Marian C Limacher

University of Florida, Gainesville, Florida, United States

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Publications (107)1079.88 Total impact

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    Circulation 12/2014; 66(4). DOI:10.1161/CIR.0000000000000156 · 14.43 Impact Factor

  • Journal of the American College of Cardiology 12/2014; DOI:10.1016/j.jacc.2014.12.018 · 16.50 Impact Factor
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    ABSTRACT: INTRODUCTION: Obesity is a major risk factor for physical disability in older adults. The contribution of early onset of obesity and weight history to physical impairment later in life remains inconclusive. METHODS: Postmenopausal women (n=76,016, 63.5 ± 7.3 years) recalled weight and height at ages 18, 35, 50 years and reported it at their baseline measurement. Standard body mass index (BMI=kg/m2) categories were used to evaluate associations between early onset obesity and weight transitions on severe physical impairment (SPI), defined as scoring < 60 on the Rand 36-Item Health survey. RESULTS: Women reporting being overweight or obese at 18 years had a higher likelihood of SPI (1.48, 95% Confidence Interval (CI): 1.32-1.65; and 2.07, 95% CI: 1.66-2.58, respectively) than normal weight counterparts. Weight changes from normal to high (overweight/obese) or underweight BMI’s yielded higher SPI rates [1.98 (1.82-2.12) and 1.34 (1.07-1.70), respectively] compared to women who remained weight stable. Women shifting from underweight to high BMI’s were more likely to have SPI [1.57 (1.15-2.14)]. High to normal BMI transitions resulted in a lower SPI rate [0.52 (0.39-0.70)]. Results were adjusted for demographics, behaviors, comorbidities and medications. DISCUSSION: Obesity in early adulthood was associated with higher severe physical impairment rates later in life. Weight transitions toward being underweight, overweight or obese also increased the risk of SPI. In contrast, overweight women who lost weight over their lifetime show reduced risk of impairment. Maintenance of a healthy body weight throughout life is important for reducing risk of physical impairment.
    142nd APHA Annual Meeting and Exposition 2014; 11/2014
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    ABSTRACT: Objective To evaluate the effects and costs of three doses of behavioral weight-loss treatment delivered via Cooperative Extension Offices in rural communities.Methods Obese adults (N = 612) were randomly assigned to low, moderate, or high doses of behavioral treatment (i.e., 16, 32, or 48 sessions over two years) or to a control condition that received nutrition education without instruction in behavior modification strategies.ResultsTwo-year mean reductions in initial body weight were 2.9% (95% Credible Interval = 1.7-4.3), 3.5% (2.0-4.8), 6.7% (5.3-7.9), and 6.8% (5.5-8.1) for the control, low-, moderate-, and high-dose conditions, respectively. The moderate-dose treatment produced weight losses similar to the high-dose condition and significantly larger than the low-dose and control conditions (posterior probability > 0.996). The percentages of participants who achieved weight reductions ≥ 5% at two years were significantly higher in the moderate-dose (58%) and high-dose (58%) conditions compared with low-dose (43%) and control (40%) conditions (posterior probability > 0.996). Cost-effectiveness analyses favored the moderate-dose treatment over all other conditions.ConclusionsA moderate dose of behavioral treatment produced two-year weight reductions comparable to high-dose treatment but at a lower cost. These findings have important policy implications for the dissemination of weight-loss interventions into communities with limited resources.
    Obesity 11/2014; 22(11). DOI:10.1002/oby.20832 · 3.73 Impact Factor
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    ABSTRACT: Background: Conclusive data about cardiovascular toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) are sparse. We hypothesized that regular NSAID use is associated with increased risk for cardiovascular events in postmenopausal women, and that this association is stronger with greater cyclooxygenase (cox)-2 when compared with cox-1 inhibition. Methods and results: Postmenopausal women enrolled in the Women's Health Initiative were classified as regular users or nonusers of nonaspirin NSAIDs. Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total cardiovascular disease defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary analyses considered the association of selective cox-2 inhibitors (eg, celecoxib), nonselective agents with cox-2>cox-1 inhibition (eg, naproxen), and nonselective agents with cox-1>cox-2 inhibition (eg, ibuprofen) with the primary outcome. Overall, 160 801 participants were available for analysis (mean follow-up, 11.2 years). Regular NSAID use at some point in time was reported by 53 142 participants. Regular NSAID use was associated with an increased hazard for cardiovascular events versus no NSAID use (hazard ratio [HR], 1.10; 95% confidence interval, 1.06-1.15; P<0.001). Selective cox-2 inhibitors were associated with a modest increased hazard for cardiovascular events (hazard ratio, 1.13; 1.04-1.23; P=0.004 and celecoxib only: HR, 1.13; 1.01-1.27; P=0.031). Among aspirin users, concomitant selective cox-2 inhibitor use was no longer associated with increased hazard for cardiovascular events. There was an increased risk for agents with cox-2>cox-1 inhibition (HR, 1.17; 1.10-1.24; P<0.001 and naproxen only: HR, 1.22; 1.12-1.34; P<0.001). This harmful association remained among concomitant aspirin users. We did not observe a risk elevation for agents with cox-1>cox-2 inhibition (HR, 1.01; 0.95-1.07; P=0.884 and ibuprofen only: HR, 1.00; 0.93-1.07; P=0.996). Conclusions: Regular use of selective cox-2 inhibitors and nonselective NSAIDs with cox-2>cox-1 inhibition showed a modestly increased hazard for cardiovascular events. Nonselective agents with cox-1>cox-2 inhibition were not associated with increased cardiovascular risk. Clinical trial registration url: Unique identifier: NCT00000611.
    Circulation Cardiovascular Quality and Outcomes 07/2014; 7(4). DOI:10.1161/CIRCOUTCOMES.113.000800 · 5.66 Impact Factor
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    Arch G Mainous · Rebecca J Tanner · Ronald I Shorr · Marian C Limacher ·
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    ABSTRACT: Background Aspirin use has been shown to be an effective tool in cardiovascular disease (CVD) prevention among high‐risk patients. The patient‐reported physician recommendation for aspirin as preventive therapy among high‐ and low‐risk patients is unknown. Methods and Results We conducted an analysis of the National Health and Nutrition Examination Survey 2011–2012 to examine the use of aspirin for CVD prevention. Patients without previously diagnosed CVD were classified into high and low risk based on their Framingham Risk Score (10‐year coronary heart disease risk). Among patients without previously diagnosed CVD, 22.5% were classified as high risk. Of the high‐risk individuals, 40.9% reported being told by their physician to take aspirin, with 79.0% complying. Among those who were at low risk, 26.0% were told by their physician to take aspirin, with 76.5% complying. Logistic regression analysis indicated that age, access to a regular source of care, education, and insurance status were significant predictors of patient‐reported physician recommendations for aspirin use for primary prevention. Among high‐risk patients, age, race, and insurance status were significant predictors of reported recommendations for aspirin use. Among low‐risk patients, age, education, obesity, and insurance status were significant predictors of reported recommendations for aspirin use. Conclusions Patient reports indicate nonideal rates of being told to take aspirin, for both high‐ and low‐risk patients for primary prevention. Clinical decision support tools that could assist physicians in identifying patients at risk may increase patient reports of physician recommendations for aspirin use.
    Journal of the American Heart Association 06/2014; 3(4). DOI:10.1161/JAHA.114.000989 · 4.31 Impact Factor
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    ABSTRACT: Aims Thiazide diuretics are recommended as first line antihypertensive treatment, but may contribute to new onset diabetes. We aimed to describe change in fasting glucose (FG) during prolonged thiazide treatment in an observational setting. Methods We conducted an observational, non-randomized, open label, follow-up study of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 studies. We enrolled previous participants from the PEAR or PEAR-2 studies with at least six months of continuous treatment with either hydrochlorothiazide (HCTZ) or chlorthalidone. Linear regression was used to identify associations with changes in FG after prolonged thiazide and thiazide-like diuretic treatment. Results A total of 40 participants were included with a mean 29 (range 8-72) months of thiazide treatment. FG increased 6.5 (SD 13.0) mg/dL during short-term thiazide treatment and 3.6 (SD 15.3) mg/dL FG during prolonged thiazide treatment. Increased FG at follow-up was associated with longer thiazide treatment duration (beta = 0.34, p = 0.008) and lower baseline FG (beta = -0.46, p = 0.02). β blocker treatment in combination with prolonged thiazide diuretic treatment was also associated with increased FG and increased two-hour glucose obtained from OGTT. Conclusions Our results indicate that prolonged thiazide treatment duration is associated with increased FG and that overall glycemic status worsens when thiazide/thiazide-like diuretics are combined with β blockers.
    Diabetes research and clinical practice 06/2014; 104(3). DOI:10.1016/j.diabres.2014.04.004 · 2.54 Impact Factor
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    ABSTRACT: 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.
    Obesity 04/2014; 22(4). DOI:10.1002/oby.20620 · 3.73 Impact Factor
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    ABSTRACT: Many studies use medical record review for ascertaining outcomes. One large, longitudinal study, the Women's Health Initiative (WHI), ascertains strokes using participant self-report and subsequent physician review of medical records. This is resource-intensive. Herein, we assess whether Medicare data can reliably assess stroke events in the WHI. Subjects were WHI participants with fee-for-service Medicare. Four stroke definitions were created for Medicare data using discharge diagnoses in hospitalization claims: definition 1, stroke codes in any position; definition 2, primary position stroke codes; and definitions 3 and 4, hemorrhagic and ischemic stroke codes, respectively. WHI data were randomly split into training (50%) and test sets. A concordance matrix was used to examine the agreement between WHI and Medicare stroke diagnosis. A WHI stroke and a Medicare stroke were considered a match if they occurred within ±7 days of each other. Refined analyses excluded Medicare events when medical records were unavailable for comparison. Training data consisted of 24 428 randomly selected participants. There were 577 WHI strokes and 557 Medicare strokes using definition 1. Of these, 478 were a match. With regard to algorithm performance, specificity was 99.7%, negative predictive value was 99.7%, sensitivity was 82.8%, positive predictive value was 85.8%, and κ=0.84. Performance was similar for test data. Whereas specificity and negative predictive value exceeded 99%, sensitivity ranged from 75% to 88% and positive predictive value ranged from 80% to 90% across stroke definitions. Medicare data seem useful for population-based stroke research; however, performance characteristics depend on the definition selected.
    Stroke 02/2014; 45(3). DOI:10.1161/STROKEAHA.113.003408 · 5.72 Impact Factor
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    ABSTRACT: IMPORTANCE Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention. OBJECTIVE To report a comprehensive, integrated overview of findings from the 2 Women's Health Initiative (WHI) hormone therapy trials with extended postintervention follow-up. DESIGN, SETTING, AND PARTICIPANTS A total of 27 347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers. INTERVENTIONS Women with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 8506) or placebo (n = 8102). Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 5310) or placebo (n = 5429). The intervention lasted a median of 5.6 years in CEE plus MPA trial and 7.2 years in CEE alone trial with 13 years of cumulative follow-up until September 30, 2010. MAIN OUTCOMES AND MEASURES Primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and death. RESULTS During the CEE plus MPA intervention phase, the numbers of CHD cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01-1.53). Other risks included increased stroke, pulmonary embolism, dementia (in women aged ≥65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during cumulative follow-up (434 cases for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11-1.48]). The risks and benefits were more balanced during the CEE alone intervention with 204 CHD cases for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.78-1.14) and 104 vs 135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61-1.02); cumulatively, there were 168 vs 216, respectively, cases of breast cancer diagnosed (HR, 0.79; 95% CI, 0.65-0.97). Results for other outcomes were similar to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone, younger women (aged 50-59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P < .05 for trend by age). Absolute risks of adverse events (measured by the global index) per 10 000 women annually taking CEE plus MPA ranged from 12 excess cases for ages of 50-59 years to 38 for ages of 70-79 years; for women taking CEE alone, from 19 fewer cases for ages of 50-59 years to 51 excess cases for ages of 70-79 years. Quality-of-life outcomes had mixed results in both trials. CONCLUSIONS AND RELEVANCE Menopausal hormone therapy has a complex pattern of risks and benefits. Findings from the intervention and extended postintervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women. TRIAL REGISTRATION Identifier: NCT00000611.
    JAMA The Journal of the American Medical Association 10/2013; 310(13):1353-1368. DOI:10.1001/jama.2013.278040 · 35.29 Impact Factor
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    ABSTRACT: OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia in women. Large studies evaluating key AF risk factors in older women are lacking. We aimed to identify risk factors for AF in postmenopausal women and measure population burden of modifiable risk factors. DESIGN: Prospective observational study. SETTING: The Women's Health Initiative (WHI) Observational Study. PATIENTS: 93 676 postmenopausal women were followed for an average of 9.8 years for cardiovascular outcomes. After exclusion of women with prevalent AF or incomplete data, 8252 of the remaining 81 892 women developed incident AF. MAIN OUTCOME MEASURES: Incident AF was identified by WHI-ascertained hospitalisation records and diagnosis codes from Medicare claims. Multivariate Cox hazard regression analysis identified independent risk factors for incident AF. RESULTS: Age, hypertension, obesity, diabetes, myocardial infarction and heart failure were independently associated with incident AF. Hypertension and overweight status accounted for 28.3% and 12.1%, respectively, of the population attributable risk. Hispanic and African-American participants had lower rates of incident AF (HR 0.58, 95% CI 0.47 to 0.70 and HR 0.59, 95% CI 0.53 to 0.65, respectively) than Caucasians. CONCLUSIONS: Caucasian ethnicity, traditional cardiovascular risk factors and peripheral arterial disease were independently associated with higher rates of incident AF in postmenopausal women. Hypertension and overweight status accounted for a large proportion of population attributable risk. Measuring burden of modifiable AF risk factors in older women may help target interventions.
    Heart (British Cardiac Society) 06/2013; 99(16). DOI:10.1136/heartjnl-2013-303798 · 5.60 Impact Factor
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    ABSTRACT: Background: Long and short sleep duration are associated with increased risk for coronary heart disease (CHD) and cardiovascular disease (CVD); however, evidence is inconsistent. We sought to identify whether self-reported sleep duration and insomnia, based on a validated questionnaire, are associated with increased incident CHD and CVD among postmenopausal women. Methods: Women's Health Initiative Observational Study Participants (N=86,329; 50-79 years) who reported on sleep at baseline were followed for incident CVD events. Associations of sleep duration and insomnia with incident CHD and CVD were evaluated using Cox proportional hazards models over 10.3 years. Results: Women with high insomnia scores had elevated risk of CHD (38%) and CVD (27%) after adjustment for age and race, and in fully adjusted models (hazard ratio [HR]=1.19, 95% confidence interval [CI] 1.09-1.30; 1.11 95% CI 1.03-2.00). Shorter (≤5 hours) and longer (≥10 hours) sleep duration demonstrated significantly higher incident CHD (25%) and CVD (19%) in age- and race-adjusted models, but this was not significant in fully adjusted models. Formal tests for interaction indicated significant interactions between sleep duration and insomnia for risk of CHD (p<0.01) and CVD (p=0.02). Women with high insomnia scores and long sleep demonstrated the greatest risk of incident CHD compared to midrange sleep duration (HR=1.93, 95% CI 1.06-3.51) in fully adjusted models. Conclusions: Sleep duration and insomnia are associated with CHD and CVD risk, and may interact to cause almost double the risk of CHD and CVD. Additional research is needed to understand how sleep quality modifies the association between prolonged sleep and cardiovascular outcomes.
    Journal of Women's Health 05/2013; 22(6). DOI:10.1089/jwh.2012.3918 · 2.05 Impact Factor
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    ABSTRACT: BACKGROUND: After clinical trials end, continued follow-up of the assembled cohort often is desirable for additional research. Factors influencing participants' decisions to consent to additional follow-up and how these shape posttrial cohorts have not been broadly studied. PURPOSE: We examined how two re-enrollment campaigns and the passage of time altered features of the posttrial cohorts compared with the original Women's Health Initiative (WHI) Hormone Therapy clinical trials. METHODS: We examined associations that markers of sociodemography, health, lifestyle, and on-trial experiences had with re-enrollment and contrasted the characteristics of successive posttrial cohorts with those of the original enrollees. RESULTS: The posttrial enrollment campaigns re-enrolled 81.1% and 82.5% of available women, respectively. Women who re-enrolled tended to have better health characteristics than those not re-enrolled. Compared to women of comparable age in the original cohort, women retained for the second posttrial follow-up less often had a history of cardiovascular disease (odds ratio (OR) = 0.36), hypertension (OR = 0.57), diabetes (OR = 0.59), or measured cognitive deficit (OR = 0.40). These women more often had graduated from high school (OR = 1.72) and had participated in other WHI trials (OR = 1.76). LIMITATIONS: We have examined experience with creating follow-up cohorts from participants in a single study. Thus, our findings may not apply to other cohorts and protocols. CONCLUSIONS: Posttrial enrollment in follow-up studies can be successful; however, the characteristics of the resulting cohort may differ substantially from the originally assembled group of trial participants. Collection during the original trial of potential predictors of differential re-enrollment may strengthen interpretation of findings.
    Clinical Trials 03/2013; 10(3). DOI:10.1177/1740774513477931 · 1.93 Impact Factor
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    ABSTRACT: Habitual snoring may be associated with cardiovascular disease (CVD); however, limited evidence exists among women. We investigated whether frequent snoring is a predictor of coronary heart disease (CHD) and stroke among 42,244 postmenopausal women participating in the Women's Health Initiative Observational Study. Participants provided self-reported information regarding snoring habits at baseline (1993 to 1998) and were followed up for outcomes through August 2009. Physician adjudicators confirmed CHD (defined as myocardial infarction, CHD death, revascularization procedures, or hospitalized angina) and ischemic stroke. Cox proportional hazards models were used to evaluate whether snoring frequency is a significant predictor of the adjudicated outcomes. We observed 2,401 incident cases of CHD during 437,899 person-years of follow-up. After adjusting for age and race, frequent snoring was associated with incident CHD (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.39 to 1.70) and stroke (HR 1.41, 95% CI 1.19 to 1.66), and all CVD (HR 1.46, 95% CI 1.34 to 1.60). In fully adjusted models that included CVD risk factors such as obesity, hypertension, and diabetes, frequent snoring was associated with a more modest increase in incident CHD (HR 1.14, 95% CI 1.01 to 1.28), stroke (HR 1.19, 95% CI 1.02 to 1.40), and CVD (HR 1.12, 95% CI 1.01 to 1.24). In conclusion, snoring is associated with a modest increased risk of incident CHD, stroke, and CVD after adjustment for CVD risk factors. Additional studies are needed to elucidate the mechanisms by which snoring might be associated with CVD risk factors and outcomes.
    The American journal of cardiology 12/2012; 111(4). DOI:10.1016/j.amjcard.2012.10.039 · 3.28 Impact Factor
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    ABSTRACT: BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE: We sought to identify novel genetic variants associated with resting heart rate in African Americans. METHODS: Ten cohort studies participating in the CARe and COGENT consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from ten-second resting 12-lead ECGs and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (p≤ 2.5x10(-8)). RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele, p=4.98 x 10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European GWAS, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSION: An intergenic region downstream of GJA1, the gene encoding Connexin-43, the major protein of the human myocardial gap junction and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.
    Heart rhythm: the official journal of the Heart Rhythm Society 11/2012; 10(3). DOI:10.1016/j.hrthm.2012.11.014 · 5.08 Impact Factor
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    ABSTRACT: Background: Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. Methods and results: First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12,097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13,105). There was no evidence of association between genetic ancestry and QT interval (P=0.94). Genome-wide significant associations (P<2.5 × 10(-8)) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P=2 × 10(-15)) and ATP1B1 (rs1320976, P=2 × 10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values (P<10(-5)) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF, and PLN. Conclusions: We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.
    Circulation Cardiovascular Genetics 11/2012; 5(6). DOI:10.1161/CIRCGENETICS.112.962787 · 4.60 Impact Factor
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    ABSTRACT: Background: The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and results: We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0 × 10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0 × 10(-8)). Conclusions: This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.
    Circulation Cardiovascular Genetics 11/2012; 5(6). DOI:10.1161/CIRCGENETICS.112.963991 · 4.60 Impact Factor
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    ABSTRACT: OBJECTIVES: The aim of this study was to estimate the annual incidence rate of sudden cardiac death (SCD) and to identify risk factors for SCD in post-menopausal women. BACKGROUND: With the aging U.S. population, post-menopausal women now have the greatest population burden of cardiovascular disease including SCD. METHODS: We examined 161,808 women who participated in the Women's Health Initiative clinical trials and observational study. The women were recruited at 40 clinical sites across the United States, enrolled between 1993 and 1998, and followed until August 2009. Our primary endpoint is incident SCD, defined as death occurring within 1 h of symptom onset or within 1 h after the participant was last seen without symptoms and death that occurred in the absence of a potentially lethal non-coronary disease process. RESULTS: Four hundred eighteen women experienced adjudicated SCD. The incidence rate of SCD was 2.4/10,000 women/year (95% confidence interval: 2.2 to 2.7). We identified the following independent risk factors for SCD: older age, African-American race, tobacco use, higher pulse, higher waist-to-hip ratio, elevated white blood cell count, history of heart failure, diabetes, history of myocardial infarction, previous carotid artery disease, and hypertension. Population-attributable fractions were greatest for hypertension, waist-to-hip ratio, and myocardial infarction. CONCLUSIONS: Besides traditional risk factors for coronary heart disease, risk factors for sudden cardiac death in post-menopausal women include African-American race, higher pulse, higher waist-to-hip ratio, elevated white blood cell count, and heart failure. Nearly one-half of women who experienced sudden cardiac death had no previous diagnosis of coronary heart disease.
    Journal of the American College of Cardiology 11/2012; 60(25). DOI:10.1016/j.jacc.2012.09.031 · 16.50 Impact Factor
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    ABSTRACT: A major challenge after successful weight loss is continuing the behaviors required for long-term weight maintenance. This challenge can be exacerbated in rural areas with limited local support resources. This study describes and compares program costs and cost effectiveness for 12-month extended-care lifestyle maintenance programs after an initial 6-month weight-loss program. We conducted a 1-year prospective randomized controlled clinical trial. The study included 215 female participants age 50 years or older from rural areas who completed an initial 6-month lifestyle program for weight loss. The study was conducted from June 1, 2003 to May 31, 2007. The intervention was delivered through local Cooperative Extension Service offices in rural Florida. Participants were randomly assigned to a 12-month extended-care program using either individual telephone counseling (n=67), group face-to-face counseling (n=74), or a mail/control group (n=74). Program delivery costs, weight loss, and self-reported health status were directly assessed through questionnaires and program activity logs. Costs were estimated across a range of enrollment sizes to allow inferences beyond the study sample. Nonparametric and parametric tests of differences across groups for program outcomes were combined with direct program cost estimates and expected value calculations to determine which scales of operation favored alternative formats for lifestyle maintenance. Median weight regain during the intervention year was 1.7 kg for participants in the face-to-face format, 2.1 kg for the telephone format, and 3.1 kg for the mail/control format. For a typical group size of 13 participants, the face-to-face format had higher fixed costs, which translated into higher overall program costs ($420 per participant) when compared with individual telephone counseling ($268 per participant) and control ($226 per participant) programs. Although the net weight lost after the 12-month maintenance program was higher for the face-to-face and telephone programs compared with the control group, the average cost per expected kilogram of weight lost was higher for the face-to-face program ($47/kg) compared with the other two programs (approximately $33/kg for telephone and control). Both the scale of operations and local demand for programs are important considerations in selecting a delivery format for lifestyle maintenance. In this study, the telephone format had a lower cost but similar outcomes compared with the face-to-face format.
    Journal of the American Academy of Nutrition and Dietetics 07/2012; 112(9):1363-73. DOI:10.1016/j.jand.2012.05.002 · 3.47 Impact Factor
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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: Unique identifier: NCT00000611.
    Circulation 07/2012; 126(6):688-96. DOI:10.1161/CIRCULATIONAHA.111.066688 · 14.43 Impact Factor

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8k Citations
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  • 1998-2014
    • University of Florida
      • • Department of Medicine
      • • Division of Cardiovascular Medicine
      Gainesville, Florida, United States
  • 2012
    • American College of Cardiology
      Washington, Washington, D.C., United States
  • 2005
    • University of Washington Seattle
      • Department of Epidemiology
      Seattle, WA, United States
  • 2004
    • University of Florida Health Science Center-Jacksonville
      Jacksonville, Florida, United States
  • 1999
    • American Heart Association
      Dallas, Texas, United States