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1.  Distribution of 10-year and lifetime predicted risk for cardiovascular disease in the Indian Sentinel Surveillance Study population (cross-sectional survey results) 
BMJ Open  2011;1(1):e000068.
Introduction
Cardiovascular disease (CVD) prevention guidelines recommend lifetime risk stratification for primary prevention of CVD, but no such risk stratification has been performed in India to date.
Methods
The authors estimated short-term and lifetime predicted CVD risk among 10 054 disease-free, adult Indians in the 20–69-year age group who participated in a nationwide risk factor surveillance study. The study population was then stratified into high short-term (≥10% 10-year risk or diabetes), low short-term (<10%)/high lifetime and low short-term/low lifetime CVD risk groups.
Results
The mean age (SD) of the study population (men=63%) was 40.8±10.9 years. High short-term risk for coronary heart disease was prevalent in more than one-fifth of the population (23.5%, 95% CI 22.7 to 24.4). Nearly half of individuals with low short-term predicted risk (48.2%, 95% CI 47.1 to 49.3) had a high predicted lifetime risk for CVD. While the proportion of individuals with all optimal risk factors was 15.3% (95% CI 14.6% to 16.0%), it was 20.6% (95% CI 18.7% to 22.6%) and 8.8% (95% CI 7.7% to 10.5%) in the highest and lowest educational groups, respectively.
Conclusion
Approximately one in two men and three in four women in India had low short-term predicted risks for CVD in this national study, based on aggregate risk factor burden. However, two in three men and one in two women had high lifetime predicted risks for CVD, highlighting a key limitation of short-term risk stratification.
Article summary
Article focus
Lifetime risk of cardiovascular disease (CVD) in the Indian population.
Gender differences in lifetime risk of CVD.
Educational status and lifetime risk of CVD.
Key messages
Nearly half of individuals with a low short-term predicted risk had a high predicted lifetime risk for CVD.
The proportion of individuals with all optimal risk factors was 15%.
A significantly lower proportion of individuals in the lowest educational class had all optimal risk factors compared with individuals in the higher educational class.
Approximately one in two men and three in four women from working families in India had low short-term predicted risk for CVD.
Strengths and limitations of this study
These are the first estimates to combine short-term and lifetime predicted risks for CVD in India.
Our simple cardiovascular-risk-factor counting strategy provides a good way of identifying individuals at high and low lifetime risk for CVD, but the lifetime CVD risk prediction model has not been validated or calibrated in India.
doi:10.1136/bmjopen-2011-000068
PMCID: PMC3191418  PMID: 22021747
Cardiovascular disease; risk stratification; lifetime risk; cardiac epidemiology; diabetes and endocrinology; lipid disorders; epidemiology; coronary heart disease; echocardiography; hypertension; heart failure; qualitative research; research methodology; India; primary healthcare; diabetes; developing countries; adult cardiology
2.  The 30-year cardiovascular risk profile of South Africans with diagnosed diabetes, undiagnosed diabetes, pre-diabetes or normoglycaemia: the Bellville, South Africa pilot study 
Abstract
The aim of this pilot study was to assess the 30-year risk for cardiovascular disease (CVD) in the South Africa population of mixed-ancestry in individuals with non-diabetic hyperglycaemia, and undiagnosed and self-reported diabetes. Participants were drawn from an urban community of the Bellville South suburb of Cape Town. In total, 583 subjects without a history of CVD were eligible for lifetime CVD risk estimation. Gender-specific prediction for CVD risk was calculated using the 30-year CVD interactive risk calculator. High CVD risk (> 20%) was evident in normoglycaemic and younger subjects (under 35 years). The significant predictors of CVD were sibling history of diabetes, and triglyceride, low-density lipoprotein cholesterol and glycated haemoglobin levels (p < 0.001). The high lifetime risk in normoglycaemic and younger subjects may be considered a warning that CVD might take on epidemic proportions in the near future in this country. We recommend the inclusion of education on CVD in school and university curricula.
doi:10.5830/CVJA-2010-087
PMCID: PMC3721868  PMID: 22331244
cardiovascular diseases; diabetes mellitus; epidemiology; obesity; South Africa
3.  DISTRIBUTION OF 10-YEAR AND LIFETIME PREDICTED RISKS FOR CARDIOVASCULAR DISEASE IN U.S. ADULTS: FINDINGS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 2003 TO 2006 
Background
National guidelines for primary prevention suggest consideration of lifetime risk for cardiovascular disease in addition to 10-year risk, but it is currently unknown how many U.S. adults would be identified as having low short-term but high lifetime predicted risk if stepwise stratification were employed.
Methods and Results
We included 6,329 CVD-free and nonpregnant individuals aged 20 to 79 years, representing approximately 156 million U.S. adults, from the National Health and Nutrition Examination Survey 2003–2004 and 2005–2006. We assigned 10-year and lifetime predicted risks to stratify participants into three groups: low 10-year (<10%)/low lifetime (<39%) predicted risk, low 10-year (<10%)/high lifetime (≥39%) predicted risk, and high 10-year (≥10%) predicted risk or diagnosed diabetes. The majority of U.S. adults (56%, or 87 million individuals) are at low short-term but high lifetime predicted risk for cardiovascular disease. Twenty-six percent (41 million adults) are at low short-term and low lifetime predicted risk, and only 18% (28 million individuals) are at high short-term predicted risk. The addition of lifetime risk estimation to 10-year risk estimation identifies higher risk women and younger men in particular.
Conclusions
Whereas 82% of U.S. adults are at low short-term risk, two-thirds of this group, or 87 million people, are at high lifetime predicted risk for cardiovascular disease. These results provide support for use of a stepwise stratification system aimed at improving risk communication, and they provide a baseline for public health efforts aimed at increasing the proportion of Americans with low short-term and low lifetime risk for cardiovascular disease.
doi:10.1161/CIRCOUTCOMES.109.869727
PMCID: PMC3058791  PMID: 20123666
4.  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.
doi:10.1093/aje/kws169
PMCID: PMC3571256  PMID: 23043127
air pollution; atherosclerosis; cardiovascular diseases; environmental exposure; epidemiologic methods; particulate matter
5.  LIFETIME RISKS FOR CARDIOVASCULAR DISEASE MORTALITY BY CARDIORESPIRATORY FITNESS LEVELS MEASURED AT AGE 45-, 55-, AND 65-YEARS IN MEN: THE COOPER CENTER LONGITUDINAL STUDY 
Objectives
To determine the association between fitness and lifetime risk for cardiovascular disease (CVD).
Background
Higher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD.
Methods
We followed 11,049 men who underwent clinical examination at the Cooper Clinic in Dallas, TX before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by Balke protocol and categorized according to treadmill time into low-, intermediate-, and high- fitness with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45-, 55-, and 65-years with non-CVD death as the competing event.
Results
Differences in fitness levels (low- fitness versus high- fitness) were associated with marked differences in the lifetime risks for CVD death at each index age (age 45: 13.7% versus 3.4%; age 55: 34.2% versus 15.3%; age 65: 35.6% versus 17.1%). These associations were strongest among individuals with CVD risk factors.
Conclusions
A single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among individuals with a high burden of CVD risk factors.
doi:10.1016/j.jacc.2010.10.056
PMCID: PMC3608397  PMID: 21474041
cardiovascular disease; epidemiology; exercise testing; lifetime risk
6.  Burden of Cardiovascular Risk Factors, Subclinical Atherosclerosis, and Incident Cardiovascular Events Across Dimensions of Religiosity: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Circulation  2010;121(5):659-666.
Background
Religious involvement has been associated with improved health practices and outcomes; however, no ethnically-diverse community-based study has examined differences in cardiac risk factors, subclinical cardiovascular disease, and cardiovascular disease (CVD) events across levels of religiosity.
Methods and Results
We included 5474 White, Black, Hispanic, and Chinese participants who attended Exam 2 of the NHLBI’s MESA study. We compared cross-sectional differences in cardiac risk factors and subclinical CVD, and longitudinal CVD event rates across self-reported levels of religious participation, prayer/meditation, and spirituality. Multivariable-adjusted regression models were fitted to assess associations of measures of religiosity with risk factors, subclinical CVD, and CVD events. MESA participants (52.4% female, mean age 63) with greater levels of religious participation were more likely to be female and black. After adjustment for demographic covariates, participants who attended services daily, compared with never, were significantly more likely to be obese (adjusted odds ratio 1.57, 95% confidence interval [CI] 1.12 – 1.72), but less likely to smoke (adjusted odds ratio 0.39, 95% CI 0.26 – 0.58). Results were similar for those with frequent prayer/meditation or high levels of spirituality. There were no consistent patterns of association observed between measures of religiosity and presence/extent of subclinical CVD at baseline or incident CVD events during longitudinal follow up over 4 years.
Conclusions
Our results do not confirm those of previous studies associating greater religiosity with overall better health risks and status, at least with regard to CVD. There was no reduction in risk for CVD events associated with greater religiosity.
doi:10.1161/CIRCULATIONAHA.109.879973
PMCID: PMC2871276  PMID: 20100975
Religion; Cardiovascular diseases; Obesity
7.  Distribution of 10-Year and Lifetime Predicted Risk for Cardiovascular Disease Prior to Surgery in the Longitudinal Assessment of Bariatric Surgery-2 Study 
The American journal of cardiology  2012;110(8):1130-1137.
Primary prevention guidelines recommend calculation of lifetime cardiovascular disease (CVD) predicted risk among individuals who may not meet criteria for high short-term (10-year) ATP-III risk for coronary heart disease (CHD). Both extreme obesity and bariatric surgery are more common among women, who often have low short-term predicted CHD risk. The distribution and correlates of lifetime CVD predicted risk, however, have not yet been evaluated among bariatric surgery candidates. Using established 10-year (ATP-III) CHD and lifetime CVD risk prediction algorithms and pre-surgery risk factors, participants from the Longitudinal Assessment of Bariatric Surgery-2 study without prevalent CVD (n=2070) were stratified into 3 groups: low 10-year (<10%)/low lifetime (<39%) predicted risk, low 10-year (<10%)/high lifetime (≥39%) predicted risk, and high 10-year (≥10% predicted risk or diagnosed diabetes.) Participants were predominantly white (86%), women (80%), with a median age of 45 years and median BMI of 45.6 kg/m2. High 10-year CHD predicted risk was common (36.5%), and associated with diabetes, male sex and older age, but not with higher BMI or hs-c-reactive protein. Most (76%) participants with low 10-year predicted risk had high lifetime CVD predicted risk, which was associated with dyslipidemia and hypertension, but not with BMI, waist circumference, HDL cholesterol or hs-C-reactive protein. In conclusion, bariatric surgery candidates without diabetes or existing CVD are likely to have low short-term, but high lifetime CVD predicted risk. Current data support the need for long-term monitoring and treatment of elevated CVD risk factors among bariatric surgery patients, to maximize lifetime CVD risk reduction.
Clinical Trial Registration
Long-term Effects of Bariatric Surgery, #NCT00465829, http://www.clinicaltrials.gov/ct2/results?term=%23NCT00465829
doi:10.1016/j.amjcard.2012.05.054
PMCID: PMC3462227  PMID: 22742719
Cardiovascular disease; extreme obesity; bariatric surgery; lipids
8.  Lifetime Risk of Cardiovascular Disease Among Individuals With and Without Diabetes Stratified by Obesity Status in the Framingham Heart Study  
Diabetes Care  2008;31(8):1582-1584.
OBJECTIVE—We assessed the lifetime risk of cardiovascular disease (CVD) among individuals with and without obesity and diabetes.
RESEARCH DESIGN AND METHODS—Participants were drawn from the original and offspring cohorts of the Framingham Heart Study. Lifetime (30-year) risk of CVD was assessed using a modified Kaplan-Meier approach adjusting for the competing risk of death, beginning from age 50 years.
RESULTS—Over 30 years, the lifetime risk of CVD among women with diabetes was 54.8% among normal-weight women and 78.8% among obese women. Among normal-weight men with diabetes, the lifetime risk of CVD was 78.6%, whereas it was 86.9% among obese men.
CONCLUSIONS—The lifetime risk of CVD among individuals with diabetes is high, and this relationship is further accentuated with increasing adiposity.
doi:10.2337/dc08-0025
PMCID: PMC2494632  PMID: 18458146
9.  Atherosclerosis profile and incidence of cardiovascular events: a population-based survey 
Background
Atherosclerosis is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD) events. This study evaluated the characteristics of individuals with a diagnosis of atherosclerosis and estimated the incidence of CVD events to assist in the early identification of high-risk individuals.
Methods
Respondents to the US SHIELD baseline survey were followed for 2 years to observe incident self-reported CVD. Respondents had subclinical atherosclerosis if they reported a diagnosis of narrow or blocked arteries/carotid artery disease without a past clinical CVD event (heart attack, stroke or revascularization). Characteristics of those with atherosclerosis and incident CVD were compared with those who did not report atherosclerosis at baseline but had CVD in the following 2 years using chi-square tests. Logistic regression model identified characteristics associated with atherosclerosis and incident events.
Results
Of 17,640 respondents, 488 (2.8%) reported having subclinical atherosclerosis at baseline. Subclinical atherosclerosis was associated with age, male gender, dyslipidemia, circulation problems, hypertension, past smoker, and a cholesterol test in past year (OR = 2.2) [all p < 0.05]. Incident CVD was twice as high in respondents with subclinical atherosclerosis (25.8%) as in those without atherosclerosis or clinical CVD (12.2%). In individuals with subclinical atherosclerosis, men (RR = 1.77, p = 0.050) and individuals with circulation problems (RR = 2.36, p = 0.003) were at greatest risk of experiencing CVD events in the next 2 years.
Conclusion
Self-report of subclinical atherosclerosis identified an extremely high-risk group with a >25% risk of a CVD event in the next 2 years. These characteristics may be useful for identifying individuals for more aggressive diagnostic and therapeutic efforts.
doi:10.1186/1471-2261-9-46
PMCID: PMC2753582  PMID: 19754940
10.  Prediction and classification of cardiovascular disease risk in older adults with diabetes 
Diabetologia  2012;56(2):275-283.
Aims/hypothesis
We sought to derive and validate a cardiovascular disease (CVD) prediction algorithm for older adults with diabetes, and evaluate the incremental benefit of adding novel circulating biomarkers and measures of subclinical atherosclerosis.
Methods
As part of the Cardiovascular Health Study (CHS), a population-based cohort of adults aged ≥65 years, we examined the 10 year risk of myocardial infarction, stroke and cardiovascular death in 782 older adults with diabetes, in whom 265 events occurred. We validated predictive models in 843 adults with diabetes, who were followed for 7 years in a second cohort, the Multi-Ethnic Study of Atherosclerosis (MESA); here 71 events occurred.
Results
The best fitting standard model included age, smoking, systolic blood pressure, total and HDL-cholesterol, creatinine and the use of glucose-lowering agents; however, this model had a C statistic of 0.64 and poorly classified risk in men. Novel biomarkers did not improve discrimination or classification. The addition of ankle–brachial index, electrocardiographic left ventricular hypertrophy and internal carotid intima–media thickness modestly improved discrimination (C statistic 0.68; p=0.002) and classification (net reclassification improvement [NRI] 0.12; p=0.01), mainly in those remaining free of CVD. Results were qualitatively similar in the MESA, with a change in C statistic from 0.65 to 0.68 and an NRI of 0.09 upon inclusion of subclinical disease measures.
Conclusions/interpretation
Standard clinical risk factors and novel biomarkers poorly discriminate and classify CVD risk in older adults with diabetes. The inclusion of subclinical atherosclerotic measures modestly improves these features, but to develop more robust risk prediction, a better understanding of the pathophysiology and determinants of CVD in this patient group is needed.
doi:10.1007/s00125-012-2772-1
PMCID: PMC3537882  PMID: 23143166
Biological markers; Cardiovascular diagnostic techniques; Cardiovascular disease; Cohort; Diabetes; Regression analysis; Risk factors
11.  Impact of Subclinical Atherosclerosis on Cardiovascular Disease Events in Individuals With Metabolic Syndrome and Diabetes 
Diabetes Care  2011;34(10):2285-2290.
OBJECTIVE
While metabolic syndrome (MetS) and diabetes confer greater cardiovascular disease (CVD) risk, recent evidence suggests that individuals with these conditions have a wide range of risk. We evaluated whether screening for coronary artery calcium (CAC) and carotid intimal-medial thickness (CIMT) can improve CVD risk stratification over traditional risk factors (RFs) in people with MetS and diabetes.
RESEARCH DESIGN AND METHODS
We assessed CAC and CIMT in 6,603 people aged 45–84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). Cox regression examined the association of CAC and CIMT with coronary heart disease (CHD) and CVD over 6.4 years in MetS and diabetes.
RESULTS
Of the subjects, 1,686 (25%) had MetS but no diabetes and 881 (13%) had diabetes. Annual CHD event rates were 1.0% among MetS and 1.5% for diabetes. Ethnicity and RF-adjusted hazard ratios for CHD for CAC 1–99 to ≥400 vs. 0 in subjects with neither MetS nor diabetes ranged from 2.6 to 9.5; in those with MetS, they ranged from 3.9 to 11.9; and in those with diabetes, they ranged from 2.9 to 6.2 (all P < 0.05 to P < 0.001). Findings were similar for CVD. CAC increased the C-statistic for events (P < 0.001) over RFs and CIMT in each group while CIMT added negligibly to prediction over RFs.
CONCLUSIONS
Individuals with MetS or diabetes have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and CVD events is improved by CAC more than by CIMT. Screening for CAC or CIMT can stratify risk in people with MetS and diabetes and support the latest recommendations regarding CAC screening in those with diabetes.
doi:10.2337/dc11-0816
PMCID: PMC3177707  PMID: 21844289
12.  Signs of subclinical coronary atherosclerosis in relation to risk factor distribution in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR) 
European Heart Journal  2008;29(22):2782-2791.
Aims
Modern imaging technology allows us the visualization of coronary artery calcification (CAC), a marker of subclinical coronary atherosclerosis. The prevalence, quantity, and risk factors for CAC were compared between two studies with similar imaging protocols but different source populations: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR).
Methods and results
The measured CAC in 2220 MESA participants were compared with those in 3126 HNR participants with the inclusion criteria such as age 45–75 years, Caucasian race, and free of baseline cardiovascular disease. Despite similar mean levels of CAC of 244.6 among participants in MESA and of 240.3 in HNR (P = 0.91), the prevalence of CAC > 0 was lower in MESA (52.6%) compared with HNR (67.0%) with a prevalence rate ratio of CAC > 0 of 0.78 [95% confidence interval (CI): 0.72–0.85] after adjustment for known risk factors. Consequently, among participants with CAC > 0, the participants in MESA tended to have higher levels of CAC than those in HNR (ratio of CAC levels: 1.39; 95% CI: 1.19–1.63), since many HNR participants have small (near zero) CAC values.
Conclusions
The CAC prevalence was lower in the United States (MESA) cohort than in the German (HNR) cohort, which may be explained by more favourable risk factor levels among the MESA participants. The predictors for increased levels of CAC were, however, similar in both cohorts with the exception that male gender, blood pressure, and body mass index were more strongly associated in the HNR cohort.
doi:10.1093/eurheartj/ehn439
PMCID: PMC2582985  PMID: 18845666
Epidemiology; Atherosclerosis; Coronary artery calcium; Risk factors; Screening
13.  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
14.  High lifetime risk of cardiovascular disease vs low 10-year Framingham risk score in HIV-infected subjects under ART in Spain: the Coronator study 
Purpose
Due to the relative low age of HIV-infected patients, Framingham risk score (FRS) usually estimates a low CVD risk. Lifetime risk estimations use the risk of developing CVD over the course of an individual's remaining lifetime and may be useful in communicating the risk of CVD to young patients. Our aim is to estimate the lifetime risk of CVD in a representative sample of HIV patients under antiretroviral therapy in Spain.
Methods
Cross-sectional analysis in 10 HIV units across Spain, including information on demographics, HIV disease status, treatment history and cardiovascular risk factors of subject under ART. Lifetime CVD risk was calculated with the method of Berry et al, which classifies the lifetime risk in five mutually exclusive categories: 1. All risk factors are optimal; 2. At least one risk factor is not optimal; 3. At least one risk factor is elevated; 4. One major risk factor is present; and 5. Two or more major risk factors are present. Risk factors included are cholesterol level, blood pressure, diabetes and tobacco smoking. We grouped these five categories in two major groups, low-risk (groups 1+2+3) and high-risk category (groups 4+5). We calculated the prevalence of having a high lifetime risk, and its crude and aOR (adjusted by age, sex, place of origin, education level, transmission category, time since HIV diagnosis, CDC stage, current and nadir CD4 count, HCV coinfection, time on current and total ART, being on the first ART regimen, and PI vs. NNRTI regimen).
Results
We included 839 subjects free of previous CVD disease: 72% men, median age 45.6y, median CD4 count 598 cells, median time since HIV diagnosis 11y, median time on ART 6.3y, 87% had undetectable VL. Estimated 10-year CVD risk was low (<5%) in 78% of the patients, and intermediate (5–10%) in 20%. Lifetime risk estimation shows a high risk profile for 71.4% of the population studied (≥1 major risk factors). Factors significantly and independently associated with an increased lifetime risk were older age, non-Spanish origin and longer time on ART. Adjusted OR for patients on ART longer than 10 years (vs<5 years) was 2.2 [95% CI 1.13–4.34]. No relationship was found with current or nadir CD4 lymphocyte counts, CDC stage C, HCV confection or type of ART.
Conclusions
There are significant disparities between the low 10y CVD risk estimated with FRS and the elevated lifetime risk in HIV patients on ART. Prolonged ART is associated with an increased CVD lifetime risk.
doi:10.7448/IAS.15.6.18109
PMCID: PMC3512548
15.  A priori– defined dietary patterns and markers of cardiovascular disease risk in the Multi-Ethnic Study of Atherosclerosis (MESA)2 
Background
The level of detail regarding the dietary intake necessary to characterize associations between diet and cardiovascular disease (CVD) risk is uncertain.
Objective
We evaluated a unique a priori– defined dietary pattern in relation to several traditional and novel CVD risk factors.
Design
At the baseline examination, diet (by food-frequency questionnaire), markers of inflammation, subclinical atherosclerosis, renal disease, vascular compliance, and other traditional risk factors were measured in 5089 men and women aged 45−84 y without clinical CVD or diabetes from the Multi-Ethnic Study of Atherosclerosis (MESA). We defined a Comprehensive Healthy Dietary Pattern by summing weighted categorical ranks of 36 narrowly defined food groups (21 rated favorably with categorical ranks × +1.0 and 15 rated unfavorably with categorical ranks × −1.0). We also defined a Simplified Healthy Dietary Pattern composed of 3 favorable (whole grains, fruit, and seeds and nuts) and 3 unfavorable (added fats and oils, processed meats, and fried potatoes) food groups using similar scoring techniques and determined the difference between the comprehensive and simplified scores.
Results
The Comprehensive Healthy Dietary Pattern was associated with lower urinary albumin:creatinine ratios, common carotid intima-media thickness, measures of adiposity, and inflammatory marker, triacylglycerol, and insulin concentrations. The magnitudes of most of the associations were similar between the 2 dietary patterns, but some differences were observed between scores. Dietary patterns were not associated with blood pressure, coronary artery calcification, internal carotid intima-media thickness, or the ankle brachial index.
Conclusions
Many food groups contribute to the characterization of relations with a variety of CVD risk markers, although only 6 food groups contribute much of the information in MESA.
PMCID: PMC2504029  PMID: 18614740
16.  Associations Between a Parental History of Premature Cardiovascular Disease and Coronary Calcium and Carotid Intima-Media Thickness: The Coronary Artery Risk Development In Young Adults (CARDIA) Study 
European journal of preventive cardiology  2012;10.1177/2047487312462801.
Background
It is unclear if associations between a parental history of premature CVD (pCVD) and subclinical atherosclerosis are attenuated by adjustment for long-term risk factors levels through middle adulthood.
Design
Prospective community-based cohort study
Methods
CARDIA participants who attended the year 20 exam (N=2283, mean age 45 years) were grouped by pCVD status: maternal only, paternal only, any parental, and no parental history (referent). We used separate logistic regression models, adjusted for average risk factor levels over 20 years' follow-up to assess associations of parental pCVD and subclinical atherosclerosis in offspring.
Results
White participants with any parental history of pCVD had a higher odds of CAC>0 than participants with no parental history (OR 1.55; 95% CI, 1.01-2.37). This was largely driven by the association of a paternal history of pCVD with CAC>0 (OR 2.15; 95% CI, 1.42-3.23), which was minimally attenuated by multivariable adjustment (OR 2.09; 95% CI, 1.31-3.32). Similarly, adjusted associations between parental pCVD and IMT > 90%tile were observed in white participants with a paternal history of pCVD (OR=1.93; 95% CI, 1.10-3.39) and any parental history pCVD (OR 1.67; 95% CI, 1.02-2.74). No significant associations between a parental history of pCVD and the odds of subclinical atherosclerosis were observed in black participants.
Conclusions
Parental pCVD is independently associated with early development of subclinical atherosclerosis; these associations may be race-specific for participants in their 5th decade of life.
doi:10.1177/2047487312462801
PMCID: PMC3779512  PMID: 23027592
Family History of Premature Cardiovascular Disease; Coronary Artery Calcium; Carotid Intima-Media Thickness
17.  Do Neighborhood Socioeconomic Deprivation and Low Social Cohesion Predict Coronary Calcification? 
American Journal of Epidemiology  2010;172(3):288-298.
Growing evidence suggests that neighborhood characteristics may influence the risk of coronary heart disease. No studies have yet explored associations of neighborhood attributes with subclinical atherosclerosis in younger adult populations. Using data on 2,974 adults (1,699 women, 1,275 men) aged 32–50 years in 2000 from the Coronary Artery Disease Risk Development in Young Adults (CARDIA) Study and 2000 US Census block-group-level data, the authors estimated multivariable-adjusted associations of neighborhood socioeconomic deprivation and perceived neighborhood cohesion with odds of coronary artery calcification (CAC) 5 years later. Among women, the quartiles of highest neighborhood deprivation and lowest cohesion were associated with higher odds of CAC after adjustment for individual-level demographic and socioeconomic factors (for deprivation, odds ratio = 2.49, 95% confidence interval: 1.22, 5.08 (P for trend = 0.03); for cohesion, odds ratio = 1.87, 95% confidence interval: 1.10, 3.16 (P for trend = 0.02)). Associations changed only slightly after adjustment for behavioral, psychosocial, and biologic factors. Among men, neither neighborhood deprivation nor cohesion was related to CAC. However, among men in deprived neighborhoods, low cohesion predicted higher CAC odds (for interaction between neighborhood deprivation and cohesion, P = 0.03). This study provides evidence on associations of neighborhood deprivation and cohesion with CAC in younger, asymptomatic adults. Neighborhood attributes may contribute to subclinical atherosclerosis.
doi:10.1093/aje/kwq098
PMCID: PMC2917055  PMID: 20610467
atherosclerosis; coronary disease; residence characteristics; risk factors; social environment
18.  Differences in Kidney Function and Incident Hypertension: The Multi-Ethnic Study of Atherosclerosis 
Annals of internal medicine  2008;148(7):501-508.
Background
Kidney disease and hypertension commonly coexist, yet the direction of their association is still debated.
Objective
To evaluate whether early kidney dysfunction, measured by serum cystatin C levels and urinary albumin excretion, predates hypertension in adults without clinically recognized kidney or cardiovascular disease.
Design
Observational cohort study using data from 2000 to 2005.
Setting
The MESA (Multi-Ethnic Study of Atherosclerosis), a community-based study of subclinical cardiovascular disease in adults age 45 to 84 years.
Participants
2767 MESA participants without prevalent hypertension, cardiovascular disease, or clinically recognized kidney disease (an estimated glomerular filtration rate <60 mL/min per 1.73 m2 or microalbuminuria).
Measurements
Cystatin C was measured by using a nephelometer, and urinary albumin and creatinine were measured from a spot morning collection. The primary outcome was incident hypertension, defined as systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or use of an antihypertensive medication.
Results
During a median follow-up of 3.1 years, 19.7% of the cohort (545 participants) developed hypertension. After adjustment for established hypertension risk factors, each 15-nmol/L increase in cystatin C was associated with a statistically significant 15% greater incidence of hypertension (P = 0.017). The highest sex-specific quartile of urinary albumin–creatinine ratio was associated with a statistically insignificant 16% greater incidence of hypertension (P = 0.192) compared with the lowest quartile. No statistical evidence suggested a multiplicative interaction.
Limitations
Unmeasured characteristics may have confounded observed associations of kidney markers with hypertension. Follow-up was relatively short. Hypertension that may have occurred between study visits or hypertension that was not captured by standard cuff measurements may have been missed.
Conclusion
Differences in kidney function, indicated by cystatin C levels, are associated with incident hypertension among individuals without clinical kidney or cardiovascular disease. These population-based findings complement experimental work implicating early kidney damage in the pathogenesis of essential hypertension.
PMCID: PMC3044648  PMID: 18378946
19.  The Association Between A1C and Subclinical Cardiovascular Disease 
Diabetes Care  2009;32(9):1727-1733.
OBJECTIVE
To test the hypothesis that A1C is associated with subclinical cardiovascular disease (CVD) in a population without evident diabetes, after adjusting for traditional CVD risk factors and BMI.
RESEARCH DESIGN AND METHODS
This was a cross-sectional study of 5,121 participants without clinically evident CVD or diabetes (fasting glucose ≥7.0 mmol/l or use of diabetes medication), aged 47–86 years, enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Measurements included carotid intimal-medial wall thickness (CIMT) and coronary artery calcification (CAC). Results were adjusted for age, sex, ethnicity, smoking, systolic blood pressure, LDL cholesterol, HDL cholesterol, antihypertensive medication use, lipid-lowering medication use, and BMI.
RESULTS
Compared with those in the lowest quartile for A1C ([mean ± SD] 5.0 ± 0.2%), participants in the highest quartile (6.0 ± 0.3%) had higher adjusted mean values for common CIMT (0.85 vs. 0.87 mm, P = 0.003) and internal CIMT (1.01 vs. 1.08 mm, P = 0.003). A1C quartile was not associated with prevalence of CAC in the entire cohort (P = 0.27); however, the association was statistically significant in women (adjusted prevalence of CAC in lowest and highest A1C quartiles 37.5 vs. 43.0%, P = 0.01). Among those with some CAC, higher A1C quartile tended to be associated with higher CAC score, but the results were not statistically significant (adjusted P = 0.11).
CONCLUSIONS
In this multiethnic cohort, there were small, positive associations between A1C, common CIMT, and internal CIMT in the absence of clinically evident diabetes. An association between higher A1C and CAC prevalence was evident only in women.
doi:10.2337/dc09-0074
PMCID: PMC2732160  PMID: 19549732
20.  Age-Related Macular Degeneration and Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis 
Ophthalmology  2011;119(4):765-770.
Objective
To determine whether age-related macular degeneration (AMD) is a risk indicator for coronary heart disease (CHD) and cardiovascular disease (CVD) events independent of other known risk factors in a multi-ethnic cohort.
Design
Population-based prospective cohort study.
Participants
A diverse population sample of 6233 men and women aged 45–84 without known CVD from the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods
Participants in the MESA had retinal photographs taken between 2002 and 2003. Photographs were evaluated for AMD. Incident CHD/CVD events were ascertained during clinical follow-up visits for up to 8 years after the retinal images were taken.
Main Outcome Measures
Incident CHD/CVD events.
Results
Of the 6814 persons at risk of CHD, there were 893 participants with early AMD (13.1%) and 27 (0.5%) at baseline. Over a mean follow-up period of 5.4 years, there was no statistically significant difference in incident CHD or CVD between the AMD and non-AMD groups (5.0%vs. 3.9%, p=0.13 for CHD and 6.6 vs. 5.5%, p=0.19 for CVD, respectively). In Cox regression models adjusting for CVD risk factors, there was no significant relationship between presence of any AMD and any CHD/CVD events (HR=0.99, 95% CI 0.74–1.33, p=0.97). No significant association was found between subgroups of early AMD or late AMD and incident CHD/CVD events.
Conclusions
In persons without a history of cardiovascular disease, AMD was not associated with an increased risk of CHD or CVD.
doi:10.1016/j.ophtha.2011.09.044
PMCID: PMC3314126  PMID: 22197438
21.  Relationships of Mitral Annular Calcification to Cardiovascular Risk Factors: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Atherosclerosis  2010;213(2):558-562.
Background
Mitral annular calcification (MAC) is a fibrous, degenerative calcification of the mitral valve. The relationship between MAC and cardiovascular disease (CVD) risk factors is not well defined. Thus, we performed a cross-sectional study to determine which CVD risk factors are independently associated with MAC in the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods
MESA includes 6,814 women and men ages 45–84 years old without apparent CVD in 4 ethnic groups (12% Chinese, 38% Caucasian, 22% Hispanic, and 28% African-American). MAC was defined by presence of calcium in the mitral annulus by cardiac computed tomography at enrollment. Multivariable logistic regression was used to evaluate relationships between MAC and CVD risk factors.
Results
The overall prevalence of MAC was 9%. The prevalence of MAC was highest in Caucasians (12%), followed by Hispanics (10%), African Americans (7%) and was lowest in Chinese (5%). Characteristics associated with MAC included age (p<0.01), female gender (p<0.01), increased body mass index (BMI) (p=0.03), and former smoking status (p<0.008). The MAC group had a higher prevalence of hypertension, diabetes mellitus (DM), and family history of heart attack (all p<0.001). After adjusting for all variables, age, female gender, diabetes mellitus, and increased BMI remained strongly associated with MAC.
Conclusions
Age, female gender, DM, and increased BMI were significantly associated with MAC. Prevalence of MAC was strongly associated with female gender and increasing age in all ethnicities.
doi:10.1016/j.atherosclerosis.2010.08.072
PMCID: PMC2997868  PMID: 20926076
Mitral annular calcification; MESA; Cardiac CT; risk factors
22.  Age-Modification of Lipoprotein, Lipid, and Lipoprotein Ratio-Associated Risk for Coronary Artery Calcium (From the Multi-Ethnic Study of Atherosclerosis [MESA]) 
The American journal of cardiology  2009;105(3):352-358.
Though abnormal lipoproteins and lipoprotein ratios are powerful risk factors for clinical cardiovascular (CV) events, these associations are stronger in younger compared to older age. Whether age modifies the relationships of lipoproteins and lipoprotein ratios to the relative risk for subclinical CV disease (CVD), as assessed by coronary artery calcium (CAC) scores, has not been examined in a contemporary, multi-ethnic cohort. We performed multivariate relative risk regression to determine the relative risks (RRs) for associations of lipoproteins and lipoprotein ratios with prevalent CAC in participants in MESA. Participants were community-dwelling adults ages 45–84 years without baseline clinically apparent CVD. We excluded those on lipid lowering therapy (15%), and stratified results by decades of age. 5,092 participants met inclusion criteria. In fully adjusted models, per standard deviation (SD) of low-density lipoprotein (LDL), age-stratified, adjusted relative risks (RRs) for CAC were 1.17 (95% Confidence Interval (CI) 1.07–1.28) for those aged 45–54 but 1.05 (95% CI 1.01–1.10) for those aged 75–84 (p-interaction = 0.12). The RR per SD of Total/HDL cholesterol ratio was 1.20 (95% CI 1.12–1.29) for those aged 45–54 but only 1.04 (1.00–1.09) for those aged 75–84 (p-interaction <0.001). Lipoproteins and lipoprotein ratios were associated with increased RRs for CAC across all age categories. However, these associations were markedly attenuated by age. In conclusion, abnormal lipoproteins in middle age are a powerful risk factor for early atherosclerosis as manifested by prevalent CAC.
doi:10.1016/j.amjcard.2009.09.040
PMCID: PMC2855892  PMID: 20102947
lipoproteins; age; coronary artery calcium
23.  Lifetime Risks of Cardiovascular Disease 
The New England Journal of Medicine  2012;366(4):321-329.
BACKGROUND
The lifetime risks of cardiovascular disease have not been reported across the age spectrum in black adults and white adults.
METHODS
We conducted a meta-analysis at the individual level using data from 18 cohort studies involving a total of 257,384 black men and women and white men and women whose risk factors for cardiovascular disease were measured at the ages of 45, 55, 65, and 75 years. Blood pressure, cholesterol level, smoking status, and diabetes status were used to stratify participants according to risk factors into five mutually exclusive categories. The remaining lifetime risks of cardiovascular events were estimated for participants in each category at each age, with death free of cardiovascular disease treated as a competing event.
RESULTS
We observed marked differences in the lifetime risks of cardiovascular disease across risk-factor strata. Among participants who were 55 years of age, those with an optimal risk-factor profile (total cholesterol level, <180 mg per deciliter [4.7 mmol per liter]; blood pressure, <120 mm Hg systolic and 80 mm Hg diastolic; nonsmoking status; and nondiabetic status) had substantially lower risks of death from cardiovascular disease through the age of 80 years than participants with two or more major risk factors (4.7% vs. 29.6% among men, 6.4% vs. 20.5% among women). Those with an optimal risk-factor profile also had lower lifetime risks of fatal coronary heart disease or nonfatal myocardial infarction (3.6% vs. 37.5% among men, <1% vs. 18.3% among women) and fatal or nonfatal stroke (2.3% vs. 8.3% among men, 5.3% vs. 10.7% among women). Similar trends within risk-factor strata were observed among blacks and whites and across diverse birth cohorts.
CONCLUSIONS
Differences in risk-factor burden translate into marked differences in the lifetime risk of cardiovascular disease, and these differences are consistent across race and birth cohorts. (Funded by the National Heart, Lung, and Blood Institute.)
doi:10.1056/NEJMoa1012848
PMCID: PMC3336876  PMID: 22276822
24.  Subclinical Atherosclerosis is Weakly Associated with Lower Cognitive Function in Healthy Hyperhomocysteinemic Adults without Clinical Cardiovascular Disease 
OBJECTIVE
Atherosclerosis is the most common pathologic process underlying cardiovascular disease (CVD). It is not well known whether subclinical atherosclerosis is an independent risk factor for lower cognitive function among individuals without clinically evident CVD.
METHODS
We examined cross-sectional associations between subclinical atherosclerosis and cognitive function in a community-based sample of otherwise healthy adults with plasma homocysteine ≥8.5 µmol/L enrolled in the BVAIT study (n=504, mean age 61 years). Carotid artery intima-media thickness (CIMT), coronary (CAC) and abdominal aortic calcium (AAC) were used to measure subclinical atherosclerosis. Cognitive function was assessed with a battery of neuropsychological tests. A principal components analysis was used to extract five uncorrelated cognitive factors from scores on individual tests, and a measure of global cognition was derived. Multivariable linear regression was used to examine the association between subclinical atherosclerosis and cognitive function, adjusting for other correlates of cognition.
RESULTS
Increasing thickness of CIMT was associated with significantly lower scores on the verbal learning factor (β = −0.07 per 0.1 mm increase CIMT [SE(β)=0.03], p=0.01). CAC and AAC were not individually associated with any of the cognitive factors.
CONCLUSIONS
This study provides evidence that increasing CIMT is weakly associated with lower verbal learning abilities but not global cognition in a population of otherwise healthy middle-to-older aged adults with elevated plasma homocysteine but without clinically evident CVD. The association between CIMT and poor verbal learning may pertain particularly to men.
doi:10.1002/gps.2134
PMCID: PMC2661006  PMID: 18836986
cognitive function; atherosclerosis; cardiovascular disease; memory; verbal learning
25.  Lifetime Risk and Years Lived Free of Total Cardiovascular Disease 
Context
Estimates of lifetime risk (LTR) for total cardiovascular disease (tCVD) may provide projections of the future population burden of cardiovascular disease and may assist in clinician-patient risk communication. To date, no LTR estimates of tCVD have been reported.
Objective
To calculate LTR estimates of tCVD by index age [45, 55, 65, 75 years(y)] and risk factor strata and to estimate years lived free of CVD across risk factor strata.
Design, Setting, and Participants
Pooled survival analysis of up to 905,115 person-years of data from 1964 through 2008 from 5 NHLBI-funded community-based cohorts: Framingham Heart Study, Framingham Offspring Study, Atherosclerosis Risk in Communities Study, Chicago Heart Association Detection Project in Industry Study and Cardiovascular Health Study.
Participants
All participants free of CVD at baseline with risk factor data (blood pressure (BP), total cholesterol (TC), diabetes and smoking status) and tCVD outcome data
Outcome Measures
Any tCVD event (including fatal and non-fatal coronary heart disease, all forms of stroke, congestive heart failure and other CVD deaths)
Results
At an index age of 45y, overall LTR for tCVD was 60.3% (95% CI, 59.3 to 61.2) for men and 55.6% (95% CI, 54.5 to 56.7) for women. Men had higher LTR estimates than women across all index ages. At index ages 55 and 65y, men and women with ≥1 elevated risk factor (BP 140-149/90-99 mmHg or TC 200-239 mg/dL but no diabetes or smoking), or 1, or ≥ 2 major risk factors (BP ≥ 160/100mmHg or on treatment; TC ≥ 240mg/dL or on treatment, diabetes mellitus, or current smoking) had LTR estimates to age 95y that exceeded 50%. Despite an optimal risk factor profile (BP < 120/80 mmHg, TC < 180 mg/dL, and no smoking or diabetes) men and women at an index age of 55y had LTR for total CVD to age 85y > 40% and 30% respectively. Compared with participants with ≥ 2 major risk factors, those with an optimal risk factor profile lived up to 14y longer free of tCVD.
Conclusions
LTR estimates for tCVD are high (>30%) for all individuals, even those with optimal risk factors in middle age. However, maintenance of optimal risk factor levels in middle age is associated with substantially longer morbidity-free survival.
doi:10.1001/jama.2012.14312
PMCID: PMC3748966  PMID: 23117780
Lifetime Risk; Cardiovascular Disease; Compression of Morbidity

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