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1.  C-reactive protein level and the incidence of eligibility for statin therapy: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Clinical cardiology  2012;36(1):15-20.
Introduction
Given the results of the JUPITER trial, statin initiation may be considered for individuals with elevated high sensitivity C-reactive protein (CRP). However, if followed prospectively, many individuals with elevated CRP may become statin-eligible, limiting the impact of elevated CRP as a treatment indication. This analysis estimates the proportion of people with elevated CRP that become statin eligible over time.
Methods
We followed 2,153 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of cardiovascular disease (CVD) and diabetes with LDL-cholesterol (LDL-C) <130 mg/dL at baseline to determine the proportion who become eligible for statins over 4.5 years. The proportion eligible for statin therapy, defined by the National Cholesterol Education Program (NCEP) 2004 updated guidelines, was calculated at baseline and during follow-up stratified by baseline CRP level (≥2 mg/L).
Results
At baseline, 47% of the 2,153 participants had elevated CRP. Among participants with elevated CRP, 29% met NCEP criteria for statins, compared to 28% without elevated CRP at baseline. By 1.5 years later, 26% and 22% (p=0.09) of those with and without elevated CRP at baseline reached NCEP LDL-C criteria and/or had started statins, respectively. These increased to 42% and 39% (p=0.24) at 3 years and 59% and 52% (p=0.01) at 4.5 years following baseline.
Conclusions
A substantial proportion of those with elevated CRP did not achieve NCEP based statin eligibility over 4.5 years of follow-up. These findings suggest that many patients with elevated CRP may not receive the benefits of statins if CRP is not incorporated into the NCEP screening strategy.
doi:10.1002/clc.22046
PMCID: PMC3953418  PMID: 22886783
2.  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.
doi:10.1111/jch.12037
PMCID: PMC3659162  PMID: 23339729
Medication adherence; blood pressure variability; hypertension
3.  Prevalence and correlates of low medication adherence in apparent treatment resistant hypertension 
Low medication adherence may explain part of the high prevalence of apparent treatment resistant hypertension (aTRH). We assessed medication adherence and aTRH among 4,026 participants taking ≥ 3 classes of antihypertensive medication in the population-based REGARDS Study using the 4-item Morisky Medication Adherence Scale (MMAS). Low adherence was defined as a MMAS score ≥ 2. Overall, 66% of participants taking ≥ 3 classes of antihypertensive medication had aTRH. Perfect adherence on the MMAS was reported by 67.8% and 70.9% of participants with and without aTRH, respectively. Low adherence was present among 8.1% of participants with aTRH and 5.0% of those without aTRH (p<0.001). Among those with aTRH, female gender, residence outside the US stroke belt or stroke buckle, physical inactivity, elevated depressive symptoms, and a history of coronary heart disease were associated with low adherence. In the current study, a small percentage of participants with aTRH had low adherence.
doi:10.1111/j.1751-7176.2012.00690.x
PMCID: PMC3464920  PMID: 23031147
Hypertension; Treatment Resistant Hypertension; Medication adherence; Risk Factors
4.  Application of persuasion and health behavior theories for behavior change counseling: Design of the ADAPT (Avoiding Diabetes Thru Action Plan Targeting) program 
Patient education and counseling  2012;88(3):460-466.
Objective
Diabetes incidence is increasing worldwide and providers often do not feel they can effectively counsel about preventive lifestyle changes. The goal of this paper is to describe the development and initial feasibility testing of the Avoiding Diabetes Thru Action Plan Targeting (ADAPT) program to enhance counseling about behavior change for patients with pre-diabetes.
Methods
Primary care providers and patients were interviewed about their perspectives on lifestyle changes to prevent diabetes. A multidisciplinary design team incorporated this data to translate elements from behavior change theories to create the ADAPT program. The ADAPT program was pilot tested to evaluate feasibility.
Results
Leveraging elements from health behavior theories and persuasion literature, the ADAPT program comprises a shared goal-setting module, implementation intentions exercise, and tailored reminders to encourage behavior change. Feasibility data demonstrate that patients were able to use the program to achieve their behavior change goals.
Conclusion
Initial findings show that the ADAPT program is feasible for helping improve primary care providers’ counseling for behavior change in patients with pre-diabetes.
Practice Implications
If successful, the ADAPT program may represent an adaptable and scalable behavior change tool for providers to encourage lifestyle changes to prevent diabetes.
doi:10.1016/j.pec.2012.06.017
PMCID: PMC3417073  PMID: 22770813
5.  Depression severity, diet quality, and physical activity in women with obesity and depression 
Major depressive disorder (MDD) is prevalent in clinical weight loss settings and predicts poor weight loss outcomes. It is unknown whether the severity of depressive symptoms among those with MDD is associated with diet quality or physical activity levels. This knowledge is important for improving weight loss treatment for these patients. It was hypothesized that more severe depression is associated with poorer diet quality and lower physical activity levels among individuals with obesity and MDD. Participants were 161 women with current MDD and obesity enrolled in the baseline phase of a weight loss trial between 2007 and 2010. Depression severity was measured with the Beck Depression Inventory II. The Alternate Healthy Eating Index (AHEI) was applied to data from three 24-hour diet recalls to capture overall diet quality. Daily metabolic equivalents expended per day (MET-hrs/d) were calculated from three 24-hour physical activity recalls. Greater depression severity was associated with poorer overall diet quality (estimate=−.26, SE=.11, p=.02), but not with physical activity (estimate=.07, SE=.05, p=.18), in linear regression models controlling for income, education, depression-related appetite change, binge eating disorder, and other potential confounds. Associations with diet quality were primarily driven by greater intake of sugar (r=.20, p<.01), saturated fat (r=.21, p<.01), and sodium (r=.22, p<.01). More severe depression was associated with poorer overall diet quality, but not physical activity, among treatment-seeking women with MDD and obesity. Future studies should identify mechanisms linking depression to diet quality, and determine whether diet quality improves with depression treatment.
doi:10.1016/j.jand.2012.02.006
PMCID: PMC3378978  PMID: 22709773
Diet quality; Depression; Obesity; AHEI; Physical activity
6.  Predictors of Low Clopidogrel Adherence Following Percutaneous Coronary Intervention 
The American journal of cardiology  2011;108(6):822-827.
Few data are available on factors associated with low adherence or early clopidogrel discontinuation following percutaneous coronary intervention (PCI). Patients (n=284) were evaluated prior to hospital discharge following PCI to identify factors associated with low adherence to clopidogrel 30 days later. Pre-PCI adherence to daily medications was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8) and categorized as low, medium, or high (scores <6, 6 to <8 and 8, respectively). Low adherence to clopidogrel was defined as a MMAS-8 score < 6 (n=21) or having discontinued clopidogrel (n=11), both ascertained during a 30-day post-PCI interview. At 30 days post-PCI, 11% of patients had low adherence to clopidogrel. The odds ratios (95% confidence interval) for low adherence to clopidogrel was 3.78 (1.09 – 13.1), 3.06 (1.36 – 6.87), 2.46 (0.97 – 6.27) and 3.36 (0.99 – 11.4) for patients who reported, prior to PCI, taking smaller doses of medication due to cost, had difficulty filling prescriptions, had difficulty reaching their primary physician and were not comfortable asking their doctor for instructions, respectively. The odds ratios (95% CI) for low clopidogrel adherence following PCI among patients with medium and low, versus high adherence, to daily medications prior to PCI was 6.13 (1.34 – 28.2) and 10.9 (2.46 – 48.7), respectively. The c-statistic associated with pre-PCI MMAS-8 scores for discriminating low clopidogrel adherence at 30 days post-PCI was 0.733 (95% CI: 0.650 – 0.852). Pre-PCI adherence to daily medications may be a useful indicator for identifying patients who will have low clopidogrel adherence following PCI.
doi:10.1016/j.amjcard.2011.04.034
PMCID: PMC3586559  PMID: 21741610
Clopidgrel; medication adherence; percutaneous coronary intervention
8.  Development and Validation of a Self-Assessment Tool for Albuminuria: Results From the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study 
Background
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.
Outcome
Albuminuria was defined as a urinary albumin to urinary creatinine ratio ≥ 30 mg/g in spot samples.
Results
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.
Limitations
Repeat urine samples were not available to assess the persistency of albuminuria.
Conclusions
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.
doi:10.1053/j.ajkd.2011.01.027
PMCID: PMC3144301  PMID: 21620547
9.  Barriers to Physical Activity in East Harlem, New York 
Journal of Obesity  2012;2012:719140.
Background. East Harlem is an epicenter of the intertwining epidemics of obesity and diabetes in New York. Physical activity is thought to prevent and control a number of chronic illnesses, including diabetes, both independently and through weight control. Using data from a survey collected on adult (age 18+) residents of East Harlem, this study evaluated whether perceptions of safety and community-identified barriers were associated with lower levels of physical activity in a diverse sample. Methods. We surveyed 300 adults in a 2-census tract area of East Harlem and took measurements of height and weight. Physical activity was measured in two ways: respondents were classified as having met the weekly recommended target of 2.5 hours of moderate physical activity (walking) per week (or not) and reporting having engaged in at least one recreational physical activity (or not). Perceived barriers were assessed through five items developed by a community advisory board and perceptions of neighborhood safety were measured through an adapted 7-item scale. Two multivariate logistic regression models with perceived barriers and concerns about neighborhood safety were modeled separately as predictors of engaging in recommended levels of exercise and recreational physical activity, controlling for respondent weight and sociodemographic characteristics. Results. The most commonly reported perceived barriers to physical activity identified by nearly half of the sample were being too tired or having little energy followed by pain with exertion and lack of time. Multivariate regression found that individuals who endorsed a greater number of perceived barriers were less likely to report having met their weekly recommended levels of physical activity and less likely to engage in recreational physical activity controlling for covariates. Concerns about neighborhood safety, though prevalent, were not associated with physical activity levels. Conclusions. Although safety concerns were prevalent in this low-income, minority community, it was individual barriers that correlated with lower physical activity levels.
doi:10.1155/2012/719140
PMCID: PMC3403455  PMID: 22848797
10.  Meta-Analysis: Impact of Drug Class on Adherence to Antihypertensives 
Circulation  2011;123(15):1611-1621.
Background
Observational studies suggest there are differences in adherence to antihypertensive medications in different classes. Our objective was to quantify the association between antihypertensive drug class and adherence in clinical settings.
Methods and Results
Studies were identified through a systematic search of English-language articles published from inception of computerized databases till February 1, 2009. Studies were included if they measured adherence to antihypertensives using medication refill data and contained sufficient data to calculate a measure of relative risk of adherence and its variance. An inverse-variance weighted random-effects model was used to pool results. Hazard ratios (HR) and odds ratios (OR) were pooled separately, and HRs were selected as the primary outcome. Seventeen studies met inclusion criteria. The pooled mean adherence by drug class ranged from 28% for beta-blockers to 65% for angiotensin II-receptor blockers (ARBs).There was better adherence to ARBs compared to angiotensin-converting enzyme inhibitors (ACEIs) (HR 1.33, 95%CI 1.13–1.57), calcium channel blockers (HR 1.57, 95% CI 1.38–1.79), diuretics (HR 1.95, 95%CI 1.73–2.20), and beta-blockers (HR 2.09, 95%CI 1.14–3.85). Conversely, there was lower adherence to diuretics compared to the other drug classes. The same pattern was present when pooling studies that used ORs. When accounting for publication bias, there were no longer significant differences in adherence between ARBs and ACEIs or between diuretics and beta-blockers.
Conclusion
In clinical settings, there are important differences in adherence to antihypertensives in separate classes with lowest adherence to diuretics and beta-blockers and highest to ARBs and ACEIs. Yet, adherence was suboptimal regardless of drug class.
doi:10.1161/CIRCULATIONAHA.110.983874
PMCID: PMC3084582  PMID: 21464050
hypertension; medication adherence; meta-analysis
11.  Association of Left Ventricular Hypertrophy With Incident Hypertension: The Multi-Ethnic Study of Atherosclerosis 
American Journal of Epidemiology  2011;173(8):898-905.
Increased left ventricular (LV) mass and changes in LV geometry may precede hypertension onset. The authors examined the associations of LV mass and geometry, assessed by cardiac magnetic resonance imaging, with hypertension incidence in 2,567 normotensive participants enrolled in 2000–2002 in the Multi-Ethnic Study of Atherosclerosis, an ethnically diverse, population-based, US study. Over a median follow-up of 4.8 years, 745 (29%) participants developed hypertension. In a fully adjusted model including baseline blood pressure, the relative risks of incident hypertension from the lowest to highest LV mass quartile were 1.00 (referent), 1.13 (95% confidence interval (CI): 0.89, 1.43), 1.28 (95% CI: 1.00, 1.63), and 1.78 (95% CI: 1.38, 2.30) (P < 0.001 for linear trend). Higher levels of LV concentric geometry, defined by higher LV mass to end-diastolic volume quartiles, were associated with higher risk of incident hypertension in a fully adjusted model (P = 0.044 for linear trend). In a final model containing both quartiles of LV mass and LV mass/volume along with all covariates including baseline blood pressure, higher LV mass quartiles were associated with incident hypertension (P < 0.001 for linear trend), whereas higher LV mass/volume quartiles were not (P = 0.643 for linear trend). In this multiethnic cohort, alterations in LV mass preceded hypertension onset among normotensive individuals.
doi:10.1093/aje/kwq509
PMCID: PMC3105258  PMID: 21422061
hypertension; hypertrophy, left ventricular; magnetic resonance imaging; risk factors
12.  Projected impact of polypill use among US adults: medication use, cardiovascular risk reduction and side effects 
American heart journal  2011;161(4):719-725.
Background
Polypills which include multiple medications for reducing cardiovascular disease (CVD) risk in a single pill have been proposed for population-wide use. The number of US adults eligible for polypills and potential benefits are unknown.
Methods
The National Health and Nutrition Examination Survey 2003-2004 and 2007-2008 were analyzed to estimate treatment rates for medications proposed for inclusion in polypills (aspirin, statin, an ACE-inhibitor, and a thiazide-type diuretic for those without, a beta-blocker for those with, a history of myocardial infarction) among US adults. The number of coronary heart disease (CHD) and stroke events potentially prevented through polypill use was projected by published meta-analyses and three large population-based cohort studies. Two polypill eligibility criteria were analyzed (1) US adults ≥ 55 years and (2) US adults with a history of CVD.
Results
There are 67.6 million US adults ≥ 55 years and 15.4 million US adults with a history of CVD and, thus, eligible for polypills using the two outlined criteria. In 2007-2008, 37.3% of US adults ≥ 55 years and 57.0% of those with a history of CVD were taking statins. Use of other polypill medications was also low. Polypill use by US adults age ≥ 55 years is projected to potentially prevent 3.2 million CHD events and 1.7 million strokes over 10 years. Amongst those with a history of CVD, the potential to prevent of 0.9 million CHD events and 0.5 million strokes is projected.
Conclusions
Polypills have the potential to lower CVD incidence substantially among US adults.
doi:10.1016/j.ahj.2010.12.019
PMCID: PMC3093765  PMID: 21473971
13.  Increasing efficacy of primary care-based counseling for diabetes prevention: Rationale and design of the ADAPT (Avoiding Diabetes Thru Action Plan Targeting) trial 
Background
Studies have shown that lifestyle behavior changes are most effective to prevent onset of diabetes in high-risk patients. Primary care providers are charged with encouraging behavior change among their patients at risk for diabetes, yet the practice environment and training in primary care often do not support effective provider counseling. The goal of this study is to develop an electronic health record-embedded tool to facilitate shared patient-provider goal setting to promote behavioral change and prevent diabetes.
Methods
The ADAPT (Avoiding Diabetes Thru Action Plan Targeting) trial leverages an innovative system that integrates evidence-based interventions for behavioral change with already-existing technology to enhance primary care providers' effectiveness to counsel about lifestyle behavior changes. Using principles of behavior change theory, the multidisciplinary design team utilized in-depth interviews and in vivo usability testing to produce a prototype diabetes prevention counseling system embedded in the electronic health record.
Results
The core element of the tool is a streamlined, shared goal-setting module within the electronic health record system. The team then conducted a series of innovative, "near-live" usability testing simulations to refine the tool and enhance workflow integration. The system also incorporates a pre-encounter survey to elicit patients' behavior-change goals to help tailor patient-provider goal setting during the clinical encounter and to encourage shared decision making. Lastly, the patients interact with a website that collects their longitudinal behavior data and allows them to visualize their progress over time and compare their progress with other study members. The finalized ADAPT system is now being piloted in a small randomized control trial of providers using the system with prediabetes patients over a six-month period.
Conclusions
The ADAPT system combines the influential powers of shared goal setting and feedback, tailoring, modeling, contracting, reminders, and social comparisons to integrate evidence-based behavior-change principles into the electronic health record to maximize provider counseling efficacy during routine primary care clinical encounters. If successful, the ADAPT system may represent an adaptable and scalable technology-enabled behavior-change tool for all primary care providers.
Trial Registration
ClinicalTrials.gov Identifier NCT01473654
doi:10.1186/1748-5908-7-6
PMCID: PMC3274467  PMID: 22269066
14.  Impact of A1C Screening Criterion on the Diagnosis of Pre-Diabetes Among U.S. Adults 
Diabetes Care  2010;33(10):2190-2195.
OBJECTIVE
New clinical practice recommendations include A1C as an alternative to fasting glucose as a diagnostic test for identifying pre-diabetes. The impact of these new recommendations on the diagnosis of pre-diabetes is unknown.
RESEARCH DESIGN AND METHODS
Data from the National Health and Nutrition Examination Survey 1999–2006 (n = 7,029) were analyzed to determine the percentage and number of U.S. adults without diabetes classified as having pre-diabetes by the elevated A1C (5.7–6.4%) and by the impaired fasting glucose (IFG) (fasting glucose 100–125 mg/dl) criterion separately. Test characteristics (sensitivity, specificity, and positive and negative predictive values) using IFG as the reference standard were calculated.
RESULTS
The prevalence of pre-diabetes among U.S. adults was 12.6% by the A1C criterion and 28.2% by the fasting glucose criterion. Only 7.7% of U.S. adults, reflecting 61 and 27% of those with pre-diabetes by A1C and fasting glucose, respectively, had pre-diabetes according to both definitions. A1C used alone would reclassify 37.6 million Americans with IFG to not having pre-diabetes and 8.9 million without IFG to having pre-diabetes (46.5 million reclassified). Using IFG as the reference standard, pre-diabetes by the A1C criterion has 27% sensitivity, 93% specificity, 61% positive predictive value, and 77% negative predictive value.
CONCLUSIONS
Using A1C as the pre-diabetes criterion would reclassify the pre-diabetes diagnosis of nearly 50 million Americans. It is imperative that clinicians and health systems understand the differences and similarities in using A1C or IFG in diagnosis of pre-diabetes.
doi:10.2337/dc10-0752
PMCID: PMC2945159  PMID: 20628087
15.  Rationale, design, and implementation protocol of an electronic health record integrated clinical prediction rule (iCPR) randomized trial in primary care 
Background
Clinical prediction rules (CPRs) represent well-validated but underutilized evidence-based medicine tools at the point-of-care. To date, an inability to integrate these rules into an electronic health record (EHR) has been a major limitation and we are not aware of a study demonstrating the use of CPR's in an ambulatory EHR setting. The integrated clinical prediction rule (iCPR) trial integrates two CPR's in an EHR and assesses both the usability and the effect on evidence-based practice in the primary care setting.
Methods
A multi-disciplinary design team was assembled to develop a prototype iCPR for validated streptococcal pharyngitis and bacterial pneumonia CPRs. The iCPR tool was built as an active Clinical Decision Support (CDS) tool that can be triggered by user action during typical workflow. Using the EHR CDS toolkit, the iCPR risk score calculator was linked to tailored ordered sets, documentation, and patient instructions. The team subsequently conducted two levels of 'real world' usability testing with eight providers per group. Usability data were used to refine and create a production tool. Participating primary care providers (n = 149) were randomized and intervention providers were trained in the use of the new iCPR tool. Rates of iCPR tool triggering in the intervention and control (simulated) groups are monitored and subsequent use of the various components of the iCPR tool among intervention encounters is also tracked. The primary outcome is the difference in antibiotic prescribing rates (strep and pneumonia iCPR's encounters) and chest x-rays (pneumonia iCPR only) between intervention and control providers.
Discussion
Using iterative usability testing and development paired with provider training, the iCPR CDS tool leverages user-centered design principles to overcome pervasive underutilization of EBM and support evidence-based practice at the point-of-care. The ongoing trial will determine if this collaborative process will lead to higher rates of utilization and EBM guided use of antibiotics and chest x-ray's in primary care.
Trial Registration
ClinicalTrials.gov Identifier NCT01386047
doi:10.1186/1748-5908-6-109
PMCID: PMC3184082  PMID: 21929769
16.  Comparison of the Framingham Heart Study Hypertension Model with Blood Pressure Alone in the Prediction of Risk of Hypertension: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Hypertension  2010;55(6):1339-1345.
A prediction model, developed in the Framingham Heart Study (FHS), has been proposed for use in estimating a given individual’s risk of hypertension. We compared this model with systolic blood pressure (SBP) alone and age-specific diastolic blood pressure (DBP) categories for the prediction of hypertension. Participants in the Multi-Ethnic Study of Atherosclerosis, without hypertension or diabetes (n=3013), were followed for the incidence of hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or the initiation of antihypertensive medication). The predicted probability of developing hypertension between four adjacent study examinations, with a median of 1.6 years between examinations, was determined. The mean (standard deviation) age of participants was 58.5 (9.7) years and 53% were women. During follow-up, 849 incident cases of hypertension occurred. The c-statistic for the FHS model was 0.788 (95% CI: 0.773, 0.804) compared with 0.768 (95% CI: 0.751, 0.785; p=0.096 compared to the FHS model) for SBP alone and 0.699 (95% CI: 0.681, 0.717; p<0.001 compared to the FHS model) for age-specific DBP categories. The relative integrated discrimination improvement index for the FHS model versus SBP alone was 10.0% (95% CI: −1.7%, 22.7%) and versus age-specific DBP categories was 146% (95% CI: 116%, 181%). Using the FHS model, there were significant differences between observed and predicted hypertension risk (Hosmer-Lemeshow goodness of fit p<0.001); re-calibrated and best-fit models produced a better model fit (p=0.064 and 0.245, respectively). In this multi-ethnic cohort of U.S. adults, the FHS model was not substantially better than SBP alone for predicting hypertension.
doi:10.1161/HYPERTENSIONAHA.109.149609
PMCID: PMC3023992  PMID: 20439822
hypertension; epidemiology; systolic blood pressure; diastolic blood pressure; risk prediction
17.  Comparative Validity of 3 Diabetes Mellitus Risk Prediction Scoring Models in a Multiethnic US Cohort 
American Journal of Epidemiology  2010;171(9):980-988.
Several models for estimating risk of incident diabetes in US adults are available. The authors aimed to determine the discriminative ability and calibration of published diabetes risk prediction models in a contemporary multiethnic cohort. Participants in the Multi-Ethnic Study of Atherosclerosis without diabetes at baseline (2000–2002; n = 5,329) were followed for a median of 4.75 years. The predicted risk of diabetes was calculated using published models from the Framingham Offspring Study, the Atherosclerosis Risk in Communities (ARIC) Study, and the San Antonio Heart Study. The mean age of participants was 61.6 years (standard deviation, 10.2); 29.3% were obese, 53.1% had hypertension, 34.9% had a family history of diabetes, 27.5% had high triglyceride levels, 33.8% had low high density lipoprotein cholesterol levels, and 15.3% had impaired fasting glucose. There were 446 incident cases of diabetes (fasting glucose level ≥126 mg/dL or initiation of antidiabetes medication use) diagnosed during follow-up. C statistics were 0.78, 0.84, and 0.83 for the Framingham, ARIC, and San Antonio risk prediction models, respectively. There were significant differences between observed and predicted diabetes risks (Hosmer-Lemeshow goodness-of-fit chi-squared test for each model: P < 0.001). The recalibrated and best-fit models achieved sufficient goodness of fit (each P > 0.10). The Framingham, ARIC, and San Antonio models maintained high discriminative ability but required recalibration in a modern, multiethnic US cohort.
doi:10.1093/aje/kwq030
PMCID: PMC2877477  PMID: 20375194
cohort studies; diabetes mellitus; models, statistical; risk; validation studies as topic
18.  ENDOTHELIAL DYSFUNCTION AND THE RISK OF HYPERTENSION: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS 
Hypertension  2010;55(5):1210-1216.
Hypertension is associated with impaired endothelial function in cross-sectional studies. However, few longitudinal data exist on whether endothelial dysfunction precedes the development of hypertension. We examined the cross-sectional and longitudinal relationships between endothelial-dependent brachial artery flow-mediated dilation (FMD) and hypertension prevalence and incidence in 3,500 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), an ethnically diverse, community-based cohort study. At baseline, the prevalence ratios (95% CI) of hypertension from the highest to the lowest quartile of FMD were 1.00 (referent), 1.26 (1.12 – 1.40), 1.35 (1.21 – 1.52), and 1.68 (1.50 – 1.87) (linear trend P < 0.001). This association remained (P = 0.017) after adjustment for demographics (age, gender, ethnicity), MESA site, and other risk factors. Of the 1,869 participants without hypertension at baseline, 584 (31.3%) developed hypertension over a median follow-up of 4.8 years. The unadjusted relative risks (95% CI) of incident hypertension from the highest to the lowest quartile of FMD were 1.00 (referent), 1.38 (1.14 – 1.67), 1.44 (1.19 – 1.74), and 1.64 (1.36 – 1.97) (linear trend P < 0.001). However, after adjustment for demographics and MESA site, the relationship between FMD and incident hypertension was attenuated and not statistically significant: 1.00 (referent), 1.26 (1.04 – 1.52), 1.19 (0.98 – 1.44), and 1.18 (0.97 – 1.44). The longitudinal results also did not appreciably change after adjustment for additional risk factors and baseline blood pressure levels. In this sample, reduced FMD was not an independent predictor of hypertension incidence, suggesting that impaired endothelial function does not play a major role in the development of hypertension.
doi:10.1161/HYPERTENSIONAHA.109.143123
PMCID: PMC2896877  PMID: 20308612
hypertension; blood pressure; endothelium; atherosclerosis; epidemiology
19.  Overweight and obesity and elevated serum cystatin C levels in US adults 
The American journal of medicine  2008;121(4):341-348.
Background
Although high body mass index (BMI) is a risk factor for hypertension, diabetes, and cardiovascular disease, limited data exist on the association of overweight and obesity with early stages of kidney disease.
Methods
Cross-sectional data for 5083 participants of the nationally representative Third National Health and Nutrition Examination Survey with an estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 without micro- or macro-albuminuria were analyzed to determine the association between BMI and elevated serum cystatin C. Normal weight, overweight, class I obesity, and class II–III obesity were defined as a BMI of 18.5 to 24.9 kg/m2, 25.0 to 29.9 kg/m2, 30.0 to 34.9 kg/m2 and ≥ 35.0 kg/m2, respectively. Elevated serum cystatin C was defined as ≥ 1.09 mg/L (≥99th percentile for participants 20 to 39 years of age without diabetes, hypertension, micro- or macro-albuminuria or stage 3–5 chronic kidney disease).
Results
The age-standardized prevalence of elevated serum cystatin C was 9.6%, 12.9%, 17.4%, and 21.5% among adults of normal weight, overweight, class I obesity, and class II–III obesity, respectively (p-trend<0.001). After multivariate adjustment for demographics, behaviors, systolic blood pressure and serum biomarkers and compared to normal weight participants, the odds ratio (95% confidence interval) of elevated serum cystatin C was 1.46 (1.02–2.10) for overweight, 2.36 (1.56–3.57) for class I obesity, and 2.82 (1.56–5.11) for class II–III obesity.
Conclusion
A graded association exists between higher BMI and elevated serum cystatin C. Further research is warranted to assess whether reducing BMI favorably impacts elevated serum cystatin C and the development of chronic kidney disease.
doi:10.1016/j.amjmed.2008.01.003
PMCID: PMC3049932  PMID: 18374694
20.  Misconceptions About Diabetes and Its Management Among Low-Income Minorities With Diabetes 
Diabetes Care  2009;32(4):591-593.
OBJECTIVE
To determine diabetic patients' knowledge and beliefs about the disease and medications that could hinder optimal disease management.
RESEARCH DESIGN AND METHODS
A cross-sectional survey of 151 type 2 diabetic patients characterizing diabetes knowledge and beliefs about the disease and medications was conducted.
RESULTS
Mean diabetes duration was 13 years. Over half of the patients (56%) believed that normal glucose is ≤200 mg/dl, 54% reported being able to feel when blood glucose levels are high, 36% thought that they will not always have diabetes, 29% thought that their doctor will cure them of diabetes, one in four (23%) said there is no need to take diabetes medications when glucose levels are normal, and 12% believed they have diabetes only when glucose levels are high.
CONCLUSIONS
Diabetes knowledge and beliefs inconsistent with a chronic disease model of diabetes were prevalent in this sample. Suboptimal knowledge and beliefs are potentially modifiable and are logical targets for educational interventions to improve diabetes self-management.
doi:10.2337/dc08-1837
PMCID: PMC2660470  PMID: 19131457
21.  Age-related associations of hypertension and diabetes mellitus with chronic kidney disease 
BMC Nephrology  2009;10:17.
Background
Studies suggest end-stage renal disease incidence and all-cause mortality rates among patients with chronic kidney disease (CKD) differ by age. The association of diabetes mellitus and hypertension with CKD across the adult lifespan is not well established.
Methods
Data from NHANES 1999–2004 were used to determine the association of risk factors for stage 3 or 4 CKD (n = 12,518) and albuminuria (n = 12,778) by age grouping (20 to 49, 50 to 69, and ≥70 years). Stage 3 or 4 CKD was defined as an estimated glomerular filtration rate of 15 to 59 ml/min/1.73 m2 and albuminuria as an albumin to creatinine ratio ≥30 mg/g.
Results
For adults 20 to 49, 50 to 69 and ≥70 years of age, the prevalence ratios (95% confidence interval) of stage 3 or 4 CKD associated with hypertension were 1.94 (0.86 – 4.35), 1.51 (1.09 – 2.07), 1.31 (1.15 – 1.49), respectively (p-trend = 0.038). The analogous prevalence ratios (95% confidence interval) were 3.01 (1.35 – 6.74), 1.61 (1.15 – 2.25), 1.40 (1.15 – 1.69), respectively, for diagnosed diabetes mellitus (p-trend = 0.067); and 2.67 (0.53 – 13.4), 1.35 (0.69 – 2.63), 1.08 (0.78 – 1.51), respectively, for undiagnosed diabetes mellitus (p-trend = 0.369). The prevalence ratios of albuminuria associated with hypertension and diagnosed and undiagnosed diabetes mellitus were lower at older age (each p < 0.05).
Conclusion
Among US adults, diabetes mellitus and hypertension are associated with CKD and albuminuria regardless of age. However, the associations were stronger at younger ages.
doi:10.1186/1471-2369-10-17
PMCID: PMC2714514  PMID: 19563681

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