Background-Body fat distribution has been cross-sectionally associated with atherosclerotic disease risk factors, but the prospective relation with coronary heart disease remains uncertain. Methods and Results-We examined the prospective relation between fat distribution indices and coronary heart disease among 24 508 men and women 45 to 79 years of age using proportional hazards regression. During a mean 9.1 years of follow-up, 1708 men and 892 women developed coronary heart disease. The risk for developing subsequent coronary heart disease increased continuously across the range of waist-hip ratio. Hazard ratios (95% CI) of the top versus bottom fifth of waist-hip ratio were 1.55 (1.28 to 1.73) in men and 1.91 (1.44 to 2.54) in women after adjustment for body mass index and other coronary heart disease risk factors. Hazard ratios increased with waist circumference, but risk estimates for waist circumference without hip circumference adjustment were lower by 10% to 18%. After adjustment for waist circumference, body mass index, and coronary heart disease risk factors, hazard ratios for 1-SD increase in hip circumference were 0.80 (95% CI, 0.74 to 0.87) in men and 0.80 (95% CI, 0.69 to 0.93) in women. Hazard ratios for body mass index were greatly attenuated when we adjusted for waist-hip ratio or waist circumference and other covariates. Conclusions-Indices of abdominal obesity were more consistently and strongly predictive of coronary heart disease than body mass index. These simple and inexpensive measurements could be used to assess obesity-related coronary heart disease risk in relatively healthy men and women.

Today, despite decades of developments in medicine and the growing interest in precision healthcare, vast majority of diagnoses happen once patients begin to show noticeable signs of illness. Early indication and detection of diseases, however, can provide patients and carers with the chance of early intervention, better disease management, and efficient allocation of healthcare resources. The latest developments in machine learning (more specifically, deep learning) provides a great opportunity to address this unmet need. In this study, we introduce BEHRT: A deep neural sequence transduction model for EHR (electronic health records), capable of multitask prediction and disease trajectory mapping. When trained and evaluated on the data from nearly 1.6 million individuals, BEHRT shows a striking absolute improvement of 8.0-10.8%, in terms of Average Precision Score, compared to the existing state-of-the-art deep EHR models (in terms of average precision, when predicting for the onset of 301 conditions). In addition to its superior prediction power, BEHRT provides a personalised view of disease trajectories through its attention mechanism; its flexible architecture enables it to incorporate multiple heterogeneous concepts (e.g., diagnosis, medication, measurements, and more) to improve the accuracy of its predictions; and its (pre-)training results in disease and patient representations that can help us get a step closer to interpretable predictions.

We analyzed crosssectional data from 21,828 men and women who were 45 to 79 years of age, residents in Norfolk, United Kingdom, and were recruited between 1993 and 1997. Cigarette smoking habits and other lifestyle factors were assessed using selfreported questionnaires. Anthropometric measures were obtained during a health examination. Results: Waist-hip ratio was highest among current smokers and least among never smokers after adjusting for age, BMI, alcohol intake, total energy intake, physical activity, and education. Higher waist-hip ratio was directly associated with higher smoking pack-years in current and former smokers and inversely with duration since quitting smoking in former smokers. Adjusting for age, BMI, and other covariates, current smokers had higher waist circumference but lower hip circumference compared with former or never smokers. Discussion: Cigarette smoking habits seem to influence fat distribution patterns. Although smokers have lower mean BMI compared with nonsmokers, they have a more metabolically adverse fat distribution profile, with higher central adiposity. The explanation for this association may help elucidate the mechanisms underlying the adverse health consequences of cigarette smoking and abdominal obesity.

Background The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure. MethodsWe did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg). The primary outcome was a major cardiovascular event (defined as a composite of fatal and non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital), analysed as per intention to treat.Findings Data for 344 716 participants from 48 randomised clinical trials were available for this analysis. Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/89 mm Hg in participants without previous cardiovascular disease (n=186 988). There was substantial spread in participants' blood pressure at baseline, with 31 239 (19•8%) of participants with previous cardiovascular disease and 14 928 (8•0%) of individuals without previous cardiovascular disease having a systolic blood pressure of less than 130 mm Hg. The relative effects of blood pressure-lowering treatment were proportional to the intensity of systolic blood pressure reduction. After a median 4•15 years' follow-up (Q1-Q3 2•97-4•96), 42 324 participants (12•3%) had at least one major cardiovascular event. In participants without previous cardiovascular disease at baseline, the incidence rate for developing a major cardiovascular event per 1000 person-years was 31•9 (95% CI 31•3-32•5) in the comparator group and 25•9 (25•4-26•4) in the intervention group. In participants with previous cardiovascular disease at baseline, the corresponding rates were 39•7 (95% CI 39•0-40•5) and 36•0 (95% CI 35•3-36•7), in the comparator and intervention groups, respectively. Haz...

Background-Early menarche has been associated with increased risk of coronary heart disease (CHD), but most studies were relatively small and could not assess risk across a wide range of menarcheal ages; few have examined associations with other vascular diseases. We examined CHD, cerebrovascular disease, and hypertensive disease risks by age at menarche in a large prospective study of UK women. Methods and Results-In 1.2 million women (mean±SD age, 56±5 years) without previous heart disease, stroke, or cancer, menarcheal age was reported to be 13 years by 25%, ≤10 years by 4%, and ≥17 years by 1%. After 11.6 years of follow-up, 73 378 women had first hospitalization for or death from CHD, 25 426 from cerebrovascular disease, and 249 426 from hypertensive disease. Using Cox regression, we calculated relative risks for each vascular outcome by single year of menarcheal age. The relationship was U-shaped for CHD. Compared with women with menarche at 13 years, the adjusted relative risk for CHD for menarche at ≤10 years of age was 1.27 (95% confidence interval, 1.22-1.31; P<0.0001) and for menarche at ≥17 years of age was 1.23 (95% confidence interval, 1.16-1.30; P<0.0001). U-shaped relationships were also seen for cerebrovascular and hypertensive disease, although the magnitudes of these risks for early and late menarche were smaller than those for CHD. Conclusions-In this cohort, the relation of age at menarche to vascular disease risk was U shaped, with both early and late menarche being associated with increased risk. Associations were weaker for cerebrovascular and hypertensive disease than for CHD.

Poor respiratory function and obesity are associated with all-cause and cardiovascular disease mortality. Obese persons may also have impaired lung function, but the mechanism is unclear. The authors investigated the relation between abdominal pattern of obesity and respiratory function in the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk) cohort in Norfolk, United Kingdom. This analysis included 9,674 men and 11,876 women aged 45-79 years with no known preexisting serious illness who had complete anthropometric and respiratory function measures obtained at a health visit between 1993 and 1997. Waist:hip ratio was used to assess abdominal obesity, and forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), obtained by spirometry, were used to assess respiratory function. Both FEV1 and FVC were linearly and inversely related across the entire range of waist:hip ratio in both men and women. This relation persisted after adjustment for age, body mass index, cigarette smoking, social class, physical activity index, prevalent bronchitis/emphysema, and prevalent asthma. The association remained significant among nonobese nonsmokers without preexisting respiratory disease. In the general adult population, abdominal fat deposition may play a role in the impairment of respiratory function among the abdominally obese.

The authors investigated the shape, sex- and age-dependency, and possible confounding of the association between birth weight and systolic blood pressure (SBP) in 197,954 adults from 20 Nordic cohorts (birth years 1910-1987), one of which included 166,249 Swedish male conscripts. Random-effects meta-regression analyses were performed on estimates obtained from age- and sex-stratified analyses within each of the cohorts. There was an inverse association between birth weight and SBP, irrespective of adjustment for concurrent body mass index. The association was linear for males, but for females with a birth weight greater than 4 kg, SBP increased with birth weight (p < 0.01). The association was stronger in the older age groups (p < 0.05), although this could have been a birth cohort effect. The association was stronger among females than among males (p = 0.005) when birth weight was less than or equal to 4 kg. The estimated effect of birth weight on SBP at age 50 years was -1.52 mmHg/kg (95% confidence interval: -2.27, -0.77) in men and -2.80 mmHg/kg (95% confidence interval: -3.85, -1.76) in women. Exclusion of the Swedish conscripts produced nearly identical results. This meta-analysis supports the evidence of an inverse birth weight-SBP association, regardless of adjustment for concurrent body size. It also reveals important heterogeneity in the shape and strength of the association by sex and age.

For adipose tissue distribution assessment to be clinically useful, the ideal adiposity phenotype should provide a single risk estimate that captures the separate 'effects' of abdominal and peripheral adiposity. Although far from perfect, waist-hip ratio may capture separate effects of central and peripheral adiposity. This simple and inexpensive measure could be used to help improve coronary heart disease risk assessment.