Prospective US Cohort Research Articles

Bleeding disorders in adolescents with heavy menstrual bleeding in a multicenter prospective US cohort.

Heavy menstrual bleeding is common in adolescents. The frequency and predictors of bleeding disorders in adolescents, especially with anovulatory bleeding, are unknown. Adolescents referred for heavy menstrual bleeding underwent an evaluation of menstrual bleeding patterns, and bleeding disorders determined a priori. The primary outcome was the diagnosis of a bleeding disorder. Two groups were compared: anovulatory and ovulatory bleeding. Multivariable logistic regression analysis of baseline characteristics and predictors was performed. Kaplan Meier curves were constructed for the time from the first bleed to bleeding disorder diagnosis. In 200 adolescents, a bleeding disorder was diagnosed in 33% (n=67): low von Willebrand factor levels in 16%, von Willebrand disease in 11%, and qualitative platelet dysfunction in 4.5%. The prevalence of bleeding disorder was similar between ovulatory and anovulatory groups (31% vs. 36%; P=0.45). Predictors of bleeding disorder included: younger age at first bleed (OR: 0.83; 95%CI: 0.73, 0.96), Hispanic ethnicity (OR: 2.48; 95%CI: 1.13, 5.05), non-presentation to emergency department for heavy bleeding (OR: 0.14; 95%CI: 0.05, 0.38), and International Society on Thrombosis and Haemostasis (ISTH) Bleeding Assessment Tool score ≥4 (OR: 8.27; 95%CI: 2.60, 26.44). Time from onset of the first bleed to diagnosis was two years in the anovulatory, and six years in the ovulatory cohort (log-rank test, P<0.001). There is a high prevalence of bleeding disorders in adolescents with heavy periods, irrespective of the bleeding pattern. Among bleeding disorders, the prevalence of qualitative platelet dysfunction is lower than previously reported.

Mushroom consumption, biomarkers, and risk of cardiovascular disease and type 2 diabetes: a prospective cohort study of US women and men

Mushrooms are good dietary sources of important vitamins, minerals, and bioactive compounds which may be important in the prevention of chronic diseases. However, studies have not prospectively evaluated the potential health effects of mushrooms with respect to major cardiometabolic diseases. The aim of this study was to examine the association of mushroom consumption with major cardiometabolic diseases and mediating biomarkers in 2 large prospective US cohorts. We followed 67,139 women from the Nurses' Health Study (1986-2012) and 43,541 men from the Health Professionals Follow-up Study (1986-2012) who were free of chronic diseases. Mushroom consumption was assessed at baseline through the use of a food-frequency questionnaire. Cardiometabolic biomarkers were collected in subpopulations of the 2 cohorts. Cox proportional hazards models were used to estimate HRs and 95% CIs of cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, and type 2 diabetes (T2D), associated with mushroom consumption. We identified total 11,894 CVD (7,616 CHD; 4,278 stroke), and 10,206 T2D cases in >2 million person-years of follow-up. In the pooled multivariable-adjusted analysis, participants who consumed ≥5 servings of mushrooms per week had no significantly different risk of total CVD (HR: 1.02; 95% CI: 0.91, 1.14), CHD (HR: 1.00; 95% CI: 0.87, 1.16), stroke (HR: 1.05; 95% CI: 0.87, 1.25), or T2D (HR: 1.04; 95% CI: 0.93, 1.16) than participants who consumed mushrooms <1 time/mo. We consistently found no association between mushroom consumption and the aforementioned cardiometabolic diseases, in subgroups of sex, lifestyle factors, and medical conditions. Moreover, mushroom consumption was not associated with plasma biomarkers of lipids, insulin, and inflammation. We found no association of mushroom consumption with biomarkers and risks of CVD and T2D in US adults. More large prospective cohort studies are warranted to investigate this association in other racial/ethnic groups.

Association of Filaggrin Loss-of-Function Variants With Race in Children With Atopic Dermatitis

Atopic dermatitis (AD) is a common chronic illness that has been associated with variation in the filaggrin gene (FLG). Four variants are most often evaluated. To comprehensively describe and compare results from targeted sequencing of FLG loss-of-function (LoF) variants in children of African and European ancestry and the association of these variants with onset and persistence of AD. This prospective US cohort study assessed the genetic subcohort of the Pediatric Eczema Elective Registry (PEER). Children with mild to moderate AD were included in the analysis. Massively parallel sequencing (MPS) was used to focus on FLG LoF variation in white and African American children. Patients were enrolled from June 2005 through July 2017. Data were analyzed from January 25 through May 10, 2019. Associations of FLG LoF variation with white and African American ancestry and with the risk and persistence of AD. A total of 741 children were included in the analysis (394 [53.2%] female and 347 [46.8%] male; mean [SD] age at onset, 1.97 [2.72] years); of these, 394 (53.2%) were white, 326 (44.0%) were African American, and 21 (2.8%) were of other ancestries. Using MPS technology, 23 FLG LoF variants were found in children with AD. The prevalence of FLG LoF variants was 177 participants (23.9%) in the full cohort, 124 white participants (31.5%), and 50 African American participants (15.3%). The odds ratio for carrying any FLG LoF variant in a white child compared with an African American child with AD was 2.44 (95% CI, 1.76-3.39). Some FLG LoF variants are only found in children of a specific ancestry (eg, p.S3316* and p.R826* were not seen in white patients). Children with an FLG LoF were more likely to have persistent AD (odds ratio, 0.67; 95% CI, 0.56-0.80). The FLG LoF variants in a US cohort of children with mild to moderate AD differ significantly by race and their association with the persistence of AD. Conventional testing of the 4 frequently evaluated variants is inadequate. Any planned genetic diagnostic test for AD based on FLG LoF variants must be inclusive and not rely on the most frequently studied variants.

Meat intake and risk of hepatocellular carcinoma in two large US prospective cohorts of women and men.

Epidemiological evidence on the associations between meat intake and risk of hepatocellular carcinoma (HCC) was limited and inconsistent. We prospectively examined the association between consumption of meats and meat mutagens with HCC risk using data from the Nurses' Health Study and the Health Professionals Follow-up Study. Cox proportional-hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for known liver-cancer risk factors. During up to 32 years of follow-up, we documented 163 incident HCC cases. The HRs of HCC for the highest vs the lowest tertile intake levels were 1.84 (95% CI: 1.16-2.92, Ptrend = 0.04) for processed red meats and 0.61 (95% CI: 0.40-0.91, Ptrend = 0.02) for total white meats. There was a null association between unprocessed red meats and HCC risk (HR = 1.06, 95% CI: 0.68-1.63, Ptrend = 0.85). We found both poultry (HR = 0.60, 95% CI: 0.40-0.90, Ptrend = 0.01) and fish (HR = 0.70, 95% CI: 0.47-1.05, Ptrend = 0.10) were inversely associated with HCC risk. The HR for HCC risk was 0.79 (95% CI: 0.61-1.02) when 1standard deviation of processed red meats was substituted with an equivalent amount of poultry or fish intake. We also found a suggestive positive association of intake of meat-derived mutagenicity or heterocyclic amines with risk of HCC. Processed red meat intake might be associated with higher, whereas poultry or possibly fish intake might be associated with lower, risk of HCC. Replacing processed red meat with poultry or fish might be associated with reduced HCC risk.

Dietary Pattern and Risk of Multiple Myeloma in Two Large Prospective US Cohort Studies.

BackgroundThe limited data on specific dietary components and risk of multiple myeloma (MM) show no consistent association. Studies have not examined the association of dietary pattern with MM risk.MethodsIn prospective cohorts of 69 751 women (Nurses’ Health Study, 1984–2014) and 47 232 men (Health Professionals Follow-up Study, 1986–2014), we examined the association between dietary pattern and risk of MM using Cox proportional hazard models. Diet was assessed repeatedly every 4 years with food frequency questionnaires and was used to calculate dietary patterns including the Alternate Healthy Eating Index-2010, Alternate Mediterranean Diet, Dietary Approaches to Stop Hypertension, Prudent and Western patterns, the empirical dietary inflammatory pattern (EDIP), and empirical dietary indices for insulin resistance (EDIR) and hyperinsulinemia (EDIH).ResultsDuring 2 792 257 person-years of follow-up, we identified 478 incident MM cases (215 women, 263 men). In men, high EDIP was statistically significantly associated with a 16% increase in MM risk (hazard ratio [HR] = 1.16, 95% confidence interval [CI] = 1.02 to 1.32 per 1-SD increase). Moreover, EDIR and EDIH had a suggestive positive association (EDIR: HR = 1.09, 95% CI = 0.96 to 1.24; and EDIH: HR = 1.11, 95% CI = 0.97 to 1.28 per 1-SD increase). We observed no other associations with MM risk in men and no associations for any dietary pattern with MM risk in women.ConclusionsWe present the first evidence for a role of diets with higher inflammatory or insulinemic potential in MM development. Further studies are warranted to explore these associations in other populations, including the apparent restriction to men.

Associations of Monounsaturated Fatty Acids From Plant and Animal Sources With Total and Cause-Specific Mortality in Two US Prospective Cohort Studies.

Dietary monounsaturated fatty acids (MUFAs) can come from both plant and animal sources with divergent nutrient profiles that may potentially obscure the associations of total MUFAs with chronic diseases. To investigate the associations of cis-MUFA intake from plant (MUFA-P) and animal (MUFA-A) sources with total and cause-specific mortality. We followed 63 412 women from the NHS (Nurses' Health Study; 1990-2012) and 29 966 men from the HPFS (Health Professionals Follow-Up Study; 1990-2012). MUFA-Ps and MUFA-As were calculated based on data collected through validated food frequency questionnaires administered every 4 years and updated food composition databases. During 1 896 864 person-years of follow-up, 20 672 deaths occurred. Total MUFAs and MUFA-Ps were inversely associated with total mortality after adjusting for potential confounders, whereas MUFA-As were associated with higher mortality. When MUFA-Ps were modeled to isocalorically replace other macronutrients, hazard ratios (HRs, 95% CIs) of total mortality were 0.84 (0.77-0.92; P<0.001) for replacing saturated fatty acids, 5% of energy); 0.86 (0.82-0.91; P<0.001) for replacing refined carbohydrates (5% energy); 0.91 (0.85-0.97; P<0.001) for replacing trans fats (2% energy), and 0.77 (0.71-0.82; P<0.001) for replacing MUFA-As (5% energy). For isocalorically replacing MUFA-As with MUFA-Ps, HRs (95% CIs) were 0.74 (0.64-0.86; P<0.001) for cardiovascular mortality; 0.73 (0.65-0.82; P<0.001) for cancer mortality, and 0.82 (0.73-0.91; P<0.001) for mortality because of other causes. Higher intake of MUFA-Ps was associated with lower total mortality, and MUFA-As intake was associated with higher mortality. Significantly lower mortality risk was observed when saturated fatty acids, refined carbohydrates, or trans fats were replaced by MUFA-Ps, but not MUFA-As. These data suggest that other constituents in animal foods, such as saturated fatty acids, may confound the associations for MUFAs when they are primarily derived from animal products. More evidence is needed to elucidate the differential associations of MUFA-Ps and MUFA-As with mortality.

Mediterranean Diet and the Association Between Air Pollution and Cardiovascular Disease Mortality Risk.

Recent experimental evidence suggests that nutritional supplementation can blunt adverse cardiopulmonary effects induced by acute air pollution exposure. However, whether usual individual dietary patterns can modify the association between long-term air pollution exposure and health outcomes has not been previously investigated. We assessed, in a large cohort with detailed diet information at the individual level, whether a Mediterranean diet modifies the association between long-term exposure to ambient air pollution and cardiovascular disease mortality risk. The National Institutes of Health-American Association for Retired Persons Diet and Health Study, a prospective cohort (N=548 845) across 6 states and 2 cities in the United States and with a follow-up period of 17 years (1995-2011), was linked to estimates of annual average exposures to fine particulate matter and nitrogen dioxide at the residential census-tract level. The alternative Mediterranean Diet Index, which uses a 9-point scale to assess conformity with a Mediterranean-style diet, was constructed for each participant from information in cohort baseline dietary questionnaires. We evaluated mortality risks for cardiovascular disease, ischemic heart disease, cerebrovascular disease, or cardiac arrest associated with long-term air pollution exposure. Effect modification of the associations between exposure and the mortality outcomes by alternative Mediterranean Diet Index was examined via interaction terms. For fine particulate matter, we observed elevated and significant associations with cardiovascular disease (hazard ratio [HR] per 10 μg/m3, 1.13; 95% CI, 1.08-1.18), ischemic heart disease (HR, 1.16; 95% CI, 1.10-1.23), and cerebrovascular disease (HR, 1.15; 95% CI, 1.03-1.28). For nitrogen dioxide, we found significant associations with cardiovascular disease (HR per 10 ppb, 1.06; 95% CI, 1.04-1.08) and ischemic heart disease (HR, 1.08; 95% CI, 1.05-1.11). Analyses indicated that Mediterranean diet modified these relationships, as those with a higher alternative Mediterranean Diet Index score had significantly lower rates of cardiovascular disease mortality associated with long-term air pollution exposure ( P-interaction<0.05). A Mediterranean diet reduced cardiovascular disease mortality risk related to long-term exposure to air pollutants in a large prospective US cohort. Increased consumption of foods rich in antioxidant compounds may aid in reducing the considerable disease burden associated with ambient air pollution.

Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality

Cholesterol is a common nutrient in the human diet and eggs are a major source of dietary cholesterol. Whether dietary cholesterol or egg consumption is associated with cardiovascular disease (CVD) and mortality remains controversial. To determine the associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality. Individual participant data were pooled from 6 prospective US cohorts using data collected between March 25, 1985, and August 31, 2016. Self-reported diet data were harmonized using a standardized protocol. Dietary cholesterol (mg/day) or egg consumption (number/day). Hazard ratio (HR) and absolute risk difference (ARD) over the entire follow-up for incident CVD (composite of fatal and nonfatal coronary heart disease, stroke, heart failure, and other CVD deaths) and all-cause mortality, adjusting for demographic, socioeconomic, and behavioral factors. This analysis included 29 615 participants (mean [SD] age, 51.6 [13.5] years at baseline) of whom 13 299 (44.9%) were men and 9204 (31.1%) were black. During a median follow-up of 17.5 years (interquartile range, 13.0-21.7; maximum, 31.3), there were 5400 incident CVD events and 6132 all-cause deaths. The associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality were monotonic (all P values for nonlinear terms, .19-.83). Each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.17 [95% CI, 1.09-1.26]; adjusted ARD, 3.24% [95% CI, 1.39%-5.08%]) and all-cause mortality (adjusted HR, 1.18 [95% CI, 1.10-1.26]; adjusted ARD, 4.43% [95% CI, 2.51%-6.36%]). Each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06 [95% CI, 1.03-1.10]; adjusted ARD, 1.11% [95% CI, 0.32%-1.89%]) and all-cause mortality (adjusted HR, 1.08 [95% CI, 1.04-1.11]; adjusted ARD, 1.93% [95% CI, 1.10%-2.76%]). The associations between egg consumption and incident CVD (adjusted HR, 0.99 [95% CI, 0.93-1.05]; adjusted ARD, -0.47% [95% CI, -1.83% to 0.88%]) and all-cause mortality (adjusted HR, 1.03 [95% CI, 0.97-1.09]; adjusted ARD, 0.71% [95% CI, -0.85% to 2.28%]) were no longer significant after adjusting for dietary cholesterol consumption. Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner. These results should be considered in the development of dietary guidelines and updates.

Abstract 030: Dietary Inflammatory Potential is Associated with Cardiovascular Disease Risk in Two Large Prospective Cohort Studies of US Men and Women

Introduction: Chronic inflammation plays a pathogenic role in cardiovascular disease (CVD) development. Dietary factors have been implicated in CVD etiology and may have an impact on chronic inflammation. Hypothesis: Proinflammatory diets are associated with higher CVD risk. Methods: We include74,544 women in the Nurses’ Health Study (from 1984 through 2012) and 43,904 men in the Health Professionals Follow-up Study (from 1986 through 2012), who were free of heart disease, stroke, and cancer at baseline. Dietary inflammatory potentials were assessed using an empirical dietary inflammatory pattern (EDIP) score that has been pre-defined by 18 food components based on their associations with circulating levels of systemic inflammation markers C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2. Adjusted hazard ratios (HRs) and 95% confidence internals (CIs) for CVD were calculated using Cox regressions. Results: During 2,831,128 person-years of follow-up, we documented 13,249 incident CVD cases, including 8,178 coronary heart disease cases and 5,182 stroke cases. After adjusting for established risk factors and potential confounders including body-mass index and aspirin or other nonsteroidal anti-inflammatory medication use, a higher EDIP score was associated with an increased risk of CVD (in pooled analyses, HR [95% CI] comparing the highest to the lowest quintiles were 1.29 [1.22 to 1.37]; P trend &lt;0.001), CHD (HR = 1.32[1.23 to 1.42]; P trend &lt;0.001), and stroke (HR = 1.25 [1.14 to 1.37]; P trend &lt;0.001). Associations were similar among subgroups of participants, including by age, sex, family history, BMI, physical activity, and alcohol intake; but were stronger among non/past-smoking than current smoking women ( P interaction &lt;0.002). Conclusions: Findings from two large US prospective cohort studies suggest that inflammation may be a potential mechanism linking dietary patterns to CVD progression. Reducing the proinflammatory potentials of the diet may assist CVD prevention.

Vasectomy and the risk of prostate cancer in a prospective US Cohort: Data from the NIH-AARP Diet and Health Study.

Several studies have linked vasectomy with the risk of prostate cancer; however, this association has been attributed to selection bias. Since vasectomy is a common and effective form of contraception, these implications are significant. Therefore, we sought to test this association in a large observational cohort. To evaluate the potential association between prior vasectomy and the risk of developing prostate cancer. We evaluated the relationship between vasectomy and prostate cancer in the NIH-AARP Diet and Health Study. Of the 111,914 men, prostate cancer was identified in 13,885 men and vasectomies were performed in 48,657. We used multivariate analysis to examine the relationship between prostate cancer and vasectomy. We also performed propensity score-adjusted and propensity score-matched analysis. Men utilizing vasectomy were more likely to be ever married, fathers, educated, white, and screened for prostate cancer. During 4,251,863 person-years of follow-up, there was a small association between vasectomy and incident prostate cancer with a hazard ratio of 1.05 (95% CI, 1.01-1.11). However, no significant association was found when looking separately at prostate cancer by grade or stage. Conclusions were similar when using propensity adjustment and matching. Importantly, a significant interaction between vasectomy and PSA screening was identified. Estimates of the association between vasectomy and prostate cancer are sensitive to analytic method underscoring the tenuous nature of the connection. Given the differences between men who do and do not utilize vasectomy, selection bias appears likely to explain any identified association between vasectomy and prostate cancer. With over 20years of follow-up, no convincing relationship between vasectomy and prostate cancer of any grade was identified.

Changes in Types of Dietary Fats Influence Long-term Weight Change in US Women and Men

BackgroundThe relation between dietary fat intake and body weight remains controversial. Few studies have examined long-term changes in types of dietary fat and weight change in longitudinal studies. ObjectiveThe objective of this study was to examine associations between intake of different types of fat and long-term weight change in US women and men. MethodsThe association between changes in consumption of varying types of fat and weight change was examined every 4 y through the use of multivariate models adjusted for age, baseline body mass index, and change in percentage energy from protein, intake of cereal fiber, fruits, and vegetables, alcohol use, and other lifestyle covariates in 3 prospective US cohorts, including 121,335 men and women free of diabetes, cardiovascular disease, cancer, or obesity over a 20- to 24-y follow-up. Dietary intakes and body weight were assessed via validated questionnaires. Cohort-specific results were pooled with the use of a random-effect meta-analysis. ResultsCompared with equivalent changes in carbohydrate intake, a 5% increase in energy from saturated fatty acid (SFA) and a 1% increase in energy from trans-fat were associated with 0.61 kg (95% CI: 0.54, 0.68 kg) and 0.69 kg (95% CI: 0.56, 0.84 kg) greater weight gain per 4-y period, respectively. A 5% increase in energy from polyunsaturated fatty acid (PUFA) was associated with less weight gain (−0.55 kg; 95% CI: −0.81, −0.29 kg). Increased intake of monounsaturated fatty acid (MUFA) from animal sources by 1% was associated with weight gain of 0.29 kg (95% CI: 0.25, 0.33 kg), whereas MUFA from plant sources was not associated with weight gain. ConclusionsDifferent dietary fats have divergent associations with long-term weight change in US men and women. Replacing saturated and trans-fats with unsaturated fats, especially PUFAs, contributes to the prevention of age-related weight gain. These trials were registered at clinicaltrials.gov as NCT00005152 and NCT00005182.

Association Between Aspirin Use and Risk of Hepatocellular Carcinoma

Prospective data on the risk of hepatocellular carcinoma (HCC) according to dose and duration of aspirin therapy are limited. To examine the potential benefits of aspirin use for primary HCC prevention at a range of doses and durations of use within 2 prospective, nationwide populations. Pooled analysis of 2 prospective US cohort studies: the Nurses' Health Study and the Health Professionals Follow-up Study. Data were accessed from November 1, 2017, through March 7, 2018. A total of 133 371 health care professionals who reported data on aspirin use, frequency, dosage, and duration of use biennially since 1980 in women and 1986 in men were included. Individuals with a cancer diagnosis at baseline (except nonmelanoma skin cancer) were excluded. Cox proportional hazards regression models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% CIs for HCC. Of the 133 371 participants, 87 507 were women and 45 864 were men; in 1996, the median time of follow-up, the mean (SD) age was 62 (8) years for women and 64 (8) years for men. Over more than 26 years of follow-up encompassing 4 232 188 person-years, 108 incident HCC cases (65 women, 43 men) were documented. Compared with nonregular use, regular aspirin use (≥2 standard-dose [325-mg] tablets per week) was associated with reduced HCC risk (adjusted HR, 0.51; 95% CI, 0.34-0.77). This benefit appeared to be dose related: compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 standard-dose tablets per week, 0.51 (95% CI, 0.30-0.86) for more than 1.5 to 5 tablets per week, and 0.49 (95% CI, 0.28-0.96) for more than 5 tablets per week (P for trend = .006). Significantly lower HCC risk was observed with increasing duration (P for trend = .03); this decrease was apparent with use of 1.5 or more standard-dose aspirin tablets per week for 5 or more years (adjusted HR, 0.41; 95% CI, 0.21-0.77). In contrast, use of nonaspirin nonsteroidal anti-inflammatory drugs was not significantly associated with HCC risk (adjusted HR, 1.09; 95% CI, 0.78-1.51). This study suggests that regular, long-term aspirin use is associated with a dose-dependent reduction in HCC risk, which is apparent after 5 or more years of use. Similar associations were not found with nonaspirin NSAIDs. Further research appears to be needed to clarify whether aspirin use represents a feasible strategy for primary prevention against HCC.

Comparison of the association of predicted fat mass, body mass index, and other obesity indicators with type 2 diabetes risk: two large prospective studies in US men and women

Obesity, defined by body mass index (BMI), is a well-established risk factor of type 2 diabetes, but BMI has been criticized for its inability to discriminate fat mass and lean body mass. We examined the association between predicted fat mass and type 2 diabetes risk in two large US prospective cohorts, and compared the magnitude of the association with BMI and other obesity indicators. Validated anthropometric prediction equations previously developed from the National Health and Nutrition Examination Survey were used to estimate predicted fat mass and percent fat for 97,111 participants from the Health Professionals Follow-up Study (1987-2012) and the Nurses' Health Study (1986-2012) who were followedup for type 2 diabetes. Multivariable-adjusted hazard ratios for type 2 diabetes across quintiles of predicted fat mass were 1.00, 1.96, 2.96, 3.90, and 8.38 for men and 1.00, 2.20, 3.50, 5.73, and 12.1 for women; of BMI were 1.00, 1.69, 2.45, 3.54, and 6.94 for men and 1.00, 1.76, 2.86, 4.88, and 9.88 for women. Predicted FM showed the strongest association with type 2 diabetes in men followed by waist circumference (WC), waist-to-height ratio (WHtR), predicted percent fat, BMI, Waist-to-hip ratio (WHR), and a body shape index (ABSI). For women, the strongest association was shown for WHtR, followed by WC, predicted percent fat, predicted fat mass, BMI, ABSI, and WHR. Compared to BMI, predicted fat mass demonstrated consistently stronger association with type 2 diabetes risk. However, there was inconclusive evidence to suggest that predicted fat mass is substantially superior to other obesity indicators.

Bleeding complications and antithrombotic treatment in 264 pregnancies in antiphospholipid syndrome.

Purpose The purpose of this study was to evaluate the safety of antithrombotic treatments prescribed during pregnancy in patients with antiphospholipid syndrome (APS). Methods This international, multicenter study included two cohorts of patients: a retrospective French cohort and a prospective US cohort (PROMISSE study). Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow-up data until six weeks post-partum. According to APS standard of care, patients were treated with aspirin and/or low-molecular weight heparin (LMWH) at prophylactic (pure obstetric APS) or therapeutic doses (history of thrombosis). Major bleeding was defined as abnormal blood loss during the pregnancy and/or post-partum period requiring intervention for hemostasis or transfusion, or during the peripartum period greater than 500 mL and/or requiring surgery or transfusion. Other bleeding events were classified as minor. Results Two hundred and sixty-four pregnancies (87 prospectively collected) in 204 patients were included (46% with history of thrombosis, 23% with associated systemic lupus). During pregnancy, treatment included LMWH ( n = 253; 96%) or low-dose aspirin ( n = 223; 84%), and 215 (81%) patients received both therapies. The live birth rate was 89% and 82% in the retrospective and prospective cohorts, respectively. Adverse pregnancy outcomes occurred in 28% of the retrospective cohort and in 40% of the prospective cohort. No maternal death was observed in either cohort. A combined total of 45 hemorrhagic events (25%) occurred in the retrospective cohort, but major bleeding was reported in only six pregnancies (3%). Neither heparin nor aspirin alone nor combined therapy increased the risk of hemorrhage. We also did not observe an increased rate of bleeding in the case of a short interval between last LMWH (less than 24 hours) or aspirin (less than five days) doses and delivery. Only emergency Caesarean section was significantly associated with an increased risk of bleeding (odds ratio (OR) 5.03 (1.41-17.96); p=.016). In the prospective cohort, only one minor bleeding event was reported (vaginal bleeding). Conclusion Our findings support the safety of antithrombotic therapy with aspirin and/or LMWH during pregnancy in high-risk women with APS, and highlight the need for better treatments to improve pregnancy outcomes in APS. PROMISSE Study ClinicalTrials.gov identifier: NCT00198068.

Predicted lean body mass, fat mass, and all cause and cause specific mortality in men: prospective US cohort study

ObjectiveTo investigate the association of predicted lean body mass, fat mass, and body mass index (BMI) with all cause and cause specific mortality in men.DesignProspective cohort study.SettingHealth professionals in the...

Abstract 5260: Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma: A prospective analysis from the NIH-AARP Diet and Health cohort

Abstract Objective: The 2016 WCRF Continuous Update Project reported that consumption of alcoholic drinks probably causes gastric cancer, but the magnitude of the association was small, there was moderate heterogeneity among the studies included in the meta-analysis, and most studies were from Asian populations, with only 401 cases from North American studies. Therefore, we re-evaluated the association between alcohol intake and gastric cancer in a large US cohort that has accrued more than 1300 gastric cancer cases. Methods: We prospectively investigated the associations of alcohol consumption with gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA) in 490,605 members aged 50-71 years at baseline in the NIH-AARP Diet and Health Study cohort. Alcohol consumption was assessed during the baseline questionnaire in 1995/1996 and evaluated as grams of ethanol intake and as a categorical variable: never, up to or including one drink/day, one to three drinks/day, and greater than three drinks/day. We used Cox proportional hazard regression to calculate the hazard ratios and 95% confidence intervals for associations between alcohol intake and risk of gastric adenocarcinomas with adjustment for several potential confounders. Results: Through 2011, 662 incident cases of GCA and 713 of GNCA occurred in the cohort. We found no association between higher alcohol consumption and GCA or GNCA, regardless of whether analyzed as total alcoholic beverage intake or the individual beverage types of beer, wine and liquor and no evidence for a dose-response. Furthermore, we observed no association by stratum of sex, ethnic group, educational level, or smoking status. Although there were no overall associations, we found some evidence for lower risk of GNCA among people who drank up to one drink per day (HR=0.81, 95%CIs:0.67-0.97) compared to nondrinkers. Conclusion: Alcohol consumption was not associated with increased risk of gastric cardia adenocarcinoma or gastric non-cardia adenocarcinoma in this large US prospective cohort. Citation Format: ShaoMing Wang, Neal D. Freedman, Erikka Loftfield, Xing Hua, Christian C. Abnet. Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma: A prospective analysis from the NIH-AARP Diet and Health cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5260.

Prolonged Leisure Time Spent Sitting in Relation to Cause-Specific Mortality in a Large US Cohort.

The majority of leisure time is spent in sedentary behaviors such as television viewing. Studies have documented that prolonged leisure-time sitting is associated with higher risk of mortality-total, cardiovascular disease, cancer, and "all other causes"-but few have examined the "other" causes of death in detail. To examine associations of leisure-time sitting with risk of specific causes of death, we analyzed data from the Cancer Prevention Study II (CPS-II) Nutrition Cohort, a prospective US cohort including 127,554 men and women who were free of major chronic disease at study entry, and among whom 48,784 died during 21 years of follow-up (1993-2014; median follow-up, 20.3 years, interquartile range, 4.6 years). After multivariable adjustment, prolonged leisure-time sitting (≥6 vs. <3 hours per day) was associated with higher risk of mortality from all causes, cardiovascular disease (including coronary heart disease and stroke-specific mortality), cancer, diabetes, kidney disease, suicide, chronic obstructive pulmonary disease, pneumonitis due to solids and liquids, liver, peptic ulcer and other digestive disease, Parkinson disease, Alzheimer disease, nervous disorders, and musculoskeletal disorders. These findings provide additional evidence for associations between a broad range of mortality outcomes and prolonged sitting time. Given the pervasive nature of sitting in the contemporary lifestyle, this study further supports the recommendation that encouraging individuals to reduce sedentary time may provide health benefits.

Garlic intake and gastric cancer risk: Results from two large prospective US cohort studies.

Although many case-control studies suggested that garlic intake may reduce gastric cancer risk, evidence from prospective cohort studies has been lacking. We examined the association between garlic intake and subsequent risk of gastric cancer among 77,086 women in the Nurses' Health Study (1984-2014) and 46,398 men in the Health Professionals Follow-Up Study (1986-2014). Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. We additionally examined garlic intake in relation to Helicobacter pylori (H. pylori) infection among 613 participants using logistic regression. During up to 30 years of follow-up, 292 participants were diagnosed with gastric cancer. The pooled multivariable RR of gastric cancer among participants who ate garlic, as compared to those who did not, were 1.11 (95% CI = 0.81-1.51) for the intake of garlic less than once per week, 0.98 (95% CI = 0.71-1.36) for one to four times per week and 1.39 (95% CI = 0.89-2.17) for five or more times per week (p for trend = 0.23). Similarly, no statistically significant association was observed cross-sectionally between garlic intake and H. pylori infection (comparing five or more times per week to never, pooled multivariable odds ratio = 1.66, 95% CI = 0.89-3.09; p for trend = 0.11). The findings from this large prospective study do not support the hypothesis that high garlic intake reduces risk of gastric cancer.

Abstract MP27: Weight Change, BMI, and Mortality Among Survivors of Myocardial Infarction: Analysis of Two Prospective US Cohort Studies

Background: The relation between BMI, weight change and mortality among survivors of Myocardial Infarction (MI) remains controversial, with some studies reporting favorable survival outcomes among overweight and obese patients, as compared to those with normal weight. We aim to examine the relationship between BMI reported shortly before and after MI diagnosis in addition to weight change with all-cause and cardiovascular disease (CVD) mortality among MI survivors. Methods: Using the data from Nurses’ Health Study (NHS) and Health Professionals Follow up Study (HPFS) cohorts, we studied 4278 participants who were free of CVD and cancer before their MI. Weight change (in BMI units) was categorized as loss of (&gt; 4, 2-4, &lt;2-0 (reference)), or gain of (0.1-2, or &gt;2) units. Multivariable Cox models were used to estimate hazard ratios and 95 % confidence interval for mortality across BMI/weight change categories. Results: During up to 36 (NHS) and 28 (HPFS) years of follow-up post-MI, there were 2071 all-cause and 835 CVD deaths. Overweight patients with BMI before or after MI of 25-27.49 kg/m 2 had decreased mortality as compared to normal weight patients (22.5-24.9 kg/m 2 ). All-cause mortality increased progressively with higher BMI. Obese patients (BMI≥30) had the highest risk of CVD mortality (HR=1.35; 95% CI, 1.06-1.73). Among MI patients who had never smoked (N=1484) or were younger than 65 years of age at the time of diagnosis (N=1873), no survival advantage was observed for overweight/obese patients. Compared to stable weight (a BMI reduction of 0-1.99 units) from before to after MI, a reduction of 2-4 or &gt;4 BMI units was associated with increased mortality (HR=1.12; 95% CI, 0.96-1.29 and 1.42; 95% CI, 1.17-1.71 respectively, Figure). Conclusions: We observed a J-shaped association between BMI and mortality among all MI patients, but not among those who had never smoked or were younger than 65 years of age. Weight loss associated with acute MI, potentially related to disease severity, is an important predictor of higher mortality.

Abstract P086: A Population-based Study of the Bidirectional Association Between Sleep Apnea and Diabetes in Three Prospective US Cohorts

Introduction: Both sleep apnea and diabetes are strong cardiovascular disease (CVD) risk factors with substantial healthcare burden. It is hypothesized that intermittent hypoxemia and sleep fragmentation resulting from sleep apnea may contribute to diabetes through inflammation, insulin resistance and glucose intolerance. Conversely, pre-existing diabetes may promote sleep apnea development through increased abnormalities in autonomic nervous system activity and ventilatory control due to peripheral neuropathy, or through effects on inflammatory pathways. However, no population-based study has simultaneously evaluated the potential bidirectional association between these two highly prevalent disorders. Methods: We followed 161,824 participants from the Nurses' Health Study (NHS; 2002-2012), NHSII (1995-2013), and the Health Professional Follow-up Study (1996-2012) who were free of diabetes, CVD and cancer at baseline. Cox proportional hazards model was used to estimate hazard ratios (HR) for developing diabetes according to sleep apnea status. In parallel, we used similar approaches to estimate risk of developing sleep apnea according to diabetes status among 167,277 participants free of sleep apnea, CVD and cancer at baseline. In all 3 cohorts, diagnoses of diabetes or sleep apnea were identified by validated self-reports. Results: Similar results were observed across 3 cohorts. In the pooled analysis, 9,370 incident diabetes cases were identified during follow-up. After adjusting for age, sex, menopausal status in women, smoking, alcohol drinking, diet quality, physical activity, sleep duration, regular physical exams, and hypertension, the HR (95% CI) for diabetes was 2.28 (2.07, 2.51) comparing those with versus without sleep apnea. The association was attenuated but remained statistically significant after accounting for waist circumference (WC) and BMI (HR: 1.57; 95% CI: 1.42, 1.73). By contrast, we documented 9,409 incident sleep apnea cases during follow-up. Compared with those without diabetes, the multivariable HR (95% CI) for sleep apnea prior to adjustment for BMI and WC was 1.44 (1.25, 1.67) in individuals with diabetes. Although there was no overall association after the adjustment (HR: 1.04; 95% CI: 0.95, 1.14), an increased risk was observed among those with diabetes who used insulin compared with those without diabetes (HR: 1.38; 95% CI: 1.11, 1.72). Conclusions: Sleep apnea is independently associated with an increased risk of diabetes, whereas insulin-dependent diabetes is associated with a higher risk of sleep apnea. Clinical awareness of this bidirectional association may improve prevention and treatment of both diseases and reduce their adverse impact on CVD. Future research aimed at elucidating the mechanisms that underlie each association may identify novel intervention targets.