David A. Leon

The relationship between alcohol consumption and cause-specific mortality in adults aged ≥ 70 years remain unclear. This study assessed the associations between alcohol consumption with risks of cause-specific mortality in older men. This study included 4,582 London Civil Servants from the 1997–98 Whitehall-I Study resurvey with no prior cardiovascular disease or cancer. Alcohol consumption was self-reported by postal questionnaires and classified as abstainers (lifelong non-drinkers), ex-drinkers, or current drinkers. Current drinkers were further categorised by weekly intake: <7, 7–13, 14–27, 28–41, and ≥ 42 units/week. During a mean follow up of 11.8 years, 4194 deaths (91%) occurred. Compared with light drinkers (< 7 units/week), all-cause mortality risk was highest among ex-drinkers (HR: 1.21, 95% CI 1.11–1.32) and those consuming ≥ 42 units/week (HR: 1.38, 95% CI 1.15–1.67). Among current drinkers, increased alcohol consumption was associated with a higher risk of all-cause mortality (HR: 1.05, 95% CI 1.01–1.08 per 10 units/week) and non-vascular mortality (HR: 1.05, 95% CI 1.01–1.09), but not vascular mortality (HR: 1.04, 95% CI 0.99–1.10). The findings were unaltered by excluding deaths in the first five years of follow-up. The study distinguished ex-drinkers from never-drinkers and excluded participants with major disease to minimise the potential for reverse-causation bias. Alcohol consumption in older men was associated with a higher risk of all-cause mortality, with heavy drinkers experiencing a 38% higher mortality risk than light drinkers.

Background: The poor performance of the UK in reducing mortality compared to many other high-income countries following the 2008 financial crisis have been extensively studied, with particular attention to deaths of despair at working ages. However, longer-term trends in the differences in working-age mortality between the UK and peer countries have not been systematically investigated. Methods: We compared trends (1990–2019) in age-standardised mortality rates at age 25–49 years in the UK and its constituent parts (England and its 9 standard regions, Wales, Scotland, Northern Ireland) with those of 21 peer countries. Findings: Between 1990 and 2019 the UK went from having relatively low mortality rates at age 25–49 years compared to its peers to having one of the highest. This reflects both the better progress made by many other countries in reducing mortality rates as well as an absolute increase in the UK from 2013. Against the counter-factual that rates in the UK followed the median of the comparator countries (2001–2019) this resulted in 3.1 million excess years of life lost. The divergence in mortality of the UK with its peers was apparent from 1990 and was observed for all constituent parts of the UK and English regions. External cause mortality accounted for much of the divergence in rates between 2001 and 2019 (69% women; 78% men), as did the overlapping categories of drug-related deaths (42%; 28%) and suicides (17%; 20%). Alcohol-related deaths made only a small contribution. Interpretation: The divergence in mortality rates at ages 25–49 years in the UK from peer countries was already apparent from 1990, pre-dating the austerity policies two decades later. Nevertheless, austerity may well have exacerbated this longer-term deterioration in the UKs position. The fact that all areas of the UK showed deterioration relative to peer countries indicates that this is a national problem.

Objective To assess the association between educational level and cardiovascular age acceleration metric derived from ECG, and to determine whether this association is mediated by established cardiovascular disease (CVD) risk factors. Design Prospective population-based cohort study (the Tromsø Study). Setting General population of the Tromsø municipality, Norway. Participants The study sample consisted of 4367 participants of the Tromsø Study, who took part in both Tromsø6 (2007–2008) and Tromsø7 (2015–2016), had a 12-lead ECG obtained at Tromsø7 and did not report a history of heart attack, stroke or atrial fibrillation. Primary outcome measures δ-age, a biomarker of cardiovascular ageing, is defined as the difference (in years) between an individual’s ECG-predicted heart age and their chronological age. ECG-predicted heart age was estimated using a previously validated deep neural network. Results Our findings indicate an inverse association between education and δ-age, with a regression coefficient per increment increase in education of −0.24 (95% CI −0.41 to –0.07) in the overall sample, −0.38 (95% CI −0.59 to –0.16) for women and −0.04 (95% CI −0.31 to 0.23) for men. Participants with the highest level of education (university/college for 4 or more years) had the lowest estimated δ-age with a regression coefficient of −0.69 years (95% CI −1.23 to –0.16) compared with the group with primary education for the overall sample, −1.05 years (95% CI −1.73 to –0.37) for women and −0.15 years (95% CI −1.03 to 0.73) for men. CVD risk factors mediated up to 75% of the association between overall education and δ-age, and 80% of the association among those with the highest education level (university/college for 4 or more years). Among women, 50% of the effect of overall education on δ-age was mediated by CVD risk factors, rising to 53% in the category with the highest level of education. However, in the subsample of men, there was no significant association between education and δ-age, and the mediation analysis produced natural direct and indirect effects pointing in opposite directions. Conclusions Cardiovascular ageing is inversely associated with educational level, an effect that appears to be largely mediated through established risk factors.

Background The poor performance of the UK in reducing mortality compared to many other high-income countries following the 2008 financial crisis have been extensively studied, with particular attention to deaths of despair at working ages. However, longer-term trends in the differences in working-age mortality between the UK and peer countries have not been systematically investigated. Methods We compared trends (1990-2019) in age-standardised mortality rates at age 25-49 years in the UK and its constituent parts (England and its 9 standard regions, Wales, Scotland, Northern Ireland) with those of 21 peer countries. Findings Between 1990 and 2019 the UK went from having relatively low mortality rates at age 25-49 years compared to its peers to having one of the highest. This reflects both the better progress made by many other countries in reducing mortality rates as well as an absolute increase in the UK from 2013. Against the counter-factual that rates in the UK followed the median of the comparator countries (2001-2019) this resulted in 3.1 million excess years of life lost. The divergence in mortality of the UK with its peers was apparent from 1990 and was observed for all constituent parts of the UK and English regions. External cause mortality accounted for much of the divergence in rates between 2001 and 2019 (69% women; 78% men), as did the overlapping categories of drug-related deaths (42%; 28%) and suicides (17%; 20%). Alcohol-related deaths made only a small contribution. Interpretation The divergence in mortality rates at ages 25-49 years in the UK from peer countries was already apparent from 1990, pre-dating the austerity policies two decades later. Nevertheless, austerity may well have exacerbated this longer-term deterioration in the UKs position. The fact that all areas of the UK showed deterioration relative to peer countries indicates that this is a national problem.

Worldwide, mortality was strongly affected by the COVID-19 pandemic, both directly through COVID-19 deaths and indirectly through changes in other causes of death. Here, we examine the impact of the pandemic on COVID-19 and non-COVID-19 mortality in 24 countries: Australia, Austria, Brazil, Bulgaria, Canada, Chile, Croatia, Czechia, Denmark, England and Wales, Hungary, Japan, Latvia, Lithuania, The Netherlands, Northern Ireland, Poland, Russia, Scotland, South Korea, Spain, Sweden, Switzerland, and the United States. Using demographic decomposition methods, we compare age- and cause-specific contributions to changes in female and male life expectancy at birth in 2019–2020, 2020–2021, and 2021–2022 with those before the COVID-19 pandemic (2015–2019). We observe large life expectancy losses due to COVID-19 in most countries, usually followed by partial recoveries. Life expectancy losses due to cardiovascular disease (CVD) mortality were widespread during the pandemic, including in countries with substantial (Russia, Central and Eastern Europe, and the Baltic countries) and more modest (United States) improvements in CVD mortality before the pandemic. Many Anglo-Saxon countries, including Canada, Scotland, and the United States, continued their prepandemic trajectories of rising drug-related mortality. Most countries saw small changes in suicide mortality during the pandemic, while alcohol mortality increased and cancer mortality continued to decline. Patterns for other causes were more variable. By 2022, life expectancy had still not returned to prepandemic levels in several countries. Our results suggest important indirect effects of the pandemic on non-COVID-19 mortality through the consequences of COVID-19 infection, nonpharmaceutical interventions, and underreporting of COVID-19-related deaths.

On March 11th 2020, the World Health Organization characterised COVID-19 as a pandemic. Responses to containing the spread of the virus have relied heavily on policies involving restricting contact between people. Evolving policies regarding shielding and individual choices about restricting social contact will rely heavily on perceived risk of poor outcomes from COVID-19. In order to make informed decisions, both individual and collective, good predictive models are required. For outcomes related to an infectious disease, the performance of any risk prediction model will depend heavily on the underlying prevalence of infection in the population of interest. Incorporating measures of how this changes over time may result in important improvements in prediction model performance. This protocol reports details of a planned study to explore the extent to which incorporating time-varying measures of infection burden over time improves the quality of risk prediction models for COVID-19 death in a large population of adult patients in England. To achieve this aim, we will compare the performance of different modelling approaches to risk prediction, including static cohort approaches typically used in chronic disease settings and landmarking approaches incorporating time-varying measures of infection prevalence and policy change, using COVID-19 related deaths data linked to longitudinal primary care electronic health records data within the OpenSAFELY secure analytics platform.

Background: Before the COVID-19 pandemic, stagnating life expectancy trends were reported in some high-income countries (HICs). Despite previous evidence from country-specific studies, there is a lack of comparative research that provides a broader perspective and challenges existing assumptions. This study aims to examine longevity trends and patterns in six English-speaking countries (Australia, Canada, Ireland, New Zealand, United Kingdom, United States) by combining period and cohort perspectives and to compare them with other HICs. Methods: Using data from the Human Mortality and World Health Organization Mortality Databases, we estimated partial life expectancy, lifespan inequality and cohort survival differences for 1970–2021, as well as the contribution of causes of death to the gap in life expectancy between English-speaking countries and the average for other HICs in 2017–19. Results: In the pre-pandemic period, the increase in life expectancy slowed in all English-speaking countries, except Ireland, mainly due to stagnating or rising mortality at young-middle ages. Relative to other HICs, those born in Anglophone countries since the 1970s experienced relative survival disadvantage, largely attributable to injuries (mainly suicides) and substance-related mortality (mainly poisonings). In contrast, older cohorts enjoyed advantages for females in Australia and Canada and for males in all English-speaking countries except the United States. Conclusions: Although future gains in life expectancy in wealthy societies will increasingly depend on reducing mortality at older ages, adverse health trends at younger ages are a cause for concern. This emerging and avoidable threat to health equity in English-speaking countries should be the focus of further research and policy action.

In uncomplicated pregnancies, birthweight is inversely associated with adult non-communicable disease (NCD) risk. One proposed mechanism is maternal malnutrition during pregnancy. Another explanation is that shared genes link birthweight with NCDs. Both hypotheses are supported, but evolutionary perspectives address only the environmental pathway. We propose that genetic and environmental associations of birthweight with NCD risk reflect coordinated regulatory systems between mother and foetus, that evolved to reduce risks of obstructed labour. First, the foetus must tailor its growth to maternal metabolic signals, as it cannot predict the size of the birth canal from its own genome. Second, we predict that maternal alleles that promote placental nutrient supply have been selected to constrain foetal growth and gestation length when fetally expressed. Conversely, maternal alleles that increase birth canal size have been selected to promote foetal growth and gestation when fetally expressed. Evidence supports these hypotheses. These regulatory mechanisms may have undergone powerful selection as hominin neonates evolved larger size and encephalisation, since every mother is at risk of gestating a baby excessively for her pelvis. Our perspective can explain the inverse association of birthweight with NCD risk across most of the birthweight range: any constraint of birthweight, through plastic or genetic mechanisms, may reduce the capacity for homeostasis and increase NCD susceptibility. However, maternal obesity and diabetes can overwhelm this coordination system, challenging vaginal delivery while increasing offspring NCD risk. We argue that selection on viable vaginal delivery played an over-arching role in shaping the association of birthweight with NCD risk. Birthweight robustly predicts the risk of adult diseases such as hypertension, type 2 diabetes and cardiovascular disease. Potential underlying mechanisms include maternal malnutrition in pregnancy, or common alleles underlying both birthweight variability and adult disease risk. Since heavier babies have both better short-term survival and lower adult disease risk, why are most babies born with lower birthweights than would maximize these benefits? We argue that all mothers are at risk of gestating a baby that is too large to pass through the birth canal, resulting in obstructed labour. This problem increased during the evolution of the genus Homo, as neonates evolved larger head size and weight. Natural selection therefore favoured regulatory mechanisms, involving both genetic and physiological pathways, that constrain fetal growth and gestation length to match the dimensions of the maternal pelvis. These mechanisms appear to work better for maternal height, correlated with pelvic dimension, than for high maternal adiposity which was rare until recent millennia. We argue that selection on viable vaginal delivery played an over-arching role in shaping the association of birthweight with NCD risk. Public health interventions to increase birthweight through nutritional supplementation have modest impact, as they may trigger the defence mechanisms we describe.

Background: Before the COVID-19 pandemic, stagnating life expectancy trends were reported in some high-income countries (HICs). Despite previous evidence from country-specific studies, there is a lack of comparative research that provides a broader perspective and challenges existing assumptions. This study aims to examine longevity trends and patterns in six English-speaking countries (Australia, Canada, Ireland, New Zealand, UK, USA) by combining period and cohort perspectives and to compare them with other HICs. Methods: Using data from the Human Mortality and WHO Mortality Databases, we estimated partial life expectancy, lifespan inequality and cohort survival differences for 1970-2021, as well as the contribution of causes of death to the gap in life expectancy between English-speaking countries and the average for other HICs in 2017-19. Results: In the pre-pandemic period, the increase in life expectancy slowed in all English-speaking countries, except Ireland, mainly due to stagnating or rising mortality at young-middle ages. Relative to other HICs, those born in Anglophone countries since the 1970s experienced relative survival disadvantage, largely attributable to injuries (mainly suicides) and substance-related mortality (mainly poisonings). In contrast, older cohorts enjoyed advantages for females in Australia and Canada and for males in all English-speaking countries except the USA. Conclusions: Although future gains in life expectancy in wealthy societies will increasingly depend on reducing mortality at older ages, adverse health trends at younger ages are a cause for concern. This emerging and avoidable threat to health equity in English-speaking countries should be the focus of further research and policy action. Key messages: The study highlights striking similarities between English-speaking high-income countries in terms of adverse health outcomes at young-middle ages compared to a group of other high-income countries (HICs). Each of the Anglophone populations has experienced a marked mortality disadvantage for cohorts born since the early 1970s relative to the average of other HICs, which contrasts with the generally better performance of the older cohorts in some English-speaking countries, particularly for men. In the most recent pre-pandemic period, i.e. 2017-19, the negative contribution of higher mortality at ages below 50 years to the gap in life expectancy at birth between English-speaking countries (excluding Ireland) and other HICs ranged from 0.15 years for Australian women to 2.06 years for US men.