Karen L Margolis

Publications (128)1163.89 Total impact

• Article: The association of whole grain consumption with incident type 2 diabetes: the Women's Health Initiative Observational Study.

  Emily D Parker, Simin Liu, Linda Van Horn, Leslie F Tinker, James M Shikany, Charles B Eaton, Karen L Margolis
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  ABSTRACT: PURPOSE: Whole grains may offer protection from diabetes by decreasing energy intake, preventing weight gain, and direct effects on insulin resistance. This study examined associations of whole and refined grains with incident type 2 diabetes (T2D) ascertained by self-reported medication use in a cohort of postmenopausal women. METHODS: We included 72,215 women free of diabetes at baseline from the Women's Health Initiative Observational Study. Whole grain consumption was categorized as 0, less than 0.5, 0.5 to 1.0, 1.0 to less than 1.5, 1.5 to less than 2.0, and 2.0 or more servings per day. Proportional hazards regression was performed to estimate hazard ratios (HR) and 95% confidence intervals adjusting for potential confounders. RESULTS: There were 3465 cases of incident T2D over median follow-up of 7.9 years. Adjusted for age and energy intake per day, successively increasing categories of whole grain consumption were associated with statistically significant reduced risk of incident T2D (HRs, 1.00, 0.83, 0.73, 0.69, 0.61, and 0.57; P for trend < 0.0001). Results were attenuated after adjustment for confounders and other dietary components. The reduction in risk of T2D was greater among nonsmokers and those who maintained their weight within 5 pounds with higher consumption of whole grains than smokers and women who gained more weight. CONCLUSIONS: This large, prospective study found an inverse dose-response relationship between whole grain consumption and incident T2D in postmenopausal women.
  Annals of epidemiology 04/2013; · 2.95 Impact Factor
• Article: Barriers to Improving Primary Care of Depression: Perspectives of Medical Group Leaders.

  Robin R Whitebird, Leif I Solberg, Karen L Margolis, Stephen E Asche, Michael A Trangle, Arthur P Wineman
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  ABSTRACT: Using clinical trials, researchers have demonstrated effective methods for treating depression in primary care, but improvements based on these trials are not being implemented. This might be because these improvements require more systematic organizational changes than can be made by individual physicians. We interviewed 82 physicians and administrative leaders of 41 medical groups to learn what is preventing those organizational changes. The identified barriers to improving care included external contextual problems (reimbursement, scarce resources, and access to/communication with specialty mental health), individual attitudes (physician and patient resistance), and internal care process barriers (organizational and condition complexity, difficulty standardizing and measuring care). Although many of these barriers are challenging, we can overcome them by setting clear priorities for change and allocating adequate resources. We must improve primary care of depression if we are to reduce its enormous adverse social and economic impacts.
  Qualitative Health Research 03/2013; · 2.19 Impact Factor
• Article: Longitudinal changes in dietary fat intake and associated changes in cardiovascular risk factors in adults with type 2 diabetes: The ACCORD trial.

  Julienne K Kirk, Timothy Craven, Edward W Lipkin, Jeffrey Katula, Carolyn Pedley, Patrick J O'Connor, Karen L Margolis
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  ABSTRACT: AIMS: To measure dietary fat intake using the Puget Sound Eating Patterns (PEP) questionnaire, a validated 19-item food questionnaire, and to quantify how reduced dietary fat intake affects cardiovascular risk factors in adults with type 2 diabetes. METHODS: Randomized controlled trial including a subsample of 1781 Action to Control Cardiovascular Risk in Diabetes (ACCORD) participants. Participants received dietary counseling to consume a reduced-fat diet. Outcome measures included HbA1c, fasting lipid profile, blood pressure, and weight. Longitudinal linear regression analyses were used to evaluate relationships between baseline and follow-up PEP scores and cardiovascular risk factors. RESULTS: PEP scores decreased significantly from baseline to 12-month follow up with a mean difference of -0.09±0.39, P<0.001. All of the fat intake subscales showed significant improvement at 12 months from baseline. White race, female gender, and more hours per week of physical activity were correlated with a decline in PEP scores at 1-year. A longitudinal decrease in dietary fat intake was associated with significantly less weight gain at 12- and 36-months and lower serum triglycerides at 1 year. CONCLUSIONS: Reduced fat intake as measured by a brief questionnaire was associated with significant improvement in some cardiovascular risk factors (triglycerides and weight), but not in others.
  Diabetes research and clinical practice 03/2013; · 2.16 Impact Factor
• Article: Intensive Glycemic Control and Thiazolidinedione Use: Effects on Cortical and Trabecular Bone at the Radius and Tibia.

  Ann V Schwartz, Eric Vittinghoff, Karen L Margolis, Lesley M Scibora, Lisa Palermo, Walter T Ambrosius, Trisha F Hue, Kristine E Ensrud
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  ABSTRACT: Factors that contribute to bone fragility in type 2 diabetes are not well understood. We assessed the effects of intensive glycemic control, thiazolidinediones (TZDs), and A(1C) levels on bone geometry and strength at the radius and tibia. In a substudy of the Action to Control Cardiovascular Risk in Diabetes trial, peripheral quantitative computed tomographic (pQCT) scans of the radius and tibia were obtained 2 years after randomization on 73 participants (intensive n = 35, standard n = 38). TZD use and A(1C) levels were measured every 4 months during the trial. Effects of intervention assignment, TZD use, and A(1C) on pQCT parameters were assessed in linear regression models. Intensive, compared with standard, glycemic control was associated with 1.3 % lower cortical volumetric BMD at the tibia in men (p = 0.02) but not with other pQCT parameters. In women, but not men, each additional year of TZD use was associated with an 11 % lower polar strength strain index (SSIp) at the radius (p = 0.04) and tibia (p = 0.002) in models adjusted for A(1C) levels. In women, each additional 1 % increase in A(1C) was associated with an 18 % lower SSIp at the ultradistal radius (p = 0.04) in models adjusted for TZD use. There was no consistent evidence of an effect of intensive, compared with standard, glycemic control on bone strength at the radius or tibia. In women, TZD use may reduce bone strength at these sites. Higher A(1C) may also be associated with lower bone strength at the radius, but not tibia, in women.
  Calcified Tissue International 02/2013; · 2.38 Impact Factor
• Article: Sex differences in cardiovascular outcomes in patients with incident hypertension.

  Stacie L Daugherty, Frederick A Masoudi, Chan Zeng, P Michael Ho, Karen L Margolis, Patrick J O'Connor, Alan S Go, David J Magid
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  ABSTRACT: BACKGROUND:: The time of initial hypertension diagnosis represents an opportunity to assess subsequent risk of adverse cardiovascular outcomes. The extent to which women and men with newly identified hypertension are at a similar risk for adverse cardiovascular events, including chronic kidney disease (CKD), is not well known. METHODS:: Among women and men with incident hypertension from 2001 to 2006 enrolled in the Cardiovascular Research Network (CVRN) Hypertension Registry, we compared incident events including all-cause death; hospitalization for myocardial infarction (MI), heart failure or stroke; and the development of CKD. Multivariable models were adjusted for patient demographic and clinical characteristics. RESULTS:: Among 177 521 patients with incident hypertension, 55% were women. Compared with men, women were older, more likely white and had more kidney disease at baseline. Over median 3.2 years (interquartile range 1.6-4.8) of follow-up, after adjustment, women were equally likely to be hospitalized for heart failure [hazard ratio 0.90, 95% confidence interval (CI) 0.76-1.07] and were significantly less likely to die of any cause (hazard ratio 0.85, 95% CI 0.80-0.90) or be hospitalized for MI (hazard ratio 0.44, 95% CI 0.39-0.50) or stroke (hazard ratio 0.68, 95% CI 0.60-0.77) compared with men. Women were significantly more likely to develop CKD (9.60 vs. 7.15%; adjusted hazard ratio 1.17, 95% CI 1.12-1.22) than men. CONCLUSION:: In this cohort with incident hypertension, women were more likely to develop CKD and less likely to develop other cardiovascular outcomes compared with men. Future studies should investigate the potential reasons for these sex differences.
  Journal of hypertension 02/2013; 31(2):271-277. · 4.02 Impact Factor
• Article: Prehypertension and Hypertension in Community-Based Pediatric Practice.

  Joan C Lo, Alan Sinaiko, Malini Chandra, Matthew F Daley, Louise C Greenspan, Emily D Parker, Elyse O Kharbanda, Karen L Margolis, Kenneth Adams, Ronald Prineas, David Magid, Patrick J O'Connor
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  ABSTRACT: OBJECTIVE:To examine the prevalence of prehypertension and hypertension among children receiving well-child care in community-based practices.METHODS:Children aged 3 to 17 years with measurements of height, weight, and blood pressure (BP) obtained at an initial (index) well-child visit between July 2007 and December 2009 were included in this retrospective cohort study across 3 large, integrated health care delivery systems. Index BP classification was based on the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents: normal BP, <90th percentile; prehypertension, 90th to 94th percentile; hypertension, 3 BP measurements ≥95th percentile (index and 2 subsequent consecutive visits).RESULTS:The cohort included 199 513 children (24.3% aged 3-5 years, 34.5% aged 6-11 years, and 41.2% aged 12-17 years) with substantial racial/ethnic diversity (35.9% white, 7.8% black, 17.6% Hispanic, 11.7% Asian/Pacific Islander, and 27.0% other/unknown race). At the index visit, 81.9% of participants were normotensive, 12.7% had prehypertension, and 5.4% had a BP in the hypertension range (≥95th percentile). Of the 10 848 children with an index hypertensive BP level, 3.8% of those with a follow-up BP measurement had confirmed hypertension (estimated 0.3% prevalence). Increasing age and BMI were significantly associated with prehypertension and confirmed hypertension (P < .001 for trend). Among racial/ethnic groups, blacks and Asians had the highest prevalence of hypertension.CONCLUSIONS:The prevalence of hypertension in this community-based study is lower than previously reported from school-based studies. With the size and diversity of this cohort, these results suggest the prevalence of hypertension in children may actually be lower than previously reported.
  PEDIATRICS 01/2013; · 4.47 Impact Factor
• Article: Effects of menopausal hormone therapy on ductal carcinoma in situ of the breast.

  Juhua Luo, Barbara B Cochrane, Jean Wactawski-Wende, Julie R Hunt, Judith K Ockene, Karen L Margolis
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  ABSTRACT: Post-menopausal hormone therapy with estrogen plus progestin is consistently reported to be associated with an increased risk of invasive breast cancer. However, findings on an association between hormone use and ductal carcinoma in situ of the breast (DCIS), a possible precursor lesion of invasive breast cancer, are sparse and inconsistent. Women's Health Initiative data were used to assess the effects of hormone therapy on the risk of DCIS in two clinical trials of hormone therapy (16,276 women enrolled in the trial of daily conjugated equine estrogens plus medroxyprogesterone acetate (CEE + MPA) vs placebo; 10,187 women enrolled in the trial of CEE-alone vs placebo). The effects of hormone therapy on DCIS in clinical trial participants were assessed during the intervention, post-intervention, and entire followup periods, and in the observational study (OS; 30,421 CEE + MPA users and non-users and 18,657 CEE-alone users and non-users who met eligibility criteria similar to the clinical trial). Compared to placebo, CEE + MPA was non-significantly associated with higher risk of DCIS over approximate average of 11 years of follow-up (HR = 1.23; 95 % CI: 0.91-1.64). No statistical difference was detected between intervention and post-intervention phases (p = 0.32). Corresponding OS results supported an increased risk for DCIS in CEE + MPA users compared to women who were non-users (HR = 1.65; 95 % CI: 1.25-2.19) after adjusting for potential confounders. There was no clear association between CEE-alone use and risk of DCIS. CEE-alone trial data showed that the risk of DCIS was non-significantly lower in the treatment than in the placebo group, while analysis of the corresponding OS showed a non-significantly higher risk of DCIS in the CEE-alone users than non-users. Our analysis suggests that combined estrogen plus progestin use in post-menopausal women may increase risk of DCIS. Whether estrogen-alone use is associated with DCIS requires further investigation.
  Breast Cancer Research and Treatment 01/2013; · 4.43 Impact Factor
• Article: Sleep Disturbance and Incidence of Thyroid Cancer in Postmenopausal Women The Women's Health Initiative.

  Juhua Luo, Megan Sands, Jean Wactawski-Wende, Yiqing Song, Karen L Margolis
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  ABSTRACT: Sleep disturbance has been found to be associated with numerous adverse health outcomes, including cancers. However, no epidemiologic study has examined the relation between sleep disturbance and thyroid cancer risk. A total of 142,933 postmenopausal women who were 50-79 years of age and enrolled in the Women's Health Initiative between September 1, 1993, and December 31, 1998, were followed up for a mean of 11 years. Cox proportional-hazard regression models were used to estimate hazard ratios and 95% confidence intervals for sleep disturbance (insomnia and sleep duration) and risk of thyroid cancer. Insomnia score was measured using a validated 5-item Women's Health Initiative Insomnia Rating Scale. Overall, a total of 295 thyroid cancer cases were identified. After adjustment for potential confounders, women with greater insomnia scores had a significantly higher risk of thyroid cancer than did women with low scores (hazard ratio = 1.44, 95% confidence interval: 1.01, 2.05). The significant association between insomnia score and thyroid cancer was confined to nonobese women (hazard ratio = 1.71, 95% confidence interval: 1.12, 2.62) and was not seen in obese women (hazard ratio = 0.94 95% confidence interval: 0.48, 1.84) (P for interaction = 0.07). In conclusion, postmenopausal women with greater insomnia scores, especially nonobese women, had a significantly increased risk of thyroid cancer. More studies are needed to confirm these findings.
  American journal of epidemiology 12/2012; · 5.59 Impact Factor
• Article: Calcium and Vitamin D Supplementation and Cognitive Impairment in the Women's Health Initiative.

  Rebecca C Rossom, Mark A Espeland, Joann E Manson, Maurice W Dysken, Karen C Johnson, Dorothy S Lane, Erin S Leblanc, Frank A Lederle, Kamal H Masaki, Karen L Margolis
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  ABSTRACT: OBJECTIVES: To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women. DESIGN: Post hoc analysis of a randomized double-blind placebo-controlled trial. SETTING: Forty Women's Health Initiative (WHI) clinical centers across the United States. PARTICIPANTS: Four thousand one hundred forty-three women aged 65 and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D Trial and the WHI Memory Study. INTERVENTION: Two thousand thirty-four women were randomized to receive 1,000 mg of calcium carbonate combined with 400 IU of vitamin D(3) (treatment) and 2,109 to placebo. MEASUREMENTS: Primary: classifications of probable dementia or mild cognitive impairment (MCI) based on a four-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests. RESULTS: Mean age of participants was 71. During a mean follow-up of 7.8 years, 39 participants in the treatment group and 37 in the placebo group developed incident dementia (hazard ratio (HR) = 1.11, 95% confidence interval (CI) = 0.71-1.74, P = .64). Likewise, 98 treatment participants and 108 placebo participants developed incident MCI (HR = 0.95, 95% CI = 0.72-1.25, P = .72). There were no significant differences in incident dementia or MCI or in global or domain-specific cognitive function between groups. CONCLUSION: There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men, in other age and ethnic groups, and with other doses.
  Journal of the American Geriatrics Society 11/2012; · 3.74 Impact Factor
• Article: Adherence to blood pressure telemonitoring in a cluster-randomized clinical trial.

  Tessa J Kerby, Stephen E Asche, Michael V Maciosek, Patrick J O'Connor, Joann M Sperl-Hillen, Karen L Margolis
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  ABSTRACT: J Clin Hypertens (Greenwich). 2012;14:668-674. ©2012 Wiley Periodicals, Inc. Hypertension is a leading cause of cardiovascular disease and death worldwide. Advances in technology have added telemedicine as a tool for managing hypertension. The effectiveness of telemedicine depends on patients' ability to adhere to schedules of home monitoring and case management. Participants with uncontrolled hypertension in the intervention arm of a randomized trial who completed 6 months of follow-up were included in this analysis. They were asked to measure their blood pressure (BP) a minimum of 6 times per week using a telemonitor that transmitted the readings to their pharmacist case manager. Hypertensive patients in this study had high adherence to telemonitoring (73% took at least 6 BP readings per week) and phone visits (88% of expected visits were attended). In a multivariate analysis, older age, male sex, and some college education predicted better telemonitoring adherence. White non-Hispanic race/ethnicity predicted better adherence to phone visits with pharmacist case managers. Telemonitoring adherence and phone adherence were highly correlated; participants who did not send readings on schedule were more likely to skip at least one phone visit with their pharmacist case manager. The findings from this analysis indicate that hypertensive patients in this study were able to achieve and maintain high adherence to both the telemonitoring and the phone case management visits.
  Journal of Clinical Hypertension 10/2012; 14(10):668-74. · 1.83 Impact Factor
• Article: Benefits of Early Hypertension Control on Cardiovascular Outcomes in Patients With Diabetes.

  Patrick J O'Connor, Gabriela Vazquez-Benitez, Julie A Schmittdiel, Emily D Parker, Nicole K Trower, Jay R Desai, Karen L Margolis, David J Magid
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  ABSTRACT: OBJECTIVE To assess the impact of early hypertension (HT) control on occurrence of subsequent major cardiovascular events in those with diabetes and recent-onset HT.RESEARCH DESIGN AND METHODS Study subjects were 15,665 adults with diabetes but no diagnosed coronary or cerebrovascular disease at baseline who met standard criteria for new-onset HT. Poisson regression models assessed whether adequate blood pressure control within 1 year of HT onset predicts subsequent occurrence of major cardiovascular events with and without adjustment for baseline Framingham Risk Score (FRS) and other covariates.RESULTSMean age was 51.5 years, and mean blood pressure at HT onset was 136.8/80.8 mmHg. In the year after HT onset, mean blood pressure decreased to 131.4/78.0 mmHg and was <130/80 mmHg in 32.9% of subjects and <140/90 mmHg in 80.2%. Over a mean follow-up of 3.2 years, age-adjusted rates of major cardiovascular events in those with mean 1-year blood pressure measurements of <130/80, 130-139/80-89, and ≥140/90 mmHg were 5.10, 4.27, and 6.94 events/1,000 person-years, respectively (P = 0.004). In FRS-adjusted models, rates of major cardiovascular events were significantly higher in those with mean blood pressure ≥140/90 mmHg in the first year after HT onset (rate ratio 1.30 [95% CI 1.01-1.169]; P = 0.04).CONCLUSIONS Failure to adequately control BP within 1 year of HT onset significantly increased the likelihood of major cardiovascular events within 3 years. Prompt control of new-onset HT in patients with diabetes may provide important short-term clinical benefits.
  Diabetes care 09/2012; · 8.09 Impact Factor
• Article: Comparative Effectiveness of 2 β-Blockers in Hypertensive Patients.

  Emily D Parker, Karen L Margolis, Nicole K Trower, David J Magid, Heather M Tavel, Susan M Shetterly, P Michael Ho, Bix E Swain, Patrick J O'Connor
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  ABSTRACT: BACKGROUND Randomized controlled trials have demonstrated the efficacy of selected β-blockers for preventing cardiovascular (CV) events in patients following myocardial infarction (MI) or with heart failure (HF). However, the effectiveness of β-blockers for preventing CV events in patients with hypertension has been questioned recently, but it is unclear whether this is a class effect. METHODS Using electronic medical record and health plan data from the Cardiovascular Research Network Hypertension Registry, we compared incident MI, HF, and stroke in patients who were new β-blocker users between 2000 and 2009. Patients had no history of CV disease and had not previously filled a prescription for a β-blocker. Cox proportional hazards regression was used to examine the associations of atenolol and metoprolol tartrate with incident CV events using both standard covariate adjustment (n = 120 978) and propensity score-matching methods (n = 22 352). RESULTS During follow-up (median, 5.2 years), there were 3517 incident MI, 3272 incident HF, and 3664 incident stroke events. Hazard ratios for MI, HF, and stroke in metoprolol tartrate users were 0.99 (95% CI, 0.97-1.02), 0.99 (95% CI, 0.96-1.01), and 0.99 (95% CI, 0.97-1.02), respectively. An alternative approach using propensity score matching yielded similar results in 11 176 new metoprolol tartrate users, who were similar to 11 176 new atenolol users with regard to demographic and clinical characteristics. CONCLUSIONS There were no statistically significant differences in incident CV events between atenolol and metoprolol tartrate users with hypertension. Large registries similar to the one used in this analysis may be useful for addressing comparative effectiveness questions that are unlikely to be resolved by randomized trials.
  Archives of internal medicine 08/2012; · 11.46 Impact Factor
• Article: A prospective study of leukocyte telomere length and risk of type 2 diabetes in postmenopausal women.

  Nai-Chieh Y You, Brian H Chen, Yiqing Song, Xuyang Lu, Yilin Chen, Joann E Manson, Mo Kang, Barbara V Howard, Karen L Margolis, J David Curb, Lawrence S Phillips, Marcia L Stefanick, Lesley F Tinker, Simin Liu
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  ABSTRACT: Telomere length (TL) has been implicated in the pathogenesis of age-related disorders. However, there are no prospective studies directly investigating the role of TL and relevant genes in diabetes development. In the multiethnic Women's Health Initiative, we identified 1,675 incident diabetes case participants in 6 years of follow-up and 2,382 control participants matched by age, ethnicity, clinical center, time of blood draw, and follow-up duration. Leukocyte TL at baseline was measured using quantitative PCR, and Mendelian randomization analysis was conducted to test whether TL is causally associated with diabetes risk. After adjustment for matching and known diabetes risk factors, odds ratios per 1-kilobase increment were 1.00 (95% CI 0.90-1.11) in whites, 0.95 (0.85-1.06) in blacks, 0.96 (0.79-1.17) in Hispanics, and 0.88 (0.70-1.10) in Asians. Of the 80 single nucleotide polymorphisms (SNPs) in nine genes involved in telomere regulation, 14 SNPs were predictive of TL, but none were significantly associated with diabetes risk. Using ethnicity-specific SNPs as randomization instruments, we observed no statistically significant association between TL and diabetes risk (P = 0.52). Although leukocyte TL was weakly associated with diabetes risk, this association was not independent of known risk factors. These prospective findings indicate limited clinical utility of TL in diabetes risk stratification among postmenopausal women.
  Diabetes 07/2012; 61(11):2998-3004. · 8.29 Impact Factor
• Article: Racial and ethnic differences in incident hospitalized heart failure in postmenopausal women: the Women's Health Initiative.

  Charles B Eaton, Abdulrahman M Abdulbaki, Karen L Margolis, Joann E Manson, Marian Limacher, Liviu Klein, Matthew A Allison, Jennifer G Robinson, J David Curb, Lisa A Martin, Simin Liu, Barbara V Howard
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  ABSTRACT: The differences in the incidence of heart failure by race/ethnicity and the potential mechanisms for these differences are largely unexplored in women. A total of 156 143 postmenopausal women free of self-reported heart failure enrolled from 1993 to 1998 at 40 clinical centers throughout the United States as part of the Women's Health Initiative and were followed up until 2005, for an average of 7.8 years, for incident hospitalized heart failure. Incident rates, hazard ratios (HRs), and 95% confidence intervals were determined by use of the Cox proportional hazard model comparing racial/ethnic groups, and population-attributable risk percentages were calculated for each racial/ethnic group. Blacks had the highest age-adjusted incidence of heart failure (380 in 100 000 person-years), followed by whites (274), Hispanics (193), and Asian/Pacific Islanders (103). The excess risk in blacks compared with whites (age-adjusted HR=1.45) was significantly attenuated by adjustment for household income (HR=0.97) and diabetes mellitus (HR=0.89), but the lower risk in Hispanics (age-adjusted HR=0.72) and Asian/Pacific Islanders (age-adjusted HR=0.44) remained despite adjustment for traditional risk factors, socioeconomic status, lifestyle, and access-to-care variables. The effect of adjustment for interim coronary heart disease on nonwhite versus white HRs for heart failure differed by race/ethnic group. Asian/Pacific Islander and Hispanic women have a lower incidence of heart failure and black women have higher rates of heart failure compared with white women. The excess risk of incident heart failure in black women is explained largely by adjustment for lower household incomes and diabetes mellitus in black women, whereas the lower rates of heart failure in Asian/Pacific Islanders and Hispanics are largely unexplained by the risk factors measured in this study. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
  Circulation 07/2012; 126(6):688-96. · 14.74 Impact Factor
• Article: Intensive glycemic control is not associated with fractures or falls in the ACCORD randomized trial.

  Ann V Schwartz, Karen L Margolis, Deborah E Sellmeyer, Eric Vittinghoff, Walter T Ambrosius, Denise E Bonds, Robert G Josse, Adrian M Schnall, Debra L Simmons, Trisha F Hue, Lisa Palermo, Bruce P Hamilton, Jennifer B Green, Hal H Atkinson, Patrick J O'Connor, Rex W Force, Douglas C Bauer
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  ABSTRACT: Older adults with type 2 diabetes are at high risk of fractures and falls, but the effect of glycemic control on these outcomes is unknown. To determine the effect of intensive versus standard glycemic control, we assessed fractures and falls as outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial. ACCORD participants were randomized to intensive or standard glycemia strategies, with an achieved median A1C of 6.4 and 7.5%, respectively. In the ACCORD BONE ancillary study, fractures were assessed at 54 of the 77 ACCORD clinical sites that included 7,287 of the 10,251 ACCORD participants. At annual visits, 6,782 participants were asked about falls in the previous year. During an average follow-up of 3.8 (SD 1.3) years, 198 of 3,655 participants in the intensive glycemia and 189 of 3,632 participants in the standard glycemia group experienced at least one nonspine fracture. The average rate of first nonspine fracture was 13.9 and 13.3 per 1,000 person-years in the intensive and standard groups, respectively (hazard ratio 1.04 [95% CI 0.86-1.27]). During an average follow-up of 2.0 years, 1,122 of 3,364 intensive- and 1,133 of 3,418 standard-therapy participants reported at least one fall. The average rate of falls was 60.8 and 55.3 per 100 person-years in the intensive and standard glycemia groups, respectively (1.10 [0.84-1.43]). Compared with standard glycemia, intensive glycemia did not increase or decrease fracture or fall risk in ACCORD.
  Diabetes care 07/2012; 35(7):1525-31. · 8.09 Impact Factor
• Article: The association between medication adherence and treatment intensification with blood pressure control in resistant hypertension.

  Stacie L Daugherty, J David Powers, David J Magid, Frederick A Masoudi, Karen L Margolis, Patrick J O'Connor, Julie A Schmittdiel, P Michael Ho
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  ABSTRACT: Patients with resistant hypertension are at risk for poor outcomes. Medication adherence and intensification improve blood pressure (BP) control; however, little is known about these processes or their association with outcomes in resistant hypertension. This retrospective study included patients from 2002 to 2006 with incident hypertension from 2 health systems who developed resistant hypertension or uncontrolled BP despite adherence to ≥3 antihypertensive medications. Patterns of hypertension treatment, medication adherence (percentage of days covered), and treatment intensification (increase in medication class or dose) were described in the year after resistant hypertension identification. Then, the association between medication adherence and intensification with 1-year BP control was assessed controlling for patient characteristics. Of the 3550 patients with resistant hypertension, 49% were male, and mean age was 60 years. One year after resistance hypertension determination, fewer patients were taking diuretics (77.7% versus 92.2%; P<0.01), β-blockers (71.2% versus 79.4%; P<0.01), and angiotensinogen-converting enzyme inhibitor/angiotensin receptor blocker (64.8% versus 70.1%; P<0.01) compared with baseline. Rates of BP control improved over 1 year (22% versus 55%; P<0.01). During this year, adherence was not associated with 1-year BP control (adjusted odds ratio, 1.18 [95% CI: 0.94-1.47]). Treatment was intensified in 21.6% of visits with elevated BP. Increasing treatment intensity was associated with 1-year BP control (adjusted odds ratio, 1.64 [95% CI, 1.58-1.71]). In this cohort of patients with resistant hypertension, treatment intensification but not medication adherence was significantly associated with 1-year BP control. These findings highlight the need to investigate why patients with uncontrolled BP do not receive treatment intensification.
  Hypertension 06/2012; 60(2):303-9. · 6.21 Impact Factor
• Article: Prioritizing treatments in type 2 diabetes mellitus.

  Karen L Margolis, Patrick J O'Connor
  Archives of internal medicine 05/2012; 172(10):770-2. · 11.46 Impact Factor
• Article: Diabetes mellitus as a risk factor for gastrointestinal cancers among postmenopausal women.

  Juhua Luo, Rowan Chlebowski, Simin Liu, Katherine A McGlynn, Niyati Parekh, Donna L White, Karen L Margolis
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  ABSTRACT: OBJECTIVES: While diabetes has been linked to several cancers in the gastrointestinal (GI) tract, findings have been mixed for sites other than colorectal and liver cancer. We used the Women's Health Initiative (WHI) data and conducted a comprehensive assessment of associations between diabetes and GI malignancy (esophagus, stomach, liver, biliary, pancreas, colon, and rectal). METHODS: A total of 145,765 postmenopausal women aged 50-79 enrolled in the WHI were followed for a mean 10.3 years. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between GI cancers and diagnosed diabetes, including its duration and treatment. RESULTS: Diabetes at enrollment was associated with increased risk of liver (HR = 2.97; 95 % CI, 1.66-5.32), pancreatic (HR = 1.62; 95 % CI, 1.15-2.30), colon (HR = 1.38; 95 % CI, 1.14-1.66), and rectal (HR = 1.87, 95 % CI: 1.22-2.85) cancer. Diabetes severity, assessed by duration or need for pharmacotherapy, appeared to have stronger links to risk of liver, pancreatic, and rectal cancer, but not colon cancer. There was no statistically significant association of diabetes with biliary, esophageal, and stomach cancers. CONCLUSION: Type 2 diabetes is associated with a significantly increased risk of cancers of the liver, pancreas, colon, and rectum in postmenopausal women. The suggestion that diabetes severity further increases these cancer risks requires future studies.
  Cancer Causes and Control 05/2012; · 2.88 Impact Factor
• Article: Diabetes and lung cancer among postmenopausal women.

  Juhua Luo, Rowan Chlebowski, Jean Wactawski-Wende, Nicolas F Schlecht, Lesley Tinker, Karen L Margolis
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  ABSTRACT: Epidemiological evidence of diabetes as a lung cancer risk factor is limited and conflicting. Therefore, we assessed associations among diabetes, diabetes therapy, and lung cancer risk in postmenopausal women participating in the Women's Health Initiative (WHI) study. Postmenopausal women (n = 145,765), ages 50-79 years, including 8,154 women with diabetes at study entry were followed for a mean of 11 years with 2,257 lung cancers diagnosed. Information on diabetes therapy was collected via two methods (self-reported information on treatment history collected on a questionnaire at baseline and a face-to-face review of current medication containers that participants brought to the baseline visit). Lung cancers were confirmed by central medical record and pathology report review. Cox proportional hazards regression models adjusted for lung cancer risk factors were used to estimate hazard ratios (HRs) (95% CI) for diagnosis of diabetes and treatment of disease as risk factors for lung cancer. Compared with women without diabetes, women with self-reported treated diabetes had a significantly higher risk of lung cancer (HR 1.27 [95% CI 1.02-1.59]), with risks increasing for women with diabetes requiring insulin treatment (1.71 [1.15-2.53]). However, we did not observe a significant association between lung cancer risk and diabetes not treated with medication or with duration of diabetes. Postmenopausal women with treated diabetes, especially those using insulin, have a significantly higher risk of lung cancer. The influence of diabetes severity and specific classes of therapy for diabetes on lung cancer risk require future study.
  Diabetes care 05/2012; 35(7):1485-91. · 8.09 Impact Factor
• Article: Effect of intensive versus standard blood pressure control on depression and health-related quality of life in type 2 diabetes: the ACCORD trial.

  Patrick J O'Connor, K M Venkat Narayan, Roger Anderson, Patricia Feeney, Larry Fine, Mohammed K Ali, Debra L Simmons, Don G Hire, JoAnn M Sperl-Hillen, Lois Anne Katz, Karen L Margolis, Mark D Sullivan
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  ABSTRACT: We tested the hypothesis that intensive (systolic blood pressure [SBP] <120 mmHg) rather than standard (SBP 130-139 mmHg) blood pressure (BP) control improves health-related quality of life (HRQL) in those with type 2 diabetes. Subjects were 1,028 ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial HRQL substudy participants who completed baseline and one or more 12-, 36-, or 48-month HRQL evaluations. Multivariable linear regression assessed impact of BP treatment assignment on change in HRQL. Over 4.0 years of follow-up, no significant differences occurred in five of six HRQL measures. Those assigned to intensive (vs. standard) BP control had statistically significant worsening of the Medical Outcomes Study 36-item short-form health survey (SF36) physical component scores (-0.8 vs. -0.2; P = 0.02), but magnitude of change was not clinically significant. Findings persisted across all prespecified subgroups. Intensive BP control in the ACCORD trial did not have a clinically significant impact, either positive or negative, on depression or patient-reported HRQL.
  Diabetes care 05/2012; 35(7):1479-81. · 8.09 Impact Factor