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1.  Glucose, Insulin, and Incident Hypertension in the Multi-Ethnic Study of Atherosclerosis 
American Journal of Epidemiology  2010;172(10):1144-1154.
Diabetes mellitus and hypertension commonly coexist, but the nature of this link is not well understood. The authors tested whether diabetes and higher concentrations of fasting serum glucose and insulin are associated with increased risk of developing incident hypertension in the community-based Multi-Ethnic Study of Atherosclerosis. At baseline, 3,513 participants were free of hypertension, defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive medications to treat high blood pressure. Of these, 965 participants (27%) developed incident hypertension over 4.7 years’ median follow-up between 2002 and 2007. Compared with participants with normal baseline fasting glucose, those with impaired fasting glucose and diabetes had adjusted relative risks of hypertension of 1.16 (95% confidence interval (CI): 0.96, 1.40) and 1.41 (95% CI: 1.17, 1.71), respectively (P = 0.0015). The adjusted relative risk of incident hypertension was 1.08 (95% CI: 1.04, 1.13) for each mmol/L higher glucose (P < 0.0001) and 1.15 (95% CI: 1.05, 1.25) for each doubling of insulin (P = 0.0016). Further adjustment for serum cystatin C, urinary albumin/creatinine ratio, and arterial elasticity measured by tonometry substantially reduced the magnitudes of these associations. In conclusion, diabetes and higher concentrations of glucose and insulin may contribute to the development of hypertension, in part through kidney disease and arterial stiffness.
doi:10.1093/aje/kwq266
PMCID: PMC3004765  PMID: 20961972
diabetes mellitus; glucose; hypertension; insulin; kidney; nephrology
2.  Estimating ethnic differences in self-reported new use of antidepressant medications: results from the Multi-Ethnic Study of Atherosclerosis 
Introduction
There is evidence that the utilization of antidepressant medications (ADM) may vary between different ethnic groups in the United States population.
Methods
The Multi-Ethnic Study of Atherosclerosis is a population-based prospective cohort study of 6,814 US adults from 4 different ethnic groups. After excluding baseline users of ADM, we examined the relation between baseline depression and new use of ADM for 4 different ethnicities: African-Americans (n=1,822), Asians (n=784) Caucasians (n=2,300), and Hispanics (n=1,405). Estimates of the association of ethnicity and ADM use were adjusted for age, study site, gender, Center for Epidemiologic Studies Depression Scale (CES-D), alcohol use, smoking, blood pressure, diabetes, education, and exercise. Non-random loss to follow-up was present and estimates were adjusted using inverse probability of censoring weighting (IPCW).
Results
Of the four ethnicities, Caucasian participants had the highest rate of ADM use (12%) compared with African-American (4%), Asian (2%) and Hispanic (6%) participants. After adjustment, non-Caucasian ethnicity was associated with reduced ADM use: African-American (HR: 0.42; 95% Confidence Interval (CI):0.31– 0.58), Asian (HR: 0.14; 95%CI: 0.08–0.26) and Hispanic (HR: 0.47; 95%CI: 0.31–0.65). Applying IPCW to correct for non-random loss to follow-up among the study participants weakened but did not eliminate these associations: African-American (HR: 0.48; 95%CI: 0.30–0.57), Asian (HR: 0.23; 95% CI: 0.13–0.37) and Hispanic (HR: 0.58; 95%CI: 0.47–0.67).
Conclusion
Non-Caucasian ethnicity is associated with lower rates of new ADM use. After IPCW adjustment, the observed ethnicity differences in ADM use are smaller although still statistically significant.
doi:10.1002/pds.1751
PMCID: PMC2844249  PMID: 19399919
Inverse probability of censoring weighting; ethnicity; antidepressants; drug utilization; Multi-Ethnic Study of Atherosclerosis; non-random loss to follow-up
3.  Time trends in the use of anti-hypertensive medications: results from the Multi-Ethnic Study of Atherosclerosis 
Background
Previous research has suggested that emerging evidence from randomized controlled trials (RCTs) is often not reflected in physician selection of medication class for first-line anti-hypertensive therapy.
Objectives
To evaluate the association of RCT evidence in December 2002 from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) on use of anti-hypertensive medications over time in a multi-ethnic cohort.
Methods
The Multi-Ethnic Study of Atherosclerosis study, a prospective cohort study of 6,814 adults from 4 ethnic groups, had four separate assessments of drug use. Users of anti-hypertensive medications at baseline were excluded. We evaluated temporal changes in the medication class reported by new users of antihypertensive medications.
Results
After the exclusion of antihypertensive drug users at baseline, 32% of new users of anti-hypertensive drugs seen at exam 2 were prescribed a diuretic. The publication of ALLHAT was associated with a subsequent increase in the proportion of new users taking diuretics at exam 3 compared with exam 2 (Relative Risk (RR):1.31; 95% Confidence Interval (CI):1.09–1.59). After the report from ALLHAT, the proportion of users of diuretics seen at exam 3 rose to 44% (starting in 2004) and 39% in exam 4 (starting in 2005). This increase in the proportion of diuretic use among new users of anti-hypertensive medications declined slightly but could still be detected at exam 4 as compared to exam 2 (RR:1.28; 95% CI:1.04–1.57).
Conclusions
The randomized trial evidence from the ALLHAT study was temporally associated with a moderate increase in diuretic use.
doi:10.1002/pds.1788
PMCID: PMC2844254  PMID: 19551700
Multi-Ethnic Study of Atherosclerosis; antihypertensive medications; drug utilization; longitudinal
4.  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.
doi:10.1161/HYPERTENSIONAHA.110.168005
PMCID: PMC3106342  PMID: 21502561
hypertension; race/ethnicity; epidemiology; incidence
5.  Retinal vessel diameters and risk of hypertension: the Multiethnic Study of Atherosclerosis 
Journal of hypertension  2009;27(12):2386-2393.
Objective
To describe the prospective relationship of retinal vessel diameters with risk of hypertension in a multiethnic population-based cohort.
Methods
The Multi-Ethnic Study of Atherosclerosis is a population-based study of subclinical cardiovascular disease among white, African–American, Hispanic, and Chinese American adults aged 45–84 years. Retinal vessel diameters were measured using a standardized imaging software at the second examination (considered baseline in this analysis) and summarized as the central retinal artery/vein equivalent. Presence of retinopathy and retinal focal arteriolar narrowing and arteriovenous nicking was assessed by trained graders. Incidence of hypertension was defined among participants at risk as systolic blood pressure at least 140 mmHg, diastolic blood pressure at least 90 mmHg, or use of an antihypertensive medication.
Results
Of the initial 6237 participants at baseline, 2583 were at risk of hypertension. After 3.2±0.5 years of follow-up, 448 (17.3%) participants developed hypertension. After adjusting for age, sex, race/ethnicity, the average of mean arterial blood pressure in the first and second examination, and other vascular risk factors, persons with narrower retinal arteriolar diameter and wider venular diameter at baseline were more likely to develop hypertension [odds ratio per SD decrease in central retinal artery equivalent 1.20, 95% confidence intervals 1.02, 1.42; and odds ratio per SD increase in central retinal vein equivalent 1.18, 95% confidence interval 1.02, 1.37]. Persons with focal arteriolar narrowing were also more likely to develop hypertension (odds ratio 1.80, 95% confidence interval 1.09, 2.97).
Conclusion
Findings from this multiethnic population confirm that narrower retinal arteriolar diameter and wider venular diameter are associated with the development of hypertension independent of traditional risk factors.
doi:10.1097/HJH.0b013e3283310f7e
PMCID: PMC2935621  PMID: 19680136
hypertension; microcirculation; retinal vessel diameter; retinopathy; the Multi-Ethnic Study of Atherosclerosis
6.  TRAJECTORIES OF DEPRESSIVE EPISODES AND HYPERTENSION OVER 24 YEARS: THE WHITEHALL II PROSPECTIVE COHORT STUDY 
Hypertension  2011;57(4):710-716.
Prospective data on depressive symptoms and blood pressure (BP) are scarce, and the impact of age on this association is poorly understood. The present study examines longitudinal trajectories of depressive episodes and the probability of hypertension associated with these trajectories over time. Participants were 6,889 men and 3,413 women London based civil servants, aged 35–55 years at baseline, followed for 24 years between 1985 and 2009. Depressive episode (defined as scoring 4 or more on the General Health Questionnaire-Depression subscale or using prescribed antidepressant medication) and hypertension (systolic/diastolic blood pressure ≥ 140/90 mm Hg or use of antihypertensive medication) were assessed concurrently at five medical examinations. In the fully adjusted longitudinal logistic regression analyses based on Generalized-Estimating-Equations using age as the time scale, participants in the “increasing depression” group had a 24% (p<0.05) lower risk of hypertension at ages 35–39, compared to those in the “low/transient depression” group. However, there was a faster age-related increase in hypertension in the “increasing depression” group, corresponding to a 7% (p<0.01) greater increase in the odds of hypertension for every each five-year increase in age. A higher risk of hypertension in the first group of participants was not evident before age 55. A similar pattern of association was observed in men and women although it was stronger in men. This study suggests that the risk of hypertension increases with repeated experience of depressive episodes over time and becomes evident in later adulthood.
doi:10.1161/HYPERTENSIONAHA.110.164061
PMCID: PMC3065997  PMID: 21339474
Depression; hypertension; longitudinal analysis; repeated measures
7.  The Association of Framingham and Reynolds Risk Scores with Incidence and Progression of Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis 
Objectives
To compare the association of the Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) with subclinical atherosclerosis, assessed by incidence and progression of coronary artery calcium (CAC).
Background
The comparative effectiveness of competing risk algorithms for indentifying subclinical atherosclerosis is unknown.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of 6,814 participants free of baseline CVD. All participants underwent risk factor assessment, as well as baseline and follow-up CAC testing. We assessed the performance of the FRS and RRS to predict CAC incidence and progression using relative risk and robust linear regression.
Results
The study population included 5,140 individuals (61±10 years, 47% males, mean follow-up: 3.1±1.3 years). Among 53% of subjects (n=2,729) with no baseline CAC, 18% (n=510) developed incident CAC. Both the FRS and RRS were significantly predictive of incident CAC [RR 1.40 (95% CI 1.29 – 1.52), and RR 1.41 (95% CI 1.30 – 1.54) per 5% increase in risk, respectively] and CAC progression [mean CAC score change 6.92 (95% CI 5.31 – 8.54) and 6.82 (95% CI 5.51 – 8.14) per 5% increase]. Discordance in risk category classification (< or > 10% 10-year CHD risk) occurred in 13.7%, with only the RRS consistently adding predictive value for incidence and progression of CAC. These subclinical atherosclerosis findings are supported by a CHD events analysis over 5.6±0.7 year follow-up.
Conclusion
Both the RRS and FRS predict onset and progression of subclinical atherosclerosis. However, the RRS may provide additional predictive information when discordance between the scoring systems exists.
doi:10.1016/j.jacc.2011.08.022
PMCID: PMC4079464  PMID: 22051329
coronary artery calcium progression; subclinical atherosclerosis; risk prediction; Reynolds Risk Score; Framingham Risk Score
8.  Dietary phosphorus, blood pressure and incidence of hypertension in the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA) 
Hypertension  2010;55(3):776-784.
Greater phosphorus intake has been associated with lower levels of blood pressure in cross-sectional studies. This association, however, has not been assessed prospectively. We studied 13444 participants from the Atherosclerosis Risk in Communities cohort and the Multi-Ethnic Study of Atherosclerosis, with diet assessed at baseline using validated food frequency questionnaires. Blood pressure and use of antihypertensive medication were determined at baseline and during follow-up visits. Compared to individuals in the lowest quintile of phosphorus intake at baseline, those in the highest quintile had lower baseline systolic and diastolic blood pressure after adjustment for dietary and non-dietary confounders (−2.0 mmHg, 95% confidence interval −3.6, −0.5; p for trend=0.01; and −0.6, 95% confidence interval −1.6, +0.3, p for trend=0.20, respectively). During an average 6.2 years of follow-up, 3345 cases of hypertension were identified. Phosphorus intake was associated with the risk of hypertension (hazard ratio 0.80, 95% confidence interval 0.80-1.00, comparing extreme quintiles; p for trend=0.02) after adjustment for non-dietary factors, but not after additional adjustment for dietary variables (hazard ratio 1.01, 95% confidence interval 0.82-1.23, p for trend=0.88). Phosphorus from dairy products but not from other sources was associated with lower baseline blood pressure and reduced risk of incident hypertension. Hazard ratios (95% confidence interval) comparing extreme quintiles were 0.86 (0.76-0.97), p for trend=0.01, for phosphorus from dairy foods and 1.04 (0.93-1.17), p for trend=0.48, for phosphorus from other foods. These findings could indicate an effect of phosphorus in conjunction with other dairy constituents or of dairy itself without involvement of phosphorus.
doi:10.1161/HYPERTENSIONAHA.109.143461
PMCID: PMC2825283  PMID: 20083730
Phosphorus; Cohort; Dairy product; Epidemiology; Blood pressure; Hypertension
9.  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
10.  A PROSPECTIVE STUDY OF BODY MASS INDEX AND THE RISK OF DEVELOPING HYPERTENSION IN MEN 
American journal of hypertension  2007;20(4):370-377.
Background
Although obesity is known to increase the risk of hypertension, few studies have prospectively evaluated body mass index (BMI) across the range of normal weight and overweight as a primary risk factor.
Methods
In this prospective cohort, we evaluated the association between BMI and risk of incident hypertension. We studied 13,563 initially healthy, non-hypertensive men who participated in the Physicians’ Health Study. We calculated BMI from self-reported weight and height and defined hypertension as self-reported systolic blood pressure (BP) ≥140 mmHg, diastolic BP ≥90 mmHg, or new antihypertensive medication use.
Results
After a median 14.5 years, 4920 participants developed hypertension. Higher baseline BMI, even within the “normal” range, was consistently associated with increased risk of hypertension. Compared to participants in the lowest BMI quintile (<22.4 kg/m2), the relative risks (95% confidence interval) of developing hypertension for men with a BMI of 22.4–23.6, 23.7–24.7, 24.8–26.4, and >26.4 kg/m2 were 1.20 (1.09–1.32), 1.31 (1.19–1.44), 1.56 (1.42–1.72), and 1.85 (1.69–2.03), respectively (P for trend, <0.0001). Further adjustment for diabetes, high cholesterol, and baseline BP did not substantially alter these results. We found similar associations using other BMI categories and after excluding men with smoking history, those who developed hypertension in the first 2 years, and those with diabetes, obesity, or high cholesterol at baseline.
Conclusion
In this large cohort, we found a strong gradient between higher BMI and increased risk of hypertension, even among men within the “normal” and mildly “overweight” BMI range. Approaches to reduce the risk of developing hypertension may include prevention of overweight and obesity.
doi:10.1016/j.amjhyper.2006.10.011
PMCID: PMC1920107  PMID: 17386342
hypertension; obesity; body mass index
11.  The relationship between inflammation, obesity and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Journal of human hypertension  2010;25(2):73-79.
It has been suggested that inflammation is important in the aetiology of hypertension and that this may be most relevant among obese persons. To study this, we examined the independent relationships between obesity, inflammation-related proteins (interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen) and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA). Hypertension status, defined as a blood pressure ≥140/90 mm Hg or a history of hypertension and use of blood pressure medications, was determined at baseline and two subsequent exams over 5 years. Among 3543 non-hypertensives at baseline, 714 individuals developed incident hypertension by Exam 3. Cox proportional hazard models were used to determine the relationship between baseline levels of IL-6, CRP and fibrinogen and future risk of hypertension. One s.d. difference in baseline concentration of IL-6, CRP or fibrinogen was associated with 20–40% greater risk of incident hypertension. This risk was attenuated after accounting for other hypertension risk factors (hazard ratio (HR) IL-6: 1.13 (95% CI: 1.04–1.23); CRP: 1.11 (95% CI: 1.02–1.21); fibrinogen 1.0 (95% CI: 0.92–1.08)). Conversely, obesity was an independent risk factor for hypertension risk, minimally impacted by other covariates, including IL-6 and CRP (HR 1.72 (95% CI: 1.36–2.16)). IL-6 and CRP did not modify the relationship between obesity and hypertension, though an adjusted twofold greater risk was observed for obese individuals with a CRP >3 mg l−1 compared with CRP <1 mg l−1. The relationship between inflammation-related proteins and hypertension risk was predominantly explained by other hypertension risk factors. Obesity, independent of inflammation, remained a potent risk factor for future hypertension.
doi:10.1038/jhh.2010.91
PMCID: PMC4066617  PMID: 20944659
inflammation; obesity; blood pressure
12.  A Diet Pattern with More Dairy and Nuts, but Less Meat Is Related to Lower Risk of Developing Hypertension in Middle-Aged Adults: The Atherosclerosis Risk in Communities (ARIC) Study 
Nutrients  2013;5(5):1719-1733.
Dietary intake among other lifestyle factors influence blood pressure. We examined the associations of an “a priori” diet score with incident high normal blood pressure (HNBP; systolic blood pressure (SBP) 120–139 mmHg, or diastolic blood pressure (DBP) 80–89 mmHg and no antihypertensive medications) and hypertension (SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or taking antihypertensive medication). We used proportional hazards regression to evaluate this score in quintiles (Q) and each food group making up the score relative to incident HNBP or hypertension over nine years in the Atherosclerosis Risk of Communities (ARIC) study of 9913 African-American and Caucasian adults aged 45–64 years and free of HNBP or hypertension at baseline. Incidence of HNBP varied from 42.5% in white women to 44.1% in black women; and incident hypertension from 26.1% in white women to 40.8% in black women. Adjusting for demographics and CVD risk factors, the “a priori” food score was inversely associated with incident hypertension; but not HNBP. Compared to Q1, the relative hazards of hypertension for the food score Q2–Q5 were 0.97 (0.87–1.09), 0.91 (0.81–1.02), 0.91 (0.80–1.03), and 0.86 (0.75–0.98); ptrend = 0.01. This inverse relation was largely attributable to greater intake of dairy products and nuts, and less meat. These findings support the 2010 Dietary Guidelines to consume more dairy products and nuts, but suggest a reduction in meat intake.
doi:10.3390/nu5051719
PMCID: PMC3708346  PMID: 23698164
diet pattern; healthy food score; hypertension; high normal blood pressure
13.  Race/Ethnicity and Hypertension: The Role of Social Support 
American journal of hypertension  2010;23(5):534-540.
BACKGROUND
Social support is an important determinant of health, yet understanding of its contribution to racial disparities in hypertension is limited. Many studies have focused on the relationship between hypertension and social support, or race/ethnicity and social support, but few have examined the inter-relationship between race/ethnicity, social support, and hypertension. The objective of this study was to determine whether the relationship between race/ethnicity and hypertension varied by level of social support.
METHODS
Data from the National Health and Nutrition Examination Survey (NHANES) 2001–2006 were used to calculate the odds ratios (ORs) for the association between hypertension and race/ethnicity by levels of social support. Hypertension was defined as systolic blood pressure (BP) ≥140 mm Hg and/or diastolic BP ≥ 90 mm Hg or having been prescribed antihypertensive medication. Social support was defined by emotional and financial support, and marital status.
RESULTS
Black/white ORs of hypertension increased as social support decreased; that is, the race difference among those without social support was larger compared to those with social support. Contrarily, Mexican American/white ethnic differences were only observed among those with social support; Mexican Americans with social support had lower odds of hypertension than their white counterparts.
CONCLUSIONS
This study observed that the relationship between race (but not ethnicity) and hypertension varies by social support level. Results suggest there may be beneficial effects of social support on hypertension among blacks, however, the possible impact of social support on ethnic differences in hypertension remains unclear.
doi:10.1038/ajh.2010.28
PMCID: PMC3102008  PMID: 20186126
blood pressure; hypertension; psychosocial factors; Race/ethnicity; social support
14.  Inflammation and the Incidence of Type 2 Diabetes 
Diabetes Care  2010;33(4):804-810.
OBJECTIVE
Many studies have documented associations between inflammation and type 2 diabetes incidence. We assessed potential variability in this association in the major U.S. racial/ethnic groups.
RESEARCH DESIGN AND METHODS
Incident type 2 diabetes was assessed among men and women aged 45–84 years without prior clinical cardiovascular disease or diabetes in the prospective Multi-Ethnic Study of Atherosclerosis. Interleukin (IL)-6, fibrinogen, and C-reactive protein (CRP) were measured at baseline (2000–2002); fasting glucose and diabetes medication use was assessed at baseline and three subsequent in-person exams through 2007. Type 2 diabetes was defined as use of diabetes drugs or glucose ≥126 mg/dl. Covariates included baseline demographics, clinic, smoking, alcohol, exercise, hypertension medication, systolic blood pressure, insulin resistance, and BMI. Cox proportional hazards regression was used to calculate hazard ratios (HRs) by quartiles of CRP, IL-6, and fibrinogen.
RESULTS
Among 5,571 participants (mean age 61.6 years, 53% female, 42.1% white, 11.5% Chinese, 25.7% black, and 20.7% Hispanic), 410 developed incident diabetes during a median follow-up time of 4.7 years (incidence 16.8 per 1,000 person-years). CRP, IL-6, and fibrinogen levels were associated with incident diabetes in the entire sample. After adjustment, the associations were attenuated; however, quartile 4 (versus quartile 1) of IL-6 (HR 1.5 [95% CI 1.1–2.2]) and CRP (1.7 [1.3–2.4]) remained associated with incident diabetes. In stratified analyses, similar associations were observed among white, black, and Hispanic participants.
CONCLUSIONS
Higher levels of inflammation predict short-term incidence of type 2 diabetes in a multiethnic American sample.
doi:10.2337/dc09-1679
PMCID: PMC2845031  PMID: 20097779
15.  Prospective Study of Sleep-disordered Breathing and Hypertension 
Rationale: Cross-sectional epidemiologic studies show an association between sleep-disordered breathing and hypertension, but only one cohort study has examined sleep-disordered breathing as a risk factor for incident hypertension.
Objectives: To examine whether sleep-disordered breathing increases the risk of incident hypertension among persons 40 years of age and older.
Methods: In a prospective cohort study, we analyzed data from 2,470 participants who at baseline did not have hypertension, defined as blood pressure of at least 140/90 mm Hg or taking antihypertensive medication. The apnea-hypopnea index (AHI), the number of apneas plus hypopneas per hour of sleep, was measured by overnight in-home polysomnography. We estimated odds ratios for developing hypertension during 5 years of follow-up according to baseline AHI.
Measurements and Main Results: The odds ratios for incident hypertension increased with increasing baseline AHI; however, this relationship was attenuated and not statistically significant after adjustment for baseline body-mass index. Although not statistically significant, the observed association between a baseline AHI greater than 30 and future hypertension (odds ratio, 1.51; 95% confidence interval, 0.93–2.47) does not exclude the possibility of a modest association.
Conclusions: Among middle-aged and older persons without hypertension, much of the relationship between AHI and risk of incident hypertension was accounted for by obesity. After adjustment for body mass index, the AHI was not a significant predictor of future hypertension, although a modest influence of an AHI greater than 30 on hypertension could not be excluded.
doi:10.1164/rccm.200712-1809OC
PMCID: PMC2695498  PMID: 19264976
sleep apnea; sleep-disordered breathing; hypertension; cohort study
16.  Examining a Bidirectional Association Between Depressive Symptoms and Diabetes 
Context
Depressive symptoms are associated with development of type 2 diabetes, but it is unclear whether type 2 diabetes is a risk factor for elevated depressive symptoms.
Objective
To examine the bidirectional association between depressive symptoms and type 2 diabetes.
Design, Setting, and Participants
Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2004-2005.
Main Outcome Measures
Elevated depressive symptoms defined by Center for Epidemiologic Studies Depression Scale (CES-D) score of 16 or higher, use of antidepressant medications, or both. The CES-D score was also modeled continuously. Participants were categorized as normal fasting glucose (<100 mg/dL), impaired fasting glucose (100-125 mg/dL), or type 2 diabetes (≥126 mg/dL or receiving treatment). Analysis 1 included 5201 participants without type 2 diabetes at baseline and estimated the relative hazard of incidenttype2diabetesover3.2yearsforthosewithandwithoutdepressivesymptoms.Analysis 2 included 4847 participants without depressive symptoms at baseline and calculated the relative odds of developing depressive symptoms over 3.1 years for those with and without type 2 diabetes.
Results
In analysis 1, the incidence rate of type 2 diabetes was 22.0 and 16.6 per 1000 person-years for those with and without elevated depressive symptoms, respectively. The risk of incident type 2 diabetes was 1.10 times higher for each 5-unit increment in CES-D score (95% confidence interval [CI], 1.02-1.19) after adjustment for demographic factors and body mass index. This association persisted following adjustment for metabolic, inflammatory, socioeconomic, or lifestyle factors, although it was no longer statistically significant following adjustment for the latter (relative hazard, 1.08; 95% CI, 0.99-1.19). In analysis 2, the incidence rates of elevated depressive symptoms per 1000-person years were 36.8 for participants with normal fasting glucose; 27.9 for impaired fasting glucose; 31.2 for untreated type 2 diabetes, and 61.9 for treated type 2 diabetes. Compared with normal fasting glucose, the demographic–adjusted odds ratios of developing elevated depressive symptoms were 0.79 (95% CI, 0.63-0.99) for impaired fasting glucose, 0.75 (95% CI, 0.44-1.27) for untreated type 2 diabetes, and 1.54 (95% CI, 1.13-2.09) for treated type 2 diabetes. None of these associations with incident depressive symptoms were materially altered with adjustment for body mass index, socioeconomic and lifestyle factors, and comorbidities. Findings in both analyses were comparable across ethnic groups.
Conclusions
A modest association of baseline depressive symptoms with incident type 2 diabetes existed that was partially explained by lifestyle factors. Impaired fasting glucose and untreated type 2 diabetes were inversely associated with incident depressive symptoms, whereas treated type 2 diabetes showed a positive association with depressive symptoms. These associations were not substantively affected by adjustment for potential confounding or mediating factors.
doi:10.1001/jama.299.23.2751
PMCID: PMC2648841  PMID: 18560002
17.  NEIGHBORHOOD STRESSORS AND RACE/ETHNIC DIFFERENCES IN HYPERTENSION PREVALENCE (THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS) 
American Journal of Hypertension  2010;24(2):187-193.
Background
The reasons for racial/ethnic disparities in hypertension prevalence in the U.S are poorly understood.
Methods
Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated whether individual and neighborhood-level chronic stressors contribute to these disparities in cross-sectional analyses. The sample consisted of 2679 MESA participants (45–84yrs) residing in Baltimore, New York, and North Carolina. Hypertension was defined as systolic or diastolic blood pressure ≥140 or 90mmHg, or taking anti-hypertensive medications. Individual-level chronic stress was measured by self-reported chronic burden and perceived major and everyday discrimination. A measure of neighborhood (census tract) chronic stressors (i.e. physical disorder, violence) was developed using data from a telephone survey conducted with other residents of MESA neighborhoods. Binomial regression was used to estimate associations between hypertension and race/ethnicity before and after adjustment for individual and neighborhood stressors.
Results
The prevalence of hypertension was 59.5% in African Americans (AA), 43.9% in Hispanics, and 42.0% in whites. Age and sex adjusted relative prevalences of hypertension (compared to whites) were 1.30 [95% Confidence Interval (CI): 1.22–1.38] for AA and 1.16 [95% CI: 1.04–1.31] for Hispanics. Adjustment for neighborhood stressors reduced these to 1.17 [95% CI: 1.11–1.22] and 1.09 [95% CI: 1.00–1.18] respectively. Additional adjustment for individual-level stressors, acculturation, income, education, and other neighborhood features only slightly reduced these associations.
Conclusion
Neighborhood chronic stressors may contribute to race/ethnic differences in hypertension prevalence in the U.S.
doi:10.1038/ajh.2010.200
PMCID: PMC3319083  PMID: 20847728
neighborhoods; race; ethnicity; chronic stress; discrimination
18.  Traditional cardiovascular risk factors in relation to left ventricular mass, volume, and systolic function by cardiac magnetic resonance imaging: The Multi-Ethnic Study of Atherosclerosis 
Objectives
The goal of this study was to examine the cross-sectional associations of cardiovascular risk factors with left ventricular (LV) geometry and systolic function measured by cardiac magnetic resonance imaging (MRI) in the Multi-Ethnic Study of Atherosclerosis (MESA).
Background
Cardiovascular risk factors including hypertension, smoking, and obesity are known to be associated with increased LV mass, but less is known about the association of risk factors with LV systolic function, particularly in populations without clinical cardiovascular disease.
Methods
Participants were from four racial/ethnic groups and were free of clinical cardiovascular disease. Blood pressure, health habits, body mass index, lipid levels, and glucose abnormalities were assessed and MRI exams performed at baseline (N= 4869). Multivariable linear regression was used to model the association of risk factors with LV mass, end-diastolic volume, stroke volume, ejection fraction, and cardiac output.
Results
The mean age was 62 years, and 52 percent of participants were women. After adjustment for sociodemographic variables and height, higher systolic blood pressure and body mass index were associated with larger LV mass and volumes. Current smoking and diabetes were associated with greater LV mass (+7.7g, 95% confidence interval (CI) +5.5, +9.9; +3.5g, CI +1.2, +5.8), and with lower stroke volume (−1.9 ml, CI −3.3, −0.5; −4.5 ml, CI −6.0, −3.0) and lower ejection fraction (−1.6%, CI −2.1, −1.0; −0.8%, CI −1.5, −0.2).
Conclusions
In this cohort free of clinical cardiovascular disease, modifiable risk factors were associated with subclinical alterations in LV size and systolic function as detected by cardiac MRI.
CONDENSED ABSTRACT
We examined the cross-sectional associations of cardiovascular risk factors with LV geometry and systolic function measured by MRI. We studied 4869 participants without clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. After adjustment for sociodemographic variables and height, higher systolic blood pressure and body mass index were associated with larger LV mass and volumes, and current smoking and diabetes were associated with greater LV mass and lower stroke volume, although on average, the differences were small. Additional study is needed of these modifiable risk factors and their treatment in relation to the new development or progression of LV dysfunction.
doi:10.1016/j.jacc.2006.03.072
PMCID: PMC1794681  PMID: 17161261
cardiac output; cardiac volume; epidemiology; magnetic resonance imaging; hypertension; hypertrophy; LV = left ventricular; MRI = magnetic resonance imaging; MESA = Multi-Ethnic Study of Atherosclerosis; CARDIA = Coronary Artery Risk Development in Young Adults Study; ICC = intraclass correlation coefficient
19.  Association of Depression with Antihypertensive Medication Adherence in Older Adults: Cross-Sectional and Longitudinal Findings from CoSMO 
Background
Little is known about the associations between depressive symptoms, social support and antihypertensive medication adherence in older adults.
Purpose
We evaluated the cross-sectional and longitudinal associations between depressive symptoms, social support and antihypertensive medication adherence in a large cohort of older adults.
Methods
A cohort of 2,180 older adults with hypertension was administered questionnaires, which included the Center for Epidemiologic Studies-Depression Scale, the Medical Outcomes Study Social Support Index, and the hypertension-specific Morisky Medication Adherence Scale at baseline and 1 year later.
Results
Overall, 14.1% of participants had low medication adherence, 13.0% had depressive symptoms, and 33.9% had low social support. After multivariable adjustment, the odds ratios that participants with depressive symptoms and low social support would have low medication adherence were 1.96 (95% confidence interval (CI) 1.43, 2.70) and 1.27 (95% CI 0.98, 1.65), respectively, at baseline and 1.87 (95% CI 1.32, 2.66) and 1.30 (95% CI 0.98, 1.72), respectively, at 1 year follow-up.
Conclusion
Depressive symptoms may be an important modifiable barrier to antihypertensive medication adherence in older adults
doi:10.1007/s12160-010-9217-1
PMCID: PMC3109732  PMID: 20703839
Hypertension; Medication adherence; Depressive symptoms; Social support; Medication possession ratio; Older adults
20.  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
21.  Association of Plasma Sphingomyelin levels and Incident Coronary Heart Disease Events in an Adult Population: Multi Ethnic Study of Atherosclerosis 
Objectives
High plasma sphingomyelin level has been associated with subclinical atherosclerosis, coronary artery disease and worse prognosis in subjects with acute coronary syndromes. We assess the predictive value of plasma sphingomyelin levels for incident CHD events in the Multi Ethnic Study of atherosclerosis (MESA).
Method and Results
Plasma sphingomyelin was measured in 6809 out of 6814 subjects with mean age 62.2 ± 10.2 years, participating in the MESA study, a population based cohort study of adults free of clinical CVD at baseline recruited at six clinic sites in USA. The subjects consisted of 52.8% females, 38.5% Caucasian, 11.8% Chinese, 27.8% African Americans and 21.9% Hispanics. Cox proportional hazard analysis was used to examine the association between plasma sphingomyelin and five years of adjudicated incident CHD events including MI, resuscitated cardiac arrest, angina, CHD death and revascularization (CABG or PTCA). Mean (SD) plasma sphingomyelin level was 48 mg/dl (16.0). One hundred and eighty-nine subjects had an adjudicated CHD event during the five years of follow up. In the Kaplan meier analysis, subjects with plasma sphingomyelin level above the sex specific median had similar event free survival rate compared with subjects with plasma sphingomyelin level below or equal to the sex specific median (97.16% vs 97.0%, log rank p= 0.713). In the univariate Cox proportional hazard analysis, plasma sphingomyelin was not a predictor of incident CHD event [hazard ratio 0.992(0.982 – 1.004), p=0.09]. In our multistage multivariable Cox models, higher plasma sphingomyelin had modest negative association with incident CHD events when total cholesterol, HDL and triglycerides were included in the model [hazard ratio 0.985 (0.973 – 0.996), p=0.008] and also in our full model after adjusting for age, gender, total cholesterol, HDL, triglycerides, diabetes, cigarette smoking, systolic BP, diastolic BP, BP medication use, HMG CoA use [hazard ratio 0.984 (0.973 – 0.996), p=0.002]. In other models, plasma sphingomyelin was not associated with incident CHD events.
Conclusion
High plasma sphingomyelin level is not associated with increased risk of incident coronary heart disease in population based adults free of clinical cardiovascular disease at baseline.
doi:10.1161/ATVBAHA.109.199281
PMCID: PMC2862629  PMID: 20032291
Plasma sphingomyelin; prognosis; coronary heart disease events; epidemiology
22.  Prospective cohort study of retinal vessel diameters and risk of hypertension 
BMJ : British Medical Journal  2004;329(7457):79.
Objective To examine the relation between diameters of the retinal arterioles and 10 year incidence of hypertension.
Design Population based prospective cohort study.
Setting Beaver Dam eye study.
Participants 2451 normotensive people aged 43 to 84 years.
Main outcome measures Diameters of retinal arterioles and venules measured from digitised photographs of the retina taken at baseline. Measurements summarised as the arteriole:venule ratio, with a lower ratio indicating smaller arteriolar diameters. Incident hypertension, defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive drugs during follow up.
Results 721 participants developed hypertension over a 10 year period. Those with lower arteriole:venule ratio had a higher cumulative incidence of hypertension (incidences of 17.4%, 24.1%, 31.0%, and 45.1%, respectively, for decreasing quarters of distribution of arteriole:venule ratio). After adjustment for age and sex, participants with arteriole:venule ratios in the lowest quarter had a threefold higher risk of hypertension (odds ratio 2.95, 95% confidence interval 2.77 to 3.88) than those with ratios in the highest quarter. This association remained significant after further adjustment for baseline systolic and diastolic blood pressure and other risk factors (1.82, 1.39 to 2.40, for lowest versus highest ratio quarters).
Conclusions Narrowed retinal arterioles are associated with long term risk of hypertension, suggesting that structural alterations of the microvasculature may be linked to the development of hypertension.
doi:10.1136/bmj.38124.682523.55
PMCID: PMC449809  PMID: 15175230
23.  Ethnic Differences in the Incidence of Hypertension among Rural Chinese Adults: Results from Liaoning Province 
PLoS ONE  2014;9(1):e86867.
Background
This study was conducted to examine the differences in the incidence of hypertension and associated risk factors between Mongolian and Han populations in northeast China.
Methods
A population-based sample of 4753 Mongolian subjects and 20,247 Han subjects aged ≥35 years and free from hypertension at baseline were followed from 2004–2006 to 2010. Incident hypertension was defined as systolic blood pressure≥140 mmHg, diastolic blood pressure ≥90 mmHg, or current use of antihypertensive medication.
Results
During mean 4.3 years follow-up, a total of 8779 individuals developed hypertension. The age-adjusted incidence of hypertension for Mongolian subjects was 12.64 per 100 person-years, for Han subjects was 9.77 per 100 person-years (P<0.05). The incidence of hypertension was positively correlated with age, physical activity, drinking, body mass index (BMI), family of hypertension and prehypertension in the Han population. In the Mongolian population, hypertension was positively correlated with age, physical activity, education level, drinking, BMI, prehypertension and family history of hypertension. The rates of awareness, treatment and control of hypertension for newly developed cases among both Han and Mongolian populations were low. (36.5% vs. 42.3%, 13.1% vs. 18.2%, 0.7% vs. 1.3%, P<0.05, respectively).
Conclusions
The incidence rate of hypertension is higher in the Mongolian populations than that in the Han populations, and hypertension in both ethnic populations was associated with similar risk factors. Our results suggest that most newly-diagnosed cases of hypertension are not adequately treated. Improvements in hypertension prevention and control programs in rural China are urgently needed.
doi:10.1371/journal.pone.0086867
PMCID: PMC3906098  PMID: 24489797
24.  Joint Associations of Physical Activity and Aerobic Fitness on the Development of Incident Hypertension: Coronary Artery Risk Development in Young Adults (CARDIA) 
Hypertension  2010;56(1):49-55.
Fitness and physical activity are each inversely associated with the development of hypertension. We tested whether fitness and physical activity were independently associated with the 20-year incidence of hypertension in 4618 men and women. Hypertension was determined in participants who had systolic blood pressure (SBP)≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg or who reported antihypertensive medication use. Fitness was estimated based on the duration of a symptom-limited graded exercise treadmill test and physical activity was self-reported. The incidence rate of hypertension was 13.8 per 1000 person-years (n=1022). Both baseline fitness (hazard ratio [HR]=0.63, 95% confidence interval [CI]: 0.56, 0.70 per standard deviation [SD; 2.9 minutes]) and physical activity (HR=0.86, 95% CI: 0.79, 0.84 per SD [297 exercise units]) were inversely associated with incident hypertension when included jointly in a model that also adjusted for age, sex, race, baseline smoking status, SBP, alcohol intake, HDL cholesterol, dietary fiber, dietary sodium, fasting glucose and BMI. The magnitude of association between physical activity and hypertension was strongest among participants in the high fitness (HR= 0.80, 95% CI: 0.68, 0.94) category, whereas the magnitude of association between fitness and hypertension was similar across tertiles of physical activity. The estimated proportion of hypertension cases that could be prevented if participants moved to a higher fitness category (i.e., preventive fraction) was 34% and varied by race and sex group. Fitness and physical activity are each associated with incident hypertension, and low fitness may account for a substantial proportion of hypertension incidence.
doi:10.1161/HYPERTENSIONAHA.109.147603
PMCID: PMC2909350  PMID: 20516395
epidemiology; exercise; ethnicity; risk factors; special populations
25.  Stages of Systemic Hypertension and Blood Pressure as Correlates of Computed Tomography-Assessed Aortic Valve Calcium (From the Multi-Ethnic Study of Atherosclerosis) 
Hypertension has been identified as a risk factor for aortic valve calcium (AVC) but the magnitude of the risk relation with hypertension severity or whether age affects the strength of this risk association has not been studied. The relationship of hypertension severity, as defined by JNC-7 hypertension stages or blood pressure (BP), to CT-assessed AVC prevalence and severity was examined in 4,274 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) without treated hypertension. Analyses were stratified by age < or ≥ 65 years, were adjusted for common cardiovascular risk factors, and excluded those on antihypertensive medications. In age-stratified, adjusted analyses, Stage I/II hypertension was associated with prevalent AVC in those <65 but not in those ≥65 years of age [OR (95% CI): 2.31 (1.35, 3.94) vs. 1.33 (0.96, 1.85), P-interaction = 0.041]. Similarly, systolic BP and pulse pressure (PP) were more strongly associated with prevalent AVC in those <65 than those ≥65 years of age [OR (95% CI): 1.21 (1.08, 1.35) vs. 1.07 (1.01, 1.14) per 10 mmHg increase in systolic BP, Pinteraction = 0.006] and [OR (95% CI): 1.41 (1.21, 1.64) vs. 1.14 (1.05, 1.23) per 10 mmHg increase in PP]. No associations were found between either hypertension stage or BP and AVC severity. In conclusion, stage I/II hypertension, as well as higher systolic pressure and pulse pressure were associated with prevalent AVC. These risk associations were strongest in participants younger than age 65 years.
doi:10.1016/j.amjcard.2010.08.042
PMCID: PMC3032359  PMID: 21146685
Blood Pressure; Aortic Valve; Calcification

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