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1.  Procedures for assessing psychological predictors of injuries in circus artists: a pilot prospective study 
Research on psychological risk factors for injury has focused on stable traits. Our objective was to test the feasibility of a prospective longitudinal study designed to examine labile psychological states as risk factors of injury.
We measured psychological traits at baseline (mood, ways of coping and anxiety), and psychological states every day (1-item questions on anxiety, sleep, fatigue, soreness, self-confidence) before performances in Cirque du Soleil artists of the show “O”. Additional questions were added once per week to better assess anxiety (20-item) and mood. Questionnaires were provided in English, French, Russian and Japanese. Injury and exposure data were extracted from electronic records that are kept as part of routine business practices.
The 43.9% (36/82) recruitment rate was more than expected. Most artists completed the baseline questionnaires in 15 min, a weekly questionnaire in <2 min and a daily questionnaire in <1 min. We improved the formatting of some questions during the study, and adapted the wording of other questions to improve clarity. There were no dropouts during the entire study, suggesting the questionnaires were appropriate in content and length. Results for sample size calculations depend on the number of artists followed and the minimal important difference in injury rates, but in general, preclude a purely prospective study with daily data collection because of the long follow-up required. However, a prospective nested case-crossover design with data collection bi-weekly and at the time of injury appears feasible.
A prospective study collecting psychological state data from subjects who train and work regularly together is feasible, but sample size calculations suggest that the optimal study design would use prospective nested case-crossover methodology.
PMCID: PMC4064279  PMID: 24920527
Epidemiology; Injury; Psychological risk factors; Prospective
2.  The Contributions of Unhealthy Lifestyle Factors to Apparent Resistant Hypertension: Findings from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study 
Journal of hypertension  2013;31(2):10.1097/HJH.0b013e32835b6be7.
Unhealthy lifestyle factors may contribute to apparent treatment resistant hypertension (aTRH). We examined associations of unhealthy lifestyle factors with aTRH in individuals taking antihypertensive medications from three or more classes.
Participants (n=2,602) taking three or more antihypertensive medication classes were identified from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study. aTRH was defined as having systolic/diastolic blood pressure ≥140/90 mmHg despite the use of three or more antihypertensive medication classes or the use of four or more classes to achieve blood pressure control. Lifestyle factors included obesity, physical inactivity, current smoking, heavy alcohol consumption, a low DASH diet score and high sodium-to-potassium (Na/K) intake.
Among participants taking three or more antihypertensive medication classes, 1,293 (49.7%) participants had aTRH. The prevalence of unhealthy lifestyle factors in participants with and without aTRH was 55.2% and 51.7% respectively for obesity, 42.2% and 40.5% for physical inactivity, 11.3% and 11.5% for current smoking, 3.1% and 4.0% for heavy alcohol consumption, 23.1% and 21.5% for low DASH diet score, and 25.4% and 24.4% for high Na/K intake. After adjustment for age, sex, race, and geographic region of residence, none of the unhealthy lifestyle factors was associated with aTRH. The associations between each unhealthy lifestyle factor and aTRH remained non-significant after additional adjustment for education, income, depressive symptoms, total calorie intake, and co-morbidities.
Unhealthy lifestyle factors did not have independent associations with aTRH among individuals taking three or more antihypertensive medication classes.
PMCID: PMC3838894  PMID: 23303356
Hypertension; blood pressure; antihypertensive agents; epidemiology
3.  Association between antihypertensive medication adherence and visit-to-visit variability of blood pressure 
It has been hypothesized that high visit-to-visit variability (VVV) of systolic blood pressure (SBP) may be the result of poor antihypertensive medication adherence. We studied this association using data from 1,391 individuals taking antihypertensive medication selected from a large managed care organization. The 8-item Morisky Medication Adherence Scale, administered during three annual surveys, captured self-report adherence with scores <6, 6 to <8 and 8 representing low, medium and high adherence, respectively. The mean (standard deviation [SD]) for SD of SBP across study visits was 12.9 (4.4), 13.5 (4.8), and 14.1 (4.5) mmHg in participants with high, medium and low self-reported adherence, respectively. After multivariable adjustment and compared to those with high self-report adherence, SD of SBP was 0.60 (95% CI: 0.13–1.07) and 1.08 (95% CI: 0.29–1.87) mmHg higher among participants with medium and low self-report adherence, respectively. Results were consistent when pharmacy fill was used to define adherence. These data suggest low antihypertensive medication adherence explains only a small proportion of VVV of SBP.
PMCID: PMC3659162  PMID: 23339729
Medication adherence; blood pressure variability; hypertension
4.  Dietary glycemic index, dietary glycemic load, and incidence of heart failure events: a prospective study of middle-aged and elderly women 
Dietary glycemic index (GI) and glycemic load (GL), measures of the propensity of dietary carbohydrate to increase blood glucose, have been associated with risk of coronary heart disease, but their association with incidence of heart failure (HF) is unknown. We therefore assessed whether dietary GI and GL were associated with rates of HF events.
We conducted a prospective, observational study of 36,019 women 48-83 years old without baseline HF, diabetes, or myocardial infarction who were participants in the Swedish Mammography Cohort, a prospective cohort study. Diet was measured using food-frequency questionnaires. Women were followed from January 1, 1998 through December 31, 2006 for HF hospitalization or death through the Swedish inpatient and cause-of-death registers. Cox proportional hazards models adjusted for age and other risk factors were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI).
Over 9 years of follow-up, 639 of 36,019 women died of HF (n = 54) or were hospitalized for HF for the first time (n = 585). We did not find statistically significant associations between dietary GI and HF events (RR comparing highest to lowest quartile = 1.12, 95% CI 0.87-1.45, p for trend = 0.31) or between dietary GL and HF events (RR comparing highest to lowest quartile = 1.30, 95% CI 0.87-1.93, p for trend = 0.16). Results were not significantly different in normal weight and overweight women.
In this population, dietary GI did not appear to be associated with incident HF events. There was a suggestion of an association between dietary GL and HF which did not reach statistical significance.
PMCID: PMC2898730  PMID: 20595647
glycemic index; glycemic load; heart failure
5.  Adiposity and incidence of heart failure hospitalization and mortality: a population-based prospective study 
Circulation. Heart failure  2009;2(3):202-208.
Obesity is associated with heart failure (HF) incidence. We examined the strength of the association of body mass index (BMI) with HF by age and joint associations of BMI and waist circumference (WC).
Methods and Results
Women aged 48–83 (n = 36,873) and men aged 45–79 (n = 43,487) self-reported height, weight, and WC. HF hospitalization or death (n = 382 women, 718 men) between January 1, 1998 and December 31, 2004 was determined through administrative registers. Hazard ratios (HR), from Cox proportional-hazards models, for an interquartile range higher BMI were 1.39 (95% confidence interval [CI] 1.15–1.68) at age 60 and 1.13 (95% CI 1.02–1.27) at 75 in women. In men, HR were 1.54 (95% CI 1.37–1.73) at 60 and 1.25 (95% CI 1.16–1.35) at 75. A 10 cm higher WC was associated with 15% (95% CI 2%–31%) and 18% (95% CI 4%–33%) higher HF rates among women with BMI 25 and 30 kg/m2, respectively; HR for 1 kg/m2 higher BMI were 1.00 (95% CI 0.96–1.04) and 1.01 (95% CI 0.98–1.04) for WC 70 and 100 cm, respectively. In men, a 10 cm higher WC was associated with 16% and 18% higher rates for BMI 25 and 30 kg/m2, respectively; a 1 kg/m2 higher BMI was associated with 4% higher HF rates regardless of WC.
Strength of the association between BMI and HF events declined with age. In women, higher WC was associated with HF at all levels of BMI. Both BMI and WC were predictors among men.
PMCID: PMC2732194  PMID: 19808341
epidemiology; heart failure; obesity; aging
6.  Prevalence and prognosis of unrecognized myocardial infarctions in chronic kidney disease 
Nephrology Dialysis Transplantation  2011;27(9):3482-3488.
This study makes an important contribution by being one of the first to define the burden of clinically silent myocardial infarctions in the CKD community.
Unrecognized myocardial infarctions (UMIs) are common in the general population but have not been well studied in patients with chronic kidney disease (CKD). The purpose of this study was to determine the prevalence and prognosis for mortality of UMI among adults with CKD.
The current study included 18 864 participants in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study who completed a baseline examination including a 12-lead electrocardiogram (ECG). UMI was defined as the presence of myocardial infarction (MI) by Minnesota ECG classification in the absence of self-reported or recognized MI (RMI). Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and albuminuria using albumin-to-creatinine ratio from a spot urine sample. All-cause mortality was assessed over a median 4 years of follow-up.
The prevalence of UMI was 4, 6, 6 and 13% among participants with eGFR levels of ≥60, 45–59.9, 30–44.9 and <30 mL/min/1.73m2, respectively, and 4, 5, 7 and 10% among participants with albuminuria levels of <10, 10–29.9, 30–299.9 and ≥300 mg/g, respectively. Compared to those with no MI, the multivariable adjusted hazard ratio for all-cause mortality associated with UMI and RMI was 1.65 [95% confidence interval (CI): 1.09–2.49] and 1.65 (95% CI: 1.20–2.26), respectively, among individuals with an eGFR <60 mL/min/1.73m2 and 1.49 (95% CI: 1.03–2.16) and 1.88 (95% CI: 1.40–2.52) among individuals with albuminuria ≥30 mg/g.
UMIs are common among individuals with an eGFR <60 mL/min/1.73m2 and albuminuria and associated with an increased mortality risk.
PMCID: PMC3433770  PMID: 22167594
chronic kidney disease; coronary artery disease; mortality
7.  Habitual Coffee Consumption and Risk of Heart Failure: A Dose–Response Meta-Analysis 
Circulation. Heart failure  2012;5(4):401-405.
There have been discrepant findings on the association between coffee consumption and risk of incident heart failure.
Methods and Results
We conducted a systematic review and a dose-response meta-analysis of prospective studies that assessed the relationship between habitual coffee consumption and the risk of heart failure. We searched electronic databases (MEDLINE, EMBASE, and Cinahl) from January 1966 through December 2011 with the use of a standardized protocol. Eligible studies were prospective cohort studies that examined the association of coffee consumption with incident heart failure. Five independent prospective studies of coffee consumption and heart failure risk, including 6,522 heart failure events and 140,220 participants were included in the meta-analysis. We observed a statistically significant J-shaped relationship between coffee and heart failure. Compared to no consumption, the strongest inverse association was seen for 4 servings/day, and a potentially higher risk at higher levels of consumption. There was no evidence that the relationship between coffee and heart failure risk varied by sex or by baseline history of MI or diabetes.
Moderate coffee consumption is inversely associated with risk of heart failure, with the largest inverse association observed for consumption of 4 servings per day.
PMCID: PMC3425948  PMID: 22740040
dose-response meta-analysis; coffee; heart failure; epidemiology
8.  Relations between QRS|T Angle, Cardiac Risk Factors, and Mortality in the Third National Health and Nutrition Examination Survey (NHANES III) 
The American Journal of Cardiology  2012;109(7):981-987.
On the surface electrocardiogram (ECG), an abnormally wide QRS|T angle reflects changes in regional action potential duration profiles and in direction of repolarization sequence which is thought to increase the risk of ventricular arrhythmia. We investigated the relationship between abnormal QRS|T angle and mortality in a nationally representative sample of individuals without clinically evident heart disease. We studied 7,052 participants ≥ 40 years of age in the Third National Health and Nutrition Examination Survey (NHANES III) with 12-lead ECGs. Individuals with self-report or ECG evidence of a prior myocardial infarction, QRS duration ≥120 msec, or history of heart failure were excluded. Borderline and abnormal spatial QRS|T angle were defined according to sex-specific 75th and 95th percentiles of frequency distributions. All-cause (n=1093 women, n=1191 men) and cardiovascular mortality (n=462 women, n=455 men) over 14 years was assessed through linkage with the National Death Index. In multivariable analyses, abnormal spatial QRS|T angle was associated with an increased hazard ratio (HR) for cardiovascular mortality in women (HR 1.82, 95% CI 1.05-3.14) and men (HR 2.21, 95% CI 1.32-3.68). An abnormal QRS|T angle was also associated with increased multivariable adjusted HRs for all-cause mortality in women (HR 1.30, 95% CI 0.95-1.78) and men (HR 1.87, 95% CI 1.29-2.7). Borderline QRS|T angle was not associated with increased risk for all-cause or cardiovascular mortality. In conclusion, abnormal QRS|T angle, as measured on a 12-lead ECG, was associated with increased risk for cardiovascular and all-cause mortality in this population-based sample without known heart disease.
PMCID: PMC3313000  PMID: 22221946
electrocardiogram; cardiac mortality; QRS|T angle; epidemiology
9.  Assessment tools for unrecognized myocardial infarction: a cross-sectional analysis of the REasons for geographic and racial differences in stroke population 
Routine electrocardiograms (ECGs) are not recommended for asymptomatic patients because the potential harms are thought to outweigh any benefits. Assessment tools to identify high risk individuals may improve the harm versus benefit profile of screening ECGs. In particular, people with unrecognized myocardial infarction (UMI) have elevated risk for cardiovascular events and death.
Using logistic regression, we developed a basic assessment tool among 16,653 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study using demographics, self-reported medical history, blood pressure, and body mass index and an expanded assessment tool using information on 51 potential variables. UMI was defined as electrocardiogram evidence of myocardial infarction without a self-reported history (n = 740).
The basic assessment tool had a c-statistic of 0.638 (95% confidence interval 0.617 - 0.659) and included age, race, smoking status, body mass index, systolic blood pressure, and self-reported history of transient ischemic attack, deep vein thrombosis, falls, diabetes, and hypertension. A predicted probability of UMI > 3% provided a sensitivity of 80% and a specificity of 30%. The expanded assessment tool had a c-statistic of 0.654 (95% confidence interval 0.634-0.674). Because of the poor performance of these assessment tools, external validation was not pursued.
Despite examining a large number of potential correlates of UMI, the assessment tools did not provide a high level of discrimination. These data suggest defining groups with high prevalence of UMI for targeted screening will be difficult.
PMCID: PMC3617994  PMID: 23530553
Myocardial infarction; Screening; Electrocardiography
10.  Comparison of Concurrent Complications of CKD by 2 Risk Categorization Systems 
Using both estimated glomerular filtration rate (eGFR) and proteinuria to classify the severity of chronic kidney disease (CKD) has been proposed. The utility of a staging system incorporating both eGFR and proteinuria for guiding evaluation of concurrent CKD complications is not known.
Study design
Cross-sectional analysis
Setting & participants
30,528 participants in the US National Health and Nutrition Examination Survey conducted in 1988–1994 and 1999–2006 (n=8,242 for hyperparathyroidism).
Classification system that uses both eGFR and proteinuria (alternative) and a system that primarily uses eGFR (NKF-KDOQI; the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative)
Prevalence of anemia, acidosis, hyperphosphatemia, hypoalbuminemia, hyperparathyroidism and hypertension
GFR estimated from the CKD-Epidemiology Collaboration (CKD-EPI) equation and proteinuria assessed using urine albumin-creatinine ratio (ACR)
The prevalence of hypoalbuminemia, hypertension and hyperparathyroidism increased with more severe CKD using the NKF-KDOQI system. For example, the prevalence of hyperparathyroidism was 9.1%, 11.1%, 28.2% and 72.5% for Stages 1, 2, 3 and 4, respectively. Similarly the prevalence of anemia, acidosis and hyperphosphatemia increased progressively from Stage 2 through 4. With the alternative system, the prevalence of anemia, hyperphosphatemia, hypertension and hyperparathyroidism was lower in Stage 3 compared to Stage 2. For example, the prevalence of hyperparathyroidism was 13.5%, 40.3%, 22.2%, and 63.4% for stages 1, 2, 3 and 4, respectively. Applying the alternative system, participants without each complication were more likely to be appropriately reclassified to lower stages (for example, overall net reclassification index of −6.5% for hyperparathyroidism). However, participants with complications (except for hypoalbuminemia) were more likely to be inappropriately reclassified to lower stages.
Use of single creatinine to estimate GFR and single measure to assess ACR. Small number of participants with CKD Stage 4.
The NKF-KDOQI system may better identify patients with certain concurrent CKD complications compared to systems using eGFR and proteinuria.
PMCID: PMC3288542  PMID: 22113126
11.  Cardioprotective medication use and risk factor control among US adults with unrecognized myocardial infarction: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study 
Individuals with unrecognized myocardial infarction (UMI) have similar risks for cardiovascular events and mortality as those with recognized myocardial infarction (RMI). The prevalence of cardioprotective medication use and blood pressure and low-density lipoprotein cholesterol control among individuals with UMI is unknown.
Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were recruited between May 2004 and October 2007 received baseline twelve-lead electrocardiograms (n = 21,036). Myocardial infarction (MI) status was characterized as no MI, UMI (electrocardiogram abnormalities consistent with MI without self-reported history; n = 949; 4.5%), and RMI (self-reported history of MI; n = 1574; 7.5%).
For participants with no MI, UMI, and RMI, prevalence of use was 38.4%, 44.4%, and 75.7% for aspirin; 18.0%, 25.8%, and 57.2% for beta blockers; 31.7%, 38.7%, and 55.0% for angiotensin converting enzyme inhibitors or angiotensin receptor blockers; and 28.1%, 33.9%, and 64.1% for statins, respectively. Participants with RMI were 35% more likely to have low-density lipoprotein cholesterol < 100 mg/dL than participants with UMI (prevalence ratio = 1.35, 95% confidence interval 1.19–1.52). Blood pressure control (,140/90 mmHg) was similar between RMI and UMI groups (prevalence ratio = 1.03, 95% confidence interval 0.93–1.13).
Although participants with UMI were somewhat more likely to use cardioprotective medications than those with no MI, they were less likely to use cardioprotective medications and to have controlled low-density lipoprotein cholesterol than participants with RMI. Increasing appropriate treatment and risk factor control among individuals with UMI may reduce risk of mortality and future cardiovascular events.
PMCID: PMC3569379  PMID: 23404361
unrecognized myocardial infarction; secondary prevention; risk factor control
12.  Baseline Values of Candidate Urine Acute Kidney Injury (AKI) Biomarkers Vary by Gestational Age in Premature Infants 
Pediatric research  2011;70(3):302-306.
Acute kidney injury (AKI) is common in premature infants and is associated with poor outcomes. Novel biomarkers can detect AKI promptly. Because premature infants are born with underdeveloped kidneys, baseline biomarker values may differ. We describe baseline values of urinary neutrophil gelatinase associated lipocalin, (NGAL), Interleukin - 18 (IL-18), Kidney Injury Molecule -1 (KIM -1), Osteopontin (OPN), beta-2 microglobulin (B2mG) and Cystatin-C (Cys-C). Next, we test the hypothesis that these biomarkers are inversely related to gestational age (GA). Candidate markers were compared according to GA categories in 123 infants. Mixed linear regression models were performed to determine the independent association between demographics/interventions and baseline biomarker values. We found that urine NGAL, KIM-1, Cys-C and B2mG decreased with increasing GA. With correction for urine creatinine (cr), these markers and OPN/cr decreased with increasing GA. IL-18 (with or without correction for urine creatinine) did not differ across GA categories. Controlling for other potential clinical and demographic confounders with regression analysis shows that, NGAL/cr, OPN/cr and B2mG/cr are independently associated with GA. We conclude that urine values of candidate AKI biomarkers are higher in the most premature infants. These findings should be considered when designing neonatal AKI validation studies.
PMCID: PMC3152663  PMID: 21646940
13.  Development and Validation of a Self-Assessment Tool for Albuminuria: Results From the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study 
The prevalence of albuminuria in the general population is high, but awareness of it is low. Therefore, we sought to develop and validate a self-assessment tool that allows individuals to estimate their probability of having albuminuria.
Study Design
Cross-sectional study
Setting & Participants
The population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study for model development and the National Health and Nutrition Examination Survey 1999-2004 (NHANES 1999-2004) for model validation. US adults ≥ 45 years of age in the REGARDS study (n=19,697) and NHANES 1999-2004 (n=7,168)
[nijsje 1]Factor
Candidate items for the self-assessment tool were collected using a combination of interviewer- and self-administered questionnaires.
Albuminuria was defined as a urinary albumin to urinary creatinine ratio ≥ 30 mg/g in spot samples.
Eight items were included in the self-assessment tool (age, race, gender, current smoking, self-rated health, and self-reported history of diabetes, hypertension, and stroke). These items provided a c-statistic of 0.709 (95% CI, 0.699 – 0.720) and a good model fit (Hosmer-Lemeshow chi-square p-value = 0.49). In the external validation data set, the c-statistic for discriminating individuals with and without albuminuria using the self-assessment tool was 0.714. Using a threshold of ≥ 10% probability of albuminuria from the self-assessment tool, 36% of US adults ≥ 45 years of age in NHANES 1999-2004 would test positive and be recommended screening. The sensitivity, specificity, and positive and negative predictive values for albuminuria associated with a probability ≥ 10% were 66%, 68%, 23% and 93%, respectively.
Repeat urine samples were not available to assess the persistency of albuminuria.
Eight self-report items provide good discrimination for the probability of having albuminuria. This tool may encourage individuals with a high probability to request albuminuria screening.
PMCID: PMC3144301  PMID: 21620547
15.  Ethnic Differences in Hypertension Incidence among Middle-Aged and Older U. S. Adults: The Multi-Ethnic Study of Atherosclerosis 
Hypertension  2011;57(6):1101-1107.
The prevalence of hypertension is higher among African-Americans than whites. However, inconsistent findings have been reported on the incidence of hypertension among middle-aged and older African-Americans and whites and limited data are available on the incidence of hypertension among Hispanics and Asians in the US. Therefore, this study investigated the age-specific incidence of hypertension by ethnicity for 3,146 participants from the Multi-Ethnic Study of Atherosclerosis. Participants, age 45–84 years at baseline, were followed for a median of 4.8 years for incident hypertension, defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or the initiation of antihypertensive medications. The crude incidence rate of hypertension, per 1,000 person-years, was 56.8 for whites, 84.9 for African-Americans, 65.7 for Hispanics, and 52.2 for Chinese. After adjustment for age, gender, and study site, the incidence rate ratio (IRR) for hypertension was increased for African-Americans age 45–54 (IRR=2.05, 95% CI=1.47, 2.85), 55–64 (IRR=1.63, 95% CI=1.20, 2.23), and 65–74 years (IRR=1.67, 95% CI=1.21, 2.30) compared with whites, but not for those 75–84 years of age (IRR=0.97, 95% CI=0.56, 1.66). Additional adjustment for health characteristics attenuated these associations. Hispanic participants also had a higher incidence of hypertension compared with whites; however, hypertension incidence did not differ for Chinese and white participants. In summary, hypertension incidence was higher for African-Americans compared with whites between 45 and 74 years of age but not after age 75 years. Public health prevention programs tailored to middle-age and older adults are needed to eliminate ethnic disparities in incident hypertension.
PMCID: PMC3106342  PMID: 21502561
hypertension; race/ethnicity; epidemiology; incidence
16.  Transitional Probability-Based Model for HPV Clearance in HIV-1-Positive Adolescent Females 
PLoS ONE  2012;7(1):e30736.
HIV-1-positive patients clear the human papillomavirus (HPV) infection less frequently than HIV-1-negative. Datasets for estimating HPV clearance probability often have irregular measurements of HPV status and risk factors. A new transitional probability-based model for estimation of probability of HPV clearance was developed to fully incorporate information on HIV-1-related clinical data, such as CD4 counts, HIV-1 viral load (VL), highly active antiretroviral therapy (HAART), and risk factors (measured quarterly), and HPV infection status (measured at 6-month intervals).
Methodology and Findings
Data from 266 HIV-1-positive and 134 at-risk HIV-1-negative adolescent females from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort were used in this study. First, the associations were evaluated using the Cox proportional hazard model, and the variables that demonstrated significant effects on HPV clearance were included in transitional probability models. The new model established the efficacy of CD4 cell counts as a main clearance predictor for all type-specific HPV phylogenetic groups. The 3-month probability of HPV clearance in HIV-1-infected patients significantly increased with increasing CD4 counts for HPV16/16-like (p<0.001), HPV18/18-like (p<0.001), HPV56/56-like (p = 0.05), and low-risk HPV (p<0.001) phylogenetic groups, with the lowest probability found for HPV16/16-like infections (21.60±1.81% at CD4 level 200 cells/mm3, p<0.05; and 28.03±1.47% at CD4 level 500 cells/mm3). HIV-1 VL was a significant predictor for clearance of low-risk HPV infections (p<0.05). HAART (with protease inhibitor) was significant predictor of probability of HPV16 clearance (p<0.05). HPV16/16-like and HPV18/18-like groups showed heterogeneity (p<0.05) in terms of how CD4 counts, HIV VL, and HAART affected probability of clearance of each HPV infection.
This new model predicts the 3-month probability of HPV infection clearance based on CD4 cell counts and other HIV-1-related clinical measurements.
PMCID: PMC3265500  PMID: 22292027
17.  Chocolate Intake and Incidence of Heart Failure: A Population-Based, Prospective Study of Middle-Aged and Elderly Women 
Circulation. Heart failure  2010;3(5):612-616.
Randomized clinical trials have shown that chocolate intake reduces systolic and diastolic blood pressure and observational studies have found an inverse association between chocolate intake and cardiovascular disease. The aim of this study was to investigate the association between chocolate intake and incidence of heart failure (HF).
Methods and Results
We conducted a prospective cohort study of 31,823 women 48–83 years old without baseline diabetes or a history of HF or myocardial infarction who were participants in the Swedish Mammography Cohort. In addition to health and lifestyle questions, participants completed a food-frequency questionnaire. Women were followed from January 1, 1998 through December 31, 2006 for HF hospitalization or death through the Swedish inpatient and cause-of-death registers. Over 9 years of follow-up, 419 women were hospitalized for incident HF (n =379) or died of HF (n = 40). Compared to no regular chocolate intake, the multivariate-adjusted rate ratio of HF was 0.74 (95%CI 0.58–0.95) for those consuming 1–3 servings of chocolate per month, 0.68 (95%CI 0.50–0.93) for those consuming 1–2 servings per week, 1.09 (95%CI .74–1.62) for those consuming 3–6 servings per week and 1.23 (95%CI 0.73–2.08) for those consuming one or more servings per day (p for quadratic trend = 0.0005).
In this population, moderate habitual chocolate intake was associated with a lower rate of HF hospitalization or death but the protective association was not observed with intake of one or more servings per day.
PMCID: PMC3052999  PMID: 20713904
diet; epidemiology; heart failure
18.  Dietary Glycaemic Index, Dietary Glycaemic Load, and Incidence of Myocardial Infarction in Women 
The British journal of nutrition  2009;103(7):1049-1055.
The association of dietary glycaemic index (GI) and glycaemic load (GL) with cardiovascular diseases has been examined in several populations with varying results. We tested the hypothesis that women with diets high in GI or GL would have higher rates of myocardial infarction (MI) and the associations would be stronger in overweight women. We measured dietary GI and GL in 36,234 Swedish Mammography Cohort participants aged 48–83 using food-frequency questionnaires (FFQ). Cox models were used to calculate incidence rate ratios (RR) and 95% CI for hospitalization or death due to MI assessed using the Swedish inpatient and cause-of-death registers from January 1, 1998 until December 31, 2006. Over 9 years of follow-up, 1,138 women were hospitalized or died due to a first MI. In multivariable-adjusted models, the RR comparing top to bottom quartile of dietary GI was 1.12 (95% CI 0.92–1.35, P-trend = 0.24), and the RR comparing top to bottom quartile of dietary GL was 1.22 (95% CI 0.90–1.65, P-trend = 0.23). Among overweight women, the RR comparing top to bottom quartile of dietary GI was 1.20 (95% CI 0.91–1.58, P-trend = 0.22), and the RR comparing top to bottom quartile of dietary GL was 1.45 (95% CI 0.93–2.25, P-trend = 0.16). There were no statistically significant associations of dietary GI or GL with MI in this population.
PMCID: PMC2851847  PMID: 20003611
glycaemic index; glycaemic load; myocardial infarction
19.  Fatty fish, marine omega-3 fatty acids, and incidence of heart failure 
Marine omega-3 fatty acids have beneficial effects on cardiovascular risk factors. Consumption of fatty fish and marine omega-3 has been associated with lower rates of cardiovascular diseases.
We examined the association of fatty fish and marine omega-3 with heart failure (HF) in a population of middle-age and older women.
Participants in the Swedish Mammography Cohort aged 48–83 years completed 96-item food-frequency questionnaires. Women without history of HF, myocardial infarction, or diabetes at baseline (n= 36 234) were followed from January 1, 1998 until December 31, 2006 for HF hospitalization or mortality through Swedish inpatient and cause-of-death registers; 651 women experienced HF events. Cox proportional hazards models accounting for age and other confounders were used to calculate incidence rate ratios (RR) and 95% confidence intervals (CI).
Compared to women who did not eat fatty fish, RR were 0.86 (95% CI: 0.67, 1.10) for <1 serving/week, 0.80 (95% CI: 0.63, 1.01) for 1 serving/week, 0.70 (95% CI: 0.53, 0.94) for 2 servings/week, and 0.91 (95% CI: 0.59, 1.40) for ≥3 servings/week (Ptrend = 0.049). RR across quintiles of marine omega-3 fatty acids were 1 (reference), 0.85 (95% CI: 0.67, 1.07), 0.79 (95% CI: 0.61, 1.02), 0.83 (95% CI 0.65, 1.06), and 0.75 (95% CI: 0.58, 0.96) (Ptrend = 0.04).
Moderate consumption of fatty fish (one to two servings per week) and marine omega-3 fatty acids were associated with a lower rate of first HF hospitalization or death in this population.
PMCID: PMC2880209  PMID: 20332801
Heart Failure; Fatty Acids; Omega-3; Diet
20.  Relation of Consistency with the Dietary Approaches to Stop Hypertension Diet and Incidence of Heart Failure in Men Aged 45 to 79 Years 
The American journal of cardiology  2009;104(10):1416-1420.
The Dietary Approaches to Stop Hypertension (DASH) diet reduces blood pressure, and consistency with the DASH diet has been associated with lower rates of heart failure (HF) in women. The authors examined the association between consistency with DASH and rates of HF hospitalization or mortality in 38,987 participants in the Cohort of Swedish Men aged 45 to 79 years. Diet was measured using food-frequency questionnaires, and scores were created to assess consistency with DASH by ranking intake of DASH diet components. Cox models were used to calculate rate ratios of HF (807 incident cases) determined through the Swedish inpatient and cause-of-death registers between January 1, 1998 and December 31, 2006. In multivariable-adjusted analyses, men in the highest quartile of the DASH component score had a 22% lower rate of HF events then those in the lowest quartile (95% confidence interval: 5%, 35%, p for trend = 0.006). In conclusion, greater consistency with the DASH diet was associated with lower rates HF events in men aged 45 to 79 years.
PMCID: PMC2774905  PMID: 19892061
diet; heart failure; epidemiology
21.  Coffee Consumption and Risk of Heart Failure in Men: an Analysis from the Cohort of Swedish Men 
American heart journal  2009;158(4):667-672.
A previous study found that consuming 5 or more cups of coffee per day was associated with increased incidence of heart failure (HF). We sought to evaluate this association in a larger population.
We measured coffee consumption using food-frequency questionnaires among 37,315 men without history of myocardial infarction, diabetes, or HF. They were followed for HF hospitalization or mortality from January 1, 1998 until December 31, 2006 using record linkage to the Swedish inpatient and cause-of-death registries. Cox proportional hazards models adjusted for age, dietary, and demographic factors were used to calculate incidence rate ratios (RR) and 95% confidence intervals (CI).
Over 9 years of follow-up, 784 men experienced a HF event. Compared to men who drank ≤ 1 cup of coffee per day (unadjusted rate 29.9 HF events/10,000 person-years), RR were 0.87 (95% CI 0.69–1.11, unadjusted rate 29.2/10,000 person-years,) for 2 cups/day, 0.89 (95% CI 0.70–1.14, unadjusted rate 25.1/10,000 person-years) for 3 cups/day, 0.89 (95% CI 0.69–1.15, unadjusted rate 25.0/10,000 person-years) for 4 cups/day, and 0.89 (95% CI 0.69–1.15, unadjusted rate 18.1/10,000 person-years) for ≥ 5 cups/day (p for trend in RR = 0.61).
This study did not support the hypothesis that high coffee consumption is associated with increased rates of HF hospitalization or mortality.
PMCID: PMC2754877  PMID: 19781429
22.  Prospective population studies of incident heart failure without data on baseline left ventricular ejection fraction 
Left ventricular ejection fraction (LVEF) is a predictor of incident heart failure (HF). However, baseline LVEF is often unavailable in population studies of HF.
Meterial and methods
Of the 5324 Cardiovascular Health Study (CHS) participants free of baseline HF, 143 (3%) had LVEF < 45% and 1091 (21%) developed HF during 13 years of follow-up. Using public-use copies of the CHS data, we compared two predictor models of incident HF, with and without adjustment for baseline LVEF.
Baseline impaired LVEF was a strong independent predictor of incident HF (adjusted hazard ratio, 2.78; P < 0.001) but had no impact on the direction, magnitude or significance of independent associations of the other predictors of incident HF such as age, sex, race, coronary artery disease, hypertension and diabetes.
Baseline LVEF is an important predictor for incident HF but is not essential in population studies of risk factors for incident HF.
PMCID: PMC3298335  PMID: 22419925
heart failure; left ventricular ejection fraction; epidemiology; population studies
23.  Effects of Myostatin Deletion in Aging Mice 
Aging cell  2009;8(5):573-583.
Inhibitors of myostatin, a negative regulator of skeletal muscle mass, are being developed to mitigate aging-related muscle loss. Knockout mouse studies suggest myostatin also affects adiposity, glucose handling, and cardiac growth. However, the cardiac consequences of inhibiting myostatin remain unclear. Myostatin inhibition can potentiate cardiac growth in specific settings (Morissette et al. 2006), a concern since cardiac hypertrophy is associated with adverse clinical outcomes. Therefore we examined the systemic and cardiac effects of myostatin deletion in aged mice (27-30 months old). Heart mass increased comparably in both wildtype (WT) and knockout (KO) mice. Aged KO mice maintained twice as much quadriceps mass as aged WT, however both groups lost the same percentage (36%) of adult muscle mass. Dual-energy x-ray absorptiometry (DEXA) revealed increased bone density, mineral content, and area in aged KO versus aged WT mice. Serum insulin and glucose levels were lower in KO mice. Echocardiography showed preserved cardiac function with better fractional shortening (58.1 vs 49.4%, p=0.002) and smaller LV diastolic diameters (3.41 vs 2.71, p=0.012) in KO versus WT mice. Phospholamban phosphorylation was increased 3.3-fold in KO hearts (p<0.05), without changes in total phospholamban, SERCA2a, or calsequestrin. Aged KO hearts showed less fibrosis by Masson's Trichrome staining. Thus myostatin deletion does not affect aging-related increases in cardiac mass and appears beneficial for bone density, insulin sensitivity, and heart function in senescent mice. These results suggest that clinical interventions designed to inhibit skeletal muscle mass loss with aging could have beneficial effects on other organ systems as well.
PMCID: PMC2764272  PMID: 19663901
myostatin; aging; heart; muscle; sarcopenia; osteoporosis
24.  Renal Function Predicts Survival in Patients with Acute Ischemic Stroke 
Among patients with acute ischemic stroke, impaired kidney function has been shown to increase the mortality risk, but the shape of this relationship has not been evaluated in detail.
We estimated the glomerular filtration rate (eGFR) at the time of hospitalization in 1,175 consecutive patients hospitalized with acute ischemic stroke at the Beth Israel Deaconess Medical Center and examined the shape of the association between eGFR and all-cause mortality.
There were 508 deaths during a median follow-up of 40.3 months, resulting in a ‘U’-shaped relationship between eGFR and all-cause mortality. The curve was relatively flat between 75 and 110 ml/min/1.73 m2 but increased sharply at lower and higher levels of eGFR (test for nonlinearity: p < 0.0001).
Among patients with acute ischemic stroke, a reduced or highly elevated eGFR at hospital admission is associated with a higher mortality rate compared to patients with moderate levels of eGFR.
PMCID: PMC2700844  PMID: 19468220
Creatinine; Glomerular filtration rate; Renal disease; Cerebrovascular disease; Mortality
25.  Fish consumption, marine omega-3 fatty acids, and incidence of heart failure: a population-based prospective study of middle-aged and elderly men 
European Heart Journal  2009;30(12):1495-1500.
Fatty fish and marine omega-3 fatty acids were associated with lower rates of heart failure (HF) among US elderly, but this has not been confirmed in broader age ranges or other populations where source and type of fish may differ. We therefore conducted a population-based, prospective study of 39 367 middle-aged and older Swedish men.
Methods and results
Diet was measured using food-frequency questionnaires. Men were followed for HF through Swedish inpatient and cause-of-death registers from 1 January 1998 to 31 December 2004. We used proportional hazards models adjusted for age and other covariates to estimate hazard ratios (HR). Compared with no consumption, men who ate fatty fish once per week had an HR of 0.88 (95% CI 0.68–1.13). Hazard ratios for consumption two times per week and ≥3 times per week were 0.99 and 0.97, respectively. Hazard ratios across quintiles of marine omega-3 were 1, 0.94 (95% CI 0.74–1.20), 0.67 (95% CI 0.50–0.90), 0.89 (95% CI 0.68–1.16), 1.00 (95% CI 0.77–1.29).
In this population, moderate intake of fatty fish and marine omega-3 fatty acids was associated with lower rates of HF, though the association for fish intake was not statistically significant; higher intake was not associated with additional benefit.
PMCID: PMC2695952  PMID: 19383731
Heart failure; Diet; Omega-3 fatty acids; Fish

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