2018) and the seventh Tromsø Study (Tromsø7, Norway, N = 17,646, 2015-2016). Age-standardized prevalence of GO and AO was higher in KYH compared to Tromsø7 women (36.7 vs. 22.0% and 44.2 vs. 18.4%, respectively) and similar among men (26.0 vs. 25.7% and 74.8 vs. 72.2%, respectively). The positive association of age with GO and AO was stronger in KYH vs. Tromsø7 women and for AO it was stronger in men in Tromsø7 vs. KYH. Associations between GO and socio-economic characteristics were similar in KYH and Tromsø7, except for a stronger association with living with spouse/partner in KYH men. Smoking had a positive association with AO in men in Tromsø7 and in women in both studies. Frequent drinking was negatively associated with GO and AO in Tromsø7 participants and positively associated with GO in KYH men. We found similar obesity prevalence in Russian and Norwegian men but higher obesity prevalence in Russian compared to Norwegian women. Other results suggest that the stronger association of obesity with age in Russian women is the major driver of the higher obesity prevalence among them compared to women in Norway.

Comparing prevalence of chronic kidney disease and its risk factors between population-based surveys in Russia and Norway.

BACKGROUND: Little data exists on the prevalence of chronic kidney disease (CKD) in the Russian population. We aimed to estimate the prevalence of CKD in a population-based study in Russia, compare with a similar study in Norway, and investigate whether differences in risk factors explained between-study differences in CKD. METHODS: We compared age- and sex-standardised prevalence of reduced eGFR (< 60 ml/min/1.73m2 CKD-EPI creatinine equation), albuminuria and or a composite indicator of CKD (one measure of either reduced eGFR or albuminuria) between participants aged 40-69 in the population-based Know Your Heart (KYH) study, Russia (2015-2018 N = 4607) and the seventh Tromsø Study (Tromsø7), Norway (2015-2016 N = 17,646). We assessed the contribution of established CKD risk factors (low education, diabetes, hypertension, antihypertensive use, smoking, obesity) to between-study differences using logistic regression. RESULTS: Prevalence of reduced eGFR or albuminuria was 6.5% (95% Confidence Interval (CI) 5.4, 7.7) in KYH and 4.6% (95% CI 4.0, 5.2) in Tromsø7 standardised for sex and age. Odds of both clinical outcomes were higher in KYH than Tromsø7 (reduced eGFR OR 2.06 95% CI 1.67, 2.54; albuminuria OR 1.54 95% CI 1.16, 2.03) adjusted for sex and age. Risk factor adjustment explained the observed between-study difference in albuminuria (OR 0.92 95% CI 0.68, 1.25) but only partially reduced eGFR (OR 1.42 95% CI 1.11, 1.82). The strongest explanatory factors for the between-study difference was higher use of antihypertensives (Russian sample) for reduced eGFR and mean diastolic blood pressure for albuminuria. CONCLUSIONS: We found evidence of a higher burden of CKD within the sample from the population in Arkhangelsk and Novosibirsk compared to Tromsø, partly explained by between-study population differences in established risk factors. In particular hypertension defined by medication use was an important factor associated with the higher CKD prevalence in the Russian sample.

Socioeconomic inequalities in physiological risk biomarkers and the role of lifestyles among Russians aged 35-69 years.

BACKGROUND: Socioeconomic inequalities in cardiovascular (CVD) health outcomes are well documented. While Russia has one of the highest levels of CVD mortality in the world, the literature on contemporary socio-economic inequalities in biomarker CVD risk factors is sparse. This paper aims to assess the extent and the direction of SEP inequalities in established physiological CVD risk biomarkers, and to explore the role of lifestyle factors in explaining SEP inequalities in physiological CVD risk biomarkers. METHODS: We used cross-sectional data from a general population-based survey of Russians aged 35-69 years living in two cities (n = 4540, Know Your Heart study 2015-18). Logistic models were used to assess the associations between raised physiological risk biomarkers levels (blood pressure levels, cholesterol levels, triglycerides, HbA1C, and C-reactive protein) and socioeconomic position (SEP) (education and household financial constraints) adjusting for age, obesity, smoking, alcohol and health-care seeking behavior. RESULTS: High education was negatively associated with a raised risk of blood pressure (systolic and diastolic) and C-reactive protein for both men and women. High education was positively associated with total cholesterol, with higher HDL levels among women, and with low triglycerides and HbA1c levels among men. For the remaining risk biomarkers, we found little statistical support for SEP inequalities. Adjustment for lifestyle factors, and particularly BMI and waist-hip ratio, led to a reduction in the observed SEP inequalities in raised biomarkers risk levels, especially among women. High financial constraints were weakly associated with high risk biomarkers levels, except for strong evidence for an association with C-reactive protein (men). CONCLUSIONS: Notable differences in risk biomarkers inequalities were observed according to the SEP measure employed. Clear educational inequalities in raised physiological risk biomarkers levels, particularly in blood pressure and C-reactive protein were seen in Russia and are partly explained by lifestyle factors, particularly obesity among women. These findings provide evidence-based information on the need for tackling health inequalities in the Russian population, which may help to further contribute to CVD mortality decline.

Nitrate and nitrite contamination in drinking water and cancer risk: A systematic review with meta-analysis.

BACKGROUND: Pollution of water sources, largely from wide-scale agricultural fertilizer use has resulted in nitrate and nitrite contamination of drinking water. The effects on human health of raised nitrate and nitrite levels in drinking water are currently unclear. OBJECTIVES: We conducted a systematic review of peer-reviewed literature on the association of nitrate and nitrite in drinking water with human health with a specific focus on cancer. METHODS: We searched eight databases from 1 January 1990 until 28 February 2021. Meta-analyses were conducted when studies had the same exposure metric and outcome. RESULTS: Of 9835 studies identified in the literature search, we found 111 studies reporting health outcomes, 60 of which reported cancer outcomes (38 case-control studies; 12 cohort studies; 10 other study designs). Most studies were set in the USA (24), Europe (20) and Taiwan (14), with only 3 studies from low and middle-income countries. Nitrate exposure in water (59 studies) was more commonly investigated than nitrite exposure (4 studies). Colorectal (15 studies) and gastric (13 studies) cancers were the most reported. In meta-analyses (4 studies) we identified a positive association of nitrate exposure with gastric cancer, OR = 1.91 (95%CI = 1.09-3.33) per 10 mg/L increment in nitrate ion. We found no association of nitrate exposure with colorectal cancer (10 studies; OR = 1.02 [95%CI = 0.96-1.08]) or cancers at any other site. CONCLUSIONS: We identified an association of nitrate in drinking water with gastric cancer but with no other cancer site. There is currently a paucity of robust studies from settings with high levels nitrate pollution in drinking water. Research into this area will be valuable to ascertain the true health burden of nitrate contamination of water and the need for public policies to protect human health.

Between-study differences in grip strength: a comparison of Norwegian and Russian adults aged 40-69 years.

BACKGROUND: Identifying individuals with low grip strength is an initial step in many operational definitions of sarcopenia. As evidence indicates that contemporaneous Russian populations may have lower mean levels of grip strength than other populations in northern Europe, we aimed to: compare grip strength in Russian and Norwegian populations by age and sex; investigate whether height, body mass index, education, smoking status, alcohol use and health status explain observed differences and; examine implications for case-finding low muscle strength. METHODS: We used harmonized cross-sectional data on grip strength and covariates for participants aged 40-69 years from the Russian Know Your Heart study (KYH) (n = 3833) and the seventh survey of the Norwegian Tromsø Study (n = 5598). Maximum grip strength (kg) was assessed using the same protocol and device in both studies. Grip strength by age, sex and study was modelled using linear regression and between-study differences were predicted from these models. Sex-specific age-standardized differences in grip strength and in prevalence of low muscle strength were estimated using the European population standard of 2013. RESULTS: Normal ranges of maximum grip strength in both studies combined were 33.8 to 67.0 kg in men and 18.7 to 40.1 kg in women. Mean grip strength was higher among Tromsø than KYH study participants and this difference did not vary markedly by age or sex. Adjustment for covariates, most notably height, attenuated between-study differences but these differences were still evident at younger ages. For example, estimated between-study differences in mean grip strength in fully adjusted models were 2.2 kg [95% confidence interval (CI) 1.4, 3.1] at 40 years and 1.0 kg (95% CI 0.5, 1.5) at 65 years in men (age × study interaction P = 0.09) and 1.1 kg (95% CI 0.4, 1.9) at age 40 years and -0.2 kg (95% CI -0.7, 0.3) at 65 years in women (age × study interaction P < 0.01). CONCLUSIONS: We found between-study differences in mean grip strength that are likely to translate into greater future risk of sarcopenia and poorer prospects of healthy ageing for Russian than Norwegian study participants. For example, the average Russian participant had a similar level of grip strength to a Norwegian participant 7 years older. Our findings suggest these differences may have their origins in childhood highlighting the need to consider interventions in early life to prevent sarcopenia.

Socio-demographic, behavioural and psycho-social factors associated with depression in two Russian cities.

BACKGROUND: Russia has a high burden of suicide and alcohol-attributable mortality. However there have been few studies of the epidemiology of depression. METHODS: The study population was 5077 men and women aged 35-69 years from a cross-sectional population based survey in the cities of Arkhangelsk and Novosibirsk (2015-17). Moderate depression was defined as Patient Health Questionnaire-9 (PHQ-9) score≥10. Risk factors considered were socio-demographic factors (age, sex, marital status, living alone, education, employment status, financial constraints); health behaviours (smoking, alcohol use) and psycho-social factors (life events and social support). RESULTS: After mutual adjustment for all other factors, there was evidence that PHQ-9≥10 was associated with sex (higher in women), financial constraints, employment status, being a non-drinker, problem drinking, smoking, not having enough people to confide in and the number of life events in the past 6 months. Employment status was more strongly associated in men (OR 1.84 (95%CI 1.17, 2.88)) than women (OR 1.15 95% CI 0.86, 1.55). The effect size was particularly striking for financial constraints (odd ratio over 3 times higher in those with not enough money for food and clothes compared to no financial constraints), problem drinking (OR 1.72 (1.12, 2.65) among drinkers with CAGE score of 2 and 2.25 (95% CI 1.42, 3.57) in those with score ≥3 compared to zero) and life events (85% higher odds in those experiencing one life event and over 4 times higher odds in those experiencing 3 or more life events) all of which demonstrated a dose-response with PHQ-9>=10. LIMITATIONS: The study was cross-sectional in nature therefore temporal relationships could not be assessed. CONCLUSIONS: We have identified here a range of risk factors for depression among the Russian general population consistent with findings from other populations. The strikingly strong association with financial constraints indicates the importance of social inequality for the burden of depression.

What factors explain the much higher diabetes prevalence in Russia compared with Norway? Major sex differences in the contribution of adiposity.

INTRODUCTION: Compared with many other countries Russia has a high prevalence of diabetes in men and women. However, contrary to what is found in most other populations, the risk is greater among women than men. The reasons for this are unclear. RESEARCH DESIGN AND METHODS: Prevalence and risk factors for diabetes at ages 40-69 years were compared in two population-based studies: Know Your Heart (KYH) (Russia, 2015-2018, n=4121) and the seventh wave of the Tromsø Study (Tromsø 7) (Norway, 2015-2016, n=17 649). Diabetes was defined by the level of glycated hemoglobin and/or self-reported diabetes and/or diabetes medication use. Marginal structural models were used to estimate the role of key risk factors for diabetes in differences between the studies. RESULTS: Age-standardized prevalence of diabetes was higher in KYH compared with Tromsø 7 in men (11.6% vs 6.2%) and in women (13.2% vs 4.3%). Age-adjusted ORs for diabetes in KYH compared with Tromsø 7 were 2.01 (95% CI 1.68 to 2.40) for men and 3.66 (95% CI 3.13 to 4.26) for women. Adiposity (body mass index and waist circumference) explained none of this effect for men but explained 46.0% (39.6, 53.8) for women. Addition of smoking and C reactive protein, as further mediators, slightly increased the percentage explained of the difference between studies to 55.5% (46.5, 66.0) for women but only to 9.9% (-0.6, 20.8) for men. CONCLUSIONS: Adiposity is a key modifiable risk factor that appears to explain half of the almost threefold higher female prevalence of diabetes in Russia compared with Norway, but none of the twofold male difference.

Quantifying the contribution of established risk factors to cardiovascular mortality differences between Russia and Norway.

Surprisingly few attempts have been made to quantify the simultaneous contribution of well-established risk factors to CVD mortality differences between countries. We aimed to develop and critically appraise an approach to doing so, applying it to the substantial CVD mortality gap between Russia and Norway using survey data in three cities and mortality risks from the Emerging Risk Factor Collaboration. We estimated the absolute and relative differences in CVD mortality at ages 40-69 years between countries attributable to the risk factors, under the counterfactual that the age- and sex-specific risk factor profile in Russia was as in Norway, and vice-versa. Under the counterfactual that Russia had the Norwegian risk factor profile, the absolute age-standardized CVD mortality gap would decline by 33.3% (95% CI 25.1-40.1) among men and 22.1% (10.4-31.3) among women. In relative terms, the mortality rate ratio (Russia/Norway) would decline from 9-10 to 7-8. Under the counterfactual that Norway had the Russian risk factor profile, the mortality gap reduced less. Well-established CVD risk factors account for a third of the male and around a quarter of the female CVD mortality gap between Russia and Norway. However, these estimates are based on widely held epidemiological assumptions that deserve further scrutiny.

Primary care use and cardiovascular disease risk in Russian 40-69 year olds: a cross-sectional study.

BACKGROUND: The Russian Federation has very high cardiovascular disease (CVD) mortality rates compared with countries of similar economic development. This cross-sectional study compares the characteristics of CVD-free participants with and without recent primary care contact to ascertain their CVD risk and health status. METHODS: A total of 2774 participants aged 40-69 years with no self-reported CVD history were selected from a population-based study conducted in Arkhangelsk and Novosibirsk, Russian Federation, 2015-2018. A range of co-variates related to socio-demographics, health and health behaviours were included. Recent primary care contact was defined as seeing primary care doctor in the past year or having attended a general health check under the 2013 Dispansarisation programme. RESULTS: The proportion with no recent primary care contact was 32.3% (95% CI 29.7% to 35.0%) in males, 16.3% (95% CI 14.6% to 18.2%) in females, and 23.1% (95% CI 21.6% to 24.7%) overall. In gender-specific age-adjusted analyses, no recent contact was also associated with low education, smoking, very good to excellent self-rated health, no chest pain, CVD 10-year SCORE risk 5+%, absence of hypertension control, absence of hypertension awareness and absence of care-intensive conditions. Among those with no contact: 37% current smokers, 34% with 5+% 10-year CVD risk, 32% untreated hypertension, 20% non-anginal chest pain, 18% problem drinkers, 14% uncontrolled hypertension and 9% Grade 1-2 angina. The proportion without general health check attendance was 54.6%. CONCLUSION: Primary care and community interventions would be required to proactively reach sections of 40-69 year olds currently not in contact with primary care services to reduce their CVD risk through diagnosis, treatment, lifestyle recommendations and active follow-up.

Effect of adiposity on differences in carotid plaque burden in studies conducted in Norway and Russia: a cross-sectional analysis of two populations at very different risk of cardiovascular mortality.

OBJECTIVES: Large differences exist in the burden of cardiovascular disease (CVD) between Russia and Western European countries including Norway. Obesity prevalence may contribute to the differences. We investigated whether difference in the level of adiposity, assessed using body mass index and waist-to-hip ratio(WHR), could explain intercountry differences in the burden of carotid plaque, a measure of atherosclerosis, in the populations. DESIGN: Cross-sectional analysis. Logistic and linear regression models were used. SETTING: We used population-based cross-sectional Know Your Heart (KYH) study in Russia and the Tromsø 7 study (Tromsø 7) in Norway. PARTICIPANTS: 3262 and 1800 men and women aged 40-69 years in KYH and Tromsø 7, respectively. PRIMARY AND SECONDARY OUTCOME: The presence of carotid plaques and plaque score assessed using ultrasound. RESULTS: The presence of carotid plaques and plaque score were higher in KYH than Tromsø 7 regardless of age group and sex. A positive association between carotid plaque burden and adiposity was found (OR of having at least one plaque per SD in WHR 1.18 (95% CI 1.06 to 1.31) for men; 1.15 (1.06 to 1.25) for women)) adjusted for age, smoking and education in a pooled analysis of the two studies. There was little evidence of the interaction between study and adiposity. These effects did not differ between the two studies. However, neither adiposity nor CVD risk factors (smoking, systolic blood pressure, cholesterol, glycosylated haemoglobin) explained the higher carotid plaque burden in KYH compared with Tromsø 7. CONCLUSION: Adiposity, especially abdominal adiposity, is a risk factor for carotid plaque in Russia and Norway, although neither adiposity nor established CVD risk factors explained the higher plaque burden in Russia. To reduce the CVD burden in Russia, beyond prevention and treatment of adiposity, further research is required to understand why Russia has a high burden of atherosclerosis.

Untreated hypertension in Russian 35-69 year olds - a cross-sectional study.

BACKGROUND: The Russian Federation has among the highest rates of cardiovascular disease (CVD) in the world and a high rate of untreated hypertension remains an important risk factor. Understanding who is at greatest risk is important to inform approaches to primary prevention. METHODS: 2,353 hypertensive 35-69 year olds were selected from a population-based study, Know Your Heart, conducted in Arkhangelsk and Novosibirsk, Russian Federation, 2015-2018. The associations between untreated hypertension and a range of co-variates related to socio-demographics, health, and health behaviours were examined. RESULTS: The age-standardised prevalence of untreated hypertension was 51.1% (95% CI 47.8-54.5) in males, 28.8% (25.4-32.5) in females, and 40.0% (37.5-42.5) overall. The factors associated with untreated hypertension relative to treated hypertension were younger ages, self-rated general health as very good-excellent, not being obese, no history of CVD events, no evidence of diabetes or chronic kidney disease, and not seeing a primary care doctor in the past year as well as problem drinking for women and working full time, lower education, and smoking for men. CONCLUSION: The study found relatively high prevalence of untreated hypertension, especially, in men. Recent initiatives to strengthen primary care provision and implementation of a general health check programme (dispansarisation) are promising, although further studies should evaluate other, potentially more effective strategies tailored to the particular circumstances of this population.

Time trends in smoking in Russia in the light of recent tobacco control measures: synthesis of evidence from multiple sources.

BACKGROUND: The study aims at identifying long-term trends and patterns of current smoking by age, gender, and education in Russia, including the most recent period from 2008 during which tobacco control policies were implemented, and to estimate the impact on mortality of any reductions in prevalence. We present an in-depth analysis based on an unprecedentedly large array of survey data. METHODS: We examined pooled micro-data on smoking from 17 rounds of the Russian Longitudinal Monitoring Study of 1996-2016, 11 other surveys conducted in Russia in 1975-2017, and two comparator surveys from England and the USA. Standardization by age and education, regression and meta-analysis were used to estimate trends in the prevalence of current smoking by gender, age, and educational patterns. RESULTS: From the mid-1970s to the mid-2000s smoking prevalence among men was relatively stable at around 60%, after which time prevalence declined in every age and educational group. Among women, trends in smoking were more heterogeneous. Prevalence more than doubled above the age of 55 years from very low levels (< 5%). At younger ages, there were steep increases until the mid-2000s after which prevalence has declined. Trends differed by educational level, with women in the lowest educational category accounting for most of the long-term increase. We estimate that the decline in male smoking may have contributed 6.2% of the observed reduction in cardiovascular deaths among men in the period 2008-16. CONCLUSIONS: The implementation of an effective tobacco control strategy in Russia starting in 2008 coincided with a decline in smoking prevalence among men from what had been stable, high levels over many decades regardless of age and education. Among women, the declines have been more uneven, with young women showing recent downturns, while the smoking prevalence in middle age has increased, particularly among those with minimal education. Among men, these positive changes will have made a small contribution to the reduction in mortality seen in Russia since 2005.

The association between anthropometric measures of adiposity and the progression of carotid atherosclerosis.

BACKGROUND: Few reports are available on the contribution of general and abdominal obesity to the progression of carotid atherosclerosis in late adulthood. This study investigated the impact of four simple anthropometric measures of general and abdominal obesity on the progression of carotid atherosclerosis and the extent to which the association between adiposity and the progression of plaque burden is mediated by cardiometabolic markers. METHODS: Four thousand three hundred forty-five adults (median age 60) from the population-based Tromsø Study were followed over 7 years from the first carotid ultrasound screening to the next. The progression of carotid atherosclerosis was measured in three ways: incidence of plaques in previously plaque-free participants; change in the number of plaques; and total plaque area (TPA). We used generalised linear models to investigate the association between each adiposity measure - body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) - and each outcome. Models were adjusted for potential confounders (age, sex, smoking, education, physical activity). The pathways through which any associations observed might operate were investigated by further adjusting for cardiometabolic mediators (systolic blood pressure, cholesterol, and HbA1c). RESULTS: There was little evidence that adiposity was related to the formation of new plaques during follow-up. However, abdominal adiposity was associated with TPA progression. WHtR showed the largest effect size (mean change in TPA per one standard deviation (SD) increase in WHtR of 0.665 mm2, 95% confidence interval 0.198, 1.133) while BMI showed the smallest. Effect sizes were substantially reduced after the adjustment for potential mediators. CONCLUSIONS: Abdominal obesity indirectly measured with WC seems more strongly associated with the progression of TPA than general obesity. These associations appear to be largely mediated by known cardiometabolic markers.

Self-reported health as a predictor of mortality: A cohort study of its relation to other health measurements and observation time.

Self-reported health (SRH) is widely used as an epidemiological instrument given the changes in public health since its introduction in the 1980s. We examined the association between SRH and mortality and how this is affected by time and health measurements in a prospective cohort study using repeated measurements and physical examinations of 11652 men and 12684 women in Tromsø, Norway. We used Cox proportional hazard regression to estimate hazard ratios (HRs) of death for SRH, controlling for pathology, biometrics, smoking, sex and age. SRH predicted mortality independently of other, more objective health measures. Higher SRH was strongly associated with lower mortality risk. Poor SRH had HR 2.51 (CI: 2.19, 2.88). SRH is affected by disease, mental health and other risk factors, but these factors had little impact on HRs (Poor SRH: HR 1.99; CI: 1.72, 2.31). SRH predicted mortality, but with a time-dependent effect. Time strongly affected the hazard ratio for mortality, especially after ten-year follow-up (Poor SRH HR 3.63 at 0-5 years decreased to HR 1.58 at 15-21 years). SRH has both methodological and clinical value. It should not be uncritically utilised as a replacement instrument when measures of physical illness and other objective health measures are lacking.

Trends in life expectancy and age-specific mortality in England and Wales, 1970-2016, in comparison with a set of 22 high-income countries: an analysis of vital statistics data.

BACKGROUND: Since 2010, the rate of improvement in life expectancy in the UK has slowed. We aimed to put this trend in the context of changes over the long term and in relation to a group of other high-income countries. METHODS: We compared sex-specific trends in life expectancy since 1970 and age-specific mortality in England and Wales with median values for 22 high-income countries (in western Europe, Australia, Canada, New Zealand, Japan, and the USA). We used annual mortality data (1970-2016) from the Human Mortality Database. FINDINGS: Until 2011-16, male life expectancy in England and Wales followed the median life expectancy of the comparator group. By contrast, female life expectancy was below the median and is among the lowest of the countries considered. In 2011-16, the rate of improvement in life expectancy slowed sharply for both sexes in England and Wales, and slowed more moderately in the comparator group because of negative trends in all adult age groups. This deceleration resulted in a widening gap between England and Wales and the comparators from 2011 onwards. Since the mid-2000s, for the first time, mortality rates in England and Wales among people aged 25-50 years were appreciably higher than in the comparator group. INTERPRETATION: Although many countries have seen slower increases in life expectancy since 2011, trends in England and Wales are among the worst. The poor performance of female life expectancy over the long-term is in part driven by the relative timing of the smoking epidemic across countries. The previously overlooked higher mortality among young working-age adults in England and Wales relative to other countries deserves urgent attention. FUNDING: None.

Low Maternal Capital Predicts Life History Trade-Offs in Daughters: Why Adverse Outcomes Cluster in Individuals.

Background: Some individuals appear prone to multiple adverse outcomes, including poor health, school dropout, risky behavior and early reproduction. This clustering remains poorly understood. Drawing on evolutionary life history theory, we hypothesized that maternal investment in early life would predict the developmental trajectory and adult phenotype of female offspring. Specifically, we predicted that daughters receiving low investment would prioritize the life history functions of "reproduction" and "defense" over "growth" and "maintenance," increasing the risk of several adverse outcomes. Methods: We investigated 2,091 mother-daughter dyads from a birth cohort in Pelotas, Brazil. We combined data on maternal height, body mass index, income, and education into a composite index of "maternal capital." Daughter outcomes included reproductive status at 18 years, growth, adult anthropometry, body composition, cardio-metabolic risk, educational attainment, work status, and risky behavior. We tested whether daughters' early reproduction (<18 years) and exposure to low maternal capital were associated with adverse outcomes, and whether this accounted for the clustering of adverse outcomes within individuals. Results: Daughters reproducing early were shorter, more centrally adipose, had less education and demonstrated more risky behavior compared to those not reproducing. Low maternal capital was associated with greater likelihood of the daughter reproducing early, smoking and having committed violent crime. High maternal capital was positively associated with the daughter's birth weight and adult size, and the likelihood of being in school. Associations of maternal capital with cardio-metabolic risk were inconsistent. Daughters reproducing early comprised 14.8% of the population, but accounted for 18% of obesity; 20% of violent crime, low birth weight and short stature; 32% of current smoking; and 52% of school dropout. Exposure to low maternal capital contributed similarly to the clustering of adverse outcomes among daughters. Outcomes were worst among daughters characterized by both low maternal capital and early reproduction. Conclusion: Consistent with life history theory, daughters exposed to low maternal capital demonstrate "future discounting" in behavior and physiology, prioritizing early reproduction over growth, education, and health. Trade-offs associated with low maternal capital and early reproduction contribute to clustering of adverse outcomes. Our approach provides new insight into inter-generational cycles of disadvantage.

Adiposity in middle and old age and risk of death from dementia: 40-year follow-up of 19,000 men in the Whitehall study.

AIMS AND OBJECTIVES: to examine the hypothesis that obesity is protective for dementia, we compared the associations of death from dementia with body weight and body mass index (BMI) in both middle and old age. DESIGN: height and weight were measured in a prospective study of 19,019 middle-aged men in the Whitehall study in 1967-70 and in 6,158 surviving participants at resurvey in 1997. Cox regression was used to examine the associations of death from dementia over a 40-year period with weight or BMI measured by health professionals in middle and old age adjusting for age, smoking habits, employment grade and marital status. SETTING: central government employees in London, UK. MAIN OUTCOMES MEASURE: death due to dementia in 320 participants. RESULTS: body weight measured in middle age was weakly inversely associated with death from dementia (hazard ratio 0.98 [95%CI: 0.97-0.99] per kg), but neither height nor BMI were related to risk of dementia. In contrast, body weight in old age was more strongly inversely related to deaths from dementia (0.96; [0.95-0.98] per kg) as was BMI (0.92 [0.86-0.97] per kg/m2). Weight loss over the 30 years between baseline and resurvey was associated with a higher risk of death from dementia, with an adjusted HR per kg/30 years of 1.04 [95%CI: 1.02-1.08] and the association with loss of BMI was even stronger (adjusted HR of 1.10 [1.03-1.19]) per kg/m2 decrease. CONCLUSIONS: the stronger inverse associations of deaths from dementia with BMI in old age, compared with middle age, together with strong positive associations of loss of BMI or body weight between middle and old age casts doubt on previous suggestions that obesity protects against death from dementia.

Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK.

BACKGROUND: BMI is known to be strongly associated with all-cause mortality, but few studies have been large enough to reliably examine associations between BMI and a comprehensive range of cause-specific mortality outcomes. METHODS: In this population-based cohort study, we used UK primary care data from the Clinical Practice Research Datalink (CPRD) linked to national mortality registration data and fitted adjusted Cox regression models to examine associations between BMI and all-cause mortality, and between BMI and a comprehensive range of cause-specific mortality outcomes (recorded by International Classification of Diseases, 10th revision [ICD-10] codes). We included all individuals with BMI data collected at age 16 years and older and with subsequent follow-up time available. Follow-up began at whichever was the latest of: start of CPRD research-standard follow up, the 5-year anniversary of the first BMI record, or on Jan 1, 1998 (start date for death registration data); follow-up ended at death or on March 8, 2016. Fully adjusted models were stratified by sex and adjusted for baseline age, smoking, alcohol use, diabetes, index of multiple deprivation, and calendar period. Models were fitted in both never-smokers only and the full study population. We also did an extensive range of sensitivity analyses. The expected age of death for men and women aged 40 years at baseline, by BMI category, was estimated from a Poisson model including BMI, age, and sex. FINDINGS: 3 632 674 people were included in the full study population; the following results are from the analysis of never-smokers, which comprised 1 969 648 people and 188 057 deaths. BMI had a J-shaped association with overall mortality; the estimated hazard ratio per 5 kg/m2 increase in BMI was 0·81 (95% CI 0·80-0·82) below 25 kg/m2 and 1·21 (1·20-1·22) above this point. BMI was associated with all cause of death categories except for transport-related accidents, but the shape of the association varied. Most causes, including cancer, cardiovascular diseases, and respiratory diseases, had a J-shaped association with BMI, with lowest risk occurring in the range 21-25 kg/m2. For mental and behavioural, neurological, and accidental (non-transport-related) causes, BMI was inversely associated with mortality up to 24-27 kg/m2, with little association at higher BMIs; for deaths from self-harm or interpersonal violence, an inverse linear association was observed. Associations between BMI and mortality were stronger at younger ages than at older ages, and the BMI associated with lowest mortality risk was higher in older individuals than in younger individuals. Compared with individuals of healthy weight (BMI 18·5-24·9 kg/m2), life expectancy from age 40 years was 4·2 years shorter in obese (BMI ≥30·0 kg/m2) men and 3·5 years shorter in obese women, and 4·3 years shorter in underweight (BMI <18·5 kg/m2) men and 4·5 years shorter in underweight women. When smokers were included in analyses, results for most causes of death were broadly similar, although marginally stronger associations were seen among people with lower BMI, suggesting slight residual confounding by smoking. INTERPRETATION: BMI had J-shaped associations with overall mortality and most specific causes of death; for mental and behavioural, neurological, and external causes, lower BMI was associated with increased mortality risk. FUNDING: Wellcome Trust.