Prospective benchmarking of an observational analysis in the SWEDEHEART registry against the REDUCE-AMI randomized trial.

Prospective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning the protocol of the trial and the observational analysis, while the trials findings are unavailable. The Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction (REDUCE-AMI, ClinicalTrials.gov ID: NCT03278509) trial started recruitment in September 2017 and results are expected in 2024. REDUCE-AMI aimed to estimate the effect of long-term use of beta blockers on the risk of death and myocardial following a myocardial infarction with preserved left ventricular systolic ejection fraction. We specified the protocol of a target trial as similar as possible to that of REDUCE-AMI, then emulated the target trial using observational data from Swedish healthcare registries. Had everyone followed the treatment strategy as specified in the target trial protocol, the observational analysis estimated a reduction in the 5-year risk of death or myocardial infarction of 0.8 percentage points for beta blockers compared with no beta blockers; effects ranging from an absolute reduction of 4.5 percentage points to an increase of 2.8 percentage points in the risk of death or myocardial infarction were compatible with our data under conventional statistical criteria. Once results of REDUCE-AMI are published, we will compare the results of our observational analysis against those from the trial. If this prospective benchmarking is successful, it supports the credibility of additional analyses using these observational data, which can rapidly deliver answers to questions that could not be answered by the initial trial. If benchmarking proves unsuccessful, we will conduct a "postmortem" analysis to identify the reasons for the discrepancy. Prospective benchmarking shifts the investigator focus away from an endeavour to use observational data to obtain similar results as a completed randomized trial, to a systematic attempt to align the design and analysis of the trial and the observational analysis.

Accuracy of self-reported diagnoses of polymyalgia rheumatica and giant cell arteritis in the French prospective E3N- EPIC cohort: A validation study.

OBJECTIVES: To assess the accuracy of self-reported giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) diagnoses in a large French population-based prospective cohort, and to devise algorithms to improve their accuracy. METHODS: The E3N-EPIC cohort study (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale) includes 98,995 French women born between 1925 and 1950, recruited in 1990 to study risk factors of cancer and chronic diseases. They completed biennially mailed questionnaires to update their health-related information and lifestyle characteristics. In three questionnaires, women could self-report a diagnosis of GCA/PMR. Those women were additionally sent a specific questionnaire, designed to ascertain self-reported diagnoses of GCA/PMR. Four algorithms were then devised to improve their identification. Accuracies of self-reported diagnoses and of each algorithm were calculated by comparing the diagnoses with a blinded medical chart review. RESULTS: Among 98,995 participants, 1,392 women self-reported GCA/PMR. 830 women sent back the specific questionnaire, and 202 women provided medical charts. After independent review of the 202 medical charts, 87.6 % of the self-reported diagnoses of GCA/PMR were accurate. Using additional data from a specific questionnaire (diagnosis confirmation by a physician, and self-report of >3-month of glucocorticoids), and from a reimbursement database (at least two deliveries of glucocorticoids in less than 3 consecutive months) improved their accuracy (91.8 % to 92.8 %). CONCLUSION: The accuracy of self-reported diagnosis of GCA/PMR was high in the E3N-cohort but using additional data as a specific GCA/PMR questionnaire and/or corticosteroid reimbursement database further improved this accuracy. With nearly 600 detected cases of GCA/PMR, we will be able to investigate risk factors for GCA/PMR in women.

Jorvik: A membrane-containing phage that will likely found a new family within Vinavirales.

Although membrane-containing dsDNA bacterial viruses are some of the most prevalent predators in aquatic environments, we know little about how they function due to their intractability in the laboratory. Here, we have identified and thoroughly characterized a new type of membrane-containing bacteriophage, Jorvik, that infects the freshwater mixotrophic model bacterium Rhodobacter capsulatus. Jorvik is extremely virulent, can persist in the host integrated into the RuBisCo operon and encodes two experimentally verified cell wall hydrolases. Jorvik-like prophages are abundant in the genomes of Alphaproteobacteria, are distantly related to known viruses of the class Tectiliviricetes, and we propose they should be classified as a new family. Crucially, we demonstrate how widely used phage manipulation methods should be adjusted to prevent loss of virus infectivity. Our thorough characterization of environmental phage Jorvik provides important experimental insights about phage diversity and interactions in microbial communities that are often unexplored in common metagenomic analyses.

Canadian Ultralight Accidents in Water (1990 to 2020).

INTRODUCTION: Recently, an analysis of Canadian seaplane accidents terminating in water (1995-2019) was conducted, but ultralight water accidents were excluded due to differences from general aviation operations. This is the first literature that reports a series of ultralight accidents that occurred in water. The purpose of this paper is to identify the circumstances surrounding ultralight water accidents in Canada and to identify actions with the potential to improve survival.METHODS: Ultralight water accidents that were reported to the Transportation Safety Board of Canada between 1990 and 2020 were reviewed.RESULTS: Of the 1021 accidents that involved ultralights, 114 terminated in water, involving 155 occupants and 8 fatalities, yielding an occupant mortality rate of 5%. Of the accidents, 52% occurred during landing. There was less than 15 s warning in 78% of cases, which included five (63%) fatalities. The aircraft inverted in 40% of the accidents and, in 21%, it sank immediately. Loss of control was the terminal cause of the accident in 43% of cases, while adverse environmental conditions were reported in 38% of accidents. Little or no details were included on lifejacket or restraint harness use, status of emergency exits, water temperature, or occupant diving experience or underwater escape training.CONCLUSIONS: The mortality rate in ultralight aircraft water accidents was less than half that of helicopter and seaplane ditchings, but the lack of warning time was similar. All pilots and passengers need to have a well-practiced survival schema before strapping in and can benefit from underwater escape training.MacDonald C, Brooks C, McGowan R, Rosberg A. Canadian ultralight accidents in water (1990 to 2020). Aerosp Med Hum Perform. 2023; 94(6):437-443.

Risk Prediction Models for Cardiotoxicity of Chemotherapy Among Patients With Breast Cancer: A Systematic Review.

Importance: Cardiotoxicity is a serious adverse effect that can occur in women undergoing treatment for breast cancer. Identifying patients who will develop cardiotoxicity remains challenging. Objective: To identify, describe, and evaluate all prognostic models developed to predict cardiotoxicity following treatment in women with breast cancer. Evidence Review: This systematic review searched the Medline, Embase, and Cochrane databases up to September 22, 2021, to include studies developing or validating a prediction model for cardiotoxicity in women with breast cancer. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess both the risk of bias and the applicability of the prediction modeling studies. Transparency reporting was assessed with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) tool. Findings: After screening 590 publications, we identified 7 prognostic model studies for this review. Six were model development studies and 1 was an external validation study. Outcomes included occurrence of cardiac dysfunction (echocardiographic parameters), heart failure, and composite clinical outcomes. Model discrimination, measured by the area under receiver operating curves or C statistic, ranged from 0.70 (95% IC, 0.62-0.77) to 0.87 (95% IC, 0.77-0.96). The most common predictors identified in final prediction models included age, baseline left ventricular ejection fraction, hypertension, and diabetes. Four of the developed models were deemed to be at high risk of bias due to analysis concerns, particularly for sample size, handling of missing data, and not presenting appropriate performance statistics. None of the included studies examined the clinical utility of the developed model. All studies met more than 80% of the items in TRIPOD checklist. Conclusions and Relevance: In this systematic review of the 6 predictive models identified, only 1 had undergone external validation. Most of the studies were assessed as being at high overall risk of bias. Application of the reporting guidelines may help future research and improve the reproducibility and applicability of prediction models for cardiotoxicity following breast cancer treatment.

Associations between saturated fat intake and other dietary macronutrients and incident hypertension in a prospective study of French women.

PURPOSE: Saturated fat has long been associated with cardiovascular disease in multiple prospective studies, and randomized controlled trials. Few studies have assessed the relative associations between saturated fat and other macronutrients with hypertension, a major risk factor for cardiovascular disease. The aim of this study was to assess the relative associations between saturated fat, other macronutrients such as monounsaturated and polyunsaturated fat, proteins, and carbohydrates, and incident hypertension in a large prospective cohort of French women. METHODS: This study used data from the E3N cohort study, including participants free of hypertension at baseline. A food frequency questionnaire was used to determine dietary intakes of saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), animal protein (AP), vegetable protein (VP), carbohydrates (CH) and various foods. Cases of hypertension were based on self-report, validated by drug reimbursement data. Covariates were based on self-report. Cox proportional hazard models were used to estimate the relative associations between different macronutrients and hypertension risk, using the 'substitution' framework. Bootstrapping was used to generate 95% confidence intervals. RESULTS: This study included 45,854 women free of hypertension at baseline. During 708,887 person-years of follow-up, 12,338 incident cases of hypertension were identified. Compared to saturated fat, higher consumption of all other macronutrients was associated with a lower risk of hypertension (HRMUFA = 0.74 [0.67: 0.81], HRPUFA = 0.84 [0.77: 0.92], HRCH = 0.83 [0.77: 0.88], HRAP = 0.91 [0.85: 0.97], HRVP = 0.93 [0.83: 1.03]). CONCLUSION: This study finds that relative to other macronutrients such as monounsaturated or polyunsaturated fat, higher intake of saturated fat is associated with a higher risk of hypertension among women.

Relative to processed red meat, alternative protein sources are associated with a lower risk of hypertension and diabetes in a prospective cohort of French women.

Many dietary guidelines recommend restricting the consumption of processed red meat (PRM) in favour of healthier foods such as fish, to reduce the risk of chronic conditions such as hypertension and diabetes. The objective of this study was to estimate the potential effect of replacing PRM for fatty fish, lean fish, red meat, eggs, pulses, or vegetables, on the risk of incident hypertension and diabetes. This was a prospective study of women in the E3N cohort study. Cases of diabetes and hypertension were based on self-report, specific questionnaires, and drug reimbursements. In the main analysis, information on regular dietary intake was assessed with a single food history questionaire, and food substitutions were modelled using cox proportional hazard models. 95 % confidence intervals were generated via bootstrapping. 71 081 women free of diabetes and 45 771 women free of hypertension were followed for an average of 18·7 and 18·3 years, respectively. 2681 incident cases of diabetes and 12 327 incident cases of hypertension were identified. Relative to PRM, fatty fish was associated with a 15 % lower risk of diabetes (HR = 0·85, 95 CI (0·73, 0·97)) and hypertension (HR = 0 85 (0·79, 0·91)). Between 3 and 10 % lower risk of hypertension or diabetes was also observed when comparing PRM with vegetables, unprocessed red meat or pulses. Relative to PRM, alternative protein sources such as fatty fish, unprocessed red meat, vegetables or pulses was associated with a lower risk of hypertension and diabetes.

Association between beverage consumption and risk of rheumatoid arthritis: a prospective study from the French E3N Cohort.

OBJECTIVES: To assess the relationship between consumption of largely consumed beverages (coffee, tea, alcohol and soft drinks) and the risk of RA. MATERIAL AND METHODS: The E3N Study (Étude Épidémiologique auprès des femmes de la Mutuelle Générale de l'Éducation Nationale) is a French prospective cohort including 98 995 women since 1990. Food and beverage consumption was assessed using a validated food-frequency questionnaire. Hazard ratios (HR) and their 95% CI for incident RA were estimated by Cox proportional hazards model. RESULTS: Among 62 631 women, 481 incident RA cases were identified. Consumptions of tea, alcohol and sugar-sweetened soft drinks were not associated with RA risk. We observed a linear association between coffee consumption and RA risk [≥4 cups/day vs ≤1cup/day, HR = 1.24; 95% CI (0.94, 1.64), Ptrend = 0.04], and a higher risk of RA with artificially sweetened soft drinks consumption [consumers vs not, HR = 1.66; 95% CI (1.12, 2.45)], particularly in never-smokers. Among ever-smokers, moderate liquor intake was associated with a reduced risk of RA [1-3 glasses/week vs non-consumers, HR = 0.63; 95% CI (0.43, 0.91)] and moderate wine consumption with a reduced risk of seropositive RA. CONCLUSIONS: In a large cohort of women, tea, alcohol and sugar-sweetened soft drinks consumption was not associated with RA risk, whereas consumption of coffee (especially caffeinated coffee), and artificially sweetened soft drinks was associated with higher RA risk, particularly among never-smokers. If further confirmed, these results could lead to novel mechanistic hypotheses and to simple prevention measures.

A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk.

BACKGROUND: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. OBJECTIVE: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. METHODS: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. RESULTS: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. CONCLUSIONS: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.

Healthy diet associated with better asthma outcomes in elderly women of the French Asthma-E3N study.

PURPOSE: The impact of a healthy diet on asthma prevention and management, particularly among elderly women, remains poorly understood. We investigated whether a healthy diet would be associated with fewer asthma symptoms, and, among women with asthma, with reduced uncontrolled asthma and metabolic-related multimorbidity. METHODS: We included 12,991 elderly women (mean age = 63 years) from the Asthma-E3N study, a nested case-control study within the French E3N cohort. Negative binomial regressions were used to analyse associations between a healthy diet [evaluated by the Alternate Healthy Eating Index-2010 (AHEI-2010)] and a validated asthma symptom score, and logistic regressions to analyse associations between the AHEI-2010 with the asthma control test and multimorbidity profiles previously identified by clustering methods on medications used. RESULTS: After adjustment for potential confounders, a linear inverse association was found between the AHEI-2010 score and the asthma symptom score [mean score ratio (95% CI) = 0.82 (0.75-0.90) for the highest versus lowest quintile; p for trend < 0.0001]. In addition, women in the highest versus lowest AHEI-2010 tertile were at a lower risk to belong to the "Predominantly metabolic multimorbidity-related medications profile" compared to the "Few multimorbidity-related medications" profile [OR 0.80 (0.63-1.00) for tertile 3; p for trend = 0.05; n = 3474]. CONCLUSION: Our results show that a healthy dietary intake could play an important role in the prevention and management of asthma over the life course.

Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review.

BACKGROUND: Vaccines are critical cost-effective tools to control the coronavirus disease 2019 (COVID-19) pandemic. However, the emergence of variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may threaten the global impact of mass vaccination campaigns. AIMS: The objective of this study was to provide an up-to-date comparative analysis of the characteristics, adverse events, efficacy, effectiveness and impact of the variants of concern for 19 COVID-19 vaccines. SOURCES: References for this review were identified through searches of PubMed, Google Scholar, BioRxiv, MedRxiv, regulatory drug agencies and pharmaceutical companies' websites up to 22nd September 2021. CONTENT: Overall, all COVID-19 vaccines had a high efficacy against the original strain and the variants of concern, and were well tolerated. BNT162b2, mRNA-1273 and Sputnik V after two doses had the highest efficacy (>90%) in preventing symptomatic cases in phase III trials. mRNA vaccines, AZD1222, and CoronaVac were effective in preventing symptomatic COVID-19 and severe infections against Alpha, Beta, Gamma or Delta variants. Regarding observational real-life data, full immunization with mRNA vaccines and AZD1222 seems to effectively prevent SARS-CoV-2 infection against the original strain and Alpha and Beta variants but with reduced effectiveness against the Delta strain. A decline in infection protection was observed at 6 months for BNT162b2 and AZD1222. Serious adverse event rates were rare for mRNA vaccines-anaphylaxis 2.5-4.7 cases per million doses, myocarditis 3.5 cases per million doses-and were similarly rare for all other vaccines. Prices for the different vaccines varied from $2.15 to $29.75 per dose. IMPLICATIONS: All vaccines appear to be safe and effective tools to prevent severe COVID-19, hospitalization, and death against all variants of concern, but the quality of evidence greatly varies depending on the vaccines considered. Questions remain regarding a booster dose and waning immunity, the duration of immunity, and heterologous vaccination. The benefits of COVID-19 vaccination outweigh the risks, despite rare serious adverse effects.

Survival from Canadian Seaplane Water Accidents: 1995 to 2019.

INTRODUCTION: Each year in Canada, there are a number of pilots and passengers who die in seaplane water accidents. A study examining the human factors and fatality rates associated with these accidents was conducted. METHODS: Seaplane water accident investigations by the Transportation Safety Board of Canada (TSB) between 1995 and 2019 were reviewed. RESULTS: There were 487 accidents involving 1144 occupants (487 pilots, 657 passengers). There were less than 15 s warning in 86% of cases. There were 60 pilots and 88 passengers who dieda survival rate of 87%. Drowning, trapped within the cabin was the principal cause of death (54%). Loss of control on landing, wheels down landings, and other landing problems (49%) were the principal causes of the accidents and 77% of the fatalities occurred in this group. These arose because the pilot(s) misjudged wind, waves, and glassy water. Over 50% of seaplanes inverted and 10% floated briefly then sank, resulting in the highest percentage of fatalities. Wearing the seat harness incorrectly, injury, in-rushing water, and inability to locate and operate exit mechanisms (including rescuers inability to open the exits external to the fuselage) all contributed to the fatalities. Life jackets would have been of benefit in several cases. Of the accidents, 57% were private flights. CONCLUSIONS: Passengers require a thorough preflight briefing, life jackets should be worn by all pilots and passengers, and private and commercial pilots should receive Underwater Egress Training. MacDonald C, Brooks C, McGowan R. Survival from Canadian seaplane water accidents: 1995 to 2019. Aerosp Med Hum Perform. 2021; 92(10):798805.

Menopausal hormone therapy and risk of incident hypertension: role of the route of estrogen administration and progestogens in the E3N cohort.

OBJECTIVES: Although menopausal hormone therapy (MHT) remains the most effective treatment for vasomotor symptoms of menopause, its association with the development of arterial hypertension remains unclear. We sought to explore associations between different formulations of MHT and incident hypertension among menopausal women in a prospective cohort study. METHODS: We used the Etude Epidémiologique de femmes de la Mutuelle Générale de l'Education (E3N) cohort, a French prospective population-based study initiated in 1990 on 98,995 women. Out of these, 49,905 menopausal women with complete information on the use of MHT, and without prevalent hypertension at inclusion were included. RESULTS: The mean age of the population at baseline was 54.2 ±â€Š4.3 years, and 32,183 (64.5%) reported ever using MHT. Among these women, 10,173 cases of incident hypertension were identified over an average follow-up time of 10.6 years. Compared with women who never used MHT, those who ever used it had an increased risk of incident hypertension (adjusted HR 1.07, 95% CI 1.02-1.12) after adjustment for body mass index and other potential confounders. Oral but not transdermal estrogen use was associated with an increased risk of hypertension (adjusted HR = 1.09; 95% CI: 1.04-1.14 and HR = 1.03; 95% CI: 0.99-1.07, respectively). However, the HRs associated with oral and transdermal estrogens did not differ significantly (P-homogeneity = 0.09). Regarding the role of concomitant progestogens, pregnane and norpregnane derivatives were significantly associated with hypertension risk (HR = 1.12; 95% CI: 1.06-1.19 and HR = 1.06; 95% CI: 1.01-1.13, respectively). CONCLUSIONS: MHT was associated with a modest but significant increased risk of incident hypertension, especially when using oral estrogen in combination with a progestogen such as pregnane and norpregnane derivatives. Surveillance of blood pressure should be added to the medical surveillance of MHT users.

Video Summary:http://links.lww.com/MENO/A802 .

Long-term exposure to low-level ambient air pollution and incidence of stroke and coronary heart disease: a pooled analysis of six European cohorts within the ELAPSE project.

BACKGROUND: Long-term exposure to outdoor air pollution increases the risk of cardiovascular disease, but evidence is unclear on the health effects of exposure to pollutant concentrations lower than current EU and US standards and WHO guideline limits. Within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we investigated the associations of long-term exposures to fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and warm-season ozone (O3) with the incidence of stroke and acute coronary heart disease. METHODS: We did a pooled analysis of individual data from six population-based cohort studies within ELAPSE, from Sweden, Denmark, the Netherlands, and Germany (recruited 1992-2004), and harmonised individual and area-level variables between cohorts. Participants (all adults) were followed up until migration from the study area, death, or incident stroke or coronary heart disease, or end of follow-up (2011-15). Mean 2010 air pollution concentrations from centrally developed European-wide land use regression models were assigned to participants' baseline residential addresses. We used Cox proportional hazards models with increasing levels of covariate adjustment to investigate the association of air pollution exposure with incidence of stroke and coronary heart disease. We assessed the shape of the concentration-response function and did subset analyses of participants living at pollutant concentrations lower than predefined values. FINDINGS: From the pooled ELAPSE cohorts, data on 137 148 participants were analysed in our fully adjusted model. During a median follow-up of 17·2 years (IQR 13·8-19·5), we observed 6950 incident events of stroke and 10 071 incident events of coronary heart disease. Incidence of stroke was associated with PM2·5 (hazard ratio 1·10 [95% CI 1·01-1·21] per 5 µg/m3 increase), NO2 (1·08 [1·04-1·12] per 10 µg/m3 increase), and black carbon (1·06 [1·02-1·10] per 0·5 10-5/m increase), whereas coronary heart disease incidence was only associated with NO2 (1·04 [1·01-1·07]). Warm-season O3 was not associated with an increase in either outcome. Concentration-response curves indicated no evidence of a threshold below which air pollutant concentrations are not harmful for cardiovascular health. Effect estimates for PM2·5 and NO2 remained elevated even when restricting analyses to participants exposed to pollutant concentrations lower than the EU limit values of 25 µg/m3 for PM2·5 and 40 µg/m3 for NO2. INTERPRETATION: Long-term air pollution exposure was associated with incidence of stroke and coronary heart disease, even at pollutant concentrations lower than current limit values. FUNDING: Health Effects Institute.

Dietary Copper/Zinc Ratio and Type 2 Diabetes Risk in Women: The E3N Cohort Study.

The serum copper (Cu) to zinc (Zn) ratio could be an important determinant of Type 2 diabetes (T2D) risk, but prospective epidemiological data are scarce. We aimed to investigate the association between T2D incidence and the dietary Cu/Zn ratio. A total of 70,991 women from the E3N cohort study were followed for 20 years. The intakes of copper and zinc were estimated at baseline using a validated food frequency questionnaire. We identified and validated 3292 incident T2D cases. Spline analysis showed that a Cu/Zn ratio < 0.55 was associated with a lower risk of T2D. Subgroup analyses comparing women in the highest versus the lowest quintile of Cu/Zn ratio showed the same pattern of association for obese women and those with zinc intake ≥8 mg/day. However, for women with zinc intake <8 mg/day, higher Cu/Zn ratio appeared to be associated with higher T2D risk. Our findings suggest that a lower dietary Cu/Zn ratio is associated with a lower T2D risk, especially among obese women and women with zinc intake >8 mg/day. Further studies are warranted to validate our results.

BMI in the Associations of Plant-Based Diets with Type 2 Diabetes and Hypertension Risks in Women: The E3N Prospective Cohort Study.

BACKGROUND: Few studies have evaluated the quality of plant-based diets in relation to chronic diseases, and the potential role of BMI is not clearly explored. OBJECTIVES: To study the associations between plant-based diet indices and type 2 diabetes (T2D) and hypertension risks, as well as the extent to which the associations were modified and/or mediated by BMI. METHODS: The study included 74,522 women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale prospective cohort [mean (SD): age, 52.94 (6.7) years; BMI, 22.970 (3.328) kg/m2]. Dietary data were collected at baseline (1993) via an FFQ. Overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) were developed. Multivariable Cox regression models were used to derive HRs and 95% CIs. Effect modification and mediation by BMI were explored. RESULTS: There were 3292 (4.64%) incident cases of T2D and 12,504 (27.14%) incident cases of hypertension over ∼20 years of follow-up. In the multivariable model further adjusted for BMI, higher adherence to PDI and hPDI was associated with lower T2D and hypertension risks, with an HR per 1-SD increase (95% CI) of 0.88 (0.85, 0.91) and 0.96 (0.94, 0.98) for PDI and 0.88 (0.85, 0.92) and 0.94 (0.92, 0.95) for hPDI, respectively. uPDI was not associated with T2D [0.98 (0.94, 1.01)], whereas a positive association was observed with hypertension: 1.04 (1.02, 1.06). There was interaction between PDI and uPDI, as well as BMI, on T2D (P-interaction < 0.001) but not on hypertension (P-interaction > 0.05). In addition, BMI mediated 26-59% and 0.2-59% of diet-T2D and diet-hypertension associations, respectively. CONCLUSIONS: Differential associations between plant-based diets and T2D and hypertension risks were observed among women in this large prospective study. Only healthier plant foods were associated with lower risks, partly through decreasing BMI. The protocol was registered at clinicaltrials.gov as NCT03285230.

Hysterectomy, non-malignant gynecological diseases, and the risk of incident hypertension: The E3N prospective cohort.

OBJECTIVES: While it has been reported that women with uterine fibroids or endometriosis are commonly overweight and hypertensive, the association between non-malignant gynecological diseases and the risk of hypertension has been little studied prospectively. The aim of this study was to investigate in a large French cohort of women whether a history of hysterectomy, uterine fibroids, or endometriosis was prospectively related to an increased risk of incident hypertension. STUDY DESIGN: We analyzed 50,286 women from the E3N cohort who were free of hypertension at baseline, with a median follow-up of 16.4 years. MAIN OUTCOME MEASURES: Gynecological diseases were based on self-report. Cox proportional hazards models with age as the timescale were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Covariates included smoking status, body mass index (BMI), physical activity, and hormonal factors. RESULTS: A total of 12,073 women (24%) developed hypertension during follow-up. Women with a history of hysterectomy had an increased risk of incident hypertension, which persisted after adjustment for potential confounding factors (adjusted HR=1.18, 95% CI 1.12-1.24). Risk was similar in women with hysterectomy with or without oophorectomy. Risk of hypertension was higher in women with a history of endometriosis (HRendometriosis 1.19, 95%CI 1.11-1.22) or uterine fibroids (HRfibroids 1.18, 95%CI 1.13-1.22), irrespective of hysterectomy. Associations were similar after further adjustment for BMI. CONCLUSIONS: Hysterectomy and non-malignant gynecological diseases were associated with an increased risk of hypertension in this large prospective study. Women with these conditions may benefit from blood pressure monitoring. ClinicalTrials.gov identifier: NCT03285230.

Association of Migraine With Incident Hypertension After Menopause: A Longitudinal Cohort Study.

OBJECTIVE: Migraine has been identified as a potential risk factor for hypertension in prospective studies. In women, migraine prevalence decreases after menopause, but no studies have determined whether migraine is associated with hypertension after menopause. This study sought to determine whether history of migraine was associated with an increased risk of hypertension among menopausal women. METHODS: We assessed associations between migraine and hypertension in a longitudinal cohort study of 56,202 menopausal women participating in the French E3N cohort, with follow-up beginning in 1993. We included women who did not have hypertension or cardiovascular disease at the time of menopause. Migraine was classified as ever or never at each questionnaire cycle. Cox proportional hazards models were used to investigate relations between migraine and hypertension, controlling for potential confounding. A secondary analysis with baseline in 2011 considered aura status, grouping participants reporting migraine as migraine with aura, migraine without aura, or unknown migraine type. RESULTS: During 826,419 person-years, 12,501 cases of incident hypertension were identified, including 3,100 among women with migraine and 9,401 among women without migraine. Migraine was associated with an increased risk of hypertension in menopausal women (hazard ratio [HR]migraine 1.29 [95% confidence interval 1.24, 1.35]) and was consistent in post hoc sensitivity analyses, such as when controlling for common migraine medications. Associations between migraine and hypertension were similar whether or not women reported aura (HRmigraine aura 1.54 [1.04, 2.30], HRmigraine no aura 1.32 [0.87, 2.02], p heterogeneity 0.60). Associations were slightly stronger among ever users of menopausal hormone therapy (HRmigraine 1.34 [1.27, 1.41]) than among never users (HRmigraine 1.19 [1.11, 1.28]). CONCLUSIONS: Migraine was associated with an increased risk of hypertension among menopausal women. In secondary analysis, we did not observe a significant difference between migraine with aura and migraine without aura.