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BackgroundPrior research indicates that female physicians spend more time working in the electronic health record (EHR) than do male physicians.ObjectiveTo examine gender differences in EHR usage among primary care physicians and identify potential causes for those differences.DesignRetrospective study of EHR usage by primary care physicians (PCPs) in an academic hospital system.ParticipantsOne hundred twenty-five primary care physiciansInterventionsN/AMain MeasuresEHR usage including time spent working and volume of staff messages and patient messages.Key ResultsAfter adjusting for panel size and appointment volume, female PCPs spend 20% more time (1.9 h/month) in the EHR inbasket and 22% more time (3.7 h/month) on notes than do their male colleagues (p values 0.02 and 0.04, respectively). Female PCPs receive 24% more staff messages (9.6 messages/month), and 26% more patient messages (51.5 messages/month) (p values 0.03 and 0.004, respectively). The differences in EHR time are not explained by the percentage of female patients in a PCP’s panel.ConclusionsFemale physicians spend more time working in their EHR inbaskets because both staff and patients make more requests of female PCPs. These differential EHR burdens may contribute to higher burnout rates in female PCPs.

Cutting-edge lipidomic profiling measures hundreds or even thousands of lipids in plasma and is increasingly used to investigate mechanisms of cardiovascular disease (CVD). In this review, we introduce lipidomic techniques, describe distributions of lipids across lipoproteins, and summarize findings on the association of lipids with CVD based on lipidomics. The main findings of 16 cohort studies were that, independent of total and high-density lipoprotein cholesterol (HDL-c), ceramides (d18:1/16:0, d18:1/18:0, and d18:1/24:1) and phosphatidylcholines (PCs) containing saturated and monounsaturated fatty acyl chains are positively associated with risks of CVD outcomes, while PCs containing polyunsaturated fatty acyl chains (PUFA) are inversely associated with risks of CVD outcomes. Lysophosphatidylcholines (LPCs) may be positively associated with risks of CVD outcomes. Interestingly, the distributions of the identified lipids vary across lipoproteins: LPCs are primarily contained in HDLs, ceramides are mainly contained in low-density lipoproteins (LDLs), and PCs are distributed in both HDLs and LDLs. Thus, the potential mechanism behind previous findings may be related to the effect of the identified lipids on the biological functions of HDLs and LDLs. Only eight studies on the lipidomics of HDL and non-HDL particles and CVD outcomes have been conducted, which showed that higher triglycerides (TAGs), lower PUFA, lower phospholipids, and lower sphingomyelin content in HDLs might be associated with a higher risk of coronary heart disease (CHD). However, the generalizability of these studies is a major concern, given that they used case–control or cross-sectional designs in hospital settings, included a very small number of participants, and did not correct for multiple testing or adjust for blood lipids such as HDL-c, low-density lipoprotein cholesterol (LDL-c), or TAGs. Overall, findings from the literature highlight the importance of research on lipidomics of lipoproteins to enhance our understanding of the mechanism of the association between the identified lipids and the risk of CVD and allow the identification of novel lipid biomarkers in HDLs and LDLs, independent of HDL-c and LDL-c. Lipidomic techniques show the feasibility of this exciting research direction, and the lack of high-quality epidemiological studies warrants well-designed prospective cohort studies.

Experimental studies reported biochemical actions underpinning aging processes and mortality, but the relevant metabolic alterations in humans are not well understood. Here we examine the associations of 243 plasma metabolites with mortality and longevity (attaining age 85 years) in 11,634 US (median follow-up of 22.6 years, with 4288 deaths) and 1878 Spanish participants (median follow-up of 14.5 years, with 525 deaths). We find that, higher levels of N2,N2-dimethylguanosine, pseudouridine, N4-acetylcytidine, 4-acetamidobutanoic acid, N1-acetylspermidine, and lipids with fewer double bonds are associated with increased risk of all-cause mortality and reduced odds of longevity; whereas L-serine and lipids with more double bonds are associated with lower mortality risk and a higher likelihood of longevity. We further develop a multi-metabolite profile score that is associated with higher mortality risk. Our findings suggest that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality. The underlying mechanisms remain to be determined. The metabolic alterations underpinning aging processes and mortality in humans are not well understood. Here, the authors show that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality and longevity.

Objective To evaluate the association between migraine and incident cardiovascular disease and cardiovascular mortality in women.Design Prospective cohort study among Nurses’ Health Study II participants, with follow-up from 1989 and through June 2011.Setting Cohort of female nurses in United States.Participants 115 541 women aged 25-42 years at baseline and free of angina and cardiovascular disease. Cumulative follow-up rates were more than 90%.Main outcome measures The primary outcome of the study was major cardiovascular disease, a combined endpoint of myocardial infarction, stroke, or fatal cardiovascular disease. Secondary outcome measures included individual endpoints of myocardial infarction, stroke, angina/coronary revascularization procedures, and cardiovascular mortality.Results 17 531 (15.2%) women reported a physician’s diagnosis of migraine. Over 20 years of follow-up, 1329 major cardiovascular disease events occurred and 223 women died from cardiovascular disease. After adjustment for potential confounding factors, migraine was associated with an increased risk for major cardiovascular disease (hazard ratio 1.50, 95% confidence interval 1.33 to 1.69), myocardial infarction (1.39, 1.18 to 1.64), stroke (1.62, 1.37 to 1.92), and angina/coronary revascularization procedures (1.73, 1.29 to 2.32), compared with women without migraine. Furthermore, migraine was associated with a significantly increased risk for cardiovascular disease mortality (hazard ratio 1.37, 1.02 to 1.83). Associations were similar across subgroups of women, including by age (<50/≥50), smoking status (current/past/never), hypertension (yes/no), postmenopausal hormone therapy (current/not current), and oral contraceptive use (current/not current).Conclusions Results of this large, prospective cohort study in women with more than 20 years of follow-up indicate a consistent link between migraine and cardiovascular disease events, including cardiovascular mortality. Women with migraine should be evaluated for their vascular risk. Future targeted research is warranted to identify preventive strategies to reduce the risk of future cardiovascular disease among patients with migraine.

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Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (−32%; 95% confidence interval (95% CI): −21% to −42%) and type 2 diabetes (−26%; 95% CI: −15% to −35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses’ Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications. Changes in lipidome profiles, as reflected by improvements in dietary fat quality from saturated to unsaturated fats, were associated with reduced cardiometabolic disease risk, and high-risk populations with unhealthy lipidome profiles would most benefit from an olive oil-rich Mediterranean diet.

Increased respiration during physical activity may increase air pollution dose, which may attenuate the benefits of physical activity on cardiovascular disease (CVD) risk and overall mortality. We aimed to examine the multiplicative interaction between long-term ambient residential exposure to fine particulate matter ( ) and physical activity in the association with CVD risk and overall mortality. We followed 104,990 female participants of the U.S.-based prospective Nurses' Health Study from 1988 to 2008. We used Cox proportional hazards models to assess the independent associations of 24-months moving average residential exposure and physical activity updated every 4 y and the multiplicative interaction of the two on CVD (myocardial infarction and stroke) risk and overall mortality, after adjusting for demographics and CVD risk factors. During 20 years of follow-up, we documented 6,074 incident CVD cases and 9,827 deaths. In fully adjusted models, exposure was associated with modest increased risks of CVD [hazard ratio (HR) for fifth quintile compared to first quintile : 1.09, 95% confidence interval (CI): 0.99, 1.20; ] and overall mortality (HR fifth compared to first quintile: 1.10, 95% CI: 1.02, 1.19; ). Higher overall physical activity was associated with substantially lower risk of CVD [HR fourth quartile, which was equivalent of task (MET)-h/wk, compared to first quartile ( ): 0.61, 95% CI: 0.57, 0.66; ] and overall mortality (HR fourth compared to first quartile: 0.40, 95% CI: 0.37, 0.42; ). We observed no statistically significant interactions between exposure and physical activity (overall, walking, vigorous activity) in association with CVD risk and overall mortality. In this study of U.S. women, we observed no multiplicative interaction between long-term exposure and physical activity; higher physical activity was strongly associated with lower CVD risk and overall mortality at all levels of exposure. https://doi.org/10.1289/EHP7402.

ObjectiveLimited data exist on the association between menopause and atrial fibrillation (AF). We sought to examine the relationship between menopausal age, postmenopausal hormone therapy (PHT) use and incident AF.MethodsThe Women’s Health Study (WHS) enrolled 39 876 female health professionals between 1992 and 1995. We prospectively examined 30 034 women in WHS using Cox proportional-hazard models. Participants were free of cardiovascular disease and AF at baseline and had not undergone hysterectomy without bilateral oophorectomy prior to menopause. Incident AF was confirmed by medical record review.ResultsAt baseline, median age was 53 years (IQR 49–60), median menopausal age was 50 years (IQR 46–52) and 14 415 (48.0%) had prior PHT use. Over a median follow-up of 20.5 years, 1350 AF events occurred. In multivariable analysis, relative hazards for AF were lower among women with younger age at menopause but did not differ significantly from women with the oldest menopausal age (<45: HR 0.82, 95% CI 0.67 to 1.02; 45–49: HR 0.90, 95% CI 0.74 to 1.08; 50–54: HR 0.89, 95% CI 0.75 to 1.06; >54 years: referent). Use of oestrogen-alone PHT, but not oestrogen and progesterone, was independently associated with AF risk (HR 1.22; 95% CI 1.02 to 1.45 vs HR 1.04; 95% CI 0.86 to 1.26). This relationship was not attenuated by intermediary cardiovascular events.ConclusionsIn this large prospective study, menopausal age was not significantly related to incident AF, while use of oestrogen monotherapy was associated with increased AF risk. Our findings suggest a pathophysiological link between unopposed oestrogen exposure and AF in women.Clinical trial registrationNCT000000479; Post-results.

ObjectiveTryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.MethodWe analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.ResultsTryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals.ConclusionHigher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host–microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.

AbstractObjectiveTo assess the association of dietary fatty acids with cardiovascular disease mortality and total mortality among patients with type 2 diabetes.DesignProspective, longitudinal cohort study.SettingHealth professionals in the United States.Participants11 264 participants with type 2 diabetes in the Nurses’ Health Study (1980-2014) and Health Professionals Follow-Up Study (1986-2014).ExposuresDietary fat intake assessed using validated food frequency questionnaires and updated every two to four years.Main outcome measureTotal and cardiovascular disease mortality during follow-up.ResultsDuring follow-up, 2502 deaths including 646 deaths due to cardiovascular disease were documented. After multivariate adjustment, intake of polyunsaturated fatty acids (PUFAs) was associated with a lower cardiovascular disease mortality, compared with total carbohydrates: hazard ratios comparing the highest with the lowest quarter were 0.76 (95% confidence interval 0.58 to 0.99; P for trend=0.03) for total PUFAs, 0.69 (0.52 to 0.90; P=0.007) for marine n-3 PUFAs, 1.13 (0.85 to 1.51) for α-linolenic acid, and 0.75 (0.56 to 1.01) for linoleic acid. Inverse associations with total mortality were also observed for intakes of total PUFAs, n-3 PUFAs, and linoleic acid, whereas monounsaturated fatty acids of animal, but not plant, origin were associated with a higher total mortality. In models that examined the theoretical effects of substituting PUFAs for other fats, isocalorically replacing 2% of energy from saturated fatty acids with total PUFAs or linoleic acid was associated with 13% (hazard ratio 0.87, 0.77 to 0.99) or 15% (0.85, 0.73 to 0.99) lower cardiovascular disease mortality, respectively. A 2% replacement of energy from saturated fatty acids with total PUFAs was associated with 12% (hazard ratio 0.88, 0.83 to 0.94) lower total mortality.ConclusionsIn patients with type 2 diabetes, higher intake of PUFAs, in comparison with carbohydrates or saturated fatty acids, is associated with lower total mortality and cardiovascular disease mortality. These findings highlight the important role of quality of dietary fat in the prevention of cardiovascular disease and total mortality among adults with type 2 diabetes.