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Background and purpose Elevated plasma uric acid has been inconsistently associated with an increased risk of total stroke; however, data are sparse amongst women. The association between plasma uric acid concentrations and ischaemic stroke amongst women was examined and the effect modification by key cardiovascular risk factors was evaluated. Methods A nested case−control design with matching by age, race/ethnicity, smoking status, menopausal status, postmenopausal hormone therapy use, date of blood draw and fasting status was utilized amongst female participants of the Nurses' Health Study who provided blood samples between 1989 and 1990. Plasma uric acid was measured on stored blood samples. The National Survey of Stroke criteria were utilized to confirm 460 incident cases of ischaemic stroke by medical records from 1990 to 2006. Multivariable conditional logistic regression models were estimated. Results In matched analysis, risk of ischaemic stroke increased by 15% for each 1 mg/dl increase in plasma uric acid [95% confidence interval ( CI) 3%-28%], but was no longer significant after adjustment for cardiovascular risk factors, particularly history of hypertension. The highest quartile of uric acid was significantly associated with greater risk of ischaemic stroke (relative risk 1.56; 95% CI 1.06-2.29, extreme quartiles) in matched analysis, but estimates were no longer significant after adjustment for cardiovascular risk factors (relative risk 1.43; 95% CI 0.93-2.18). Significant effect modification by key cardiovascular risk factors was not observed. Conclusions Plasma uric acid levels were not independently associated with increased risk of ischaemic stroke in this cohort of women. Whilst plasma uric acid was associated with stroke risk factors, it was not independently associated with stroke risk. [ABSTRACT FROM AUTHOR]

Diabetes is known to increase mortality rate, but the degree to which mild hyperglycaemia may be associated with the risk of death is uncertain. We examined the association between HbA1c measured in stored erythrocytes and mortality rate in women with and without diabetes. We conducted a cohort study of 27,210 women ≥ 45 years old with no history of cardiovascular disease or cancer who participated in the Women’s Health Study, a randomised trial of vitamin E and aspirin. Over a median of 10 years of follow-up, 706 women died. Proportional hazards models adjusted for age, smoking, hypertension, blood lipids, exercise, postmenopausal hormone use, multivitamin use and C-reactive protein were used to estimate the relative risk of mortality. Among women without a diagnosis of diabetes and HbA1c <5.60%, those in the top quintile (HbA1c 5.19–5.59%) had a relative risk of mortality of 1.28 (95% CI 0.98–1.69, p value for linear trend = 0.14) compared with those with HbA1c 2.27–4.79%. Women with HbA1c 5.60–5.99% and no diagnosis of diabetes had a 54% increased risk of mortality (95% CI 1–136%) compared with those with HbA1c 2.27–4.79%. HbA1c was significantly associated with mortality across the range 4.50–7.00% ( p value for linear trend = 0.02); a test of deviation from linearity was not statistically significant ( p = 0.67). Diabetic women had more than twice the mortality risk of non-diabetic women. This study provides further evidence that chronic mild hyperglycaemia, even in the absence of diagnosed diabetes, is associated with increased risk of mortality. ClinicalTrials.gov ID no.: NCT00000479 [ABSTRACT FROM AUTHOR]

BACKGROUND: Waist circumference is a simpler measure of abdominal adiposity than waist/hip ratio (WHR), but few studies have directly compared the two measures as predictors of coronary heart disease (CHD) in men. In addition, whether the association of abdominal adiposity is independent of total adiposity as measured by body mass index (BMI) in men remains uncertain. OBJECTIVE: To compare waist circumference and WHR as predictors of CHD in men, and to determine whether the association is independent of BMI. DESIGN: Prospective cohort study. METHODS: We compared WHR, waist circumference and BMI with risk of CHD (myocardial infarction or coronary revascularization) among men in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among 22 071 apparently healthy US male physicians, aged 40-84 y at baseline in 1982. Men reported height at baseline, and weight, waist and hip measurements on the 9 y follow-up questionnaire. RESULTS: Among the 16 164 men who reported anthropometric measurements and were free from prior CHD, stroke or cancer, a total of 552 subsequent CHD events occurred during an average follow-up of 3.9 y. After adjusting for age, randomized study agent, smoking, physical activity, parental history of myocardial infarction, alcohol intake, multivitamin and aspirin use, men in the highest WHR quintile (≥0.99) had a relative risk (RR) for CHD of 1.50 (95% CI 1.14-1.98) compared with those in the lowest quintile (< 0.90). Men in the highest waist circumference quintile (≥103.6 cm) had a RR of 1.60 (CI, 1.21-2.11 ) for CHD compared with men in the lowest quintile (<88.4 cm). Further adjustment for BMI substantially attenuated these associations: men in the highest WHR and waist circumference quintiles had relative risks for CHD of 1.23 (CI, 0.92-1.66) and 1.06 (CI, 0.741.53), respectively. Men in the highest BMI quintile (≥27.6 kg/m²) had a multivariate RR of CHD of 1.73 (CI, 1.29-2.32), after adjustment for WHR.... [ABSTRACT FROM AUTHOR]

Context: Physically active women have lower coronary heart disease (CHD) rates than inactive women. However, whether the association differs by intensity of activity or in women at high risk for CHD is unclear.Objective: To examine the relation between physical activity, specifically investigating walking (a light-to-moderate activity depending on pace), and CHD among women, including those at high risk for CHD.Design, Setting, and Participants: Cohort study of 39 372 healthy female health professionals aged 45 years or older, enrolled throughout the United States between September 1992 and May 1995, with follow-up to March 1999. Recreational activities, including walking and stair climbing, were reported at study entry.Main Outcome Measure: Correlation of CHD with energy expended on all activities, vigorous activities, and walking.Results: A total of 244 cases of CHD occurred. Adjusting for potential confounders, the relative risks (RRs) of CHD for less than 200, 200-599, 600-1499, and 1500 or more kcal/wk expended on all activities were 1.00 (referent), 0.79 (95% confidence interval [CI], 0.56-1.12), 0.55 (95% CI, 0.37-0.82), and 0.75 (95% CI, 0.50-1.12), respectively (P for linear trend =.03). Vigorous activities were associated with lower risk (RR, 0.63; 95% CI, 0.38-1.04 comparing highest and lowest categories). Walking also predicted lower risk among women without vigorous activities. Among these women, the multivariate RRs for walking 1 to 59 min/wk, 1.0 to 1.5 h/wk, and 2 or more h/wk, compared with no regular walking, were 0.86 (95% CI, 0.57-1.29), 0.49 (95% CI, 0.28-0.86), and 0.48 (95% CI, 0.29-0.78), respectively. For walking paces of less than 3.2 km/h (2.0 mph), 3.2 to 4.7 km/h (2.0-2.9 mph), and 4.8 km/h (3.0 mph) or more, compared with no regular walking, RRs were 0.56 (95% CI, 0.32-0.97), 0.71 (95% CI, 0.47-1.05), and 0.52 (95% CI, 0.30-0.90), respectively. When analyzed simultaneously, time spent walking (P for linear trend =.01) but not walking pace (P for linear trend =.55) predicted lower risk. The inverse association between physical activity and CHD risk did not differ by weight or cholesterol levels (P for interaction =.95 and.71, respectively), but there were significant interactions by smoking and hypertension status. Physical activity was inversely related to risk in current smokers but not hypertensive women (P for interaction =.01 and.001, respectively).Conclusions: These data indicate that even light-to-moderate activity is associated with lower CHD rates in women. At least 1 hour of walking per week predicted lower risk. The inverse association with physical activity was also present in women at high risk for CHD, including those who were overweight, had increased cholesterol levels, or were smokers. [ABSTRACT FROM AUTHOR]

Objective: It is biologically plausible for physical activity to decrease breast cancer risk; however, epidemiologic studies have yielded inconsistent findings. We therefore examined physical activity and breast cancer risk in the Women's Health Study.Methods: We assessed physical activity among 39,322 apparently healthy women, aged > or = 45 years, and prospectively followed them for an average of 48 months. Four hundred eleven women developed breast cancer, with 222 positive for both estrogen and progesterone receptors.Results: Among all women the multivariate relative risks of all breast cancer associated with < 840, 840-2519, 2520-6299, and > or = 6300 kJ/week expended on recreational activities and stair climbing were 1.00 (referent), 1.04 (95% confidence interval, 0.77-1.40), 0.86 (0.64-1.17), and 0.80 (0.58-1.12), respectively; p-trend = 0.11. However, among postmenopausal women there was a significant inverse trend for all breast cancer; the corresponding relative risks were 1.0 (referent), 0.97 (0.68-1.4), 0.78 (0.54-1.1), and 0.67 (0.44-1.0), respectively; p-trend = 0.03. Physical activity was unrelated to breast cancers positive for both estrogen and progesterone receptors either among all or postmenopausal women (p-trend = 0.50 and 0.26, respectively). When we assessed only vigorous recreational activity, requiring > or = 6 METs or multiples of resting metabolic rate, we observed no significant associations with all or steroid hormone receptor positive breast cancer, either among all or postmenospausal women.Conclusions: These data suggest that physical activity during middle age and older is not uniformly associated with decreased breast cancer risk. Among postmenopausal women only, higher levels of physical activity may decrease the risk of breast cancer. This study, however, had limited statistical power to detect small effects. [ABSTRACT FROM AUTHOR]

Context: Although increased intake of grain products has been recommended to prevent cardiovascular disease (CVD), prospective data examining the relation of whole grain intake to risk of ischemic stroke are sparse, especially among women.Objective: To examine the hypothesis that higher whole grain intake reduces the risk of ischemic stroke in women.Design, Setting, and Participants: A prospective cohort of 75,521 US women aged 38 to 63 years without previous diagnosis of diabetes mellitus, coronary heart disease, stroke, or other CVDs in 1984, who completed detailed food frequency questionnaires (FFQs) in 1984, 1986, 1990, and 1994, and were followed up for 12 years as part of the Nurses' Health Study.Main Outcome Measure: Incidence of ischemic stroke, confirmed by medical records, by quintile of whole grain intake according to FFQ responses.Results: During 861,900 person-years of follow-up, 352 confirmed incident cases of ischemic stroke occurred. We observed an inverse association between whole grain intake and ischemic stroke risk. The age-adjusted relative risks (RRs) from the lowest to highest quintiles of whole grain intake were 1.00 (referent), 0.68 (95% confidence interval [CI], 0.49-0.94), 0.69 (95% CI, 0.51-0.95), 0.49 (95% CI, 0.35-0.69), and 0.57 (95% CI, 0.42-0.78; P =.003 for trend). Adjustment for smoking modestly attenuated this association (RR comparing extreme quintiles, 0.64; 95% CI, 0.47-0.89). This inverse association remained essentially unchanged with further adjustment for known CVD risk factors, including saturated fat and transfatty acid intake (multivariate-adjusted RR comparing extreme quintiles, 0.69; 95% CI, 0.50-0.98). The inverse relation between whole grain intake and risk of ischemic stroke was also consistently observed among subgroups of women who never smoked, did not drink alcohol, did not exercise regularly, or who did not use postmenopausal hormones. No significant association was observed between total grain intake and risk of ischemic stroke.Conclusions: In this cohort, higher intake of whole grain foods was associated with a lower risk of ischemic stroke among women, independent of known CVD risk factors. These prospective data support the notion that higher intake of whole grains may reduce the risk of ischemic stroke. [ABSTRACT FROM AUTHOR]

Context: Persuasive evidence has demonstrated that increased physical activity is associated with substantial reduction in risk of coronary heart disease. However, the role of physical activity in the prevention of stroke is less well established.Objective: To examine the association between physical activity and risk of total stroke and stroke subtypes in women.Design and Setting: The Nurses' Health Study, a prospective cohort study of subjects residing in 11 US states.Subjects: A total of 72,488 female nurses aged 40 to 65 years who did not have diagnosed cardiovascular disease or cancer at baseline in 1986 and who completed detailed physical activity questionnaires in 1986, 1988, and 1992.Main Outcome Measure: Incident stroke occurring between baseline and June 1, 1994, compared among quintiles of physical activity level as measured by metabolic equivalent tasks (METs) in hours per week.Results: During 8 years (560,087 person-years) of follow-up, we documented 407 incident cases of stroke (258 ischemic strokes, 67 subarachnoid hemorrhages, 42 intracerebral hemorrhages, and 40 strokes of unknown type). In multivariate analyses controlling for age, body mass index, history of hypertension, and other covariates, increasing physical activity was strongly inversely associated with risk of total stroke. Relative risks (RRs) in the lowest to highest MET quintiles were 1. 00, 0.98, 0.82, 0.74, and 0.66 (P for trend=.005). The inverse gradient was seen primarily for ischemic stroke (RRs across increasing MET quintiles, 1.00, 0.87, 0.83, 0.76, and 0.52; P for trend=.003). Physical activity was not significantly associated with subarachnoid hemorrhage or intracerebral hemorrhage. After multivariate adjustment, walking was associated with reduced risk of total stroke (RRs across increasing walking MET quintiles, 1.00, 0. 76, 0.78, 0.70, and 0.66; P for trend=.01) and ischemic stroke (RRs across increasing walking MET quintiles, 1.00, 0.77, 0.75, 0.69, and 0.60; P for trend=.02). Brisk or striding walking pace was associated with lower risk of total and ischemic stroke compared with average or casual pace.Conclusion: These data indicate that physical activity, including moderate-intensity exercise such as walking, is associated with substantial reduction in risk of total and ischemic stroke in a dose-response manner. JAMA. 2000. [ABSTRACT FROM AUTHOR]

Background: Low-carbohydrate diets have been advocated for weight loss and to prevent obesity, but the long-term safety of these diets has not been determined.Methods: We evaluated data on 82,802 women in the Nurses' Health Study who had completed a validated food-frequency questionnaire. Data from the questionnaire were used to calculate a low-carbohydrate-diet score, which was based on the percentage of energy as carbohydrate, fat, and protein (a higher score reflects a higher intake of fat and protein and a lower intake of carbohydrate). The association between the low-carbohydrate-diet score and the risk of coronary heart disease was examined.Results: During 20 years of follow-up, we documented 1994 new cases of coronary heart disease. After multivariate adjustment, the relative risk of coronary heart disease comparing highest and lowest deciles of the low-carbohydrate-diet score was 0.94 (95% confidence interval [CI], 0.76 to 1.18; P for trend=0.19). The relative risk comparing highest and lowest deciles of a low-carbohydrate-diet score on the basis of the percentage of energy from carbohydrate, animal protein, and animal fat was 0.94 (95% CI, 0.74 to 1.19; P for trend=0.52), whereas the relative risk on the basis of the percentage of energy from intake of carbohydrates, vegetable protein, and vegetable fat was 0.70 (95% CI, 0.56 to 0.88; P for trend=0.002). A higher glycemic load was strongly associated with an increased risk of coronary heart disease (relative risk comparing highest and lowest deciles, 1.90; 95% CI, 1.15 to 3.15; P for trend=0.003).Conclusions: Our findings suggest that diets lower in carbohydrate and higher in protein and fat are not associated with increased risk of coronary heart disease in women. When vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of coronary heart disease. [ABSTRACT FROM AUTHOR]

Aims: Migraine and post-traumatic stress disorder (PTSD) are both twice as common in women as men. Cross-sectional studies have shown associations between migraine and several psychiatric conditions, including PTSD. PTSD is disproportionally common among patients in headache clinics, and individuals with migraine and PTSD report greater disability from migraines and more frequent medication use. To further clarify the nature of the relationship between PTSD and migraine, we conducted bidirectional analyses of the association between (1) migraine and incident PTSD and (2) PTSD and incident migraine., Methods: We used longitudinal data from 1989-2020 among the 33,327 Nurses' Health Study II respondents to the 2018 stress questionnaire. We used log-binomial models to estimate the relative risk of developing PTSD among women with migraine and the relative risk of developing migraine among individuals with PTSD, trauma-exposed individuals without PTSD, and individuals unexposed to trauma, adjusting for race, education, marital status, high blood pressure, high cholesterol, alcohol intake, smoking, and body mass index., Results: Overall, 48% of respondents reported ever experiencing migraine, 82% reported experiencing trauma and 9% met the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for PTSD. Of those reporting migraine and trauma, 67% reported trauma before migraine onset, 2% reported trauma and migraine onset in the same year and 31% reported trauma after migraine onset. We found that migraine was associated with incident PTSD (adjusted relative risk [RR]: 1.26, 95% confidence interval [CI]: 1.14-1.39). PTSD, but not trauma without PTSD, was associated with incident migraine (adjusted RR: 1.20, 95% CI: 1.14-1.27). Findings were consistently stronger in both directions among those experiencing migraine with aura., Conclusions: Our study provides further evidence that migraine and PTSD are strongly comorbid and found associations of similar magnitude between migraine and incident PTSD and PTSD and incident migraine.

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is more prevalent in postmenopausal women, and it has been postulated that this relationship is hormonally driven by lower circulating levels of estrogens. We examined the association between circulating plasma estrogen levels and subsequent development of aSAH in women., Methods: Women from the Nurses' Health Study with confirmed aSAH (n = 38) were matched with controls (n = 38) on age, smoking, menopausal status, and other reproductive factors. Plasma estriol, estradiol, and sex hormone-binding globulin were measured at baseline, prior to the development of aSAH. Conditional logistic regressions were performed to assess the association between hormone levels and incident aSAH., Results: Plasma estradiol, estriol, and sex hormone-binding globulin were not associated with the subsequent development of aSAH. Women with a history of current or former smoking were associated with lower levels of circulating estriol (β = -0.35 ± 0.12, P = 0.004) and estradiol (β = -0.63 ± 0.16, P = 0.0002)., Conclusions: In this study, we did not find an association between estrogen levels and the incidence of aSAH in women., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess the feasibility of integrating a pregnancy intention assessment screening algorithm into the electronic medical record (EMR) at a multispecialty clinic focused on the health of women and people assigned female at birth (AFAB)., Study Design: This pilot quality improvement project implemented a series of clinician reminders, new data fields in the patient record, and templated clinical notes to prompt care providers across specialties to ask AFAB reproductive age individuals about their desire for future pregnancies. Investigators created a novel screening question based on prior literature and expert input. Prospective observational study of one year of during-intervention EMR data on screening uptake and documentation, contraceptive use, and referrals to obstetrics and gynecology (OBGYN) for preconception care, contraceptive care, and related services., Results: SUPPORT launched in February 2020 and was paused for 6 months due to the COVID-19 pandemic. During the intervention period through July 2021, 18% of patients for whom the automated screening reminder was activated had a documented pregnancy intention. Patients were screened in OBGYN, internal medicine, and eight subspecialty medical clinics. Among those screened, individuals who reported they did not desire pregnancy in the next year were more likely to use contraception (aOR 1.8, 95% CI 1.1, 3.1). Individuals that did desire pregnancy in the next year were more likely to be subsequently referred to OBGYN (aOR 2.7, 95% CI 1.2, 6.0)., Conclusions: Despite the competing demands of the COVID-19 pandemic, the SUPPORT intervention was utilized at higher rates than prior similar interventions and across multiple disease specialties., Implications: Results from the SUPPORT pilot suggest that pregnancy intention screening of reproductive age AFAB individuals with an EMR-based screening prompt is feasible at scale., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Janiak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There is limited research examining aircraft noise and cardiovascular disease (CVD) risk. The objective of this study was to investigate associations of aircraft noise with CVD among two US cohorts, the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII)., Methods: Between 1994 and 2014, we followed 57,306 NHS and 60,058 NHSII participants surrounding 90 airports. Aircraft noise was modeled above 44 A-weighted decibels (dB(A)) and linked to geocoded addresses. Based on exposure distributions, we dichotomized exposures at 50 dB(A) and tested sensitivity of this cut-point by analyzing aircraft noise as categories ( < 45, 45-49, 50-54, ≥55) and continuously. We fit cohort-specific Cox proportional hazards models to estimate relationships between time-varying day-night average sound level (DNL) and CVD incidence and CVD and all-cause mortality, adjusting for fixed and time-varying individual- and area-level covariates. Results were pooled using random effects meta-analysis., Results: Over 20 years of follow-up, there were 4529 CVD cases and 14,930 deaths. Approximately 7% (n = 317) of CVD cases were exposed to DNL ≥50 dB(A). In pooled analyses comparing ≥50 with <50 dB(A), the adjusted hazard ratio for CVD incidence was 1.00 (95% confidence interval: 0.89, 1.12). The corresponding adjusted hazard ratio for all-cause mortality was 1.02 (95% confidence interval: 0.96, 1.09). Patterns were similar for CVD mortality in NHS yet underpowered., Conclusions: Among participants in the NHS and NHSII prospective cohorts who generally experience low exposure to aircraft noise, we did not find adverse associations of aircraft noise with CVD incidence, CVD mortality, or all-cause mortality., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background and Objective: Migraine is a highly prevalent neurovascular disorder among reproductive-aged women. Whether migraine history and migraine phenotype might serve as clinically useful markers of obstetric risk is not clear. The primary objective of this study was to examine associations of prepregnancy migraine and migraine phenotype with risks of adverse pregnancy outcomes., Methods: We estimated associations of self-reported physician-diagnosed migraine and migraine phenotype with adverse pregnancy outcomes in the prospective Nurses' Health Study II (1989-2009). Log-binomial and log-Poisson models with generalized estimating equations were used to estimate relative risks (RRs) and 95% CIs for gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension, preterm delivery, and low birthweight., Results: The analysis included 30,555 incident pregnancies after cohort enrollment among 19,694 participants without a history of cardiovascular disease, diabetes, or cancer. After adjusting for age, adiposity, and other health and behavioral factors, prepregnancy migraine (11%) was associated with higher risks of preterm delivery (RR = 1.17; 95% CI = 1.05-1.30), gestational hypertension (RR = 1.28; 95% CI = 1.11-1.48), and preeclampsia (RR = 1.40; 95% CI = 1.19-1.65) compared with no migraine. Migraine was not associated with low birthweight (RR = 0.99; 95% CI = 0.85-1.16) or GDM (RR = 1.05; 95% CI = 0.91-1.22). Risk of preeclampsia was somewhat higher among participants with migraine with aura (RR vs no migraine = 1.51; 95% CI = 1.22-1.88) than migraine without aura (RR vs no migraine = 1.30; 95% CI = 1.04-1.61; p- heterogeneity = 0.32), whereas other outcomes were similar by migraine phenotype. Participants with migraine who reported regular prepregnancy aspirin use had lower risks of preterm delivery (<2×/week RR = 1.24; 95% CI = 1.11-1.38; ≥2×/week RR = 0.55; 95% CI = 0.35-0.86; p -interaction < 0.01) and preeclampsia (<2×/week RR = 1.48; 95% CI = 1.25-1.75; ≥2×/week RR = 1.10; 95% CI = 0.62-1.96; p -interaction = 0.39); however, power for these stratified analyses was limited., Discussion: Migraine history, and to a lesser extent migraine phenotype, appear to be important considerations in obstetric risk assessment and management. Future research should determine whether aspirin prophylaxis may be beneficial for preventing adverse pregnancy outcomes among pregnant individuals with a history of migraine., (© 2023 American Academy of Neurology.)

Objective: The current study aims to prospectively examine the association between postdiagnosis low-carbohydrate diet (LCD) patterns and mortality among individuals with type 2 diabetes (T2D)., Research Design and Methods: Among participants with incident diabetes identified in the Nurses' Health Study and Health Professionals Follow-up Study, an overall total LCD score (TLCDS) was calculated based on the percentage of energy as total carbohydrates. In addition, vegetable (VLCDS), animal (ALCDS), healthy (HLCDS), and unhealthy (ULCDS) LCDS were further derived that emphasized different sources and quality of macronutrients. Multivariable-adjusted Cox models were used to assess the association between the LCDS and mortality., Results: Among 10,101 incident T2D cases contributing 139,407 person-years during follow-up, we documented 4,595 deaths of which 1,389 cases were attributed to cardiovascular disease (CVD) and 881 to cancer. The pooled multivariable-adjusted hazard ratios (HRs, 95% CIs) of total mortality per 10-point increment of postdiagnosis LCDS were 0.87 (0.82, 0.92) for TLCDS, 0.76 (0.71, 0.82) for VLCDS, and 0.78 (0.73, 0.84) for HLCDS. Both VLCDS and HLCDS were also associated with significantly lower CVD and cancer mortality. Each 10-point increase of TLCDS, VLCDS, and HLCDS from prediagnosis to postdiagnosis period was associated with 12% (7%, 17%), 25% (19%, 30%), and 25% (19%, 30%) lower total mortality, respectively. No significant associations were observed for ALCDS and ULCDS., Conclusions: Among people with T2D, greater adherence to LCD patterns that emphasize high-quality sources of macronutrients was significantly associated with lower total, cardiovascular, and cancer mortality., (© 2023 by the American Diabetes Association.)

Short and long sleep duration are associated with adverse metabolic outcomes, such as obesity and diabetes. We evaluated cross-sectional differences in metabolite levels between women with self-reported habitual short (<7 h), medium (7-8 h), and long (≥9 h) sleep duration to delineate potential underlying biological mechanisms. In total, 210 metabolites were measured via liquid chromatography-mass spectrometry in 9207 women from the Nurses' Health Study (NHS; N = 5027), the NHSII (N = 2368), and the Women's Health Initiative (WHI; N = 2287). Twenty metabolites were consistently (i.e. praw < .05 in ≥2 cohorts) and/or strongly (pFDR < .05 in at least one cohort) associated with short sleep duration after multi-variable adjustment. Specifically, levels of two lysophosphatidylethanolamines, four lysophosphatidylcholines, hydroxyproline and phenylacetylglutamine were higher compared to medium sleep duration, while levels of one diacylglycerol and eleven triacylglycerols (TAGs; all with ≥3 double bonds) were lower. Moreover, enrichment analysis assessing associations of metabolites with short sleep based on biological categories demonstrated significantly increased acylcarnitine levels for short sleep. A metabolite score for short sleep duration based on 12 LASSO-regression selected metabolites was not significantly associated with prevalent and incident obesity and diabetes. Associations of single metabolites with long sleep duration were less robust. However, enrichment analysis demonstrated significant enrichment scores for four lipid classes, all of which (most markedly TAGs) were of opposite sign than the scores for short sleep. Habitual short sleep exhibits a signature on the human plasma metabolome which is different from medium and long sleep. However, we could not detect a direct link of this signature with obesity and diabetes risk., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Systemic rheumatic conditions affect reproductive-aged patients and often require potentially teratogenic medications. We assessed the feasibility and impact of a standardized pregnancy intention screening question (One Key Question [OKQ]) in a large academic rheumatology practice., Methods: This 6-month pilot quality improvement initiative prompted rheumatologists to ask female patients aged 18 to 49 years about their pregnancy intentions using OKQ. We administered surveys to assess rheumatologists' barriers to and comfort with reproductive health issues. We performed chart reviews to assess uptake and impact on documentation, comparing charts with OKQ documented with 100 randomly selected charts eligible for pregnancy intention screening but without OKQ documented., Results: When we compared 32 of 43 preimplementation responses with 29 of 41 postimplementation responses, the proportion of rheumatologists who reported they were very comfortable with assessing their patients' reproductive goals increased (31%-38%) and the proportion reporting obstetrics and gynecology (OB/GYN) referral challenges as barriers to discussing reproductive goals decreased (41%-21%). During the implementation period, 83 of 957 (9%) eligible patients had OKQ documented in their chart. Female providers were more likely to screen than male providers (odds ratio 2.42, 95% confidence interval 1.21-4.85). Screened patients were more likely to have their contraceptive method documented (P < 0.001) and more likely to have been referred to OB/GYN for follow-up (P = 0.003) compared with patients who were not screened with OKQ., Conclusion: Although uptake was low, this tool improved provider comfort with assessing reproductive goals, the quality of documentation, and the likelihood of OB/GYN referral. Future studies should examine whether automated medical record alerts to prompt screening increase uptake., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background and Objectives: Subarachnoid hemorrhage from cerebral aneurysm remains a devastating disease with high mortality and morbidity. Cerebral aneurysm and its rupture are more prevalent in postmenopausal women and have been postulated to be hormonally influenced. The goal of this study was to investigate the associations of female-specific factors, including reproductive life span, age at menarche, and age at menopause, with the incidence of aneurysmal subarachnoid hemorrhage (aSAH) in women., Methods: Participants in the Nurses' Health Study were followed up from 1980 or the time of reaching menopause until 2018. Only women with natural menopause or surgical menopause due to bilateral oophorectomy were included. Reproductive life span was defined by subtracting the age at menarche from the age at menopause. Multivariable-stratified proportional hazards models were used to study reproductive life span, age at menarche, and age at menopause with the incidence of aSAH. Multivariable models were adjusted for age, race, smoking, hysterectomy, hypertension, hyperlipidemia, body mass index, hormone therapy use, oral contraceptive use, and parity., Results: A total of 97,398 postmenopausal women with reproductive life span data were included; 138 participants developed aSAH, which was confirmed on medical record review by a physician. A shorter reproductive life span (≤35 years) was associated with a 2-fold higher incidence of aSAH after multivariable adjustment (hazard ratio [HR] 2.0 [95% CI 1.4-2.8]). Early age at menopause (age <45 years) was similarly associated with a higher risk of aSAH (HR 2.1 [95% CI 1.4-3.1]), but age at menarche was not. Use of oral contraceptives and postmenopausal hormone therapy was not associated with the incidence of aSAH., Discussion: An earlier age at menopause and a shorter reproductive life span duration (≤35 years) were associated with a higher risk of incident aSAH in women. No associations were noted for age at menarche, parity, oral contraceptive use, or postmenopausal therapy use., (© 2022 American Academy of Neurology.)

Background Epidemiologic studies on the relationship between avocado intake and long-term cardiovascular disease (CVD) risk are lacking. Methods and Results This study included 68 786 women from the NHS (Nurses' Health Study) and 41 701 men from the HPFS (Health Professionals Follow-up Study; 1986-2016) who were free of cancer, coronary heart disease, and stroke at baseline. Diet was assessed using validated food frequency questionnaires at baseline and then every 4 years. Cox proportional hazards regressions were used to estimate hazard ratios and 95% CIs. A total of 14 274 incident cases of CVD (9185 coronary heart disease events and 5290 strokes) were documented over 30 years of follow-up. After adjusting for lifestyle and other dietary factors, compared with nonconsumers, those with analysis-specific higher avocado intake (≥2 servings/week) had a 16% lower risk of CVD (pooled hazard ratio, 0.84; 95% CI, 0.75-0.95) and a 21% lower risk of coronary heart disease (pooled hazard ratio, 0.79; 95% CI, 0.68-0.91). No significant associations were observed for stroke. Per each half serving/day increase in avocado intake, the pooled hazard ratio for CVD was 0.80 (95% CI, 0.71-0.91). Replacing half a serving/day of margarine, butter, egg, yogurt, cheese, or processed meats with the equivalent amount of avocado was associated with a 16% to 22% lower risk of CVD. Conclusions Higher avocado intake was associated with lower risk of CVD and coronary heart disease in 2 large prospective cohorts of US men and women. The replacement of certain fat-containing foods with avocado could lead to lower risk of CVD.

Objectives: To describe the imaging findings of intimate partner violence (IPV)-related injury and to evaluate the role of longitudinal imaging review in detecting IPV., Methods: Radiology studies were reviewed in chronological order and IPV-related injuries were recorded among 400 victims of any type of abuse (group 1) and 288 of physical abuse (group 2) from January 2013 to June 2018. The likelihood of IPV was assessed as low/moderate/high based on the review of (1) current and prior anatomically related studies only and (2) longitudinal imaging history consisting of all prior studies. The first radiological study date with moderate/high suspicion was compared to the self-reported date by the victim., Results: A total of 135 victims (33.8%) in group 1 and 144 victims (50%) in group 2 demonstrated IPV-related injuries. Musculoskeletal injury was most common (58.2% and 44.5% in groups 1 and 2, respectively; most commonly lower/upper extremity fractures), followed by neurologic injury (20.9% and 32.9% in groups 1 and 2, respectively; most commonly facial injury). With longitudinal imaging history, radiologists were able to identify IPV in 31% of group 1 and 46.5% of group 2 patients. Amongst these patients, earlier identification by radiologists was provided compared to the self-reported date in 62.3% of group 1 (median, 64 months) and in 52.6% of group 2 (median, 69.3 months)., Conclusions: Musculoskeletal and neurological injuries were the most common IPV-related injuries. Knowledge of common injuries and longitudinal imaging history may help IPV identification when victims are not forthcoming., Key Points: • Musculoskeletal injuries were the most common type of IPV-related injury, followed by neurological injuries. • With longitudinal imaging history, radiologists were able to better raise the suspicion of IPV compared to the selective review of anatomically related studies only. • With longitudinal imaging history, radiologists were able to identify IPV earlier than the self-reported date by a median of 64 months in any type of abuse, and a median of 69.3 months in physical abuse., (© 2021. The Author(s) under exclusive licence to European Society of Radiology.)

Purpose: Stroke is a leading cause of mortality worldwide, and air pollution is the third largest contributor to global stroke burden. Existing studies investigating the association between long-term exposure to particulate matter (PM) and stroke incidence have been mixed and very little is known about the associations with medium-term exposures. Therefore, we wanted to evaluate these associations in an cohort of male health professionals., Methods: We assessed the association of PM exposures in the previous 1 and 12 months with incident total, ischemic, and hemorrhagic stroke in 49,603 men in the prospective US-based Health Professionals' Follow-up Study 1988-2007. We used spatiotemporal prediction models to estimate monthly PM less than 10 (PM 10 ) and less than 2.5 (PM 2.5 ), and PM 2.5-10 at all mailing addresses. We used time-varying Cox proportional hazards models adjusted for potential confounders based on previous literature to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for each 10-μg/m 3 increase in exposure in the preceding 1 and 12 months. We explored possible effect modification by age, obesity, smoking, aspirin use, diet quality, physical activity, diabetes, and Census region., Results: We observed 1,467 cases of incident stroke. Average levels of 12-month PM 10 , PM 2.5-10 , and PM 2.5 were 20.7, 8.4, and 12.3 µg/m 3 , respectively. In multivariable adjusted models, we did not observe consistent associations between PM and overall or ischemic stroke. There was a suggestion of increased risk of hemorrhagic stroke (12-month PM 10 multivariable HR: 1.13 [0.86, 1.48]; PM 2.5-10 : 1.12 [0.78, 1.62]; PM 2.5 :1.17 [0.76, 1.81], all per 10 µg/m 3 ). There was little evidence of effect modification., Conclusions: We observed only weak evidence of an association between long-term exposure to PM and risks of overall incident stroke. There was a suggestion of increasing hemorrhagic stroke risk., Competing Interests: G.A.W. has received consulting fees from the Health Effects Institute (Boston, MA) and recently served as a paid visiting scientist at Google LLC (Mountain View, CA). The remaining authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background Intimate partner violence (IPV) is a global social and public health problem, but published literature regarding the exacerbation of physical IPV during the coronavirus disease 2019 (COVID-19) pandemic is lacking. Purpose To assess the incidence, patterns, and severity of injuries in IPV victims during the COVID-19 pandemic in 2020 compared with the prior 3 years. Materials and Methods The demographics, clinical presentation, injuries, and radiologic findings of patients reporting physical abuse arising from IPV during the statewide COVID-19 pandemic between March 11 and May 3, 2020, were compared with data from the same period for the past 3 years. Pearson χ 2 and Fisher exact tests were used for analysis. Results A total of 26 victims of physical IPV from 2020 (mean age, 37 years ± 13 [standard deviation]; 25 women) were evaluated and compared with 42 victims of physical IPV (mean age, 41 years ± 15; 40 women) from 2017 to 2019. Although the overall number of patients who reported IPV decreased during the pandemic, the incidence of physical IPV was 1.8 times greater (95% CI: 1.1, 3.0; P = .01). The total number of deep injuries was 28 during 2020 versus 16 from 2017 to 2019; the number of deep injuries per victim was 1.1 during 2020 compared with 0.4 from 2017 to 2019 ( P < .001). The incidence of high-risk abuse defined by mechanism was two times greater in 2020 (95% CI: 1.2, 4.7; P = .01). Patients who experienced IPV during the COVID-19 pandemic were more likely to be White; 17 (65%) victims in 2020 were White compared with 11 (26%) in the prior years ( P = .007). Conclusion There was a higher incidence and severity of physical intimate partner violence (IPV) during the coronavirus disease 2019 (COVID-19) pandemic compared with the prior 3 years. These results suggest that victims of IPV delayed reaching out to health care services until the late stages of the abuse cycle during the COVID-19 pandemic. © RSNA, 2020.

Background: Although vitamin D inhibits breast tumor growth in experimental settings, the findings from population-based studies remain inconclusive. Our goals were to investigate the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] concentration and breast cancer recurrence in prospective epidemiologic studies and to explore the molecular underpinnings linking 25(OH)D to slower progression of breast cancer in the Nurses' Health Studies (NHS, N = 659)., Methods: Plasma 25(OH)D was measured with a high-affinity protein-binding assay and a radioimmunoassay. We profiled transcriptome-wide gene expression in breast tumors using microarrays. Hazard ratios (HR) of breast cancer recurrence were estimated from covariate-adjusted Cox regressions. We examined differential gene expression in association with 25(OH)D and employed pathway analysis. We derived a gene expression score for 25(OH)D, and assessed associations between the score and cancer recurrence., Results: Although 25(OH)D was not associated with breast cancer recurrence overall [HR = 0.97; 95% confidence interval (CI), 0.88-1.08], the association varied by estrogen-receptor (ER) status ( P interaction = 0.005). Importantly, among ER-positive stage I to III cancers, every 5 ng/mL increase in 25(OH)D was associated with a 13% lower risk of recurrence (HR = 0.87; 95% CI, 0.76-0.99). A null association was observed for ER-negative cancers (HR = 1.07; 95% CI, 0.91-1.27). Pathway analysis identified multiple gene sets that were significantly (FDR < 5%) downregulated in ER-positive tumors of women with high 25(OH)D (≥30 ng/mL), compared with those with low levels (<30 ng/mL). These gene sets are primarily involved in tumor proliferation, migration, and inflammation. 25(OH)D score derived from these gene sets was marginally associated with reduced risk of recurrence in ER-positive diseases (HR = 0.77; 95% CI, 0.59-1.01) in the NHS studies; however no association was noted in METABRIC, suggesting that further refinement is need to improve the generalizability of the score., Conclusions: Our findings support an intriguing line of research for studies to better understand the mechanisms underlying the role of vitamin D in breast tumor progression, particularly for the ER-positive subtype., Impact: Vitamin D may present a personal-level secondary-prevention strategy for ER-positive breast cancer., (©2020 American Association for Cancer Research.)

Background and Purpose- Long-term effect of lifestyle changes on stroke incidence has not been estimated in randomized trials. We used observational data to estimate the incidence of stroke under hypothetical lifestyle strategies in the NHS (Nurses' Health Study). Methods- We considered 3 nondietary strategies (smoking cessation, exercising ≥30 min/d, gradual body mass index reduction if overweight/obese) and several dietary strategies (eating ≥3 servings/wk of fish, ≤3 servings/wk of unprocessed red meat, no processed red meat, ≥1 servings/d of nuts, etc). We used the parametric g-formula to estimate the 26-year risk of stroke under these strategies. Results- In 59 727 women, mean age 52 years at baseline in 1986, the estimated 26-year risks under no lifestyle interventions were 4.7% for total stroke, 2.4% for ischemic stroke, and 0.7% for hemorrhagic stroke. Under the combined nondietary interventions, the estimated 26-year risk of total stroke was 3.5% (95% CI, 2.6%-4.3%) and ischemic stroke was 1.6% (95% CI, 1.1%-2.1%). Smaller reductions in total stroke risk were estimated under isolated dietary strategies of increased intake of fish and nuts and reduced intake of unprocessed red meat. Ischemic stroke risk was lower under reduced intake of unprocessed and processed red meat, and hemorrhagic stroke risk was lower under a strategy of increased fish consumption. Conclusions- In this population of middle-aged women, sustained, lifestyle modifications were estimated to reduce the 26-year risk of total stroke by 25% and ischemic stroke by 36%. Sustained dietary modifications were estimated to reduce the 26-year risk of total stroke by 23%.

Background: Genome-wide association studies have identified multiple loci associated with stroke. However, the specific stroke subtypes affected, and whether loci influence both ischemic and hemorrhagic stroke, remains unknown. For loci associated with stroke, we aimed to infer the combination of stroke subtypes likely to be affected, and in doing so assess the extent to which such loci have homogeneous effects across stroke subtypes., Methods: We performed Bayesian multinomial regression in 16 664 stroke cases and 32 792 controls of European ancestry to determine the most likely combination of stroke subtypes affected for loci with published genome-wide stroke associations, using model selection. Cases were subtyped under 2 commonly used stroke classification systems, TOAST (Trial of Org 10172 Acute Stroke Treatment) and causative classification of stroke. All individuals had genotypes imputed to the Haplotype Reference Consortium 1.1 Panel., Results: Sixteen loci were considered for analysis. Seven loci influenced both hemorrhagic and ischemic stroke, 3 of which influenced ischemic and hemorrhagic subtypes under both TOAST and causative classification of stroke. Under causative classification of stroke, 4 loci influenced both small vessel stroke and intracerebral hemorrhage. An EDNRA locus demonstrated opposing effects on ischemic and hemorrhagic stroke. No loci were predicted to influence all stroke subtypes in the same direction, and only one locus (12q24) was predicted to influence all ischemic stroke subtypes., Conclusions: Heterogeneity in the influence of stroke-associated loci on stroke subtypes is pervasive, reflecting differing causal pathways. However, overlap exists between hemorrhagic and ischemic stroke, which may reflect shared pathobiology predisposing to small vessel arteriopathy. Stroke is a complex, heterogeneous disorder requiring tailored analytic strategies to decipher genetic mechanisms.

The Consortium of Metabolomics Studies (COMETS) was established in 2014 to facilitate large-scale collaborative research on the human metabolome and its relationship with disease etiology, diagnosis, and prognosis. COMETS comprises 47 cohorts from Asia, Europe, North America, and South America that together include more than 136,000 participants with blood metabolomics data on samples collected from 1985 to 2017. Metabolomics data were provided by 17 different platforms, with the most frequently used labs being Metabolon, Inc. (14 cohorts), the Broad Institute (15 cohorts), and Nightingale Health (11 cohorts). Participants have been followed for a median of 23 years for health outcomes including death, cancer, cardiovascular disease, diabetes, and others; many of the studies are ongoing. Available exposure-related data include common clinical measurements and behavioral factors, as well as genome-wide genotype data. Two feasibility studies were conducted to evaluate the comparability of metabolomics platforms used by COMETS cohorts. The first study showed that the overlap between any 2 different laboratories ranged from 6 to 121 metabolites at 5 leading laboratories. The second study showed that the median Spearman correlation comparing 111 overlapping metabolites captured by Metabolon and the Broad Institute was 0.79 (interquartile range, 0.56-0.89)., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019.)

Objective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts., Methods: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI., Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10 -8 ; and LINC00539/ZDHHC20, p = 5.82 × 10 -9 . Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits ( p value for BI, p [BI] = 9.38 × 10 -25 ; p [SSBI] = 5.23 × 10 -14 for hypertension), smoking ( p [BI] = 4.4 × 10 -10 ; p [SSBI] = 1.2 × 10 -4 ), diabetes ( p [BI] = 1.7 × 10 -8 ; p [SSBI] = 2.8 × 10 -3 ), previous cardiovascular disease ( p [BI] = 1.0 × 10 -18 ; p [SSBI] = 2.3 × 10 -7 ), stroke ( p [BI] = 3.9 × 10 -69 ; p [SSBI] = 3.2 × 10 -24 ), and MRI-defined white matter hyperintensity burden ( p [BI] = 1.43 × 10 -157 ; p [SSBI] = 3.16 × 10 -106 ), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI ( p ≤ 0.0022), without indication of directional pleiotropy., Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The association between long-term blood pressure (BP) patterns in community-dwelling adults and risk of intracerebral hemorrhage and cerebral infarction is not well characterized. This prospective study included 79 385 participants, free of stroke, myocardial infarction, and cancer in or before 2010 (baseline). Systolic BP trajectories were identified using latent mixture modeling with data from 2006, 2008, and 2010. Incident cases of intracerebral hemorrhage and cerebral infarction occurred during 2010 to 2014, confirmed by review of medical records, by 3 physicians. We identified 5 distinct systolic BP trajectories during 2006 to 2010. Each of the trajectories was labeled according to their BP range and pattern over time: normotensive-stable (n=26 740), prehypertension-stable (n=35 674), stage 1 hypertension-increasing (n=8215), stage 1 hypertension-decreasing (n=6422), and stage 2 hypertension-stable (n=2334). We documented 1034 incident cases of cerebral infarction and 187 cases of intracerebral hemorrhage. Although the prehypertension-stable trajectory exhibited systolic BP range within the normal range (120-140 mm Hg) during 2006 to 2010, this group had higher stroke risk relative to the normotensive-stable group (<120 mm Hg) (adjusted hazard ratio was 3.11 for intracerebral hemorrhage and 1.99 for cerebral infarction; P <0.001 for both), after adjusting for possible confounders. Individuals in the stage 2 hypertension-stable systolic BP trajectory (175-179 mm Hg) had the highest risk of intracerebral hemorrhage (adjusted hazard ratio was 12.4) and cerebral infarction (adjusted hazard ratio was 5.07), relative to the normotensive-stable group ( P <0.001 for both). BP trajectories were associated with the risk of stroke and increasing BP trajectories within the currently designated normal range may still increase the risk for stroke., (© 2017 American Heart Association, Inc.)