Although several modifiable risk factors have been independently associated with risk of breast cancer, few studies have investigated their joint association with breast cancer risk. Using a healthy lifestyle index (HLI) score, we assessed the association of a combination of selected modifiable risk factors (diet, alcohol, physical activity, BMI, and smoking) with risk of invasive breast cancer in the Women's Health Initiative (WHI). This study comprised 131,833 postmenopausal women, of whom 8,168 had breast cancer, who were enrolled in the WHI Observational Study or the WHI clinical trials. Cox proportional hazards regression was used to estimate the HRs and 95% confidence intervals (CI) for the association of the score with the risk of developing breast cancer overall and according to specific breast cancer clinicopathologic characteristics. There was a 4% reduction in the risk of breast cancer per unit increase in the HLI score. Compared with those with an HLI score in the lowest quintile level, those in the highest quintile level had 30%, 37%, and 30% lower risk for overall, ER⁺/PR⁺, and HER2⁺ breast cancer, respectively (HR = 0.70; 95% CI, 0.64-0.76; 0.63, 0.57-0.69; and 0.70; 0.55-0.90, respectively). We also observed inverse associations between the score and risk of breast cancer irrespective of nodal status, tumor grade, and stage of the disease. Most individual lifestyle factors were independently associated with the risk of breast cancer. Our findings support the view that promoting healthy lifestyle practices may be beneficial with respect to lowering risk of breast cancer among postmenopausal women. Cancer Prev Res; 11(6); 317-26. ©2018 AACRSee related editorial by Friedenreich and McTiernan, p. 313.

This study examined the longitudinal association of depressive symptoms and stressful life events with inflammation in the Women's Health Initiative. Women aged 50 years and older ( N = 7477) completed questionnaires assessing depressive symptoms and stressful life events at baseline and 15 years later. Serum measures of C-reactive protein were collected at both assessments. In bivariate analyses, C-reactive protein predicted 15-year depressive symptoms and stressful life events ( ps < .03) and baseline depressive symptoms and stressful life events predicted later C-reactive protein ( ps < .03). These longitudinal relationships were not maintained in multivariate adjusted analyses. Combined with previous research, this suggests the relationship between depression, stressful life events and inflammation attenuates with time.

Background

Midlife obesity has been linked to age-related brain atrophy and risk of dementia, but the relationships are less clear for older individuals. These associations may be explained by changes in appetite or metabolism in the dementia prodrome; thus, prospective studies with adequate follow-up are needed. We examined the associations that obesity (body mass index, BMI) and change in BMI over an average of 6.6 (1.0-9.1) years have with global and regional brain and white matter lesion volumes in a sample of 1,366 women aged 65-80.

Methods

Least square means for regional brain volumes and white matter lesion loads for women grouped by BMI and changes in BMI were generated from multivariable linear models with and without adjustment for demographic and health covariates.

Results

Both global obesity and increase in BMI were associated with lower cerebrospinal fluid and higher specific brain volumes (ps < .05), after controlling for diabetes and other cerebrovascular disease risk factors. Obesity, but not change in BMI, predicted lower lesion loads for the total, parietal, and occipital white matter (ps < .05).

Conclusions

Obesity in this cohort is associated with less brain atrophy and lower ischemic lesion loads. The findings are consistent with our previous report of worse cognitive performance in association with weight loss (probably not due to frailty) in this cohort and in line with the idea of the "obesity paradox" as differences in dementia risk vary across time, whereby midlife obesity seems to be a predictor of dementia, whereas weight loss seems to be a better predictor at older ages.

Background

Known risk factors for intracerebral hemorrhage (ICH) include age, hypertension, smoking, alcohol intake, and anticoagulant use. Some previous reports have indicated that hemostatic factors measured many years before the onset of ICH might predict the later occurrence of ICH. The objective of this analysis was to test whether selected hemostatic factors measured years before the onset of ICH could identify patients at higher risk for future ICH.

Methods

We performed a nested case-control study within the Women's Health Initiative (WHI) cohort. Postmenopausal women aged 50-79 years (mean 68) at baseline (1993-1998) were enrolled at 40 Clinical Centers in the United States and followed for adjudicated ICH for a mean of 11.4 years. ICH cases (N = 75) and controls (N = 75) were matched on age, ethnicity, blood pressure, anticoagulant use, and treated hypertension. Stored blood samples from the baseline WHI examination were tested for von Willebrand factor (vWF), a disintegrin-like and metalloprotease domain with thrombospondin type-1 motif, number 13 (ADAMTS13), tissue plasminogen activator (t-PA), and urokinase plasminogen activator (u-PA). Platelet count, white blood cell count, and hemoglobin concentration were also measured.

Results

Mean baseline levels of vWF (1.03 and .95 U/mL), ADAMTS13 (1.0 and 1.1 µg/mL), vWF : ADAMTS13 ratio (.99 and .92), t-PA (14.75 and 14.80 IU/mL), and u-PA (.09 and .10 IU/mL) were not significantly different by case-control status. Significant differences were also not identified for platelet count, hemoglobin, white blood count, or reported alcohol use.

Conclusion

None of the 4 baseline hemostatic factors nor the platelet count was predictive of future ICH risk in this long-term study of older postmenopausal women.

Introduction

Lower grip strength and measures of physical functioning are associated with all-cause mortality. Relationships among long-term weight loss, physical functioning, and mortality in older women are understudied.

Methods

Participants were 5039 women who were part of the Long Life Study (LLS) ancillary study to the Woman's Health Initiative (WHI). Average age was 78.76 ± 6.92. We defined long-term weight loss or gain as a decrease or increase of 5% or more of baseline body weight. Our primary outcome was all-cause mortality and our secondary outcomes were vascular death, and coronary heart disease (CHD). The mean follow-up time was 5.4 years. Cox regression modeling was performed for each outcome of interest. Variables of interest were weight change, grip strength, and functional status as measured by the Short Physical Performance Battery (SPPB) controlling for multiple potential confounders.

Results

Weight loss of 5% or more percent body weight was associated with a hazard ratio of 1.66 (1.37-2.01) for all-cause mortality. Weight gain was not related to mortality or cardiovascular outcomes. Those in the highest grip strength quartile had a hazard ratio of 0.51 (0.39-0.66) for all-cause mortality. For the SPPB the hazard ratio was 0.29 (0.21-0.40), adjusting for changes in weight, race, smoking, history CHD, smoking, and diabetes. Higher grip strength and SPPB were associated with lower risks for vascular death, and CHD, independently of weight change.

Conclusions

Weight loss was associated with increased mortality. Stronger grip strength and higher SPPB scores were associated with lower mortality risk independent of weight change.

BACKGROUND: Women who reach menarche and menopause at earlier ages have been shown to be at increased risk for numerous conditions including cardiovascular disease, cancer, depression, and obesity; however, risk factors for earlier ages of menarche and menopause are not fully understood. Therefore, we aimed to perform a retrospective investigation of the associations between a personal birthweight and/or being born preterm and the age of and menarche and menopause and related events in the Womens Health Initiative, a large, racially and ethnically diverse cohort of postmenopausal women. METHODS: At study entry, women reported their birthweight by category (< 6 lbs., 6-7 lbs. 15 oz, 8-9 lbs. 15 oz, or ≥ 10 lbs.) and preterm birth status (4 or more weeks premature). Ages at events related to menarche and menopause were also self-reported. Linear regression and logistic regression models were used to estimate unadjusted and adjusted effect estimates (β) and odds ratios (OR), respectively (n ≤ 86,857). Individuals born preterm were excluded from all birthweight analyses. RESULTS: After adjustments, individuals born weighing < 6lbs. were more likely to reach natural menopause at an earlier age (adjusted β=-0.361, SE = 0.09, P = < 0.001) and have a shorter reproductive window (adjusted β = -0.287, SE = 0.10, p < 0.004) compared to individuals weighing 6-7 lbs. 15 oz. Individuals born preterm were also more likely to reach natural menopause at an earlier age (adjusted β=-0.506, SE = 0.16, P = 0.001) and have a shorter reproductive window (adjusted β = -0.418, SE = 0.17, p < 0.006). CONCLUSIONS: These findings raise concerns that, as more preterm and low birthweight individuals survive to adulthood, the prevalence of earlier-onset menarche and menopause may increase. Clinical counseling and interventions aimed at reducing the incidence of preterm and low birthweight births, as well as intensification of lifestyle modifications to reduce CVD risk among women with these early-life risk factors, should be prioritized.

The effect of calcium plus vitamin D (CaD) supplementation on risk of ductal carcinoma in situ (DCIS) of the breast, a nonobligate precursor of invasive ductal carcinoma, is not well understood. In this secondary analysis, we examined this association in the Women's Health Initiative CaD trial over approximately 20 years of follow-up. A total of 36 282 cancer-free postmenopausal women (50-79 years) were randomly assigned to daily (d) calcium (1000 mg) plus vitamin D (400 IU) supplementation or to a placebo. Personal supplementation with vitamin D (≤600 IU/d, subsequently raised to 1000 IU/d) and calcium (≤1000 mg/d) was allowed. The intervention phase (median = 7.1 years), was followed by a postintervention phase (additional 13.8 years), which included 86.0% of the surviving women. A total of 595 incident DCIS cases were ascertained. Hazard ratios (HRs) plus 95% confidence intervals (CIs) were calculated. The intervention group had a lower risk of DCIS throughout follow-up (HR = 0.82, 95% CI = 0.70 to 0.96) and during the postintervention phase (HR = 0.76, 95% CI = 0.61 to 0.94). The group that used CaD personal supplements in combination with the trial intervention had a lower risk of DCIS compared with the trial placebo group that did not use personal supplementation (HR = 0.72, 95% CI = 0.56 to 0.91). CaD supplementation in postmenopausal women was associated with reduced risk of DCIS, raising the possibility that consistent use of these supplements might provide long-term benefits for the prevention of DCIS.

Background

This post hoc analysis determined if the Women's Health Initiative (WHI) Diet Modification intervention (DM-I) resulted in a significantly different rate of incident hypertension (HTN), as well as longitudinal changes in blood pressure.

Methods

Participants were 48,835 postmenopausal women aged 50-79 years who were randomly assigned to either the intervention or comparison group. HTN was defined as self-report of treated HTN collected semiannually or blood pressure ≥140/90mm Hg at one of the annual follow-up clinic visits.

Results

After a mean follow-up of 8.3 years, and among those who did not have HTN at baseline (n = 31,146), there were 16,174 (51.9%) HTN cases and those assigned to the intervention group had a 4% lower overall risk of developing incident HTN (hazard ratio (HR): 0.96, 95% confidence interval (CI): 0.93-0.99). Although the risk of HTN was lower in the DM-I group in the first few years, the HR became greater than 1 after year 5 (P-trend < 0.01). Similarly, randomization to the DM-I arm resulted in a small but significantly lower average systolic blood pressure (SBP) at 1 year of follow-up (-0.66mm Hg, 0.44-0.89) that increased over the following 8 years (0.16mm Hg/year, 0.11-0.21), such that any early benefit was eliminated by year 5 and a minimal deleterious effect emerged by year 7.

Conclusion

Randomization to an intensive behavioral dietary modification program aimed at a lower total fat intake is not associated with sustained reductions in blood pressure or risk of HTN in postmenopausal women.

Clinical trial registration

url http://www.clinicaltrials.gov, unique identifier nct00000611.

Objectives

To examine prestroke lifestyle factors associated with poststroke mortality and recovery in older women.

Design

Longitudinal prospective cohort study.

Setting

The Women's Health Initiative (WHI, clinical trials and observational study), 40 clinical centers in the United States.

Participants

WHI participants, women aged 50 to 79, who were stroke-free at baseline (1993/98), with incident stroke before 2005.

Measurements

Participants were followed for mortality through 2010. Prestroke characteristics were from the last examination before the stroke event. Annual follow-up for clinical events ascertained hospitalization for stroke that was subsequently physician adjudicated with medical records. Multivariable regression models were used to analyze factors associated with poststroke mortality and poststroke recovery at hospital discharge (poststroke Glasgow score), adjusting for stroke type.

Results

Of 3,173 women with incident stroke, 1,111 (35%) died. Individuals who were overweight or obese before stroke had lower poststroke mortality than those who were normal weight (obese: hazard ratio (HR) = 0.69, 95% confidence interval (CI) = 0.53-0.88; overweight: HR = 0.72, 95% CI = 0.58-0.90); individuals who were underweight before stroke had nonsignificantly greater poststroke mortality (HR = 2.02, 95% CI = 0.98-4.16, P = .06). Other prestroke factors associated with poststroke mortality included diabetes mellitus (HR = 1.28, 95% CI = 1.01-1.64), current smoking (vs nonsmoker, HR = 2.13, 95% CI = 1.53-3.00), physical inactivity (vs >150 min of exercise per week, HR = 1.39, 95% CI = 1.09-1.78), and lowest physical function quartile (vs highest, HR = 1.54, 95% CI = 1.18-2.02). Prestroke diabetes mellitus was associated with lower odds of good recovery after stroke (odds ratio (OR) = 0.60, 95% CI = 0.44-0.82). Current hormone use before stroke was associated with greater odds of moderate than of severe disability after stroke (OR = 1.29, 95% CI = 1.00-1.66).

Conclusion

Potentially modifiable factors before stroke, including smoking, diabetes mellitus, and being underweight, were associated with greater poststroke mortality in older women. Being overweight or obese and physical activity before stroke were associated with lower poststroke mortality in older women.

BACKGROUND: High sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups. METHODS: Depressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-<3 mg/L, intermediate; ≥ 3mg/L, high). RESULTS: Mean CES-D, STAI scores, and hsCRP levels were 7.0 (SD = 5.9), 17.0 (SD = 5.7), and 3.84 (SD = 7.85), respectively. Generalized linear modeling, adjusted for sociodemographic characteristics revealed significant associations between depression (exp(β) = 1.12; p<0.01) and anxiety symptoms (exp(β) = 1.10; p<0.05) with continuous hsCRP levels. For categorical values of hsCRP, one SD increase in CES-D and STAI scores was associated with a 10% and 8% increase in the RRRs of high vs. low hsCRP, respectively. However, these relationships between CES-D or STAI and hsCRP were no longer statistically significant after adjustment for CVD risk factors and medications. CONCLUSION: We found modest associations between anxiety and depressive symptoms and systemic inflammation measured by hsCRP among diverse Hispanics/Latinos that did not appreciably differ between heritage groups.