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1.  Cruciferous vegetables, glutathione S-transferase polymorphisms and the risk of colorectal cancer among Chinese men 
Annals of epidemiology  2013;24(1):10.1016/j.annepidem.2013.10.003.
To assess the associations between cruciferous vegetable (CV) intake, GST gene polymorphisms and colorectal cancer (CRC) in a population of Chinese men.
Using incidence density sampling, CRC cases (N = 340) diagnosed prior to December 31, 2010 within the Shanghai Men’s Health Study were matched to non-cases (N = 673). CV intake was assessed from a food frequency questionnaire and by isothiocyanate (ITC) levels from spot urine samples. GSTM1 and GSTT1 were categorized as null (0 copies) versus non-null (1 or 2 copies). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between CV intake and GST gene variants with CRC and statistical interactions were evaluated.
CRC risk was not associated with CV intake, whether measured by self-report or by urinary ITC, nor with GST gene variants. No statistical interactions were detected between CV intake and GST gene variants on the odds of CRC. Stratifying by timing of urine sample collection and excluding CRC cases diagnosed in the first two years did not materially alter the results.
This study provides no evidence supporting the involvement of CV intake in the development of CRC in Chinese men.
PMCID: PMC3864981  PMID: 24238877
brassicaceae; China; colorectal neoplasms; glutathione S-transferase M1; glutathione S-transferase T1; men
2.  Fruit and vegetable intake and the risk of colorectal cancer: Results from the Shanghai Men's Health Study 
Cancer causes & control : CCC  2013;24(11):1935-1945.
The observed associations of fruit and vegetable consumption with the risk of colorectal cancer have been inconsistent. Therefore, we aimed to evaluate the association of fruit and vegetable consumption with the risk of colorectal cancer within Chinese men.
61,274 male participants aged 40 to 74 years were included. A validated food frequency questionnaire was administered to collect information on usual dietary intake, including 8 fruits and 38 vegetables commonly consumed by residents of Shanghai. Follow-up for diagnoses of colon or rectal cancer were available through December 31, 2010. Dietary intakes were analyzed both as categorical (quintiles) and continuous variables. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for colorectal, colon, and rectal cancer using Cox proportional hazards models.
After 390,688 person-years of follow-up, 398 cases of colorectal cancer (236 colon and 162 rectal) were observed in the cohort. Fruit consumption was inversely associated with the risk of colorectal cancer (5th vs. 1st quintile HR: 0.67; 95% CI: 0.48, 0.95; P trend = 0.03), whereas vegetable intake was not significantly associated with risk. The associations for sub-groups of fruits and legumes, but not other vegetable categories, were generally inversely associated with the risk of colon and rectal cancer.
Fruit intake was generally inversely associated with the risk of colorectal cancer while vegetable consumption was largely unrelated to risk among middle aged and older Chinese men.
PMCID: PMC3805771  PMID: 23913012
Colorectal cancer; fruits; vegetables; cohort study; Chinese men
3.  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
4.  Risk for recurrent coronary heart disease and all-cause mortality among individuals with chronic kidney disease compared with diabetes mellitus, metabolic syndrome, and cigarette smokers 
American heart journal  2013;166(2):373-380.e2.
Lipid-lowering guidelines endorse a low-density lipoprotein cholesterol goal of <100 mg/dL for people with coronary heart disease (CHD). A more stringent threshold of <70 mg/dL is recommended for those with CHD and “very high-risk” conditions such as diabetes mellitus, metabolic syndrome, or cigarette smoking. Whether chronic kidney disease (CKD) confers a similar risk for recurrent CHD events is unknown.
Methods and Results
We evaluated the risk for recurrent CHD events and all-cause mortality among 3,938 participants ≥45 years with CHD in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Chronic kidney disease was defined by estimated glomerular filtration rate <60 mL/min per 1.73 m2 or urinary albumin to creatinine ratio ≥30 mg/g. Participants were categorized by the presence or absence of CKD and any very high-risk condition. Over a median of 4.1 years, the crude incidence (95% CI) of recurrent CHD events were 12.1 (9.0–15.2), 18.9 (15.5–22.3), 35.0 (25.4–44.6), and 34.2 (28.2–40.3) among those without CKD or high-risk conditions; very high-risk conditions alone; and CKD alone and both CKD and very high-risk conditions. After multivariable adjustment, compared with those without CKD or very high-risk conditions, the hazard ratio (95% CI) for recurrent CHD events was 1.45 (1.02–2.05), 2.24 (1.50–3.34), and 2.10 (1.47–2.98) among those with very high-risk conditions alone, CKD alone, and both CKD and very high-risk conditions, respectively. Results were consistent for all-cause mortality.
Chronic kidney disease is associated with risk for recurrent CHD events that approximates or is larger than other established very high-risk conditions.
PMCID: PMC4139360  PMID: 23895822
5.  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
6.  DASH Eating Pattern Is Associated with Favorable Left Ventricular Function in the Multi-Ethnic Study of Atherosclerosis 
Potential associations between consistency with the Dietary Approaches to Stop Hypertension (DASH) diet and preclinical stages of heart failure (HF) in a large multiethnic cohort have not been evaluated. This study sought to determine the cross-sectional relationship between the DASH eating pattern and left ventricular (LV) function in the Multi-Ethnic Study of Atherosclerosis (MESA).
A total of 4506 men and women from four ethnic groups (40% white, 24% African American, 22% Hispanic American, and 14% Chinese American) aged 45–84 years and free of clinical cardiovascular disease (CVD) were studied. Diet was assessed using a validated food-frequency questionnaire. LV functional parameters including end-diastolic volume, stroke volume, and LV ejection fraction were measured by magnetic resonance imaging. Multivariate analyses were conducted to examine the association between LV function and DASH eating pattern (including high consumption of fruits, vegetables, whole grains, poultry, fish, nuts, and low-fat dairy products and low consumption of red meat, sweets, and sugar-sweetened beverages).
A 1-unit increase in DASH eating pattern score was associated with a 0.26 ml increase in end-diastolic volume and increases of 0.10 ml/m2 in stroke volume, adjusted for key confounders. A 1-unit increase in DASH eating pattern score was also associated with a 0.04% increase in ejection fraction, but the relationship was marginally significant (p = 0.08).
In this population, greater DASH diet consistency is associated with favorable LV function. DASH dietary patterns could be protective against HF.
PMCID: PMC4119794  PMID: 23756584
DASH diet; LV function; preclinical heart failure
7.  Development and Evaluation of a Self-Report Tool to Predict Low Pharmacy Refill Adherence in Elderly Patients with Uncontrolled Hypertension 
Pharmacotherapy  2013;33(8):798-811.
To develop and evaluate a short self-report tool to predict low pharmacy refill adherence by using pharmacy refill data in older patients with uncontrolled hypertension.
Cross-sectional analysis of survey and administrative data data from the Cohort Study of Medication Adherence among Older Adults (CoSMO).
Three hundred ninety-four adults with uncontrolled blood pressure; mean ± SD age was 76.6 ± 5.6 years, 33.0% were black, 66.0% were women, and 23.4% had a low medication possession ratio (MPR).
Measurements and Main Results
We considered 164 self-reported candidate items for development of a prediction rule for low (< 0.8) vs. high (≥ 0.8) MPR from pharmacy refill data. Risk prediction models were evaluated by using best subsets analyses, and the final model was chosen based on clinical relevance and model parsimony. Bootstrap simulations assessed internal validity. The performance of the final 4-item model was compared to the 8-item Morisky Medication Adherence Scale (MMAS-8) and the 9-item Hill-Bone Compliance Scale. The 4-item self-report tool for predicting pharmacy refill adherence showed moderate discrimination (C statistic 0.704, 95% CI 0.683–0.714) and good model fit (Hosmer-Lemeshow χ2 = 1.238, p=0.743). Sensitivity and specificity were 67.4% and 67.8%, respectively. The C statistics for MMAS-8 and the Hill-Bone Compliance Scale were lower at 0.665 (95% CI 0.632–0.683) and 0.660 (95% CI 0.622–0.674), respectively.
A 4-item self-report tool moderately discriminated low from high pharmacy refill adherers, and its test performance was comparable to existing 8- and 9-item adherence scales. Parsimonious self-report tools predicting low pharmacy refill in patients with uncontrolled blood pressure could facilitate hypertension management in the elderly.
PMCID: PMC3729884  PMID: 23649849
hypertension; medication adherence; pharmacy refill; uncontrolled blood pressure; risk prediction
8.  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
9.  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
10.  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
11.  Claims-based algorithms for identifying Medicare beneficiaries at high estimated risk for coronary heart disease events: a cross-sectional study 
Databases of medical claims can be valuable resources for cardiovascular research, such as comparative effectiveness and pharmacovigilance studies of cardiovascular medications. However, claims data do not include all of the factors used for risk stratification in clinical care. We sought to develop claims-based algorithms to identify individuals at high estimated risk for coronary heart disease (CHD) events, and to identify uncontrolled low-density lipoprotein (LDL) cholesterol among statin users at high risk for CHD events.
We conducted a cross-sectional analysis of 6,615 participants ≥66 years old using data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study baseline visit in 2003–2007 linked to Medicare claims data. Using REGARDS data we defined high risk for CHD events as having a history of CHD, at least 1 risk equivalent, or Framingham CHD risk score >20%. Among statin users at high risk for CHD events we defined uncontrolled LDL cholesterol as LDL cholesterol ≥100 mg/dL. Using Medicare claims-based variables for diagnoses, procedures, and healthcare utilization, we developed algorithms for high CHD event risk and uncontrolled LDL cholesterol.
REGARDS data indicated that 49% of participants were at high risk for CHD events. A claims-based algorithm identified high risk for CHD events with a positive predictive value of 87% (95% CI: 85%, 88%), sensitivity of 69% (95% CI: 67%, 70%), and specificity of 90% (95% CI: 89%, 91%). Among statin users at high risk for CHD events, 30% had LDL cholesterol ≥100 mg/dL. A claims-based algorithm identified LDL cholesterol ≥100 mg/dL with a positive predictive value of 43% (95% CI: 38%, 49%), sensitivity of 19% (95% CI: 15%, 22%), and specificity of 89% (95% CI: 86%, 90%).
Although the sensitivity was low, the high positive predictive value of our algorithm for high risk for CHD events supports the use of claims to identify Medicare beneficiaries at high risk for CHD events.
PMCID: PMC4101858  PMID: 24779477
High risk; Coronary heart disease; Risk stratification; Medicare claims
12.  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
13.  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
14.  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
15.  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
16.  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
17.  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
18.  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
19.  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
20.  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
21.  High sodium:potassium intake ratio increases the risk for all-cause mortality: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study 
Increased dietary Na intake and decreased dietary K intake are associated with higher blood pressure. It is not known whether the dietary Na:K ratio is associated with all-cause mortality or stroke incidence and whether this relationship varies according to race. Between 2003 and 2007, the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort enrolled 30 239 black and white Americans aged 45 years or older. Diet was assessed using the Block 98 FFQ and was available on 21 374 participants. The Na:K ratio was modelled in race- and sex-specific quintiles for all analyses, with the lowest quintile (Q1) as the reference group. Data on other covariates were collected using both an in-home assessment and telephone interviews. We identified 1779 deaths and 363 strokes over a mean of 4·9 years. We used Cox proportional hazards models to obtain multivariable-adjusted hazard ratios (HR). In the highest quintile (Q5), a high Na:K ratio was associated with all-cause mortality (Q5 v. Q1 for whites: HR 1·22; 95 % CI 1·00, 1·47, P for trend = 0·084; for blacks: HR 1·36; 95 % CI 1·04, 1·77, P for trend = 0·028). A high Na:K ratio was not significantly associated with stroke in whites (HR 1·29; 95 % CI 0·88, 1·90) or blacks (HR 1·39; 95 % CI 0·78, 2·48), partly because of the low number of stroke events. In the REGARDS study, a high Na:K ratio was associated with all-cause mortality and there was a suggestive association between the Na:K ratio and stroke. These data support the policies targeted at reduction of Na from the food supply and recommendations to increase K intake.
PMCID: PMC4153038  PMID: 25191561
Stroke; Death; Race; Sodium; HR, hazard ratio; REGARDS, REasons for Geographic And Racial Differences in Stroke
22.  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
23.  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
25.  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

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