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1.  Glutamic Acid – the Main Dietary Amino Acid – and Blood Pressure: The INTERMAP Study 
Circulation  2009;120(3):221-228.
Data are available indicating an independent inverse relationship of dietary vegetable protein to the blood pressure (BP) of individuals. Here we assess whether BP is associated with glutamic acid intake (the predominant dietary amino acid, especially in vegetable protein) and with each of four other amino acids higher relatively in vegetable than animal protein (proline, phenylalanine, serine, cystine).
Methods and Results
Cross-sectional epidemiological study; 4,680 persons ages 40–59 -- 17 random population samples in China, Japan, U.K., U.S.A.; BP measurement 8 times at 4 visits; dietary data (83 nutrients, 18 amino acids) from 4 standardized multi-pass 24-hour dietary recalls and 2 timed 24-hour urine collections. Dietary glutamic acid (percent of total protein intake) was inversely related to BP. Across multivariate regression models (Model 1 controlled for age, gender, sample, through Model 5 controlled for 16 non-nutrient and nutrient possible confounders) estimated average BP differences associated with glutamic acid intake higher by 4.72% total dietary protein (2 s.d.) were −1.5 to −3.0 mm Hg systolic and −1.0 to −1.6 mm Hg diastolic (Z-values −2.15 to −5.11). Results were similar for the glutamic acid-BP relationship with each other amino acid also in the model, e.g., with control for 15 variables plus proline, systolic/diastolic pressure differences −2.7/−2.0 (Z −2.51, −2.82). In these 2-amino acid models, higher intake (2 s.d.) of each other amino acid was associated with small BP differences and Z-values.
Dietary glutamic acid may have independent BP lowering effects, possibly contributing to the inverse relation of vegetable protein to BP.
PMCID: PMC4048930  PMID: 19581495
dietary amino acids; glutamic acid; blood pressure; population study
2.  Prevalence of Major Cardiovascular Risk Factors and Cardiovascular Diseases Among Hispanic/Latino Individuals of Diverse Backgrounds in the United States 
Major cardiovascular diseases (CVDs) are leading causes of mortality among US Hispanic and Latino individuals. Comprehensive data are limited regarding the prevalence of CVD risk factors in this population and relations of these traits to socioeconomic status (SES) and acculturation.
To describe prevalence of major CVD risk factors and CVD (coronary heart disease [CHD] and stroke) among US Hispanic/Latino individuals of different backgrounds, examine relationships of SES and acculturation with CVD risk profiles and CVD, and assess cross-sectional associations of CVD risk factors with CVD.
Design, Setting, and Participants
Multicenter, prospective, population-based Hispanic Community Health Study/Study of Latinos including individuals of Cuban (n =2201), Dominican (n = 1400), Mexican (n=6232), Puerto Rican (n=2590), Central American (n=1634), and South American backgrounds (n = 1022) aged 18 to 74 years. Analyses involved 15 079 participants with complete data enrolled between March 2008 and June 2011.
Main Outcome Measures
Adverse CVD risk factors defined using national guidelines for hypercholesterolemia, hypertension, obesity, diabetes, and smoking. Prevalence of CHD and stroke were ascertained from self-reported data.
Age-standardized prevalence of CVD risk factors varied by Hispanic/Latino background; obesity and current smoking rates were highest among Puerto Rican participants (for men, 40.9% and 34.7%; for women, 51.4% and 31.7%, respectively); hypercholesterolemia prevalence was highest among Central American men (54.9%) and Puerto Rican women (41.0%). Large proportions of participants (80% of men, 71% of women) had at least 1 risk factor. Age- and sex-adjusted prevalence of 3 or more risk factors was highest in Puerto Rican participants (25.0%) and significantly higher (P<.001) among participants with less education (16.1%), those who were US-born (18.5%), those who had lived in the United States 10 years or longer (15.7%), and those who preferred English (17.9%). Overall, self-reported CHD and stroke prevalence were low (4.2% and 2.0% in men; 2.4% and 1.2% in women, respectively). In multivariate-adjusted models, hypertension and smoking were directly associated with CHD in both sexes as were hypercholesterolemia and obesity in women and diabetes in men (odds ratios [ORs], 1.5–2.2). For stroke, associations were positive with hypertension in both sexes, diabetes in men, and smoking in women (ORs, 1.7–2.6).
Among US Hispanic/Latino adults of diverse backgrounds, a sizeable proportion of men and women had adverse major risk factors; prevalence of adverse CVD risk profiles was higher among participants with Puerto Rican background, lower SES, and higher levels of acculturation.
PMCID: PMC3777250  PMID: 23117778
3.  Lifetime Risk for Heart Failure Among White and Black Americans: Cardiovascular Lifetime Risk Pooling Project 
To estimate lifetime risk for HF by sex and race.
Prior estimates of lifetime risk for developing heart failure (HF) range from 20% to 33% in predominantly white cohorts. Short-term risks for HF appear higher for blacks than whites, but only limited comparisons of lifetime risk for HF have been made.
Using public-release and internal datasets from NHLBI-sponsored cohorts, we estimated lifetime risks for developing HF to age 95, with death free of HF as the competing event, among participants in Chicago Heart Association Detection Project in Industry (CHA), Atherosclerosis Risk in Communities (ARIC), and Cardiovascular Health Study (CHS) cohorts.
There were 39,578 participants (33,652 [85%] white; 5,926 [15%] black) followed for 716,976 person-years; 5,983 participants developed HF. At age 45 years, lifetime risks for HF through age 95 years in CHA and CHS were 30-42% in white men, 20-29% in black men, 32-39% in white women, and 24-46% in black women. Results for ARIC demonstrated similar lifetime risks for HF in blacks and whites through age 75 years (limit of follow-up). Lifetime risk for HF was higher with higher BP and BMI at all ages in both blacks and whites and did not diminish substantially with advancing index age.
These are among the first data to compare lifetime risks for HF between blacks and whites. Lifetime risks for HF are high and appear similar for black and white women, yet are somewhat lower for black compared with white men due to competing risks.
PMCID: PMC3618527  PMID: 23500287
lifetime risk; heart failure; epidemiology
4.  Nutrient and food intakes of middle-aged adults at low risk of cardiovascular disease: the international study of macro-/micronutrients and blood pressure (INTERMAP) 
European journal of nutrition  2011;51(8):917-926.
Individuals with favorable levels of readily measured cardiovascular disease (CVD) risk factors (low risk, LR) experience low long-term rates of CVD mortality and greater longevity. The purpose of the current study was to compare nutrient/food intakes of LR participants with participants not LR in the INTERMAP study.
Men and women (40–59 years) from 17 population samples in four countries (China, Japan, UK, US) provided four 24-h dietary recalls and two timed 24-h urine collections. LR was defined as meeting all of the following CVD risk criteria: systolic/diastolic blood pressure (BP) ≤120/≤80 mmHg; no drug treatment for high BP, hyperlipidemia, or CVD; non-smoking; BMI <25.0 kg/m2 (US, UK) or <23.0 kg/m2 (China, Japan); alcohol consumption <26.0 g/day (men)/<13.0 g/day (women); and no history of diabetes or CVD. Multivariate logistic regression was used to examine associations of nutrient/food intakes with LR.
LR individuals reported higher intake of vegetable protein, fiber, magnesium, non-heme iron, potassium; lower energy intake; lower intake of cholesterol, saturated fatty acids, animal protein; and lower 24-h urinary sodium compared with individuals not LR. With regard to foods, LR individuals reported higher intake of fruits, vegetables, grains, pasta/rice, fish; lower intakes of meats, processed meats, high-fat dairy, and sugar-sweetened beverages than individuals not LR.
Lower energy intake and differential intake of multiple specific nutrients and foods are characteristic of individuals at low risk for developing CVD. Identification of dietary habits associated with LR is important for further development of public health efforts aimed at reduction/prevention of CVD.
PMCID: PMC3939781  PMID: 22057680
Cardiovascular disease; Diet; Foods; Low cardiovascular risk; Nutrients; Risk factors
5.  Relationship of Body Mass Index in Young Adulthood and Health-Related Quality of Life Two Decades Later: The Coronary Artery Risk Development in Young Adults (CARDIA) Study 
International journal of obesity (2005)  2010;35(1):10.1038/ijo.2010.120.
The expanding overweight and obesity epidemic notwithstanding, little is known about their long-term effect on health-related quality of life (HRQoL). The main objective of this study was to investigate whether overweight (body mass index [BMI] 25–<30 kg/m2) and obese (BMI ≥ 30 kg/m2) young adults have poorer HRQoL 20 years later.
The authors studied 3014 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal, community-dwelling, biracial cohort from four cities. BMI was measured at baseline and 20 years later. HRQoL was assessed via the physical component summary (PCS) and the mental component summary (MCS) scores of the Medical Outcomes Study 12-Item Short Form Health Survey at year 20. Higher PCS or MCS scores indicate better HRQoL.
Mean year 20 PCS score was 52.2 for normal weight participants at baseline, 50.3 for overweight, and 46.4 for obese (P-trend <0.001). This relation persisted after adjustment for baseline demographics, general health, and physical and behavioral risk factors and after further adjustment for 20-year changes in risk factors. No association was observed for MCS scores (P-trend 0.43).
Overweight and obesity in early adulthood are adversely associated with self-reported physical HRQoL, but not mental HRQoL 20 years later.
PMCID: PMC3875360  PMID: 20548305
6.  Maintaining a High Physical Activity Level Over 20 Years and Weight Gain 
JAMA : the journal of the American Medical Association  2010;304(23):10.1001/jama.2010.1843.
Data supporting physical activity guidelines to prevent long-term weight gain are sparse, particularly during the period when the highest risk of weight gain occurs.
To evaluate the relationship between habitual activity levels and changes in body mass index (BMI) and waist circumference over 20 years.
Design, Setting, and Participants
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective longitudinal study with 20 years of follow-up, 1985-86 to 2005-06. Habitual activity was defined as maintaining high, moderate, and low activity levels based on sex-specific tertiles of activity scores at baseline. Participants comprised a population-based multi-center cohort (Chicago, Illinois; Birmingham, Alabama; Minneapolis, Minnesota; and Oakland, California) of 3554 men and women aged 18 to 30 years at baseline.
Main Outcome Measures
Average annual changes in BMI and waist circumference
Over 20 years, maintaining high levels of activity was associated with smaller gains in BMI and waist circumference compared with low activity levels after adjustment for race, baseline BMI, age, education, cigarette smoking status, alcohol use, and energy intake. Men maintaining high activity gained 2.6 fewer kilograms (+ 0.15 BMI units per year; 95 % confidence interval [CI] 0.11-0.18 vs +0.20 in the lower activity group; 95% CI, 0.17-0.23) and women maintaining higher activity gained 6.1 fewer kilograms (+0.17 BMI units per year; 95 % CI, 0.12-0.21 vs. +0.30 in the lower activity group; 95 % CI, 0.25-0.34). Men maintaining high activity gained 3.1 fewer centimeters in waist circumference (+0.52 cm per year; 95 % CI, 0.43-0.61 cm vs 0.67 cm in the lower activity group; 95 % CI, 0.60-0.75) and women maintaining higher activity gained 3.8 fewer centimeters (+0.49 cm per year; 95 % CI, 0.39-0.58 vs 0.67 cm in the lower activity group; 95 % CI, 0.60-0.75).
Maintaining high activity levels through young adulthood may lessen weight gain as young adults transition to middle age, particularly in women.
PMCID: PMC3864556  PMID: 21156948
7.  Understanding Ethnic and Nativity-Related Differences in Low Cardiovascular Risk Status among Mexican-Americans and Non-Hispanic Whites 
Preventive medicine  2012;55(6):597-602.
Recent guidelines highlight the importance of improving cardiovascular health in the general population in addition to disease prevention among high risk individuals. We investigated factors associated with ethnic and nativity-related differences in the prevalence of low cardiovascular risk (optimal levels of all major cardiovascular risk factors).
We used logistic regression to estimate differences in likelihood of being low risk (not currently smoking; no diabetes; untreated total cholesterol < 200 mg/dL; untreated blood pressure <120/<80; and body mass index < 25 kg/m2) among 8,693 foreign- and U.S.-born Mexican-American and non-Hispanic White 2003–2008 U.S. National Health and Nutrition Examination Survey participants before and after adjustment for socioeconomic, lifestyle, and acculturation-related factors.
Foreign-born Mexican-Americans were more likely to be low risk than non-Hispanic Whites after adjustment for all covariates (Odds Ratio [OR]: 1.53; 95% Confidence Interval [CI]: 1.00, 2.34). In contrast, U.S.-born Mexican-Americans were less likely to be low risk compared to Whites (OR: 0.60; 95% CI: 0.43, 0.84). Differences between foreign-born and U.S.-born Mexican-Americans were largely attenuated after adjustment for acculturation indicators.
Our findings support the healthy migrant hypothesis and suggest acculturation-related factors may be important drivers of ethnic and nativity-related differences in low cardiovascular risk.
PMCID: PMC3544946  PMID: 23036519
health disparities; cardiovascular; acculturation; Hispanics/Latinos
8.  Prospective Study of Particulate Air Pollution Exposures, Subclinical Atherosclerosis, and Clinical Cardiovascular Disease 
American Journal of Epidemiology  2012;176(9):825-837.
The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) was initiated in 2004 to investigate the relation between individual-level estimates of long-term air pollution exposure and the progression of subclinical atherosclerosis and the incidence of cardiovascular disease (CVD). MESA Air builds on a multicenter, community-based US study of CVD, supplementing that study with additional participants, outcome measurements, and state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, and black carbon. More than 7,000 participants aged 45–84 years are being followed for over 10 years for the identification and characterization of CVD events, including acute myocardial infarction and other coronary artery disease, stroke, peripheral artery disease, and congestive heart failure; cardiac procedures; and mortality. Subcohorts undergo baseline and follow-up measurements of coronary artery calcium using computed tomography and carotid artery intima-medial wall thickness using ultrasonography. This cohort provides vast exposure heterogeneity in ranges currently experienced and permitted in most developed nations, and the air monitoring and modeling methods employed will provide individual estimates of exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand and reduce uncertainty in health effect estimation regarding long-term exposure to air pollution and CVD.
PMCID: PMC3571256  PMID: 23043127
air pollution; atherosclerosis; cardiovascular diseases; environmental exposure; epidemiologic methods; particulate matter
9.  Diet composition and activity level of at risk and metabolically healthy obese American adults 
Obesity (Silver Spring, Md.)  2013;21(3):10.1002/oby.20257.
Obesity often clusters with other major cardiovascular disease risk factors, yet a subset of the obese appears to be protected from these risks. Two obesity phenotypes are described, 1) “metabolically healthy” obese, broadly defined as body mass index (BMI) ≥ 30 kg/m2 and favorable levels of blood pressure, lipids, and glucose; and 2) “at risk” obese, BMI ≥ 30 with unfavorable levels of these risk factors. More than 30% of obese American adults are metabolically healthy. Diet and activity determinants of obesity phenotypes are unclear. We hypothesized that metabolically healthy obese have more favorable behavioral factors, including less adverse diet composition and higher activity levels than at risk obese in the multi-ethnic group of 775 obese American adults ages 40–59 years from the International Population Study on Macro/Micronutrients and Blood Pressure (INTERMAP) cohort. In gender stratified analyses, mean values for diet composition and activity behavior variables, adjusted for age, race, and education, were compared between metabolically healthy and at risk obese. Nearly 1 in 5 (149/775, or 19%) of obese American INTERMAP participants were classified as metabolically healthy obese. Diet composition and most activity behaviors were similar between obesity phenotypes, although metabolically healthy obese women reported higher sleep duration than at risk obese women. These results do not support hypotheses that diet composition and/or physical activity account for the absence of cardiometabolic abnormalities in metabolically healthy obese.
PMCID: PMC3416914  PMID: 23592673
10.  Racial/Ethnic Differences in the Development of Disability among Older Adults 
American journal of public health  2007;97(12):2209-2215.
This study investigates differences in developing activities of daily living (ADL) disability among non-Hispanic Whites, African Americans, Hispanics interviewed in Spanish (Hispanic/Spanish), and Hispanics interviewed in English (Hispanic/English)
Six-year risk for disability development is estimated from 8161 participants age 65 or older free of baseline disability in a population-based sample. Mediating factors amenable to clinical and public health intervention on racial/ethnic difference are evaluated.
The risk for developing disability among Hispanic/English was similar to Whites (hazard ratio [HR] = 0.99, 95% confidence interval [CI]: 0.6, 1.4), but substantially elevated for African Americans (HR=1.6, 95%CI: 1.3, 1.9) and Hispanic/Spanish (HR=1.8, 95%CI: 1.4, 2.1). Adjustment for demographics, health, and socioeconomic status reduced a large portion of those disparities (African American adjusted HR=1.1, Hispanic/Spanish adjusted HR=1.2).
Excess risks for developing disability among older African Americans and Hispanic/Spanish compared to Whites are largely attenuated by health and socioeconomic differences. Language and culture specific programs to increase physical activity and promote weight maintenance may prove to be efficient strategies to both reduce national ADL disability rates in the future and reduce racial/ethnic disparities in disability.
PMCID: PMC2089103  PMID: 17971548
ADL; African American; Hispanic; Chronic Disease; Aging
Hypertension  2011;58(3):410-416.
High salt intake may affect left ventricular mass (LVM). We hypothesized that urinary sodium (UNa) and sodium / potassium ratio (UNa/K) are associated with LVM in a predominantly normotensive cohort young adults. The Coronary Artery Risk Development in Young Adults (CARDIA) study is a multicenter cohort of black and white men and women aged 30 ± 3.6 years at the time of baseline echocardiographic examination (1990–1991). Two-dimensionally guided M-mode LVM indexed to body size (gm/m2.7) was calculated and urinary sodium (UNa) and potassium (UK) excretion assessed (average of three 24-hour urinary samples, n=1,042). Linear and logistic regression analysis was used. Participants were 57% women, and 55% black. Only 4% were hypertensive. Mean±SD UNa, UK, and UNa/K ratio were 175.6±131.0 mmol/24hour, 56.4±46.3 mmol/24hour and 3.4±1.4, respectively. Participants in the highest vs. lowest UNa excretion quartile had the greatest LVM (37.5 vs. 34.0 g/m2.7, p<0.001). Adjusted for age, sex, education and race, LVM averaged 0.945gm/m2.7 higher per SD of UNa/K (p=0.001). The relationship between UNa/K and LVM persisted among 399 participants with repeat echocardiographic measures five years later. In logistic regression analysis adjusted for age, sex, education and race, each SD higher baseline UNa/K was associated with 23% and 38% greater chance of being in the highest quartile of LVM at baseline (OR 1.23; p=0.005) and five years later (OR 1.38; p=0.02). A higher sodium to potassium excretion ratio is significantly related to cardiac structure even among healthy young adults.
PMCID: PMC3726308  PMID: 21788603
urinary sodium; urinary potassium; sodium / potassium ratio; left ventricular mass
12.  Self-perceived physical health predicts cardiovascular disease incidence and death among postmenopausal women 
BMC Public Health  2013;13:468.
Physical and Mental Component Summary (PCS, MCS, respectively) scales of SF- 36 health-related-quality-of-life have been associated with all-cause and cardiovascular disease (CVD) mortality. Their relationships with CVD incidence are unclear. This study purpose was to test whether PCS and/or MCS were associated with CVD incidence and death.
Postmenopausal women (aged 50–79 years) in control groups of the Women’s Health Initiative clinical trials (n = 20,308) completed the SF-36 and standardized questionnaires at trial entry. Health outcomes, assessed semi-annually, were verified with medical records. Cox regressions assessed time to selected outcomes during the trial phase (1993–2005).
A total of 1075 incident CVD events, 204 CVD-specific deaths, and 1043 total deaths occurred during the trial phase. Women with low versus high baseline PCS scores had less favorable health profiles at baseline. In multivariable models adjusting for baseline confounders, participants in the lowest PCS quintile (reference = highest quintile) exhibited 1.8 (95%CI: 1.4, 2.3), 4.7 (95%CI: 2.3, 9.4), and 2.1 (95%CI: 1.7, 2.7) times greater risk of CVD incidence, CVD-specific death, and total mortality, respectively, by trial end; whereas, MCS was not significantly associated with CVD incidence or death.
Physical health, assessed by self-report of physical functioning, is a strong predictor of CVD incidence and death in postmenopausal women; similar self-assessment of mental health is not. PCS should be evaluated as a screening tool to identify older women at high risk for CVD development and death.
PMCID: PMC3706392  PMID: 23672763
Physical component summary; Mental component summary; Cardiovascular disease; All-cause death
13.  Chronic Kidney Disease in United States Hispanics: A Growing Public Health Problem 
Ethnicity & disease  2009;19(4):466-472.
Hispanics are the fastest growing minority group in the United States. The incidence of end-stage renal disease (ESRD) in Hispanics is higher than non-Hispanic Whites and Hispanics with chronic kidney disease (CKD) are at increased risk for kidney failure. Likely contributing factors to this burden of disease include diabetes and metabolic syndrome, both are common among Hispanics. Access to health care, quality of care, and barriers due to language, health literacy and acculturation may also play a role. Despite the importance of this public health problem, only limited data exist about Hispanics with CKD. We review the epidemiology of CKD in US Hispanics, identify the factors that may be responsible for this growing health problem, and suggest gaps in our understanding which are suitable for future investigation.
PMCID: PMC3587111  PMID: 20073150
Chronic Kidney Disease; Hispanics; Health Care Disparities
14.  Healthy Lifestyle through Young Adulthood and Presence of Low Cardiovascular Disease Risk Profile in Middle Age: The Coronary Artery Risk Development in (Young) Adults (CARDIA) Study 
Circulation  2012;125(8):996-1004.
A low cardiovascular disease (CVD) risk profile (untreated cholesterol < 200 mg/dl, untreated blood pressure < 120/<80 mmHg, never smoking, and no history of diabetes and myocardial infarction) in middle age is associated with markedly better health outcomes in older age, but few middle aged adults have this low risk profile. We examined whether adopting a healthy lifestyle throughout young adulthood is associated with presence of the low CVD risk profile in middle age.
Methods and Results
The CARDIA study sample consisted of 3,154 black and white participants aged 18 to 30 years at Year 0 (Y0, 1985-86) who attended the Year 0, 7 and 20 (Y0, Y7 and Y20) examinations. Healthy lifestyle factors (HLFs) defined at Y0, Y7 and Y20 included: 1) Average BMI < 25 kg/m2; 2) No or moderate alcohol intake; 3) higher healthy diet score; 4) higher physical activity score; and 5) Never smoking. Mean age (25 years) and percentage of women (56%) were comparable across groups defined by number of HLFs. The age-, sex- and race-adjusted prevalences of low CVD risk profile at Y20 were 3.0%, 14.6%, 29.5%, 39.2% and 60.7% for people with 0 or 1, 2, 3, 4, and 5 HLFs, respectively (p-trend <0.0001). Similar graded relationships were observed for each sex-race group (all p-trend<0.0001).
Maintaining a healthy lifestyle throughout young adulthood is strongly associated with low CVD risk profile in middle age. Public health and individual efforts are needed to improve adoption and maintenance of healthy lifestyles in young adults.
PMCID: PMC3353808  PMID: 22291127
epidemiology; follow-up studies; risk factors; prevention
15.  Prevalence of Electrocardiographic Abnormalities in a Middle-Aged, Biracial Population: Coronary Artery Risk Development in Young Adults (CARDIA) Study 
Journal of electrocardiology  2010;43(5):385.e1-385.e9.
Few studies to date have described the prevalence of electrocardiographic (ECG) abnormalities in a biracial middle-aged cohort.
Methods and Results
Participants underwent measurement of traditional risk factors and 12-lead ECGs coded using both Minnesota Code (MC) and Novacode (NC) criteria. Among 2585 participants, of whom 57% were women and 44% were black (mean age 45 years), the prevalence of major and minor abnormalities were significantly higher (all P<0.001) among black men and women compared to whites. These differences were primarily due to higher QRS voltage and ST/T wave abnormalities among blacks. There was also a higher prevalence of Q waves (MC 1-1, 1-2, 1-3) than described by previous studies. These racial differences remained after multivariate adjustment for traditional cardiovascular (CV) risk factors.
Black men and women have a significantly higher prevalence of ECG abnormalities, independent of traditional CV risk factors, than whites in a contemporary cohort middle-aged participants.
PMCID: PMC3569004  PMID: 20374967
16.  Prospective Relationship of Low Cardiovascular Risk Factor Profile at Younger Ages to Ankle-Brachial Index: 39-Year Follow-Up—The Chicago Healthy Aging Study 
Data are sparse regarding the long-term association of favorable levels of all major cardiovascular disease risk factors (RFs) (ie, low risk [LR]) with ankle-brachial index (ABI).
Methods and Results
In 2007–2010, the Chicago Healthy Aging Study reexamined a subset of participants aged 65 to 84 years from the Chicago Heart Association Detection Project in Industry cohort (baseline examination, 1967–1973). RF groups were defined as LR (untreated blood pressure ≤120/≤80 mm Hg, untreated serum cholesterol <200 mg/dL, body mass index <25 kg/m2, not smoking, no diabetes) or as 0 RFs, 1 RF, or 2+ RFs based on the presence of blood pressure ≥140/≥90 mm Hg or receiving treatment, serum cholesterol ≥240 mg/dL or receiving treatment, body mass index ≥30 kg/m2, smoking, or diabetes. ABI at follow-up was categorized as indicating PAD present (≤0.90), as borderline PAD (0.91 to 0.99), or as normal (1.00 to 1.40). We included 1346 participants with ABI ≤1.40. After multivariable adjustment, the presence of fewer baseline RFs was associated with a lower likelihood of PAD at 39-year follow-up (P for trend is <0.001). Odds ratios (95% CIs) for PAD in persons with LR, 0 RFs, or 1 RF compared with those with 2+ RFs were 0.14 (0.05 to 0.44), 0.28 (0.13 to 0.59), and 0.33 (0.16 to 0.65), respectively; findings were similar for borderline PAD (P for trend is 0.005). The association was mainly due to baseline smoking status, cholesterol, and diabetes. Remaining free of adverse RFs or improving RF status over time was also associated with PAD.
LR profile in younger adulthood (ages 25 to 45) is associated with the lowest prevalence of PAD and borderline PAD 39 years later.
PMCID: PMC3540658  PMID: 23316312
aging; atherosclerosis; cardiovascular disease; peripheral artery disease; risk factors
17.  Longitudinal association between animal and vegetable protein intake and obesity among adult males in the United States: the Chicago Western Electric Study 
Literature on the association of protein intake with body weight is inconsistent. Little is known about the relation of long-term protein intake to obesity. This study aimed to determine the association between protein intake and obesity. A cohort of 1,730 employed white men ages 40–55 years from the Chicago Western Electric Study was followed from 1958 to 1966. Diet was assessed twice with Burke’s comprehensive diet history method, at two baseline examinations; height, weight, and other covariates were measured annually by trained interviewers. Generalized estimating equation (GEE) was used to examine the relation of baseline total, animal, and vegetable protein intake to likelihood of being overweight or obese at sequential annual examinations. Dietary animal protein was positively related to overweight and obesity over seven years of follow up. With adjustment for potential confounders (age, education, cigarette smoking, alcohol intake, energy, carbohydrate and saturated fat intake, and history of diabetes or other chronic disease), the odds ratios (95% confidence intervals) for obesity were 4.62 (2.68–7.98, p for trend<0.01) for participants in the highest compared to the lowest quartile of animal protein and 0.58 (0.36, 0.95, p for trend=0.053) for those in the highest quartile of vegetable protein intake. A statistically significant, positive association was seen between animal protein intake and obesity; those in higher quartiles of vegetable protein intake had lower odds of being obese. These results indicate that animal and vegetable protein may relate differently to occurrence of obesity in the long run.
PMCID: PMC3158996  PMID: 21802560
Dietary protein intake; overweight; obesity; nutrition; epidemiology
Hypertension  2011;57(4):695-701.
The obesity epidemic has focused attention on relationships of sugars and sugar-sweetened beverages (SSB) to cardiovascular risk factors. Here we report cross-sectional associations of SSB, diet beverages, sugars with blood pressure (BP) for UK and USA participants of the International Study of Macro/Micro-nutrients and Blood Pressure (INTERMAP). Data collected includes four 24-h dietary recalls, two 24-h urine collections, eight BP readings, questionnaire data for 2,696 people ages 40-59 from 10 USA/UK population samples. Associations of SSB, diet beverages, and sugars (fructose, glucose, sucrose) with BP were assessed by multiple linear regression. Sugar-sweetened beverage intake related directly to BP, P-values 0.005 to <0.001 (systolic BP), 0.14 to <0.001 (diastolic BP). Sugar-sweetened beverage intake higher by 1 serving/day (355 ml/24-h) was associated with systolic/diastolic BP differences of +1.6/+0.8 mm Hg (both P <0.001); +1.1/+0.4 mm Hg (P <0.001/<0.05) with adjustment for weight, height. Diet beverage intake was inversely associated with BP, P 0.41 to 0.003. Fructose- and glucose-BP associations were direct, with significant sugar-sodium interactions: for individuals with above-median 24-h urinary sodium excretion, fructose intake higher by 2 SD (5.6 %kcal) was associated with systolic/diastolic BP differences of +3.4/+2.2 mm Hg (both P <0.001); 2.5/1.7 mm Hg (both P 0.002) with adjustment for weight, height. Observed independent, direct associations of SSB intake and BP are consistent with recent trial data. These findings, plus adverse nutrient intakes among SSB consumers, and greater sugar-BP differences for persons with higher sodium excretion, lend support to recommendations that intake of SSB, sugars, and salt be substantially reduced.
PMCID: PMC3086758  PMID: 21357284
Sugar-sweetened beverages; sodium; nutrition; blood pressure; epidemiology; population study
19.  Design and Implementation of the Hispanic Community Health Study / Study of Latinos 
Annals of epidemiology  2010;20(8):629-641.
The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a comprehensive multi-center community based cohort study of Hispanics/Latinos in the United States. Its rationale, objectives, design and implementation are described in this paper.
The HCHS/SOL will recruit 16,000 men and women who self-identify as Hispanic or Latino, age 18-74 years, from a random sample of households in defined communities in the Bronx, Chicago, Miami and San Diego. The sites were selected so that the overall sample would consist of at least 2000 persons in each of the following origin designations: Mexican, Puerto Rican and Dominican, Cuban, and Central and South American. The study includes research in the prevalence of and risk factors for heart, lung, blood and sleep disorders, kidney and liver function, diabetes, cognitive function, dental conditions, and hearing disorders.
The HCHS/SOL will 1) characterize the health status and disease burden in the largest minority population in the U.S; 2) describe the positive and negative consequences of immigration and acculturation of Hispanics/Latinos to the mainstream U.S. life-styles, environment and health care opportunities; and 3) identify likely causal factors of many diseases in a population with diverse environmental exposures, genetic backgrounds and early life experiences.
PMCID: PMC2904957  PMID: 20609343
20.  Activated TLR Signaling in Atherosclerosis among Women with Lower Framingham Risk Score: The Multi-Ethnic Study of Atherosclerosis 
PLoS ONE  2011;6(6):e21067.
Atherosclerosis is the leading cause of cardiovascular disease (CVD). Traditional risk factors can be used to identify individuals at high risk for developing CVD and are generally associated with the extent of atherosclerosis; however, substantial numbers of individuals at low or intermediate risk still develop atherosclerosis.
A case-control study was performed using microarray gene expression profiling of peripheral blood from 119 healthy women in the Multi-Ethnic Study of Atherosclerosis cohort aged 50 or above. All participants had low (<10%) to intermediate (10% to 20%) predicted Framingham risk; cases (N = 48) had coronary artery calcium (CAC) score >100 and carotid intima-media thickness (IMT) >1.0 mm, whereas controls (N = 71) had CAC<10 and IMT <0.65 mm. We identified two major expression profiles significantly associated with significant atherosclerosis (odds ratio 4.85; P<0.001); among those with Framingham risk score <10%, the odds ratio was 5.30 (P<0.001). Ontology analysis of the gene signature reveals activation of a major innate immune pathway, toll-like receptors and IL-1R signaling, in individuals with significant atherosclerosis.
Gene expression profiles of peripheral blood may be a useful tool to identify individuals with significant burden of atherosclerosis, even among those with low predicted risk by clinical factors. Furthermore, our data suggest an intimate connection between atherosclerosis and the innate immune system and inflammation via TLR signaling in lower risk individuals.
PMCID: PMC3116882  PMID: 21698167
21.  Dietary Starch Intake of Individuals and Their Blood Pressure: The INTERMAP Study 
Journal of hypertension  2009;27(2):231-236.
Data from the Multiple Risk Factor Intervention Trial (MRFIT) show an independent direct association between starch intake and blood pressure (BP) in American men at higher risk of coronary heart disease (CHD). Cross-sectional INTERMAP data were used to assess relations of dietary starch intake to BP in men and women from four countries.
Data include 83 nutrients from four multi-pass 24-h dietary recalls and two timed 24-h urine collections; eight BP readings; and questionnaire data, for 4,680 participants ages 40–59 yr from 17 population samples in Japan, People's Republic of China, United Kingdom, and United States of America.
In multiple linear regression analyses – adjusted for urinary sodium, urinary potassium, consumption of alcohol, cholesterol, saturated fatty acids, polyunsaturated fatty acids, calcium, and other variables – starch intake higher by two standard deviations (14.1% kJ) was associated with systolic/diastolic BP differences of −1.0/−0.9 mm Hg (p =0.09, p <0.05). Results were similar with additional control for fibre, magnesium, or phosphorus; reduced to −0.5/−0.7 mm Hg (p =0.47, p =0.13) with separate adjustment for vegetable protein. Findings were similar for all INTERMAP men, for American men, and for American men at higher CHD risk.
INTERMAP data indicate that – if any – relations of starch intake to BP are modestly inverse. Current dietary guidelines for hypertension prevention and control remain relevant.
PMCID: PMC3111912  PMID: 19155780
Blood pressure; cross-sectional studies; diet; dietary carbohydrates; dietary starch; epidemiology
22.  Associations of Toenail Selenium Levels With Inflammatory Biomarkers of Fibrinogen, High-Sensitivity C-Reactive Protein, and Interleukin-6 
American Journal of Epidemiology  2010;171(7):793-800.
The authors examined the associations of toenail selenium levels with blood concentrations of fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) in an 18-year follow-up study comprising 4,032 Americans aged 20–32 years at baseline (1987) from the Coronary Artery Risk Development in Young Adults (CARDIA) Trace Element Study. Toenail samples were collected in 1987, and selenium concentrations were measured by means of instrumental neutron-activation analysis. Fibrinogen level was analyzed in 1990, 1992, and 2005; hs-CRP was assessed in 1992, 2000, and 2005; and IL-6 was measured in 2005. After adjustment for potential confounders, no statistically significant associations between toenail selenium levels and any of the 3 inflammatory biomarkers were documented. Comparing the highest quintile of toenail selenium level with the lowest, odds ratios for elevated levels of fibrinogen (>460 mg/mL), hs-CRP (>3 μg/mL), and IL-6 (>3.395 pg/mL, 80th percentile) were 1.03 (95% confidence interval (CI): 0.77, 1.38; P for trend = 0.76), 1.02 (95% CI: 0.83, 1.27; P for trend = 0.92), and 0.98 (95% CI: 0.71, 1.36; P for trend = 0.82), respectively. Gender, race/ethnicity, smoking status, and selenium supplementation did not appreciably modify these results. This study found no associations between toenail selenium and inflammation as measured by fibrinogen, hs-CRP, and IL-6.
PMCID: PMC2877482  PMID: 20219762
C-reactive protein; fibrinogen; inflammation; interleukin-6; nails; selenium
23.  Air Pollution and the Microvasculature: A Cross-Sectional Assessment of In Vivo Retinal Images in the Population-Based Multi-Ethnic Study of Atherosclerosis (MESA) 
PLoS Medicine  2010;7(11):e1000372.
Sara Adar and colleagues show that residing in locations with higher air pollution concentrations and experiencing daily increases in air pollution are associated with narrower retinal arteriolar diameters in older individuals, thus providing a link between air pollution and cardiovascular disease.
Long- and short-term exposures to air pollution, especially fine particulate matter (PM2.5), have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature.
Methods and Findings
Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE) and central retinal venular equivalents (CRVE), were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2002 and 2003. Study participants (46 to 87 years of age) were without clinical cardiovascular disease at the baseline examination (2000–2002). Long-term outdoor concentrations of PM2.5 were estimated at each participant's home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long- and short-term levels of PM2.5. These relationships were observed in a joint exposure model with −0.8 µm (95% confidence interval [CI] −1.1 to −0.5) and −0.4 µm (95% CI −0.8 to 0.1) decreases in CRAE per interquartile increases in long- (3 µg/m3) and short-term (9 µg/m3) PM2.5 levels, respectively. These reductions in CRAE are equivalent to 7- and 3-year increases in age in the same cohort. Similarly, living near a major road was also associated with a −0.7 µm decrease (95% CI −1.4 to 0.1) in CRAE. Although the chronic association with CRAE was largely influenced by differences in exposure between cities, this relationship was generally robust to control for city-level covariates and no significant differences were observed between cities. Wider CRVE were associated with living in areas of higher PM2.5 concentrations, but these findings were less robust and not supported by the presence of consistent acute associations with PM2.5.
Residing in regions with higher air pollution concentrations and experiencing daily increases in air pollution were each associated with narrower retinal arteriolar diameters in older individuals. These findings support the hypothesis that important vascular phenomena are associated with small increases in short-term or long-term air pollution exposures, even at current exposure levels, and further corroborate reported associations between air pollution and the development and exacerbation of clinical cardiovascular disease.
Please see later in the article for the Editors' Summary
Editors' Summary
Cardiovascular disease (CVD)—disease that affects the heart and/or the blood vessels—is a common cause of illness and death among adults in developed countries. In the United States, for example, the leading cause of death is coronary heart disease, a CVD in which narrowing of the heart's arteries by atherosclerotic plaques (fatty deposits that build up with age) slows the blood supply to the heart and may eventually cause a heart attack (myocardial infarction). Other types of CVD include stroke (in which atherosclerotic plaques interrupt the brain's blood supply) and peripheral arterial disease (in which the blood supply to the limbs is blocked). Smoking, high blood pressure, high blood levels of cholesterol (a type of fat), having diabetes, being overweight, and being physically inactive all increase a person's risk of developing CVD. Treatments for CVD include lifestyle changes and taking drugs that lower blood pressure or blood cholesterol levels.
Why Was This Study Done?
Another risk factor for CVD is exposure to long-term and/or short-term air pollution. Fine particle pollution or PM2.5 is particularly strongly associated with an increased risk of CVD. PM2.5—particulate matter 2.5 µm in diameter or 1/30th the diameter of a human hair—is mainly produced by motor vehicles, power plants, and other combustion sources. Why PM2.5 increases CVD risk is not clear but one possibility is that it alters the body's microvasculature (fine blood vessels known as capillaries, arterioles, and venules), thereby impairing the blood flow through the heart and brain. In this study, the researchers use noninvasive digital retinal photography to investigate whether there is an association between air pollution and changes in the human microvasculature. The retina—a light-sensitive layer at the back of the eye that converts images into electrical messages and sends them to the brain—has a dense microvasculature. Retinal photography is used to check the retinal microvasculature for signs of potentially blinding eye diseases such as diabetic retinopathy. Previous studies have found that narrower than normal retinal arterioles and wider than normal retinal venules are associated with CVD.
What Did the Researchers Do and Find?
The researchers used digital retinal photography to measure the diameters of retinal blood vessels in the participants of the Multi-Ethnic Study of Atherosclerosis (MESA). This study is investigating CVD progression in people aged 45–84 years of various ethnic backgrounds who had no CVD symptoms when they enrolled in the study in 2000–2002. The researchers modeled the long-term outdoor concentration of PM2.5 at each participant's house for the 2-year period preceding the retinal examination (which was done between 2002 and 2003) using data on PM2.5 levels collected by regulatory monitoring stations as well as study-specific air samples collected outside of the homes and in the communities of study participants. Outdoor PM2.5 measurements taken the day before the examination provided short-term PM2.5 levels. Among the 4,607 MESA participants who had complete data, retinal arteriolar diameters were narrowed among those who lived in regions with increased long- and short-term PM2.5 levels. Specifically, an increase in long-term PM2.5 concentrations of 3 µg/m3 was associated with a 0.8 µm decrease in arteriolar diameter, a reduction equivalent to that seen for a 7-year increase in age in this group of people. Living near a major road, another indicator of long-term exposure to PM2.5 pollution, was also associated with narrowed arterioles. Finally, increased retinal venular diameters were weakly associated with long-term high PM2.5 concentrations.
What Do These Findings Mean?
These findings indicate that living in areas with long-term air pollution or being exposed to short-term air pollution is associated with narrowing of the retinal arterioles in older individuals. They also show that widening of retinal venules is associated with long-term (but not short-term) PM2.5 pollution. Together, these findings support the hypothesis that long- and short-term air pollution increases CVD risk through effects on the microvasculature. However, they do not prove that PM2.5 is the constituent of air pollution that drives microvascular changes—these findings could reflect the toxicity of another pollutant or the pollution mixture as a whole. Importantly, these findings show that microvascular changes can occur at the PM2.5 levels that commonly occur in developed countries, which are well below those seen in developing countries. Worryingly, they also suggest that the deleterious cardiovascular effects of air pollution could occur at levels below existing regulatory standards.
Additional Information
Please access these Web sites via the online version of this summary at 10.1371/journal.pmed.1000372.
The American Heart Association provides information for patients and caregivers on all aspects of cardiovascular disease (in several languages), including information on air pollution, heart disease, and stroke
The US Centers for Disease Control and Prevention has information on heart disease and on stroke
Information is available from the British Heart Foundation on cardiovascular disease
The UK National Health Service Choices website provides information for patients and caregivers about cardiovascular disease
MedlinePlus provides links to other sources of information on heart disease and on vascular disease (in English and Spanish)
The AIRNow site provides information about US air quality and about air pollution and health
The Air Quality Archive has up-to-date information about air pollution in the UK and information about the health effects of air pollution
The US Environmental Protection Agency has information on PM2.5
The following Web sites contain information available on the MESA and MESA Air studies
PMCID: PMC2994677  PMID: 21152417
24.  Association of Electrocardiographic Abnormalities with Coronary Artery Calcium and Carotid Artery Intima-Media Thickness in Individuals without Clinical Coronary Heart Disease (From the Multi-Ethnic Study of Atherosclerosis [MESA]) 
The American journal of cardiology  2009;104(8):1086-1091.
Isolated minor non-specific ST-segment and T-wave (NSSTA), minor and major electrocardiographic (ECG) abnormalities are established, independent risk markers for incident cardiovascular events. Their association with subclinical atherosclerosis has been postulated but is not clearly defined. The aim of this study is to define the association between ECG abnormalities and measures of subclinical atherosclerosis. We studied participants from MESA, a multi-ethnic sample of men and women aged 45–84 and free of clinical cardiovascular disease at enrollment. Baseline examination included measurement of traditional risk factors, resting 12-lead electrocardiograms, coronary artery calcium (CAC) measurement and common carotid intima-media thickness (CCIMT). Electrocardiograms were coded using Novacode criteria and were defined as having either minor abnormalities (e.g., minor non-specific STTA, first degree atrioventricular block, and QRS axis deviations) or major abnormalities (e.g., pathologic Q waves, major ST-segment and T-wave abnormalities, significant dysrhythmias and conduction system delays). Multivariable logistic and linear regressions were used to determine the cross-sectional associations of ECG abnormalities with CAC and common carotid-IMT. Among 6710 participants, 52.7% were women, with a mean age of 62 years. After multivariable-adjustment, isolated minor STTA, minor and major ECG abnormalities were not associated with the presence of CAC (>0) among men (OR 1.04, 95% CI 0.81–1.33; 1.10, 0.91–1.32; and 1.03, 0.81–1.31, respectively) or women (1.01, 0.82–1.24; 1.04, 0.87–1.23; and 0.94, 0.73–1.22, respectively). Lack of association remained consistent when using both log CAC and CC-IMT as continuous variables. ECG abnormalities are not associated with markers of subclinical atherosclerosis in a large multi-ethnic cohort.
PMCID: PMC2871277  PMID: 19801030
25.  Long-chain omega-3 polyunsaturated fatty acids are inversely associated with depressive symptoms in women 
Experimental and observational data suggest higher dietary intake of long-chain omega-3 polyunsaturated acids may lead to decreased risk of depressive disorders. We assessed multivariable-adjusted associations of fish consumption and dietary intakes of eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] with depressive symptoms in a population-based sample of 3,317 African American and Caucasian men and women from the Coronary Artery Risk Development in Young Adults study (CARDIA).
Diet was assessed in Year 7 (1992–93) and depressive symptoms were measured in Years 10 (1995–96), 15 (2000–01), and 20 (2005–06) by the 20-item Center for Epidemiological Studies Depression Scale (CES-D). Depressive symptoms were defined as CES-D score ≥ 16 or self-reported use of antidepressant medication.
In the entire cohort, the highest quintiles of intakes of EPA (at least 0.03% energy), DHA (at least 0.05% energy), and EPA+DHA (at least 0.08% energy) were associated with lower risk of depressive symptoms at Year 10 (p-trends: 0.16, 0.10, 0.03, respectively). The observed inverse associations were more pronounced in women. For the total number of occasions with depressive symptoms, the multivariable adjusted odds ratios (95% confidence interval) in women were 0.75 (0.55–1.01) for fish intake; 0.66 (0.50–0.89), for EPA; 0.66 (0.49–0.89) for DHA; and 0.71 (0.52–0.95) for EPA+DHA, when comparing highest to lowest quintiles. Analyses of continuous CES-D scores revealed inverse associations with fourth root transformed omega-3 variables in women.
Our findings suggest that dietary intakes of fish and long-chain omega-3 fatty acids may be inversely associated with chronic depressive symptoms in women.
PMCID: PMC2798585  PMID: 19195841
omega-3 fatty acids; depressive symptoms; EPA; DHA; fish

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