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Hypertension is associated with a 71% increase in the risk of heart failure.A 20 mmHg increment in systolic blood pressure is associated with a 28% increment in heart failure risk, and a 10 mmHg increment in diastolic blood pressure is associated with a 12% increase in heart failure risk.The results support public health policies and interventions to reduce the prevalence of elevated blood pressure (e.g. through lifestyle changes and medication use).

ObjectiveAortic dissection and aortic aneurysm rupture are aortic emergencies and their clinical outcomes have improved over the past two decades; however, whether this has translated into lower mortality across countries remains an open question. The purpose of this study was to compare mortality trends from aortic dissection and rupture between the UK, Japan, the USA and Canada.MethodsWe analysed the WHO mortality database to determine trends in mortality from aortic dissection and rupture in four countries from 2000 to 2019. Age-standardised mortality rates per 100 000 persons were calculated, and annual percentage change was estimated using joinpoint regression.ResultsAge-standardised mortality rates per 100 000 persons from aortic dissection and rupture in 2019 were 1.04 and 1.80 in the UK, 2.66 and 1.16 in Japan, 0.76 and 0.52 in the USA, and 0.67 and 0.81 in Canada, respectively. There was significantly decreasing trends in age-standardised mortality from aortic rupture in all four countries and decreasing trends in age-standardised mortality from aortic dissection in the UK over the study period. There was significantly increasing trends in mortality from aortic dissection in Japan over the study period. Joinpoint regression identified significant changes in the aortic dissection trends from decreasing to increasing in the USA from 2010 and Canada from 2012. In sensitivity analyses stratified by sex, similar trends were observed.ConclusionsTrends in mortality from aortic rupture are decreasing; however, mortality from aortic dissection is increasing in Japan, the USA and Canada. Further study to explain these trends is warranted.

ObjectiveTo investigate the association between walking speed and the risk of type 2 diabetes.DesignSystematic review and meta-analysis.Data sourcesPubMed, Scopus, CENTRAL and Web of Science to 30 May 2023.Eligibility criteria for selecting studiesWe included cohort studies that explored the association between walking speed and the risk of type 2 diabetes in adults. We used random-effects meta-analyses to calculate relative risk (RR) and risk difference (RD). We rated the credibility of subgroup differences and the certainty of evidence using the Instrument to assess the Credibility of Effect Modification ANalyses (ICEMAN) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) tools, respectively.ResultsTen cohort studies were included. Compared with easy/casual walking (<3.2 km/hour), the RR of type 2 diabetes was 0.85 (95% CI 0.70 to 1.00); RD=0.86 (95% CI 1.72 to 0) fewer cases per 100 patients; n=4, GRADE=low) for average/normal walking (3.2–4.8 km/hour), 0.76 (95% CI 0.65 to 0.87); RD=1.38 (95% CI 2.01 to 0.75) fewer cases per 100 patients; n=10, GRADE=low) for fairly brisk walking (4.8–6.4 km/hour) and 0.61 (95% CI 0.49 to 0.73; RD=2.24 (95% CI 2.93 to 1.55) fewer cases per 100 patients; n=6, GRADE=moderate) for brisk/striding walking (>6.4 km/hour). There was no significant or credible difference across subgroups based on adjustment for the total volume of physical activity and time spent walking per day. Dose–response analysis suggested that the risk of type 2 diabetes decreased significantly at a walking speed of 4 km/h and above.ConclusionsLow to moderate certainty evidence, mainly from studies with a high risk of bias, suggests that walking at faster speeds is associated with a graded decrease in the risk of type 2 diabetes.PROSPERO registration numberCRD42023432795.

Food processing has been hypothesised to play a role in cancer development; however, data from large-scale epidemiological studies are scarce. This study investigated the association between dietary intake according to amount of food processing and risk of cancer at 25 anatomical sites using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

There is an equivocal and inconsistent association between legume consumption and health outcomes and longevity. The purpose of this study was to examine and quantify the potential dose–response relationship between legume consumption and all-cause and cause-specific mortality in the general population. We conducted a systematic literature search on PubMed/Medline, Scopus, ISI Web of Science, and Embase from inception to September 2022, as well as reference lists of relevant original papers and key journals. A random-effects model was used to calculate summary HRs and their 95% CIs for the highest and lowest categories, as well as for a 50 g/d increment. We also modeled curvilinear associations using a 1-stage linear mixed-effects meta-analysis. Thirty-two cohorts (31 publications) involving 1,141,793 participants and 93,373 deaths from all causes were included. Higher intakes of legumes, compared with lower intakes, were associated with a reduced risk of mortality from all causes (HR: 0.94; 95% CI: 0.91, 0.98; n= 27) and stroke (HR: 0.91; 95% CI: 0.84, 0.99; n= 5). There was no significant association for CVD mortality (HR: 0.99; 95% CI: 0.91, 1.09; n=11), CHD mortality (HR: 0.93; 95% CI: 0.78, 1.09; n= 5), or cancer mortality (HR: 0.85; 95% CI: 0.72, 1.01; n= 5). In the linear dose–response analysis, a 50 g/d increase in legume intake was associated with a 6% reduction in the risk of all-cause mortality (HR: 0.94; 95% CI: 0.89, 0.99; n= 19), but no significant association was observed for the remaining outcomes. The certainty of evidence was judged from low to moderate. A higher legume intake was associated with lower mortality from all causes and stroke, but no association was observed for CVD, CHD, and cancer mortality. These results support dietary recommendations to increase the consumption of legumes.

ObjectiveThe purpose of this study is to describe recent mortality trends from aortic stenosis (AS) among eight high-income countries.MethodsWe analysed the WHO mortality database to determine trends in mortality from AS in the UK, Germany, France, Italy, Japan, Australia, the USA and Canada from 2000 to 2020. Crude and age-standardised mortality rates per 100 000 persons were calculated. We calculated age-specific mortality rates in three groups (<64, 65–79 and ≥80 years). Annual percentage change was analysed using joinpoint regression.ResultsDuring the observation period, the crude mortality rates per 100 000 persons increased in all the eight countries (from 3.47 to 5.87 in the UK, from 2.98 to 8.93 in Germany, from 3.84 to 5.52 in France, from 1.97 to 4.33 in Italy, from 1.12 to 5.49 in Japan, from 2.14 to 3.38 in Australia, from 3.58 to 4.22 in the USA and from 2.12 to 5.00 in Canada). In joinpoint regression of age-standardised mortality rates, trend changes towards a decrease were observed in Germany after 2012 (−1.2%, p=0.015), Australia after 2011 (−1.9%, p=0.005) and the USA after 2014 (−3.1%, p<0.001). Age-specific mortality rates in age group ≥80 years had shifts towards decreasing trends in all the eight countries in contrast to other younger age groups.ConclusionsWhile crude mortality rates increased in the eight countries, shifts towards decreasing trends were identified in age-standardised mortality rates in three countries and in the elderly aged ≥80 years in the eight countries. Further multidimensional observation is warranted to clarify the mortality trends.

Higher dietary calcium consumption is associated with lower colorectal cancer (CRC) risk. However, little data are available on the association between circulating calcium concentrations and CRC risk.

Consumption of nuts and seeds is associated with a range of health outcomes. Summarizing the best evidence on essential health outcomes from the consumption of nuts is essential to provide optimal recommendations. Our objective is to comprehensively assess health outcome associations related to the consumption of nuts and seeds, using a culinary definition including tree nuts and peanuts (registered in PROSPERO: CRD42021258300). Health outcomes of interest include cardiovascular disease, cancer, diabetes, obesity, respiratory disease, mortality, and their disease biomarkers. We present associations for high compared with low consumption, per serving, and dose–response relations. MEDLINE, Embase, Cochrane, and Epistemonikos were searched and screened for systematic reviews and meta-analyses. Evidence was extracted from 89 articles on the consumption of nuts and relevant health outcomes, including 23 articles with meta-analysis on disease and mortality, 66 articles on biomarkers for disease, and 9 articles on allergy/adverse outcomes. Intake of nuts was associated with reduced risk of cardiovascular diseases and related risk factors, with moderate quality of evidence. An intake of 28 g/d nuts compared with not eating nuts was associated with a 21% RR reduction of cardiovascular disease (including coronary heart disease incidence and mortality, atrial fibrillation, and stroke mortality), an 11% risk reduction of cancer deaths, and 22% reduction in all-cause mortality. Nut consumption was also inversely associated with mortality from respiratory diseases, infectious diseases, and diabetes; however, associations between nut consumption and diabetes incidence were mixed. Meta-analyses of trials on biomarkers for disease generally mirrored meta-analyses from observational studies on cardiovascular disease, cancers, and diabetes. Allergy and related adverse reactions to nuts were observed in 1–2% of adult populations, with substantial heterogeneity between studies. Overall, the current evidence supports dietary recommendations to consume a handful of nuts and seeds per day for people without allergies to these foods.

Graphical Abstract

Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting to more sustainable diets, we aimed to investigate the associations of dietary greenhouse gas emissions and land use with all-cause and cause-specific mortality and cancer incidence rates.

IMPORTANCE: Premature death from all causes and cardiovascular disease (CVD) causes is higher among persons with diabetes. OBJECTIVE: To investigate the association between time spent cycling and all-cause and CVD mortality among persons with diabetes, as well as to evaluate the association between change in time spent cycling and risk of all-cause and CVD mortality. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 7459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition study. Questionnaires regarding medical history, sociodemographic, and lifestyle information were administered in 10 Western European countries from 1992 through 2000 (baseline examination) and at a second examination 5 years after baseline. A total of 5423 participants with diabetes completed both examinations. The final updated primary analysis was conducted on November 13, 2020. EXPOSURES: The primary exposure was self-reported time spent cycling per week at the baseline examination. The secondary exposure was change in cycling status from baseline to the second examination. MAIN OUTCOMES AND MEASURES: The primary and secondary outcomes were all-cause and CVD mortality, respectively, adjusted for other physical activity modalities, diabetes duration, and sociodemographic and lifestyle factors. RESULTS: Of the 7459 adults with diabetes included in the analysis, the mean (SD) age was 55.9 (7.7) years, and 3924 (52.6%) were female. During 110 944 person-years of follow-up, 1673 deaths from all causes were registered. Compared with the reference group of people who reported no cycling at baseline (0 min/wk), the multivariable-adjusted hazard ratios for all-cause mortality were 0.78 (95% CI, 0.61-0.99), 0.76 (95% CI, 0.65-0.88), 0.68 (95% CI, 0.57-0.82), and 0.76 (95% CI, 0.63-0.91) for cycling 1 to 59, 60 to 149, 150 to 299, and 300 or more min/wk, respectively. In an analysis of change in time spent cycling with 57 802 person-years of follow-up, a total of 975 deaths from all causes were recorded. Compared with people who reported no cycling at both examinations, the multivariable-adjusted hazard ratios for all-cause mortality were 0.90 (95% CI, 0.71-1.14) in those who cycled and then stopped, 0.65 (95% CI, 0.46-0.92) in initial noncyclists who started cycling, and 0.65 (95% CI, 0.53-0.80) for people who reported cycling at both examinations. Similar results were observed for CVD mortality. CONCLUSION AND RELEVANCE: In this cohort study, cycling was associated with lower all-cause and CVD mortality risk among people with diabetes independent of practicing other types of physical activity. Participants who took up cycling between the baseline and second examination had a considerably lower risk of both all-cause and CVD mortality compared with consistent noncyclists.

Tea is one of the most widely consumed beverages, but its association with cancer risk remains controversial and unclear. We performed an umbrella review to clarify and determine the associations between tea consumption and various types of cancer by summarizing and recalculating the existing meta-analyses. Meta-analyses of observational studies reporting associations between tea consumption and cancer risk were searched on PubMed and Embase. Associations found to be statistically significant were further classified into levels of evidence (convincing, suggestive, or weak), based on Pvalue, between-study heterogeneity, prediction intervals, and small study effects. Sixty-four observational studies (case-control or cohort) corresponding to 154 effect sizes on the incidence of 25 types of cancer were included. Forty-three (27.9%) results in 15 different types of cancer were statistically significant. When combining all studies on the same type of cancer, 19 results in 11 different types of cancer showed significant associations with lower risk of gastrointestinal tract organ cancer (oral, gastric, colorectal, biliary tract, and liver cancer), breast cancer, and gynecological cancer (endometrial and ovarian cancer) as well as leukemia, lung cancer, and thyroid cancer. Only the reduced risk of oral cancer in tea-consuming populations (OR = 0.62; 95% CI: 0.55, 0.72; Pvalue < 10−6) was supported by convincing evidence. Suggestive evidence was found for 6 results on biliary tract, breast, endometrial, liver, and oral cancer. To summarize, tea consumption was shown to have protective effects on some types of cancer, particularly oral cancer. More well-designed prospective studies are needed with consideration of other factors that can cause biases.

Although a high intake of plant foods such as fruits, vegetables, whole grains, nuts, and legumes has been recommended for chronic disease prevention, it has been unclear what is the optimal amount of intake of these foods and whether specific subtypes are particularly beneficial. The evidence from several recently published meta-analyses on plant foods and antioxidants and various health outcomes is reviewed as well as more recently published studies. In meta-analyses of prospective studies, inverse associations were observed between intake of fruits, vegetables, whole grains, and nuts and the risk of coronary artery disease, stroke, cardiovascular disease overall, total cancer, and all-cause mortality. The strongest reductions in risk were observed at an intake of 800 g/d for fruits and vegetables, 225 g/d for whole grains, and 15–20 g/d for nuts, respectively. Whole-grain and nut consumption was also inversely associated with mortality from respiratory disease, infections, and diabetes. Stronger and more linear inverse associations were observed between blood concentrations of antioxidants (vitamin C, carotenoids, vitamin E) and cardiovascular disease, cancer, and all-cause mortality than for dietary intake. Most studies that have since been published have been consistent with these results; however, further studies are needed on subtypes of plant foods and less common causes of death. These results strongly support dietary recommendations to increase intake of plant foods, and suggest optimal intakes for chronic disease prevention may be ∼800 g/d for intakes of fruits and vegetables, 225 g/d for whole grains, and 15–20 g/d for nuts. Diets high in plant foods could potentially prevent several million premature deaths each year if adopted globally.

Background We conducted a systematic review and meta-analysis to clarify the association between smoking and the risk of developing heart failure.Methods PubMed and Embase databases were searched up to 24 July 2018. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of heart failure associated with smoking. Summary RRs and 95% CIs were estimated using a random effects model.Results Twenty-six studies were included. The summary RR was 1.75 (95% CI: 1.54–1.99, I2 = 81%, n = 10) for current smokers, 1.16 (95% CI: 1.08–1.24, I2 = 51%, n = 9) for former smokers, and 1.44 (1.34–1.55, I2 = 83%, n = 10) for ever smokers compared with never smokers. The summary RR was 1.41 (95% CI: 1.01–1.96, I2 = 82%, n = 2) per 10 cigarettes per day, 1.11 (95% CI: 1.04–1.18, I2 = 70%, n = 3) and 1.08 (95% CI: 1.02–1.14, I2 = 34%, n = 2) per 10 pack-years among ever smokers and former smokers, respectively, and 0.79 (95% CI: 0.63–1.00, I2 = 96%, n = 2) per 10 years since quitting smoking. The association between smoking cessation and heart failure reached significance at 15 years of smoking cessation, and at 30 years the summary RR was 0.72 (95% CI: 0.57–0.90), only slightly higher than the summary RR for never smokers (0.64 (95% CI: 0.57–0.72)) when compared with current smokers.Conclusion Smoking is associated with increased risk of heart failure, but the risk decreases with increasing duration since smoking cessation. Any further studies should investigate the association between number of cigarettes per day, duration, pack-years and time since quitting smoking and risk of heart failure.

Background Epidemiological studies on smoking and atrial fibrillation have been inconsistent, with some studies showing a positive association while others have found no association. It is also unclear whether there is a dose–response relationship between the number of cigarettes smoked or pack-years and the risk of atrial fibrillation. We conducted a systematic review and meta-analysis to clarify the association.Design Systematic review and meta-analysis.Methods We searched the PubMed and Embase databases for studies of smoking and atrial fibrillation up to 20 July 2017. Prospective studies and nested case–control studies within cohort studies reporting adjusted relative risk estimates and 95% confidence intervals (CIs) of atrial fibrillation associated with smoking were included. Summary relative risks (95% CIs) were estimated using a random effects model.Results Twenty nine prospective studies (22 publications) were included. The summary relative risk was 1.32 (95% CI 1.12–1.56, I2= 84%, n= 11 studies) for current smokers, 1.09 (95% CI 1.00–1.18, I2= 33%, n= 9) for former smokers and 1.21 (95% CI 1.12–1.31, I2= 80%, n= 14) for ever smokers compared to never smokers. Comparing current versus non-current smokers the summary relative risk was 1.33 (95% CI 1.14–1.56, I2= 78%, n= 10). The summary relative risk was 1.14 (95% CI 1.10–1.20, I2= 0%, n= 3) per 10 cigarettes per day and 1.16 (95% CI 1.09–1.25, I2= 49%, n= 2) per 10 pack-years and there was no evidence of a non-linear association for cigarettes per day, Pnon-linearity= 0.17.Conclusions The current meta-analysis suggests that smoking is associated with an increased risk of atrial fibrillation in a dose-dependent matter, but the association is weaker among former smokers compared to current smokers.

ObjectiveTo systematically review outcomes of infants ≤28+6 weeks gestation randomised to resuscitation with low (≤0.3) vs high (≥0.6) fraction of inspired oxygen (FiO2) at delivery.DesignSystematic review of randomised controlled trials of low (≤0.3) vs high (≥0.6) FiO2resuscitation. Information was obtained from databases (Medline/Pub Med, EMBASE, ClinicalTrials.gov, Cochrane) and meeting abstracts between 1990 to 2015. Search index terms: preterm/ resuscitation/oxygen. Data for infants ≤28+6 weeks gestation were independently extracted and pooled using a random effects model. Analyses were performed with Revman V.5.Main outcome measuresDeath in hospital, bronchopulmonary dysplasia (BPD), retinopathy of prematurity >grade 2 (ROP), intraventricular haemorrhage >grade 2 (IVH), patent ductus arteriosus (PDA) and necrotising enterocolitis (NEC).ResultsA total of 251 and 253 infants were enrolled in 8 studies (6 masked, 2 unmasked) in the lower and higher oxygen groups, respectively, (mean gestation 26 weeks) between 2005 and 2014. There were no differences in BPD (relative risk, 95% CIs 0.88 (0.68 to 1.14)), IVH (0.81 (0.52 to 1.27)), ROP (0.82 (0.46 to 1.46)), PDA (0.95 (0.80 to 1.14)) and NEC (1.61 (0.67 to 3.36)) and overall mortality (0.99 (0.52 to 1.91)). Mortality was lower in low oxygen arms of masked studies (0.46 (0.23 to 0.92), p=0.03) and higher in low oxygen arms of unmasked studies (1.94 (1.02 to 3.68), p=0.04).ConclusionsThere is no difference in the overall risk of death or other common preterm morbidities after resuscitation is initiated at delivery with lower (≤0.30) or higher (≥0.6) FiO2in infants ≤28+6 weeks gestation. The opposing results for masked and unmasked trials may represent a Type I error, emphasising the need for larger, well designed studies.

Introduction:Aortic dissection and aneurysm rupture are aortic emergencies. Surgical outcomes and interventional procedures have improved over the past two decades; however, whether this has translated into lower mortality across countries remains an open question.Hypothesis:We hypothesized that given improved surgical mortality, there will be improvement in mortality from aortic dissection and rupture in the UK, Japan, USA, and Canada.Methods:We analyzed the WHO mortality database to determine trends in mortality from aortic dissection and rupture in 4 countries from 2000 to 2019. Crude mortality rate and age-standardized mortality rate per 100,000 persons were calculated, and annual percentage change was estimated using joinpoint regression.Results:In 2019, crude and age-standardized mortality rates from aortic dissection were 2.15 and 1.04 in UK, 8.67 and 2.66 in Japan, 1.21 and 0.76 in USA, and 1.30 and 0.67 in Canada, respectively. In 2019, crude and age-standardized mortality rates from aortic rupture were 4.86 and 1.80 in UK, 5.22 and 1.16 in Japan, 1.04 and 0.52 in USA, and 1.99 and 0.81 in Canada, respectively. There was a significantly decreasing trend in age-standardized mortality from aortic aneurysm rupture in all 4 countries over the study period, and a decreasing trend in age-standardized mortality from aortic dissection in the UK over the study period, in USA until 2010, and in Canada until 2012. There was a significantly increasing trend in mortality from aortic dissection in Japan over the study period, in the USA after 2010, and in Canada after 2012. Joinpoint regression identified significant changes in the trends from decreasing to increasing in USA and Canada. In sensitivity analyses stratified by sex, similar trends were observed.Conclusions:Trends in mortality from aortic aneurysm rupture are decreasing, however, mortality from aortic dissection is increasing in Japan, USA, and Canada. Further study to explain these trends is warranted.

Physical activity has been hypothesized to reduce the risk of preeclampsia, but epidemiologic studies have not shown consistent results. Therefore, we conducted a systematic review and dose–response meta-analysis of epidemiologic studies.

SUMMARY This systematic review compares convenience of administration, adverse events and tolerability of buprenorphine patch with fentanyl patch in patients with chronic pain. Methods of quantitative and qualitative research were combined. Seventeen databases were searched up to December 2010. A total of 49 unique trials (56 publications) were included. Patients regarded the use of patches, both transdermal buprenorphine and fentanyl, as easy and convenient. Compared with buprenorphine patch, fentanyl can cause more cases of constipation and could lead to a higher number of serious adverse events. There were no differences between buprenorphine patch and fentanyl patch regarding dizziness, somnolence, nausea and treatment discontinuation. Overall, transdermal administration of buprenorphine and fentanyl can be seen as an alternative pathway for delivering these drugs. Use of transdermal buprenorphine might be favorable in certain groups of patients, such as renally impaired, elderly and immunosuppressed patients.

The aim of this study was to evaluate subcutaneous transcapillary fluid balance during pulsatile and nonpulsatile extracorporeal circulation (ECC). Changes in the transcapillary fluid balance were studied by measuring subcutaneous interstitial fluid pressure (Pif) using the 'wick in needle' (WIN) method, as well as measuring subcutaneous interstitial fluid colloid osmotic pressure (COPif), using either the wick technique or the blister suction technique. The measurements were performed on the chest wall at the heart level. Simultaneous recordings of plasma colloid osmotic pressure (COPpl) were carried out. Nineteen male patients undergoing aortocoronary bypass grafting were subjected to nonpulsatile flow (group I, n= 11) or pulsatile flow (group II, n= 8) during ECC. Preoperatively there was no difference in the Starling forces between the two groups. During ECC the COP gradient (COPpl-COP if) was reversed to the same extent in the two groups. At three hours and six hours following ECC, COPifin the pulsatile group (12.1 mmHg and 11.4mmHg respectively) was significantly higher than in the nonpulsatile group (10.8mmHg and 10.3mmHg respectively). When weaning from ECC as well as three hours and six hours following ECC, Pifin the pulsatile group was significantly lower than in the nonpulsatile group. Conclusion: in the early postoperative period there is less dilution of the subcutaneous interstitial tissue following application of pulsatile flow during ECC compared to nonpulsatile flow.

ObjectiveTo examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease (CVD), and cancer.DesignSystematic review and meta-analysis of prospective cohort studies.Data sourcesPubMed, Scopus, ISI Web of Science, and Google Scholar to 30 April 2021.Study selectionProspective cohort studies that reported the risk estimates for death from all causes, CVD, and cancer.Data synthesisSummary relative risks and 95% confidence intervals were calculated for the highest versus lowest categories of ALA intake using random effects and fixed effects models. Linear and non-linear dose-response analyses were conducted to assess the dose-response associations between ALA intake and mortality.Results41 articles from prospective cohort studies were included in this systematic review and meta-analysis, totalling 1 197 564 participants. During follow-up ranging from two to 32 years, 198 113 deaths from all causes, 62 773 from CVD, and 65 954 from cancer were recorded. High intake of ALA compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled relative risk 0.90, 95% confidence interval 0.83 to 0.97, I2=77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I2=48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I2=5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I2=3.8%, n=10). In the dose-response analysis, a 1 g/day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut) was associated with a 5% lower risk of all cause (0.95, 0.91 to 0.99, I2=76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I2=30.7%, n=14). The pooled relative risks for the highest compared with lowest tissue levels of ALA indicated a significant inverse association with all cause mortality (0.95, 0.90 to 0.99, I2=8.2%, n=26). Also, based on the dose-response analysis, each 1 standard deviation increment in blood concentrations of ALA was associated with a lower risk of CHD mortality (0.92, 0.86 to 0.98, I2=37.1%, n=14).ConclusionsThe findings show that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and CHD, and a slightly higher risk of cancer mortality, whereas higher blood levels of ALA are associated with a reduced risk of all cause and CHD mortality only.Systematic review registrationPROSPERO CRD42021229487.

ObjectiveTo investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.DesignProspective case-cohort study.SettingPopulations from eight European countries.Participants9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.Main outcome measureIncident type 2 diabetes.ResultsIn a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.ConclusionsThese findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.

ObjectiveTo summarise the evidence of associations between dietary factors and incidence of type 2 diabetes and to evaluate the strength and validity of these associations.DesignUmbrella review of systematic reviews with meta-analyses of prospective observational studies.Data sourcesPubMed, Web of Science, and Embase, searched up to August 2018.Eligibility criteriaSystematic reviews with meta-analyses reporting summary risk estimates for the associations between incidence of type 2 diabetes and dietary behaviours or diet quality indices, food groups, foods, beverages, alcoholic beverages, macronutrients, and micronutrients.Results53 publications were included, with 153 adjusted summary hazard ratios on dietary behaviours or diet quality indices (n=12), food groups and foods (n=56), beverages (n=10), alcoholic beverages (n=12), macronutrients (n=32), and micronutrients (n=31), regarding incidence of type 2 diabetes. Methodological quality was high for 75% (n=115) of meta-analyses, moderate for 23% (n=35), and low for 2% (n=3). Quality of evidence was rated high for an inverse association for type 2 diabetes incidence with increased intake of whole grains (for an increment of 30 g/day, adjusted summary hazard ratio 0.87 (95% confidence interval 0.82 to 0.93)) and cereal fibre (for an increment of 10 g/day, 0.75 (0.65 to 0.86)), as well as for moderate intake of total alcohol (for an intake of 12-24 g/day vno consumption, 0.75 (0.67 to 0.83)). Quality of evidence was also high for the association for increased incidence of type 2 diabetes with higher intake of red meat (for an increment of 100 g/day, 1.17 (1.08 to 1.26)), processed meat (for an increment of 50 g/day, 1.37 (1.22 to 1.54)), bacon (per two slices/day, 2.07 (1.40 to 3.05)), and sugar sweetened beverages (for an increase of one serving/day, 1.26 (1.11 to 1.43)).ConclusionsOverall, the association between dietary factors and type 2 diabetes has been extensively studied, but few of the associations were graded as high quality of evidence. Further factors are likely to be important in type 2 diabetes prevention; thus, more well conducted research, with more detailed assessment of diet, is needed.Systematic review registrationPROSPERO CRD42018088106.

Greater maternal body mass index (BMI) before or during early pregnancy is associated with an increased risk of fetal death, stillbirth, perinatal death, neonatal death, and infant death. This systematic review and meta-analysis of cohort studies was conducted to determine the strength of these associations, the shape of the dose-response relationship, potential confounding, and potential sources of heterogeneity.

Objective To conduct a systematic review and meta-analysis of cohort studies of body mass index (BMI) and the risk of all cause mortality, and to clarify the shape and the nadir of the dose-response curve, and the influence on the results of confounding from smoking, weight loss associated with disease, and preclinical disease.Data sources PubMed and Embase databases searched up to 23 September 2015.Study selection Cohort studies that reported adjusted risk estimates for at least three categories of BMI in relation to all cause mortality.Data synthesis Summary relative risks were calculated with random effects models. Non-linear associations were explored with fractional polynomial models.Results 230 cohort studies (207 publications) were included. The analysis of never smokers included 53 cohort studies (44 risk estimates) with >738 144 deaths and >9 976 077 participants. The analysis of all participants included 228 cohort studies (198 risk estimates) with >3 744 722 deaths among 30 233 329 participants. The summary relative risk for a 5 unit increment in BMI was 1.18 (95% confidence interval 1.15 to 1.21; I2=95%, n=44) among never smokers, 1.21 (1.18 to 1.25; I2=93%, n=25) among healthy never smokers, 1.27 (1.21 to 1.33; I2=89%, n=11) among healthy never smokers with exclusion of early follow-up, and 1.05 (1.04 to 1.07; I2=97%, n=198) among all participants. There was a J shaped dose-response relation in never smokers (Pnon-linearity<0.001), and the lowest risk was observed at BMI 23-24 in never smokers, 22-23 in healthy never smokers, and 20-22 in studies of never smokers with ≥20 years’ follow-up. In contrast there was a U shaped association between BMI and mortality in analyses with a greater potential for bias including all participants, current, former, or ever smokers, and in studies with a short duration of follow-up (<5 years or <10 years), or with moderate study quality scores.Conclusion Overweight and obesity is associated with increased risk of all cause mortality and the nadir of the curve was observed at BMI 23-24 among never smokers, 22-23 among healthy never smokers, and 20-22 with longer durations of follow-up. The increased risk of mortality observed in underweight people could at least partly be caused by residual confounding from prediagnostic disease. Lack of exclusion of ever smokers, people with prevalent and preclinical disease, and early follow-up could bias the results towards a more U shaped association.

Objective To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality.Data sources PubMed and Embase searched up to 3 April 2016.Study selection Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality.Data synthesis Summary relative risks and 95% confidence intervals calculated with a random effects model.Results 45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings—for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I2=9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I2=56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I2=40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I2=37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I2=83%, n=11) for all causes, 0.78 (0.70 to 0.87; I2=0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I2=85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I2=0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I2=79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I2=0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular disease and/or all cause mortality, but there was little evidence of an association with refined grains, white rice, total rice, or total grains.Conclusions This meta-analysis provides further evidence that whole grain intake is associated with a reduced risk of coronary heart disease, cardiovascular disease, and total cancer, and mortality from all causes, respiratory diseases, infectious diseases, diabetes, and all non-cardiovascular, non-cancer causes. These findings support dietary guidelines that recommend increased intake of whole grain to reduce the risk of chronic diseases and premature mortality.

OBJECTIVE: To investigate the association between intake of dietary fibre and whole grains and risk of colorectal cancer. Design Systematic review and meta-analysis of prospective observational studies. DATA SOURCES: PubMed and several other databases up to December 2010 and the reference lists of studies included in the analysis as well as those listed in published meta-analyses. STUDY SELECTION: Prospective cohort and nested case-control studies of dietary fibre or whole grain intake and incidence of colorectal cancer. RESULTS: 25 prospective studies were included in the analysis. The summary relative risk of developing colorectal cancer for 10 g daily of total dietary fibre (16 studies) was 0.90 (95% confidence interval 0.86 to 0.94, I2=0%), for fruit fibre (n=9) was 0.93 (0.82 to 1.05, I2=23%), for vegetable fibre (n=9) was 0.98 (0.91 to 1.06, I2=0%), for legume fibre (n=4) was 0.62 (0.27 to 1.42, I2=58%), and for cereal fibre (n=8) was 0.90 (0.83 to 0.97, I2=0%). The summary relative risk for an increment of three servings daily of whole grains (n=6) was 0.83 (0.78 to 0.89, I2=18%). CONCLUSION: A high intake of dietary fibre, in particular cereal fibre and whole grains, was associated with a reduced risk of colorectal cancer. Further studies should report more detailed results, including those for subtypes of fibre and be stratified by other risk factors to rule out residual confounding. Further assessment of the impact of measurement errors on the risk estimates is also warranted.