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1.  Obesity and Survival to Age 85 Years without Major Disease or Disability in Older Women 
JAMA internal medicine  2014;174(1):98-106.
Context
The impact of obesity on late-age survival without disease or disability in women is unknown.
Objective
To investigate if higher baseline body mass index and waist circumference affects women’s survival to age 85 years without major chronic disease (coronary disease, stroke, cancer, diabetes, or hip fracture) and mobility disability.
Design, Setting, Participants
Examination of 36,611 women from the Women’s Health Initiative who could have reached age 85 years or older if they survived to the last outcomes evaluation on September 17, 2012. Recruitment was from 40 US Clinical Centers from October 1993–December 1998. Multinomial logistic regression models were used to estimate odds ratios and 95% confidence intervals for the association of baseline body mass index and waist circumference with the outcomes, adjusting for demographic, behavioral, and health characteristics.
Main Outcome Measures
Mutually-exclusive classifications: 1) survived without major chronic disease and without mobility disability (“healthy”); 2) survived with ≥1 major chronic disease at baseline, but without new disease or disability (“prevalent diseased”); 3) survived and developed ≥1 major chronic disease but not disability during study follow-up (“incident diseased”); 4) survived and developed mobility disability with or without disease (“disabled”); and 5) did not survive (“died”).
Results
Mean (SD) baseline age was 72.4 (3.0) years (range: 66–81). The distribution of women classified as healthy, prevalent diseased, incident diseased, disabled, and died was 19%, 15%, 23%, 18%, and 25%, respectively. Compared to normal-weight women, underweight and obese women were more likely to die before age 85 years. Overweight and obese women had higher risks of incident disease and mobility disability. Disability risks were striking. Relative to normal-weight women, adjusted odds ratios (95% confidence intervals) of mobility disability was 1.6 (1.5–1.8) for overweight women and 3.2 (2.9–3.6), 6.6 (5.4–8.1), and 6.7 (4.8–9.2), for class I, II, and III obesity, respectively. Waist circumference >88 centimeters was also associated with higher risk of earlier death, incident disease, and mobility disability.
Conclusions
Overall and abdominal obesity were important and potentially modifiable factors associated with dying or developing mobility disability and major chronic disease before age 85 years in older women.
doi:10.1001/jamainternmed.2013.12051
PMCID: PMC3963496  PMID: 24217806
2.  Change in physical activity after a diabetes diagnosis: opportunity for intervention 
Introduction
Moderate intensity physical activity is recommended for individuals with diabetes to control glucose and prevent diabetes-related complications. The extent to which a diabetes diagnosis motivates patients to increase physical activity is unclear. This study used data from the Women’s Health Initiative Observational Study (baseline data collected from 1993-1998) to examine change in physical activity and sedentary behavior in women who reported a diabetes diagnosis compared to women who did not report diabetes over 7 years of follow-up (up to 2005).
Methods
Participants (n=84,300) were post-menopausal women who did not report diabetes at baseline [mean age=63.49; standard deviation (SD)=7.34; mean BMI=26.98 kg/m2; SD=5.67]. Linear mixed model analyses were conducted adjusting for study year, age, race/ethnicity, BMI, education, family history of diabetes, physical functioning, pain, energy/fatigue, social functioning, depression, number of chronic diseases and vigorous exercise at age 18. Analyses were completed in August 2012.
Results
Participants who reported a diabetes diagnosis during follow-up were more likely to report increasing their total physical activity (p=0.002), walking (p<0.001) and number of physical activity episodes (p<0.001) compared to participants who did not report a diabetes diagnosis. On average, participants reporting a diabetes diagnosis reported increasing their total physical activity by 0.49 MET-hours/week, their walking by 0.033 MET-hours/week and their number of physical activity episodes by 0.19 MET-hours/week. No differences in reported sedentary behavior change were observed (p=0.48).
Conclusion
A diabetes diagnosis may prompt patients to increase physical activity. Healthcare professionals should consider how best to capitalize on this opportunity to encourage increased physical activity and maintenance.
doi:10.1249/MSS.0b013e3182a33010
PMCID: PMC4028702  PMID: 23860414
type 2 diabetes; exercise; sedentary behavior; sedentary activity; Women’s Health Initiative
3.  All-Cause, Cardiovascular, and Cancer Mortality Rates in Postmenopausal White, Black, Hispanic, and Asian Women With and Without Diabetes in the United States 
American Journal of Epidemiology  2013;178(10):1533-1541.
Using data from the Women's Health Initiative (1993–2009; n = 158,833 participants, of whom 84.1% were white, 9.2% were black, 4.1% were Hispanic, and 2.6% were Asian), we compared all-cause, cardiovascular, and cancer mortality rates in white, black, Hispanic, and Asian postmenopausal women with and without diabetes. Cox proportional hazard models were used for the comparison from which hazard ratios and 95% confidence intervals were computed. Within each racial/ethnic subgroup, women with diabetes had an approximately 2–3 times higher risk of all-cause, cardiovascular, and cancer mortality than did those without diabetes. However, the hazard ratios for mortality outcomes were not significantly different between racial/ethnic subgroups. Population attributable risk percentages (PARPs) take into account both the prevalence of diabetes and hazard ratios. For all-cause mortality, whites had the lowest PARP (11.1, 95% confidence interval (CI): 10.1, 12.1), followed by Asians (12.9, 95% CI: 4.7, 20.9), blacks (19.4, 95% CI: 15.0, 23.7), and Hispanics (23.2, 95% CI: 14.8, 31.2). To our knowledge, the present study is the first to show that hazard ratios for mortality outcomes were not significantly different between racial/ethnic subgroups when stratified by diabetes status. Because of the “amplifying” effect of diabetes prevalence, efforts to reduce racial/ethnic disparities in the rate of death from diabetes should focus on prevention of diabetes.
doi:10.1093/aje/kwt177
PMCID: PMC3888272  PMID: 24045960
diabetes; health disparities; menopause; mortality; obesity; women's health
4.  Modifying effect of obesity on the association between sitting time and incident diabetes in post-menopausal women 
Obesity (Silver Spring, Md.)  2013;22(4):1133-1141.
Objective
To evaluate the association between self-reported daily sitting time and the incidence of type II diabetes in a cohort of postmenopausal women.
Design and Methods
Women (N = 88,829) without diagnosed diabetes reported the number of hours spent sitting over a typical day. Incident cases of diabetes were identified annually by self-reported initiation of using oral medications or insulin for diabetes over 14.4 years follow-up.
Results
Each hour of sitting time was positively associated with increased risk of diabetes (Risk ratio (RR): 1.05; 95% confidence interval (CI): 1.02–1.08]. However, sitting time was only positively associated with incident diabetes in obese women. Obese women reporting sitting 8–11 (RR: 1.08; 95% CI 1.0–1.1), 12–15 (OR: 1.13; 95% CI 1.0–1.2), and ≥16 hours (OR: 1.25; 95% CI 1.0–1.5) hours per day had an increased risk of diabetes compared to women sitting ≤ 7 hours per day. These associations were adjusted for demographics, health conditions, behaviors (smoking, diet and alcohol intake) and family history of diabetes. Time performing moderate to vigorous intensity physical activity did not modify these associations.
Conclusion
Time spent sitting was independently associated with increased risk of diabetes diagnosis among obese women— a population already at high risk of the disease.
doi:10.1002/oby.20620
PMCID: PMC3968183  PMID: 24123945
sedentary; glucose control; overweight; glycemia
5.  Obesity, Physical Activity, and Their Interaction in Incident Atrial Fibrillation in Postmenopausal Women 
Background
Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased risk of stroke and death. Obesity is an independent risk factor for AF, but modifiers of this risk are not well known. We studied the roles of obesity, physical activity, and their interaction in conferring risk of incident AF.
Methods and Results
The Women's Health Initiative (WHI) Observational Study was a prospective observational study of 93 676 postmenopausal women followed for an average of 11.5 years. Incident AF was identified using WHI‐ascertained hospitalization records and diagnostic codes from Medicare claims. A multivariate Cox's hazard regression model adjusted for demographic and clinical risk factors was used to evaluate the interaction between obesity and physical activity and its association with incident AF. After exclusion of women with prevalent AF, incomplete data, or underweight body mass index (BMI), 9792 of the remaining 81 317 women developed AF. Women were, on average, 63.4 years old, 7.8% were African American, and 3.6% were Hispanic. Increased BMI (hazard ratio [HR], 1.12 per 5‐kg/m2 increase; 95% confidence interval [CI], 1.10 to 1.14) and reduced physical activity (>9 vs. 0 metabolic equivalent task hours per week; HR, 0.90; 95% CI, 0.85 to 0.96) were independently associated with higher rates of AF after multivariate adjustment. Higher levels of physical activity reduced the AF risk conferred by obesity (interaction P=0.033).
Conclusions
Greater physical activity is associated with lower rates of incident AF and modifies the association between obesity and incident AF.
doi:10.1161/JAHA.114.001127
PMCID: PMC4310412  PMID: 25142057
atrial fibrillation; electrophysiology; epidemiology; exercise; obesity
6.  The Relationship of Sedentary Behavior and Physical Activity to Incident Cardiovascular Disease: Results from the Women’s Health Initiative 
Objectives
The aim was to examine the independent and joint associations of sitting time and physical activity with risk of incident cardiovascular disease (CVD).
Background
Sedentary behavior is recognized as a distinct construct beyond lack of leisure-time physical activity, but limited data exists on the interrelationship between these two components of energy balance.
Methods
Participants in the prospective Women’s Health Initiative Observational Study (N = 71,018), aged 50–79 and free of CVD at baseline (1993–1998), provided information on sedentary behavior, defined as hours of sitting per day, and usual physical activity at baseline and during follow-up through September 2010. First CVD (coronary heart disease or stroke) events were centrally adjudicated.
Results
Sitting ≥ 10 hours/day compared to ≤ 5 hours/day was associated with increased CVD risk (HR=1.18, 95% CI 1.09, 1.29) in multivariable models including physical activity. Low physical activity was also associated with higher CVD risk (P, trend <0.001). When women were cross-classified by sitting time and physical activity (P, interaction = 0.94), CVD risk was highest in inactive women (≤1.7 MET-hrs/week) who also reported ≥10 hrs/day of sitting. Results were similar for CHD and stroke when examined separately. Associations between prolonged sitting and risk of CVD were stronger in overweight versus normal weight women and women aged 70 years and older compared to younger women.
Conclusions
Prolonged sitting time was associated with increased CVD risk, independent of leisure-time physical activity, in postmenopausal women without a history of CVD. A combination of low physical activity and prolonged sitting augments CVD risk.
doi:10.1016/j.jacc.2013.03.031
PMCID: PMC3676694  PMID: 23583242
cardiovascular disease; women; physical activity; sedentary behavior
7.  Statins, Angiotensin-Converting Enzyme Inhibitors and Physical Performance in Older Women 
OBJECTIVES
Angiotensin-converting enzyme (ACE) inhibitor and statin medications may preserve skeletal muscle. We examined associations between each medication class and baseline and mean annual change in physical performance measures and muscle strength in older women.
DESIGN
Prospective cohort study
PARTICIPANTS
Participants from the Women’s Health Initiative Clinical Trials who were aged 65–79 at baseline and had physical performance measures, self-report of health insurance and no prior history of stroke or congestive heart failure were included (n=5777). Women were recruited between 1993 and 1998.
MEASUREMENTS
Medication use was ascertained through a baseline inventory. Physical performance measures (timed 6-meter walk, repeated chair stands in 15 seconds) and grip strength were assessed at baseline and follow-up years 1, 3 and 6. Multivariable adjusted linear repeated- measures models adjusted for demographic and health characteristics.
RESULTS
ACE inhibitor use was negatively associated with mean grip strength at baseline (22.40 kg, 95% confidence interval [CI] 21.89, 22.91 versus 23.18 kg, 95% CI 23.02, 23.34; P = .005) and a greater mean annual change in number of chair stands (−.182, 95% CI −.217, −.147 versus −.145, 95% CI −.156, −.133; P = .05) compared to non-use. Statin use was not significantly associated with baseline or mean annual change for any outcome. A subgroup analysis suggested that statin use was associated with less mean annual change in chair stands (P = .006) in the oldest women.
CONCLUSION
These results do not support an association of statin or ACE inhibitor use with slower decline in physical performance or muscle strength, and thus do not support the use of these medications for preserving functional status in older adults.
doi:10.1111/jgs.12029
PMCID: PMC3521070  PMID: 23176078
ACE inhibitors; statins; physical performance; grip strength
8.  Associations between smoking and tooth loss according to reason for tooth loss 
Background
Smoking is associated with tooth loss. However, smoking's relationship to the specific reason for tooth loss in postmenopausal women is unknown.
Methods
Postmenopausal women (n = 1,106) who joined a Women's Health Initiative ancillary study (The Buffalo OsteoPerio Study) underwent oral examinations for assessment of the number of missing teeth, as well as the self-reported reasons for tooth loss. The authors obtained information about smoking status via a self-administered questionnaire. The authors calculated odds ratios (ORs) and 95 percent confidence intervals (CIs) by means of logistic regression to assess smoking's association with overall tooth loss, as well as with tooth loss due to periodontal disease (PD) and with tooth loss due to caries.
Results
After adjusting for age, education, income, body mass index (BMI), history of diabetes diagnosis, calcium supplement use and dental visit frequency, the authors found that heavy smokers (≥ 26 pack-years) were significantly more likely to report having experienced tooth loss compared with never smokers (OR = 1.82; 95 percent CI, 1.10-3.00). Smoking status, packs smoked per day, years of smoking, pack-years and years since quitting smoking were significantly associated with tooth loss due to PD. For pack-years, the association for heavy smokers compared with that for never smokers was OR = 6.83 (95 percent CI, 3.40-13.72). The study results showed no significant associations between smoking and tooth loss due to caries.
Conclusions and Practical Implications
Smoking may be a major factor in tooth loss due to PD. However, smoking appears to be a less important factor in tooth loss due to caries. Further study is needed to explore the etiologies by which smoking is associated with different types of tooth loss. Dentists should counsel their patients about the impact of smoking on oral health, including the risk of tooth loss due to PD.
PMCID: PMC3842224  PMID: 23449901
Tooth loss; periodontal diseases; caries; smoking; menopause; women's health
9.  Determinants of Racial/Ethnic Disparities in Incidence of Diabetes in Postmenopausal Women in the U.S. 
Diabetes Care  2012;35(11):2226-2234.
OBJECTIVE
To examine determinants of racial/ethnic differences in diabetes incidence among postmenopausal women participating in the Women’s Health Initiative.
RESEARCH DESIGN AND METHODS
Data on race/ethnicity, baseline diabetes prevalence, and incident diabetes were obtained from 158,833 women recruited from 1993–1998 and followed through August 2009. The relationship between race/ethnicity, other potential risk factors, and the risk of incident diabetes was estimated using Cox proportional hazards models from which hazard ratios (HRs) and 95% CIs were computed.
RESULTS
Participants were aged 63 years on average at baseline. The racial/ethnic distribution was 84.1% non-Hispanic white, 9.2% non-Hispanic black, 4.1% Hispanic, and 2.6% Asian. After an average of 10.4 years of follow-up, compared with whites and adjusting for potential confounders, the HRs for incident diabetes were 1.55 for blacks (95% CI 1.47–1.63), 1.67 for Hispanics (1.54–1.81), and 1.86 for Asians (1.68–2.06). Whites, blacks, and Hispanics with all factors (i.e., weight, physical activity, dietary quality, and smoking) in the low-risk category had 60, 69, and 63% lower risk for incident diabetes. Although contributions of different risk factors varied slightly by race/ethnicity, most findings were similar across groups, and women who had both a healthy weight and were in the highest tertile of physical activity had less than one-third the risk of diabetes compared with obese and inactive women.
CONCLUSIONS
Despite large racial/ethnic differences in diabetes incidence, most variability could be attributed to lifestyle factors. Our findings show that the majority of diabetes cases are preventable, and risk reduction strategies can be effectively applied to all racial/ethnic groups.
doi:10.2337/dc12-0412
PMCID: PMC3476929  PMID: 22833490
10.  Association between Annual Visit-to-Visit Blood Pressure Variability and Stroke in Postmenopausal Women: Data from the Women's Health Initiative 
Hypertension  2012;60(3):625-630.
Accumulating evidence suggests that increased visit-to-visit variability (VVV) of blood pressure is associated with stroke. No study has examined the association between VVV of blood pressure and stroke in postmenopausal women, and scarce data exists as to whether this relation is independent of the temporal trend of blood pressure. We examined the association of VVV of blood pressure with stroke in 58,228 postmenopausal women enrolled in the Women's Health Initiative. Duplicate blood pressure readings, which were averaged, were taken at baseline and at each annual visit. VVV was defined as the standard deviation about the participant's mean systolic blood pressure (SBP) across visits (SD), and about the participant's regression line with SBP regressed across visits (SDreg). Over a median follow-up of 5.4 years, 997 strokes occurred. In an adjusted model including mean SBP over time, the hazard ratios (95% CI) of stroke for higher quartiles of SD of SBP compared to the lowest quartile (referent) were 1.39 (1.03-1.89) for quartile 2, 1.52 (1.13-2.03) for quartile 3, and 1.72 (1.28-2.32) for quartile 4 (P trend<0.001). The relation was similar for SDreg of SBP quartiles in a model that additionally adjusted for the temporal trend in SBP (P trend<0.001). The associations did not differ by stroke type (ischemic vs. hemorrhagic). There was a significant interaction between mean SBP and SDreg on stroke with the strongest association seen below 120 mmHg. In postmenopausal women, greater VVV of SBP was associated with increased risk of stroke, particularly in the lowest range of mean SBP.
doi:10.1161/HYPERTENSIONAHA.112.193094
PMCID: PMC3427141  PMID: 22753206
hypertension; blood pressure; stroke; postmenopause; women
11.  Plasma 25-hydroxyvitamin D concentrations and periodontal disease in postmenopausal women 
Journal of periodontology  2012;84(9):1243-1256.
Background
Vitamin D has anti-inflammatory and anti-microbial properties that, together with its influence on bone health, may confer periodontal benefit.
Methods
We investigated cross-sectional associations (1997–2000) between plasma 25-hydroxyvitamin D concentrations [25(OH)D] and periodontal measure among 920 postmenopausal women. Chronic measures of disease were defined based on: 1) alveolar crestal height (ACH) measures from intraoral radiographs and tooth loss, and the 2) Center for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) criteria using measures of clinical attachment level (CAL) and probing pocket depth (PD). Acute oral inflammation was assessed by the % of gingival sites that bled upon assessment with a probe. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for periodontal disease among participants with adequate ([25(OH)D]≥50 nmol/L) compared to deficient/inadequate ([25(OH)D]<50 nmol/L) vitamin D status adjusted for age, dental visit frequency, and body mass index.
Results
No association was observed between vitamin D status and periodontal disease defined by ACH and tooth loss (adjusted OR=0.96, 95% CI: 0.68–1.35). In contrast, women with adequate compared to deficient/inadequate vitamin D status had a 33% lower odds (95% CI: 5%–53%) of periodontal disease defined using the CDC/AAP definition and a 42% lower odds (95% CI: 21%-58%) of having ≥50% of gingival sites that bled.
Conclusion
Vitamin D status was inversely associated with gingival bleeding, an acute measure of oral health and inflammation and inversely associated with clinical categories of chronic periodontal disease that incorporated PD, an indicator of oral inflammation. However, vitamin D was not associated with chronic periodontal disease based on measures of ACH in combination with tooth loss.
doi:10.1902/jop.2012.120445
PMCID: PMC3745794  PMID: 23259413
vitamin D; 25-hydroxyvitamin D; periodontal diseases; postmenopausal period; epidemiology; women
12.  Health Benefits of Gastric Bypass Surgery after 6 Years 
Context
Extreme obesity is associated with health and cardiovascular disease risks. Although gastric bypass surgery induces rapid weight loss and ameliorates many of these risks in the short term, long-term outcomes are uncertain.
Objective
To examine the association of Roux-en-Y gastric bypass (RYGB) with weight loss, diabetes mellitus, and other health risks 6 years after surgery.
Design, Setting, and Participants
A prospective Utah-based study conducted between July 2000 and June 2011 of 1156 severely obese (body mass index [BMI] ≥35) participants aged 18–72 years (82% women; mean BMI 45.9; 95% CI, 31.2–60.6) who sought and received RYGB surgery (n=418), sought but did not have surgery (n=417; control group 1), or were randomly selected from a population-based sample not seeking weight loss surgery (n=321; control group 2).
Main Outcome Measures
Weight loss, diabetes, hypertension, dyslipidemia, and health-related quality of life were compared between participants having RYGB surgery and control participants using propensity score adjustment.
Results
Six years after surgery, patients who received RYGB surgery (with 92.6% follow-up) lost 27.7% (95% CI, 26.6%–28.9%) of their initial body weight compared with 0.2% (95% CI, -1.1% to 1.4%) gain in control group 1 and 0% (95% CI, −1.2 to 1.2%) in control group 2. Weight loss maintenance was superior in patients who received RYGB surgery, with 94% (95% CI, 92%–96%) and 76% (95% CI, 72%–81%) of patients receiving RYGB surgery maintaining at least 20% weight loss 2 and 6 years after surgery, respectively. Diabetes remission rates 6 years after surgery were 62% (95% CI, 49%–75%) in the RYGB surgery group, 8% (95% CI, 0%–16%) in control group 1, and 6% (95% CI, 0%–13%) in control group 2, with remission odds ratios (ORs) of 16.5 (95% CI, 4.7–57.6; P<.001) vs control group 1 and 21.5 (95% CI, 5.4–85.6; P<.001) vs control group 2. The incidence of diabetes throughout the course of the study was reduced after RYGB surgery (2%; 95% CI, 0%–4%; versus 17%; 95% CI, 10%–24%; OR, 0.11; 95% CI, 0.04–0.34 compared with control group 1 and 15%; 95% CI, 9%–21%; OR, 0.21; 95% CI, 0.06–0.67 compared with control group 2; both P<.001). The numbers of participants with bariatric surgery-related hospitalizations were 33 (7.9%), 13 (3.9%), and 6 (2.0%) for RYGB surgery group and 2 control groups, respectively.
Conclusion
Among severely obese patients, compared with nonsurgical control patients, the use of RYGB surgery was associated with higher rates of diabetes remission and lower risk of cardiovascular and other health outcomes over 6 years.
doi:10.1001/2012.jama.11164
PMCID: PMC3744888  PMID: 22990271
13.  Cardiorespiratory Fitness and Health-Related Quality of Life in Bariatric Surgery Patients 
Obesity surgery  2011;21(4):457-464.
Background
Health-Related Quality of Life (HRQOL) is impaired in severely obese individuals presenting for bariatric surgery. Little is known about the relationship between cardiorespiratory fitness (CRF) and HRQOL in these individuals. We hypothesized that better HRQOL would be reported by those with higher CRF.
Methods
In 326 gastric bypass patients (mean BMI = 46.5 ± 7.0; mean age = 40.9 ± 10.1; 83.4 % female), pre-surgical CRF was quantified as duration (minutes) of a submaximal treadmill test to 80% of age-predicted maximal heart rate (MHR). Patients completed both a general measure of HRQOL [the Medical Outcome Short-Form 36 (SF-36)] and a weight-specific measure of HRQOL [Impact of Weight on Quality of Life-Lite (IWQOL-Lite)]. Mean HRQOL scores were examined, controlling for age, gender, and BMI.
Results
Mean treadmill duration was 9.9 ± 3.1 minutes, and percent age-predicted MHR was 81.2 ± 3.0 percent. Higher cardiorespiratory fitness tended to be associated with better physical and weight-specific HRQOL. Adjustment for differences in gender, age, and BMI attenuated the significance of associations between fitness and physical measures from the SF-36, whereas adjustment eliminated significance of associations between fitness and weight-specific HRQOL in most cases.
Conclusions
Results suggest that CRF confers some HRQOL benefits in severely obese adults, though these benefits may largely be explained by differences in age, gender, and BMI.
doi:10.1007/s11695-010-0261-5
PMCID: PMC3718563  PMID: 20820940
cardiorespiratory fitness; health-related quality of life; IWQOL-Lite; SF-36; gastric bypass surgery; treadmill test
14.  Predicting sleep apnea in bariatric surgery patients 
Background
Because of the high prevalence and potentially serious complications of obstructive sleep apnea (OSA) in obese individuals, several prediction models have been developed to detect moderate-to-severe OSA in patients undergoing bariatric surgery. Using commonly collected variables (body mass index [BMI], age, observed sleep apnea, hemoglobin A1c, fasting plasma insulin, gender, and neck circumference), Dixon et al. developed a model with a sensitivity of 89% and specificity of 81% for patients undergoing laparoscopic adjustable gastric band surgery suspected to have OSA. The present study evaluated the prediction model of Dixon et al. in 310 gastric bypass patients (mean BMI 46.8 kg/m2, age 41.6 years, 84.5% women), with no preselection for OSA symptoms in a bariatric surgery partnership.
Methods
The patients underwent overnight limited polysomnography to determine the presence and severity of OSA as measured using the apnea-hypopnea index.
Results
Of the 310 patients, 44.2% had moderate-to-severe OSA (apnea-hypopnea index ≥15/h). Most variables in the Dixon model were associated with a greater prevalence of OSA. The sensitivity (75%) and specificity (57%) for the model-based classification of OSA were considerably lower in the present sample than originally reported. An alternate prediction model identified 10 unique predictors of OSA. The presence of ≥5 of these predictors modestly improved the sensitivity (77%) and greatly improved the specificity (77%) in predicting an apnea-hypopnea index of ≥15/h. When applied to the validation sample, the sensitivity (76%) and specificity (72%) were essentially the same.
Conclusion
Although the Dixon model and our model included overlapping predictors (BMI, gender, age, neck circumference), when applied in our sample of gastric bypass patients, neither model achieved the sensitivity and specificity for predicting OSA previously reported by Dixon et al.
doi:10.1016/j.soard.2011.04.226
PMCID: PMC3713768  PMID: 21684219
Sleep apnea; Prediction; Bariatric surgery
15.  Intraindividual variation in plasma 25-hydroxyvitamin D measures 5 years apart among postmenopausal women 
Background
Current literature examining associations between vitamin D and chronic disease generally use a single assessment of 25-hydroxyvitamin D (25(OH)D), assuming an individual’s 25(OH)D concentration is consistent over time.
Methods
We investigated the intraindividual variability between two measures of plasma 25(OH)D concentrations collected ~5 years apart (1997-2000 to 2002-2005) in 672 postmenopausal women participating in the Women’s Health Initiative. Plasma 25(OH)D was assessed using the DiaSorin LIAISON® chemiluminescence immunoassay. The within-pair coefficient of variation (CV) was 4.9% using blinded quality control samples. Mean and standard deviations (SD) of 25(OH)D at the two time points were compared using a paired t-test. An intraindividual CV and intra-class correlation coefficient (ICC) were used to assess intraindividual variability. A Spearman correlation coefficient (r) assessed the strength of the association between the two measures and concordance in vitamin D status at two time points
Results
Mean 25(OH)D concentrations (nmol/L) significantly increased over time from 60.0 (SD=22.2) to 67.8 (SD=22.2) (p<0.05). The CV was 24.6%, the ICC (95% Confidence Interval (CI)) was 0.59 (0.54-0.64), and the Spearman r was 0.61 (95% CI=0.56-0.66). Greater concordance over 5 years was observed in participants with sufficient compared to deficient or inadequate baseline 25(OH)D concentrations (weighted kappa=0.39). Reliability measures were moderately influenced by season of blood draw and vitamin D supplement use.
Conclusion
There is moderate intraindividual variation in 25(OH)D concentrations over approximately 5 years.
Impact
These data support the use of a one-time measure of blood 25(OH)D in prospective studies with ≤ 5 years of follow-up.
doi:10.1158/1055-9965.EPI-12-0026
PMCID: PMC3372646  PMID: 22523182
25-hydroxyvitamin D; intraindividual variation; vitamin D; biomarkers; postmenopausal women
16.  Performance of Multiplex Cytokine Assays in Serum and Saliva among Community-Dwelling Postmenopausal Women 
PLoS ONE  2013;8(4):e59498.
Multiplexing arrays increase the throughput and decrease sample requirements for studies employing multiple biomarkers. The goal of this project was to examine the performance of Multiplex arrays for measuring multiple protein biomarkers in saliva and serum. Specimens from the OsteoPerio ancillary study of the Women’s Health Initiative Observational Study were used. Participants required the presence of at least 6 teeth and were excluded based on active cancer and certain bone issues but were not selected on any specific condition. Quality control (QC) samples were created from pooled serum and saliva. Twenty protein markers were measured on five multiplexing array panels. Sample pretreatment conditions were optimized for each panel. Recovery, lower limit of quantification (LLOQ) and imprecision were determined for each analyte. Statistical adjustment at the plate level was used to reduce imprecision estimates and increase the number of usable observations. Sample pre-treatment improved recovery estimates for many analytes. The LLOQ for each analyte agreed with manufacturer specifications except for MMP-1 and MMP-2 which were significantly higher than reported. Following batch adjustment, 17 of 20 biomarkers in serum and 9 of 20 biomarkers in saliva demonstrated acceptable precision, defined as <20% coefficient of variation (<25% at LLOQ). The percentage of cohort samples having levels within the reportable range for each analyte varied from 10% to 100%. The ratio of levels in saliva to serum varied from 1∶100 to 28∶1. Correlations between saliva and serum were of moderate positive magnitude and significant for CRP, MMP-2, insulin, adiponectin, GM-CSF and IL-5. Multiplex arrays exhibit high levels of analytical imprecision, particularly at the batch level. Careful sample pre-treatment can enhance recovery and reduce imprecision. Following statistical adjustments to reduce batch effects, we identified biomarkers that are of acceptable quality in serum and to a lesser degree in saliva using Multiplex arrays.
doi:10.1371/journal.pone.0059498
PMCID: PMC3618114  PMID: 23577067
17.  Duration of Physical Activity and Serum 25-hydroxyvitamin D Status of Postmenopausal Women 
Annals of epidemiology  2011;21(6):440-449.
Purpose
To investigate whether the association between physical activity and serum 25-hydroxyvitamin D (25(OH)D) concentrations is independent of sun exposure, body size, and other potential explanatory variables.
Methods
Using data from a sample of 1,343 postmenopausal women, from the Women’s Health Initiative, linear regression was used to examine the associations of duration (minutes/week) of recreational activity and of yard work with 25(OH)D concentrations (nmol/L).
Results
In age-adjusted analyses, positive associations were observed between 25(OH)D concentrations and both duration of recreational physical activity (β=0.71, SE(0.09), P<0.001) and yard work (β=0.36, SE(0.10), P=0.004). After further adjustment for vitamin D intake, self-reported sunlight exposure, waist circumference, and season of blood draw, 25(OH)D was significantly associated with recreational activity (β=0.21, SE(0.09), P=0.014) but not with yard work (β=0.18, SE(0.09), P=0.061). Interactions were observed between season and both recreational activity (Pinteraction=0.082) and yard work (Pinteraction=0.038) such that these activity-25(OH)D associations were greater during summer/fall compared to winter/spring. Self-reported sunlight exposure and measures of body size did not modify the associations.
Conclusion
The observed age-adjusted activity-25(OH)D associations were attenuated after adjusting for explanatory variables and were modified by season of blood draw. Adopting a lifestyle that incorporates outdoor physical activity during summer/fall, consuming recommended amounts of vitamin D, and maintaining a healthy weight may improve or maintain vitamin D status in postmenopausal women.
doi:10.1016/j.annepidem.2010.11.011
PMCID: PMC3090482  PMID: 21414803
25-hydroxyvitamin D; vitamin D; serum; sunlight exposure; physical activity; epidemiology; women
18.  SHORT SLEEP DURATION IS ASSOCIATED WITH THE DEVELOPMENT OF IMPAIRED FASTING GLUCOSE: THE WESTERN NEW YORK HEALTH STUDY 
Annals of epidemiology  2010;20(12):883-889.
Purpose
To examine whether sleep duration was associated with incident impaired fasting glucose (IFG) over six years of follow-up in the Western New York Health Study.
Methods
Participants (n= 1,455, 68% response rate) who were free of type 2 diabetes and known cardiovascular disease at baseline (1996-2001) were reexamined in 2003-2004. A nested case-control study was conducted. Cases had fasting plasma glucose (FPG) < 100 mg/dl at baseline and 100 to 125 mg/dl at follow-up: controls (n=272) had FPG <100 mg/dl at both exams. Cases (n=91) were individually matched to three controls (n=272) on sex, race, and year of study enrollment. Average sleep duration was categorized as short < 6h, mid-range 6 to 8h, and long-sleep > 8h.
Results
In multivariate conditional logistic regression after adjustment for several diabetes risk factors the Odds Ratio (OR) of IFG among short sleepers was 3.0 (95% CI 1.05, 8.59) compared to mid-range sleepers. There was no association between long sleep and IFG: OR 1.6 (95% CI: 0.45.-5.42). Adjustment for insulin resistance attenuated the association only among short sleepers OR 2.5 (95% CI: 0.83, 7.46).
Conclusion
Short sleep duration was associated with an elevated risk of IFG. Insulin resistance appears to mediate this association.
doi:10.1016/j.annepidem.2010.05.002
PMCID: PMC2962429  PMID: 20620078
impaired fasting glucose; glucose metabolism; sleep duration; nested case-control study; population-based
19.  Metabolic syndrome and risk of death from cancers of the digestive system 
We tested the hypothesis that risk of early mortality from cancers of the digestive system will be greater in men with, compared to men without, the metabolic syndrome (MetS). Participants were 33,230 men who were seen at the Cooper Clinic in Dallas, Texas and followed for 14.4 (SD=7.0) yrs. MetS was defined as having at least three of the following risk factors: abdominal obesity, fasting hypertriglyceridemia, low high-density lipoprotein cholesterol, high blood pressure, or high fasting glucose level or diabetes. MetS was associated with higher mortality (HR=1.90 [95% Confidence Interval=1.42-2.55]), and there was a graded positive association for the addition of more syndrome components (p < 0.01). Adjustment for cardiorespiratory fitness attenuated the risk estimates by 20 to 30%, but they remained significant following this adjustment. Evaluation of the independent contribution of each of the syndrome components revealed that both abdominal obesity (HR=1.89 [1.36-2.62]) and high glucose (HR=1.38 [1.02-1.87]) were independently associated with cancer mortality. Our results support the hypothesis that MetS is positively associated with mortality from cancers of the digestive system. Interventions which reduce abnormalities associated with the syndrome could reduce risk of premature death from these cancers.
doi:10.1016/j.metabol.2009.11.019
PMCID: PMC2891079  PMID: 20045534
20.  Metabolic Syndrome and Risk of Cancer Mortality in Men 
Background
Metabolic syndrome (MetS) has been linked with an increased risk of developing cancer; however the association between MetS and cancer mortality remains less clear. Little research has focused on pre-cancer risk factors that may affect the outcome of treatment. The purpose of this study was to examine the association between MetS and all-cancer mortality in men.
Methods
The participants included 33,230 men aged 20-88 years who were enrolled in the Aerobics Center Longitudinal Study and free of known cancer at baseline.
Results
At baseline 28% of all the participants had MetS. During an average of 14 years follow-up there were a total of 685 deaths due to cancer. MetS at baseline was associated with a 56% greater age-adjusted risk in cancer mortality.
Conclusion
These data show that MetS is associated with an increased risk of all-cause cancer mortality in men. Based on these findings it is evident that successful interventions should be identified to attenuate the negative effects of MetS.
doi:10.1016/j.ejca.2009.01.031
PMCID: PMC2700189  PMID: 19250819
Insulin resistance; epidemiology; hypertension; obesity; dyslipedemia; lung cancer; colorectal cancer
21.  Health Outcomes of Gastric Bypass Patients Compared to Nonsurgical, Nonintervened Severely Obese 
Obesity (Silver Spring, Md.)  2009;18(1):121-130.
Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight-loss intervention. Three groups of severely obese subjects (N = 1,156, BMI ≥ 35 kg/m2) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population-based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes-related variables, resting metabolic rate (RMR), sleep apnea, and health-related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF-36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux-en-Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight-loss intervention was highly effective for weight loss, improved health-related quality of life, and resolution of major obesity-associated complications measured at 2 years.
doi:10.1038/oby.2009.178
PMCID: PMC2864142  PMID: 19498344
22.  Cardiorespiratory Fitness and Adiposity as Mortality Predictors in Older Adults 
Context
Associations among cardiorespiratory fitness (thus referred to as “fitness”), adiposity, and mortality in older adults have not been adequately examined.
Objectives
To examine these associations, we report on a 12-year follow-up of adults ages 60 years and older, in whom fitness was assessed by a maximal exercise test and adiposity was assessed by body mass index (BMI), waist circumference (WC), and percent body fat.
Design, Setting, and Patients
2603 adults (age 64.4±4.8 yr; 19.8% women) completed a baseline health examination at the Cooper Clinic during 1979-2001. Low fitness was defined as the lowest fifth of the gender-specific distribution of maximal treadmill exercise test duration. The distributions of BMI, WC, and percent body fat were grouped for analysis according to clinical guidelines.
Main Outcome Measures
All-cause mortality.
Results
There were 450 deaths during an average follow-up of 12 years and 31 236 person-years of exposure. Death rates per 1000 person-years, adjusted for age, gender, and examination year were: 13.9, 13.3, 18.3, and 31.8 across BMI groups of 18.5-24.9, 25.0-29.9, 30.0-34.9, and ≥35 kg/m2, respectively (trend P=.01); 13.3 and 18.2 for normal and high WC (≥102 cm in men; ≥88 cm in women), respectively (P=.004); 13.7 and 14.6 for normal and high percent body fat (≥25% in men; ≥30% in women), respectively (P=.51); and 32.6, 16.6, 12.8, 12.3 and 8.1 across incremental fifths of fitness, respectively (P<.001). The association between WC and mortality persisted after further adjustment for smoking, baseline health status, and BMI (P=.02), but not after additional adjustment for fitness (P=.86). Fitness predicted mortality risk after further adjustment for smoking, baseline health, and either WC, BMI or percent body fat (P<.001).
Conclusions
Fitness is a significant mortality predictor in older adults independent of overall or abdominal adiposity. Practitioners should consider the importance of preserving functional capacity, by recommending regular physical activity for older individuals, normal weight and overweight alike.
doi:10.1001/jama.298.21.2507
PMCID: PMC2692959  PMID: 18056904
23.  Cardiorespiratory Fitness as a Predictor of Nonfatal Cardiovascular Events in Asymptomatic Women and Men 
American journal of epidemiology  2007;165(12):1413-1423.
Prospective data relating cardiorespiratory fitness (CRF) with nonfatal cardiovascular disease (CVD) events are limited to studies in men or studies of combined fatal and nonfatal CVD endpoints. The authors examined the association between CRF and nonfatal CVD events in 20,728 men and 5,909 women without CVD at baseline. All participants performed a maximal treadmill exercise test and completed a follow-up health survey in the Aerobics Center Longitudinal Study (Dallas, Texas) between 1971 and 2004. There were 1,512 events in men and 159 events in women during an average follow-up of 10 years. Across incremental CRF groups, age- and examination year-adjusted event rates per 10,000 person-years were 107.9, 75.2, and 50.3 in men (p trend <0.001) and 41.9, 27.7, and 20.8 in women (p trend = 0.002). After further adjustment for smoking, alcohol intake, family history of CVD, and abnormal exercise ECG responses, hazard ratios (95% confidence interval) were 1.00 (referent), 0.82 (0.72, 0.94), and 0.61 (0.53, 0.71) in men, p trend <0.001, and were 1.00 (referent), 0.74 (0.49, 1.13), and 0.63 (0.40, 0.98) in women, p trend = 0.05. After adjustment for other CVD predictors, the association remained significant in men but not in women.
doi:10.1093/aje/kwm031
PMCID: PMC2685148  PMID: 17406007
exercise; cardiovascular diseases; stroke; women; primary prevention
24.  Cardiorespiratory Fitness and Risk of Nonfatal Cardiovascular Disease in Women and Men With Hypertension 
American journal of hypertension  2007;20(6):608-615.
Background
Whether the cardioprotective characteristic of higher cardiorespiratory fitness (CRF) extends to adults with manifest hypertension (HTN) is poorly understood.
Methods
We examined the association between CRF and nonfatal cardiovascular disease (CVD) events in 8147 men and 1268 women, who, at baseline, were free of known CVD and had HTN based on a history of physician diagnosis or a measured resting blood pressure (BP) ≥140/90 mm Hg. The CVD events (myocardial infarction, stroke, coronary revascularization) were ascertained from mail-back surveys. The CRF was quantified as maximal treadmill exercise test duration and was grouped for analysis as low (lowest 20% of exercise duration), moderate (middle 40%), and high (upper 40%).
Results
A total of 71 CVD events occurred during 12,224 woman-years, and 837 CVD events occurred during 82,366 man-years of follow-up. Age and examination year adjusted CVD rates per 1000 person-years according to low, moderate, and high CRF groups were 10.8, 8.4, and 3.8 (trend P = .001) in women, and were 15.3, 10.9, and 7.2 (trend P < .001) in men. After further controlling for CVD risk factors, abnormal exercise electrocardiogram (ECG) responses, and family history of CVD, hazards ratios (95% CI) for CVD events across incremental CRF categories were 1.00 (referent), 0.88 (0.74 to 1.06), 0.70 (0.57 to 0.86), trend P < .001, in men, and were 1.00 (referent), 0.87 (0.48 to 1.58), 0.41 (0.20 to 0.84), trend P = .01, in women.
Conclusions
In adults with HTN, higher CRF is associated with lower risk of nonfatal CVD events, independent of other clinical risk predictors. Am J Hypertens 2007;20:608 - 615
doi:10.1016/j.amjhyper.2007.01.009
PMCID: PMC1975681  PMID: 17531916
Physical fitness; hypertension; cardiovascular diseases; morbidity

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