Use of Artificial Intelligence in Improving Outcomes in Heart Disease: A Scientific Statement From the American Heart Association.

A major focus of academia, industry, and global governmental agencies is to develop and apply artificial intelligence and other advanced analytical tools to transform health care delivery. The American Heart Association supports the creation of tools and services that would further the science and practice of precision medicine by enabling more precise approaches to cardiovascular and stroke research, prevention, and care of individuals and populations. Nevertheless, several challenges exist, and few artificial intelligence tools have been shown to improve cardiovascular and stroke care sufficiently to be widely adopted. This scientific statement outlines the current state of the art on the use of artificial intelligence algorithms and data science in the diagnosis, classification, and treatment of cardiovascular disease. It also sets out to advance this mission, focusing on how digital tools and, in particular, artificial intelligence may provide clinical and mechanistic insights, address bias in clinical studies, and facilitate education and implementation science to improve cardiovascular and stroke outcomes. Last, a key objective of this scientific statement is to further the field by identifying best practices, gaps, and challenges for interested stakeholders.

WHO cardiovascular disease risk prediction model performance in 10 regions, China.

Objective: To validate the World Health Organization (WHO) non-laboratory-based cardiovascular disease risk prediction model in regions of China. Methods: We performed an external validation of the WHO model for East Asia using the data set of China Kadoorie Biobank, an ongoing cohort study with 512 725 participants recruited from 10 regions of China from 2004-2008. We also recalculated the recalibration parameters for the WHO model in each region and evaluated the predictive performance of the model before and after recalibration. We assessed discrimination performance by Harrell's C index. Findings: We included 412 225 participants aged 40-79 years. During a median follow-up of 11 years, 58 035 and 41 262 incident cardiovascular disease cases were recorded in women and men, respectively. Harrell's C of the WHO model was 0.682 in women and 0.700 in men but varied among regions. The WHO model underestimated the 10-year cardiovascular disease risk in most regions. After recalibration in each region, discrimination and calibration were both improved in the overall population. Harrell's C increased from 0.674 to 0.749 in women and from 0.698 to 0.753 in men. The ratios of predicted to observed cases before and after recalibration were 0.189 and 1.027 in women and 0.543 and 1.089 in men. Conclusion: The WHO model for East Asia yielded moderate discrimination for cardiovascular disease in the Chinese population and had limited prediction for cardiovascular disease risk in different regions in China. Recalibration for diverse regions greatly improved discrimination and calibration in the overall population.

Device-measured movement behaviours in over 20,000 China Kadoorie Biobank participants.

BACKGROUND: Movement behaviours, including physical activity, sedentary behaviour, and sleep have been shown to be associated with several chronic diseases. However, they have not been objectively measured in large-scale prospective cohort studies in low-and middle-income countries. We aim to describe the patterns of device-measured movement behaviours collected in the China Kadoorie Biobank (CKB) study. METHODS: During 2020 and 2021, a random subset of 25,087 surviving CKB individuals participated in the 3rd resurvey of the CKB. Among them, 22,511 (89.7%) agreed to wear an Axivity AX3 wrist-worn triaxial accelerometer for seven consecutive days to assess their habitual movement behaviours. We developed a machine-learning model to infer time spent in four movement behaviours [i.e. sleep, sedentary behaviour, light intensity physical activity (LIPA), and moderate-to-vigorous physical activity (MVPA)]. Descriptive analyses were performed for wear-time compliance and patterns of movement behaviours by different participant characteristics. RESULTS: Data from 21,897 participants (aged 65.4 ± 9.1 years; 35.4% men) were received for demographic and wear-time analysis, with a median wear-time of 6.9 days (IQR: 6.1-7.0). Among them, 20,370 eligible participants were included in movement behavior analyses. On average, they had 31.1 mg/day (total acceleration) overall activity level, accumulated 7.7 h/day (32.3%) of sleep time, 8.8 h/day (36.6%) sedentary, 5.7 h/day (23.9%) in light physical activity, and 104.4 min/day (7.2%) in moderate-to-vigorous physical activity. There was an inverse relationship between age and overall acceleration with an observed decline of 5.4 mg/day (17.4%) per additional decade. Women showed a higher activity level than men (32.3 vs 28.8 mg/day) and there was a marked geographical disparity in the overall activity level and time allocation. CONCLUSIONS: This is the first large-scale accelerometer data collected among Chinese adults, which provides rich and comprehensive information about device-measured movement behaviour patterns. This resource will enhance our knowledge about the potential relevance of different movement behaviours for chronic disease in Chinese adults.

DAS28(3)CRP is a reliable measure of disease activity in pregnant women with rheumatoid arthritis.

OBJECTIVES: The disease activity of rheumatoid arthritis (RA) in pregnancy is most commonly assessed with the modified Disease Activity Score (DAS)-28, the DAS28(3)CRP. However, the performance of the DAS28(3)CRP in pregnancy has not been compared to musculoskeletal ultrasound (MSK-US) as a gold standard. We performed a prospective pilot study to test the hypothesis that pregnancy-related factors limit the reliability of the DAS28(3)CRP. METHODS: Pregnant women with RA were recruited from an Obstetric Rheumatology clinic and assessed during pregnancy (second (T2) and third (T3) trimesters) and postpartum with DAS28(3)CRP and MSK-US scores, with quantification of power Doppler (PD) signal in small joints (hands and feet). Age-matched non-pregnant women with RA underwent equivalent assessments. PD scores were calculated as mean scores of all joints scanned. RESULTS: We recruited 27 pregnant and 20 non-pregnant women with RA. DAS28(3)CRP was sensitive and specific for active RA in pregnancy and postpartum as defined by positive PD signal, but not in non-pregnancy. There were significant correlations between DAS28(3)CRP and PD scores throughout pregnancy (T2, r=0.82 (95% CI [0.42, 0.95], p<0.01); T3, r=0.68 (95% CI [0.38, 0.86], p<0.01)) and postpartum, r=0.84 (95% CI [0.60, 0.94], p<0.01), while this correlation in non-pregnancy was weaker (r=0.47 (95% CI [0, 0.77], p<0.05). CONCLUSIONS: This pilot study found that DAS28(3)CRP is a reliable measure of disease activity in pregnant women with RA. Based on these data, pregnancy does not appear to confound clinical evaluation of the tender and/or swollen joint counts.

Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults.

Adiposity is associated with multiple diseases and traits, but little is known about the causal relevance and mechanisms underlying these associations. Large-scale proteomic profiling, especially when integrated with genetic data, can clarify mechanisms linking adiposity with disease outcomes. We examined the associations of adiposity with plasma levels of 1463 proteins in 3977 Chinese adults, using measured and genetically-instrumented BMI. We further used two-sample bi-directional MR analyses to assess if certain proteins influenced adiposity, along with other (e.g. enrichment) analyses to clarify possible mechanisms underlying the observed associations. Overall, the mean (SD) baseline BMI was 23.9 (3.3) kg/m2, with only 6% being obese (i.e. BMI ≥ 30 kg/m2). Measured and genetically-instrumented BMI was significantly associated at FDR < 0.05 with levels of 1096 (positive/inverse: 826/270) and 307 (positive/inverse: 270/37) proteins, respectively, with FABP4, LEP, IL1RN, LSP1, GOLM2, TNFRSF6B, and ADAMTS15 showing the strongest positive and PON3, NCAN, LEPR, IGFBP2 and MOG showing the strongest inverse genetic associations. These associations were largely linear, in adiposity-to-protein direction, and replicated (> 90%) in Europeans of UKB (mean BMI 27.4 kg/m2). Enrichment analyses of the top > 50 BMI-associated proteins demonstrated their involvement in atherosclerosis, lipid metabolism, tumour progression and inflammation. Two-sample bi-directional MR analyses using cis-pQTLs identified in CKB GWAS found eight proteins (ITIH3, LRP11, SCAMP3, NUDT5, OGN, EFEMP1, TXNDC15, PRDX6) significantly affect levels of BMI, with NUDT5 also showing bi-directional association. The findings among relatively lean Chinese adults identified novel pathways by which adiposity may increase disease risks and novel potential targets for treatment of obesity and obesity-related diseases.

Genetic associations of adult height with risk of cardioembolic and other subtypes of ischemic stroke: A mendelian randomization study in multiple ancestries.

BACKGROUND: Taller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke. METHODS AND FINDINGS: Height-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations. Two-sample MR approaches were used to examine the associations of genetically determined height with ischemic stroke and its subtypes (cardioembolic stroke, large-artery stroke, and small-vessel stroke) in multiple ancestries (the MEGASTROKE consortium, which included genome-wide studies of stroke and stroke subtypes: 60,341 ischemic stroke cases) supported by additional cases in individuals of white British ancestry (UK Biobank [UKB]: 4,055 cases) and Chinese ancestry (China Kadoorie Biobank [CKB]: 10,297 cases). The associations of genetically determined height with established cardiovascular and other risk factors were examined in 336,750 participants from UKB and 58,277 participants from CKB. In MEGASTROKE, genetically determined height was associated with a 4% lower risk (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.94, 0.99; p = 0.007) of ischemic stroke per 1 standard deviation (SD) taller height, but this masked a much stronger positive association of height with cardioembolic stroke (13% higher risk, OR 1.13 [95% CI 1.07, 1.19], p < 0.001) and stronger inverse associations with large-artery stroke (11% lower risk, OR 0.89 [0.84, 0.95], p < 0.001) and small-vessel stroke (13% lower risk, OR 0.87 [0.83, 0.92], p < 0.001). The findings in both UKB and CKB were directionally concordant with those observed in MEGASTROKE, but did not reach statistical significance: For presumed cardioembolic stroke, the ORs were 1.08 (95% CI 0.86, 1.35; p = 0.53) in UKB and 1.20 (0.77, 1.85; p = 0.43) in CKB; for other subtypes of ischemic stroke in UKB, the OR was 0.97 (95% CI 0.90, 1.05; p = 0.49); and for other nonlacunar stroke and lacunar stroke in CKB, the ORs were 0.89 (0.80, 1.00; p = 0.06) and 0.99 (0.88, 1.12; p = 0.85), respectively. In addition, genetically determined height was also positively associated with atrial fibrillation (available only in UKB), and with lean body mass and lung function, and inversely associated with low-density lipoprotein (LDL) cholesterol in both British and Chinese ancestries. Limitations of this study include potential bias from assortative mating or pleiotropic effects of genetic variants and incomplete generalizability of genetic instruments to different populations. CONCLUSIONS: The findings provide support for a causal association of taller adult height with higher risk of cardioembolic stroke and lower risk of other ischemic stroke subtypes in diverse ancestries. Further research is needed to understand the shared biological and physical pathways underlying the associations between height and stroke risks, which could identify potential targets for treatments to prevent stroke.

Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis.

BACKGROUND: Blood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials. METHODS: We performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of follow-up in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons. FINDINGS: 145 939 participants (88 500 [60·6%] men and 57 429 [39·4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4·5 years (IQR 2·0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0·89 [95% CI 0·84-0·95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0·84 [95% 0·76-0·93]) and angiotensin II receptor blockers (RR 0·84 [0·76-0·92]) reduced the risk of new-onset type 2 diabetes; however, the use of ß blockers (RR 1·48 [1·27-1·72]) and thiazide diuretics (RR 1·20 [1·07-1·35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1·02 [0·92-1·13]). INTERPRETATION: Blood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes. FUNDING: British Heart Foundation, National Institute for Health Research, and Oxford Martin School.

Gender differences in modifiable risk factors for hip fracture: 10-year follow-up of a prospective study of 0.5 million Chinese adults.

BACKGROUND: Little is known about the incidence rates and importance of major modifiable risk factors for hip and major osteoporotic fractures in low- and middle-income countries. We estimated the age- and sex-specific incidence of hip, major osteoporotic, and any fractures and their associated risk factors in Chinese adults. METHODS: This was a prospective study of 512,715 adults, aged 30-79 years, recruited from 10 diverse areas in China from 2004 to 2008 and followed up for 10 years. Age- and sex-specific incidence rates were estimated, and Cox regression was used to yield adjusted hazard ratios (HRs) and population attributable fractions for risk factors. RESULTS: The incidence rates of hip fracture in Chinese adults were 5.1 (95% confidence interval [CI] 5.0-5.3) per 10,000 person-years; they were higher in women than in men and increased by two- to threefold per 10-year older age. Among men, five risk factors for hip fracture, including low education (HR = 1.23; 95% CI 1.04-1.45), regular smoker (1.22, 1.03-1.45), lower weight (1.59, 1.34-1.88), alcohol drinker (1.18, 1.02-1.36), and prior fracture (1.62, 1.33-1.98), accounted for 44.3% of hip fractures. Among women, lower weight (1.30, 1.15-1.46), low physical activity (1.22, 1.10-1.35), diabetes (1.62, 1.41-1.86), prior fracture (1.54, 1.33-1.77), and self-rated poor health (1.29, 1.13-1.47) accounted for 24.9% of hip fractures. Associations of risk factors with major osteoporotic or any fractures were weaker than those with hip fractures. CONCLUSIONS: The age- and sex-specific incidence rates of hip fracture in Chinese adults were comparable with those in Western populations. Five potentially modifiable factors accounted for half of the hip fractures in men and one quarter in women.

Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study.

BACKGROUND: Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD. METHODS AND FINDINGS: We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013-2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range [IQR]): 5.2 (1.2) years) using Cox regression models. We found a linear dose-response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51); for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46); and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies. CONCLUSIONS: In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level.

Correction: Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.1003487.].

Long-term solid fuel use and risks of major eye diseases in China: A population-based cohort study of 486,532 adults.

BACKGROUND: Over 3.5 billion individuals worldwide are exposed to household air pollution from solid fuel use. There is limited evidence from cohort studies on associations of solid fuel use with risks of major eye diseases, which cause substantial disease and economic burden globally. METHODS AND FINDINGS: The China Kadoorie Biobank recruited 512,715 adults aged 30 to 79 years from 10 areas across China during 2004 to 2008. Cooking frequency and primary fuel types in the 3 most recent residences were assessed by a questionnaire. During median (IQR) 10.1 (9.2 to 11.1) years of follow-up, electronic linkages to national health insurance databases identified 4,877 incident conjunctiva disorders, 13,408 cataracts, 1,583 disorders of sclera, cornea, iris, and ciliary body (DSCIC), and 1,534 cases of glaucoma. Logistic regression yielded odds ratios (ORs) for each disease associated with long-term use of solid fuels (i.e., coal or wood) compared to clean fuels (i.e., gas or electricity) for cooking, with adjustment for age at baseline, birth cohort, sex, study area, education, occupation, alcohol intake, smoking, environmental tobacco smoke, cookstove ventilation, heating fuel exposure, body mass index, prevalent diabetes, self-reported general health, and length of recall period. After excluding participants with missing or unreliable exposure data, 486,532 participants (mean baseline age 52.0 [SD 10.7] years; 59.1% women) were analysed. Overall, 71% of participants cooked regularly throughout the recall period, of whom 48% used solid fuels consistently. Compared with clean fuel users, solid fuel users had adjusted ORs of 1.32 (1.07 to 1.37, p < 0.001) for conjunctiva disorders, 1.17 (1.08 to 1.26, p < 0.001) for cataracts, 1.35 (1.10 to 1.66, p = 0.0046) for DSCIC, and 0.95 (0.76 to 1.18, p = 0.62) for glaucoma. Switching from solid to clean fuels was associated with smaller elevated risks (over long-term clean fuel users) than nonswitching, with adjusted ORs of 1.21 (1.07 to 1.37, p < 0.001), 1.05 (0.98 to 1.12, p = 0.17), and 1.21 (0.97 to 1.50, p = 0.088) for conjunctiva disorders, cataracts, and DSCIC, respectively. The adjusted ORs for the eye diseases were broadly similar in solid fuel users regardless of ventilation status. The main limitations of this study include the lack of baseline eye disease assessment, the use of self-reported cooking frequency and fuel types for exposure assessment, the risk of bias from delayed diagnosis (particularly for cataracts), and potential residual confounding from unmeasured factors (e.g., sunlight exposure). CONCLUSIONS: Among Chinese adults, long-term solid fuel use for cooking was associated with higher risks of not only conjunctiva disorders but also cataracts and other more severe eye diseases. Switching to clean fuels appeared to mitigate the risks, underscoring the global health importance of promoting universal access to clean fuels.

Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016.

BACKGROUND: The lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases. METHODS: We used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate. RESULTS: The estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation. CONCLUSIONS: In 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).

Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.

OBJECTIVE: Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH. METHODS: We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses. RESULTS: We identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10-100 ). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85-0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81-0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65-0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42-0.82; p = 0.002), respectively. INTERPRETATION: Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66.

Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers.

This review has been withdrawn because it has been found to be in breach of the Cochrane Commercial Sponsorship policy clause 2:  'Individuals who are currently employed or where employed any time in the last three years by a company that has a real or potential financial interest in the outcome of the review (including but not limited to drug companies or medical device manufacturers); or who hold or have applied for a patent related to the review are prohibited from being Cochrane Review authors. In most cases, current or previous employment would be characterized by the affiliation statement made by the author at the title registration, protocol, or review stage of the review'.

Reallocation of time between device-measured movement behaviours and risk of incident cardiovascular disease.

OBJECTIVE: To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults. METHODS: Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours. Using compositional data analysis Cox regression, we investigated how reallocating time between movement behaviours was associated with CVD incidence. RESULTS: In leave-one-participant-out analysis, our machine-learning method classified free-living movement behaviours with mean accuracy 88% (95% CI 87% to 89%) and Cohen's kappa 0.80 (95% CI 0.79 to 0.82). Among 87 498 UK Biobank participants, there were 4105 incident CVD events. Reallocating time from any behaviour to MVPA, or reallocating time from sedentary behaviour to any behaviour, was associated with lower CVD risk. For an average individual, reallocating 20 min/day to MVPA from all other behaviours proportionally was associated with 9% (95% CI 7% to 10%) lower risk, while reallocating 1 hour/day to sedentary behaviour from all other behaviours proportionally was associated with 5% (95% CI 3% to 7%) higher risk. CONCLUSION: Machine-learning methods classified movement behaviours accurately in free-living accelerometer data. Reallocating time from other behaviours to MVPA, and from sedentary behaviour to other behaviours, was associated with lower risk of incident CVD, and should be promoted by interventions and guidelines.

Association of physical activity with risk of hepatobiliary diseases in China: a prospective cohort study of 0.5 million people.

OBJECTIVE: There is limited prospective evidence on the association of physical activity with hepatobiliary cancer subtypes and other major hepatobiliary diseases, especially in China. We aimed to quantify the associations with risk of these diseases. METHODS: The study population involved 460 937 participants of the prospective China Kadoorie Biobank aged 30-79 years from 10 diverse areas in China without history of cancer or hepatobiliary disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with self-reported total and domain-specific physical activity (occupational and non-occupational, ie, leisure time, household and commuting). RESULTS: During ~10 years of follow-up, 22 012 incident cases of hepatobiliary diseases were recorded. The overall mean (SD) total physical activity was 21.2 (13.9) metabolic equivalent of task (MET)-hours/day, with 62% from occupational activity. Total physical activity was inversely associated with hospitalised non-alcoholic fatty liver disease (HR comparing top vs bottom quintile: 0.62, 95% confidence interval (CI) 0.53 to 0.72), viral hepatitis (0.73, 95% CI 0.62 to 0.87), cirrhosis (0.76, 95% CI 0.66 to 0.88) and liver cancer (0.81, 95% CI 0.71 to 0.93), as well as gallstone disease (0.86, 95% CI 0.81 to 0.90), gallbladder cancer (0.51, 95% CI 0.32 to 0.80) and biliary tract cancer (0.55, 95% CI 0.38 to 0.78). The associations for occupational physical activity were similar to those for total physical activity, but for non-occupational physical activity they differed by disease subtype. For leisure-time physical activity, there was an inverse association with liver cancer and an inverse trend for gallstone disease (HR comparing ≥7.5 MET-hours/day with none: 0.83, 95% CI 0.75 to 0.91 and 0.82, 95% CI 0.66 to 1.01). CONCLUSION: Among Chinese adults, high total physical activity, particularly occupational physical activity, was inversely associated with risk of major hepatobiliary cancers and diseases, including non-alcoholic fatty liver disease, cirrhosis and certain types of cancer.

Red meat, poultry and fish consumption and risk of diabetes: a 9 year prospective cohort study of the China Kadoorie Biobank.

AIMS/HYPOTHESIS: Previous evidence linking red meat consumption with diabetes risk mainly came from western countries, with little evidence from China, where patterns of meat consumption are different. Moreover, global evidence remains inconclusive about the associations of poultry and fish consumption with diabetes. Therefore we investigated the associations of red meat, poultry and fish intake with incidence of diabetes in a Chinese population. METHODS: The prospective China Kadoorie Biobank recruited ~512,000 adults (59% women, mean age 51 years) from ten rural and urban areas across China in 2004-2008. At the baseline survey, a validated interviewer-administered laptop-based questionnaire was used to collect information on the consumption frequency of major food groups including red meat, poultry, fish, fresh fruit and several others. During ~9 years of follow-up, 14,931 incidences of new-onset diabetes were recorded among 461,036 participants who had no prior diabetes, cardiovascular diseases or cancer at baseline. Cox regression analyses were performed to calculate adjusted HRs for incident diabetes associated with red meat, poultry and fish intake. RESULTS: At baseline, 47.0%, 1.3% and 8.9% of participants reported a regular consumption (i.e. ≥4 days/week) of red meat, poultry and fish, respectively. After adjusting for adiposity and other potential confounders, each 50 g/day increase in red meat and fish intake was associated with 11% (HR 1.11 [95% CI 1.04, 1.20]) and 6% (HR 1.06 [95% CI 1.00, 1.13]) higher risk of incident diabetes, respectively. For both, the associations were more pronounced among men and women from urban areas, with an HR (95% CI) of 1.42 (1.15, 1.74) and 1.18 (1.03, 1.36), respectively, per 50 g/day red meat intake and 1.15 (1.02, 1.30) and 1.11 (1.01, 1.23), respectively, per 50 g/day fish intake. There was no significant association between diabetes and poultry intake, either overall (HR 0.96 [95% CI 0.83, 1.12] per 50 g/day intake) or in specific population subgroups. CONCLUSIONS/INTERPRETATION: In Chinese adults, both red meat and fish, but not poultry, intake were positively associated with diabetes risk, particularly among urban participants. Our findings add new evidence linking red meat and fish intake with cardiometabolic diseases. DATA AVAILABILITY: Details of how to access the China Kadoorie Biobank data and rules of China Kadoorie Biobank data release are available from www.ckbiobank.org/site/Data+Access.

Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China.

BACKGROUND: Moderate alcohol intake has been associated with reduced cardiovascular risk in many studies, in comparison with abstinence or with heavier drinking. Studies in east Asia can help determine whether these associations are causal, since two common genetic variants greatly affect alcohol drinking patterns. We used these two variants to assess the relationships between cardiovascular risk and genotype-predicted mean alcohol intake in men, contrasting the findings in men with those in women (few of whom drink). METHODS: The prospective China Kadoorie Biobank enrolled 512 715 adults between June 25, 2004, and July 15, 2008, from ten areas of China, recording alcohol use and other characteristics. It followed them for about 10 years (until Jan 1, 2017), monitoring cardiovascular disease (including ischaemic stroke, intracerebral haemorrhage, and myocardial infarction) by linkage with morbidity and mortality registries and electronic hospital records. 161 498 participants were genotyped for two variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984. Adjusted Cox regression was used to obtain the relative risks associating disease incidence with self-reported drinking patterns (conventional epidemiology) or with genotype-predicted mean male alcohol intake (genetic epidemiology-ie, Mendelian randomisation), with stratification by study area to control for variation between areas in disease rates and in genotype-predicted intake. FINDINGS: 33% (69 897/210 205) of men reported drinking alcohol in most weeks, mainly as spirits, compared with only 2% (6245/302 510) of women. Among men, conventional epidemiology showed that self-reported alcohol intake had U-shaped associations with the incidence of ischaemic stroke (n=14 930), intracerebral haemorrhage (n=3496), and acute myocardial infarction (n=2958); men who reported drinking about 100 g of alcohol per week (one to two drinks per day) had lower risks of all three diseases than non-drinkers or heavier drinkers. In contrast, although genotype-predicted mean male alcohol intake varied widely (from 4 to 256 g per week-ie, near zero to about four drinks per day), it did not have any U-shaped associations with risk. For stroke, genotype-predicted mean alcohol intake had a continuously positive log-linear association with risk, which was stronger for intracerebral haemorrhage (relative risk [RR] per 280 g per week 1·58, 95% CI 1·36-1·84, p<0·0001) than for ischaemic stroke (1·27, 1·13-1·43, p=0·0001). For myocardial infarction, however, genotype-predicted mean alcohol intake was not significantly associated with risk (RR per 280 g per week 0·96, 95% CI 0·78-1·18, p=0·69). Usual alcohol intake in current drinkers and genotype-predicted alcohol intake in all men had similarly strong positive associations with systolic blood pressure (each p<0·0001). Among women, few drank and the studied genotypes did not predict high mean alcohol intake and were not positively associated with blood pressure, stroke, or myocardial infarction. INTERPRETATION: Genetic epidemiology shows that the apparently protective effects of moderate alcohol intake against stroke are largely non-causal. Alcohol consumption uniformly increases blood pressure and stroke risk, and appears in this one study to have little net effect on the risk of myocardial infarction. FUNDING: Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, National Natural Science Foundation of China, British Heart Foundation, Cancer Research UK, GlaxoSmithKline, Medical Research Council, and Wellcome Trust.

Health Effects of Overweight and Obesity in 195 Countries over 25 Years.

BACKGROUND: Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain. METHODS: We analyzed data from 68.5 million persons to assess the trends in the prevalence of overweight and obesity among children and adults between 1980 and 2015. Using the Global Burden of Disease study data and methods, we also quantified the burden of disease related to high body-mass index (BMI), according to age, sex, cause, and BMI in 195 countries between 1990 and 2015. RESULTS: In 2015, a total of 107.7 million children and 603.7 million adults were obese. Since 1980, the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most other countries. Although the prevalence of obesity among children has been lower than that among adults, the rate of increase in childhood obesity in many countries has been greater than the rate of increase in adult obesity. High BMI accounted for 4.0 million deaths globally, nearly 40% of which occurred in persons who were not obese. More than two thirds of deaths related to high BMI were due to cardiovascular disease. The disease burden related to high BMI has increased since 1990; however, the rate of this increase has been attenuated owing to decreases in underlying rates of death from cardiovascular disease. CONCLUSIONS: The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence-based interventions to address this problem. (Funded by the Bill and Melinda Gates Foundation.).

Morbidity and mortality from road injuries: results from the Global Burden of Disease Study 2017.

BACKGROUND: The global burden of road injuries is known to follow complex geographical, temporal and demographic patterns. While health loss from road injuries is a major topic of global importance, there has been no recent comprehensive assessment that includes estimates for every age group, sex and country over recent years. METHODS: We used results from the Global Burden of Disease (GBD) 2017 study to report incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years for all locations in the GBD 2017 hierarchy from 1990 to 2017 for road injuries. Second, we measured mortality-to-incidence ratios by location. Third, we assessed the distribution of the natures of injury (eg, traumatic brain injury) that result from each road injury. RESULTS: Globally, 1 243 068 (95% uncertainty interval 1 191 889 to 1 276 940) people died from road injuries in 2017 out of 54 192 330 (47 381 583 to 61 645 891) new cases of road injuries. Age-standardised incidence rates of road injuries increased between 1990 and 2017, while mortality rates decreased. Regionally, age-standardised mortality rates decreased in all but two regions, South Asia and Southern Latin America, where rates did not change significantly. Nine of 21 GBD regions experienced significant increases in age-standardised incidence rates, while 10 experienced significant decreases and two experienced no significant change. CONCLUSIONS: While road injury mortality has improved in recent decades, there are worsening rates of incidence and significant geographical heterogeneity. These findings indicate that more research is needed to better understand how road injuries can be prevented.