Impact of pulmonary artery intramural hematoma on patients with acute type A aortic dissection.

OBJECTIVES: To investigate the short-term/long-term impact of pulmonary artery intramural hematoma (PA-IMH) in patients with acute Stanford type A aortic dissection (ATAAD) following surgical repair. MATERIALS AND METHODS: Consecutive patients with ATAAD who received surgical repair at Beijing and Yunnan Fuwai Hospital in 2010-2021 were retrospectively reviewed. Patients with hemorrhage extending along the PA were identified as the PA-IMH group. Multivariable logistics regression was used to obtain the odds ratio (OR), and the Kaplan-Meier method was used to estimate the survival rate. RESULTS: Of the 2046 ATAAD patients, 324 (15.8%) patients were identified with PA-IMH, and 1722 (84.2%) were without PA-IMH. PA-IMH had a higher prevalence in patients with older age, female gender, aortic IMH, and type II aortic dissection. PA-IMH patients incurred excess early mortality compared with non-PA-IMH patients (9.3% vs. 5.6%, OR = 1.86, 95%CI 1.19-2.91, p = 0.006). The results were stable in the subgroup analysis, with an increased risk in older (> 70 years) or DeBakey type II ATAAD patients. Notably, an increase in the degree and extent of PA-IMH exacerbated the risk of early mortality. However, after landmark analysis at 30-day postsurgery, no significant difference was noted in the long-term outcomes between PA-IMH and non-PA-IMH groups (p = 0.440). The 5-year survival rates were 87.1% (95%CI: 83.3%, 91.1%) and 90.1% (95%CI: 88.5%, 91.7%), respectively. CONCLUSIONS: The presence of PA-IMH in ATAAD patients is common and is independently associated with increased early mortality after surgical repair, especially in those with older age (> 70) or type II dissection. However, such detrimental effects do not persist in the long-term follow-up among patients who survived hospital discharge. CLINICAL RELEVANCE STATEMENT: We confirmed that PA-IMH significantly increases early postoperative mortality in patients with acute type A aortic dissection, especially in older patients or DeBakey type II dissection. This should prompt further investigation of the incremental role of PA-IMH in this pathology. KEY POINTS: Acute type A aortic dissection mortality gets worse when pulmonary artery intramural hematoma is present. Pulmonary artery-intramural hematoma increased the risk of early mortality but not affect long-term prognosis. Further research should investigate the effects of pulmonary artery intramural thrombus on aortic dissection.

Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. METHODS: In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men). INTERPRETATION: Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women. FUNDING: Funding sources are listed at the end of the Article.

Associations of dietary copper intake with cardiovascular disease and mortality: findings from the Chinese Perspective Urban and Rural Epidemiology (PURE-China) Study.

BACKGROUND: Previous in vitro and animal experiments have shown that copper plays an important role in cardiovascular health. Dietary copper is the main source of copper in the human body and the association between dietary copper and cardiovascular disease remains unclear. Our study aimed to investigate the associations of dietary copper intake with the risk of major cardiovascular disease incidence, cardiovascular disease mortality, and all-cause mortality in Chinese adults. METHODS: Our study is based on Prospective Urban Rural Epidemiology China (PURE-China), a large prospective cohort study of 47 931 individuals aged 35-70 years from 12 provinces in China. Dietary intake was recorded using a validated semi-quantitative food frequency questionnaire designed specifically for the Chinese population. The daily intake of copper was obtained by multiplying the daily food intake with the nutrient content provided in the Chinese Food Composition Table (2002). Cox frailty proportional hazards models were developed to evaluate the association between dietary copper intake with mortality, major cardiovascular disease events, and their composite. RESULTS: A total of 45 101 participants (mean age: 51.1 ± 9.7 years old) with complete information were included in the current study. The mean dietary copper intake was 2.6 ± 1.1 mg/d. During the 482 833 person-years of follow-up, 2 644(5.9%) participants died, 4 012(8.9%) developed new cardiovascular diseases, and 5 608(12.4%) participants experienced the composite endpoint. Compared with those in the first and second quartile of dietary copper intake, individuals in the third and fourth quantile had higher risk of composite outcomes, all-cause death, cardiovascular disease death, major cardiovascular disease and stroke occurrences. The associations remained similar in the subgroup and sensitivity analyses. CONCLUSIONS: Our findings demonstrated that excessive dietary copper intake was associated with higher risks of death and cardiovascular diseases in Chinese adults. Further studies in populations with different dietary characteristics are needed to obtain dose-response relationships and to refine global dietary recommendations.

Different Oral Antithrombotic Therapy for the Treatment of Ventricular Thrombus: An Observational Study from 2010 to 2019.

Methods: This retrospective observational study was conducted from 2010 to 2019 in National Center of Cardiovascular Diseases of China. We included patients with VT confirmed by imaging. The primary outcome was the rate of thrombus resolution. Hazard ratio (HR) was calculated with or without adjustment for covariates using Cox proportional hazards regression models. Results: 463 patients were included. 43.0% received VKAs, 16.6% received NOACs, and 40.4% received APT. Over a median of 468 days' follow-up, NOACs group was more likely to have the thrombus resolved within 12 months' follow-up than VKAs (HR 2.28, 95% CI 1.57 to 3.31) or APT (HR 2.92, 95% CI 1.97 to 4.33). After adjustment for baseline variables, the significance remained in the comparison of NOACs versus VKAs (HR 2.13, 95% CI 1.41 to 3.22) as well as NOACs versus APT (HR 2.55, 95% CI 1.53 to 4.27). No significant differences were identified in bleeding rate, thromboembolism rate, or all-cause death in 12 months' follow-up. Conclusion: Our findings showed that patients who were male, diagnosed with MI with or without ventricular aneurysm, or diagnosed with coronary artery diseases medical history had a risk of thrombus unresolved. Patients with NOACs had a higher resolution and a similar safety profile comparing VKAs or APT, which persisted after adjusting for other factors. Large randomized controlled trials are required urgently. This trial is registered with NCT05006677.

The effects of Japanese encephalitis virus antibodies on Zika virus infection.

Recently, Zika virus (ZIKV) has become more widespread, thus attracting global attention. The vaccine against Japanese encephalitis virus (JEV) is currently used in China, being included in planned immunisation regimes. Although ZIKV and JEV are closely related mosquito-borne Flaviviruses, and a complex cross-immune response within flaviviruses has been demonstrated, the effect of JEV vaccination on ZIKV infection has not been well described. Thus, this study aimed to explore the impact of different titres of anti-JEV antibodies (Abs) against ZIKV infection using sera from healthy human donors in Guangzhou and anti-JEV rabbit polyclonal antibodies (pAbs) in vitro and vivo. Human anti-JEV Ab titres were tested at decreasing concentrations as the age increased. A neutralising effect on ZIKV infection was observed when anti-JEV Ab titres in human sera or rabbit pAbs were high (the corresponding age was under 30 years). Even though a lower titre in human sera showed no apparent effect, whereas rabbit pAbs had an antibody-dependent enhancement(ADE)effect, we proved an ADE effect in vivo for the first time. This study suggests that individuals over 60 years of age are at high risk for JEV and ZIKV infection, and screening this age group for infection should strengthen. Furthermore, a deep exploration of the relationship between anti-JEV Abs and ZIKV infection is needed.

Research advancements in the neurological presentation of flaviviruses.

Owing to the large-scale epidemic of Zika virus disease and its association with microcephaly, properties that allow flaviviruses to cause nervous system diseases are an important area of investigation. At present, although potential pathogenic mechanisms of flaviviruses in the nervous system have been examined, they have not been completely elucidated. In this paper, we review the possible mechanisms of blood-brain barrier penetration, the pathological effects on neurons, and the association between virus mutations and neurotoxicity. A hypothesis on neurotoxicity caused by the Zika virus is presented. Clarifying the mechanisms of virulence of flaviviruses will be helpful in finding better antiviral drugs and optimizing the treatment of symptoms.

The prevalence and outcomes in STEMI patients aged ≥75 undergoing primary percutaneous coronary intervention in China.

Objective: To investigate the prevalence and outcomes of primary percutaneous coronary intervention (PCI) in Chinese patients with ST-segment elevation myocardial infarction (STEMI) aged ≥75 years. Methods: We identified STEMI patients aged ≥75 years between 2013 and 2014 from a multicenter registry. The primary outcome was all-cause mortality. The secondary outcome was major adverse cardiac and cerebrovascular event (MACCE) including a composite of all-cause mortality, cardiac death, recurrent MI, stroke, revascularization, and major bleeding. Hazard ratios (HR) and associated 95% confidence interval (CI) were calculated. Results: Approximately 32.9% (n = 999) patients received primary PCI. Primary PCI was associated with lower risks of two-year all-cause mortality (18.0% vs. 36.4%; adjusted HR: 0.54, 95% CI: 0.45 to 0.65, P < 0.0001), MACCE (28.7% vs. 43.5%; adjusted HR: 0.68, 95% CI: 0.59 to 0.80, P < 0.0001), and cardiac death (10.0% vs. 23.6%; adjusted HR: 0.49, 95% CI: 0.38 to 0.62, P < 0.0001) relative to no reperfusion (n = 2041) in patients aged ≥75 years. The better outcomes in two-year all-cause mortality, MACCE, and cardiac death were consistently observed in STEMI patients aged ≥85 years. No differences were observed in recurrent MI, stroke, revascularization, and major bleeding between the two groups. Additionally, in patients with relatively high-risk profiles such as cardiogenic shock or delaying hospital admission, primary PCI was also superior to no reperfusion. Conclusion: Primary PCI may decrease two-year all-cause mortality, MACCE, and cardiac death in STEMI patients aged ≥75 years, even in these with age ≥85 years, cardiogenic shock, or delaying hospital admission. However, primary PCI was underutilized in Chinese clinical practice.

Achievement of Guideline-Recommended Targets for Secondary Prevention of Cardiovascular Disease in 38 Low-Income and Middle-Income Countries.

BACKGROUND: This study aimed to estimate the prevalence of achieving the secondary prevention targets recommended in the World Health Organization (WHO) guidelines for cardiovascular disease (CVD) in 38 low-income and middle-income countries (LMICs). METHODS: We pooled nationally representative cross-sectional surveys from 38 LMICs between 2013 and 2020. Treatment, metabolic and lifestyle targets were assessed for individuals with a self-reported history of CVD according to WHO's recommendations. Associations between the prevalence of guideline adherence and sociodemographic characteristics were assessed using multivariate Poisson regression models. RESULTS: The pooled sample included 126 106 participants, of whom 9821 (6.8% [95% CI 6.4-7.2]) reported a history of CVD. Overall, the prevalence of achieving treatment targets in patients with CVD was 22.7% (95% CI, 21.0-24.5%) for antihypertensive drugs, 19.6% (17.9-21.4%) for aspirin, and 13.6% (12.0-15.44%) for statins. The prevalence of achieving metabolic targets was 54.9% (52.5-57.3%) for BMI, 39.9% (37.7-42.2%) for blood pressure, 46.1% (43.6-48.6%) for total cholesterol, and 84.9% (83.1-86.5%) for fasting blood glucose. The prevalence of achieving lifestyle targets was 83.2% (81.5-84.7%) for not smoking, 83.1% (81.2-84.9%) for not drinking, 65.5% (63.1-67.7%) for sufficient physical activity and 16.2% (14.5-18.0%) for healthy diet. Only 6.1% (5.1-7.4%) achieved three treatment targets, 16.0% (14.3-17.9%) achieved four metabolic targets, and 6.9% (5.8-8.0%) achieved four lifestyle targets. Upper-middle income countries were better than low-income countries at achieving the treatment, non-drinking and dietary targets. Being younger and female were associated with poorer achievement of metabolic targets. CONCLUSION: In LMICs, achieving the targets recommended in the guideline for treatment, metabolism and healthy lifestyles for patients with CVD is notably low. This highlights an urgent need for effective, systematic secondary prevention strategies to improve CVD management.

Clinical Results of a Modified Doty's Technique for Supravalvular Aortic Stenosis.

This study aimed to assess the early and mid-term results of the modified Doty's technique compared with the traditional Doty's technique in patients with congenital supravalvular aortic stenosis (SVAS). We retrospectively included 73 consecutive SVAS patients in Beijing and Yunnan Fuwai Hospitals between 2014 and 2021. Patients were divided into the modified technique (n = 9) and the traditional technique group (n = 64). The modified technique involves altering the right head of the symmetrical inverted pantaloon-shaped patch into an asymmetrical triangular form to prevent compression of the right coronary artery ostium. The primary safety outcome was in-hospital surgery-related complications and the primary effectiveness outcome was re-operation at follow-up. The Mann-Whitney U test and Fisher's exact test were used to test the group difference. The median age at operation was 50 months (IQR 27.0-96.0). Twenty-two (30.1%) of the patients were female. The median follow-up was 23.5 months (IQR 3.0-46.0). No in-hospital surgery-related complications and follow-up re-operation occurred in the modified technique group, but the traditional technique group had 14 (21.8%) surgery-related complications and 5 (7.9%) re-operation. Patients with the modified technique had a well-developed aortic root and no aortic regurgitation occurred. A modified technique could be considered for patients with poor aortic root development to reduce postoperative surgery-related complications.

Effectiveness and Safety of Mitral Valve Plasty in Patients with an Anomalous Origin of the Coronary Artery from the Pulmonary Artery.

The study aimed to determine the effectiveness and safety of anomalous coronary artery from pulmonary artery (ACAPA) patients with moderate or severe mitral valve regurgitation (MVR) receiving mitral valve plasty (MVP) concurrently. Consecutive ACAPA patients undergoing surgery between 2015 and 2021 were retrospectively included. Patients were divided into three groups: moderate MVR without MVP (non-MVP (moderate) N = 14), moderate MVR with MVP (MVP (moderate) N = 13), and severe MVR with MVP (MVP (severe) N = 13). The primary safety endpoint was in-hospital surgery-related complications. The primary effectiveness outcome was left ventricular ejection function (LVEF) and left ventricular end-diastolic diameter (LVEDD) z-score at 2- and 24-month follow-ups. Multivariable linear regression models were used to obtain the ß coefficient. The median age of the included patients was 7.5 years (IQR 1.4-26.5). The in-hospital surgery-related complication rates were 7.1%, 15.4%, and 7.7% in non-MVP (moderate), MVP (moderate), and MVP (severe) groups, separately. At the 2-month follow-up, the non-MVP (moderate) group had a better LVEF and LVEDD z-score compared with the MVP (moderate) group (LVEF ß = 9.22, 95%CI 1.09 to 17.35; LVEDD z-score ß = -2.49, 95%CI -4.53 to -0.45). At the 24-month follow-up, the LVEF of all patients and the LVEDD z-score of 90% of patients in the three groups returned to normal. For ACAPA patients with moderate MVR, MVP was not necessary, especially for pediatric patients (age < 3 years) and patients with secondary MVR. Further studies for ACAPA patients with severe MVR are still needed.

The effects of low-fat, high-carbohydrate diets vs. low-carbohydrate, high-fat diets on weight, blood pressure, serum liquids and blood glucose: a systematic review and meta-analysis.

Our aim was to determine the relative effectiveness of two dietary macronutrient patterns (LFHC (low-fat, high-carbohydrate) diets and LCHF (low-carbohydrate, high-fat) diets) on weight loss and cardiovascular risk factors. We searched four databases including MEDLINE, EMBASE, Cochrane Library, and Web of Science to identify the eligible studies on March 13, 2020. Randomized clinical trials (RCT) were included which compared the effect of two diets (LFHC and LCHF) on weight loss, blood pressure, serum liquids, and blood glucose in overweight or obesity adults. Standardized mean difference (SMD) and 95% confidence interval (CI) were used for the pooled results. This paper included eleven studies involving 739 participants. Compared with LFHC diets, LCHF diets had a greater effect on weight loss (SMD = -1.01 kg; 95% CI -1.99 to -0.04, p = 0.04) and HDL-cholesterol changes (SMD = 0.82 mmol/l; 95% CI 0.43 to 1.21, p < 0.0001), but a smaller effect on total cholesterol decrease (SMD = 0.63 mmol/l; 95% CI 0.18-1.08, p = 0.006) and LDL-cholesterol decrease (SMD = 0.59 mmol/l; 95% CI 0.11-1.18, p = 0.05). Between the two groups, changes in lean mass, fat mass, systolic blood pressure, diastolic blood pressure, triglycerides, and glucose were non-significant. To conclude, both diets are effective for weight control and reduction of cardiovascular risk factors. And further studies with long-term follow-up are needed to confirm our results.

Assessment of three types of surgical procedures for supravalvar aortic stenosis: A systematic review and meta-analysis.

Importance: The safety and efficacy of different surgical repairs of supravalvar aortic stenosis (SVAS) are inconsistent. Objective: To compare the prognosis of single-, two- and three-patch repair for patients with SVAS. Data sources: PubMed, EMBASE, Cochrane Library, Web of Science, and clinicaltrials.gov were searched until April 17, 2022. Study selection: Study reported SVAS patients treated with single-, two- or three-patch repair. Data extraction and synthesis: Two reviewers independently extracted the data of study characteristics and clinical outcomes. Multiple pairwise and frequentist network meta-analyses were conducted. And a fixed-effect model was used when no heterogeneity existed. Main outcomes and measures: Outcomes included the rate of reintervention, aortic insufficiency, early mortality and late mortality, cardiopulmonary bypass (CPB) time, cross-clamping (CCP) time, and postoperative/ follow-up pressure gradient. Binary variables were evaluated by odds ratio (OR) and its 95% confidence interval (CI), while continuous variables were assessed by standardized mean difference (SMD) and its 95% CI. Results: Twenty-seven retrospective cohort studies were included, comprising 1,162 patients, undergoing single-patch (46.6% of cases), two-patch (33.9%), and three-patch repair (19.4%). Two-patch method had a lower rate of reintervention compared with single-patch (OR = 0.47, 95 % CI 0.28-0.89), and three-patch (OR = 0.31, 95 % CI 0.15-0.64). This finding also applied to juvenile and non-Asian patients. Three-patch method had a lower rate of aortic insufficiency compared with single-patch (OR = 0.11, 95 % CI 0.01-0.63), and two-patch (OR = 0.11, 95 % CI 0.02-0.83). But this repair had the longest CCP time, which was significantly longer than that of single- (SMD = 0.76, 95 % CI 0.36-1.17) or two-patch repair (SMD = 0.61, 95 % CI 0.06-1.16). No significant difference was found in mortality and pressure gradient among three procedures. Conclusion and relevance: Two-patch repair has the lowest reintervention rate and relatively reasonable operation time. Complex and severe SVAS is suggested to be treated with two-patch repair. Further prospective studies of a reasonable sample size will be required with a special focus on the use of different patch materials and surgeons' unique working experience. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022328146.

Appropriate Surrogate Endpoint in Drug-Coated Balloon Trials for Coronary Artery Diseases.

Background: The appropriateness of using late lumen loss (LLL) as a surrogate endpoint was established in drug-eluting stent (DES) studies, but it was less supportive for drug-coated balloon (DCB) trials. Methods: Studies published until 23 June 2021 were searched from PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. The correlation between LLL, MLD (minimal lumen diameter), and %DS (percentage diameter stenosis) and clinical endpoints was evaluated by linear regression. Standardized effect size and its 95% CIs were used to illustrate the difference among LLL, MLD, and %DS. Results: A total of 24 clinical trials were eligible [16 DCB vs. DES, 7 DCB vs. plain old balloon angioplasty (POBA), and 1 DCB vs. DES vs. POBA]. Thirteen (54.2%) trials used LLL as the primary endpoint. LLL, MLD, and %DS all had significant associations with clinical endpoints. For DCB vs. DES trials, the number of studies that reported inconsistent results between LLL and MLD was 12/16 (75.0%) and between LLL and %DS was 10/15 (66.7%), while in MLD and %DS, it was 1/16 (6.3%). The difference of standardized effect size between LLL and MLD was -0.47 (95% CI, -0.69 to -0.25, p < 0.001) and LLL and %DS was-0.31 (95%CI,-0.43 to-0.20, p < 0.001) while in MLD and %DS, there was no difference, 0.1 (95%CI,-0.02 to 0.22, p = 0.084). Conclusions: For DCB trials, an appropriate surrogate is associated with the control device. The traditional LLL could be used in the DCB vs. POBA trials. However, MLD/%DS should be considered a more suitable surrogate endpoint when comparing DCB with DES.

Interaction of Depression and Unhealthy Diets on the Risk of Cardiovascular Diseases and All-Cause Mortality in the Chinese Population: A PURE Cohort Substudy.

This study aimed to identify the interaction of depression and diets on cardiovascular diseases (CVD) incident and death in China and key subpopulations. We included 40,925 participants from the Prospective Urban Rural Epidemiology (PURE)-China cohort which recruited participants aged 35-70 years from 45 urban and 70 rural communities. Depression was measured by the adapted Short-Form (CIDI-SF). The unhealthy diet was considered when the score of Alternative Healthy Eating Index was below the lowest tertile. The primary outcome was a composite outcome of incident CVD and all-cause mortality. Cox frailty models were used to examine the associations. During a median follow-up of 11.9 years (IQR: 9.6-12.6 years), depression significantly increased the risk of the composite outcome (HR = 2.00; 95% CI, 1.16-3.27), major CVD (HR = 1.82; 95% CI, 1.48-2.23), and all-cause mortality (HR = 2.21; 95% CI, 1.51-3.24) for the unhealthy diet group, but not for the healthy diet group. The interaction between depression and diet for the composite outcome was statistically significant (RERI = 1.19; 95% CI, 0.66-1.72; AP = 0.42, 95% CI, 0.27-0.61; SI = 3.30, 95% CI, 1.42-7.66; multiplicative-scale = 1.74 95% CI, 1.27-2.39), even in the subgroup and sensitivity analyses. In addition, the intake of vegetable and polyunsaturated fatty acids contributed most to the interaction of diets and depression. Depressive participants should focus on healthy diets, especially vegetables and polyunsaturated fatty acids, to avoid premature death and CVD.

Variations in risks from smoking between high-income, middle-income, and low-income countries: an analysis of data from 179 000 participants from 63 countries.

BACKGROUND: Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. METHODS: We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. FINDINGS: In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65-2·12) than in MICs (1·41, 1·34-1·49) and LICs (1·35, 1·25-1·46; interaction p<0·0001). Similar patterns were observed for each component of the composite outcome in PURE, myocardial infarction in INTERHEART, and stroke in INTERSTROKE. The median levels of tar, nicotine, and carbon monoxide displayed on the cigarette packs from PURE HICs were higher than those on the packs from MICs. In PURE, the proportion of never smokers reporting high second-hand smoke exposure (≥1 times/day) was 6·3% in HICs, 23·2% in MICs, and 14·0% in LICs. The adjusted geometric mean total nicotine equivalent was higher among current smokers in HICs (47·2 µM) than in MICs (31·1 µM) and LICs (25·2 µM; ANCOVA p<0·0001). By contrast, it was higher among never smokers in LICs (18·8 µM) and MICs (11·3 µM) than in HICs (5·0 µM; ANCOVA p=0·0001). INTERPRETATION: The variations in risks from smoking between country income groups are probably related to the higher exposure of tobacco-derived toxicants among smokers in HICs and higher rates of high second-hand smoke exposure among never smokers in MICs and LICs. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).