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1.  A Multilevel Assessment of Barriers to Adoption of Dietary Approaches to Stop Hypertension (DASH) among African Americans of Low Socioeconomic Status 
Background
We examined perceptions of Dietary Approaches to Stop Hypertension (DASH) and the food environment among African Americans (AA) with high blood pressure living in two low-income communities and objectively assessed local food outlets.
Methods
Focus groups were conducted with 30 AAs; participants discussed DASH and the availability of healthy foods in their community. Sessions were transcribed and themes identified. Fifty-four stores and 114 restaurants were assessed using the Nutrition Environment Measures Survey (NEMS).
Results
Common themes included poor availability, quality, and cost of healthy foods; tension between following DASH and feeding other family members; and lack of congruity between their preferred foods and DASH. Food outlets in majority AA census tracts had lower NEMS scores (stores: −11.7, p=.01, restaurants: −8.3, p=.001) compared with majority White areas.
Conclusions
Interventions promoting DASH among lower income AAs should reflect the food customs, economic concerns, and food available in communities.
doi:10.1353/hpu.2011.0142
PMCID: PMC3769217  PMID: 22080704
Hypertension; diet; food deserts; African American
2.  Translating the Dietary Approaches to Stop Hypertension (DASH) Diet for Use in Underresourced, Urban African American Communities, 2010 
Introduction
Randomized trials have demonstrated the effectiveness of the Dietary Approaches to Stop Hypertension (DASH) program for lowering blood pressure; however, program participation has been limited in some populations. The objective of this pilot study was to test the feasibility of using a culturally modified version of DASH among African Americans in an underresourced community.
Methods
This randomized controlled pilot study recruited African Americans in 2 North Carolina neighborhoods who had high blood pressure and used fewer than 3 antihypertension medications. We offered 2 individual and 9 group DASH sessions to intervention participants and 1 individual session and printed DASH educational materials to control participants. We collected data at baseline (March 2010) and 12 weeks (June 2010).
Results
Of 152 potential participants, 25 were randomly assigned to either the intervention (n = 14) or the control (n = 11) group; 22 were women, and 21 were educated beyond high school. At baseline, mean blood pressure was 130/78 mm Hg; 19 participants used antihypertension medications, and mean body mass index was 35.9 kg/m2. Intervention participants attended 7 of 9 group sessions on average. After 12 weeks, we observed significant increases in fruit and vegetable consumption and increases in participants’ confidence in their ability to reduce salt and fat consumption and eat healthier snacks in intervention compared with control participants. We found no significant decreases in blood pressure.
Conclusion
Implementation of a culturally modified, community-based DASH intervention was feasible in our small sample of African Americans, which included people being treated for high blood pressure. Future studies should evaluate the long-term effect of this program in a larger sample.
doi:10.5888/pcd10.120088
PMCID: PMC3545703  PMID: 23306077
4.  Impact of a Multifaceted Intervention on Cholesterol Management in Primary Care Practices 
Archives of internal medicine  2009;169(7):678-686.
Background
Physician adherence to National Cholesterol Education Program clinical practice guidelines has been poor.
Methods
We recruited 68 primary care family and internal medicine practices; 66 were randomly allocated to a study arm; 5 practices withdrew, resulting in 29 receiving the Third Adult Treatment Panel (ATP III) intervention and 32 receiving an alternative intervention focused on the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7). The ATP III providers received a personal digital assistant providing the Framingham risk scores and ATP III–recommended treatment. All practices received copies of each clinical practice guideline, an introductory lecture, 1 performance feedback report, and 4 visits for intervention-specific academic detailing. Data were abstracted at 61 practices from random samples of medical records of patients treated from June 1, 2001, through May 31, 2003 (baseline), and from May 1, 2004, through April 30, 2006 (follow-up). The proportion screened with subsequent appropriate decision making (primary outcome) was calculated. Generalized estimating equations were used to compare results by arm, accounting for clustering of patients within practices.
Results
We examined 5057 baseline and 3821 follow-up medical records. The screening rate for lipid levels increased from 43.6% to 49.0% (ATP III practices) and from 40.1% to 50.8% (control practices) (net difference, −5.3% [P=.22]). Appropriate management of lipid levels decreased slightly (73.4% to 72.3%) in ATP III practices and more markedly (79.7% to 68.9%) in control practices. The net change in appropriate management favored the intervention (+9.7%; 95% confidence interval [CI], 2.8%-16.6% [P<.01]). Appropriate drug prescription within 4 months decreased in both arms (38.8% to 24.8% in ATP III practices and 45.3% to 24.1% in control practices; net change, +7.2% [P=.37]) Overtreat-ment declined from 6.6% to 3.9% in ATP III and rose from 4.2% to 6.4% in control practices (net change, −4.9% [P=.01]).
Conclusions
A multifactor intervention including personal digital assistant–based decision support may improve primary care physician adherence to the ATP III guidelines.
doi:10.1001/archinternmed.2009.44
PMCID: PMC2937279  PMID: 19364997
5.  The Association Between Physical Activity and Subclinical Atherosclerosis 
American Journal of Epidemiology  2008;169(4):444-454.
Prior reports regarding the association between physical activity and subclinical cardiovascular disease have not been consistent. The authors assessed physical activity and walking pace via questionnaire among 6,482 US adults aged 45–84 years without prior clinical cardiovascular disease participating in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2002. Ankle-brachial index (ABI), coronary artery calcification, and internal and common carotid intima-media thickness (IMT) were measured. Metabolic equivalent-hours/week of physical activity were calculated. These data were analyzed by using multivariable linear or relative prevalence regression in gender-specific strata. After adjustment for age, race/ethnicity, clinic site, education, income, and smoking (model 1), increasing total, moderate + vigorous, and intentional-exercise physical activity were not associated with IMT or coronary artery calcification in either gender. These factors were associated with increased ABI (P < 0.05) in women only. Walking pace was associated favorably with common carotid IMT, ABI, and coronary artery calcification in men and with common carotid IMT and ABI in women (all P < 0.05) after adjustment for model 1 variables. These associations were attenuated and, for common carotid IMT, no longer significant when lipids, hypertension, diabetes, and body mass index were added to the model. These data suggest that walking pace is associated with less subclinical atherosclerosis; these associations may be mediated by cardiovascular disease risk factors.
doi:10.1093/aje/kwn350
PMCID: PMC2726643  PMID: 19075250
atherosclerosis; carotid arteries; coronary vessels; exercise; motor activity; peripheral vascular diseases
6.  Age at Menopause and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis 
Menopause (New York, N.Y.)  2014;21(6):585-591.
Objective
To evaluate associations of early menopause (menopause occurring before 45 years of age) and age at menopause with incident heart failure (HF) in post-menopausal women. We also explored associations of early, and age at menopause with left ventricular (LV) measures of structure and function in post-menopausal women.
Methods
We included 2947 post-menopausal women, aged 45-84 years, without known cardiovascular disease (2000-2002), from the Multi-Ethnic study of Atherosclerosis. Cox-Proportional hazards models were used to examine associations of early, and age at menopause with incident HF. In 2123 post-menopausal women in whom cardiac magnetic resonance imaging was obtained at baseline, we explored associations of early, and age at menopause with LV measures using multivariable linear regression.
Results
Over a median follow-up of 8.5 years, we observed 71 HF events. There were no significant interactions with ethnicity for incident HF (Pinteraction>0.05). In adjusted analysis, early menopause was associated with increased risk of incident HF [1.66 (1.01-2.73)], while each year increase in age at menopause was associated with decreased risk of incident HF [0.96 (0.94-0.99)]. We observed significant interactions between early menopause and ethnicity for LV mass to volume ratio (LVMVR), Pinteraction=0.02. In Chinese-American women, early menopause was associated with higher LVMVR (+0.11, p=0.0002), while each year increase in age at menopause was associated with lower LVMVR (−0.004, p=0.04) at baseline.
Conclusion
An older menopausal age is independently associated with decreased risk of incident HF. Concentric LV remodelling, indicated by a higher LVMVR was present in Chinese-American women with early menopause at baseline.
doi:10.1097/GME.0000000000000138
PMCID: PMC4031284  PMID: 24423934
Menopause; Heart failure; Estrogen
7.  Effect of a Long-Term Behavioral Weight Loss Intervention on Nephropathy in Overweight or Obese Adults with Type 2 Diabetes: the Look AHEAD Randomized Clinical Trial 
Background
Long-term effects of behavioral weight loss interventions on diabetes complications are unknown. We assessed whether an intensive lifestyle intervention (ILI) affects the development of nephropathy in Look AHEAD, a multicenter randomized clinical trial in type 2 diabetes.
Methods
5145 overweight or obese persons aged 45–76 years with type 2 diabetes were randomized to ILI designed to achieve and maintain weight loss through reduced caloric consumption and increased physical activity or to a diabetes support and education (DSE) group. Randomization to ILI or DSE, in a 1:1 ratio, was implemented in a central web-based data management system, stratified by clinical center, and blocked with random block sizes. Outcomes assessors and laboratory staff were masked to treatment. The interventions ended early because of lack of effect on the primary outcome of cardiovascular disease events. Albuminuria and estimated glomerular filtration rate were prespecified “other” outcomes and were assessed from baseline through 9.6 years (median) of follow-up until the interventions ended. They were combined post-hoc to define the main outcome for this report: very-high-risk chronic kidney disease (CKD) based on the 2013 Kidney Disease Improving Global Outcomes classification. Data were analyzed by intention to treat. The trial is registered as Clinicaltrials.gov NCT00017953.
Findings
The incidence rate of very-high-risk CKD was 31% lower in ILI than DSE with hazard rates of 0.90 cases/100 person-years in DSE and 0.63 in ILI (difference=0.27 cases/100 person-years, hazard ratio and 95% confidence interval: HR=0.69, 0.55 to 0.87). This effect was partly attributable to reductions in weight, HbA1c, and blood pressure.
Interpretation
Weight loss should be considered as an adjunct to medical therapies to prevent or delay progression of CKD in overweight or obese persons with type 2 diabetes.
Primary Funding
National Institute of Diabetes and Digestive and Kidney Diseases.
doi:10.1016/S2213-8587(14)70156-1
PMCID: PMC4443484  PMID: 25127483
8.  Heart Rate–Corrected QT Interval Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Individuals With Type 2 Diabetes: The Diabetes Heart Study 
Diabetes Care  2014;37(5):1454-1461.
OBJECTIVE
Heart rate–corrected QT (QTc) interval is associated with mortality in the general population, but this association is less clear in individuals with type 2 diabetes. We assessed the association of QTc interval with all-cause and cardiovascular disease (CVD) mortality in the Diabetes Heart Study.
RESEARCH DESIGN AND METHODS
We studied 1,020 participants with type 2 diabetes (83% European Americans; 55% women; mean age 61.4 years) who were free of atrial fibrillation, major ventricular conduction defects, and antiarrhythmic therapy at baseline. QT duration was automatically calculated from a standard 12-lead electrocardiogram (ECG). Following American Heart Association/American College of Cardiology Foundation recommendations, a linear scale was used to correct the QT for heart rate. Using Cox regression, risk was estimated per 1-SD increase in QTc interval as well as prolonged QTc interval (>450 ms) vs. normal QTc interval for mortality.
RESULTS
At baseline, the mean (SD) QTc duration was 414.9 ms (18.1), and 3.0% of participants had prolonged QTc. After a median follow-up time of 8.5 years (maximum follow-up time 13.9 years), 204 participants were deceased. In adjusted multivariate models, a 1-SD increase in QTc interval was associated with an 18% higher risk for all-cause mortality (hazard ratio 1.18 [95% CI 1.03–1.36]) and 29% increased risk for CVD mortality (1.29 [1.05–1.59]). Similar results were obtained when QTc interval was used as a categorical variable (prolonged vs. normal) (all-cause mortality 1.73 [0.95–3.15]; CVD mortality 2.86 [1.35–6.08]).
CONCLUSIONS
Heart rate QTc interval is an independent predictor of all-cause and CVD mortality in this population with type 2 diabetes, suggesting that additional prognostic information may be available from this simple ECG measure.
doi:10.2337/dc13-1257
PMCID: PMC4182905  PMID: 24574343
9.  Racial and ethnic disparities in cardiac catheterization for acute myocardial infarction in the United States, 1995--2001. 
OBJECTIVE: To examine recent trends in racial and ethnic disparities in cardiac catheterization for acute myocardial infarction (AMI) to determine whether disparities documented from the 1980s through mid-1990s persist, and evaluate whether patient and hospital characteristics are associated with any observed disparities METHODS: Cross-sectional analyses of 585,710 white, 51,369 black and 31,923 Hispanic discharges from hospitals in the Nationwide Inpatient Sample (which includes data on all discharges from 951 representative hospitals in 23 states) that had performed cardiac catheterization from 1995--2001 with a primary diagnosis of AMI. Adjusted procedure rates and prevalence ratios (PR) were computed to compare catheterization rates by race and ethnicity. MEASUREMENTS AND MAIN RESULTS: Catheterization rates were higher for whites than blacks for all years examined; rates among Hispanics increased during this period and approached the rate among whites. After adjustment for age, demographics, comorbidity, year and hospital characteristics, rates (per 100 discharges) were 58.4 for whites, 50.1 for blacks (PR 0.87; 95% CI 0.84-0.91) and 55.2 for Hispanics (PR 0.95; 95% CI 0.90-0.99). CONCLUSIONS: These nationwide data suggest blacks remain less likely than whites and Hispanics to undergo catheterization during a hospitalization for AMI. Whether this disparity stems from patient or provider factors remains to be determined.
PMCID: PMC2568623  PMID: 15779495
10.  Comparison of risks of cardiovascular events in the elderly using standard survival analysis and multiple-events and recurrent-events methods 
Background
Epidemiological studies about cardiovascular diseases often rely on methods based on time-to-first-event for data analysis. Without taking into account multiple event-types and the recurrency of a specific cardiovascular event, this approach may underestimate the overall cardiovascular burden of some risk factors, if that is the goal of the study.
Methods
In this study we compare four different statistical approaches, all based on the Weibull distribution family of survival model, in analyzing cardiovascular risk factors. We use data from the Cardiovascular Health Study as illustration. The four models respectively are time-to-first-event only, recurrent-events only, multiple-event-types only, and joint recurrent and multiple-event-type models.
Results
Although the four models produce consistent results regarding the significance of the risk factors, the magnitude of the hazard ratios and their confidence intervals are different. The joint model produces hazard ratios that are substantially higher than the time-to-first-event model especially for the risk factors of smoking and diabetes.
Conclusion
Our findings suggest that for people with diabetes and are currently smoking, the overall cardiovascular burden of these risk factors would be substantially higher than that estimated using time-to-first-event method.
Electronic supplementary material
The online version of this article (doi:10.1186/s12874-015-0004-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12874-015-0004-3
PMCID: PMC4364095  PMID: 25887387
Cardiovascular disease; Cardiovascular risk factor; Survival analysis; Weibull distribution
11.  DASH Eating Pattern Is Associated with Favorable Left Ventricular Function in the Multi-Ethnic Study of Atherosclerosis 
Objective
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).
Design
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).
Results
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).
Conclusions
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
12.  Association Between Coronary Artery Calcification Progression and Microalbuminuria 
JACC. Cardiovascular imaging  2010;3(6):595-604.
OBJECTIVES
This study sought to evaluate the relationship between microalbuminuria (MA) and the development and progression of atherosclerosis, as assessed by incident and progression of coronary artery calcification (CAC).
BACKGROUND
MA is associated with an increased risk of cardiovascular disease, but the mechanism by which MA imparts this increased risk is not known.
METHODS
The MESA (Multi-Ethnic Study of Atherosclerosis) study is a prospective cohort study of 6,814 self-identified White, African-American, Hispanic, or Chinese participants free of clinical cardiovascular disease at entry. Of the 6,775 individuals with available urine albumin data, we excluded 97 subjects with macroalbuminuria and 1,023 with missing follow-up CAC data. The final study population consists of 5,666 subjects.
RESULTS
At baseline, individuals with MA were more likely to have CAC >0 compared with those without MA (62% vs. 48%, p < 0.0001). During a mean follow-up of 2.4 ± 0.8 years, those with MA and no CAC at baseline were more likely to develop CAC (relative risk [RR]: 2.05, 95% confidence interval [CI]: 1.41 to 3.02, p < 0.0001) as compared with those without MA in demographic-adjusted analyses. After multivariant adjustment, the relationship was attenuated but remained statistically significant (RR: 1.76, 95% CI: 1.19 to 2.61, p = 0.005). Among those with CAC at baseline, those with versus those without MA had a 15 (95% CI: 8 to 22, p < 0.0001) volume units higher median increase in CAC in demographic-adjusted analyses. After multivariant adjustment, MA remained associated with incident CAC (RR: 1.76, 95% CI: 1.19 to 2.61, p = 0.005) and with progression of CAC (median increase in CAC volume score of 9 [95% CI: 2 to 16, p = 0.009]), relative to those without MA.
CONCLUSIONS
This large multiethnic, population-based study of asymptomatic individuals demonstrates an increased risk of incident CAC as well as greater CAC progression among those with MA. Further study is needed to determine the degree to which MA precedes and predicts progression of atherosclerosis and how this information can be used to reduce cardiovascular events.
doi:10.1016/j.jcmg.2010.01.008
PMCID: PMC4083743  PMID: 20541715
coronary artery calcium; microalbuminuria; risk prediction; coronary heart disease; Multi-Ethnic Study of Atherosclerosis
13.  Carotid Intima‐Media Thickness is Associated With Incident Heart Failure Among Middle‐Aged Whites and Blacks: The Atherosclerosis Risk in Communities Study 
Background
Increased carotid intima‐media thickness (IMT) is associated with subclinical left ventricular myocardial dysfunction, suggesting a possible role of carotid IMT in heart failure (HF) risk determination.
Methods and Results
Mean far wall carotid IMT, measured by B‐mode ultrasound, was available for 13 590 Atherosclerosis Risk in Communities study participants aged 45 to 64 years and free of HF at baseline. HF was defined using ICD‐9 428 and ICD‐10 I‐50 codes from hospitalization records and death certificates. The association between carotid IMT and incident HF was assessed using Cox proportional hazards analysis with models adjusted for demographic variables, major CVD risk factors, and interim CHD. There were 2008 incident HF cases over a median follow‐up of 20.6 years (8.1 cases per 1000 person‐years). Mean IMT was higher in those with HF than in those without (0.81 mm±0.23 versus 0.71 mm±0.17, P<0.001). Unadjusted rate of HF for the fourth compared with the first quartile of IMT was 15.4 versus 3.9 per 1000 person‐years; P<0.001. In multivariable analysis, after adjustment, each standard deviation increase in IMT was associated with incident HF (HR 1.20 [95% CI: 1.16 to 1.25]). After adjustment, the top quartile of IMT was associated with HF (HR 1.60 [95% CI: 1.37 to 1.87]). Results were similar across race and gender groups.
Conclusions
Increasing carotid IMT is associated with incident HF in middle‐aged whites and blacks, beyond risks explained by major CVD risk factors and CHD. This suggests that carotid IMT may be associated with HF through mechanisms different from myocardial ischemia or infarction.
doi:10.1161/JAHA.114.000797
PMCID: PMC4309069  PMID: 24815496
carotid intima‐media thickness; heart failure; subclinical atherosclerosis
14.  Pulse Pressure and Subclinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis 
American Journal of Hypertension  2013;26(5):636-642.
BACKGROUND
Brachial pulse pressure (PP) has been found to be associated with markers of subclinical cardiovascular disease, including carotid intima–media thickness and left-ventricular mass index (LVMI), but it is unclear whether these associations are independent of traditional cardiovascular risk factors and of the steady, nonpulsatile component of blood pressure (BP). Moreover, it is unknown whether these associations are modified by gender, age, or race/ethnicity.
METHODS
We used multivariate linear regression models to assess the relationship between brachial PP and three markers of subclinical cardiovascular disease (CVD) (common carotid intima–media thickness (CC-IMT), internal carotid intima–media thickness (IC-IMT), and LVMI) in four race/ethnic groups in the Multi-Ethnic Study of Atherosclerosis. The models were adjusted for traditional Framingham risk factors (age, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, diabetes, smoking status), use of lipid-lowering medication, use of antihypertensive medication, study site, and mean arterial pressure (MAP).
RESULTS
The assessment was done on 6,776 participants (2,612 non-Hispanic white, 1,870 African-American, 1,494 Hispanic, and 800 Chinese persons). The associations between brachial PP and CC-IMT, IC-IMT, and LVMI were significant in fully adjusted models. The three subclinical markers also showed significant interactions with gender (P < 0.0001), with stronger interactions in men. There was an interaction with age for LVMI (P = 0.004) and IC-IMT (P = 0.008). Race/ethnicity modified the association of PP with CC-IMT.
CONCLUSIONS
Brachial PP was independently associated with subclinical CVD after adjustment for cardiovascular risk factors and mean arterial pressure (MAP). The strength of the association differed significantly for strata of gender, age, and race/ethnicity.
doi:10.1093/ajh/hps092
PMCID: PMC3657481  PMID: 23388832
pulse pressare; subclinical cardiovascular disease; carotid intima–media thickness; left ventricular mass index; aging; hypertension; arterial stiffness; blood pressure.
15.  Association of Lipids With Incident Heart Failure Among Adults With and Without Diabetes Mellitus 
Circulation. Heart failure  2013;6(3):371-378.
Background
Dyslipidemia is a known risk factor for coronary disease, but its role in heart failure (HF) development is less well-defined.
Methods and Results
We included 5688 participants, aged 45 to 84 years, without clinical cardiovascular disease, and not receiving lipid-lowering medications at baseline, from the Multiethnic Study of Atherosclerosis. Cox-proportional hazards models were used to evaluate associations of triglyceride, total cholesterol/high-density lipoprotein–cholesterol (HDL-C) ratio, HDL-C, and non HDL-C with incident HF. We investigated for effect-modification by diabetes mellitus status and sex. During a median follow-up of 8.5 years, there were 152 incident HF cases. There were no interactions by sex. We observed significant interactions between triglyceride and diabetes mellitus (Pinteraction<0.05). We stratified our analyses by diabetes mellitus status. In participants with diabetes, the hazard ratios were 2.03 (0.97–4.27) and 1.68 (1.18–2.38) for high triglyceride and log of triglyceride, respectively, after adjusting for confounders, comorbidities, and diabetes mellitus severity/treatment. The association of high triglyceride with incident HF was attenuated by interim myocardial infarction. The hazard ratios were greatest in participants with diabetes who also had high triglyceride, low HDL-C, or high total cholesterol/HDL-C ratio (3.59 [2.03–6.33], 3.62 [2.06–6.36], and 3.54 [1.87–6.70], respectively). Lipid measures were not associated with incident HF in individuals without diabetes.
Conclusions
The risk of incident HF is greater in individuals with diabetes mellitus who also have high triglyceride, low HDL-C, or high total cholesterol/HDL-C ratio. The association of high triglyceride with incident HF is partly mediated by myocardial infarction.
doi:10.1161/CIRCHEARTFAILURE.112.000093
PMCID: PMC3991930  PMID: 23529112
diabetes mellitus; heart failure; lipids
16.  Relations of the Mediterranean dietary pattern with insulin resistance and diabetes incidence in the Multi-Ethnic Study of Atherosclerosis (MESA) 
The British journal of nutrition  2012;109(8):1490-1497.
Type 2 diabetes is a highly prevalent but preventable disorder. We assessed the association between an a priori Mediterranean diet score (MeDiet) and fasting glucose and insulin at baseline and incident type 2 diabetes after 6-year follow-up in MESA. Dietary intake was measured at baseline by a 127-item food frequency questionnaire in 5,390 men and women aged 45-84 years free of prevalent diabetes and clinical CVD. A MeDiet score was created based on intake of 10 food components: vegetables, whole grains, nuts, legumes, fruits, ratio of monounsaturated to saturated fat, red and processed meat, dairy, fish and alcohol. Multivariable linear and proportional hazard models were used to estimate the association of MeDiet, categorized in quintiles, with baseline insulin and glucose, and incident diabetes, respectively. Models adjusted for demographic, physiologic and behavioral characteristics. After multivariable adjustment, individuals with a higher MeDiet score had lower baseline mean (95% CI) insulin levels [mean Q1: = 5.8 (5.6-6.0) umol/l; mean Q5: = 4.8 (4.6-5.0) umol/l; p-trend= <0.0001]. A higher MeDiet score was also associated with significantly lower glucose levels after basic adjustment, but was attenuated after adjustment for waist circumference. During follow-up, 412 incident diabetes events accrued. MeDiet was not significantly related to risk of incident diabetes (p-trend=0.64). In summary, greater consistency with a Mediterranean-style diet, reflected by a higher a priori Mediterranean diet score, was cross-sectionally associated with lower insulin levels among non-diabetics, and lower blood glucose prior to adjustment for obesity, but not with lower incidence of diabetes.
doi:10.1017/S0007114512003339
PMCID: PMC4002212  PMID: 22932232
17.  Transferability and Fine Mapping of Type 2 Diabetes Loci in African Americans 
Diabetes  2013;62(3):965-976.
Type 2 diabetes (T2D) disproportionally affects African Americans (AfA) but, to date, genetic variants identified from genome-wide association studies (GWAS) are primarily from European and Asian populations. We examined the single nucleotide polymorphism (SNP) and locus transferability of 40 reported T2D loci in six AfA GWAS consisting of 2,806 T2D case subjects with or without end-stage renal disease and 4,265 control subjects from the Candidate Gene Association Resource Plus Study. Our results revealed that seven index SNPs at the TCF7L2, KLF14, KCNQ1, ADCY5, CDKAL1, JAZF1, and GCKR loci were significantly associated with T2D (P < 0.05). The strongest association was observed at TCF7L2 rs7903146 (odds ratio [OR] 1.30; P = 6.86 × 10−8). Locus-wide analysis demonstrated significant associations (Pemp < 0.05) at regional best SNPs in the TCF7L2, KLF14, and HMGA2 loci as well as suggestive signals in KCNQ1 after correction for the effective number of SNPs at each locus. Of these loci, the regional best SNPs were in differential linkage disequilibrium (LD) with the index and adjacent SNPs. Our findings suggest that some loci discovered in prior reports affect T2D susceptibility in AfA with similar effect sizes. The reduced and differential LD pattern in AfA compared with European and Asian populations may facilitate fine mapping of causal variants at loci shared across populations.
doi:10.2337/db12-0266
PMCID: PMC3581206  PMID: 23193183
18.  The Relationship between Measures of Obesity and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis 
Obesity (Silver Spring, Md.)  2013;21(9):1915-1922.
Objective
To evaluate the strength of association of body mass index (BMI) and waist circumference (WC) with incident heart failure (HF), exploring our associations by ethnicity and age.
Design and Methods
We included 6,809 participants, aged 45–84 years, without clinical cardiovascular disease (2000–2002), from the Multi-Ethnic Study of Atherosclerosis. Cox-Proportional hazards models were used to examine associations of BMI and WC with incident HF. The predictive abilities of BMI and WC were compared using receiver operating characteristic curves.
Results
Over a median follow-up of 7.6 years, there were 176 cases. BMI and WC were associated with incident HF in men [1.33 (1.10–1.61) and 1.38 (1.18–1.62) respectively] and women [1.70 (1.33–2.17) and 1.64 (1.29–2.08) respectively]. These associations became non-significant after adjusting for obesity-related conditions (hypertension, dysglycemia, hypercholesterolemia, left ventricular hypertrophy, kidney disease and inflammation). The associations of BMI and WC did not vary significantly by ethnicity or age-group, but were inverse in Hispanic men. The area under the curve for BMI and WC was 0.749 and 0.750, respectively, in men and 0.782 and 0.777, respectively, in women.
Conclusions
The association between obesity and incident HF is largely mediated by obesity-related conditions. BMI and WC have similar predictive abilities for incident HF.
doi:10.1002/oby.20298
PMCID: PMC3664654  PMID: 23441088
Obesity; heart failure; body mass index and waist circumference
19.  Does Elevated Plasma Triglyceride Level Independently Predict Impaired Fasting Glucose? 
Diabetes Care  2013;36(2):342-347.
OBJECTIVE
Elevated plasma triglycerides (TGs) have been included in diabetes risk prediction models. This study examined whether elevated TGs predict risk for impaired fasting glucose (IFG).
RESEARCH DESIGN AND METHODS
This study used the baseline and longitudinal follow-up data from the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included non-Hispanic whites, African Americans, Hispanics, and Chinese Americans 45–84 years of age who had fasting glucose <100 mg/dL at baseline and who did not have clinically evident cardiovascular disease or diabetes. Cox proportional regression models were used to examine the association of elevated TGs with incidence of IFG adjusting for central obesity, low HDL cholesterol, elevated blood pressure, baseline fasting glucose, and BMI. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of elevated TGs in predicting IFG were calculated.
RESULTS
The incidence rate of developing IFG was 59.1 per 1,000 person-years during the median 4.75 years of follow-up. African Americans and Hispanics had a higher incidence rate of IFG compared with non-Hispanic whites among people with normal TG concentrations. Elevated TGs (>150 mg/dL) at baseline were independently associated with the incidence of IFG with an adjusted hazard ratio of 1.19 (95% CI 1.04–1.37). However, its predictive value for identifying people at risk for IFG was poor, with <57% AUC. Interactions of elevated TGs with race/ethnicity in predicting IFG were not statistically significant.
CONCLUSIONS
Elevated TGs were moderately associated with risk for IFG, and it was a poor risk prediction tool for IFG.
doi:10.2337/dc12-0355
PMCID: PMC3554324  PMID: 23033247
20.  The Association of Health Professional Shortage Areas and Cardiovascular Risk Factor Prevalence, Awareness and Control in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Circulation. Cardiovascular quality and outcomes  2011;4(5):10.1161/CIRCOUTCOMES.111.960922.
Background
Individuals living in primary care health professional shortage areas (PC-HPSA) often have difficulty obtaining medical care; however, no previous studies have examined association of PC-HPSA residence with prevalence of CVD risk factors.
Methods and Results
To examine this question, the authors used data from the Multi-Ethnic Study of Atherosclerosis baseline exam (2000–2002). Outcomes included the prevalence of diabetes, hypertension, hyperlipidemia, smoking and obesity as well as the awareness and control of diabetes, hypertension, and hyperlipidemia. Multivariable Poisson models were used to examine the independent association of PC-HPSA residence with each outcome. Models were sequentially adjusted for demographics, acculturation, socioeconomic status, access to health care and neighborhood socioeconomic status. Similar to the national average, 16.7% of MESA participants lived in a PC-HPSA. In unadjusted analyses, prevalence rates of diabetes (14.8% vs 11.0%), hypertension (48.2% vs 43.1%), obesity (35.7% vs 31.1%) and smoking (15.5% vs 12.1%) were significantly higher among residents of PC-HPSAs. There were no significant differences in the awareness or control of diabetes, hypertension, or hyperlipidemia. After adjustment, residence in a PC-HPSA was not independently associated with CVD risk factor prevalence, awareness or control.
Conclusions
This study suggests that increased prevalence of CVD risk factors in PC-HPSAs are explained by the demographic and socioeconomic characteristics of their residents. Future interventions aimed at increasing the number of primary care physicians may not improve cardiovascular risk without first addressing other factors underlying healthcare disparities.
doi:10.1161/CIRCOUTCOMES.111.960922
PMCID: PMC3857032  PMID: 21878669
epidemiology; prevention; risk factors
21.  Value of Recruitment Strategies Used in a Primary Care Practice-based Trial 
Contemporary clinical trials  2006;28(3):258-267.
Purpose
“Physicians-recruiting-physicians” is the preferred recruitment approach for practice-based research. However, yields are variable; and the approach can be costly and lead to biased, unrepresentative samples. We sought to explore the potential efficiency of alternative methods.
Methods
We conducted a retrospective analysis of the yield and cost of 10 recruitment strategies used to recruit primary care practices to a randomized trial to improve cardiovascular disease risk factor management. We measured response and recruitment yields and the resources used to estimate the value of each strategy. Providers at recruited practices were surveyed about motivation for participation.
Results
Response to 6 opt-in marketing strategies was 0.40% (53/13290), ranging from 0% to 2.86% by strategy; 33.96% (18/53) of responders were recruited to the study. Of those recruited from opt-out strategies, 8.68% joined the study, ranging from 5.35% to 41.67% per strategy. A strategy that combined both opt-in and opt-out approaches resulted in a 51.14% (90/176) response and a 10.80% (19/90) recruitment rate. Cost of recruitment was $613 per recruited practice. Recruitment approaches based on in-person meetings (41.67%), previous relationships (33.33%), and borrowing an Area Health Education Center’s established networks (10.80%), yielded the most recruited practices per effort and were most cost efficient. Individual providers who chose to participate were motivated by interest in improving their clinical practice (80.5%); contributing to CVD primary prevention (54.4%); and invigorating their practice with new ideas (42.1%).
Conclusions
This analysis provides suggestions for future recruitment efforts and research. Translational studies with limited funds could consider multi-modal recruitment approaches including in-person presentations to practice groups and exploitation of previous relationships, which require the providers to opt-out, and interactive opt-in approaches which rely on borrowed networks. These approaches can be supplemented with non-relationship-based opt-out strategies such as cold calls strategically targeted to underrepresented provider groups.
doi:10.1016/j.cct.2006.08.009
PMCID: PMC3760001  PMID: 17030154
22.  Diurnal Salivary Cortisol and Urinary Catecholamines Are Associated With Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis 
Metabolism  2011;61(7):986-995.
Objective
To examine the cross-sectional association of diurnal salivary cortisol curve components and urinary catecholamines with diabetes status.
Methods
Up to 18 salivary cortisol samples over 3 days and overnight urinary catecholamines were collected from 1,002 participants in the Multi-Ethnic Study of Atherosclerosis. Diabetes was defined as a fasting blood glucose ≥126 mg/dL or medication use. Cortisol curve measures included awakening cortisol, cortisol awakening response (CAR), early decline, late decline, and cortisol area under the curve (AUC). Urinary catecholamines included epinephrine, norepinephrine, and dopamine.
Results
Participants with diabetes had significantly lower CAR (β=−0.19; 95% CI: −0.34 to −0.04) than those without diabetes in multivariable models. While men with diabetes had a non-significant trend toward lower total AUC (β=−1.56; 95% CI: −3.93 to 0.80), women with diabetes had significantly higher total AUC (β=2.62; 95% CI: 0.72 to 4.51) (p=0.02 for interaction) compared to those without diabetes. Men but not women with diabetes had significantly lower urinary catecholamines, compared to those without diabetes (p<0.05).
Conclusions
Diabetes is associated with neuroendocrine dysregulation, which may differ by sex. Further studies are needed to determine the role of the neuroendocrine system in the pathophysiology of diabetes.
doi:10.1016/j.metabol.2011.11.006
PMCID: PMC3319636  PMID: 22209664
diabetes; hypothalamic-pituitary-adrenal (HPA) axis; salivary cortisol; catecholamines; epidemiology
23.  Prediction of Incident Heart Failure in General Practice: The ARIC Study 
Circulation. Heart failure  2012;5(4):422-429.
Background
A simple and effective Heart Failure (HF) risk score would facilitate the primary prevention and early diagnosis of HF in general practice. We examined the external validity of existing HF risk scores, optimized a 10-year HF risk function, and examined the incremental value of several biomarkers, including NT-proBNP.
Methods and Results
During 15.5 years (210,102 person-years of follow-up), 1487 HF events were recorded among 13,555 members of the bi-ethnic Atherosclerosis Risk in Communities (ARIC) Study cohort. The area under curve (AUC) from the Framingham-published, Framingham-recalibrated, Health ABC HF recalibrated, and ARIC risk scores were 0.610, 0.762, 0.783, and 0.797, respectively. Upon addition of NT-pro-BNP, the optimism corrected AUC of the ARIC HF risk score increased from 0.773 (95% CI: 0.753 – 0.787) to 0.805 (95% CI: 0.792 – 0.820). Inclusion of NT-proBNP improved the overall classification of re-calibrated Framingham, re-calibrated Health ABC, and ARIC risk scores by 18%, 12%, and 13%, respectively. In contrast, Cystatin C or hs-CRP did not add towards incremental risk prediction.
Conclusions
The ARIC HF risk score is more parsimonious yet performs slightly better than the extant risk scores in predicting 10-year risk of incident HF. The inclusion of NT-proBNP markedly improves HF risk prediction. A simplified risk score restricted to a patient’s age, race, gender, and NT-proBNP performs comparably to the full score (AUC = 0.745), and is suitable for automated reporting from laboratory panels and electronic medical records.
doi:10.1161/CIRCHEARTFAILURE.111.964841
PMCID: PMC3412686  PMID: 22589298
heart failure; risk prediction; external validation; NT-proBNP; Cystatin C; hs-CRP; biomarkers
24.  Diurnal Salivary Cortisol is Associated With Body Mass Index and Waist Circumference: The Multi-Ethnic Study of Atherosclerosis 
Obesity (Silver Spring, Md.)  2013;21(1):E56-E63.
Neuroendocrine abnormalities, such as activation of the hypothalamic-pituitary-adrenal (HPA) axis, are associated with obesity; however, few large-scale population-based studies have examined HPA axis and markers of obesity. We examined the cross-sectional association of the cortisol awakening response (CAR) and diurnal salivary cortisol curve with obesity. The Multi-Ethnic Study of Atherosclerosis (MESA) Stress Study includes 1,002 White, Hispanic, and Black men and women (mean age 65±9.8 years) who collected up to 18 salivary cortisol samples over 3 days. Cortisol profiles were modeled using regression spline models that incorporated random parameters for subject-specific effects. Cortisol curve measures included awakening cortisol, CAR (awakening to 30 minutes post-awakening), early decline (30 minutes to 2 hours post-awakening), late decline (2 hours post-awakening to bedtime), and the corresponding areas under the curve (AUC). Body-mass-index (BMI) and waist circumference (WC) were used to estimate adiposity. For the entire cohort, both BMI and WC were negatively correlated with awakening cortisol (p<0.05), AUC during awakening rise and early decline and positively correlated to the early decline slope (p<0.05) after adjustments for age, race/ethnicity, gender, diabetes status, socioeconomic status, beta blockers, steroids, hormone replacement therapy and smoking status. No heterogeneities of effects were observed by gender, age, and race/ethnicity. Higher BMI and WC are associated with neuroendocrine dysregulation, which is present in a large population sample, and only partially explained by other covariates.
doi:10.1002/oby.20047
PMCID: PMC3602310  PMID: 23404865
adiposity; hypothalamic-pituitary-adrenal (HPA) axis; salivary cortisol; diurnal cortisol; cortisol awakening response; epidemiology; obesity; body mass index; waist circumference; epidemiology
25.  Metabolic Syndrome, Diabetes, and Incidence and Progression of Coronary Calcium: The Multiethnic Study of Atherosclerosis (MESA) 
Jacc. Cardiovascular Imaging  2012;5(4):358-366.
Objectives
The purpose of the study was to examine and compare the incidence and progression of coronary artery calcium (CAC) among persons with metabolic syndrome (MetS) and diabetes mellitus (DM), compared to those with neither condition.
Background
MetS and DM are associated with subclinical atherosclerosis as evidenced by coronary artery calcium (CAC).
Methods
The Multiethnic Study of Atherosclerosis included 6,814 African-American, Asian, Caucasian, and Hispanic adults aged 45–84 free of cardiovascular disease at baseline. 5,662 subjects (51% female, mean age 61.0 ± 10.3 years) received baseline and follow-up (mean 2.4 years) cardiac CT scans. We compared the incidence of CAC in 2,927 subjects without CAC at baseline and progression of CAC in 2,735 subjects with CAC at baseline in those with MetS without DM (25.2%), DM without MetS (3.5%), or both DM and MetS (9.0%), compared to neither MetS nor DM (58%). Progression of CAC was also examined in relation to coronary heart disease events over an additional 4.9 years.
Results
Relative to those with neither MetS nor DM, adjusted relative risks (95% confidence intervals) for incident CAC were 1.7 (1.4–2.0), 1.9 (1.4–2.4), and 1.8 (1.4–2.2) (all p<0.01) and absolute differences in mean progression (volume score) were 7.8 (4.0–11.6; p<0.01), 11.6 (2.7–20.5; p<0.05), and 22.6 (17.2–27.9; p<0.01) for those with MetS without DM, DM without MetS, and both DM and MetS, respectively. Similar findings were seen in analysis using Agatston calcium score. In addition, progression predicted CHD events in those with MetS without DM (adjusted hazard ratio 4.1, 95% CI=2.0–8.5, p<0.01) and DM (4.9 [1.3–18.4], p<0.05) among those in highest tertile of CAC increase vs. no increase).
Conclusions
Individuals with MetS and DM have a greater incidence and absolute progression of CAC compared to individuals without these conditions, with progression also predicting CHD events in those with MetS and DM.
doi:10.1016/j.jcmg.2011.12.015
PMCID: PMC3327555  PMID: 22498324
atherosclerosis; diabetes; risk factors; calcification

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