Predictors of angina pectoris versus myocardial infarction from the Women's Health Initiative Observational Study

Although risk factors for acute coronary syndromes have been extensively studied, characteristics distinguishing women who will develop unstable angina rather than acute myocardial infarction (MI) are less well understood. This analysis evaluates baseline demographic, physical, and medical characteristics as predictors of angina versus MI in the Women's Health Initiative Observational Study. During a prospective 4.5-year follow-up of 92,152 postmenopausal women, 1,527 hospitalizations for angina and 797 for MI were confirmed by centrally trained physician adjudicators. In a multivariate analysis of women with incident angina or MI, high cholesterol (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.47 to 0.80; p = 0.0004) and prior coronary disease (OR 0.70, 95% CI 0.55 to 0.89; p = 0.004) independently predicted angina (referent), whereas current cigarette smoking (OR 1.60, 95% CI 1.13 to 2.26; p = 0.007) and diabetes mellitus (1.44, 95% CI 1.10 to 1.87; p = 0.007) predicted MI. Older age and hypertension were independently, but less strongly, predictive of MI. Aspirin or statin use, physical activity, body mass index, and educational levels were not independently associated with one or the other type of acute coronary syndrome. Thus, specific risk factors strongly and independently predicted whether women with an acute coronary syndrome would present with angina or with MI.     

Protein Intake and Incident Frailty in the Women's Health Initiative Observational Study

OBJECTIVES: To evaluate the association between protein intake and incident frailty. DESIGN: Prospective cohort study. SETTING: Subset of the Women's Health Initiative Observational Study conducted at 40 clinical centers. PARTICIPANTS: Twenty‐four thousand four hundred seventeen women aged 65 to 79 who were free of frailty at baseline with plausible self‐reported energy intakes (600–5,000 kcal/day) according to the Food Frequency Questionnaire (FFQ). MEASUREMENTS: Baseline protein intake was estimated from the FFQ. Calibrated estimates of energy and protein intake were corrected for measurement error using regression calibration equations estimated from objective measures of total energy expenditure (doubly labeled water) and dietary protein (24‐hour urinary nitrogen). After 3 years of follow‐up, frailty was defined as having at least three of the following components: low physical function (measured using the Rand‐36 questionnaire), exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models estimated associations for uncalibrated and calibrated protein intake. RESULTS: Of the 24,417 eligible women, 3,298 (13.5%) developed frailty over 3 years. After adjustment for confounders, a 20% increase in uncalibrated protein intake (%kcal) was associated with a 12% (95% confidence interval (CI)=8–16%) lower risk of frailty, and a 20% increase in calibrated protein intake was associated with a 32% (95% CI=23–50%) lower risk of frailty. CONCLUSION: Higher protein consumption, as a fraction of energy, is associated with a strong, independent, dose‐responsive lower risk of incident frailty in older women. Using uncalibrated measures underestimated the strength of the association. Incorporating more protein into the diet may be an intervention target for frailty prevention.     

Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women's Health Initiative Observational Study

Objective

Farming and agricultural pesticide use has been associated with 2 autoimmune rheumatic diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, risk associated with other residential or work place insecticide use is unknown.

Methods

We analyzed data from the Women's Health Initiative Observational Study (n = 76,861 postmenopausal women, ages 50–79 years). Incident cases (n = 213: 178 for RA, 27 for SLE, and 8 for both) were identified based on self‐report and use of disease‐modifying antirheumatic drugs at year 3 of followup. We examined self‐reported residential or work place insecticide use (personally mixing/applying by self and application by others) in relation to RA/SLE risk, overall and in relation to farm history. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were adjusted for age, race, region, education, occupation, smoking, reproductive factors, asthma, other autoimmune diseases, and comorbidities.

Results

Compared with never used, personal use of insecticides was associated with increased RA/SLE risk, with significant trends for greater frequency (HR 2.04, 95% CI 1.17–3.56 for ≥6 times/year) and duration (HR 1.97, 95% CI 1.20–3.23 for ≥20 years). Risk was also associated with long‐term insecticide application by others (HR 1.85, 95% CI 1.07–3.20 for ≥20 years) and frequent application by others among women with a farm history (HR 2.73, 95% CI 1.10–6.78 for ≥6 times/year).

Conclusion

These results suggest residential and work place insecticide exposure is associated with the risk of autoimmune rheumatic diseases in postmenopausal women. Although these findings require replication in other populations, they support a role for environmental pesticide exposure in the development of autoimmune rheumatic diseases.     

Risk of fracture in women with type 2 diabetes: the Women's Health Initiative Observational Study

CONTEXT: Some but not all studies have shown higher rates of fracture in individuals with type 2 diabetes. OBJECTIVE: The objective of the study was to determine the risk of fracture in postmenopausal women with type 2 diabetes and determine whether risk varies by fracture site, ethnicity, and baseline bone density. DESIGN, SETTING, AND PARTICIPANTS: Women with clinically diagnosed type 2 diabetes at baseline in the Women's Health Initiative Observational Cohort, a prospective study of postmenopausal women (n = 93,676), were compared with women without diagnosed diabetes and risk of fracture overall and at specific sites determined. MAIN OUTCOME MEASURES: All fractures and specific sites separately (hip/pelvis/upper leg; lower leg/ankle/knee; foot; upper arm/shoulder/elbow; lower arm/wrist/hand; spine/tailbone) were measured. Bone mineral density (BMD) in a subset also was measured. RESULTS: The overall risk of fracture after 7 yr of follow-up was higher in women with diabetes at baseline after controlling for multiple risk factors including frequency of falls [adjusted relative risk (RR) 1.20, 95% confidence interval (CI) 1.11-1.30]. In a subsample of women with baseline BMD scores, women with diabetes had greater hip and spine BMD. The elevated fracture risk was found at multiple sites (hip/pelvis/upper leg; foot; spine/tailbone) among black women (RR 1.33, 95% CI 1.00-1.75) and women with increased baseline bone density (RR 1.26, 95% CI 0.96-1.66). CONCLUSION: Women with type 2 diabetes are at increased risk for fractures. This risk is also seen among black and non-Hispanic white women after adjustment for multiple risk factors including frequent falls and increased BMD (in a subset).     

Cigarette smoking and the risk of rheumatoid arthritis among postmenopausal women: results from the Iowa Women's Health Study

PURPOSE: To determine whether cigarette smoking increases the risk of rheumatoid arthritis among postmenopausal women. SUBJECTS AND METHODS: We followed a cohort of 31 336 women in Iowa who were aged 55 to 69 years in 1986 and who had no history of rheumatoid arthritis. Through 1997, 158 cases of rheumatoid arthritis were identified and validated based on review of medical records and supplementary information provided by physicians. Multivariable Cox proportional hazards regression was used to derive rate ratios (RRs) and 95% confidence intervals (CIs) for the association between cigarette smoking and rheumatoid arthritis. RESULTS: Compared with women who had never smoked, women who were current smokers (RR = 2.0; 95% CI: 1.3 to 2.9) or who had quit 10 years or less before study baseline (RR = 1.8; 95% CI: 1.1 to 3.1) were at increased risk of rheumatoid arthritis, but women who had quit more than 10 years before baseline were not at increased risk (RR = 0.9; 95% CI: 0.5 to 2.6). Both the duration and intensity of smoking were associated with rheumatoid arthritis. Multivariable adjustments for age, marital status, occupation, body mass index, age at menopause, oral contraceptive use, hormone replacement therapy, alcohol use, and coffee consumption did not alter these results. CONCLUSION: These results suggest that abstinence from smoking may reduce the risk of rheumatoid arthritis among postmenopausal women.     

Frailty: emergence and consequences in women aged 65 and older in the Women's Health Initiative Observational Study

OBJECTIVES: To define frailty using simple indicators; to identify risk factors for frailty as targets for prevention; and to investigate the predictive validity of this frailty classification for death, hospitalization, hip fracture, and activity of daily living (ADL) disability. DESIGN: Prospective study, the Women's Health Initiative Observational Study. SETTING: Forty U.S. clinical centers. PARTICIPANTS: Forty thousand six hundred fifty-seven women aged 65 to 79 at baseline. MEASUREMENTS: Components of frailty included self-reported muscle weakness/impaired walking, exhaustion, low physical activity, and unintended weight loss between baseline and 3 years of follow-up. Death, hip fractures, ADL disability, and hospitalizations were ascertained during an average of 5.9 years of follow-up. RESULTS: Baseline frailty was classified in 16.3% of participants, and incident frailty at 3-years was 14.8%. Older age, chronic conditions, smoking, and depressive symptom score were positively associated with incident frailty, whereas income, moderate alcohol use, living alone, and self-reported health were inversely associated. Being underweight, overweight, or obese all carried significantly higher risk of frailty than normal weight. Baseline frailty independently predicted risk of death (hazard ratio (HR)=1.71, 95% confidence interval (CI)=1.48-1.97), hip fracture (HR=1.57, 95% CI=1.11-2.20), ADL disability (odds ratio (OR)=3.15, 95% CI=2.47-4.02), and hospitalizations (OR=1.95, 95% CI=1.72-2.22) after adjustment for demographic characteristics, health behaviors, disability, and comorbid conditions. CONCLUSION: These results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women. Underweight, obesity, smoking, and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention.     

Hormone replacement therapy and risk of cardiovascular disease: implications of the results of the Women's Health Initiative

The higher rates of coronary heart disease (CHD), stroke, and venous thrombosis among women taking estrogen and progesterone (E+P) compared with placebo in the Women's Health Initiative clinical trial have important implications for women's health. Previous studies in both men and women have shown that estrogen therapy lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol. The changes in these lipoproteins should be associated with at least a 30% decline in CHD risk. Estrogens increased very-low-density lipoprotein (VLDL) triglyceride levels and C-reactive protein. There is evidence that estrogens increase thrombin generation and fibrinolysis. The increase in VLDL triglycerides may enhance thrombotic risk as well as higher levels of atherogenic lipoproteins, such as dense low-density lipoprotein. Genetic variations in estrogen receptors and thrombosis or fibrinolysis may also be important in risks associated with E+P therapy. The increased risk of CHD and stroke with E+P therapy may be attributable to rise in VLDL triglycerides and thrombosis.     

Statin use and incident frailty in women aged 65 years or older: prospective findings from the Women's Health Initiative Observational Study

BACKGROUND: Inflammatory biomarkers have shown consistent associations with disability and frailty in older adults. Statin medications may reduce the incidence the frailty because of their anti-inflammatory effects. This study examines associations between current use, duration, and potency of statin medications and incident frailty in initially nonfrail women 65 years old or older. METHODS: The authors conducted a prospective analysis of data from the Women's Health Initiative Observational Study (WHI-OS) conducted at 40 clinical centers in the United States. Eligible women were nonfrail and 65-79 years old at baseline (n = 25,378). Current statin use at baseline was ascertained through direct inspection of medicine containers during clinic visits. Frailty was ascertained through self-reported indicators and physical measurements at baseline and 3-year clinic contacts. Components of frailty included self-reported low physical function, exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models were used to adjust for covariates predicting incident frailty. RESULTS: Among the 25,378 eligible women, 3453 (13.6%) developed frailty by the 3-year follow-up contact. Current statin use had no association with incident frailty (multivariate-adjusted odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.85-1.16). Duration and potency of statin use were also not significantly associated with incident frailty. Among low potency statin users, longer duration of use was associated with reduced risk of frailty (p for trend =.02). A similar pattern of results was observed when frailty was studied in the absence of intervening, incident cardiovascular events. CONCLUSIONS: Overall, incidence of frailty was similar in current statin users and nonusers.     

Health literacy among cancer survivors: Results from the 2016 behavioral risk factor surveillance system survey

Health literacy is a set of knowledge and skills that enables individuals to obtain, communicate, process and understand information, and services to make appropriate health decisions and to successfully navigate the health care system. Health literacy is important to quality of cancer survivorship care and patient self-management of their disease.We examined health literacy among cancer survivors, using data from the 2016 Behavioral Risk Factor Surveillance System. We compared health literacy across various demographic and socioeconomic groups and estimated the adjusted odds in favor of low health literacy for these characteristics.We found that about 16% of the cancer survivors had low health literacy. The prevalence was higher among Hispanic and Black individuals, and among those with poor health status, low income and educational attainment.A sizeable percentage of cancer survivors have low health literacy which is likely to complicate their ability to self-manage their disease and navigate the health care system for optimal care. In order to ensure the quality and appropriateness of cancer survivorship care, effective interventions are needed to address low health literacy in these populations.     

Angiotensin-Converting Enzyme Inhibitor Use and Incident Frailty in Women Aged 65 and Older: Prospective Findings from the Women's Health Initiative Observational Study

OBJECTIVES: To examine the associations between current use, duration, and potency of angiotensin-converting enzyme (ACE) inhibitors and incident frailty in women aged 65 and older who were not frail at baseline.
DESIGN: Data were from the Women's Health Initiative Observational Study (WHI-OS), a prospective study conducted at 40 U.S. clinical centers.
PARTICIPANTS: Women aged 65 to 79 at baseline who were not frail (N=27,378).
MEASUREMENTS: Current ACE inhibitor use was ascertained through direct inspection of medicine containers at baseline. Components of frailty were self-reported low physical function or impaired walking, exhaustion, low physical activity, and unintended weight. Frailty was ascertained through self-reported and physical measurements data at baseline and 3-year clinic contacts.
RESULTS: By the 3-year follow-up, 3,950 (14.4%) women had developed frailty. Current ACE inhibitor use had no association with incident frailty (multivariate adjusted odds ratio=0.96, 95% confidence interval=0.82–1.13). Duration and potency of ACE inhibitor use were also not significantly associated with incident frailty. A similar pattern of results was observed when incident cardiovascular disease events were studied as a separate outcome or when the sample was restricted to subjects with hypertension.
CONCLUSION: Overall, incidence of frailty was similar in current ACE inhibitor users and nonusers.     

Interaction between body mass index and central adiposity and risk of incident cognitive impairment and dementia: results from the Women's Health Initiative Memory Study

OBJECTIVES: To assess the relationship between body mass index (BMI) and waist–hip ratio (WHR) and the clinical end points of cognitive impairment and probable dementia in a cohort of older women enrolled in the Women's Health Initiative Memory Study (WHIMS). DESIGN: Prospective, randomized clinical trial of hormone therapies with annual cognitive assessments and anthropometrics. SETTING: Fourteen U.S. clinical sites of the WHIMS. PARTICIPANTS: Seven thousand one hundred sixty‐three postmenopausal women aged 65 to 80 without dementia. MEASUREMENTS: Annual cognitive assessments, average follow‐up of 4.4 years, including classification of incident cognitive impairment and probable dementia. Height, weight, waist, and hip measurements were assessed at baseline, and a waist–hip ratio (WHR) of 0.8 or greater was used as a marker of central adiposity. RESULTS: There were statistically significant interactions between BMI and WHR and incident cognitive impairment and probable dementia with and without adjustment for a panel of cognitive risk factors. Women with a WHR of 0.80 or greater with a BMI of 20.0 to 24.9 kg/m² had a greater risk of cognitive impairment and probable dementia than more‐obese women or women with a WHR less than 0.80, although women with a WHR less than 0.80 and a BMI of 20.0 to 24.9 kg/m² had poorer scores on cognitive assessments. CONCLUSION: WHR affects the relationship between BMI and risk of cognitive impairment and probable dementia in older women. Underweight women (BMI<20.0 kg/m²) with a WHR less than 0.80 had a greater risk than those with higher BMIs. In normal‐weight to obese women (20.0–29.9 kg/m²), central adiposity (WHR≥0.80) is associated with greater risk of cognitive impairment and probable dementia than in women with higher BMI. These data suggest that central adiposity as a risk factor for cognitive impairment and probable dementia in normal‐weight women.