Women ’s Health Study Research Articles

Abstract P243: Association Between a Brain Care Score and Risk of Cerebrovascular Events in American Women

Background: The McCance Brain Care Score (MBCS) is a novel tool derived through a modified Delphi process to motivate lifestyle changes to reduce the risk of cerebrovascular events (CVE) based on prior studies and expert knowledge. However, few studies to date have determined the association between the MBCS and incident CVE. Studying this potential association is particularly important given the higher risk of stroke among women and the potential for unique risk profiles given physiologic and pharmacologic hormonal changes across the lifespan. Methods: The study population was participants in the Women’s Health study (WHS) who had available risk factor information needed to calculate the modified MBCS 5 years after enrollment and no prior history of CVE. The WHS-adaptation of the MBCS is illustrated in Figure 1; higher scores suggest better brain health. Participants were followed from MBCS assessment until first CVE (Stroke or Transient Ischemic Attack), end of study, loss to follow-up, or death, whichever occurred first. CVE were confirmed by medical record review. Cox proportional hazards models were used to examine the association between the MBCS, modeled as a continuous variable, and incident CVE adjusted for potential confounders. Results: In total, 22,965 women were eligible with a median age of 58.0 (Interquartile Range 54.0-63.9) and median MBCS of 15 (14-17). There were 1,364 (5.9%) incident CVE events during a median follow-up of 22.5 (16.8-23.6) years. A one-point higher baseline MBCS was associated with 11% decreased risk of incident CVE after adjusting for age, postmenopausal status, and use of hormonal replacement therapy (HR=0.89; 95%CI=0.87-0.91). This association remained significant after adjusting for comorbidities, race, educational attainment, and income (HR=0.90; 95%CI=0.88-0.93). Conclusion: Higher baseline MBCS was associated with a decreased risk of incident CVE among women. Future studies are needed to understand how longitudinal changes in the MBCS impact risk of CVE.

Association of Parkinson’s disease status with accelerometer-derived physical activity and sedentary behavior in older women: The Women’s Health Study (WHS)

Evidence suggests that individuals diagnosed with Parkinson’s Disease (PD) spend less time in moderate-to-vigorous intensity physical activity (MVPA) compared to those without PD. However, prior studies primarily included men and did not consider movement across the entire intensity spectrum. To address these gaps, the association of PD status with total volume physical activity and time spent in sedentary, low light-intensity physical activity (LLPA), high light-intensity physical activity (HLPA), and MVPA among older women was examined. This is a cross-sectional analysis of 17,466 ambulatory women enrolled in the Women’s Health Study (WHS) with a median (IQR) age of 70 (67–75) years who were asked to wear an accelerometer for 7 days from 2011 to 2015 for the ancillary study. Reported PD status was assessed via annual mail-in questionnaires prior to device wear. Compared to those without PD (n = 16,661), PD (n = 80) was associated with 98,400 fewer vector magnitude (VM) counts per day and with spending an average of 23.2 more minutes per day sedentary and 10.5 more minutes per day in LLPA. Further, PD was associated with spending 6.4 and 27.3 fewer minutes per day in HLPA and MVPA, respectively, compared to women without PD. PD in women is associated with more daily sedentary time and less time spent in health-enhancing physical activity. Prevention strategies to promote physical activity should be emphasized to enhance health and limit progression of disability in women living with PD.

The epidemiology of dry eye disease in the UK: The Aston dry eye study

PurposeCross-sectional studies on dry eye disease (DED) have relied on different diagnoses hindering conclusions about the disease epidemiology. This study offers an insight into DED epidemiology in the UK using prior and recent diagnostic recommendations. MethodsStudy participants comprised 282 volunteers from Birmingham, UK (median 40 years, range 18–88 years, 56% females). DED was defined by the Tear Film Ocular Surface Dry Eye Workshop II (TFOS DEWS II) criteria, based on a positive symptom score with the Dry Eye Questionnaire (DEQ-5) and Ocular Surface Disease Index (OSDI), and one of the following homeostasis markers: non-invasive tear break-up time of < 10 s (Oculus Keratograph 5M); the highest osmolarity value of ≥ 308 mOsm/L among eyes or an interocular osmolarity difference of > 8 mOsm/L (TearLab Osmolarity System); or > 5 corneal spots, >9 conjunctival spots or lower/upper lid-wiper-epitheliopathy staining of ≥ 2 mm length and ≥ 25% width (Oculus Keratograph 5 M). In addition, the Women’s Health Study (WHS) criteria, based on symptoms or a prior dry eye diagnosis, was assessed. DED risk factors were gathered using a self-administered questionnaire. ResultsDED prevalence by the TFOS DEWS II criteria was 32.1% (95% confidence interval 25.5–37.7% and 29.5% (95% confidence interval 24.4–35.1% by the WHS criteria. Female sex, systemic and/or ocular health conditions, short sleep duration and prolonged outdoor leisure time spent were significant DED risk factors (p ≤ 0.05). ConclusionsApproximately one-third of the adult UK population have DED, aligning with the prevalence reported in multiple counties globally. Female sex, systemic/ocular health conditions, short sleep duration and prolonged outdoor leisure time are positive predictors of DED.

Prevalence and associated risk factors for dry eye disease among Brazilian undergraduate students.

PurposeDry eye is a common, complex, and multifactorial disease of the ocular surface and tear film that results in discomfort and visual disturbances. Prevalence rates vary and largely rely on studies involving older populations. This study sought to evaluate dry eye among a sample of young students in Brazil.MethodsCross-sectional survey included 2,140 students using 2 self-applicable questionnaires of dry eye symptoms: the Ocular Surface Disease Index (OSDI) and the Women’s Health Study (WHS) questionnaire and a list of risk factors associated with dry eye. Participants with dry eye symptoms underwent a clinical evaluation.ResultsParticipants were 23.4±5.2 years of age, 56.1% female and 43.9% male, 34.4% had an OSDI score greater than 22, and 23.5% had dry eye according to the WHS. Dry eye frequency differed consistently between the sexes: 42.6% women and 24.0% men based on the OSDI, and 27.1% women and 18.5% men based on the WHS. Univariate and multivariate analyses demonstrated that female sex, contact lens wear, the screen use for more than 6 hours per day, less than 6 hours of sleep a night, and certain medications were relevant related risk factors for dry eye. Despite symptoms, clinical evaluations demonstrated mild signs of dry eye.ConclusionsDry eye symptoms were found to be a prevalent condition among Brazilian undergraduate students. Compared to the rates of dry eye among the general Brazilian population over 40 years of age, students present at higher dry eye symptoms rates and distinct odds for related risk factors were identified.

Cohort profile: the Women’s Health Accelerometry Collaboration

PurposeThis paper describes the Women’s Health Accelerometry Collaboration, a consortium of two prospective cohort studies of women age 62 years or older, harmonised to explore the association of accelerometer-assessed physical...

Branched-Chain Amino Acids and Risk of Breast Cancer.

BackgroundCirculating branched-chain amino acid (BCAA) levels reflect metabolic health and dietary intake. However, associations with breast cancer are unclear.MethodsWe evaluated circulating BCAA levels and breast cancer risk within the Nurses’ Health Study (NHS) and NHSII (1997 cases and 1997 controls). A total of 592 NHS women donated 2 blood samples 10 years apart. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer risk in multivariable logistic regression models. We conducted an external validation in 1765 cases in the Women’s Health Study (WHS). All statistical tests were 2-sided.ResultsAmong NHSII participants (predominantly premenopausal at blood collection), elevated circulating BCAA levels were associated with lower breast cancer risk (eg, isoleucine highest vs lowest quartile, multivariable OR = 0.86, 95% CI = 0.65 to 1.13, Ptrend = .20), with statistically significant linear trends among fasting samples (eg, isoleucine OR = 0.74, 95% CI = 0.53 to 1.05, Ptrend = .05). In contrast, among postmenopausal women, proximate measures (<10 years from blood draw) were associated with increased breast cancer risk (eg, isoleucine OR = 1.63, 95% CI = 1.12 to 2.39, Ptrend = .01), with stronger associations among fasting samples (OR = 1.73, 95% CI = 1.15 to 2.61, Ptrend = .01). Distant measures (10-20 years since blood draw) were not associated with risk. In the WHS, a positive association was observed for distant measures of leucine among postmenopausal women (OR = 1.23, 95% CI = 0.96 to 1.58, Ptrend = .04).ConclusionsNo statistically significant associations between BCAA levels and breast cancer risk were consistent across NHS and WHS or NHSII and WHS. Elevated circulating BCAA levels were associated with lower breast cancer risk among predominantly premenopausal NHSII women and higher risk among postmenopausal women in NHS but not in the WHS. Additional studies are needed to understand this complex relationship.

Homocysteine Is Associated With Future Venous Thromboembolism in 2 Prospective Cohorts of Women.

[Figure: see text].

Abstract 17418: Religious Attendance and Ideal Cardiovascular Health in Older Women

Introduction: Although religious attendance can act as a protective health factor likely through social support and inherent beliefs, little is known about the relationship between the frequency of religious attendance and ideal cardiovascular health (ICH), particularly in older women, many of whom attend religious activities. Methods: We utilized the Women’s Health Study (WHS) follow-up psychosocial stress cohort (n=24360; mean age=71.8, SD= 5.8 years) to evaluate the cross-sectional relationship between current religious service attendance and ICH, as defined by the American Heart Association 2020 ICH score. Frequency of religious attendance was classified as never, at least once a year, at least once a month, and at least once a week. Results: Compared to women who never attend religious services, women who participate in religious services at least once a week are more likely to be hypertensive and hypercholesterolemic, less likely to be smokers or to use alcohol, less physically active, had lower education levels and more likely to earn &lt; $50,000 annually/household. In age-adjusted models, religious service attendance at least once a month and once a week was associated with a 17% and 36 % higher odds of ICH, respectively. This relationship persisted in models that additionally adjusted for race/ethnicity, education, income, psychological status and social support for women who attended religious services at least once a week [Table]. Conclusion: Among women in the Women’s Health Study, compared to non-attenders women who attended religious services weekly displayed a 30% higher odds of ideal cardiovascular health, despite adjustment for social support and other risk factors. These data suggest that religious attendance may be beneficial to the cardiovascular health of older women via additional mechanisms beyond social support.

One-Year Effects of Omega-3 Treatment on Fatty Acids, Oxylipins, and Related Bioactive Lipids and Their Associations with Clinical Lipid and Inflammatory Biomarkers: Findings from a Substudy of the Vitamin D and Omega-3 Trial (VITAL).

Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined these VITAL200, a nested substudy of 200 subjects balanced on demographics and treatment and randomly selected from the Vitamin D and Omega-3 Trial (VITAL). VITAL is a randomized double-blind trial of 840 mg/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) vs. placebo among 25,871 individuals. Small polar bioactive lipid features, oxylipins and FAs from plasma and red blood cells were measured using three independent assaying techniques at baseline and one year. The Women’s Health Study (WHS) was used for replication with dietary n-3 intake. Randomized n-3 treatment led to changes in 143 FAs, oxylipins and bioactive lipids (False Discovery Rate (FDR) < 0.05 in VITAL200, validated (p-values < 0.05)) in WHS with increases in 95 including EPA, DHA, n-3 docosapentaenoic acid (DPA-n3), and decreases in 48 including DPA-n6, dihomo gamma linolenic (DGLA), adrenic and arachidonic acids. N-3 related changes in the bioactive lipidome were heterogeneously associated with changes in clinical lipid and inflammatory biomarkers. N-3 treatment significantly modulates the bioactive lipidome, which may contribute to its clinical benefits.

COMT Effects on Vitamin E and Colorectal Cancer, in-vitro and in Two Randomized Trials (P15-005-19)

ObjectivesDespite promising observational data and compelling mechanisms of action, vitamin E has failed to demonstrate evidence of benefit in randomized clinical trials (RCTs). In two large long-term placebo-controlled RCTs, we reported that vitamin E effects on total cancer were modified by genetic variation in catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. Here we investigate COMT effects on colorectal cancer (CRC) in the two RCTs and a CRC cell line. MethodsWe analyzed COMT rs4680 association with rates of CRC in the Women’s Health Study (WHS), N = 23,294 and a case/control (N = 2396/2235) subset of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC). Cell survival and apoptosis were examined in-vitro in HCT116 cells treated with increasing doses of vitamin E when COMT gene expression was inhibited by silencing RNA (siRNA). ResultsRates of CRC were higher with randomized vitamin E compared to placebo among COMT high-activity val/val homozygotes in ATBC (HR, [CI] = 3.00, [1.48–6.09]), but not WHS (HR, [CI] = 0.99, [0.63–1.57]). Among low-activity met/met homozygotes randomized to vitamin E compared to placebo, rates of CRC were borderline lower in WHS (HR, [CI] = 0.66, [0.44–1.01]), but not in ATBC (HR, [CI] = 0.93, [0.63–1.62]).In cell culture, vitamin E at 3 μg/ml and 10 μg/mL had no effect on cell viability or apoptosis. However, silencing COMT resulted in a modest apoptotic effect that vitamin E enhanced in a dose-dependent manner. Human apoptosis arrays indicated that in the absence of COMT expression, vitamin E induced protein expression related to the intrinsic apoptotic pathway through p53 activation, dysregulation of Bcl-2 family protein expression and down-regulation of IAP family protein expression. ConclusionsDifferential COMT effects on vitamin E and CRC were similar to those previously reported for all invasive cancers, but were only significant for val/val homozygotes. Further, inhibiting COMT in the presence of vitamin E in a CRC in-vitro model, recapitulated the RCT observation that among individuals homozygous for the low-activity allele (met/met) vitamin E tended to reduce invasive cancer and here CRC. Funding SourcesNational Institutes of Health: NCI and NHLBI.

Abstract P268: Long and Short Sleep and Obesity in the Women’s Health Study

Background: Although evidence suggests that extremes of sleep (i.e. long and short) are associated with cardiovascular disease-related risk factors in the general population, research examining the association between the extremes of sleep and obesity in older women is limited. Methods and Results: We used the Women’s Health Study (WHS) 2012-2013 follow-up cohort of 21,726 older women (mean age = 72.1 ± 6.0 years old) to examine the cross-sectional association between extremes of sleep and obesity. Women with cancer or missing body mass index (BMI) data were excluded. Long sleep was defined as &gt; 9 hours/day, short sleep as &lt; 6 hours/day, and sleep of 6-9 hours/day was the reference. Sleep duration and BMI were self-reported measures. Approximately 23.3% of women were obese (BMI ≥ 30 kg/m 2 ). Overall, women who were obese and had either long or short sleep were less likely to exercise, and more likely to have history of diabetes, depression symptoms, and lower education and income levels. Women who were obese and long sleepers were more likely to use alcohol and have history of hypertension, while short sleepers were more likely to be current smokers. Logistic regression analyses revealed that older women with long sleep and short sleep had 30% higher odds of obesity, respectively, compared to women who slept 6-9 hours, adjusting for age and race/ethnicity. These relationships were attenuated and lost significance when controlling for potential important confounders (Table 1). Conclusion: Older women reporting extremes of sleep had higher odds of obesity compared to women who sleep 6-9 hours, after control for age and race/ethnicity. Further adjustment for traditional cardiovascular risk factors and socioeconomic parameters resulted in loss of significance.

Abstract 16588: Relationship Between Sleep Debt and Obesity in Older Women: Findings From the Women’s Health Study

Background: Obesity is increasingly prevalent in older women and is associated with heightened risk of cardiovascular disease (CVD) and Type II diabetes (diabetes). Sleep disturbance has been shown to affect weight through numerous mechanisms, including metabolic and hormone dysregulation and diet. However, whether sleep debt, a measure of sleep deficiency during the week compared to the weekend,is associated with greater risk of obesity among older women with and without diabetes is relatively unknown. Methods and Results: Among women participating in the Women’s Health Study (WHS) 2012-2013 follow-up stress cohort, we examined the relationship between sleep debt and obesity in 21,726 women without a history of cancer or CVD. Sleep debt was defined as the difference between self-reported total weekday and weekend sleep hours of ≥ 2 hours (dichotomizedas ‘yes’ = 1 or ‘no’ = 0). Mean age was 72.0 ±6.0 years, 23.1% of women reported a body mass index ≥30 kg/m 2 , and 9.9% of participants had diabetes. Sleep debt was reported by 6.5% of women. Compared to women without sleep debt, women with sleep debt were more likely to be less physically active and diabetic, and to report more cumulative psychological stress (e.g., a composite score of acute and chronic stressors including work, work-family spillover, financial, traumatic life events, negative life events, discrimination, relationship, and neighborhood). Logistic regression models revealed a positive association between sleep debt and obesity (OR=1.16, 95% CI: 1.02-1.33) after adjusting for age, race/ethnicity, education and income levels, physical activity, alcohol use, smoking history, and depression and anxiety symptoms (Table). However, this association does not remain significant after control for cumulative psychological stress. In analyses stratified by diabetes status, sleep debt is similarly associated with greater risk of obesity among non-diabetic women (OR=1.17, 95% CI: 1.02-1.36), however, this association does not remain significant once depression and anxiety symptoms and cumulative stress are added to the model. There was no association found between sleep debt and obesity among women with diabetes. Conclusion: Among older, non-diabetic women participating in the WHS, sleep debt was associated with greater risk of obesity.

Using Devices to Assess Physical Activity and Sedentary Behavior in a Large Cohort Study, the Women's Health Study.

In recent years, it has become feasible to use devices for assessing physical activity and sedentary behavior among large numbers of participants in epidemiologic studies, allowing for more precise assessments of these behaviors and quantification of their associations with health outcomes. Between 2011 and 2015, the Women's Health Study (WHS) used the Actigraph GT3X+ device to measure physical activity and sedentary behavior over 7 days, during waking hours, among 17,708 women (mean age, 72 years) living throughout the United States. Devices were sent to and returned by participants via mail. We describe here the methods used to collect and process the accelerometer data for epidemiologic data analyses. We also provide metrics that describe the quality of the accelerometer data collected, as well as expanded findings regarding previously published associations of physical activity or sedentary behavior with all-cause mortality during an average follow-up of 2.3 years (207 deaths). The WHS is one of the earliest "next generation" epidemiologic studies of physical activity, utilizing wearable devices, in which long-term follow-up of participants for various health outcomes is anticipated. It therefore serves as a useful case study in which to discuss unique challenges and issues faced.

Abstract P323: Sleep Debt and Type II Diabetes Mellitus in Middle Aged and Older Women

Background: Sleep disturbances can be both a cause and consequence of circadian disruption resulting in cardiometabolic dysregulation. However, little is known about sleep debt, defined as the average sleep duration difference &gt;=2 hours between weekend versus weekday and type II diabetes (T2D) mellitus particularly in older women. Methods and Results: We analyzed 25,335 women free of cardiovascular disease (CVD) in the ongoing follow-up cohort from the Women’s Health Study (WHS). Utilizing the WHS stress questionnaire (2012-13) that assessed sleep duration among other chronic and acute stress measures, we computed sleep debt as the average sleep duration difference &gt;=2 hours between weekend versus weekday. Of the 2539 women with physician confirmed T2D at the time of questionnaire administration, 216 women had sleep debt. Mean age for women with sleep debt and T2D versus no sleep debt and diabetes were 69.3 ± 4.4 and 72.7 +/- 6.1 years old respectively. Women with sleep debt and T2D were younger, more likely to have hypertension and hypercholesterolemia, use alcohol, be current smokers, had higher body mass index and be anxious or depressed. In logistic regression analyses, women with sleep debt had a 47% higher odds of T2D independent of age, race/ethnicity, and socioeconomic status (income and education) [odds ratio (OR): 1.47, 95% confidence interval (CI): 1.25 to 1.72, P&lt;0.0001]. Adjustment for CVD risk factors, depression and anxiety symptoms resulted in attenuation of the relationship which maintained statistical significance [OR: 1.31, 95% CI: 1.10 to 1.55, P= 0.0002]. When cumulative psychological stress (combination of chronic and acute stressors: e.g., life events, job stress, discrimination) was accounted for, the observed relationship between sleep debt and T2D persisted [OR: 1.28, 95% CI 1.09 to 1.53, P= 0.004]. (Table 1) Conclusion: Sleep debt was associated with higher odds of type 2 diabetes prevalence in middle-aged and older women.

Menopausal age, postmenopausal hormone therapy and incident atrial fibrillation

ObjectiveLimited data exist on the association between menopause and atrial fibrillation (AF). We sought to examine the relationship between menopausal age, postmenopausal hormone therapy (PHT) use and incident AF.MethodsThe Women’s...

Abstract P178: Vitamin D Biomarkers with Risk of Hypertension and Renin-Angiotensin System

Background: Experimental studies suggest that vitamin D may potentially prevent the development of hypertension through down-regulation of the renin-angiotensin system. However, evidence from epidemiologic studies remains limited. Objective: In parallel nested case-control studies of women from the Women’s Health Study (WHS) and men from the Physicians’ Health Study (PHS) with &gt;10 years follow-up, we examined the prospective associations between the circulating biomarkers of vitamin D status with risk of hypertension, as well as the inter-relation between vitamin D biomarkers and renin production. Methods: In each cohort, 500 incident hypertension cases and 500 controls were randomly selected from participants who were free of cardiovascular disease, cancer, and hypertension and provided bloods at baseline. Hypertension cases were identified based on self-reported blood pressure, physician’s diagnosis, or medication use. Controls were matched to cases on gender, age, race, follow-up time, and month of blood draw. Baseline plasma 25(OH)-vitamin D, parathyroid hormone (PTH), and total renin (pro-renin plus active renin) concentrations were measured. Analyses were first performed in each cohort separately and, given the similar results, finally combined for both cohorts. Results: Baseline concentrations of 25(OH)-vitamin D (mean of 26.6 vs. 27.0 ng/mL) and PTH (32.6 vs. 32.2 pg/mL) were similar in hypertension cases and controls. In the crude matched model, the risk of hypertension did not change with 25(OH)-vitamin D or PTH concentrations. Additional adjustment for other known hypertension-related risk factors minimally affected the associations. After adjusting for baseline smoking, alcohol use, exercise, menopausal status and hormone therapy use among women, body mass index, and history of diabetes and hypercholesterolemia, the relative risks of incident hypertension across increasing quintiles of 25(OH)-vitamin D were 1.00, 1.42 (95% CI: 0.94-2.16), 0.94 (95% CI: 0.60-1.48), 0.99 (95% CI: 0.61-1.61), and 1.03 (95% CI: 0.63-1.69) (p, trend, 0.48), and across increasing quintiles of PTH were 1.00, 1.26 (95% CI: 0.83-1.92), 0.91 (95% CI: 0.60-1.40), 1.10 (95% CI: 0.70-1.71), 0.92 (95% CI: 0.59-1.44) (p, trend, 0.50). These associations were similar in men and women. Among controls, plasma 25(OH)-vitamin D was inversely correlated with PTH (Pearson r: -0.24, p&lt;0.0001), while neither 25(OH)-vitamin D (r: -0.02, p=0.53) nor PTH (r: -0.01, p=0.69) was correlated with total renin concentrations. Conclusions: In prospective cohorts of men and women, we found no association between either baseline plasma 25(OH)-vitamin D or PTH with the risk of hypertension, or between either 25(OH)-vitamin D or PTH with total renin concentration. More research is needed to further elucidate the specific effect of vitamin D in the development of hypertension.

Abstract 110: Cumulative Negative Life Events and Risk of Myocardial Infarction: The Women’s Health Study

Background: Although psychosocial stressors such as negative life events predict adverse physical and mental health outcomes, significant gaps remain in the literature regarding whether such associations appear with cardiovascular disease (CVD) in middle-aged and older women, a demographic at higher risk for CVD than younger women. Hence, we investigated the relationship of cumulative negative life events and risk of myocardial infarction in the Women’s Health Study (WHS). Methods and Results: We performed a prospective, nested case-control study of apparently healthy post-menopausal women participating in the ongoing follow-up cohort of the Women’s Health Study; 26,763 women were followed for an average of 9 years to ascertain MI risk. Participants answered 12 standardized questions about negative life events within 5 years of survey completion (e.g. death/illness/accidental injury of someone close, fired from job, legal trouble, unemployment, marital infidelity, serious financial problems), and 3 questions about lifetime traumatic events (life-threatening illness, accident involving child or spouse, or victim of serious assault). Our cumulative life events score (CLES) was the count of items endorsed on all 15 questions, whereas our traumatic life events score counted positive responses to the 3 traumatic event questions. Women with a CLES score of zero were compared to women with scores &gt;0 who were divided into tertiles; thus defining 4 categories. Among 267 women with a history of MI and 281 age and smoking matched controls, the median age of participants was 56.0 years old (Interquartile range: 51.3 - 60.6). Logistic regression analyses revealed that while increasing CLES was associated with increasing MI risk [Odds Ratio: OR unadjusted model: 1.00, 1.21, 1.52, 1.87; p-trend 0.16], the trend did not reach statistical significance. In models adjusted for CVD risk factors, there was a significant interaction with household income: CLES was associated with MI only in women with household income &lt; $50,000 yearly (OR = 1.24, 95% CI: 1.05-1.49. The odds of MI was significantly higher in women who reported traumatic life events compared to women who did not (ORtraumatic life event score =1.65: 95% CI: 1.02, 2.68); women with traumatic life event(s) had a 65% increase in odds of MI when compared to women without, after adjusting for CVD risk factors and socio-economic status. In question specific analyses, women reporting serious financial problems as a life event had significantly higher odds of MI than women who did not (OR=2.60, 95% CI: 1.20 - 5.64). Conclusion: In this analysis among middle aged and older women, we found supportive evidence that negative cumulative life events were associated with MI risk, especially in low-income women and those suffering major traumatic life events. Further research is warranted particularly in women who also have limited socioeconomic resources.

A prospective study of erythrocyte polyunsaturated fatty acid, weight gain, and risk of becoming overweight or obese in middle-aged and older women.

ω3 and ω6 fatty acids (FA) may have divergent effects on the development of obesity. We examined the association of baseline erythrocyte ω3 and ω6 FA composition with body weight change and the risk of becoming overweight or obese in the Women's Health Study (WHS) participants. We identified 534 women who had baseline erythrocyte FA measured and a baseline body mass index (BMI) of 18.5-<25 kg/m(2). Body weight was updated at a total of six time points during follow-up. Weight gain during a mean of 10.4-year follow-up increased with increasing quartiles of baseline erythrocyte cis ω6 FA, ω6/ω3 ratio, and trans FA while decreased with increasing cis ω3 FA. After multivariable adjustment including total energy intake and physical activity, the weight gain (kg) in the highest versus the lowest quartile was 3.08 versus 2.32 for erythrocyte cis ω6 FA (p trend 0.04), 2.07 versus 2.92 for cis ω3 FA (p trend 0.08), 2.93 versus 2.05 for ω6/ω3 ratio (p trend 0.046), and 3.03 versus 2.27 for trans FA (p trend 0.06). Among individual FA, the associations were significant for 18:2ω6, 18:3ω6, and trans 18:1 and marginally significant for 20:3ω6 and trans 18:2. The risk of becoming overweight or obese (defined as BMI ≥25 kg/m(2) at any follow-up time point) increased across increasing ω6/ω3 ratio (multivariable model p trend 0.04). In this prospective study, we found suggestive evidence that erythrocyte cis ω6 FA may be positively associated, and cis ω3 FA inversely associated with weight gain in initially normal-weight women.

Abstract 19: Dietary Lipophilic Load and Dietary Lipophilic Index with Risk of Coronary Heart Disease in Middle-Aged Women: Beyond Conventional Fat Classifications

Introduction: Studies indicate dietary types of fats are associated with risk of coronary heart disease (CHD). Traditional broad classifications may incompletely capture the diversity of fatty acids on CHD. The novel lipid index Dietary Lipophilic Load (DLL) reflects a unique combination of fatty acid fluidity, intermolecular attraction, plus relative fat quantity, while Dietary Lipophilic Index (DLI) is a measure of average fat fluidity, regardless of fat quantity. Thus, we evaluated the association, DLL and DLI, with risk of incident CHD. METHODS: Participants included 30,932 women in the Women’s Health Study (WHS), who were free of major chronic diseases at baseline. DLL was calculated by weighted summation of the multiplicative product of each fatty acid’s intakes (g/day) and its melting points (Celcius); DLI was calculated by dividing DLL by total fat intake (g/day). Hazard ratios (HRs) were adjusted for established risk factors, with updated dietary data, and potential mediators. We also investigated hypothesized interactions with C-Reactive Protein (CRP). RESULTS: There were 1137 cases of incident CHD in 525,828 person-years over 19 years follow-up. At baseline in over 27,000 women with blood samples, DLL and DLI were not correlated with serum cholesterol, triglyceride, HbA1c, ICAM-1, or CRP biomarkers (r&lt;0.02 for all). In overall multivariate analysis, DLL was associated with higher risk of CHD (extreme quintile HR=1.40, 95%CI: 1.11-1.76, P trend=0.0002), while DLI was not (HR=0.83, 95%CI: 0.67-1.03, P trend=0.75). DLL results were independent beyond adjustment for dietary trans, saturated, monounsaturated, and polyunsaturated fats, nor their aggregate adjustment or the P:S ratio. DLL effects persisted even adjusting for CRP (HR=1.29, P-trend=1 mg/dL for DLL (extreme quintile HR=1.38, 1.02-1.88), than among individuals with low CRP &lt;1 mg/dl for DLL (HR=1.08, 0.68-1.72), with P-interaction&lt;0.0001. Furthermore, CRP also modified DLI, where effects again diverged among higher CRP (HR=0.98, 0.73-1.31) versus low CRP (HR=0.45, 0.27-0.74), with P-interaction&lt;0.0001. Moreover, adjustment of triglycerides, HbA1c, ICAM-1, LDL or HDL cholesterol also did not materially affect overall results. CONCLUSION: Results indicate that DLL is associated with increased risk of incident CHD, independent of traditional risk factors, conventional dietary fat classifications, and major CHD biomarkers. Effects of DLL and DLI appear to be modified by levels of CRP. DLL appears to be an important novel dietary fat index that captures additional CHD risk information beyond biomarkers and traditional dietary fat categories. Further studies are warranted.

Abstract P191: Erythrocyte Polyunsaturated Fatty Acid, Weight Gain, and Risk of Becoming Overweight in Middle-aged and Older Women

Background: Laboratory studies suggest that ω3 and ω6 polyunsaturated fatty acids (PUFA) may have divergent effects on the development of obesity. Epidemiologic studies comparing the associations for ω3 and ω6 PUFA are limited. Objective: We prospectively examined whether the baseline proportions of ω3 and ω6 PUFAs on erythrocyte membranes were associated with the risk of becoming overweight and changes in body weight in the Women’s Health Study (WHS). Methods: We identified WHS participants in a previous nested case-control study of hypertension who reported a body mass index (BMI) &lt;25 kg/m 2 at baseline. Baseline fatty acid (FA) composition of erythrocyte membranes was measured as biomarkers of dietary FA intake using gas chromatography. Women who subsequently reported a BMI ≥25 kg/m 2 during follow-up were defined as becoming overweight. Body weight change was calculated as the difference in reported body weight from baseline to annual follow-up questionnaires. Results: Among 534 women with baseline BMI &lt;25 kg/m 2 , 186 became overweight during an average of 10 years of follow-up. After initial adjustment for age, race, randomized treatment, the hazard ratios (HR) and 95% confidence interval (95% CI) for becoming overweight across increasing quartiles of erythrocyte PUFA were 1.00, 0.77 (0.49-1.21), 1.12 (0.75-1.67), and 1.19 (0.79-1.77) for cis ω6 PUFA (p, trend: 0.31), 1.00, 0.90 (0.61-1.31), 0.76 (0.51-1.13), 0.71 (0.45-1.10) for cis ω3 PUFA (p, trend: 0.09), and 1.00, 1.37 (0.84-2.22), 1.57 (1.01-2.43), and 1.58 (1.01-2.46) for ω6 to ω3 PUFA ratio (p, trend: 0.046). Additional adjustment for lifestyle and dietary factors did not substantially attenuate these associations, with HR (95% CI) of 1.00, 1.26 (0.76-2.08), 1.44 (0.91-2.28), and 1.56 (0.97-2.51) across increasing quartiles of ω6 to ω3 PUFA ratio (p, trend: 0.064). Analysis of longitudinal change in body weight showed similar associations. After multivariable adjustment, the mean±standard error of weight gain over an average of 10 years of follow-up across increasing quartiles of erythrocyte PUFA were 2.34±0.49, 1.92±0.53, 2.86±0.54, and 3.10±0.53 kg for cis ω6 PUFA (p, trend: 0.04), 2.97±0.52, 2.60±0.53, 2.74±0.53, 2.16±0.51 kg for cis ω3 PUFA (p, trend: 0.095), and 2.13±0.51, 2.65±0.54, 2.77±0.53, 2.98±0.52 kg for ω6 to ω3 PUFA ratio (p, trend: 0.05). trans PUFA 18:2 was not associated with the risk of becoming overweight or longitudinal weight gain. Analyses of joint categories of ω3 and ω6 PUFA did not show significant interaction . Conclusion: In this prospective study, we found suggestive evidence that the proportion of cis ω6 PUFA on erythrocyte membrane was positively associated, and cis ω3 PUFA inversely associated, with the risk of becoming overweight and weight gain in initially normal-weight women.