The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
BACKGROUND - Coronary artery calcified plaque (CAC) is strongly predictive of cardiovascular disease (CVD) events and mortality, both in general populations and individuals with type 2 diabetes at high risk for CVD. CAC is typically reported as an Agatston score, which is weighted for increased plaque density. However, the role of CAC density in CVD risk prediction, independently and with CAC volume, remains unclear.
METHODS - We examined the role of CAC density in individuals with type 2 diabetes from the family-based Diabetes Heart Study and the African American-Diabetes Heart Study. CAC density was calculated as mass divided by volume, and associations with incident all-cause and CVD mortality [median follow-up 10.2 years European Americans (n = 902, n = 286 deceased), 5.2 years African Americans (n = 552, n = 93 deceased)] were examined using Cox proportional hazards models, independently and in models adjusted for CAC volume.
RESULTS - In European Americans, CAC density, like Agatston score and volume, was consistently associated with increased risk of all-cause and CVD mortality (p ≤ 0.002) in models adjusted for age, sex, statin use, total cholesterol, HDL, systolic blood pressure, high blood pressure medication use, and current smoking. However, these associations were no longer significant when models were additionally adjusted for CAC volume. CAC density was not significantly associated with mortality, either alone or adjusted for CAC volume, in African Americans.
CONCLUSIONS - CAC density is not associated with mortality independent from CAC volume in European Americans and African Americans with type 2 diabetes.
BACKGROUND - Coronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European Americans. Genetic factors likely contribute to the observed ethnic differences. To identify genes associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association study (GWAS) was performed using the Illumina 5 M chip in 691 African American-Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart Study (JHS) participants with T2D. Genetic association tests were performed on the genotyped and 1000 Genomes-imputed markers separately for each study, and combined in a meta-analysis.
RESULTS - Single nucleotide polymorphisms (SNPs), rs11353135 (2q22.1), rs16879003 (6p22.3), rs5014012, rs58071836 and rs10244825 (all on chromosome 7), rs10918777 (9q31.2), rs13331874 (16p13.3) and rs4459623 (18q12.1) were associated with presence and/or quantity of CAC in the AA-DHS and JHS, with meta-analysis p-values ≤8.0 × 10. The strongest result in AA-DHS alone was rs6491315 in the 13q32.1 region (parameter estimate (SE) = -1.14 (0.20); p-value = 9.1 × 10). This GWAS peak replicated a previously reported AA-DHS CAC admixture signal (rs7492028, LOD score 2.8).
CONCLUSIONS - Genetic association between SNPs on chromosomes 2, 6, 7, 9, 16 and 18 and CAC were detected in AAs with T2D from AA-DHS and replicated in the JHS. These data support a role for genetic variation on these chromosomes as contributors to CAC in AAs with T2D, as well as to variation in CAC between populations of African and European ancestry.
BACKGROUND - Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk.
METHODS - We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a value of <1.0×10 (Bonferroni correction for 50 tests).
RESULTS - We identified novel gene-smoking interaction for a variant upstream of the gene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers (=1.3×10) in comparison with 5% in ever-smokers (=2.5×10), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interaction value=8.7×10). The protective T allele at rs7178051 was also associated with reduced expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction of CONCLUSIONS: Allelic variation at rs7178051 that associates with reduced expression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascular expression may contribute to the loss of CHD protection in smokers.
© 2017 American Heart Association, Inc.
BACKGROUND & AIMS - While a recent meta-analysis of prospective studies reported that coffee consumption is associated with a lower risk of cardiovascular disease mortality, limited and inconsistent data are available on the relation of coffee intake with subclinical disease. Thus, the aim of the present study was to see the association of coffee consumption with the prevalence of atherosclerotic plaque in the coronary arteries in NHLBI Family Heart Study.
METHODS - In a cross-sectional design, we studied 1929 participants of the NHLBI Family Heart Study without known coronary heart disease. Coffee consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac computed tomography. We defined prevalent CAC as an Agatston score of ≥100 and used generalized estimating equations to calculate prevalence ratios of CAC as well as a sensitivity analysis at a range of cutpoints for CAC.
RESULTS - Mean age was 56.7 years and 59% of the study subjects were female. In adjusted analysis for age, sex, BMI, smoking, alcohol, physical activity, field center, and energy intake, prevalence ratio (95% CI) for CAC was 1.0 (reference), 0.92 (0.57-1.49), 1.34 (0.86-2.08), 1.30 (0.84-2.02), and 0.99 (0.60-1.64) for coffee consumption of almost never, <1/day, 1/day, 2-3/day, and ≥4 cups/day, respectively. In a sensitivity analysis, there was no evidence of association between coffee consumption and prevalent CAC when CAC cut points of 0, 50, 150, 200, and 300 were used.
CONCLUSIONS - These data do not provide evidence for an association between coffee consumption and prevalent CAC in adult men and women.
Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
Importance - Coronary artery calcium (CAC) is associated with coronary heart disease (CHD) and cardiovascular disease (CVD); however, prognostic data on CAC are limited in younger adults.
Objective - To determine if CAC in adults aged 32 to 46 years is associated with incident clinical CHD, CVD, and all-cause mortality during 12.5 years of follow-up.
Design, Setting, and Participants - The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014.
Main Outcomes and Measures - Incident CHD included fatal or nonfatal myocardial infarction, acute coronary syndrome without myocardial infarction, coronary revascularization, or CHD death. Incident CVD included CHD, stroke, heart failure, and peripheral arterial disease. Death included all causes. The probability of developing CAC by age 32 to 56 years was estimated using clinical risk factors measured 7 years apart between ages 18 and 38 years.
Results - At year 15 of the study among 3043 participants (mean [SD] age, 40.3 [3.6] years; 1383 men and 1660 women), 309 individuals (10.2%) had CAC, with a geometric mean Agatston score of 21.6 (interquartile range, 17.3-26.8). Participants were followed up for 12.5 years, with 57 incident CHD events and 108 incident CVD events observed. After adjusting for demographics, risk factors, and treatments, those with any CAC experienced a 5-fold increase in CHD events (hazard ratio [HR], 5.0; 95% CI, 2.8-8.7) and 3-fold increase in CVD events (HR, 3.0; 95% CI, 1.9-4.7). Within CAC score strata of 1-19, 20-99, and 100 or more, the HRs for CHD were 2.6 (95% CI, 1.0-5.7), 5.8 (95% CI, 2.6-12.1), and 9.8 (95% CI, 4.5-20.5), respectively. A CAC score of 100 or more had an incidence of 22.4 deaths per 100 participants (HR, 3.7; 95% CI, 1.5-10.0); of the 13 deaths in participants with a CAC score of 100 or more, 10 were adjudicated as CHD events. Risk factors for CVD in early adult life identified those above the median risk for developing CAC and, if applied, in a selective CAC screening strategy could reduce the number of people screened for CAC by 50% and the number imaged needed to find 1 person with CAC from 3.5 to 2.2.
Conclusions and Relevance - The presence of CAC among individuals aged between 32 and 46 years was associated with increased risk of fatal and nonfatal CHD during 12.5 years of follow-up. A CAC score of 100 or more was associated with early death. Adults younger than 50 years with any CAC, even with very low scores, identified on a computed tomographic scan are at elevated risk of clinical CHD, CVD, and death. Selective use of screening for CAC might be considered in individuals with risk factors in early adulthood to inform discussions about primary prevention.
CONTEXT - Relative to European Americans, calcified atherosclerotic plaque (CP) is less prevalent and severe in African-Americans (AAs).
OBJECTIVE - Predictors of progression of CP in the aorta, carotid, and coronary arteries were examined in AAs over a mean 5.3 ± 1.4-year interval.
DESIGN - This is the African American-Diabetes Heart Study.
SETTING - A type 2 diabetes (T2D)-affected cohort was included.
PARTICIPANTS - A total of 300 unrelated AAs with T2D; 50% female, mean age 55 ± 9 years, baseline hemoglobin A1c 8.1 ± 1.8% was included.
MAIN OUTCOME MEASURES - Glycemic control, renal parameters, vitamin D, and computed tomography-derived measures of adiposity, vascular CP, and volumetric bone mineral density (vBMD) in lumbar and thoracic vertebrae were obtained at baseline and follow-up.
RESULTS - CP increased in incidence and quantity/mass in all three vascular beds over the 5-year study (P < .0001). Lower baseline lumbar and thoracic vBMD were associated with progression of abdominal aorta CP (P < .008), but not progression of carotid or coronary artery CP. Lower baseline estimated glomerular filtration rate was associated with progression of carotid artery CP (P = .0004), and higher baseline pericardial adipose volume was associated with progression of coronary artery (P = .001) and aorta (P = .0006) CP independent of body mass index. There was a trend for an inverse relationship between change in thoracic vBMD and change in aortic CP (P = .05).
CONCLUSIONS - In this longitudinal study, lower baseline thoracic and lumbar vBMD and estimated glomerular filtration rate and higher pericardial adipose volumes were associated with increases in CP in AAs with T2D. Changes in these variables and baseline levels and/or changes in glycemic control, albuminuria, and vitamin D were not significantly associated with progression of CP.
OBJECTIVE - Studies have reported mixed findings on the association between physical activity and subclinical atherosclerosis. We sought to examine whether walking is associated with prevalent coronary artery calcification (CAC) and aortic calcification.
APPROACH AND RESULTS - In a cross-sectional design, we studied 2971 participants of the National Heart, Lung, and Blood Institute Family Heart Study without a history of myocardial infarction, coronary artery bypass grafting, or percutaneous transluminal angioplasty. A standardized questionnaire was used to ascertain the number of blocks walked daily to compute walking metabolic equivalent hours. CAC was measured by cardiac computed tomography. We defined prevalent CAC and aortic calcification using an Agatston score of at least 100 and used generalized estimating equations to calculate adjusted prevalence ratios. Mean age was 55 years, and 60% of participants were women. Compared with the ≤3.75-Met-h/wk group, prevalence ratios for CAC after adjusting for age, sex, race, smoking, alcohol use, total physical activity (excluding walking), and familial clustering were 0.53 (95% confidence interval, 0.35-0.79) for >3.75 to 7.5 Met-h/wk, 0.72 (95% confidence interval, 0.52-0.99) for >7.5 to 15 Met-h/wk, and 0.54 (95% confidence interval, 0.36-0.81) for >15 to 22.5 Met-h/wk, (P trend=0.01). The walking-CAC relationship remained significant for those with body mass index ≥25 (P trend=0.02) and persisted with CAC cutoffs of 300, 200, 150, and 50 but not 0. When examined as a continuous variable, a J-shaped association between walking and CAC was found. The walking-aortic calcification association was not significant.
CONCLUSIONS - Our findings suggest that walking is associated with lower prevalent CAC (but not aortic calcification) in adults without known heart disease.
© 2016 American Heart Association, Inc.
BACKGROUND - The improvement in discrimination gained by adding nontraditional cardiovascular risk markers cited in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines to the atherosclerotic cardiovascular disease (ASCVD) risk estimator (pooled cohort equation [PCE]) is untested.
OBJECTIVES - This study assessed the predictive accuracy and improvement in reclassification gained by the addition of the coronary artery calcium (CAC) score, the ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) levels, and family history (FH) of ASCVD to the PCE in participants of MESA (Multi-Ethnic Study of Atherosclerosis).
METHODS - The PCE was calibrated (cPCE) and used for this analysis. The Cox proportional hazards survival model, Harrell's C statistics, and net reclassification improvement analyses were used. ASCVD was defined as myocardial infarction, coronary heart disease-related death, or fatal or nonfatal stroke.
RESULTS - Of 6,814 MESA participants not prescribed statins at baseline, 5,185 had complete data and were included in this analysis. Their mean age was 61 years; 53.1% were women, 9.8% had diabetes, and 13.6% were current smokers. After 10 years of follow-up, 320 (6.2%) ASCVD events occurred. CAC score, ABI, and FH were independent predictors of ASCVD events in the multivariable Cox models. CAC score modestly improved the Harrell's C statistic (0.74 vs. 0.76; p = 0.04); ABI, hsCRP levels, and FH produced no improvement in Harrell's C statistic when added to the cPCE.
CONCLUSIONS - CAC score, ABI, and FH were independent predictors of ASCVD events. CAC score modestly improved the discriminative ability of the cPCE compared with other nontraditional risk markers.
Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
BACKGROUND - Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in disorders of serum phosphorus concentration and vitamin D. The role of FGF23 in vascular calcification remains controversial.
METHODS - Relationships between FGF23 and coronary artery calcified atherosclerotic plaque (CAC), aortoiliac calcified plaque (CP), carotid artery CP, volumetric bone mineral density (vBMD), albuminuria, and estimated glomerular filtration rate (eGFR) were determined in 545 African Americans with type 2 diabetes (T2D) and preserved kidney function in African American-Diabetes Heart Study participants. Generalized linear models were fitted to test associations between FGF23 and cardiovascular, bone, and renal phenotypes, and change in measurements over time, adjusting for age, gender, African ancestry proportion, body mass index, diabetes duration, hemoglobin A1c, blood pressure, renin-angiotensin-system inhibitors, statins, calcium supplements, serum calcium, and serum phosphate.
RESULTS - The sample was 56.7% female with a mean (SD) age of 55.6 (9.6) years, diabetes duration of 10.3 (8.2) years, eGFR 90.9 (22.1) ml/min/1.73 m2, urine albumin:creatinine ratio (UACR) 151 (588) (median 13) mg/g, plasma FGF23 161 (157) RU/ml, and CAC 637 (1,179) mg. In fully adjusted models, FGF23 was negatively associated with eGFR (p < 0.0001) and positively associated with UACR (p < 0.0001) and CAC (p = 0.0006), but not with carotid CP or aortic CP. Baseline FGF23 concentration did not associate with changes in vBMD or CAC after a mean of 5.1 years follow-up.
CONCLUSIONS - Plasma FGF23 concentrations were independently associated with subclinical coronary artery disease, albuminuria, and kidney function in the understudied African American population with T2D. Findings support relationships between FGF23 and vascular calcification, but not between FGF23 and bone mineral density, in African Americans lacking advanced nephropathy.
© 2016 S. Karger AG, Basel.
With the increasing use of coronary artery calcium (CAC) scoring to risk stratify asymptomatic patients for future cardiovascular events, there have been concerns raised regarding the theoretical risk of radiation exposure to this potentially large patient population. Newer CT protocols have sought to reduce radiation exposure without compromising image quality, but the reported radiation exposures in the literature remains widely variable (0.7-10.5 mSv). In this study, we report the radiation exposure of calcium scoring from our MESA cohort across several modern CT scanners with the aim of clarifying the radiation exposure of this imaging modality. To evaluate the mean effective doses of radiation, using dose length product, utilized for coronary artery calcium scoring in the MESA cohort, in an effort to understand estimated population quantity effective dose using individual measurements of scanner radiation output using current CT scanners. We reviewed effective dose in milliSieverts (mSv) for 3442 participants from the MESA cohort undergoing coronary artery calcium scoring, divided over six sites with four different modern CT scanners (Siemens64, Siemens Somatom Definition, GE64, and Toshiba 320). For effective dose calculation (milliSieverts, mSv), we multiplied the dose length product by conversion factor k (0.014). The mean effective dose amongst all participants was 1.05 mSv, a median dose of 0.95 mSV. The mean effective dose ranged from 0.74 to 1.26 across the six centers involved with the MESA cohort. The Siemens Somatom Definition scanner had effective dose of 0.53 (n = 123), Siemens 64 with 0.97 (n = 1684), GE 64 with 1.16 (n = 1219), and Toshiba 320 with 1.26 mSv (n = 416). Subgroup analysis by BMI, age, and gender showed no variability between scanners, gender, ages 45-74 years old, or BMI less than 30 kg/m(2). Subjects over age 75 yo had a mean effective dose of 1.29 ± 0.31 mSv, while the <75 yo subgroup was 0.78 ± 0.09 mSv (p < 0.05). Effective doses in subjects with BMI > 40 kg/m(2) was significantly greater than other subgroups, with mean dose of 1.47 ± 0.51 mSv (p < 0.01). Using contemporary CT scanners and protocols, the effective dose for coronary artery calcium is approximately 1 mSv, an estimate which is consistently lower than previously reported for CAC scanning, regardless of age, gender, and body mass index.