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1.  Loci influencing blood pressure identified using a cardiovascular gene-centric array 
Ganesh, Santhi K. | Tragante, Vinicius | Guo, Wei | Guo, Yiran | Lanktree, Matthew B. | Smith, Erin N. | Johnson, Toby | Castillo, Berta Almoguera | Barnard, John | Baumert, Jens | Chang, Yen-Pei Christy | Elbers, Clara C. | Farrall, Martin | Fischer, Mary E. | Franceschini, Nora | Gaunt, Tom R. | Gho, Johannes M.I.H. | Gieger, Christian | Gong, Yan | Isaacs, Aaron | Kleber, Marcus E. | Leach, Irene Mateo | McDonough, Caitrin W. | Meijs, Matthijs F.L. | Mellander, Olle | Molony, Cliona M. | Nolte, Ilja M. | Padmanabhan, Sandosh | Price, Tom S. | Rajagopalan, Ramakrishnan | Shaffer, Jonathan | Shah, Sonia | Shen, Haiqing | Soranzo, Nicole | van der Most, Peter J. | Van Iperen, Erik P.A. | Van Setten, Jessica | Vonk, Judith M. | Zhang, Li | Beitelshees, Amber L. | Berenson, Gerald S. | Bhatt, Deepak L. | Boer, Jolanda M.A. | Boerwinkle, Eric | Burkley, Ben | Burt, Amber | Chakravarti, Aravinda | Chen, Wei | Cooper-DeHoff, Rhonda M. | Curtis, Sean P. | Dreisbach, Albert | Duggan, David | Ehret, Georg B. | Fabsitz, Richard R. | Fornage, Myriam | Fox, Ervin | Furlong, Clement E. | Gansevoort, Ron T. | Hofker, Marten H. | Hovingh, G. Kees | Kirkland, Susan A. | Kottke-Marchant, Kandice | Kutlar, Abdullah | LaCroix, Andrea Z. | Langaee, Taimour Y. | Li, Yun R. | Lin, Honghuang | Liu, Kiang | Maiwald, Steffi | Malik, Rainer | Murugesan, Gurunathan | Newton-Cheh, Christopher | O'Connell, Jeffery R. | Onland-Moret, N. Charlotte | Ouwehand, Willem H. | Palmas, Walter | Penninx, Brenda W. | Pepine, Carl J. | Pettinger, Mary | Polak, Joseph F. | Ramachandran, Vasan S. | Ranchalis, Jane | Redline, Susan | Ridker, Paul M. | Rose, Lynda M. | Scharnag, Hubert | Schork, Nicholas J. | Shimbo, Daichi | Shuldiner, Alan R. | Srinivasan, Sathanur R. | Stolk, Ronald P. | Taylor, Herman A. | Thorand, Barbara | Trip, Mieke D. | van Duijn, Cornelia M. | Verschuren, W. Monique | Wijmenga, Cisca | Winkelmann, Bernhard R. | Wyatt, Sharon | Young, J. Hunter | Boehm, Bernhard O. | Caulfield, Mark J. | Chasman, Daniel I. | Davidson, Karina W. | Doevendans, Pieter A. | FitzGerald, Garret A. | Gums, John G. | Hakonarson, Hakon | Hillege, Hans L. | Illig, Thomas | Jarvik, Gail P. | Johnson, Julie A. | Kastelein, John J.P. | Koenig, Wolfgang | März, Winfried | Mitchell, Braxton D. | Murray, Sarah S. | Oldehinkel, Albertine J. | Rader, Daniel J. | Reilly, Muredach P. | Reiner, Alex P. | Schadt, Eric E. | Silverstein, Roy L. | Snieder, Harold | Stanton, Alice V. | Uitterlinden, André G. | van der Harst, Pim | van der Schouw, Yvonne T. | Samani, Nilesh J. | Johnson, Andrew D. | Munroe, Patricia B. | de Bakker, Paul I.W. | Zhu, Xiaofeng | Levy, Daniel | Keating, Brendan J. | Asselbergs, Folkert W.
Human Molecular Genetics  2013;22(16):3394-3395.
doi:10.1093/hmg/ddt177
PMCID: PMC3888295
2.  Competing Cardiovascular Outcomes Associated with Subclinical Atherosclerosis (From the Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2013;111(11):1541-1546.
Subclinical atherosclerosis measured by coronary artery calcium (CAC) is associated with increased risk for multiple cardiovascular disease (CVD) outcomes and non-CVD death simultaneously, and we sought to determine the competing risks of specific cardiovascular disease (CVD) events and non-CVD death associated with varying burdens of subclinical atherosclerosis. We included 3095 men and 3486 women from the Multi-Ethnic Study of Atherosclerosis, aged 45–84 years, and from 4 ethnic groups. Participants were stratified by CAC scores: 0, 1–99, and ≥ 100. We used competing Cox models to determine competing cumulative incidences and hazards ratios within a group (e.g., among those with CAC ≥ 100) and hazards ratios for specific events between groups (e.g., CAC ≥ 100 vs. CAC = 0). We compared risks for specific CVD events and also compared against non-CVD death. In women, during a mean follow up of 7.1 years, the hazards ratios (HR) for any CVD event compared with a non-CVD death occurring first for CAC = 0 and CAC ≥ 100 were 1.40 (95% CI, 0.97–2.04) and 3.07 (2.02–4.67), respectively. CHD was the most common first CVD event type at all levels of CAC, and CHD rates were 9.5% vs. 1.6% (HR 6.24; 3.99–9.75) for women with CAC ≥100 compared with CAC = 0. We observed similar results in men. In conclusion, at all levels of CAC, CHD was the most common first CVD event and this analysis represents a novel approach to understanding the temporal sequence of cardiovascular events associated with atherosclerosis.
doi:10.1016/j.amjcard.2013.02.003
PMCID: PMC3657323  PMID: 23499272
coronary artery calcium; competing risks
3.  Comparison of Factors Associated with Carotid Intima-Media Thickness in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR) 
Background
The measurement of carotid intima-media thickness (CIMT) is a valid method to quantify levels of atherosclerosis. The present study was conducted to compare the strengths of associations between CIMT and cardiovascular risk factors in two different populations.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR) are two population-based prospective cohort studies of subclinical cardiovascular disease. All Caucasian subjects aged 45 to 75 years from these cohorts who were free of baseline cardiovascular disease (n = 2,820 in HNR, n = 2,270 in MESA) were combined. CIMT images were obtained using B-mode sonography at the right and left common carotid artery and measured 1 cm starting from the bulb.
Results
In both studies, age, male sex, and systolic blood pressure showed the strongest association (P < .0001 for each) for a higher CIMT. The mean of mean far wall CIMT was slightly higher in MESA participants (0.71 vs 0.67 mm). Almost all significant variables were consistent between the two cohorts in both magnitude of association with CIMT and statistical significance, including age, sex, smoking, diabetes, cholesterol levels, and blood pressure. For example, the association with systolic blood pressure was (ΔSD = 0.011; 95% confidence interval, 0.0009 to 0.014) per mm Hg in MESA and (ΔSD = 0.010; 95% confidence interval, 0.005 to 0.021) per mm Hg in HNR. This consistency persisted throughout the traditional (Framingham) risk factors.
Conclusions
A comparison of the associations between traditional cardiovascular risk factors and CIMT across two culturally diverse populations showed remarkable consistency.
doi:10.1016/j.echo.2013.03.011
PMCID: PMC3694173  PMID: 23611058
Carotid intima-media thickness; Subclinical atherosclerosis; Multi-Ethnic Study of Atherosclerosis; MESA; Heinz Nixdorf Recall Study; HNR
4.  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 
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
5.  Pulse Pressure and Subclinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis 
American Journal of Hypertension  2013;26(5):636-642.
BACKGROUND
Brachial pulse pressure (PP) has been found to be associated with markers of subclinical cardiovascular disease, including carotid intima–media thickness and left-ventricular mass index (LVMI), but it is unclear whether these associations are independent of traditional cardiovascular risk factors and of the steady, nonpulsatile component of blood pressure (BP). Moreover, it is unknown whether these associations are modified by gender, age, or race/ethnicity.
METHODS
We used multivariate linear regression models to assess the relationship between brachial PP and three markers of subclinical cardiovascular disease (CVD) (common carotid intima–media thickness (CC-IMT), internal carotid intima–media thickness (IC-IMT), and LVMI) in four race/ethnic groups in the Multi-Ethnic Study of Atherosclerosis. The models were adjusted for traditional Framingham risk factors (age, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, diabetes, smoking status), use of lipid-lowering medication, use of antihypertensive medication, study site, and mean arterial pressure (MAP).
RESULTS
The assessment was done on 6,776 participants (2,612 non-Hispanic white, 1,870 African-American, 1,494 Hispanic, and 800 Chinese persons). The associations between brachial PP and CC-IMT, IC-IMT, and LVMI were significant in fully adjusted models. The three subclinical markers also showed significant interactions with gender (P < 0.0001), with stronger interactions in men. There was an interaction with age for LVMI (P = 0.004) and IC-IMT (P = 0.008). Race/ethnicity modified the association of PP with CC-IMT.
CONCLUSIONS
Brachial PP was independently associated with subclinical CVD after adjustment for cardiovascular risk factors and mean arterial pressure (MAP). The strength of the association differed significantly for strata of gender, age, and race/ethnicity.
doi:10.1093/ajh/hps092
PMCID: PMC3657481  PMID: 23388832
pulse pressare; subclinical cardiovascular disease; carotid intima–media thickness; left ventricular mass index; aging; hypertension; arterial stiffness; blood pressure.
6.  Loci influencing blood pressure identified using a cardiovascular gene-centric array 
Ganesh, Santhi K. | Tragante, Vinicius | Guo, Wei | Guo, Yiran | Lanktree, Matthew B. | Smith, Erin N. | Johnson, Toby | Castillo, Berta Almoguera | Barnard, John | Baumert, Jens | Chang, Yen-Pei Christy | Elbers, Clara C. | Farrall, Martin | Fischer, Mary E. | Franceschini, Nora | Gaunt, Tom R. | Gho, Johannes M.I.H. | Gieger, Christian | Gong, Yan | Isaacs, Aaron | Kleber, Marcus E. | Leach, Irene Mateo | McDonough, Caitrin W. | Meijs, Matthijs F.L. | Mellander, Olle | Molony, Cliona M. | Nolte, Ilja M. | Padmanabhan, Sandosh | Price, Tom S. | Rajagopalan, Ramakrishnan | Shaffer, Jonathan | Shah, Sonia | Shen, Haiqing | Soranzo, Nicole | van der Most, Peter J. | Van Iperen, Erik P.A. | Van Setten, Jessic A. | Vonk, Judith M. | Zhang, Li | Beitelshees, Amber L. | Berenson, Gerald S. | Bhatt, Deepak L. | Boer, Jolanda M.A. | Boerwinkle, Eric | Burkley, Ben | Burt, Amber | Chakravarti, Aravinda | Chen, Wei | Cooper-DeHoff, Rhonda M. | Curtis, Sean P. | Dreisbach, Albert | Duggan, David | Ehret, Georg B. | Fabsitz, Richard R. | Fornage, Myriam | Fox, Ervin | Furlong, Clement E. | Gansevoort, Ron T. | Hofker, Marten H. | Hovingh, G. Kees | Kirkland, Susan A. | Kottke-Marchant, Kandice | Kutlar, Abdullah | LaCroix, Andrea Z. | Langaee, Taimour Y. | Li, Yun R. | Lin, Honghuang | Liu, Kiang | Maiwald, Steffi | Malik, Rainer | Murugesan, Gurunathan | Newton-Cheh, Christopher | O'Connell, Jeffery R. | Onland-Moret, N. Charlotte | Ouwehand, Willem H. | Palmas, Walter | Penninx, Brenda W. | Pepine, Carl J. | Pettinger, Mary | Polak, Joseph F. | Ramachandran, Vasan S. | Ranchalis, Jane | Redline, Susan | Ridker, Paul M. | Rose, Lynda M. | Scharnag, Hubert | Schork, Nicholas J. | Shimbo, Daichi | Shuldiner, Alan R. | Srinivasan, Sathanur R. | Stolk, Ronald P. | Taylor, Herman A. | Thorand, Barbara | Trip, Mieke D. | van Duijn, Cornelia M. | Verschuren, W. Monique | Wijmenga, Cisca | Winkelmann, Bernhard R. | Wyatt, Sharon | Young, J. Hunter | Boehm, Bernhard O. | Caulfield, Mark J. | Chasman, Daniel I. | Davidson, Karina W. | Doevendans, Pieter A. | FitzGerald, Garret A. | Gums, John G. | Hakonarson, Hakon | Hillege, Hans L. | Illig, Thomas | Jarvik, Gail P. | Johnson, Julie A. | Kastelein, John J.P. | Koenig, Wolfgang | März, Winfried | Mitchell, Braxton D. | Murray, Sarah S. | Oldehinkel, Albertine J. | Rader, Daniel J. | Reilly, Muredach P. | Reiner, Alex P. | Schadt, Eric E. | Silverstein, Roy L. | Snieder, Harold | Stanton, Alice V. | Uitterlinden, André G. | van der Harst, Pim | van der Schouw, Yvonne T. | Samani, Nilesh J. | Johnson, Andrew D. | Munroe, Patricia B. | de Bakker, Paul I.W. | Zhu, Xiaofeng | Levy, Daniel | Keating, Brendan J. | Asselbergs, Folkert W.
Human Molecular Genetics  2013;22(8):1663-1678.
Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10−6). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
doi:10.1093/hmg/dds555
PMCID: PMC3657476  PMID: 23303523
7.  Variations in Common Carotid Artery Intima-Media Thickness (cIMT) during the Cardiac Cycle: Implications for Cardiovascular Risk Assessment 
Introduction
Common carotid artery (CCA) intima-media thickness (cIMT), a measure of atherosclerosis, varies between peak-systole (PS) and end-diastole (ED). This difference might affect cardiovascular risk assessment.
Materials and methods
IMT measurements of the right and left CCA were synchronized with an electrocardiogram: R-wave for ED and T-wave for PS. IMT was measured in 2930 members of the Framingham Offspring Study. Multivariable regression models were generated with ED-IMT, PS-IMT and change in IMT as dependent variables and Framingham risk factors as independent variables. ED-IMT estimates were compared to the upper quartile of IMT based on normative data obtained at PS.
Results
The average age of our population was 57.9 years. Average difference in IMT during the cardiac cycle was 0.037 mm (95% CI: 0.035–0.038 mm). ED-IMT and PS-IMT had similar associations with Framingham risk factors (total R2= 0.292 versus 0.275) and were significantly associated with all risk factors. In a fully adjusted multivariable model, a thinner IMT at peak-systole was associated with pulse pressure (p < 0.0001), LDL-cholesterol (p = 0.0064), age (p = 0.046), and no other risk factors. Performing ED-IMT measurements while using upper quartile PS-IMT normative data lead to inappropriately increasing by 42.1% the number of individuals in the fourth IMT quartile (high cardiovascular risk category).
Conclusion
The difference in IMT between peak-systole and end-diastole is associated with pulse pressure, LDL-cholesterol, and age. In our study, mean IMT difference during the cardiac cycle lead to an overestimation by 42.1% of individuals at high risk for cardiovascular disease.
doi:10.1016/j.echo.2012.05.007
PMCID: PMC3544292  PMID: 22721828
Ultrasonics; Risk Factors; Carotid Arteries; Blood Pressure; systole; diastole
8.  Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data 
Lancet  2012;379(9831):2053-2062.
Summary
Background
Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is frequently assumed but has rarely been reported. Our aim was to test this association.
Methods
We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis.
Findings
Of 21 eligible studies, 16 with 36 984 participants were included. During a mean follow-up of 7·0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2–7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0·97 (95% CI 0·94–1·00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0·98 (0·95–1·01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1·16, 95% CI 1·10–1·22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r=−0·06 and r=−0·02).
Interpretation
The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials.
Funding
Deutsche Forschungsgemeinschaft.
doi:10.1016/S0140-6736(12)60441-3
PMCID: PMC3918517  PMID: 22541275
9.  Vascular Responses to Long- and Short-Term Exposure to Fine Particulate Matter 
Objectives
This study evaluated the association of long- and short-term air pollutant exposures with flow-mediated dilation (FMD) and baseline arterial diameter (BAD) of the brachial artery using ultrasound in a large multicity cohort.
Background
Exposures to ambient air pollution, especially long-term exposure to particulate matter <2.5 μm in aerodynamic diameter (PM2.5), are linked with cardiovascular mortality. Short-term exposure to PM2.5 has been associated with decreased FMD and vasoconstriction, suggesting that adverse effects of PM2.5 may involve endothelial dysfunction. However, long-term effects of PM2.5 on endothelial dysfunction have not been investigated.
Methods
FMD and BAD were measured by brachial artery ultrasound at the initial examination of the Multi-Ethnic Study of Atherosclerosis. Long-term PM2.5 concentrations were estimated for the year 2000 at each participant’s residence (n = 3,040) using a spatio-temporal model informed by cohort-specific monitoring. Short-term PM2.5 concentrations were based on daily central-site monitoring in each of the 6 cities.
Results
An interquartile increase in long-term PM2.5 concentration (3 μg/m3) was associated with a 0.3% decrease in FMD (95% confidence interval [CI] of difference: −0.6 to −0.03; p = 0.03), adjusting for demographic characteristics, traditional risk factors, sonographers, and 1/BAD. Women, nonsmokers, younger participants, and those with hypertension seemed to show a greater association of PM2.5 with FMD. FMD was not significantly associated with short-term variation in PM2.5 (−0.1% per 12 μg/m3 daily increase [95% CI: −0.2 to 0.04] on the day before examination).
Conclusions
Long-term PM2.5 exposure was significantly associated with decreased endothelial function according to brachial ultrasound results. These findings may elucidate an important pathway linking air pollution and cardiovascular mortality.
doi:10.1016/j.jacc.2012.08.973
PMCID: PMC3665082  PMID: 23103035
air pollution; atherosclerosis; cardiovascular mortality; endothelial function; flow-mediated dilation; traffic
10.  Kidney stones and subclinical atherosclerosis in young adults: Coronary Artery Risk Development in Young Adults (CARDIA) study 
The Journal of urology  2011;185(3):10.1016/j.juro.2010.10.086.
Purpose
Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. There has been no previous examination of the relationship between kidney stones and subclinical atherosclerotic disease Here we assessed the relationship between nephrolithiasis and carotid wall thickness and carotid stenosis assessed by B-mode ultrasound in the general community using data from The Coronary Artery Risk Development in Young Adults (CARDIA) study.
Methods
CARDIA is a U.S. population-based, observational study of 5,115 white and African-American men and women between the ages of 18 and 30 years at recruitment in 1985-1986.
Results
By the year 20 exam, 200 (3.9%) of CARDIA participants had reported ever having kidney stones. Symptomatic kidney stones were associated with greater carotid wall thickness measured at the year 20 exam, particularly of the internal carotid/bulb region. Using a composite dichotomous endpoint of carotid stenosis and/or upper quartile of internal carotid/bulb wall thickness, the association of kidney stones with carotid atherosclerosis was significant (odds ratio=1.6; 95% confidence interval 1.1-2.3; p=0.01) even after adjusting for major atherosclerotic risk factors.
Conclusions
The association between a history of kidney stones and subclinical carotid atherosclerosis in young adults adds further support to the notion that nephrolithiasis and atherosclerosis share common systemic risk factors and/or pathophysiology.
doi:10.1016/j.juro.2010.10.086
PMCID: PMC3827917  PMID: 21251678
urolithiasis; atherosclerosis
11.  Common carotid artery intima-media thickness (IMT) progression as a predictor of stroke in MESA (Multi-Ethnic Study of Atherosclerosis) 
Background
Carotid artery intima-media thickness (IMT) is a marker of cardiovascular disease associated with incident stroke. We study whether IMT rate-of-change is associated with stroke.
Materials and Methods
We studied 5028 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) composed of whites, Chinese, Hispanic and African-Americans free of cardiovascular disease. In this MESA IMT progression study, IMT rate-of-change (mm/year) was the difference in right common carotid artery (CCA) far-wall IMT (mm) divided by the interval between two ultrasound examinations (median interval of 32 months). CCA IMT was measured in a region free of plaque. Cardiovascular risk factors and baseline IMT were determined when IMT rate-of-change was measured. Multivariable Cox proportional hazards models generated Hazard risk Ratios (HR) with cardiovascular risk factors, ethnicity and education level/income as predictors.
Results
There were 42 first time strokes seen during a mean follow-up of 3.22 years (median 3.0 years). Average age was 64.2 years, with 48% males. In multivariable models, age (HR: 1.05 per year), systolic blood pressure (HR 1.02 per mmHg), lower HDL cholesterol levels (HR: 0.96 per mg/dL) and IMT rate-of-change (HR 1.23 per 0.05 mm/year; 95% C.L. 1.02, 1.48) were significantly associated with incident stroke. The upper quartile of IMT rate-of-change had an HR of 2.18 (95% C.L.: 1.07, 4.46) compared to the lower three quartiles combined.
Conclusion
Common carotid artery IMT progression is associated with incident stroke in this cohort free of prevalent cardiovascular disease and atrial fibrillation at baseline.
doi:10.1161/STROKEAHA.111.625186
PMCID: PMC3202068  PMID: 21885840
Ultrasonography; Risk Factors; Carotid Arteries; Carotid Intima Media Thickness; stroke
12.  Associations of cardiovascular risk factors, carotid intima-media thickness and left ventricular mass with inter-adventitial diameters of the common carotid artery: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Atherosclerosis  2011;218(2):344-349.
Background
Common carotid artery inter-adventitial diameter (IAD) and intima-media thickness (IMT) are measurable by ultrasound. IAD may be associated with left ventricular mass (LV mass) while IMT is a marker of subclinical atherosclerosis. It is not clear if IAD is associated with LV mass after accounting for IMT and traditional cardiovascular risk factors.
Methods
IAD and IMT were measured on participants of the Multi-Ethnic Study of Atherosclerosis (MESA) IMT progression study. A total of 5641 of the originally enrolled 6814 MESA participants were studied. LV mass was measured by magnetic resonance imaging. Multivariable linear regression was used with IAD as the outcome and adjustment for risk factors, as well as IMT and LV mass.
Results
Traditional cardiovascular risk factors, height, weight and ethnicity were significantly associated with IAD. After adjustment for risk factors, a one mm difference in IMT was associated with a 1.802 mm (95% CI: 1.553, 2.051) higher mean IAD. A one gm difference in LV mass was associated with a 0.006 mm (95% CI: 0.005, 0.007) higher mean IAD. LV mass was independently associated with IAD after adjusting for cardiovascular risk factors and IMT. These associations were slightly different for men and women.
Conclusions
Inter-adventitial diameters are associated with left ventricular mass after adjusting for cardiovascular risk factors and IMT. IAD might serve as a surrogate for left ventricular mass and have predictive value for cardiovascular outcomes.
doi:10.1016/j.atherosclerosis.2011.05.033
PMCID: PMC3186064  PMID: 21726862
carotid arteries; ultrasonics; hypertrophy; magnetic resonance imaging; remodeling; risk factors; left ventricle
13.  Changes in Carotid Intima-Media Thickness During the Cardiac Cycle: The Multi-Ethnic Study of Atherosclerosis 
Background
Common carotid artery intima-media thickness (IMT), a measure of subclinical cardiovascular disease, changes during the cardiac cycle. The magnitude of this effect and its implications have not been well studied.
Methods and Results
Far-wall IMT measurements of the right common carotid artery were measured at end diastole and peak systole in 5633 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA). Multivariable regression models were generated with end-diastolic IMT, peak-systolic IMT, and change in IMT during the cardiac cycle as dependent variables and traditional cardiovascular risk factors as independent variables. The average age of our population was 61.9 (45 to 84) years. Average change in carotid IMT during the cardiac cycle was 0.041 mm (95% confidence interval: 0.039 to 0.042 mm), with a mean IMT of 0.68 mm. End-diastolic IMT and peak-systolic IMT were similarly associated with risk factors. In a fully adjusted model, change in carotid IMT during the cardiac cycle was associated with ethnicity and pulse pressure (P=0.001) and not age, sex, or other risk factors. Chinese and Hispanics had less of a change in IMT than did non-Hispanic whites. With peak-systolic IMT reference values used as normative data, 31.3% more individuals were classified as being in the upper quartile of IMT and at high risk for cardiovascular disease than would be expected when IMT is measured at end diastole.
Conclusions
Measurable differences in IMT are seen during the cardiac cycle. This affects the interpretation of IMT measurements used for cardiovascular risk assessment, given published normative data with IMT measured at peak systole.
Clinical Trial Registration
URL: www.ClinicalTrials.gov. Unique identifier: NCT00063440. (J Am Heart Assoc. 2012;1:e001420 doi: 10.1161/JAHA.112.001420.)
doi:10.1161/JAHA.112.001420
PMCID: PMC3487346  PMID: 23130162
atherosclerosis; blood pressure; carotid arteries; diastole; epidemiology; risk factors; systole; ultrasonics
14.  Associations of edge detected and manual traced common carotid intima-media thickness (IMT) measurements with Framingham risk factors: the Multi-Ethnic Study of Atherosclerosis 
Background
Carotid intima-media thickness (IMT) is a marker of cardiovascular disease derived from ultrasound images of the carotid artery. In most outcome studies, human readers identify and trace the key IMT interfaces. We evaluate an alternate approach using automated edge detection.
Methods
We study a subset of 5640 participants with an average age 61.7 years (48% men) of the Multi-Ethnic Study of Atherosclerosis composed of whites, Chinese, Hispanic and African-Americans that are part of the MESA IMT progression study. Manual tracing IMT (mt_IMT) and edge-detected IMT (ed_IMT) measurements of the far wall of the common carotid artery (CCA) served as outcome variables for multivariable linear regression models using Framingham cardiovascular risk factors and ethnicity as independent predictors.
Results
Measurements of mt_IMT was obtainable in 99.9% (5633/5640) and of ed_IMT in 98.9% (5579/5640) of individuals. Average ed_IMT was 0.19 mm larger than mt_IMT. Inter-reader systematic differences (bias) in IMT measurements were apparent for mt_IMT but not ed_IMT. Based on complete data on 5538 individuals, associations of IMT with risk factors were stronger (p < 0.0001) for mt_IMT (model r2: 19.5%) than ed_IMT (model r2: 18.5%).
Conclusion
We conclude that this edge-detection process generates IMT values equivalent to manually traced ones since it preserves key associations with cardiovascular risk factors. It also decreases inter-reader bias, potentially making it applicable for use in cardiovascular risk assessment.
doi:10.1161/STROKEAHA.110.603449
PMCID: PMC3169166  PMID: 21546477
Ultrasonography; Risk Factors; Carotid Arteries; Carotid Intima Media Thickness
15.  Genetics of coronary artery calcification among African Americans, a meta-analysis 
BMC Medical Genetics  2013;14:75.
Background
Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.
Methods
We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis.
Results
Heritability of CAC was lower in AA (~30%) than previously reported for EA (~50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached nominal significance for CAC in AA, with concordant direction. Among AA, rs16905644 (p = 4.08E-05) had the strongest association in the 9p21 region.
Conclusions
While we observed substantial heritability for CAC in AA, we failed to identify loci for CAC at genome-wide significant levels despite having adequate power to detect alleles with moderate to large effects. Although suggestive signals in AA were apparent at 9p21 and additional CAC and CAD EA loci, overall the data suggest that even larger samples and an ethnic specific focus will be required for GWAS discoveries for CAC in AA populations.
doi:10.1186/1471-2350-14-75
PMCID: PMC3733595  PMID: 23870195
Atherosclerosis; Coronary artery calcium; Genetics; Meta-analysis; African-American
16.  Associations of Carotid Artery Intima-Media Thickness (IMT) With Risk Factors and Prevalent Cardiovascular Disease 
Objective
The goal of this study was to compare internal carotid artery (ICA) intima-media thickness (IMT) with common carotid artery (CCA) IMT as global markers of cardiovascular disease (CVD).
Methods
Cross-sectional measurements of the mean CCA IMT and maximum ICA IMT were made on ultrasound images acquired from the Framingham Offspring cohort (n = 3316; mean age, 58 years; 52.7% women). Linear regression models were used to study the associations of the Framingham risk factors with CCA and ICA IMT. Multivariate logistic regression models and receiver operating characteristic (ROC) curve analysis were used to compare the associations of prevalent CVD with CCA and ICA IMT and determine sensitivity and specificity.
Results
The association between age and the mean CCA IMT corresponded to an increase of 0.007 mm/y; the increase was 0.037 mm/y for the ICA IMT. Framingham risk factors accounted for 28.6% and 27.5% of the variability in the CCA and ICA IMT, respectively. Age and gender contributed 23.5% to the variability of the CCA IMT and 22.5% to that of the ICA IMT, with the next most important factor being systolic blood pressure (1.9%) for the CCA IMT and smoking (1.6%) for the ICA IMT. The CCA IMT and ICA IMT were statistically significant predictors of prevalent CVD, with the ICA IMT having a larger area under the ROC curve (0.756 versus 0.695).
Conclusions
Associations of risk factors with CCA and ICA IMT are slightly different, and both are independently associated with prevalent CVD. Their value for predicting incident cardiovascular events needs to be compared in outcome studies.
PMCID: PMC3186063  PMID: 21098848
atherosclerosis; carotid artery; disease prevalence; intima-media thickness; risk factors
17.  Segment-Specific Associations of Carotid IMT with Cardiovascular Risk Factors: The Coronary Artery Risk Development in Young Adults (CARDIA) Study 
Background and Purpose
We propose to study possible differences in the associations between risk factors for cardiovascular disease (myocardial infarction and stroke) and Carotid Intima-Media thickness (IMT) measurements made at three different levels of the carotid bifurcation. Methods: Cross-sectional study of a cohort of Whites and African Americans of both genders with mean age 45 years. Traditional cardiovascular risk factors were determined in cohort members. Carotid IMT was measured from high-resolution B-mode ultrasound images at three levels: the common carotid artery (CCA), the carotid artery bulb (Bulb) and the internal carotid artery (ICA). Associations with risk factors were evaluated by multivariate linear regression analyses.
Results
Of 3258 who underwent carotid IMT measurements, CCA, Bulb, and ICA IMT were measured at all three separate levels in 3023 (92.7%). A large proportion of the variability of CCA IMT was explained by cardiovascular risk factors (26.8%) but less so for the Bulb (11.2%) and ICA (8.0%). Carotid IMT was consistently associated with age, LDL-cholesterol, smoking and hypertension in all segments. Associations with fasting glucose and diastolic blood pressure were stronger for CCA than for the other segments. Hypertension, diabetes and current smoking had qualitatively stronger associations with Bulb IMT, and LDL cholesterol with ICA IMT. Conclusion: In our cohort of relatively young white and African-American men and women, a greater proportion of the variability in common carotid IMT can be explained by traditional cardiovascular risk factors than for the carotid artery bulb and internal carotid arteries.
doi:10.1161/STROKEAHA.109.566596
PMCID: PMC3163306  PMID: 19910544
Carotid Intimal Medial Thickness; Risk Factors; Carotid Ultrasound
18.  Association of number of live births with left ventricular structure and function. The Multi-Ethnic Study of Atherosclerosis (MESA) 
American heart journal  2012;163(3):470-476.
Background
Pregnancy is associated with marked maternal cardiovascular/hemodynamic changes. A greater number of pregnancies may be associated with long-term subclinical changes in left ventricular (LV) remodeling.
Methods
Among 2,234 white, black, Hispanic, and Chinese women (mean age 62 years) in the MESA, we used linear regression to relate live births and cardiac magnetic resonance imaging LV measures. Covariates included age, ethnicity, height, income, education, birth country, smoking, menopause, and oral contraceptive duration. Models were additionally adjusted for potential mediators: systolic blood pressure, antihypertensive use, total/high-density lipoprotein cholesterol, triglycerides, diabetes, and body mass index. We performed sensitivity analyses excluding 763 women in the lowest socioeconomic group: annual income <$25,000 and lower high school level of education.
Results
With each live birth, LV mass increased 1.26 g; LV end-diastolic volume, 0.74 mL; and LV end-systolic volume, 0.45 mL; LV ejection fraction decreased 0.18% (P trend <0.05). Changes were most notable for the category of women with ≥5 pregnancies. Upon adjustment for potential biologic mediators, live births remained positively associated with LV mass and end-systolic volume. Live births remained significantly associated with LV end-systolic, end-diastolic volumes, and LV mass (P trend ≤0.02) after excluding women in the lowest socioeconomic group.
Conclusions
Number of live births is associated with key LV structural and functional measures in middle to older ages, even after adjustment for sociodemographic factors and cardiovascular disease risk factors. Hemodynamic changes during pregnancy may be associated with cardiac structure/function beyond childbearing years.
doi:10.1016/j.ahj.2011.12.011
PMCID: PMC3656723  PMID: 22424019
19.  Particulate matter components and subclinical atherosclerosis: common approaches to estimating exposure in a Multi-Ethnic Study of Atherosclerosis cross-sectional study 
Environmental Health  2013;12:39.
Background
Concentrations of outdoor fine particulate matter (PM2.5) have been associated with cardiovascular disease. PM2.5 chemical composition may be responsible for effects of exposure to PM2.5.
Methods
Using data from the Multi-Ethnic Study of Atherosclerosis (MESA) collected in 2000–2002 on 6,256 US adults without clinical cardiovascular disease in six U.S. metropolitan areas, we investigated cross-sectional associations of estimated long-term exposure to total PM2.5 mass and PM2.5 components (elemental carbon [EC], organic carbon [OC], silicon and sulfur) with measures of subclinical atherosclerosis (coronary artery calcium [CAC] and right common carotid intima-media thickness [CIMT]). Community monitors deployed for this study from 2007 to 2008 were used to estimate exposures at baseline addresses using three commonly-used approaches: (1) nearest monitor (the primary approach), (2) inverse-distance monitor weighting and (3) city-wide average.
Results
Using the exposure estimate based on nearest monitor, in single-pollutant models, increased OC (effect estimate [95% CI] per IQR: 35.1 μm [26.8, 43.3]), EC (9.6 μm [3.6,15.7]), sulfur (22.7 μm [15.0,30.4]) and total PM2.5 (14.7 μm [9.0,20.5]) but not silicon (5.2 μm [−9.8,20.1]), were associated with increased CIMT; in two-pollutant models, only the association with OC was robust to control for the other pollutants. Findings were generally consistent across the three exposure estimation approaches. None of the PM measures were positively associated with either the presence or extent of CAC. In sensitivity analyses, effect estimates for OC and silicon were particularly sensitive to control for metropolitan area.
Conclusion
Employing commonly-used exposure estimation approaches, all of the PM2.5 components considered, except silicon, were associated with increased CIMT, with the evidence being strongest for OC; no component was associated with increased CAC. PM2.5 chemical components, or other features of the sources that produced them, may be important in determining the effect of PM exposure on atherosclerosis. These cross-sectional findings await confirmation in future work employing longitudinal outcome measures and using more sophisticated approaches to estimating exposure.
doi:10.1186/1476-069X-12-39
PMCID: PMC3663826  PMID: 23641873
Atherosclerosis; Cardiovascular diseases; Coronary artery disease; Air pollution; Particulate matter
20.  Association of Small Artery Elasticity With Incident Cardiovascular Disease in Older Adults 
American Journal of Epidemiology  2011;174(5):528-536.
Functional biomarkers like large artery elasticity (LAE) and small artery elasticity (SAE) may predict cardiovascular disease (CVD) events beyond blood pressure. The authors examined the prognostic value of LAE and SAE for clinical CVD events among 6,235 Multi-Ethnic Study of Atherosclerosis participants who were initially aged 45–84 years and without symptomatic CVD. LAE and SAE were derived from diastolic pulse contour analysis. During a median 5.8 years of follow-up between 2000 and 2008, 454 adjudicated CVD events occurred, including 256 cases of coronary heart disease (CHD), 93 strokes, and 126 heart failures (multiple diagnoses were possible). After adjustment for age, race/ethnicity, sex, clinic, height, heart rate, body mass index, systolic and diastolic blood pressure, use of antihypertensive and cholesterol-lowering medications, smoking, total cholesterol, high density lipoprotein cholesterol, triglycerides, diabetes, and high-sensitivity C-reactive protein, the hazard ratio for any CVD per standard-deviation increase in SAE was 0.71 (95% confidence interval: 0.61, 0.83; P < 0.0001). The lowest (stiffest) SAE quartile had a hazard ratio of 2.28 (95% confidence interval: 1.55, 3.36) versus the highest (most elastic) quartile. The net reclassification index, conditional on base risk, was 0.11. SAE was significantly associated with future CHD, stroke, and heart failure. After adjustment, LAE was not significantly related to CVD. In asymptomatic participants free of overt CVD, lower SAE added prognostic information for CVD, CHD, stroke, and heart failure events.
doi:10.1093/aje/kwr120
PMCID: PMC3202150  PMID: 21709134
arteries; cardiovascular diseases; elasticity; risk factors
21.  Sex Differences in Subclinical Atherosclerosis by Race/Ethnicity in the Multi-Ethnic Study of Atherosclerosis 
American Journal of Epidemiology  2011;174(2):165-172.
Sex differences in cardiovascular disease mortality are more pronounced among non-Hispanic whites than other racial/ethnic groups, but it is unknown whether this variation is present in the earlier subclinical stages of disease. The authors examined racial/ethnic variation in sex differences in coronary artery calcification (CAC) and carotid intimal media thickness at baseline in 2000–2002 among participants (n = 6,726) in the Multi-Ethnic Study of Atherosclerosis using binomial and linear regression. Models adjusted for risk factors in several stages: age, traditional cardiovascular disease risk factors, behavioral risk factors, psychosocial factors, and adult socioeconomic position. Women had a lower prevalence of any CAC and smaller amounts of CAC when present than men in all racial/ethnic groups. Sex differences in the prevalence of CAC were more pronounced in non-Hispanic whites than in African Americans and Chinese Americans after adjustment for traditional cardiovascular disease risk factors, and further adjustment for behavioral factors, psychosocial factors, and socioeconomic position did not modify these results (for race/sex, Pinteraction = 0.047). Similar patterns were observed for amount of CAC among adults with CAC. Racial/ethnic variation in sex differences for carotid intimal media thickness was less pronounced. In conclusion, coronary artery calcification is differentially patterned by sex across racial/ethnic groups.
doi:10.1093/aje/kwr088
PMCID: PMC3167681  PMID: 21685409
calcification, physiologic; continental population groups; coronary vessels; sex; social class
22.  Reduced Kidney Function and Preclinical Atherosclerosis in HIV-Infected Individuals: The Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) 
American Journal of Nephrology  2011;33(5):453-460.
Background/Aims
Reduced kidney function and albuminuria are associated with higher risk for cardiovascular disease (CVD) and mortality in HIV-infected individuals. We investigated whether reduced estimated glomerular filtration rate (eGFR) and albuminuria are associated with subclinical vascular disease, as assessed by carotid intima-medial thickness (cIMT).
Methods
Cross-sectional analysis of 476 HIV-infected individuals without clinical evidence of CVD enrolled in the Fat Redistribution and Metabolic Change in HIV infection (FRAM) study, using multivariable linear regression. eGFRCys and eGFRCr were calculated from cystatin C and creatinine levels. Albuminuria was defined as a positive urine dipstick (≥1+) or urine albumin-to-creatinine ratio ≥30 mg/g. Common and internal cIMT were measured by high-resolution B-mode ultrasound.
Results
In unadjusted analyses, eGFRCys and eGFRCr were strongly associated with common and internal cIMT. Each 10 ml/min/1.73 m2 decrease in eGFRCys and eGFRCr was associated with a 0.008 mm higher common cIMT (p = 0.003, p = 0.01) and a 0.024 and 0.029 mm higher internal cIMT (p = 0.003), respectively. These associations were eliminated after adjustment for age, gender, and race. Albuminuria showed little association with common or internal cIMT in all models.
Conclusions
In HIV-infected individuals without prior CVD, reduced kidney function and albuminuria were not independently associated with subclinical vascular disease, as assessed by cIMT. These results suggest that research should focus on searching for novel mechanisms by which kidney disease confers cardiovascular risk in HIV-infected individuals.
doi:10.1159/000327606
PMCID: PMC3100378  PMID: 21508633
Cystatin C; Intima-medial thickness; HIV; Atherosclerosis; Cardiovascular disease; Kidney
23.  Pericardial Fat is Associated with Carotid Stiffness in the Multi-Ethnic Study of Atherosclerosis 
Background and Aims
Arterial stiffness is a prominent feature of vascular aging and a risk factor for cardiovascular disease (CVD). Fat around the heart and blood vessels (i.e. pericardial fat, Pfat) may contribute to arterial stiffness via a local paracrine effect of adipose tissue on the surrounding vasculature. Thus, we determined the association between Pfat and carotid stiffness in 5,770 participants (mean age 62 yrs, 53% female, 25% African American, 24% Hispanic, and 13% Chinese) from the Multi-Ethnic Study of Atherosclerosis.
Methods and Results
Pfat was measured by computed tomography, and ultrasonography of the common carotid artery was used to calculate the distensibility coefficient (DC) and young’s modulus (YM). Lower DC and higher YM values indicate stiffer arteries. Pfat quartile was highly associated with demographic, behavioral, anthropometric, hemodynamic, metabolic, and disease variables in both men and women. After adjusting for height, clinical site, CVD risk factors, and medications, a 1-standard deviation (41.91 cm3) increment in Pfat was associated with a 0.00007±0.00002 1/mmHg lower DC (p=0.0002) in men and a 48.1±15.1 mmHg/mm higher YM in women (p=0.002). Additional adjustment for C-reactive protein, coronary artery calcification, and carotid intima-media thickness had only modest effects. More importantly, adjusting for body mass index and waist circumference did not significantly change the overall results.
Conclusion
Higher Pfat is associated with higher carotid stiffness, independent of traditional CVD risk factors and obesity.
doi:10.1016/j.numecd.2009.10.010
PMCID: PMC2929306  PMID: 20153618
pericardial fat; arterial stiffness; distensibility; carotid artery
24.  Usefulness of Baseline Obesity to Predict Development of a High Ankle Brachial Index (From the Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2011;107(9):1386-1391.
An abnormally high ankle brachial index (ABI) is associated with increased all-cause and cardiovascular mortality. The relationship of obesity to incident high-ABI has not been characterized. We investigated the hypothesis that increased obesity—quantified by body weight, BMI, waist circumference, and waist-to-hip-ratio—is positively associated with a high-ABI (ABI ≥ 1.3) and with mean ABI increases over a four year follow-up. Prevalence and incidence ratios for a high-ABI were obtained for 6540 and 5045 participants respectively in the Multi-Ethnic Study of Atherosclerosis (MESA), using log-binomial regression models adjusted for demographic, cardiovascular, and inflammatory/novel risk factors. Linear regression was used to analyze mean ABI change. Both prevalence and incidence of a high-ABI were significantly higher for the highest versus the lowest quartile of every baseline measure of obesity, with weight and BMI demonstrating the highest incidence ratios (2.7 and 2.4, respectively). All prevalence and incidence ratios were positive and graded across obesity quartiles, and were persistent in the subpopulation without diabetes. Among those with normal baseline ABI values, one MESA-standard deviation increase in every baseline measure of obesity was associated with significant increases in mean ABI values. In conclusion, we observed an independent, positive and graded association of increasing obesity to both prevalent and incident high-ABI, and to mean increases in ABI values over time. Weight and BMI seemed to be at least as strongly, if not more strongly, associated with a high-ABI than were measures of abdominal obesity.
doi:10.1016/j.amjcard.2010.12.050
PMCID: PMC3079000  PMID: 21377643
obesity; anthropometric measures; peripheral vascular disease; ankle-brachial index; epidemiology
25.  Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque 
Bis, Joshua C. | Kavousi, Maryam | Franceschini, Nora | Isaacs, Aaron | Abecasis, Gonçalo R | Schminke, Ulf | Post, Wendy | Smith, Albert V. | Cupples, L. Adrienne | Markus, Hugh S | Schmidt, Reinhold | Huffman, Jennifer E. | Lehtimäki, Terho | Baumert, Jens | Münzel, Thomas | Heckbert, Susan R. | Dehghan, Abbas | North, Kari | Oostra, Ben | Bevan, Steve | Stoegerer, Eva-Maria | Hayward, Caroline | Raitakari, Olli | Meisinger, Christa | Schillert, Arne | Sanna, Serena | Völzke, Henry | Cheng, Yu-Ching | Thorsson, Bolli | Fox, Caroline S. | Rice, Kenneth | Rivadeneira, Fernando | Nambi, Vijay | Halperin, Eran | Petrovic, Katja E. | Peltonen, Leena | Wichmann, H. Erich | Schnabel, Renate B. | Dörr, Marcus | Parsa, Afshin | Aspelund, Thor | Demissie, Serkalem | Kathiresan, Sekar | Reilly, Muredach P. | Uitterlinden, Andre | Couper, David J. | Sitzer, Matthias | Kähönen, Mika | Illig, Thomas | Wild, Philipp S. | Orru, Marco | Lüdemann, Jan | Shuldiner, Alan R. | Eiriksdottir, Gudny | White, Charles C. | Rotter, Jerome I. | Hofman, Albert | Seissler, Jochen | Zeller, Tanja | Usala, Gianluca | Ernst, Florian | Launer, Lenore J. | D'Agostino, Ralph B. | O'Leary, Daniel H. | Ballantyne, Christie | Thiery, Joachim | Ziegler, Andreas | Lakatta, Edward G. | Chilukoti, Ravi Kumar | Harris, Tamara B. | Wolf, Philip A. | Psaty, Bruce M. | Polak, Joseph F | Li, Xia | Rathmann, Wolfgang | Uda, Manuela | Boerwinkle, Eric | Klopp, Norman | Schmidt, Helena | Wilson, James F | Viikari, Jorma | Koenig, Wolfgang | Blankenberg, Stefan | Newman, Anne B. | Witteman, Jacqueline | Heiss, Gerardo | van Duijn, Cornelia | Scuteri, Angelo | Homuth, Georg | Mitchell, Braxton D. | Gudnason, Vilmundur | O’Donnell, Christopher J.
Nature Genetics  2011;43(10):940-947.
doi:10.1038/ng.920
PMCID: PMC3257519  PMID: 21909108
genome-wide association study; genetic epidemiology; genetics; subclinical atherosclerosis; carotid intima media thickness; cardiovascular disease; cohort study; meta-analysis; risk

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