M Shipley’s research while affiliated with Van London Co. and other places

Background The prevalence of type 2 diabetes is increasing rapidly, particularly among younger adults. It is estimated that people with diabetes die, on average, six years earlier than people without diabetes. Our aim was to provide reliable estimates of the associations of age at diagnosis of diabetes with all-cause and cause-specific mortality and reductions in life expectancy. Methods We conducted a combined analysis of individual-participant-data from two large-scale data sources in 19 high-income countries, Emerging Risk Factors Collaboration (96 cohorts, baseline years 1961-2020, latest follow up years 1980-2020) and UK Biobank (baseline year 2006, latest follow up year 2020). We calculated age- and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes in 1,515,718 participants, in whom deaths were recorded during 23.1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to contemporary age-specific death rates in US and Europe. Findings We observed a log-linear dose-response association between earlier age at diagnosis of diabetes and higher risk of all-cause mortality as compared to concurrent participants without diabetes. HRs were 2.69 (95% CI: 2.43-2.97) at 30-39 years, 2.26 (2.08-2.45) at 40-49 years, 1.84 (1.72-1.97) at 50-59 years, 1.57 (1.47-1.67) at 60-69 years, and 1.39 (1.25-1.51) at age ≥70 years. HRs per decade earlier diagnosis were similar for men and women. Using US death rates, a 50-year-old with diabetes, diagnosed at age 30, 40, or 50 years died on average 14, 10, or 6 years earlier, respectively, than an individual without diabetes. Corresponding estimates were 13, 9, or 5 years earlier using EU death rates. Interpretation Every decade of earlier diagnosis of diabetes was associated with about three to four years of lower life expectancy, highlighting the potential value of early interventions that delay or prevent diabetes. Funding BHF, MRC, NIHR, HDRUK

2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. Methods: In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. Results: Individual participant-level data were analysed from 980 793 adults. During 9·8 million person-years of follow-up, among participants aged between 35 and 89 years, 19 686 (25·6%) of 76 965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2·10, 95% CI 1·97–2·24) and tripled risk among women (3·00, 2·71–3·33; χ2 test for heterogeneity p<0·0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35–59 years: 2·60, 2·30–2·94) than in older individuals (aged 70–89 years: 2·01, 1·85–2·19; p=0·0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35–59 years had the highest death RR across all age and sex groups (5·55, 4·15–7·44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35–59 years, the excess absolute risk was 0·05% (95% CI 0·03–0·07) per year in women compared with 0·08% (0·05–0·10) per year in men; the corresponding excess at ages 70–89 years was 1·08% (0·84–1·32) per year in women and 0·91% (0·77–1·05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes. Interpretation: Independent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained. Funding: UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union BIOMED programme, and National Institute on Aging (US National Institutes of Health).

Background: Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. Methods: In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. Results: Individual participant-level data were analysed from 980 793 adults. During 9·8 million person-years of follow-up, among participants aged between 35 and 89 years, 19 686 (25·6%) of 76 965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2·10, 95% CI 1·97-2·24) and tripled risk among women (3·00, 2·71-3·33; χ2 test for heterogeneity p<0·0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35-59 years: 2·60, 2·30-2·94) than in older individuals (aged 70-89 years: 2·01, 1·85-2·19; p=0·0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35-59 years had the highest death RR across all age and sex groups (5·55, 4·15-7·44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35-59 years, the excess absolute risk was 0·05% (95% CI 0·03-0·07) per year in women compared with 0·08% (0·05-0·10) per year in men; the corresponding excess at ages 70-89 years was 1·08% (0·84-1·32) per year in women and 0·91% (0·77-1·05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes. Interpretation: Independent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained. Funding: UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union BIOMED programme, and National Institute on Aging (US National Institutes of Health).

Background There are steep social class differences in smoking in Western countries, but less is known about these differences in other countries. Even less is known about how class differences in smoking change over time across national contexts. We followed up changes in the magnitude of social class differences in smoking in occupational cohorts from Britain, Finland and Japan, and examined whether sociodemographic, health and work related factors explained these changes. Methods Data from the …

Objectives Depression and mortality have been studied separately in patients with coronary heart disease (CHD) and in populations healthy at study inception. This does not allow comparisons across risk-factor groups based on the cross-classification of depression and CHD status. We prospectively examined the effects of depressive symptoms, assessed in 2002-2004, on all-cause and cardiovascular -mortality in a large sample of 5936 middle-aged participants, with and without established CHD, followed over 5.6 years Methods-results We created 4-risk-factor groups based on the cross classification of depressive symptoms and CHD status. The age-and-sex-adjusted hazard ratios for all causes death were 1.67-fold (p< 0.05) higher for participants with only CHD, 2.10-fold (p< 0.001) higher for those with only depressive symptoms and 4.99-fold (p< 0.001) higher for those with both CHD and depressive symptoms when compared to participants without either condition. The two latter risk-factor groups remained at increased risk after adjustments for relevant confounders. Further comparisons indicated that the risks of all-cause death were also higher, but to a lesser extent, for participants with both depressive-symptoms and CHD when compared to those with only one of these conditions. These associations were also observed for cardiovascular mortality Conclusions This study provides evidence that depressive symptoms are associated with an increased risk of all-cause and CVD death and that this risk is particularly marked in depressive participants with co-morbid CHD. Several clinical guidelines have recommended screening, referral, and treatment of depression in primary and cardiovascular care units. These findings suggest that these recommendations need further consideration.

Background: Aortic stiffness is a strong predictor of cardiovascular disease endpoints. Cross-sectional studies have shown associations of various cardiovascular risk factors with aortic pulse wave velocity, a measure of aortic stiffness, but the long-term impact of these factors on aortic stiffness is unknown.

Objective To examine the relationship between binge drinking at baseline and the onset of new depression during 24?years of follow-up after adjustment for age, socio-economic status, education and marital status. Design and setting Data from phases 1 (1985?1988) to 9 (2007?2009) of the Whitehall II prospective cohort were used. Participants 5985 (male=4161, female=1824) British civil servants aged 35?55?years who were free from depression at baseline. Comparison groups Cohort members were grouped, at phase 1, according to their self-reported usual and maximum number of alcoholic drinks consumed in a single sitting?abstainers, non-bingers (reference category) and bingers. Alcohol consumption was split into two categories and number of drinks consumed was converted to units for analysis: wine and spirits (1 unit per drink), and beer (2 units per drink). For usual drinking sessions those who reported consuming 5+ units of wine/spirits and 10+ units of beer were categorised as bingers, those consuming 1?4 units of wine/spirits or 1?9 units of beer were classified as non-bingers. For maximum drinking sessions, participants were defined as bingers following the Department of Health guidelines as those consuming 8+ or 6+ units of alcohol for males and females respectively for both categories of consumption. Those who reported consuming no drinks were classified as abstainers in all analyses. Main outcome measures The 30-item General Health Questionnaire (GHQ-30) was administered at all phases of data collection. The depression subscale of the GHQ-30 was used to identify new cases of depression (scores of 4 or more) across all phases. Results Adjusted HRs and 95% CIs were estimated using Cox proportional hazard models fitted in the total cohort and stratified by gender. Usual drinking session spirit/wine bingers had an elevated risk of depression (HR 1.28, CI 1.02 to to 1.60) compared to non-bingers in the total sample. Maximum drinking session spirit/wine bingers had a greater risk of depression in the total (HR 1.23, CI 1.04 to to 1.44) and male (HR 1.27, CI 1.03 to to 1.56) samples. There were no statistically significant effects when using beer measures as exposures or for abstainers in any alcohol measures after adjustment for confounders. Conclusion Binge drinking on wine and spirits, but not beer, in midlife increases the risk of having a depressive episode over the course of the following 22?24?year period. Future work will examine other covariates and explore bidirectional issues in this relationship.

Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20,842 patients with coronary heart disease, 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12,785 incident cases of coronary heart disease during 2.79 million person-years at risk). We analysed -1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy. The minor allele frequency of -1131T>C was 8% (95% CI 7-9). -1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3.5% [95% CI 2.6-4.6]; 0.053 mmol/L [0.039-0.068]), lower apolipoprotein AI (1.3% [0.3-2.3]; 0.023 g/L [0.005-0.041]), and higher apolipoprotein B (3.2% [1.3-5.1]; 0.027 g/L [0.011-0.043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% (95% CI 12.9-18.7), or 0.25 mmol/L (0.20-0.29), higher (p=4.4x10(-24)). The odds ratio for coronary heart disease was 1.18 (95% CI 1.11-1.26; p=2.6x10(-7)) per C allele, which was concordant with the hazard ratio of 1.10 (95% CI 1.08-1.12) per 16% higher triglyceride concentration recorded in prospective studies. -1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12.2 nmol/L [95% CI 7.7-16.7]; p=9.3x10(-8)) and smaller HDL particle size (0.14 nm [0.08-0.20]; p=7.0x10(-5)), factors that could mediate the effects of triglyceride. These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease. British Heart Foundation, UK Medical Research Council, Novartis.