METHODS: In this international, community-based cohort study, we prospectively enrolled adults aged 35-70 years who had no intention of moving residences for 4 years from rural and urban communities across 17 countries. A portable spirometer was used to assess FEV1. FEV1 values were standardised within countries for height, age, and sex, and expressed as a percentage of the country-specific predicted FEV1 value (FEV1%). FEV1% was categorised as no impairment (FEV1% ≥0 SD from country-specific mean), mild impairment (FEV1% <0 SD to -1 SD), moderate impairment (FEV1% cardiovascular disease outcomes (including myocardial infarction, stroke, sudden death, or congestive heart failure), and respiratory hospitalisations (from chronic obstructive pulmonary disease, asthma, pneumonia, tuberculosis, or other pulmonary conditions). Fully adjusted hazard ratios (HRs) were calculated by multilevel Cox regression.

FINDINGS: Among 126 359 adults with acceptable spirometry data available, during a median 7·8 years (IQR 5·6-9·5) of follow-up, 5488 (4·3%) deaths, 5734 (4·5%) cardiovascular disease events, and 1948 (1·5%) respiratory hospitalisation events occurred. Relative to the no impairment group, mild to severe FEV1% impairments were associated with graded increases in mortality (HR 1·27 [95% CI 1·18-1·36] for mild, 1·74 [1·60-1·90] for moderate, and 2·54 [2·26-2·86] for severe impairment), cardiovascular disease (1·18 [1·10-1·26], 1·39 [1·28-1·51], 2·02 [1·75-2·32]), and respiratory hospitalisation (1·39 [1·24-1·56], 2·02 [1·75-2·32], 2·97 [2·45-3·60]), and this pattern persisted in subgroup analyses considering country income level and various baseline risk factors. Population-attributable risk for mortality (adjusted for age, sex, and country income) from mildly to moderately reduced FEV1% (24·7% [22·2-27·2]) was larger than that from severely reduced FEV1% (3·7% [2·1-5·2]) and from tobacco use (19·7% [17·2-22·3]), previous cardiovascular disease (5·5% [4·5-6·5]), and hypertension (17·1% [14·6-19·6]). Population-attributable risk for cardiovascular disease from mildly to moderately reduced FEV1 was 17·3% (14·8-19·7), second only to the contribution of hypertension (30·1% [27·6-32·5]).

INTERPRETATION: FEV1 is an independent and generalisable predictor of mortality, cardiovascular disease, and respiratory hospitalisation, even across the clinically normal range (mild to moderate impairment).

METHODS: We assessed use of antiplatelet, cholesterol, and blood-pressure-lowering drugs in 8492 individuals with self-reported cardiovascular disease from 21 countries enrolled in the Prospective Urban Rural Epidemiology (PURE) study. Defining one or more drugs as a minimal level of secondary prevention, wealth-related inequality was measured using the Wagstaff concentration index, scaled from -1 (pro-poor) to 1 (pro-rich), standardised by age and sex. Correlations between inequalities and national health-related indicators were estimated.

FINDINGS: The proportion of patients with cardiovascular disease on three medications ranged from 0% in South Africa (95% CI 0-1·7), Tanzania (0-3·6), and Zimbabwe (0-5·1), to 49·3% in Canada (44·4-54·3). Proportions receiving at least one drug varied from 2·0% (95% CI 0·5-6·9) in Tanzania to 91·4% (86·6-94·6) in Sweden. There was significant (p<0·05) pro-rich inequality in Saudi Arabia, China, Colombia, India, Pakistan, and Zimbabwe. Pro-poor distributions were observed in Sweden, Brazil, Chile, Poland, and the occupied Palestinian territory. The strongest predictors of inequality were public expenditure on health and overall use of secondary prevention medicines.

INTERPRETATION: Use of medication for secondary prevention of cardiovascular disease is alarmingly low. In many countries with the lowest use, pro-rich inequality is greatest. Policies associated with an equal or pro-poor distribution include free medications and community health programmes to support adherence to medications.

METHODS: This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used country-specific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause.

RESULTS: In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease.

OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden.

METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility.

RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75.

METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Library from inception to May 1, 2019, for relevant original research articles without any language restrictions. The literature search and data extraction were done independently by two investigators. Primary outcomes were the prevalence of non-obese or lean people within the NAFLD group and the prevalence of non-obese or lean NAFLD in the general, non-obese, and lean populations; the incidence of NAFLD among non-obese and lean populations; and long-term outcomes of non-obese people with NAFLD. We also aimed to characterise the demographic, clinical, and histological characteristics of individuals with non-obese NAFLD.

FINDINGS: We identified 93 studies (n=10 576 383) from 24 countries or areas: 84 studies (n=10 530 308) were used for the prevalence analysis, five (n=9121) were used for the incidence analysis, and eight (n=36 954) were used for the outcomes analysis. Within the NAFLD population, 19·2% (95% CI 15·9-23·0) of people were lean and 40·8% (36·6-45·1) were non-obese. The prevalence of non-obese NAFLD in the general population varied from 25% or lower in some countries (eg, Malaysia and Pakistan) to higher than 50% in others (eg, Austria, Mexico, and Sweden). In the general population (comprising individuals with and without NAFLD), 12·1% (95% CI 9·3-15·6) of people had non-obese NAFLD and 5·1% (3·7-7·0) had lean NAFLD. The incidence of NAFLD in the non-obese population (without NAFLD at baseline) was 24·6 (95% CI 13·4-39·2) per 1000 person-years. Among people with non-obese or lean NALFD, 39·0% (95% CI 24·1-56·3) had non-alcoholic steatohepatitis, 29·2% (21·9-37·9) had significant fibrosis (stage ≥2), and 3·2% (1·5-5·7) had cirrhosis. Among the non-obese or lean NAFLD population, the incidence of all-cause mortality was 12·1 (95% CI 0·5-38·8) per 1000 person-years, that for liver-related mortality was 4·1 (1·9-7·1) per 1000 person-years, cardiovascular-related mortality was 4·0 (0·1-14·9) per 1000 person-years, new-onset diabetes was 12·6 (8·0-18·3) per 1000 person-years, new-onset cardiovascular disease was 18·7 (9·2-31·2) per 1000 person-years, and new-onset hypertension was 56·1 (38·5-77·0) per 1000 person-years. Most analyses were characterised by high heterogeneity.

INTERPRETATION: Overall, around 40% of the global NAFLD population was classified as non-obese and almost a fifth was lean. Both non-obese and lean groups had substantial long-term liver and non-liver comorbidities. These findings suggest that obesity should not be the sole criterion for NAFLD screening. Moreover, clinical trials of treatments for NAFLD should include participants across all body-mass index ranges.

AIM: To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD).

METHODS: This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia (referred to as "GO ASIA") workgroup. All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation (QRISK2-2017; developed by researchers at the United Kingdom National Health Service; https://qrisk.org/2017/; 10-year cardiovascular risk estimation) were included and compared to healthy controls with the same age, sex, and ethnicity. Relative risk was reported. QRISK2 score > 10% was defined as the high-CVD-risk group. Fibrosis stages 3 and 4 (F3 and F4) were considered advanced fibrosis.

RESULTS: A total of 1122 patients (73%) had complete data and were included in the final analysis; 314 (28%) had advanced fibrosis. The median age (interquartile range [IQR]) of the study population was 53 (44-60) years, 532 (47.4%) were females, and 492 (43.9%) were of Chinese ethnicity. The median 10-year CVD risk (IQR) was 5.9% (2.6-10.9), and the median relative risk of CVD over 10 years (IQR) was 1.65 (1.13-2.2) compared to healthy individuals with the same age, sex, and ethnicity. The high-CVD-risk group was significantly older than the low-risk group (median [IQR]: 63 [59-67] vs 49 [41-55] years; P < 0.001). Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk (P < 0.001). Median GGT level was not different between the two groups (GGT [U/L]: Median [IQR], high risk 60 [37-113] vs low risk 66 [38-103], P = 0.56). There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score (r = 0.02).