Prevalence, Epidemiological Characteristics, and Pharmacotherapy of Coronary Artery Disease among Patients with Atrial Fibrillation: Data from Jo-Fib Study

Background and Objectives: Patients with AF are at increased risk for Coronary Artery Disease (CAD) owing to their shared etiologies and risk factors. This study aimed to assess the prevalence, cardiovascular risk factors, and used medications of CAD in AF patients. Materials and Methods: This retrospective, case-control study utilized data from the Jordanian Atrial Fibrillation (Jo-Fib) registry. Investigators collected clinical features, history of co-existing comorbidities, CHA2DS2-VASc, and HAS BLED scores for all AF patients aged >18 visiting 19 hospitals and 30 outpatient cardiology clinics. A multivariable binary logistic regression was used to asses for factors associated with higher odds of having CAD. Results: Out of 2000 patients with AF, 227 (11.35%) had CAD. Compared to the rest of the sample, those with CAD had significantly higher prevalence of hypertension (82.38%; p < 0.01), hypercholesterolemia (66.52%, p < 0.01), diabetes (56.83%, p < 0.01), and smoking (18.06%, p = 0.04). Patients with AF and CAD had higher use of anticoagulants/antiplatelet agents combination (p < 0.01) compared to the rest of the sample. Females had lower CAD risk than males (OR = 0.35, 95% CI: 0.24–0.50). AF Patients with dyslipidemia (OR = 2.5, 95% CI: 1.8–3.4), smoking (OR = 1.7, 95% CI: 1.1–2.6), higher CHA2DS2-VASc score (OR = 1.5, 95% CI: 1.4–1.7), and asymptomatic AF (OR = 1.9, 95% CI: 1.3–2.6) had higher risk for CAD. Conclusions: Owing to the increased prevalence of CAD in patients with AF, better control of cardiac risk factors is recommended for this special group. Future studies should investigate such interesting relationships to stratify CAD risk in AF patients. We believe that this study adds valuable information regarding the prevalence, epidemiological characteristics, and pharmacotherapy of CAD in patients with AF.

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Antithrombotic therapy: what the dental surgeon has to know

Faculty Dental Journal ◽

10.1308/204268510x12804095143762 ◽

2010 ◽

Vol 1 (3) ◽

pp. 92-98

Author(s):

Nadzeya Kuzniatsova ◽

Gregory YH Lip

Keyword(s):

Atrial Fibrillation ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Elective Surgery ◽

Antiplatelet Agents ◽

Invasive Procedures ◽

Antithrombotic Drugs ◽

Risk Of Bleeding ◽

Increased Risk ◽

Artery Disease

Antithrombotic drugs are prescribed more and more often in medical practice. With a progressively aging population, the proportion of patients having prothrombotic medical conditions such as coronary artery disease, atrial fibrillation, venous thrombosis and many others increases dramatically. Anticoagulants or antiplatelet agents save thousands of lives annually but also introduce concerns of increased risk of bleeding, especially in the settings of elective surgery or invasive procedures.

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Abstract 12291: Contribution of Rare Mutations in Mendelian Hypercholesterolemia Genes to Risk for Premature Coronary Artery Disease in the Population

Circulation ◽

10.1161/circ.130.suppl_2.12291 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Hong-Hee Won ◽

Ron Do ◽

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Null Allele ◽

Coronary Revascularization ◽

Null Alleles ◽

Premature Coronary Artery Disease ◽

Rare Mutations ◽

Increased Risk ◽

Artery Disease ◽

Cad Risk

Introduction: Low-density lipoprotein cholesterol (LDL-C) is a causal risk factor for coronary artery disease (CAD). Rare mutations in at least 6 genes lead to Mendelian forms of high or reduced LDL-C; three ( APOB, LDLR, PCSK9 ) act in a dominant pattern whereas three ( ABCG5, ABCG8, LDLRAP1 ) in a recessive pattern. We address to what extent rare mutations in Mendelian LDL-C genes contribute to early CAD risk in the population. Methods: We sequenced the exons of the 6 genes in 9,329 early CAD cases (myocardial infarction, angiographic CAD, or coronary revascularization in men≤50 and women≤60) and 10,245 controls from 9 studies using targeted and whole exome next-generation sequencing. We tested 3 sets: ‘Null alleles’ (nonsense, splice-site, or frameshift); ‘Deleterious (7/7)’ (null and missense annotated as damaging by 7 algorithms); and ‘Deleterious (6/7)’ (null and missense annotated as damaging by at least 6 algorithms). Given the rarity of deleterious mutations, we aggregated these mutations in each gene and tested for an excess or deficit in cases vs . controls. Results: Counts of mutations are provided in Table. Null mutations in LDLR , carried by 1:500 participants, confered a 8-fold increase in CAD risk (P=8х10 -7 ) whereas heterozygosity for a null mutation in ABCG5 (1:650 frequency) was associated with a 3-fold increased risk (P=5х10 -3 ). ‘Deleterious (7/7)’ mutations in LDLR , carried by 1:100 participants, confered a 4-fold increased risk (P=8х10 -17 ) whereas heterozygosity for a ‘Deleterious (7/7)’ mutation in ABCG5 (1:250 frequency) was associated with a 2-fold increased risk (P=2х10 -3 ). Heterozygous null allele carriers at LDLR and ABCG5 had increased LDL-C (P<0.001). Conclusions: Of early CAD cases, 2-3% carry a rare, deleterious mutation at LDLR or ABCG5 associated with increased risk. Although previously reported to cause recessive sitosterolemia, we find that heterozygosity for a null allele at ABCG5 is associated with markedly higher early CAD risk.

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Should the Presence or Extent of Coronary Artery Disease be Quantified in the CHA2DS2-VASc Score in Atrial Fibrillation? A Report from the Western Denmark Heart Registry

Thrombosis and Haemostasis ◽

10.1055/s-0038-1675401 ◽

2018 ◽

Vol 118 (12) ◽

pp. 2162-2170 ◽

Cited By ~ 11

Author(s):

Kamilla Steensig ◽

Kevin Olesen ◽

Troels Thim ◽

Jens Nielsen ◽

Svend Jensen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Coronary Artery Disease ◽

Risk Factor ◽

Coronary Artery ◽

Coronary Angiography ◽

Ischaemic Stroke ◽

Independent Risk Factor ◽

Oral Anticoagulants ◽

Increased Risk ◽

Artery Disease

Background Patients with atrial fibrillation (AF) have an increased risk of ischaemic stroke. The risk can be predicted by the CHA2DS2-VASc score, in which the vascular component refers to previous myocardial infarction, peripheral artery disease and aortic plaque, whereas coronary artery disease (CAD) is not included. Objectives This article explores whether CAD per se or extent provides independent prognostic information of future stroke among patients with AF. Materials and Methods Consecutive patients with AF and coronary angiography performed between 2004 and 2012 were included. The endpoint was a composite of ischaemic stroke, transient ischaemic attack and systemic embolism. The risk of ischaemic events was estimated according to the presence and extent of CAD. Incidence rate ratios (IRR) were calculated in reference to patients without CAD and adjusted for parameters included in the CHA2DS2-VASc score and treatment with anti-platelet agents and/or oral anticoagulants. Results Of 96,430 patients undergoing coronary angiography, 12,690 had AF. Among patients with AF, 7,533 (59.4%) had CAD. Mean follow-up was 3 years. While presence of CAD was an independent risk factor for the composite endpoint (adjusted IRR, 1.25; 1.06–1.47), extent of CAD defined as 1-, 2-, 3- or diffuse vessel disease did not add additional independent risk information. Conclusion Presence, but not extent, of CAD was an independent risk factor of the composite thromboembolic endpoint beyond the components already included in the CHA2DS2-VASc score. Consequently, we suggest that significant angiographically proven CAD should be included in the vascular disease criterion in the CHA2DS2-VASc score.

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Mendelian randomization analyses reveal mediating factors of the causal effect of height on coronary artery disease

10.1101/2021.12.16.21267869 ◽

2021 ◽

Author(s):

Daniel Hui ◽

Christopher S. Thom ◽

Kimberly Lorenz ◽

Scott M. Damrauer ◽

Themistocles L. Assimes ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Lung Function ◽

Mendelian Randomization ◽

Causal Effect ◽

Multivariable Analysis ◽

Inverse Correlation ◽

Artery Disease ◽

Cad Risk

An inverse correlation between stature and risk of coronary artery disease (CAD) has been observed in several epidemiologic studies, and recent Mendelian randomization (MR) experiments have suggested evidence that this association may be causal. However, the extent to which the effect estimated by MR can be explained by established cardiovascular risk factors is unclear, with a recent report suggesting that lung function traits could fully explain the height-CAD effect. To clarify this relationship, we utilized the largest set of genetic instruments for human stature to date, comprising >2,000 genetic variants for height and CAD. In univariable analysis, we confirmed that a one standard deviation decrease in height (~6.5 cm) was associated with a 12.0% increase in the risk of CAD, consistent with previous reports. In multivariable analysis accounting for effects from up to 12 established risk factors, we observed a >3-fold attenuation in the causal effect of height on CAD susceptibility (3.7%, p = 2.1x10-2). We observed minimal effects of lung function traits on CAD risk in our analyses, indicating that these traits are unlikely to explain the residual association between height and CAD risk. In sum, these results suggest that height does not add meaningful clinical impact on CAD risk prediction beyond established risk factors.

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Predictive potential assessment of preoperative risk factors for atrial fibrillation in patients with coronary artery disease after coronary artery bypass grafting

The Siberian Journal of Clinical and Experimental Medicine ◽

10.29001/2073-8552-2020-35-4-128-136 ◽

2020 ◽

Vol 35 (4) ◽

pp. 128-136

Author(s):

K. I. Shakhgeldyan ◽

V. Y. Rublev ◽

B. I. Geltser ◽

B. O. Shcheglov ◽

V. G. Shirobokov ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Coronary Artery Bypass Grafting ◽

Artery Bypass ◽

Bypass Grafting ◽

Preoperative Risk ◽

Preoperative Risk Factors ◽

Artery Disease

Introduction. Postoperative atrial fibrillation (POAF) is one of the most common complications of coronary artery bypass grafting (CABG) and occurs in 25–65% of patients.Aim. The study aimed to assess the predictive potential of preoperative risk factors for POAF in patients with coronary artery disease (CAD) after CABG based on machine learning (ML) methods.Material and Methods. An observational retrospective study was carried out based on data from 866 electronic case histories of CAD patients with a median age of 63 years and a 95% confidence interval [63; 64], who underwent isolated CABG on cardiopulmonary bypass. Patients were assigned to two groups: group 1 comprised 147 (18%) patients with newly registered atrial fibrillation (AF) paroxysms; group 2 included 648 (81.3%) patients without cardiac arrhythmia. The preoperative clinical and functional status was assessed using 100 factors. We used statistical analysis methods (Chi-square, Fisher, Mann – Whitney, and univariate logistic regression (LR) tests) and ML tests (multivariate LR and stochastic gradient boosting (SGB)) for data processing and analysis. The models’ accuracy was assessed by three quality metrics: area under the ROC-curve (AUC), sensitivity, and specificity. The cross-validation procedure was performed at least 1000 times on randomly selected data.Results. The processing and analysis of preoperative patient status indicators using ML methods allowed to identify 10 predictors that were linearly and nonlinearly related to the development of POAF. The most significant predictors were the anteroposterior dimension of the left atrium, tricuspid valve insufficiency, ejection fraction <40%, duration of the P–R interval, and chronic heart failure of functional class III–IV. The accuracy of the best predictive multifactorial model of LR was 0.61 in AUC, 0.49 in specificity, and 0.72 in sensitivity. The values of similar quality metrics for the best model based on SGB were 0.64, 0.6, and 0.68, respectively.Conclusion. The use of SGB made it possible to verify the nonlinearly related predictors of POAF. The prospects for further research on this problem require the use of modern medical care methods that allow taking into account the individual characteristics of patients when developing predictive models.

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Association between Polymorphisms of Antioxidant Gene (MnSOD, CAT, and GPx1) and Risk of Coronary Artery Disease

BioMed Research International ◽

10.1155/2018/5086869 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Hseng-Long Yeh ◽

Li-Tang Kuo ◽

Fung-Chang Sung ◽

Chih-Ching Yeh

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Manganese Superoxide Dismutase ◽

Medical Center ◽

Stress Test ◽

Genetic Effect ◽

Multivariate Logistic Regression Model ◽

Increased Risk ◽

Artery Disease ◽

Cad Risk

Objective. Reactive oxygen species (ROS) been cited as one of the major causes of atherosclerosis and coronary artery disease which are possible agents inducing DNA damage. Manganese superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase-1 (GPx1) have evolved to address primary defense against free radical mediated damage in mitochondria. The aim of this study was to delineate the association ofMnSOD,CAT, andGPx1polymorphisms and risk of CAD in Taiwan.Methods. We conducted a case-control study with 657 participants recruited at a medical center. All subjects were evaluated by noninvasive stress test and then quantitative coronary angiography to confirm the diagnosis of CAD. 447 CAD cases were defined as >50% stenosis of coronary artery and 210 controls were stenosed below 50%. Polymorphisms ofMnSOD(Val16Ala),CAT(C-262T), andGPx1(Pro198Leu) genes were determined by polymerase chain reaction methods. Multivariate logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs).Results. TheMnSODVal/Ala+Ala/Ala genotype was significantly associated with an increased risk of CAD compared to the Val/Val genotype (OR = 1.86, 95% CI = 1.15-3.01). This polymorphism was also associated with the severity of CAD of single and two vessel diseases. The corresponding ORs were 2.31 (95% CI = 1.32-4.03) and 1.92 (95% CI = 1.02-3.61), respectively. Among cigarette smokers, the harmful genetic effect ofMnSODAla allele on CAD risk was much higher (OR = 2.23, 95% CI = 1.02-4.88). However, the interaction betweenMnSODgenotype and cigarette smoking on CAD risk was not significant. No significant association betweenCATandGPx1polymorphisms and CAD risk was observed.Conclusion. Our results suggest thatMnSODpolymorphism is an independent risk factor for susceptibility to CAD in the Chinese population.

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Genetic susceptibility of five tagSNPs in the endothelin-1 (EDN1) gene to coronary artery disease in a Chinese Han population

Bioscience Reports ◽

10.1042/bsr20171320 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 4

Author(s):

Li-li Liang ◽

Lin Chen ◽

Meng-yuan Zhou ◽

Meng-yun Cai ◽

Jie Cheng ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Chinese Han Population ◽

Chinese Han ◽

Han Population ◽

Endothelin 1 ◽

Increased Risk ◽

Artery Disease ◽

Cad Risk

Endothelin-1 (ET-1) plays important roles in endothelial dysfunction, vascular physiology, inflammation, and atherosclerosis. Nonetheless, the role of ET-1 (EDN1) gene variants on coronary artery disease (CAD) risk remains poorly understood. The aim of the present study was to evaluate the role of EDN1 gene polymorphisms on individual susceptibility to CAD. We genotyped five tagSNPs (single-nucleotide polymorphisms) (rs6458155, rs4145451, rs9369217, rs3087459, and rs2070699) within EDN1 gene in 525 CAD patients and 675 control subjects. In a multivariate logistic regression analysis, we detected an association of rs6458155 in EDN1 gene with the CAD risk; compared with the TT homozygotes, the CT heterozygotes (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.02–2.29, P=0.040) and the CC homozygotes (OR = 1.55, 95% CI = 1.01–2.36, P=0.043) were statistically significantly associated with the increased risk for CAD. A similar trend of the association was found in dominant model (OR = 1.53, 95% CI = 1.05–2.25, P=0.029). Consistently, the haplotype rs6458155C-rs4145451C containing rs6458155 C allele exhibited the increased CAD risk (OR = 1.22, 95% CI = 1.03–1.43, and P=0.018). In addition, CT genotype of rs6458155 conferred the increased plasma ET-1 levels compared with TT genotype (P<0.05). No association of the other four tagSNPs in EDN1 gene with CAD risk was observed. In conclusion, our study provides the first evidence that EDN1 tagSNP rs6458155 is associated with CAD risk in the Chinese Han population, which is probably due to the influence of the circulating ET-1 levels.

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Abstract 5070: Progression of Urine Albumin Excretion Despite of Optimized Therapies to Reduce Atherosclerotic Risk Factors has an Adverse Outcome in Patients with Coronary Artery Disease

Circulation ◽

10.1161/circ.118.suppl_18.s_1139-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Yoshinobu Kitta ◽

Mitsumasa Hirano ◽

Takamitsu Nakamura ◽

Yasushi Kodama ◽

Keita Sano ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Adverse Outcome ◽

Coronary Risk Factors ◽

Urine Albumin Excretion ◽

Albumin Excretion ◽

Urine Albumin ◽

Artery Disease ◽

Cad Risk

Although microalbuminuria is considered a strong risk factor of future cardiovascular disease (CVD), it remains unclear whether changes in urine albumin excretion (UAE) in response to a reduction of coronary risk factors may provide prognostic information in patients with coronary artery disease (CAD). Thus, this study assessed the hypothesis that changes in UAE in response to optimized therapy for reduction of CAD risk may predict future CVD events in patients with CAD. This study enrolled of 213 patients with newly diagnosed CAD who had microalbuminuria (30 mg/day ≤ UAE < 300 mg/day) at entry. Patients with late-stage chronic kidney disease (GFR < 60 ml/min/1.73 m 2 ) at entry were excluded. All patients had individualized, optimized therapies including medications and recommended life style changes to reduce risk factors for CAD according to AHA guidelines. All patients had a repeated test of UAE at 6 months (2 nd test) after the 1 st UAE test. Thereafter, all patients were prospectively followed up for 3 years or until the occurrence of 1 of the following events: CVD death, nonfatal myocardial infarction, unstable angina pectoris requiring revascularization, or ischemic stroke. Progression of UAE at the 2 nd test was defined as > 50% increase from the UAE at the 1 st test. UAE at 2 nd test was progressed in 62 (29%) patients, while it was not progressed in the remaining 151 (71%) patients. UAE at entry was comparable between patients with and without progression of UAE (52 ± 6.2 vs.61 ± 4.7 mg/day, respectively, p = ns). During follow-up period, events occurred in 15 (24%) of the 62 patients with progression of UAE and in 16 (10%) of the 151 patients without progression of UAE (p < 0.01 by chi-square test). Using a multivariate Cox hazards analysis, progression of UAE was a predictor of future CVD events that was independent of UAE at 1 st test, use of medications, age, and traditional CAD risk factors (HR 2.5, 95%CI 1.2 – 4.8, p = 0.01). Progression of urine albumin excretion despite individualized and optimized therapies to reduce CAD risk factors represents an adverse outcome in CAD patients. Periodic measurement of urine albumin excretion may be useful for risk stratification in CAD.

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A new model to implement a structured enhanced education and follow-up program in primary prevention for coronary artery disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.1419 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

O Soran ◽

P.G Karadeniz ◽

I.G Aktas ◽

C.C Genc ◽

M.H Ilkaya ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Medical Students ◽

Primary Prevention ◽

Behavioral Outcomes ◽

Prevention Measures ◽

Artery Disease ◽

Cad Risk

Abstract Background Primary prevention programs for coronary artery disease (CAD) may be effective in improving health-related behavioral outcomes. However, the implementation and especially the maintanance of these programs can be very challenging mainly due to staffing cost. Thus, the present study was designed to assess the feasibility and effectiveness of a longitudinally structured, enhanced education and follow-up program for CAD prevention in an area where the diverse population and economy are major problems. Methods SANKO Coronary Artery Disesae Prevention Project (SCAD-PPI) was designed as a longitudinal study and utilized medical school students to conduct the entire project under the supervision of professors. It started in 2014 and had 2 different education and training phases. In the first phase; every school year, 2nd year Medical students underwent a one-year, specially designed training program on primary prevention for CAD. In the second phase, which took place in the 2nd year of the study, a series of conferences on primary prevention for CAD were organized by the University and local municipalities for underserved populations. Participants were prospectively assigned to an intervention where pre and post conference knowledge were collected and assessed. Every intervention was conducted by specially trained 3rd year Medical students and an education booklet which was specifically designed for this study was given to the participants. Every other month thereafter, for 6 months, each participant was followed by phone. At the 6 month follow -up, data was collected to assess the impact of enhanced education and follow-up program on behavioral outcomes. Results A total of 135 participant were enrolled; 79% were women, mean age was 41±13 years, only 29% had a graduate school degree; 56% were not working. Mean BMI was 28.3±5.1kg/m2. Overall knowledge on CAD risk factors, primary prevention measures, diet and daily exercise habits were very poor. After the enhanced education and follow-up program there was a significant improvement on the knowledge of CAD risk factors and primary prevention measures (p<0.001). More importantly, the follow-up program led participants to implement those positive changes into their lives and maintain a healthy life style. A separate cost analysis showed significant savings. Conclusion This is the first study which showed that a longitudinally structured training program of medical students could be utilized to implement an enhanced education and follow–up program for primary prevention of CAD in an economically challenged, underserved population with successful outcomes. This model program is not only cost-effective and beneficial for public interest but also enhances active interaction of medical students with patients at a very early stage of their career. Funding Acknowledgement Type of funding source: None

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Breast artery calcium noted on screening mammography is predictive of high risk coronary calcium in asymptomatic women: a case control study

VASA ◽

10.1024/0301-1526/a000312 ◽

2013 ◽

Vol 42 (6) ◽

pp. 429-433 ◽

Cited By ~ 19

Author(s):

Martin E. Matsumura ◽

Crystal Maksimik ◽

Matthew W. Martinez ◽

Michael Weiss ◽

James Newcomb ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

High Risk ◽

Coronary Artery Calcium ◽

Screening Mammography ◽

Artery Disease ◽

The Relationship ◽

Asymptomatic Women ◽

Cad Risk

Background: The relationship between breast artery calcification (BAC) noted on mammography and both coronary artery disease and cardiovascular risk remains controversial. Few studies have examined the clinical significance of BAC in asymptomatic women. In the present study we evaluated the relationship between BAC and coronary artery calcium (CAC) as identified by multi-slice CT scanning (MSCT). Patients and methods: Consecutive women (n = 98) with BAC noted on routine mammography but without known coronary artery disease (CAD) were assessed for CAD risk factors and had assessment of coronary calcium by MSCT. A control cohort of consecutive women who were BAC(-) (n = 104) underwent an identical assessment. Results: Women who were BAC(+) were older than those who were BAC(-); otherwise, there were no differences between the 2 groups with regard to traditional cardiac risk factors. Significantly more BAC(+) vs. BAC(-) women were found to have high risk CAC scores, defined as CAC > 400 (11.2 % vs. 1.0 %, p = 0.006). However, the rates of CAC scores of 0 were not different between the two groups (50.0 % vs. 54.8 % for BAC(+) and BAC(-) , respectively, p = 0.586). When examined in a multivariate model including the traditional risk factors of diabetes, increasing age, smoking, hyperlipidemia, and family history of CAD, the presence of BAC remained significantly associated with CAC > 400 (OR = 22.6, 95 % CI = 2.1 - 237.1). Conclusions: The presence of breast artery calcium on screening mammography was a strong independent predictor (odds ratio > 22) of high risk coronary artery calcium scores (defined as CAC > 400). The presence of BAC in those with significant CAD risk factors may warrant further evaluation.

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