Lewis Kuller

Publications (68)524.89 Total impact

• Article: Insulin Resistance and Risk of Incident Heart Failure: Cardiovascular Health Study.

  Dipanjan Banerjee, Mary L Biggs, Laina Mercer, Kenneth Mukamal, Robert Kaplan, Joshua Barzilay, Lewis Kuller, Jorge R Kizer, Luc Djousse, Russell Tracy, Susan Zieman, Donald Lloyd-Jones, David Siscovick, Mercedes Carnethon
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  ABSTRACT: BACKGROUND: -Patients with heart failure (HF) have higher fasting insulin levels and a higher prevalence of insulin resistance (IR) as compared with matched controls. IR leads to structural abnormalities in the heart, such as increased left atrial (LA) size, left ventricular (LV) mass, and alterations in transmitral velocity that can precede the diagnosis of HF. It is not known whether IR precedes the development of HF or whether the relationship between IR and HF is present among adults with HF due to non-ischemic heart disease. METHODS AND RESULTS: -We examined 4425 participants (60% female) from the Cardiovascular Health Study after excluding those with HF, myocardial infarction, or treated diabetes at baseline. We used Cox proportional hazards models to estimate the relative risk of incident HF associated with fasting insulin measured at study entry. There were 1216 cases of incident HF (1103 without antecedent MI) during a median follow-up of 12 years (maximum, 19 years). Fasting insulin levels were positively associated with the risk of incident HF (HR = 1.10, 95% CI 1.05, 1.15, per SD change) when adjusted for age, gender, race, field center, physical activity, smoking, alcohol intake, HDL cholesterol, total cholesterol, and systolic blood pressure, and waist circumference. The association between fasting insulin levels and incident HF was similar for HF without antecedent MI (HR= 1.10, 95% CI 1.05, 1.15). Measures of LA size, LV mass, and peak A velocity at baseline were associated both with fasting insulin levels and with heart failure ; however, additional statistical adjustment for these parameters did not completely attenuate the insulin-HF estimate (HR= 1.08, 95% CI 1.03, 1.14 per1-SD increase in fasting insulin). CONCLUSIONS: -Fasting insulin was positively associated with adverse echocardiographic features and risk of subsequent HF in CHS participants, including those without an antecedent MI.
  Circulation Heart Failure 04/2013; · 6.29 Impact Factor
• Article: Adiposity and Cognitive Decline in the Cardiovascular Health Study.

  José A Luchsinger, Mary L Biggs, Jorge R Kizer, Joshua Barzilay, Annette Fitzpatrick, Anne Newman, William T Longstreth, Oscar Lopez, David Siscovick, Lewis Kuller
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  ABSTRACT: Background: Studies relating adiposity to cognition in the elderly show conflicting results, which may be explained by the choice of adiposity measures. Thus, we studied the longitudinal associations of different adiposity measures, fat mass by bioelectrical impedance analysis, body mass index (BMI) and waist circumference (WC), with cognitive performance in the Cardiovascular Health Study. Methods: Cognitive performance was assessed with the modified Mini-Mental State Examination, the Digit Symbol Substitution Test, and a composite of both. We used linear mixed models to estimate rates of change in cognitive function scores associated with adiposity measured at baseline. Results: The final sample was comprised of 2,681 women (57.9%) and 1,949 men (42.1%) aged 73 ± 5.2 and 73.9 ± 5.6 years, respectively. Adiposity was associated with slower cognitive decline in most analyses. Results were similar for fat mass, BMI and WC. Higher fat-free mass was also related to slower cognitive decline. Results were similar in analyses excluding persons with cancer, smokers, and persons with short follow-up, poor self-reported health, or persons with cardiovascular disease. Conclusions: Higher adiposity and higher fat-free mass in the elderly was related to better cognitive performance. This finding was not explained by confounding by preexisting conditions.
  Neuroepidemiology 02/2013; 40(4):274-281. · 2.31 Impact Factor
• Article: Relationships of coronary heart disease with 27-hydroxycholesterol, low-density lipoprotein cholesterol, and menopausal hormone therapy.

  Jacques E Rossouw, Ross L Prentice, Joann E Manson, Aaron K Aragaki, Judith Hsia, Lisa W Martin, Lewis Kuller, Karen C Johnson, Charles Eaton, Rebecca Jackson, Maurizio Trevisan, Matthew Allison, Ron C Hoogeveen
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  ABSTRACT: Menopausal hormone therapy (MHT) increases the risk of coronary heart disease (CHD) in older women with elevated low-density lipoprotein (LDLC) levels. The endogenous estrogen receptor antagonist 27-hydroxycholesterol (27OHC) is correlated with LDLC levels and may block the beneficial effects of estrogen on the cardiovascular system. We conducted a nested case-control study in the Women's Health Initiative trials of 350 CHD cases and 813 matched controls to explore potential mediation by 27OHC of the dependence of the CHD risk elevation with MHT on LDLC. Baseline levels of 27OHC were not associated with CHD risk when LDLC was included in the multivariable models. The odds ratio for CHD associated with increased LDLC was 1.15 (95% confidence interval, 1.08-1.23) and was unchanged at 1.14 (95% confidence interval, 1.07-1.22) when 27OHC was added to the model. Baseline 27OHC did not interact with MHT on CHD risk (P=0.81). In contrast, LDLC levels modified the effect of MHT on CHD risk (P for interaction=0.02), and adding 27OHC did not affect this result. With the use of log scales, the effect of MHT on CHD increased linearly with increasing level of baseline LDLC, with a transition from no risk to increased risk at ≈3.36 mmol/L (130 mg/dL). This study found that 27OHC does not independently increase the risk of CHD, does not modify the increased risk of CHD resulting from MHT, and does not mediate the interaction of LDLC with MHT. Measuring blood lipids may aid in counseling individual women about initiating MHT and cardiovascular risk mitigation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
  Circulation 08/2012; 126(13):1577-86. · 14.74 Impact Factor
• Article: Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy.

  Jacques E Rossouw, Karen C Johnson, Mary Pettinger, Mary Cushman, Per Morten Sandset, Lewis Kuller, Frits Rosendaal, Jan Rosing, Sylvia Wasserthal-Smoller, Lisa W Martin, Joann E Manson, Kamakshi Lakshminarayan, Jose G Merino, John Lynch
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  ABSTRACT: To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized activated protein C resistance ratio [nAPCsr]) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy. Nested case-control study of 455 cases of ischemic stroke and 565 matched control subjects in the Women's Health Initiative trials of postmenopausal hormone therapy. Baseline free TFPI was associated with ischemic stroke risk (OR per SD increase, 1.17; 95% CI, 1.01-1.37; P=0.039), but baseline nAPCsr was not (OR per SD increase, 0.89; 95% CI, 0.75-1.05; P=0.15). Baseline TFPI levels and nAPCsr did not modify the effect of postmenopausal hormone therapy on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction P=0.452 and 0.971, respectively). In subgroup analyses, baseline nAPCsr was inversely associated with lacunar strokes (OR per SD increase, 0.74; 95% CI, 0.57-0.96; P=0.025) and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes (P=0.008). Procoagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to postmenopausal hormone therapy. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT 00000611.
  Stroke 02/2012; 43(4):952-7. · 5.73 Impact Factor
• Article: Lipid and lipoprotein biomarkers and the risk of ischemic stroke in postmenopausal women.

  Jeffrey S Berger, Aileen P McGinn, Barbara V Howard, Lewis Kuller, Joann E Manson, Jim Otvos, J David Curb, Charles B Eaton, Robert C Kaplan, John K Lynch, Daniel M Rosenbaum, Sylvia Wassertheil-Smoller
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  ABSTRACT: Few studies simultaneously investigated lipids and lipoprotein biomarkers as predictors of ischemic stroke. The value of these biomarkers as independent predictors of ischemic stroke remains controversial. We conducted a prospective nested case-control study among postmenopausal women from the Women's Health Initiative Observational Study to assess the relationship between fasting lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), lipoproteins (LDL, HDL, and very low-density lipoprotein [VLDL] particle number and size, intermediate-density lipoprotein [IDL] particle number, and lipoprotein (a)), and risk of ischemic stroke. Among women free of stroke at baseline, 774 ischemic stroke patients were matched according to age and race to control subjects, using a 1:1 ratio. In bivariate analysis, baseline triglycerides (P<0.001), IDL particles (P<0.01), LDL particles (P<0.01), VLDL triglyceride (P<0.001), VLDL particles (P<0.01), VLDL size (P<0.001), LDL size (P=0.03), and total/HDL cholesterol ratio (P<0.01) were significantly higher among women with incident ischemic stroke, whereas levels of HDL-C (P<0.01) and HDL size (P<0.01) were lower. No significant baseline difference for total cholesterol (P=0.15), LDL-C (P=0.47), and lipoprotein (a) (P=0.11) was observed. In multivariable analysis, triglycerides (odds ratio for the highest versus lowest quartile, 1.56; 95% confidence interval, 1.13-2.17; P for trend=0.02), VLDL size (odds ratio, 1.59; 95% confidence interval, 1.10-2.28; P for trend=0.03), and IDL particle number (odds ratio, 1.46; 95% confidence interval, 1.04-2.04; P for trend=0.02) were significantly associated with ischemic stroke. Among a panel of lipid and lipoprotein biomarkers, baseline triglycerides, VLDL size, and IDL particle number were significantly associated with incident ischemic stroke in postmenopausal women.
  Stroke 02/2012; 43(4):958-66. · 5.73 Impact Factor
• Article: Inflammation predicts changes in high-density lipoprotein particles and apolipoprotein A1 following initiation of antiretroviral therapy.

  Jason V Baker, Jacqueline Neuhaus, Daniel Duprez, David A Cooper, Jennifer Hoy, Lewis Kuller, Fiona C Lampe, Angelike Liappis, Nina Friis-Moller, Jim Otvos, Nicholas I Paton, Russell Tracy, James D Neaton
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  ABSTRACT: The effects of HIV infection and antiretroviral therapy (ART) on usual lipid levels have been reported. The effects of initiating versus deferring ART on high-density and low-density lipoprotein particle (HDL-P and LDL-P, respectively) concentrations and apolipoprotein (Apo) levels are not well described. In a subgroup of participants not taking ART at study entry who were randomized in the Strategies for Management of Antiretroviral Therapy (SMART) trial to immediately initiate ART ('viral suppression group') or to defer it ('drug conservation group'), lipoprotein particle concentrations and ApoA1 and ApoB levels were measured at baseline and at 2 and 6 months following randomization. Compared with drug conservation group (n = 126), HDL-P and ApoA1 levels increased among viral suppression participants (n = 128) after starting ART. At 6 months, viral suppression participants had 13% higher total HDL-P (P < 0.001) and 9% higher ApoA1 (P < 0.001). LDL-P, very low density lipoprotein particle, and ApoB did not differ significantly between the viral suppression and drug conservation groups. Among viral suppression participants, predictors of HDL-P and ApoA1 increases included baseline levels of high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6), but not HIV RNA level, CD4 cell count, or traditional cardiovascular disease risk factors. The effect of starting ART on changes in HDL-P and ApoA1 was greater for those with higher versus lower baseline levels of IL-6 (P = 0.001 and 0.08, respectively, for interaction) or hsCRP (P = 0.01 and 0.04, respectively, for interaction). HDL-P and ApoA1 increase following ART initiation, to a degree that depends on the degree of inflammation present at entry. These findings suggest that activation of inflammatory pathways contribute to HIV-associated changes in HDL.
  AIDS (London, England) 08/2011; 25(17):2133-42. · 4.91 Impact Factor
• Article: Risk of heart failure with human immunodeficiency virus in the absence of prior diagnosis of coronary heart disease.

  Adeel A Butt, Chung-Chou Chang, Lewis Kuller, Matthew Bidwell Goetz, David Leaf, David Rimland, Cynthia L Gibert, Krisann K Oursler, Maria C Rodriguez-Barradas, Joseph Lim, Lewis E Kazis, Stephen Gottlieb, Amy C Justice, Matthew S Freiberg
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  ABSTRACT: Whether human immunodeficiency virus (HIV) infection is a risk factor for heart failure (HF) is not clear. The presence of coronary heart disease and alcohol consumption in this population may confound this association. To determine whether HIV infection is a risk factor for incident HF, we conducted a population-based, retrospective cohort study of HIV-infected and HIV-uninfected veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC) and the 1999 Large Health Study of Veteran Enrollees (LHS) from January 1, 2000, to July 31, 2007. There were 8486 participants (28.2% HIV-infected) enrolled in the VACS-VC who also participated in the 1999 LHS. During the median 7.3 years of follow-up, 286 incident HF events occurred. Age- and race/ethnicity-adjusted HF rates among HIV-infected and HIV-uninfected veterans were 7.12 (95% confidence interval [CI], 6.90-7.34) and 4.82 (95% CI, 4.72-4.91) per 1000 person-years, respectively. Compared with HIV-uninfected veterans, those who were HIV infected had an increased risk of HF (adjusted hazard ratio [HR], 1.81; 95% CI, 1.39-2.36). This association persisted among veterans who did not have a coronary heart disease event or a diagnosis related to alcohol abuse or dependence before the incident HF event (adjusted HR, 1.96; 95% CI, 1.29-2.98). Compared with HIV-uninfected veterans, those who were HIV infected with a baseline Human immunodeficiency virus 1 (HIV-1) RNA level of 500 or more copies/mL had a higher risk of HF (adjusted HR, 2.28; 95% CI, 1.57-3.32), while those with baseline and a recent HIV-1 RNA level less than 500 copies/mL did not (adjusted HR, 1.10; 95% CI, 0.64-1.89; P < .001 for comparison between high and low HIV-1 RNA groups). Our data suggest that HIV infection is a risk factor for HF. Ongoing viral replication is associated with a higher risk of developing HF.
  Archives of internal medicine 04/2011; 171(8):737-43. · 11.46 Impact Factor
• Article: Resting heart rate and coronary artery calcium in postmenopausal women.

  Matthew A Allison, Joann E Manson, Aaron Aragaki, Charles B Eaton, Judith Hsai, Lawrence Phillips, Lewis Kuller, Maurizio Trevisan
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  ABSTRACT: To test the hypothesis of a significant association between resting heart rate (RHR) and coronary artery calcium (CAC). This is a cross-sectional study of a subset of women enrolled in the estrogen-alone clinical trial of the Women's Health Initiative (WHI). We used a longitudinal study that enrolled 998 postmenopausal women with a history of hysterectomy between the ages of 50 and 59 at enrollment at 40 different clinical centers. RHR was measured at enrollment and throughout the study, and CAC was determined approximately 7 years after the baseline clinic visit. The mean (standard deviation [SD]) age was 55 (2.8) years. With adjustment for age and ethnicity, a 10-unit increment in RHR was significantly associated with CAC (SD 1.18, 95% confidence interval [CI] 1.01-1.38), but this was no longer significant after adjustment for body mass index (BMI), income, education, dyslipidemia, diabetes, smoking, and hypertension (SD 1.06, 95% CI 0.90-1.25). In a fully adjusted multivariable model, however, there was a significant interaction (p=0.03) between baseline RHR and systolic blood pressure (SBP) for the presence of any CAC. Compared to women with an RHR < 80 beats per minute (BPM) and an SBP < 140 mm Hg, those who had an RHR ≥ 80 BPM and an SBP ≥ 140 mm Hg had 2.66-fold higher odds (1.08-6.57) for the presence of any CAC. Compared to those with normal BP and RHR, postmenopausal, hysterectomized women with an elevated SBP and RHR have a significantly higher odds for the presence of calcified coronary artery disease.
  Journal of Women s Health 03/2011; 20(5):661-9. · 1.57 Impact Factor
• Article: Smoking and alcohol consumption in relation to risk of triple-negative breast cancer in a cohort of postmenopausal women.

  Geoffrey C Kabat, Mimi Kim, Amanda I Phipps, Christopher I Li, Catherine R Messina, Jean Wactawski-Wende, Lewis Kuller, Michael S Simon, Shagufta Yasmeen, Sylvia Wassertheil-Smoller, Thomas E Rohan
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  ABSTRACT: Little is known about the risk factors for triple-negative breast cancer (TNBC), which has a worse prognosis compared to hormone receptor-positive breast cancer. We examined the association of smoking and alcohol intake with TNBC and estrogen receptor-positive (ER+) breast cancer. Among 148,030 women enrolled in the Women's Health Initiative, 300 TNBC cases and 2,479 ER+ cases were identified over a median of 8.0 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Cigarette smoking was not associated with TNBC, whereas drinkers had reduced risk compared to never drinkers. In contrast, both exposures showed slight positive associations with ER+ breast cancer: for women with ≥ 40 pack-years of smoking, the HR was 1.24, 95% CI 1.06-1.44; for women consuming ≥ 7 servings of alcohol per week, the HR was 1.26, 95% CI 1.06-1.50. Intakes of wine and hard liquor were also significantly positively associated with ER+ breast cancer. These findings from a large cohort of postmenopausal women suggest that smoking and alcohol consumption are not associated with increased risk of TNBC, but may be modestly associated with increased risk of ER+ breast cancer.
  Cancer Causes and Control 03/2011; 22(5):775-83. · 2.88 Impact Factor
• Article: Trajectory of cognitive decline as a predictor of psychosis in early Alzheimer disease in the cardiovascular health study.

  James E Emanuel, Oscar L Lopez, Patricia R Houck, James T Becker, Elise A Weamer, Mary Ann A Demichele-Sweet, Lewis Kuller, Robert A Sweet
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  ABSTRACT: To compare the trajectories of cognitive decline between groups with, and without, the later development of psychotic symptoms during Alzheimer disease (AD) or mild cognitive impairment (MCI). : The authors examined cognitive function in a new analysis of an existing data set, the Cardiovascular Health Study, an epidemiologic, longitudinal follow-up study. Our analyses examined 9 years of follow-up data. Community. The authors examined subjects who were without dementia at study entry, received a diagnosis of AD or MCI during follow-up, and had been rated on the Neuropsychiatric Inventory for the presence of psychosis; 362 participants for the modified Mini-Mental State Examination (3MS) analysis and 350 participants for the digit symbol substitution test (DSST) analysis had sufficient follow-up data and apolipoprotein-∊ (APOE) genotyping. The 3MS and DSST were administered annually and analyzed using mixed-effects models including APOE4 status. : Mean 3MS and DSST scores did not differ between AD with psychosis (AD + P) and without psychosis groups at baseline. The 3MS and DSST scores decreased more rapidly in subjects who ultimately developed psychosis. Individuals who ultimately develop psychosis have more rapid cognitive deterioration during the earliest phases of AD than individuals with AD not developing psychosis. The genetic and other neurobiologic factors leading to the expression of AD + P may exert their effects by acceleration of the neurodegenerative process.
  The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 02/2011; 19(2):160-8. · 3.35 Impact Factor
• Article: Attitudes and cardiovascular disease.

  Hilary Tindle, Esa Davis, Lewis Kuller
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  ABSTRACT: Psychological attitudes are prospectively related to cardiovascular disease (CVD), but a causal relationship has not been demonstrated. Trait optimism/pessimism (positive or negative future expectation, respectively), and cynical hostility (mistrust of people), are attitudes with features of personality traits. These attitudes may affect CVD risk in several ways, by influencing an individual's (1) adoption of health behaviors, (2) maladaptive stress responding resulting in direct alteration of physiology (i.e., autonomic dysfunction, thrombosis, arrhythmias), (3) development of traditional CVD risk factors, and (4) lack of adherence to therapy in both primary and secondary prevention. More adaptive attitudes may favorably influence CVD risk at each of these critical junctures. The genetic and environmental (i.e., social, economic, racial/ethnic) determinants of attitudes have not been extensively studied. In addition, it is important to understand how some of these environmental determinants may also moderate the association between attitudes and CVD. Clinical trials to modify attitudes for CVD risk reduction (either by reducing negative attitudes or by increasing positive attitudes) are difficult to conduct, but are necessary to determine whether attitudes can indeed be modified, and if, so, to quantify any CVD-related benefits. To address these questions we present a broad, multidisciplinary research agenda utilizing mixed methods and integrating principles of epidemiology, genetics, psychophysiology, and behavioral medicine over the lifecourse (first figure). This overview focuses on attitudes and CVD, but has broader implications for understanding how psychological factors relate to chronic diseases of adulthood.
  Maturitas 10/2010; 67(2):108-13. · 2.77 Impact Factor
• Source

  Available from: rochester.edu

  Article: Effects of diet and physical activity interventions on weight loss and cardiometabolic risk factors in severely obese adults: a randomized trial.

  Bret H Goodpaster, James P Delany, Amy D Otto, Lewis Kuller, Jerry Vockley, Jeannette E South-Paul, Stephen B Thomas, Jolene Brown, Kathleen McTigue, Kazanna C Hames, Wei Lang, John M Jakicic
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  ABSTRACT: The prevalence of severe obesity is increasing markedly, as is prevalence of comorbid conditions such as hypertension and type 2 diabetes mellitus; however, apart from bariatric surgery and pharmacotherapy, few clinical trials have evaluated the treatment of severe obesity. To determine the efficacy of a weight loss and physical activity intervention on the adverse health risks of severe obesity. Single-blind randomized trial conducted from February 2007 through April 2010 at the University of Pittsburgh. Participants were 130 (37% African American) severely obese (class II or III) adult participants without diabetes recruited from the community. One-year intensive lifestyle intervention consisting of diet and physical activity. One group (initial physical activity) was randomized to diet and physical activity for the entire 12 months; the other group (delayed physical activity) had the identical dietary intervention but with physical activity delayed for 6 months. Changes in weight. Secondary outcomes were additional components comprising cardiometabolic risk, including waist circumference, abdominal adipose tissue, and hepatic fat content. Of 130 participants randomized, 101 (78%) completed the 12-month follow-up assessments. Although both intervention groups lost a significant amount of weight at 6 months, the initial-activity group lost significantly more weight in the first 6 months compared with the delayed-activity group (10.9 kg [95% confidence interval {CI}, 9.1-12.7] vs 8.2 kg [95% CI, 6.4-9.9], P = .02 for group × time interaction). Weight loss at 12 months, however, was similar in the 2 groups (12.1 kg [95% CI, 10.0-14.2] vs 9.9 kg [95% CI, 8.0-11.7], P = .25 for group × time interaction). Waist circumference, visceral abdominal fat, hepatic fat content, blood pressure, and insulin resistance were all reduced in both groups. The addition of physical activity promoted greater reductions in waist circumference and hepatic fat content. Among patients with severe obesity, a lifestyle intervention involving diet combined with initial or delayed initiation of physical activity resulted in clinically significant weight loss and favorable changes in cardiometabolic risk factors. clinicaltrials.gov Identifier: NCT00712127.
  JAMA The Journal of the American Medical Association 10/2010; 304(16):1795-802. · 30.03 Impact Factor
• Article: Alcohol consumption and risk of postmenopausal breast cancer by subtype: the women's health initiative observational study.

  Christopher I Li, Rowan T Chlebowski, Matthew Freiberg, Karen C Johnson, Lewis Kuller, Dorothy Lane, Lawrence Lessin, Mary Jo O'Sullivan, Jean Wactawski-Wende, Shagufta Yasmeen, Ross Prentice
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  ABSTRACT: Alcohol consumption is a well-established risk factor for breast cancer. This association is thought to be largely hormonally driven, so alcohol use may be more strongly associated with hormonally sensitive breast cancers. Few studies have evaluated how alcohol-related risk varies by breast cancer subtype. We assessed the relationship between self-reported alcohol consumption and postmenopausal breast cancer risk among 87 724 women in the Women's Health Initiative Observational Study prospective cohort from 1993 through 1998. Multivariable adjusted Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. A total of 2944 invasive breast cancer patients were diagnosed during follow-up through September 15, 2005. In multivariable adjusted analyses, alcohol consumption was positively related to risk of invasive breast cancer overall, invasive lobular carcinoma, and hormone receptor-positive tumors (all P(trend) ≤ .022). However, alcohol consumption was more strongly related to risk of certain types of invasive breast cancer compared with others. Compared with never drinkers, women who consumed seven or more alcoholic beverages per week had an almost twofold increased risk of hormone receptor-positive invasive lobular carcinoma (HR = 1.82; 95% CI = 1.18 to 2.81) but not a statistically significant increased risk of hormone receptor-positive invasive ductal carcinoma (HR = 1.14; 95% CI = 0.87 to 1.50; difference in HRs per drink per day among current drinkers = 1.15; 95% CI = 1.01 to 1.32, P = .042). The absolute rates of hormone receptor-positive lobular cancer among never drinkers and current drinkers were, 5.2 and 8.5 per 10 000 person-years, respectively, whereas for hormne receptor-positive ductal cancer they were 15.2 and 17.9 per 10 000 person-years, respectively. Alcohol use may be more strongly associated with risk of hormone-sensitive breast cancers than hormone-insensitive subtypes, suggesting distinct etiologic pathways for these two breast cancer subtypes.
  CancerSpectrum Knowledge Environment 09/2010; 102(18):1422-31. · 14.07 Impact Factor
• Article: Hydroxychloroquine and glycemia in women with rheumatoid arthritis and systemic lupus erythematosus.

  Sara Kaprove Penn, Amy H Kao, Laura L Schott, Jennifer R Elliott, Frederico G S Toledo, Lewis Kuller, Susan Manzi, Mary Chester M Wasko
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  ABSTRACT: To determine the relationship between current hydroxychloroquine (HCQ) use and 2 indicators of glycemic control, fasting glucose and insulin sensitivity, in nondiabetic women with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). Nondiabetic women with SLE (n = 149) or RA (n = 177) recruited between 2000 and 2005 for a cross-sectional evaluation of cardiovascular risk factors were characterized by HCQ usage status. Unadjusted and multivariately adjusted mean fasting glucose, median insulin, and insulin resistance [assessed by the homeostasis model assessment (HOMA-IR) calculation] were compared among HCQ users and nonusers for disease-specific groups. More women with SLE were taking HCQ than those with RA (48% vs 18%; p < 0.0001; mean dose ~ 400 mg vs ~ 200 mg). For women with SLE or RA, after adjustment for age, waist circumference, disease duration, prednisone dosage, C-reactive protein, menopausal status, nonsteroidal antiinflammatory drugs, and disease-specific indicators, serum glucose was lower in HCQ users than in nonusers (SLE: 85.9 vs 89.3 mg/dl, p = 0.04; RA: 82.5 vs 86.6 mg/dl, p = 0.05). In women with SLE, HCQ use also was associated with lower (log)HOMA-IR (0.97 vs 1.12, p = 0.09); in those with RA, no differences in (log)HOMA-IR were seen. HCQ usage was not associated with fasting insulin levels in either patient group. HCQ use was associated with lower fasting glucose in women with SLE or RA and also lower (log)HOMA-IR in the SLE group. The use of HCQ may be beneficial for reducing cardiovascular risk by improving glycemic control in these patients.
  The Journal of Rheumatology 06/2010; 37(6):1136-42. · 3.69 Impact Factor
• Article: Issues in accelerometer methodology: the role of epoch length on estimates of physical activity and relationships with health outcomes in overweight, post-menopausal women

  Kelley Gabriel, James McClain, Kendra Schmid, Kristi Storti, Robin High, Darcy Underwood, Lewis Kuller, Andrea Kriska
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  ABSTRACT: Abstract Background Current accelerometer technology allows for data collection using brief time sampling intervals (i.e., epochs). The study aims were to examine the role of epoch length on physical activity estimates and subsequent relationships with clinically-meaningful health outcomes in post-menopausal women. Methods Data was obtained from the Woman On the Move through Activity and Nutrition Study (n = 102). Differences in activity estimates presented as 60s and 10s epochs were evaluated using paired t-tests. Relationships with health outcomes were examined using correlational and regression analyses to evaluate differences by epoch length. Results Inactivity, moderate- and vigorous-intensity activity (MVPA) were significantly higher and light-intensity activity was significantly lower (all P < 0.001) when presented as 10s epochs. The correlation between inactivity and self-reported physical activity was stronger with 10s estimates ( P < 0.03); however, the regression slopes were not significantly different. Conversely, relationships between MVPA and body weight, BMI, whole body and trunk lean and fat mass, and femoral neck bone mineral density was stronger with 60s estimates (all P < 0.05); however, regression slopes were similar. Conclusion These findings suggest that although the use of a shorter time sampling interval may suggestively reduce misclassification error of physical activity estimates, associations with health outcomes did not yield strikingly different results. Additional studies are needed to further our understanding of the ways in which epoch length contributes to the ascertainment of physical activity in research studies. Trial Registration Clinical Trials Identifier: NCT00023543
  International Journal of Behavioral Nutrition and Physical Activity. 01/2010;
• Article: Combined association of lipids and blood pressure in relation to incident cardiovascular disease in the elderly: the cardiovascular health study.

  Nathan D Wong, Victor A Lopez, Craig S Roberts, Henry A Solomon, Gregory L Burke, Lewis Kuller, Russell Tracy, David Yanez, Bruce M Psaty
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  ABSTRACT: Hypertension and dyslipidemia are highly prevalent in the elderly. We studied the combined impact of both conditions on cardiovascular disease (CVD) events. We studied 4,311 participants aged 65-98 (61.2% female) from the Cardiovascular Health Study (CHS), a longitudinal epidemiologic study, with no prior CVD. We evaluated the relation of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or non-HDL-cholesterol combined with blood pressure (BP) categories to incident CVD-including coronary heart disease (CHD) (angina, myocardial infarction (MI), angioplasty, coronary bypass surgery, or CHD death), stroke, claudication, and CVD death over 15 years. CVD incidence (per 1,000 person years) ranged from 38.4 when BP <120/80 mm Hg and LDL-C <100 mg/dl to 94.8 when BP >or=160/100 mm Hg and LDL-C >or=160 mg/dl, and from 28.9 when BP <120/80 mm Hg and HDL >60 mg/dl to 87.1 for a BP >or=160/100 and HDL-C <40 mg/dl. Compared with those with BP <120/80 mm Hg with either LDL-C <100 mg/dl or HDL-C >60 mg/dl, hazard ratios (HRs) for CVD events were 2.1 when BP >or=160/100 mm Hg and LDL-C >or=160 mg/dl and 2.1 when BP >or=160/100 and HDL-C <40 mg/dl (all P < 0.01), with similar results for non-HDL-C. Elevated BP was associated with increased risk across all lipid levels. Increased LDL-C added risk mainly when BP <140/90 mm Hg, but lower HDL-C also predicted CVD in those with higher BP. Increased BP confers increased risks for CVD in elderly persons across all lipid levels. Although increased LDL-C added risk mainly when BP <140/90 mm Hg, low HDL-C added risk also in those with hypertension. These results document the importance of combined hypertension and dyslipidemia.
  American Journal of Hypertension 11/2009; 23(2):161-7. · 3.18 Impact Factor
• Article: Depressed mood is not a risk factor for incident dementia in a community-based cohort.

  James T Becker, Yue-Fang Chang, Oscar L Lopez, Mary Amanda Dew, Robert A Sweet, Deborah Barnes, Kristine Yaffe, Jeffrey Young, Lewis Kuller, Charles F Reynolds
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  ABSTRACT: To determine the relationship between depressed mood and the development of Alzheimer disease in cognitively normal individuals. Longitudinal and observational. Community-based cohort study. A total of 288 participants in the Cardiovascular Health Study-Cognition Study (mean age: 77.52, SD =3.65, range: 70-89). All of the participants were adjudicated as cognitively normal in 1998/1999, and all had at least three visits before 1998/1999 with measures of cognition and mood state. The mean length of follow-up from 1998-1999 to 2007 was 7.1 years (range: 1-9 years, median =9 years). The Center for Epidemiological Studies-Depression Scale (CESD) was used to index mood state, and the Modified Mini-Mental State Examination (3MSE) was the index of cognitive function among participants before 1998/1999. These measures were considered in two ways: participants were classified according to: 1) whether they showed a high-negative correlation between their CESD and 3MSE scores (i.e., indicating that greater depression was linked to poorer cognition) and 2) whether they showed persistently elevated CESD scores. The study outcome, development of dementia (N = 48), was based on consensus classifications, which was based on detailed neuropsychological and neurological exams. The authors could find no consistent relationship between mood state, either alone or in relation to cognitive status, and the subsequent development of dementia. Those individuals whose cognitive functions were highly correlated with their mood state were no more likely to develop dementia than other participants. Those who had persistently depressed mood were also no more likely to develop dementia than those without persistently depressed mood. Within the confines of this prospective, community-based study of elderly adults, the authors could not find strong evidence to support the hypothesis that mood disturbance was linked with the development of dementia.
  The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 09/2009; 17(8):653-63. · 3.35 Impact Factor
• Article: Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: results from the Cardiovascular Health Study.

  Kaycee M Sink, Xiaoyan Leng, Jeff Williamson, Stephen B Kritchevsky, Kristine Yaffe, Lewis Kuller, Sevil Yasar, Hal Atkinson, Mike Robbins, Bruce Psaty, David C Goff
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  ABSTRACT: Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control. Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n = 1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs). Among 414 participants who were exposed to ACE inhibitors and 640 who were not, there were 158 cases of incident dementia. Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88-1.15), difference in 3MSE scores (-0.32 points per year; P = .15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95% CI, 0.99-1.14). Adjusted results were similar. However, centrally active ACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure (P = .01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95% CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95% CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs. While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.
  Archives of internal medicine 08/2009; 169(13):1195-202. · 11.46 Impact Factor
• Article: Prevalence of hearing loss in Black and White elders: results of the Cardiovascular Health Study.

  Sheila R Pratt, Lewis Kuller, Evelyn O Talbott, Kathleen McHugh-Pemu, Alhaji M Buhari, Xiaohui Xu
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  ABSTRACT: The goal of this study was to determine the impact of age, gender, and race on the prevalence and severity of hearing loss in elder adults, aged 72-96 years, after accounting for income, education, smoking, and clinical and subclinical cardiovascular disease. Methods Air-conduction thresholds for standard and extended high-frequency pure-tones were obtained from a cohort of 548 (out of 717) elderly adults (ages 72-96 years) who were recruited during the Year 11 clinical visit (1999-2000) of the Cardiovascular Health Study (CHS) at the Pittsburgh, Pennsylvania site. Participant smoking, income, education, and cardiovascular disease histories were obtained from the CHS database and were included as factors. Hearing loss was more common and more severe for the participants in their 80s than for those in their 70s-the men more than the women and the White participants more than the Black participants. The inclusion of education, income, smoking, and cardiovascular disease (clinical and subclinical) histories as factors did not substantively impact the overall results. Although the data reported in this article were cross-sectional and a cohort phenomenon might have been operational, they suggested that hearing loss is more substantive in the 8th than the 7th decade of life and that race and gender influence this decline in audition. Given the high prevalence in the aging population and the differences across groups, there is a clear need to understand the nature and causes of hearing loss across various groups in order to improve prevention and develop appropriate interventions.
  Journal of Speech Language and Hearing Research 05/2009; 52(4):973-89. · 1.88 Impact Factor
• Article: Interruption of antiretroviral therapy is associated with increased plasma cystatin C.

  Amanda Mocroft, Christina Wyatt, Lynda Szczech, Jacquie Neuhaus, Wafaa El-Sadr, Russell Tracy, Lewis Kuller, Michael Shlipak, Brian Angus, Harting Klinker, Michael Ross
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  ABSTRACT: Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4 cell count (drug conservation) had altered cystatin C levels compared with those randomized to continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the drug conservation and viral suppression groups, respectively. Logistic regression was used to model the odds of at least 0.15 mg/dl increase in cystatin C (1 SD) in the first month after randomization, adjusting for demographic and clinical characteristics. At randomization, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug conservation and viral suppression arms, respectively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl increase in cystatin C in the drug conservation and viral suppression arms, respectively (P = 0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, participants in the viral suppression arm had significantly reduced odds of at least 0.15 mg/dl increase in cystatin C in the first month (odds ratio 0.42; 95% confidence interval 0.23-0.74, P = 0.0023). These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function.
  AIDS (London, England) 02/2009; 23(1):71-82. · 4.91 Impact Factor