Mortality in individuals without known coronary artery disease but with discordance between the Framingham risk score and coronary artery calcium

A risk-management approach based on the Framingham risk score (FRS), although useful in preventing future coronary artery disease (CAD) events, is unable to identify a considerable portion of patients with CAD who need aggressive medical management. Coronary artery calcium (CAC), an anatomic marker of atherosclerosis, correlates well with presence and extent of CAD. This study investigated mortality risk associated with CAC score and FRS in subjects classified as "low risk" versus "high risk" based on FRS. In total 730 veterans without known CAD (61 ± 10 years old, 12.8% women) underwent measurement of their FRS and CAC. Subjects were classified as "discordant low risk" (DLR) if their FRS was <10% and CAC score was ≥ 100 (n = 108, 14.8%) or "discordant high risk" (DHR) if their FRS was ≥ 20% and CAC score was 0 (n = 104, 14.2%). Survival analysis was used to compare mortality rates associated with FRS and CAC in DLR versus DHR subjects. Mortality rate during the mean 48-month follow-up was 7.3% (n = 53) including 18.5% (n = 20) in the DLR group and 7.7% (n = 8) in the DHR group, respectively. Adjusted relative risks of mortality were 5.46 (95% confidence interval [CI] 2.44 to 12.20, p = 0.0001) in subjects with CAC score ≥ 100 compared to CAC score 0 and 1.35 (95% CI 1.01 to 4.32, p = 0.04) in subjects with FRS ≥ 20% compared to FRS <10%. Adjusted relative risk of mortality was 3.6 (95% CI 1.57 to 8.34, p = 0.003) for DLR compared to DHR. Areas under the receiver operator curve to predict mortality were 0.72 for FRS, 0.82 for CAC score, and 0.92 for the combination. In conclusion, the prognostic value of CAC to predict future mortality is superior to the FRS. Addition of CAC score to FRS significantly improves the identification and prognostication of patients without known CAD.     

Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients.

OBJECTIVES: The purpose of this study was to develop risk-adjusted multivariable models that include risk factors and coronary artery calcium (CAC) scores measured with electron-beam tomography in asymptomatic patients for the prediction of all-cause mortality. BACKGROUND: Several smaller studies have documented the efficacy of CAC testing for assessment of cardiovascular risk. Larger studies with longer follow-up will lend strength to the hypothesis that CAC testing will improve outcomes, cost-effectiveness, and safety of primary prevention efforts. METHODS: We used an observational outcome study of a cohort of 25,253 consecutive, asymptomatic individuals referred by their primary physician for CAC scanning to assess cardiovascular risk. Multivariable Cox proportional hazards models were developed to predict all-cause mortality. Risk-adjusted models incorporated traditional risk factors for coronary disease and CAC scores. RESULTS: The frequency of CAC scores was 44%, 14%, 20%, 13%, 6%, and 4% for scores of 0, 1 to 10, 11 to 100, 101 to 400, 401 to 1,000, and >1,000, respectively. During a mean follow-up of 6.8 +/- 3 years, the death rate was 2% (510 deaths). The CAC was an independent predictor of mortality in a multivariable model controlling for age, gender, ethnicity, and cardiac risk factors (model chi-square = 2,017, p < 0.0001). The addition of CAC to traditional risk factors increased the concordance index significantly (0.61 for risk factors vs. 0.81 for the CAC score, p < 0.0001). Risk-adjusted relative risk ratios for CAC were 2.2-, 4.5-, 6.4-, 9.2-, 10.4-, and 12.5-fold for scores of 11 to 100, 101 to 299, 300 to 399, 400 to 699, 700 to 999, and >1,000, respectively (p < 0.0001), when compared with a score of 0. Ten-year survival (after adjustment for risk factors, including age) was 99.4% for a CAC score of 0 and worsened to 87.8% for a score of >1,000 (p < 0.0001). CONCLUSIONS: This large observational data series shows that CAC provides independent incremental information in addition to traditional risk factors in the prediction of all-cause mortality.     

Autosomal genome-wide scan for coronary artery calcification loci in sibships at high risk for hypertension

Coronary artery disease (CAD) is the leading cause of mortality in the developed world. Although several CAD risk factors, including measures of lipid metabolism, obesity, and blood pressure, have a genetic basis, many genes for CAD susceptibility have yet to be identified. Coronary atherosclerosis is the major cause of CAD, but many with coronary atherosclerosis lack symptoms. Thus, a major limitation of using symptomatic CAD endpoints (eg, sudden coronary death, myocardial infarction) as a study outcome is substantial disease misclassification. Coronary artery calcification (CAC) is part of the atherosclerotic process and is an independent predictor of CAD endpoints. In the present study, CAC was noninvasively quantified by electron beam computed tomography. We performed genome-wide multipoint mode-of-inheritance-free linkage analysis on affected sib pairs, defined as being > or = the 70th sex- and age-specific percentile for CAC quantity, in a sample of 29 families enriched for hypertension. Almost 95% of participants were asymptomatic for CAD. Our LOD score (log10 odds in favor of linkage) results provide evidence that chromosomal regions 6p21.3 (maximum LOD score=2.22, P=0.00070) and 10q21.3 (maximum LOD score=3.24, P=0.000057) may harbor genes associated with subclinical coronary atherosclerosis.     

Comparison of prognostic usefulness of coronary artery calcium in men versus women (results from a meta- and pooled analysis estimating all-cause mortality and coronary heart disease death or myocardial infarction)

Women with coronary heart disease (CHD) have higher mortality compared with men. Atherosclerotic imaging risk markers are associated with higher mortality and relative risk of CHD events in women compared with men. However, data on the predictive accuracy of coronary artery calcium (CAC) in women are scarce. We performed a systematic review of the published literature from 2003 to 2006 on the prognostic value of CAC in women and men. Two investigators reviewed Medline for prospective registries on annual rates of CHD death or myocardial infarction (MI) by CAC results. Three studies in 6,481 women and 13,697 men reported results by gender. We also analyzed 2 observational registries for annual all-cause death rates by CAC scores in women (n = 17,779) and men (n = 17,850). Summary relative risk ratios and 95% confidence intervals were calculated using a random effects model. For all-cause mortality, rates were 0.1% to 1.6% per year for women and 0.1% to 2.6% for men with CAC scores from 0 to 10 to > or =1,000, respectively (p <0.0001). For CHD death or MI, annual rates were 0.2% to 1.3% in women and 0.3% to 2.4% for men with low- to high-risk CAC scores. For women with a CAC score of 0, annual CHD death or MI rates were 0.16%, similar to that of men (p = 0.55). Summary relative risk ratios increased 4.9-fold (p = 0.006), 5.5-fold (p = 0.002), and 8.7-fold (p <0.0001) for mild-, moderate-, and high-risk CAC scores, respectively. A comparative analysis of gender differences showed no significant differences between women and men for mild- to high-risk CAC scores (p = 0.66), suggesting an equivalent ability to risk stratify by gender. In conclusion, this meta- and pooled analysis revealed that CAC screening is equally accurate in stratifying risk in women and men.     

Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study

OBJECTIVES: The purpose of this study was to determine the prognostic accuracy of electron beam computed tomographic (CT) scanning of the coronary arteries and the relationship of coronary calcification to standard coronary disease risk factors and C-reactive protein (CRP) in the prediction of atherosclerotic cardiovascular disease (ASCVD) events in apparently healthy middle-age persons. BACKGROUND: As a screening test for coronary artery disease (CAD), electron beam CT scanning remains controversial. METHODS: In a prospective, population-based study, 4,903 asymptomatic persons age 50 to 70 years underwent electron beam CT scanning of the coronary arteries. RESULTS: At 4.3 years, follow-up was available in 4,613 participants (94%), and 119 had sustained at least one ASCVD event. Subjects with ASCVD events had higher baseline coronary calcium scores (median [interquartile range], Agatston method) than those without events: 384 (127, 800) versus 10 (0, 86) (p < 0.0001). For coronary calcium score threshold > or = 100 versus < 100, relative risk (95% confidence interval) was 9.6 (6.7 to 13.9) for all ASCVD events, 11.1 (7.3 to 16.7) for all CAD events, and 9.2 (4.9 to 17.3) for non-fatal myocardial infarction and death. The coronary calcium score predicted CAD events independently of standard risk factors and CRP (p = 0.004), was superior to the Framingham risk index in the prediction of events (area under the receiver-operating characteristic curve of 0.79 +/- 0.03 vs. 0.69 +/- 0.03, p = 0.0006), and enhanced stratification of those falling into the Framingham categories of low, intermediate, and high risk (p < 0.0001). CONCLUSIONS: The electron beam CT coronary calcium score predicts CAD events independent of standard risk factors, more accurately than standard risk factors and CRP, and refines Framingham risk stratification.     

Relation of a coronary artery calcium score higher than 400 to coronary stenoses detected using multidetector computed tomography and to traditional cardiovascular risk factors

Coronary artery calcium (CAC) is an excellent surrogate for atherosclerosis. However, this calcium is nonspecific for obstructive heart disease. This study sought to determine (1) the frequency of significant computed tomographic (CT) angiographic stenoses as a function of CAC scores, and (2) whether high CAC scores were associated with these stenoses independent of traditional risk factors. Subjects (n = 664) underwent Agatston CAC scoring and multidetector CT angiography using current 64-slice technology. Significant stenoses were defined as >60% diameter compromise. Self-reported risk factors and frequency of stenoses were analyzed as a function of CAC scores. The prevalence of risk factors increased significantly as CAC scores increased. Significant univariate associations included age (p <0.001), male gender (p <0.001), hypertension (p <0.001), and hyperlipidemia (p <0.001). There was also a significant association between CAC scores and the frequency of significant CT angiographic stenoses (p <0.001 for trend). The frequency of CT angiographic stenoses increased as CAC scores increased, with 7.9%, 8.3%, 14.5%, and 27.2% prevalences of significant stenoses in those with CAC scores of 1 to 100, 101 to 400, 401 to 1,000, and >1,000, respectively. Conversely, no significant lesions were found in those with no CAC. Multivariable logistic regression analysis controlling for traditional risk factors showed odds ratios for CAC score of 401 to 1,000 and >1,000 for having significant stenoses of 3.1 (95% confidence interval 1.6 to 6.0) and 6.9 (95% confidence interval 3.5 to 13.5), respectively. In conclusion, a CAC score >400 was significantly associated with multidetector CT angiographic stenoses independently of traditional risk factors.     

Relationship Between Coronary Artery Calcium and Atherosclerosis Progression Among Patients With Suspected Coronary Artery Disease

BackgroundAmong symptomatic patients, it remains unclear whether a coronary artery calcium (CAC) score alone is sufficient or misses a sizeable burden and progressive risk associated with obstructive and nonobstructive atherosclerotic plaque.ObjectivesAmong patients with low to high CAC scores, our aims were to quantify co-occurring obstructive and nonobstructive noncalcified plaque and serial progression of atherosclerotic plaque volume.MethodsA total of 698 symptomatic patients with suspected coronary artery disease (CAD) underwent serial coronary computed tomographic angiography (CTA) performed 3.5 to 4.0 years apart. Atherosclerotic plaque was quantified, including by compositional subgroups. Obstructive CAD was defined as ≥50% stenosis. Multivariate linear regression models were used to measure atherosclerotic plaque progression by CAC scores. Cox proportional hazard models estimated CAD event risk (median of 10.7 years of follow-up).ResultsAcross baseline CAC scores from 0 to ≥400, total plaque volume ranged from 30.4 to 522.4 mm³ (P < 0.001) and the prevalence of obstructive CAD increased from 1.4% to 49.1% (P < 0.001). Of those with a 0 CAC score, 97.9% of total plaque was noncalcified. Among patients with baseline CAC <100, nonobstructive CAD was prevalent (40% and 89% in CAC scores of 0 and 1-99), with plaque largely being noncalcified. On the follow-up coronary CTA, volumetric plaque growth (P < 0.001) and the development of new or worsening stenosis (P < 0.001) occurred more among patients with baseline CAC ≥100. Progression varied compositionally by baseline CAC scores. Patients with no CAC had disproportionate growth in noncalcified plaque, and for every 1 mm³ increase in calcified plaque, there was a 5.5 mm³ increase in noncalcified plaque volume. By comparison, patients with CAC scores of ≥400 exhibited disproportionate growth in calcified plaque with a volumetric increase 15.7-fold that of noncalcified plaque. There was a graded increase in CAD event risk by the CAC with rates from 3.3% for no CAC to 21.9% for CAC ≥400 (P < 0.001).ConclusionsCAC imperfectly characterizes atherosclerotic disease burden, but its subgroups exhibit pathogenic patterns of early to advanced disease progression and stratify long-term prognostic risk.     

Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality.

OBJECTIVES: The purpose of this study was to examine the association of all-cause death with the coronary computed tomographic angiography (CCTA)-defined extent and severity of coronary artery disease (CAD). BACKGROUND: The prognostic value of identifying CAD by CCTA remains undefined. METHODS: We examined a single-center consecutive cohort of 1,127 patients > or =45 years old with chest symptoms. Stenosis by CCTA was scored as minimal (<30%), mild (30% to 49%), moderate (50% to 69%), or severe (> or =70%) for each coronary artery. Plaque was assessed in 3 ways: 1) moderate or obstructive plaque; 2) CCTA score modified from Duke coronary artery score; and 3) simple clinical scores grading plaque extent and distribution. A 15.3 +/- 3.9-month follow-up of all-cause death was assessed using Cox proportional hazards models adjusted for pretest CAD likelihood and risk factors. Deaths were verified by the Social Security Death Index. RESULTS: The CCTA predictors of death included proximal left anterior descending artery stenosis and number of vessels with > or =50% and > or =70% stenosis (all p < 0.0001). A modified Duke CAD index, an angiographic score integrating proximal CAD, plaque extent, and left main (LM) disease, improved risk stratification (p < 0.0001). Patients with <50% stenosis had the highest survival at 99.7%. Survival worsened with higher-risk Duke scores, ranging from 96% survival for 1 stenosis > or =70% or 2 stenoses > or =50% (p = 0.013) to 85% survival for > or =50% LM artery stenosis (p < 0.0001). Clinical scores measuring plaque burden and distribution predicted 5% to 6% higher absolute death rate (6.6% vs. 1.6% and 8.4% vs. 2.5%; p = 0.05 for both). CONCLUSIONS: In patients with chest pain, CCTA identifies increased risk for all-cause death. Importantly, a negative CCTA portends an extremely low risk for death.     

Relation of coronary artery calcium to flow-mediated dilation and C-reactive protein levels in asymptomatic patients with heterozygous familial hypercholesterolemia

The extent of coronary artery calcium (CAC) is correlated with coronary artery disease prognosis. However, the relation of CAC to endothelial function and high-sensitivity C-reactive protein (hs-CRP) in patients with asymptomatic heterozygous familial hypercholesterolemia (FH) requires clarification. The study aim was to investigate the relations among CAC, endothelial function, and hs-CRP in patients with asymptomatic heterozygous FH. Thirty-two patients with asymptomatic heterozygous FH (mean age 42 years) and 34 healthy control subjects (mean age 36 years) were enrolled. We measured CAC by electron-beam computed tomography and endothelial function by flow-mediated dilation of the brachial artery. A higher percentage of patients with FH had a positive CAC score compared with the control group. Comparing the FH group with detectable CAC (CAC score >0) and undetectable CAC (CAC score of 0), we found higher hs-CRP levels (0.29 +/- 0.23 vs 0.07 +/- 0.08 mg/dl, p = 0.001) and reduced flow-mediated dilation (0.04 +/- 0.03 vs 0.08 +/- 0.03, p = 0.005) in the detectable CAC group. Multivariate analysis showed an independent correlation of hs-CRP with detectable CAC (relative risk 5.034, 95% confidence interval 1.525 to 16.613, p = 0.04). In conclusion, FH subjects with positive CAC scores have decreased flow-mediated dilation and increased hs-CRP levels. Furthermore, hs-CRP level is the only independent predictor of the presence of CAC.     

Coronary atherosclerotic burden in veteran male recreational athletes with low to intermediate cardiovascular risk

IntroductionAlthough there is evidence that a significant proportion of veteran athletes have coronary atherosclerotic disease (CAD), its prevalence in recreational athletes with low to intermediate cardiovascular (CV) risk is not established. This study aimed to characterize the coronary atherosclerotic burden in veteran male recreational athletes with low to intermediate CV risk.MethodsAsymptomatic male athletes aged ≥40 years with low to intermediate risk, who exercised >4 hours/week for >5 years, underwent cardiac computed tomography (CT) for coronary artery calcium (CAC) scoring and CT angiography. High coronary atherosclerotic burden was defined as at least one of the following: CAC score >100; CAC score ≥75th percentile; obstructive CAD; disease involving the left main, three vessels or two vessels including the proximal left anterior descending artery; segment involvement score >5; or CT Leaman score ≥5. Athletes were categorized by tertiles of exercise volume, calculated by metabolic equivalent of task (MET) scores.ResultsA total of 105 athletes were included, all with SCORE <4%, mainly engaged in high-dynamic sports. Median exercise volume was 66 (44-103) METs/hour/week, with 8±5 hours training/week and 17±10 years of exercise. A high coronary atherosclerotic burden was present in 27 (25.7%) athletes. Ten (9.5%) athletes had CAC score >100, 13 (12.4%) had CAC score ≥75th percentile and six (5.7%) had obstructive lesions. The extent and severity of coronary plaques did not differ according to exercise volume.ConclusionsThe prevalence of subclinical CAD detected by cardiac CT in veteran male recreational athletes with low to intermediate CV risk was high. Up to a quarter of our cohort had a high coronary atherosclerotic burden.     

Age and the power of zero CAC in cardiac risk assessment: overview of the literature and a cautionary case

The coronary artery calcium (CAC) score is a marker of advanced coronary atherosclerosis. Numerous prospective cohorts have validated CAC as an independent marker that improves prognostication in atherosclerotic cardiovascular disease (ASCVD) beyond traditional risk factors. Accordingly, CAC is now incorporated into international cardiovascular guidelines as a tool to inform medical decision-making. Particular interest concerns the significance of zero CAC score (CAC=0). While many studies report CAC=0 to virtually exclude obstructive coronary artery disease (CAD), non-negligible rates of obstructive CAD despite CAC=0 are reported in certain populations. Overall, the current literature supports the power of zero CAC as a strong downward risk classifier in older patients, whose CAD burden predominantly involves calcified plaque. However, with their higher burden of non-calcified plaque, CAC=0 does not reliably exclude obstructive CAD in patients under 40 years. Illustrating this point, we present a cautionary case of a 31-year-old patient found to have severe two-vessel CAD despite CAC=0. We highlight the value of coronary computed tomography angiography (CCTA) as the gold-standard non-invasive imaging modality when the diagnosis of obstructive CAD is in question.Key words: calcium score, coronary artery calcium, coronary computed tomography angiography (CCTA), heart disease risk factors     

Usefulness of impaired chronotropic response to exercise as a predictor of mortality, independent of the severity of coronary artery disease

Chronotropic incompetence, or an attenuated heart rate response to exercise, has been shown to be associated with an adverse outcome. It is not known whether chronotropic incompetence predicts all-cause mortality independent of angiographic severity of coronary artery disease (CAD). Study subjects included consecutive patients who underwent first-time, symptom-limited exercise treadmill testing and coronary angiography within 90 days; no patient was taking beta blockers or had a history of heart failure, valve disease, or prior revascularization. Chronotropic response was measured in 2 ways: (1) failure to reach 85% of the age-predicted maximum heart rate, and (2) a low chronotropic index, a measure of exercise heart rate response that accounts for effects of age, physical fitness, and resting heart rate. Angiographic severity of CAD was assessed using the Duke Prognostic Weight Score, with a score > or = 42 considered to be indicative of severe CAD. Among 384 eligible patients, failure to reach 85% of the age-predicted maximum heart rate occurred in 61 (16%) and a low chronotropic index was noted in 133 (35%). Severe CAD was present in 63 (16%). During 6 years of follow-up there were 56 deaths. Mortality was predicted by failure to reach target heart rate (RR 1.85, 95% confidence interval [CI] 1.01 to 3.39, chi-square = 4, p = 0.05), by severe CAD (RR 2.21, 95% CI 1.24 to 3.95, chi-square = 8, p = 0.007), and, most strongly, by a low chronotropic index (RR 2.72, 95% CI 1.60 to 4.61, chi-square = 15, p = 0.0002). In a multivariable model, low chronotropic index remained predictive of death (adjusted RR 2.22, 95% CI 1.29 to 3.82, p = 0.004), whereas severe CAD no longer predicted death (adjusted RR 1.27, 95% CI 0.70 to 2.31, p > 0.4). Thus, chronotropic incompetence is a strong and independent predictor of death, even after accounting for the angiographic severity of CAD.     

Clinical significance of the coronary calcification score by multidetector row computed tomography for the evaluation of coronary stenosis in Japanese patients.

BACKGROUND: The coronary artery calcification (CAC) score measured by multidetector row computed tomography (MDCT) has emerged as a marker for predicting coronary artery disease (CAD). To evaluate the clinical significance of the CAC score, coronary artery stenosis as assessed by coronary angiography (CAG) was compared with the CAC score determined by MDCT, risk factors and medications. METHODS AND RESULTS: Subjects included 374 consecutive patients who underwent ECG-gate CT angiography using MDCT. The accuracy in patients with a CAC score >or=400 was 84%, and significantly lower than that in patients with a CAC score =0. In addition 92 patients (68 males, 24 females; mean age, 63+/-11 years) who underwent both MDCT and CAG within a 1-month period were selected for further investigation. Patients with significant coronary stenosis had a significantly higher CAC score than those without stenosis. In addition, a higher number of stenosed vessels was associated with a higher CAC score. The subjects were divided into 3 groups according to the CAC score: low (0-12), intermediate (13-444) and high (>or=445). The CAC score was significantly associated with age, and plasma levels of total cholesterol and hemoglobinA1c, and logistic regression analysis revealed that significant coronary stenosis as assessed by CAG was most closely correlated with the CAC score (p=0.03). CONCLUSIONS: The CAC score determined by MDCT can predict CAD independent of other factors, such as age, metabolic diseases and medications, when coronary stenosis can not be diagnosed because of severe calcification.     

Mean Versus Peak Coronary Calcium Density on Non-Contrast CT: Calcium Scoring and ASCVD Risk Prediction

ObjectivesThis study sought to assess the relationship between mean vs peak calcified plaque density and their impact on calculating coronary artery calcium (CAC) scores and to compare the corresponding differential prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) mortality.BackgroundThe Agatston CAC score is quantified per lesion as the product of plaque area and a 4-level categorical peak calcium density factor. However, mean calcium density may more accurately measure the heterogenous mixture of lipid-rich, fibrous, and calcified plaque reflective of ASCVD risk.MethodsWe included 10,373 individuals from the CAC Consortium who had CAC >0 and per-vessel measurements of peak calcium density factor and mean calcium density. Area under the curve and continuous net reclassification improvement analyses were performed for CHD and ASCVD mortality to compare the predictive abilities of mean calcium density vs peak calcium density factor when calculating the Agatston CAC score.ResultsParticipants were on average 53.4 years of age, 24.4% were women, and the median CAC score was 68 Agatston units. The average values for mean calcium density and peak calcium density factor were 210 ± 50 HU and 3.1 ± 0.5, respectively. Individuals younger than 50 years of age and/or those with a total plaque area <100 mm² had the largest differences between the peak and mean density measures. Among persons with CAC 1-99, the use of mean calcium density resulted in a larger improvement in ASCVD mortality net reclassification improvement (NRI) (NRI = 0.49; P < 0.001 vs. NRI = 0.18; P = 0.08) and CHD mortality discrimination (Δ area under the curve (AUC) = +0.169 vs +0.036; P < 0.001) compared with peak calcium density factor. Neither peak nor mean calcium density improved mortality prediction at CAC scores >100.ConclusionMean and peak calcium density may differentially describe plaque composition early in the atherosclerotic process. Mean calcium density performs better than peak calcium density factor when combined with plaque area for ASCVD mortality prediction among persons with Agatston CAC 1-99.     

Comparison of coronary calcium in firefighters with abnormal stress test findings and in asymptomatic nonfirefighters with abnormal stress test findings

Firefighters are known to have an elevated rate of sudden cardiac death compared to the general population. It is unclear whether this finding is related to underlying cardiovascular risk factors or whether firefighting inherently carries additional risk. Our objective was to determine whether Los Angeles county firefighters have higher coronary artery calcium (CAC) scores and increased atherosclerosis as determined using 64-slice cardiac, multidetector computed tomography. A total of 647 asymptomatic firefighters evaluated as a part of a wellness protocol were referred for cardiac multidetector computed tomography to evaluate abnormal exercise treadmill test findings. They were matched by age and cardiovascular risk factors, with 2,533 asymptomatic subjects undergoing cardiac computed tomography because of abnormal electrocardiographic or exercise treadmill test findings. CAC and the prevalence of obstructive coronary artery disease by vessel were derived. Finally, the predictors of CAC were analyzed using regression analysis. Of the firefighters, 49% had detectable CAC compared to 43% of controls (p = 0.015). Although the lesions were most prevalent in the left anterior descending artery in both groups, more firefighters had any left anterior descending artery stenosis compared to the controls (p <0.0001). The firefighters also had more left main coronary artery lesions than did the controls (p <0.0001). The firefighters had significantly greater CAC scores than did with the controls (p <0.001). Furthermore, the firefighters had significantly greater mean CAC scores (66 ± 8 in firefighters vs 33 ± 4 for controls, p <0.001). Firefighter status was independently associated with a 41-point increase in the CAC score (p <0.001). In conclusion, asymptomatic firefighters had more atherosclerosis and CAC than the matched controls.     

The prevalence of coronary artery calcium among diabetic individuals without known coronary artery disease

OBJECTIVES: We sought to examine the age and gender distribution of coronary artery calcium (CAC) by diabetes status in a large cohort of asymptomatic individuals. BACKGROUND: Among individuals with diabetes, coronary artery disease (CAD) is a major cause of morbidity and mortality. Electron-beam tomography (EBT) quantifies CAC, a marker for atherosclerosis. METHODS: Screening for CAC by EBT was performed in 30,904 asymptomatic individuals stratified by their self-reported diabetes status, gender, and age. The distribution of CAC across the strata and the association between diabetes and CAC were examined. RESULTS: Compared with nondiabetic individuals (n = 29,829), those with diabetes (n = 1,075) had higher median CAC scores across all but two age groups (women 40 to 44 years old and men and women > or =70 years old). Overall, the likelihood of having a CAC score in the highest age/gender quartile was 70% greater for diabetic individuals than for their nondiabetic counterparts. CONCLUSIONS: Younger diabetic individuals appear to have calcified plaque burden comparable to that of older individuals without diabetes. These findings call for future research to determine if EBT-CAC screening has an incremental value over the current CAD risk assessment of individuals with diabetes.     

Comparative value of coronary artery calcium and multiple blood biomarkers for prognostication of cardiovascular events

The value of coronary artery calcium (CAC) scoring versus multiple biomarkers in increasing risk prediction for cardiovascular disease (CVD) remains unknown. The study group consisted of 1,286 asymptomatic participants (mean ± SD 59 ± 8 years old) with no known coronary heart disease. Mean follow-up time was 4.1 ± 0.4 years with the primary outcome of combined CVD (cardiac death, myocardial infarction, stroke, and late target vessel revascularization). CAC was calculated by the method of Agatston. Biomarkers measured were C-reactive protein, interleukin-6, myeloperoxidase, B-type natriuretic peptide, and plasminogen activator-1. During follow-up 35 participants developed CVD events including cardiac deaths (6%), myocardial infarction (23%), strokes (17%), and late revascularizations (54%). In Cox proportional-hazards models adjusted for Framingham Risk Score (FRS), presence of log CAC beyond FRS was associated with increased hazards for CVD events (hazard ratio 1.7, 95% confidence interval [CI] 1.4 to 2.0, p <0.001). Multiple biomarkers score was also associated with increased risk beyond FRS (hazard ratio 2.1, p = 0.02) per 1-U increase in score; however, the c-statistic did not increase significantly (0.75, 95% CI 0.68 to 0.84, p = 0.32). The c-statistic increased when log CAC was incorporated into FRS without or with multiple biomarkers score (c-statistic 0.84, p = 0.003 and p = 0.008 respectively). Addition of CAC to risk factors showed significant reclassification (net reclassification improvement 0.35 (95% CI 0.11 to 0.58, p = 0.007; integrated discrimination index 0.076, p = 0.0001), whereas addition of multiple biomarkers score did not show significant reclassification. In conclusion, in this study of asymptomatic subjects without known CVD, addition of CAC but not biomarkers substantially improved risk reclassification for future CVD events beyond traditional risk factors.     

Nonalcoholic fatty liver disease is associated with coronary artery calcification

Nonalcoholic fatty liver disease (NAFLD) is related to risk factors of coronary artery disease, such as dyslipidemia, diabetes, and metabolic syndrome, which are closely linked with visceral adiposity. The aim of this study was to investigate whether NAFLD was associated with coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis independent of computed tomography (CT)-measured visceral adiposity. Out of 5,648 subjects who visited one of our health screening centers between 2003 and 2008, we enrolled 4,023 subjects (mean age, 56.9 ± 9.4 years; 60.7% males) without known liver disease or a history of ischemic heart disease. CAC score was evaluated using the Agatston method. On univariate analysis, the presence of CAC (score >0) was significantly associated with age, sex, body mass index, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, triglycerides, and increased risk of diabetes, hypertension, smoking, and NAFLD. Increasing CAC scores (0, <10, 10-100, ≥ 100) were associated with higher prevalence of NAFLD (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.61-2.10; P<0.001). Multivariable ordinal regression analysis was adjusted for traditional risk factors, and CT-measured visceral adipose tissue area in a subgroup of subjects showed that the increased CAC scores were significantly associated with the presence of NAFLD (OR, 1.28, 95% CI, 1.04-1.59; P = 0.023) independent of visceral adiposity. CONCLUSION: Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors, including visceral adiposity. These data suggest that NAFLD might be an independent risk factor for coronary artery disease.     

Relation of epicardial and pericoronary fat to coronary atherosclerosis and coronary artery calcium in patients undergoing coronary angiography

Fat surrounding coronary arteries might aggravate coronary artery disease (CAD). We investigated the relation between epicardial adipose tissue (EAT) and pericoronary fat and coronary atherosclerosis and coronary artery calcium (CAC) in patients with suspected CAD and whether this relation is modified by total body weight. This was a cross-sectional study of 128 patients with angina pectoris (61 +/- 6 years of age) undergoing coronary angiography. EAT volume and pericoronary fat thickness were measured with cardiac computed tomography. Severity of coronary atherosclerosis was assessed by the number of stenotic (> or =50%) coronary vessels; extent of CAC was determined by the Agatston score. Patients were stratified for median total body weight (body mass index [BMI] 27 kg/m(2)). Overall, EAT and pericoronary fat were not associated with severity of coronary atherosclerosis and extent of CAC. In patients with low BMI, those with multivessel disease had increased EAT volume (100 vs 67 cm(3), p = 0.04) and pericoronary fat thickness (9.8 vs 8.4 mm, p = 0.06) compared with those without CAD. Also, patients with severe CAC had increased EAT volume (108.0 vs 69 cm(3), p = 0.02) and pericoronary fat thickness (10.0 vs 8.2 mm, p value = 0.01) compared with those with minimal/absent CAC. In conclusion, EAT and pericoronary fat were not associated with severity of coronary atherosclerosis and CAC in patients with suspected CAD. However, in those with low BMI, increased EAT and pericoronary fat were related to more severe coronary atherosclerosis and CAC. Fat surrounding coronary arteries may be involved in the process of coronary atherosclerosis, although this is different for patients with low and high BMIs.