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Background: Age- and gender-adjusted percentiles of coronary artery calcium (CAC) score are commonly reported to compare a patient's coronary atherosclerosis burden to that of others of the same age and gender. The number of calcified plaques (numCP) detected on CAC scanning, a measure of plaque diffusivity, is associated with increased cardiovascular risk and, in the intermediate CAC range, adds to the CAC score in predicting mortality. This study aims to develop adjusted percentiles for numCP to provide a better context for understanding CAC scan findings., Methods and Results: Using nonparametric modeling techniques, the distribution of numCP was analyzed in 70,320 consecutive, asymptomatic patients without prior clinically-diagnosed cardiovascular disease who were part of the Coronary Artery Calcium Consortium and supplemented by additional patients referred for clinical CAC scanning in a single center between 1998 and 2016. Nomograms for age-adjusted numCP percentiles for each gender were generated using quantile regression. The prevalence and average number of calcified coronary plaque were found to be higher in men than women. Distribution of numCP in women was found to closely mirror that of men approximately a decade younger. NumCP increased consistently across age groups in both men and women for each quantile category., Conclusions: A nomogram for age and gender-adjusted percentiles for the numCP on CAC scans has been developed in a large population of asymptomatic patients studied across multiple centers. This numCP nomogram may provide an additional tool for refining physician recommendations regarding treatment and expressing to patients how their CAC findings relate to others of similar age and gender. The numCP percentiles may also provide a meaningful way to evaluate and report the rate of progression of CAC on serial studies., (Copyright © 2019 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: The Society of Cardiovascular Computed Tomography (SCCT) recommends consideration of coronary artery calcium (CAC) scoring among individuals with a family history (FH) of coronary heart disease (CHD) and atherosclerotic cardiovascular disease (ASCVD) risk <5%. No dedicated study has examined the prognostic significance of CAC scoring among this population., Methods: The CAC Consortium is a multi-center observational cohort study from four clinical centers linked to long-term follow-up for cause-specific mortality. All CAC scans were physician referred and performed in patients without a history of CHD. Our analysis includes 14,169 patients with ASCVD scores <5% and self-reported FH of CHD., Results: This cohort had a mean age of 48.1 (SD 7.4), was 91.3% white, 47.4% female, had an average ASCVD score of 2.3% (SD 1.3), and 59.4% had a CAC = 0. The event rate for all-cause mortality was 1.2 per 1000 person-years, 0.3 per 1000 person-years for CVD-specific mortality, and 0.2 per 1000 person-years for CHD-specific mortality. In multivariable Cox proportional hazard models, those with CAC>100 had a 2.2 (95% CI 1.5-3.3) higher risk of all-cause mortality, 4.3 (95% CI 1.9-9.5) times higher risk of CVD-specific mortality, and a 10.4 (95% CI 3.2-33.7) times higher risk of CHD-specific mortality compared to individuals with CAC = 0. The NNS to detect CAC >100 in this sample was 9., Conclusion: In otherwise low risk patients with FH of CHD, CAC>100 were associated with increased risk of all-cause and CHD mortality with event rates in a range that may benefit with preventive pharmacotherapy. These data strongly support new SCCT recommendations regarding testing of patients with a family history of CHD., (Copyright © 2019. Published by Elsevier Inc.)

We examined the utility of coronary artery calcium (CAC) for cardiovascular risk stratification among hypertensive adults, including those fitting eligibility for SPRINT (Systolic Blood Pressure Intervention Trial). Additionally, we used CAC to identify hypertensive adults with cardiovascular disease (CVD) mortality rates equivalent to those observed in SPRINT who may, therefore, benefit from the most intensive blood pressure therapy. Our study population included 16 167 hypertensive patients from the CAC Consortium, among whom 6375 constituted a "SPRINT-like" population. We compared multivariable-adjusted hazard ratios of coronary heart disease and CVD deaths by CAC category (0, 1-99, 100-399, ≥400). Additionally, we generated a CAC-CVD mortality curve for patients aged >50 years to determine what CAC scores were associated with CVD death rates observed in SPRINT. Mean age was 58.1±10.6 years. During a mean follow-up of 11.6±3.6 years, there were 409 CVD deaths and 207 coronary heart disease deaths. Increasing CAC scores were associated with increased coronary heart disease and CVD mortality (coronary heart disease-CAC 100-399: hazard ratio [95% CI] 1.88 [1.04-3.40], CAC ≥400: 4.16 [2.34-7.39]; CVD-CAC 100-399: 1.93 [1.31-2.83], CAC ≥400: 3.51 [2.40-5.13]). A similar increased risk was observed across 10-year atherosclerotic CVD risk categories and in the SPRINT-like population. A CAC score of 220 (confidence range, 165-270) was associated with the CVD mortality rate observed in SPRINT. CAC risk stratifies adults with hypertension, including those who are SPRINT eligible. A CAC score of 220 can identify hypertensive adults with SPRINT-level CVD mortality risk and, therefore, may be reasonable for identifying candidates for aggressive blood pressure therapy.

Aims: Coronary artery calcium (CAC) is the strongest predictor of cardiovascular disease (CVD), yet is also associated with chronic non-CVD such as cancer. We performed this analysis in order to describe the association of CAC with CVD vs. cancer mortality., Methods and Results: The CAC Consortium is comprised of 66 636 scans performed in asymptomatic patients without known CVD. The mean age was 54 ± 11 years and 67% of participants were men. Cause of death was ascertained from death certificates. The association of CAC with cause-specific mortality was calculated using Fine and Gray sub-distribution hazard ratio (SHR) models, which account for competing causes of death. There were 3158 deaths over a median 12 ± 4 years follow-up (37% cancer and 32% CVD). Cancer was the leading cause of death when CAC = 0 (50%) with CVD overtaking cancer when baseline CAC >300. Compared to participants with CAC = 0, the SHR for CVD mortality was 1.44 [95% confidence interval (CI) 1.14-1.81], 2.26 (95% CI 1.76-2.90), and 3.68 (95% CI 2.90-4.67) for patients with CAC 1-99, 100-299, and ≥300, and the SHR for cancer was 1.04 (95% CI 0.88-1.23), 1.19 (95% CI 0.98-1.46), and 1.30 (95% CI 1.07-1.58)., Conclusion: Cancer was the leading cause of death for patients with baseline CAC = 0, whereas CVD overtook cancer above a threshold of CAC >300. These results argue for a focused approach for patients at the extremes of CAC scoring while suggesting that combined CVD and cancer primary prevention strategies for patients with intermediate CAC scores may significantly decrease mortality from the two leading causes of death., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background Coronary artery calcium (CAC) predicts cardiovascular disease (CVD) events; however, less is known about how its prognostic implications vary by race/ethnicity. Methods and Results A total of 38 277 whites, 1621 Asians, 977 blacks, and 1349 Hispanics from the CAC Consortium (mean age 55 years, 35% women) were followed over a median of 11.7 years. Modeling CAC in continuous and categorical (CAC=0; CAC 1-99; CAC 100-399; CAC ≥400) forms, we assessed its predictive value for all-cause and CVD mortality by race/ethnicity using Cox proportional hazards and Fine and Gray competing-risk regression, respectively. We also assessed the impact of race/ethnicity on risk within individual CAC strata, using whites as the reference. Models were adjusted for traditional cardiovascular risk factors. Increased CAC was associated with higher total and CVD mortality risk in all race/ethnicity groups, including Asians. However, the risk gradient with increasing CAC was more pronounced in blacks and Hispanics. In Fine and Gray subdistribution hazards models adjusted for traditional cardiovascular risk factors and CAC (continuous), blacks (subdistribution hazard ratio 3.4, 95% confidence interval, 2.5-4.8) and Hispanics (subdistribution hazard ratio 2.3, 95% confidence interval, 1.6-3.2) showed greater risk of CVD mortality when compared with whites, while Asians had risk similar to whites. These race/ethnic differences persisted when CAC=0. Conclusions CAC predicts all-cause and CVD mortality in all studied race/ethnicity groups, including Asians and Hispanics, who may be poorly represented by the Pooled Cohort Equations. Blacks and Hispanics may have greater mortality risk compared with whites and Asians after adjusting for atherosclerosis burden, with potential implications for US race/ethnic healthcare disparities research.

Background: Although coronary artery calcium (CAC) has been investigated for over two decades, there is very limited data on the association of CAC with cause of death. The CAC Consortium is a large ongoing multi-center observational cohort of individuals who underwent non-contrast cardiac-gated CAC testing and systematic, prospective, long-term follow-up for mortality with ascertainment of cause of death., Methods: Four participating institutions from three states within the US (California, Minnesota, and Ohio) have contributed individual-level patient data to the CAC Consortium (spanning years 1991-2010). All CAC scans were clinically indicated and physician-referred in patients without a known history of coronary heart disease. Using strict inclusion and exclusion criteria to minimize missing data and to eliminate non-dedicated CAC scans (i.e. concomitant CT angiography), a sharply defined and well-characterized cohort of 66,636 patients was assembled. Mortality status was ascertained using the Social Security Administration Death Master File and a validated algorithm. In addition, death certificates were obtained from the National Death Index and categorized using ICD (International Classification of Diseases) codes into common causes of death., Results: Mean patient age was 54 ± 11 years and the majority were male (67%). Prevalence of CVD risk factors was similar across sites and 55% had a <5% estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk. Approximately 45% had a Calcium score of 0 and 11% had an Agatston Score ≥400. Over a mean follow-up of 12 ± 4 years, there were 3158 deaths (4.15 per 1000 person-years). The majority of deaths were due to cancer (37%) and CVD (32%). Most CVD deaths were due to CHD (54%) followed by stroke (17%). In general, CAC score distributions were similar across sites, and there were similar cause of death patterns., Conclusions: The CAC Consortium is large and highly generalizable data set that is uniquely positioned to expand the understanding of CAC as a predictor of mortality risk across the spectrum of disease states, allowing innovative modeling of the competing risks of cardiovascular and non-cardiovascular death., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Risk assessment in the extensive calcified plaque phenotype has been limited by small sample size., Objective: We studied all-cause mortality rates among asymptomatic patients with markedly elevated Agatston scores > 1000., Methods: We studied a clinical cohort of 44,052 asymptomatic patients referred for coronary calcium scans. Mean follow-up was 5.6 years (range, 1-13 years). All-cause mortality rates were calculated after stratifying by Agatston score (0, 1-1000, 1001-1500, 1500-2000, and >2000). A multivariable Cox regression model adjusting for self-reported traditional risk factors was created to assess the relative mortality hazard of Agatston scores 1001 to 1500, 1501 to 2000, and >2000. With the use of post-estimation modeling, we assessed for the presence of an upper threshold of risk with high Agatston scores., Results: A total of 1593 patients (4% of total population) had Agatston score > 1000. There was a continuous graded decrease in estimated 10-year survival across increasing Agatston score, continuing when Agatston score > 1000 (Agatston score 1001-1500, 78%; Agatston score 1501-2000, 74%; Agatston score > 2000, 51%). After multivariable adjustment, Agatston scores 1001 to 1500, 1501 to 2000, and >2000 were associated with an 8.05-, 7.45-, and 13.26-fold greater mortality risk, respectively, than for Agatston score of 0. Compared with Agatston score 1001 to 1500, Agatston score 1501 to 2000 had a similar all-cause mortality risk, whereas Agatston score > 2000 had an increased relative risk (Agatston score 1501-2000: hazard ratio [HR], 1.01 [95% CI, 0.67-1.51]; Agatston score > 2000: HR, 1.79 [95% CI, 1.30-2.46]). Graphical assessment of the predicted survival model suggests no upper threshold for risk associated with calcified plaque in coronary arteries., Conclusion: Increasing calcified plaque in coronary arteries continues to predict a graded decrease in survival among patients with extensive Agatston score > 1000 with no apparent upper threshold., (Published by Elsevier Inc.)

Background: Coronary artery calcium (CAC) has emerged as an important prognostic indicator for coronary heart disease risk. The purpose of this study was to assess the impact of increasing CAC burden among those with and without hypertension (HTN)., Methods: The study cohort consisted of 44,052 consecutive asymptomatic individuals free of known coronary heart disease referred for electron beam computed tomography (EBT) for the assessment of subclinical atherosclerosis. Patients were followed for a mean of 5.6 ± 2.6 years (range 1-13 years). The primary endpoint for the study cohort was mortality from any cause., Results: About one third (34%) of the subjects were affected by hypertension. There were 901 deaths (2.05%) in the total study population over a mean follow-up of 5.6 ± 2.6 years (range 1-13 years). The lowest event rate was observed in those with no CAC among those without hypertension (1.6 events per 1000 person years), whereas those with CAC ≥400 and hypertension had the highest all fatality rate (9.8 per 1000 person years). Compared to a CAC score of 0, increasing CAC scores (1-99, 100-399, and ≥400) were associated with increases in all-cause mortality. The hazard ratio was 2.19-7.74-fold among those without HTN and 3.00-5.83 fold among those with HTN. Overall likelihood ratio chi square statistics demonstrated that the addition of CAC scores increased mortality prediction beyond traditional risk among those with hypertension., Conclusion: Addition of CAC scores contributed significantly in predicting mortality in addition to just traditional risk factors alone among those with and without hypertension., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of this study was to further explore the interplay between smoking status, coronary artery calcium (CAC), and all-cause mortality., Background: Prior studies have not directly compared the relative prognostic impact of CAC in smokers versus nonsmokers. In particular, although a calcium score of zero (CAC = 0) is a known favorable prognostic marker, whether smokers with CAC = 0 have as good a prognosis as nonsmokers with CAC = 0 is unknown. Given that computed tomography (CT) screening for lung cancer appears effective in smokers, the relative prognostic implications of visualizing any CAC versus no CAC on such screening also deserve study., Methods: Our study cohort consisted of 44,042 asymptomatic individuals referred for noncontrast cardiac CT (age 54 ± 11 years, 54% men). Subjects were followed for a mean of 5.6 years. The primary endpoint was all-cause mortality., Results: Approximately 14% (n = 6,020) of subjects were active smokers at enrollment. There were 901 deaths (2.05%) overall, with increased mortality in smokers versus nonsmokers (4.3% vs. 1.7%, p < 0.0001). Smoking remained a risk factor for mortality across increasing strata of CAC scores (1 to 100, 101 to 400, and >400). At each stratum of elevated CAC score, mortality in smokers was consistently higher than mortality in nonsmokers from the CAC stratum above. In multivariable analysis within these strata, we found mortality hazard ratios of 3.8 (95% confidence interval [CI]: 2.8 to 5.2), 3.5 (95% CI: 2.6 to 4.9), and 2.7 (95% CI: 2.1 to 3.5), respectively, in smokers compared with nonsmokers. However, among the 19,898 individuals with CAC = 0, the mortality hazard ratio for smokers without CAC was 3.6 (95% CI: 2.3 to 5.7), compared with nonsmokers without CAC., Conclusions: Smoking is a risk factor for death across the entire spectrum of subclinical coronary atherosclerosis. Smokers with any CAC had significantly higher mortality than smokers without CAC, a finding with implications for smokers undergoing lung cancer CT-based screening. However, the absence of CAC might not be as useful a "negative risk factor" in active smokers, because this group has mortality rates similar to nonsmokers with mild-to-moderate atherosclerosis., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Current guidelines recommend the use of coronary artery calcium (CAC) scoring for intermediate-risk patients; however, the potential role of CAC among individuals who have no risk factors (RFs) is less established. We sought to examine the relationship between the presence and burden of traditional RFs and CAC for the prediction of all-cause mortality., Methods and Results: The study cohort consisted of 44,052 consecutive asymptomatic individuals free of known coronary heart disease referred for computed tomography for the assessment of CAC. The following RFs were considered: (1) current cigarette smoking, (2) dyslipidemia, (3) diabetes mellitus, (4) hypertension, and (5) family history of coronary heart disease. Patients were followed for a mean of 5.6 ± 2.6 years for the primary end point of all-cause mortality. Among individuals who had no RF, Cox proportional model adjusted for age and sex identified that increasing CAC scores were associated with 3.00- to 13.38-fold higher mortality risk. The lowest survival rate was observed in those with no CAC and no RF, whereas those with CAC ≥ 400 and ≥3 RFs had the highest all-cause fatality rate. Notably, individuals with no RF and CAC ≥ 400 had a substantially higher mortality rate compared with individuals with ≥3 RFs in the absence of CAC (16.89 versus 2.72 per 1000 person-years)., Conclusions: By highlighting that individuals without RFs but elevated CAC have a substantially higher event rates than those who have multiple RFs but no CAC, these findings challenge the exclusive use of traditional risk assessment algorithms for guiding the intensity of primary prevention therapies.

Safety and efficacy of a biologically active derivative of vitamin B(5) (pantethine) on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) metabolism was studied in North American subjects at conventional low to moderate cardiovascular disease (CVD) risk. A total of 120 subjects initiated a therapeutic lifestyle change (TLC) diet 4 weeks before randomization (baseline) and maintained the diet throughout a 16-week study period; at baseline, subjects were randomized in a triple-blinded manner to either pantethine (600 mg/d, baseline to week 8, and 900 mg/d, weeks 9-16) or identically labeled, nonbiologically active placebo (n = 60 per group). We hypothesized that pantethine would lower TC and low-density lipoprotein in low-CVD-risk North American subjects in a similar manner as reported in high-CVD-risk subjects studied mainly in Italy and Japan. While sustaining a TLC diet and in comparison with placebo, pantethine demonstrated significant (P < .005) and sustained reductions (from baseline to week 16) in TC (6 mg/dL, 0.16 mmol/L, 3%), LDL-C (4 mg/dL, 0.10 mmol/L, 4%), and apolipoprotein B (4 mg/dL, 0.04 g/L, 5%). Our data suggest that pantethine supplementation for 16 weeks (600 mg/d for weeks 1-8 then 900 mg/d for weeks 9-16) is safe and significantly lowers TC and LDL-C over and above the effect of TLC diet alone. Although the absolute magnitude of these effects was small in these low- to moderate-risk North Americans (4-6 mg/dL), the results are noteworthy as prior studies have shown that, for each 1 mg/dL (0.026 mmol/L) reduction in LDL-C, there is a concomitant 1% reduction in overall future CVD risk., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aortic valve calcium (AVC) can be quantified on the same computed tomographic scan as coronary artery calcium (CAC). Although CAC is an established predictor of cardiovascular events, limited evidence is available for an independent predictive value for AVC. We studied a cohort of 8,401 asymptomatic subjects (mean age 53 ± 10 years, 69% men), who were free of known coronary heart disease and were undergoing electron beam computed tomography for assessment of subclinical atherosclerosis. The patients were followed for a median of 5 years (range 1 to 7) for the occurrence of mortality from any cause. Multivariate Cox regression models were developed to predict all-cause mortality according to the presence of AVC. A total of 517 patients (6%) had AVC on electron beam computed tomography. During follow-up, 124 patients died (1.5%), for an overall survival rate of 96.1% and 98.7% for those with and without AVC, respectively (hazard ratio 3.39, 95% confidence interval 2.09 to 5.49). After adjustment for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking, and a family history of premature coronary heart disease, AVC remained a significant predictor of mortality (hazard ratio 1.82, 95% confidence interval 1.11 to 2.98). Likelihood ratio chi-square statistics demonstrated that the addition of AVC contributed significantly to the prediction of mortality in a model adjusted for traditional risk factors (chi-square = 5.03, p = 0.03) as well as traditional risk factors plus the presence of CAC (chi-square = 3.58, p = 0.05). In conclusion, AVC was associated with increased all-cause mortality, independent of the traditional risk factors and the presence of CAC., (Copyright © 2010. Published by Elsevier Inc.)

Background: Elevated low-density lipoprotein cholesterol (LDL-C) levels are a major cardiovascular disease risk factor. Genetic factors are an important determinant of LDL-C levels., Methods: To identify single nucleotide polymorphisms associated with LDL-C and subclinical coronary atherosclerosis, we performed a genome-wide association study of LDL-C in 841 asymptomatic Amish individuals aged 20 to 80 years, with replication in a second sample of 663 Amish individuals. We also performed scanning for coronary artery calcification (CAC) in 1018 of these individuals., Results: From the initial genome-wide association study, a cluster of single nucleotide polymorphisms in the region of the apolipoprotein B-100 gene (APOB) was strongly associated with LDL-C levels (P < 10(-68)). Additional genotyping revealed the presence of R3500Q, the mutation responsible for familial defective apolipoprotein B-100, which was also strongly associated with LDL-C in the replication sample (P < 10(-36)). The R3500Q carrier frequency, previously reported to be 0.1% to 0.4% in white European individuals, was 12% in the combined sample of 1504 Amish participants, consistent with a founder effect. The mutation was also strongly associated with CAC in both samples (P < 10(-6) in both) and accounted for 26% and 7% of the variation in LDL-C levels and CAC, respectively. Compared with noncarriers, R3500Q carriers on average had LDL-C levels 58 mg/dL higher, a 4.41-fold higher odds (95% confidence interval, 2.69-7.21) of having detectable CAC, and a 9.28-fold higher odds (2.93-29.35) of having extensive CAC (CAC score ≥400)., Conclusion: The R3500Q mutation in APOB is a major determinant of LDL-C levels and CAC in the Amish.

Background: The effect of aggressive medical therapy on quantitative coronary plaque burden is not generally known, especially in ethnic Chinese., Aims: We reasoned that Cardiac CT could conveniently quantify early coronary atherosclerosis in our patient population, and hypothesized that serial observation could differentiate the efficacy of aggressive medical therapy regarding progression and regression of the atherosclerotic process, as well as evaluating the additional impact of life-style modification and the relative effects of the application of statin therapy., Methods: We employed a standardized Cardiac CT protocol to serially scan 113 westernized Hong Kong Chinese individuals (64 men and 49 women) with Chest Pain and positive coronary risk factors. In all cases included for this serial investigation, subsequent evaluation showed no significantly-obstructive coronary disease by functional studies and angiography. After stringent risk factor modification, including aggressive statin therapy to achieve LDL-cholesterol lowering conforming to N.C.E.P. ATP III guidelines, serial CT scans were performed 1-12 years apart for changes in coronary artery calcification (CAC), using the Agatston Score (AS) for quantification., Results: At baseline, the mean AS was 1413.6 for males (mean age 54.4 years) and 2293.3 for females (mean age 62.4 years). The average increase of AS in the entire study population was 24% per year, contrasting with 16.4% per year on strict risk factor modification plus statin therapy, as opposed to 33.2% per year for historical control patients (p < 0.001). Additionally, 20.4% of the 113 patients demonstrated decreasing calcium scores. Medical therapy also yielded a remarkably low adverse event rate during the follow-up period --- 2 deaths, 2 strokes and only 1 case requiring PCI., Conclusions: This study revealed that aggressive medical therapy can positively influence coronary plaque aiding in serial regression of calcium scores.

Background: The presence of coronary artery calcium (CAC) is an independent marker of increased risk of cardiovascular disease (CVD) events and mortality. However, the predictive value of thoracic aorta calcification (TAC), which can be additionally identified without further scanning during assessment of CAC, is unknown., Methods: We followed a cohort of 8401 asymptomatic individuals (mean age: 53+/-10 years, 69% men) undergoing cardiac risk factor evaluation and TAC and CAC testing with electron beam computed tomography. Multivariable Cox proportional hazards models were developed to predict all-cause mortality based on the presence of TAC., Results: During a median follow-up period of 5 years, 124 (1.5%) deaths were observed. Overall survival was 96.9% and 98.9% for those with and without detectable TAC, respectively (p<0.0001). Compared to those with no TAC, the hazard ratio for mortality in the presence of TAC was 3.25 (95% CI: 2.28-4.65, p<0.0001) in unadjusted analysis. After adjusting for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking and family history of premature coronary artery disease, and presence of CAC the relationship remained robust (HR 1.61, 95% CI: 1.10-2.27, p=0.015). Likelihood ratio chi(2) statistics demonstrated that the addition of TAC contributed significantly in predicting mortality to traditional risk factors alone (chi(2)=13.62, p=0.002) as well as risk factors+CAC (chi(2)=5.84, p=0.02) models., Conclusion: In conclusion, the presence of TAC was associated with all-cause mortality in our study; this relationship was independent of conventional CVD risk factors as well as the presence of CAC.

Objectives: We sought to quantify the mortality rates associated with absent and low positive (CAC 1 to 10) coronary artery calcium (CAC)., Background: There is increasing interest in the absence of CAC as a "negative" cardiovascular risk factor. However, published event rates for individuals with no CAC vary, likely owing to differences in baseline risk, follow-up period, and outcome ascertainment. The prognostic significance of low CAC (CAC 1 to 10) is not well described., Methods: Annualized all-cause mortality rates were assessed in 44,052 consecutive asymptomatic patients referred for CAC testing. Mean follow-up of the cohort was 5.6 +/- 2.6 years (range 1 to 13 years)., Results: A total of 19,898 patients (45%) had no CAC on screening electron beam tomography, whereas 5,388 (12%) had low levels of CAC (CAC 1 to 10), and 18,766 (43%) had CAC >10. There were 104 deaths in those with no CAC (0.52%), 58 deaths in those with CAC 1 to 10 (1.06%), and 739 deaths in those with CAC >10 (3.96%). Annualized all-cause mortality rates for CAC = 0, CAC 1 to 10, and CAC >10 were 0.87, 1.92, and 7.48 deaths/1,000 person-years, respectively. The hazard ratio (HR) for all-cause mortality among CAC 1 to 10 versus CAC = 0 after adjustment for traditional risk factors was 1.99 (95% confidence interval [CI]: 1.44 to 2.75). Smoking (HR: 3.97, 95% CI: 2.75 to 5.41) and diabetes mellitus (HR: 3.36, 95% CI: 2.09 to 5.41) were associated with few events observed in CAC = 0 group., Conclusions: In appropriately selected asymptomatic patients, the absence of CAC predicts excellent survival with 10-year event rates of approximately 1%. A finding of 0 CAC might be used as a rationale to emphasize lifestyle therapies rather than pharmacotherapy and to forgo repeated imaging studies. Individuals with low CAC score (CAC 1 to 10) are at increased risk above individuals with a 0 score and could be considered a distinct risk group by physicians and investigators.

Background: Bone-marrow derived progenitor cells (PCs) may play a role in maintaining vascular health by actively repairing damaged endothelium. The purpose of this study in asymptomatic Old Order Amish men (n = 90) without hypertension or diabetes was to determine if PC count, as determined by CD34+ cell count in peripheral blood, was associated with 10-year risk of cardiovascular disease (CVD) and measures of subclinical atherosclerosis., Methods and Results: CD34+ cell count by fluorescence-activated cell sorting, coronary artery calcification (CAC) by electron beam computed tomography, and CVD risk factors were obtained. Carotid intimal-medial thickness (CIMT) also was obtained in a subset of 57 men. After adjusting for 10-year CVD risk, CD34+ cell count was significantly associated with CAC quantity (p = 0.03) and CIMT (p < 0.0001). A 1-unit increase in natural-log transformed CD34+ cell count was associated with an estimated 55.2% decrease (95% CI: -77.8% to -9.3%) in CAC quantity and an estimated 14.3% decrease (95% CI: -20.1% to -8.1%) in CIMT., Conclusions: Increased CD34+ cell count was associated with a decrease in extent of subclinical atherosclerosis in multiple arterial beds, independent of 10-year CVD risk. Further investigations of associations of CD34+ cell count with subclinical atherosclerosis in asymptomatic individuals could provide mechanistic insights into the atherosclerotic process.

The Agatston total coronary artery calcium (CAC) score, derived from a non-contrast CT scan of the heart (also known as the "heartscan") in asymptomatic and symptomatic patients, has been shown to provide incremental and independent assessment to conventional risk factors based upon literally hundreds of studies published from around the world. However, recent data have emerged to indicate that there is additional information which can be derived from a "heartscan" beyond the calcium score. These include recent data on the applicability across ethnic sub-groups, prognostication in the elderly, defining "heart age" versus chronological age for individual risk stratification, evaluating CAC distribution in addition to total CAC score, and looking beyond the coronary arteries regarding left ventricular size, aortic root/thoracic aorta diameter, and epicardial fat.

Coronary artery calcification (CAC) and common carotid artery intima-media thickness (CIMT) are measures of subclinical vascular disease. This 2000-2006 study aimed to characterize the associations among coronary artery disease risk factors, CAC quantity, and CIMT and to estimate shared genetic and environmental contributions to both CAC and CIMT among 478 asymptomatic Amish adults in Lancaster County, Pennsylvania. Heritability for CAC quantity and CIMT, adjusted for age and sex, was 0.42 (P = 0.0001) and 0.29 (P = 0.003), respectively. CAC quantity and CIMT were modestly correlated (adjusted r = 0.14, P = 0.003) but showed little evidence of shared genetic or environmental factors. However, significant genetic correlations were found for CAC quantity and total cholesterol (0.44 (standard error, 0.19); P = 0.03), for CAC quantity and low density lipoprotein cholesterol (0.55 (standard error, 0.17); P = 0.005), and for CIMT and waist circumference (0.58 (standard error, 0.25); P = 0.046), suggesting shared genes for these risk factors and measures of subclinical disease. Results suggest that some of the same genes influence variation in CAC and low density lipoprotein cholesterol, whereas a different set of genes influences variation in CIMT and waist circumference.

Awareness of coronary artery calcium scanning by computed tomography as a reproducible, low-radiation dose means to estimate plaque burden in patients necessitates clinical recommendations for interpretation. Coronary artery calcium scanning is best applied in the intermediate risk, asymptomatic adult population. Calcium scores >100 or >75th percentile transform the intermediate risk patient to high risk with recommendations for more aggressive therapy. Scores exceeding the 90th percentile or >400 define the group at the highest risk of a cardiovascular event and may suggest further cardiac testing. Scores from 11 to 100 and <75th percentile confirm intermediate risk status, and scores from 0 to 10 and <75th percentile convert the patient to low or very low risk.

Clinical cardiac computed tomography (CT) began with electron-beam CT in the early 1980s and continues now with multidetector CT in the 21st Century. The major applications of noncontrast cardiac CT are currently for the quantification of coronary artery calcium - a reliable and repeatable means to estimate atherosclerotic plaque burden. The major applications of contrast-enhanced CT (CT angiography) is for a more detailed estimation of total plaque burden by qualitatively defining noncalcified and complex plaque as well as ruling out obstructive coronary artery disease. Both of these applications are discussed and comments are made from the author regarding clinical applications based upon reviewing the published literature and through personal experience.

Background: Comparison of atherosclerosis and its risk factors among diverse populations may provide insights into the pathogenesis of the disease. We investigated differences in traditional coronary artery disease (CAD) risk factors and presence and quantity of coronary artery calcification (CAC), a marker of subclinical coronary atherosclerosis, between two diverse non-Hispanic white populations living in the US., Methods and Results: Members of the Old Order Amish (OOA), a unique culture with a physically active rural lifestyle who rarely use prescription medications, were compared to another non-Hispanic white population with a more typical US lifestyle, Epidemiology of Coronary Artery Calcification (ECAC), Study participants from Rochester, Minnesota. Although age- and sex-adjusted presence and quantity of CAC in those with detectable CAC were similar between study groups, there were significant differences in the distribution of many traditional CAD risk factors. OOA had significantly less abdominal adiposity and history of cigarette smoking but a less advantageous lipid profile than ECAC participants. Importantly, after adjusting for CAD risk factors, presence of CAC and quantity of CAC among those with detectable CAC were significantly higher among OOA than ECAC participants., Conclusions: Identification of factors contributing to differences in subclinical disease across groups could increase our understanding of mechanisms for coronary atherosclerosis.

Vascular calcification and osteoporosis are common age-related processes that are influenced by both genetic and nongenetic factors. Whether common genes underlie these processes is not known. We measured coronary artery calcification (CAC), aortic calcification (AC), and bone mineral density (BMD) in 682 men and women from large Old-Order Amish families. We assessed the heritabilities of these traits and then evaluated, using variance decomposition procedures, whether variation in the traits was influenced by a common set of genes (i.e., pleiotropy). Significant heritabilities were detected for BMD of the femoral neck and spine (0.65, 0.63) and CAC and AC (0.43, 0.42). Mean BMD did not differ significantly across quartiles of either CAC or AC in either sex. In neither the total group nor any single subgroup (men, women, postmenopausal women) did any of the genetic or environmental correlations between BMD and vascular calcification achieve statistical significance. However, subjects with a history of cardiovascular disease (CVD) events had significantly lower BMD at the femoral neck compared to subjects who reported no prior history of CVD (age-, sex-, body mass index-, and family structure-adjusted P = 0.003). We detected no evidence for shared genes affecting the joint distribution of bone and vascular calcification. However, our results do reveal a lower BMD in subjects with a prior history of CVD in the Old-Order Amish.

We utilized coronary artery calcium scores (CACS) to assess differences in atherosclerosis burden between asymptomatic White populations living in continents with different cardiovascular disease rates. The similarities in the genetic pool between Brazilian and Portuguese Caucasian subjects offered an opportunity to assess the influence of environmental factors on the development of atherosclerosis. We reviewed CACS data from 17,563 individuals (12,378 men and 5169 women) collected in the USA (74% of the subjects), Brazil (15% of the subjects) and Portugal (11% of the subjects). CACS was absent in 80 and 88% of Portuguese men and women, compared with 46 and 62% and 33 and 59% of Brazilian and US counterparts (p<0.0001). Although the US subjects showed the lowest prevalence of risk factors they had a higher median (interquartile range) CACS than the Brazilian and the Portuguese cohorts: 4 (0;87), 1 (0;68) and 0 (0;0), respectively (p<0.0001). After adjusting for differences in age and cardiovascular risk factors, US men showed higher relative risk ratios of having any CACS than either Brazilian or Portuguese men. Brazilian and US women did not differ as far as risk of CACS although they demonstrated a greater risk than Portuguese women. In this study, significant differences in CACS were detected among three nations in different continents. The CACS differences paralleled the respective cardiovascular mortality rates.

Cardiovascular disease (CVD) is the leading cause of mortality and a major cause of morbidity. Coronary heart disease (CHD) accounts for nearly half of all CVD deaths. Currently estimation of risk in primary prevention is based on the Framingham risk equations, which inputs traditional risk factors and is helpful in predicting the development of CHD in asymptomatic individuals. However many individuals suffer events in the absence of established risk factors for atherosclerosis and broad based population risk estimations may have little precision when applied to a given individual. To meet the challenge of CHD risk assessment, several tools have been developed to identify atherosclerotic disease in its preclinical stages. This paper aims to incorporate information from coronary artery calcification (CAC) scoring from a computed tomographic "heartscan" (using Electron Beam Tomography (EBT) as the validated prototype) along with current Framingham risk profiling in order to refine risk on an absolute scale by combining imaging and clinical data to affect a more comprehensive calculation of absolute risk in a given individual. For CAC scores above the 75th percentile but <90th percentile, 10 years is added to chronological age, and for CAC scores above the 90th percentile, 20 years is added to current chronological age. Among those in whom a positive CAC score is the norm such as older individuals (men> or =55 years, women> or =65 years) a CAC = 0 will result in an age point score corresponding to the age-group whose median CAC score is zero i.e., 40-44 years for men and 55-59 years for women. The utilization of CAC scores allows the inclusion of sub-clinical disease definition into the context of modifiable risk factors as well as identifies high-risk individuals requiring aggressive treatment.

Background: Coronary artery calcium (CAC) scanning is being increasingly used for cardiac risk assessment in asymptomatic patients, particularly in those with a Framingham 10-year risk of 10% to 20%. Physician awareness of this technology and its appropriate uses and limitations is crucial to appropriate use., Methods: With the goal of establishing clinical paradigms, this document integrates the results of key published articles, Framingham Risk Score, National Cholesterol Education Program Adult Treatment Plan III guidelines, American College of Cardiology/American Heart Association exercise testing and angiographic guidelines, and the authors' extensive clinical experience., Results: Coronary artery calcium scanning is best used in the asymptomatic population with a 10% to 20% risk of cardiac events over 10 years, with selected application in higher and lower risk categories. In the 10%-20% risk patient, coronary artery calcium scores >100 or >75th percentile for age and sex transform the moderately high-risk patient to higher risk status with the attendant recommendation for more aggressive therapy; scores from 11 to 100 and <75th percentile are consistent with the 10%-20% 10-year risk status and scores from 0 to 10 and <75th percentile convert the patient to lesser risk categories. If stress testing is planned in the asymptomatic patient, it should be preceded by coronary artery calcium scanning and performed only for scores >400; it should always precede coronary angiography in these patients., Conclusions: Coronary artery calcium scanning is an important risk assessment tool with direct clinical applications; it is of particular utility in the Framingham 10%-20% 10-year risk population.

Background: Coronary heart disease (CHD) is the leading cause of death among American women. Currently, global risk assessment derived by Framingham risk equation (FRE) is used to identify women at increased risk for CHD. Electron-beam computed tomography (EBCT) derived coronary artery calcium (CAC) scores are validated markers for future CHD events among asymptomatic individuals. However, the adequacy of FRE for identifying asymptomatic women with CAC is unknown., Methods and Results: We studied 2447 consecutive non-diabetic asymptomatic females (55 +/- 10 years). Based upon FRE, 90% were classified as low-risk (FRE < or = 9% 10-year risk of hard CHD events), 10% intermediate-risk (10-20%), and none were considered as high-risk (> 20%). Coronary artery calcium was present in 33%, whereas CAC > or = 100 and CAC > or = 400 were seen in 10 and 3% of women, respectively. Overall, 20% of women had age-gender derived > or = 75th percentile CAC. According to FRE, the majority (84%) of women with significant CAC > or = 75th percentile were classified as low-risk. Approximately half (45%) of low-risk women with > or = 2 CHD risk factors and a family history of premature CHD had significant CAC., Conclusion: Framingham risk equation frequently classifies women as being low-risk, even in the presence of significant CAC. Determination of CAC may provide incremental value to FRE in identifying asymptomatic women who will benefit from targeted preventative measures.

Cardiovascular disease (CVD) is the leading cause of mortality in women and a major cause of morbidity. Coronary artery disease (CAD) accounts for nearly half of all CVD deaths. Traditional risk factors are very helpful in predicting the development of CAD in women; however, many women suffer events in the absence of established risk factors for atherosclerosis. To meet the challenge of CAD, several tools have been developed to identify atherosclerotic disease in its preclinical stages, with the hope of modifying its natural history. In this article, we review the current literature on utilization of electron beam tomography (EBT) for detection of CAD as a tool to conduct risk stratification in the general asymptomatic female population as well as among asymptomatic women. In conclusion, EBT can be used to estimate the overall coronary atherosclerotic plaque burden in women. It can also be used to diagnose its presence and determine its extent; furthermore, information from the coronary artery calcium scores can be used to assess the likelihood of obstructive disease and to provide prognostic information. Finally, EBT has the potential to determine the consequences of therapeutic interventions regarding progression, stabilization, or regression of coronary atherosclerotic disease.

We studied 6,141 consecutive, asymptomatic, nondiabetic patients who underwent electron beam tomography and explored the interaction between metabolic risk factors (RFs) and premature family history (FH) of coronary heart disease (CHD) in predicting the presence and severity of coronary arterial calcium (CAC). In the presence of >2 metabolic RFs, patients with a positive FH of premature CHD had a significantly higher prevalence of any CAC, CAC >/=100, and CAC >/=75th age-gender percentile than those without a FH of CHD. Our study demonstrated that a familial propensity to subclinical atherosclerosis interacts with the presence of >/=2 metabolic RFs, magnifying the risks for those exposed to both.

Background: Traditional risk factors predict the 10-year risk of developing coronary heart disease (CHD). Underlying risk factors like physical inactivity, obesity (BMI >30 kg/m2), and family history of premature CHD are independently associated with CHD. High burden of coronary artery calcification (CAC) on electron beam tomography (EBT) is a CHD risk equivalent., Goals: To determine the association between CAC and traditional risk assessment and whether the presence of added underlying risk factors is associated with advanced CAC in low- and intermediate-risk individuals., Methods: After excluding patients with CHD, we studied 8549 asymptomatic individuals referred for EBT for cardiac risk assessment. Traditional myocardial infarction risk score was estimated according to Framingham criteria, and individuals were divided into 3 groups: low-risk (< or =9% MI risk over the next 10 years), intermediate-risk (10%-20% risk), and high-risk (>20 % risk). Advanced CAC was defined as a calcium score > or =75th percentile based on sex and age., Results: The prevalence of advanced CAC was 20% in low-risk, 27% in intermediate-risk, and 31% in high-risk individuals (P < .001). Underlying risk factors were incrementally associated with advanced CAC in low- and intermediate-risk individuals (P < .001). A receiver operating characteristic curve analysis revealed that addition of underlying risk factors to traditional risk assessment increased the area under the curve significantly from 0.56 to 0.62 (P < .001)., Conclusion: A substantial proportion of low- and intermediate-risk individuals have advanced CAC. Adding family history, obesity, and physical inactivity to traditional risk assessment improves prediction of advanced CAC, which may lead these individuals to be treated more aggressively at an earlier age.

Lack of physical activity (PA) increases risk of coronary heart disease. Metabolic risk factors increase the risk of coronary heart disease and development of advanced coronary artery calcium (CAC). We hypothesized that, in a population with multiple metabolic risk factors (> or =2), the degree of PA would be inversely associated with the degree and prevalence of CAC. After excluding subjects who had known diabetes and coronary heart disease, we studied 779 asymptomatic patients referred for electron beam tomography. All patients had > or =2 of the following metabolic risk factors: blood pressure > 130/85 mm Hg, serum triglycerides >150 mg/dl, serum high-density lipoprotein < 40 and < 50 mg/dl in men and women, respectively, and body mass index >30 kg/m(2). Advanced CAC was defined as a calcium score >75th percentile based on gender and age. In the study, 37% patients were sedentary, 26% engaged in moderate-duration (< 30 minutes 1 to 2 times/week) PA, and 37% engaged in long-duration (> or =30 minutes > or =3 times/week) PA. The median CAC scores were 24 (sedentary), 18 (moderate PA), and 11 (long-duration PA; p <0.002). Advanced CAC was prevalent in 26% of sedentary patients, 24% of patients who performed moderate PA, and 16% of patients who engaged in long-duration PA (p <0.05). On logistic regression analysis, long-duration PA had an independent inverse association with advanced CAC. Thus, asymptomatic patients who have > or =2 metabolic risk factors and who regularly engage in long-duration PA have a lower prevalence of CAC than do those who are sedentary or participate in moderate-duration PA.

Electron beam computed tomography has been available clinically for 20 years. It is the only computed tomography scanner specifically developed for cardiac imaging. Over the past decade, with improvements in methodology and computer software, electron beam computed tomography has been shown to provide an excellent method to perform noninvasive coronary angiography. This article looks at the historical aspects of electron beam computed tomography and comments on how to perform and interpret electron beam angiography studies. The expanding development of noninvasive coronary and peripheral angiography methods using computed tomography will have a significant influence on cardiovascular specialists and their practices.

We developed age- and gender-specific normative tables of calcium volume scores by using data from 12,936 asymptomatic patients who underwent electron beam tomographic scanning and compared the volume with the Agatston scores obtained in the same subjects. The 2 scores increased as the number of atherosclerotic risk factors increased. The volume scores were statistically smaller than the Agatston scores at the upper quartile level.

EBT has undergone rigorous testing for reliability and validity of CAC measurements, and has been proven to be useful in identifying individuals with, or at risk for, coronary heart disease. Although MDCT is a promising tool for coronary calcium scoring, more studies are needed that compare EBT and MDCT scans in the same patients, especially with calcium scores of less than 100. Further radiation dose reduction strategies for MDCT are currently being evaluated. MDCT studies of progression, reproducibility, and outcomes are needed to fully evaluate its potential to measure and serially follow atherosclerosis compared to EBT. Studies examining the benefit of serial coronary calcium scoring to non-invasively assess the progression or regression of coronary calcium are currently underway. EBT is a method that can be used to estimate the overall coronary atherosclerotic plaque burden. It can be used to diagnose the presence and determine the extent of coronary atherosclerosis; furthermore, the calcium score information can be used to assess the likelihood of advanced obstructive disease and to provide prognostic information. Finally, serial CAC measurements by EBT have the potential to determine the efficacy of therapeutic interventions by demonstrating progression, stabilization, or regression of coronary atherosclerotic disease during therapy.

Objective: We introduce stratification data for three methods (Agatston, volume, mass) obtained from one single patient population., Materials and Methods: Measurements in 11,490 individuals scanned from 1999 to 2002 with electron-beam CT were used for this study., Results: Our Agatston score ranges agree reasonably well with the Kondos values except for measurements in patients at the extreme ages, at which we sampled a wider age range and consequently had different biases of averages. Neither method is preferable because except for a small percentage of individuals near the dividing lines, stratification is the same for the three methods. When we matched them against a known "lesion" phantom, the Agatston and volume scores behave nonlinearly, and the latter grossly overestimates volume. The mass method is linear except for lesions near the edge of detectability and matches known volumes to within a small percentage., Conclusion: We provide validated risk stratification data for use with mass scoring methods.

X-ray computed tomography (CT) is widely available in the world and has the ability to provide high-definition, thin-section imaging of any body part. In particular, CT over the past decade has been shown in numerous publications to allow for quantitation of coronary calcification, a proven surrogate for coronary artery atheromatous plaque. Electron beam tomography (EBT) and multidetector CT (MDCT) have been studied for these purposes. However, there are methodological differences between types of CT scanners and precision of calcium scoring is a function of their individual technical capabilities and limitations. These technical aspects are detailed here. Although MDCT has shown considerable improvements in recent years, EBT remains the clinical reference standard for noninvasive definition of atherosclerotic plaque.

Background: Electron-beam CT (EBCT) quantification of coronary artery calcification (CAC) allows noninvasive assessment of coronary atherosclerosis. We undertook a follow-up study to determine whether CAC extent, measured at the time of angiography by EBCT, predicted future hard cardiac events, comprising cardiac death and nonfatal myocardial infarction (MI). We also assessed the potential of selected coronary artery disease (CAD) risk factors, prior CAD event history (MI or revascularization), and angiographic findings (number of diseased vessels and overall disease burden) to predict subsequent hard events., Methods and Results: Two hundred eighty-eight patients who underwent contemporaneous coronary angiography and EBCT scanning were contacted after a mean of 6.9 years. Vital status and history of MI during follow-up were determined. Cox proportional hazards models were used to compare the predictive ability of CAC extent with selected CAD risk factors, CAD event history, and angiographic findings. Median CAC score was 160 (range 0 to 7633). The 22 patients who experienced hard events during follow-up were older and had more extensive CAC and angiographic disease (P<0.05). Only 1 of 87 patients with CAC score <20 experienced a subsequent hard event during follow-up. Event-free survival was significantly higher for patients with CAC scores <100 than for those with scores >/=100 (relative risk 3.20; 95% CI 1.17 to 8.71). When a stepwise multivariable model was used, only age and CAC extent predicted hard events (risk ratios 1.72 and 1.88, respectively; P<0.05)., Conclusions: In patients undergoing angiography, CAC extent on EBCT is highly predictive of future hard cardiac events and adds valuable prognostic information.

Tomographic coronary artery plaque imaging is possible noninvasively using x-ray computed tomography (CT) and magnetic resonance imaging (MRI). The pathophysiology of coronary plaque disease is one of repeated inflammation and repair. Imaging of coronary artery calcium, a consequence of this process, is possible using CT, whereas MRI has the potential to examine the lipid and fibrous components of plaque acquisition and 3-dimensional slice registration. Quantitation of coronary artery calcium has been validated using electron-beam CT [EBCT], a unique device that images the entire heart in a single breathold from rapid [100 msec] tomographic scans done in synchrony with the heart cycle. Current mechanical CT devices require 300 to 500 msec per scan and acquire hundreds of tomographic images that then must be retrospectively separated to the required phase of the heart cycle. There are limited correlations with calcium scoring by EBCT versus mechanical CT and the later device has a limitation in situations of low plaque volume and necessitates increased radiation exposure to the patient. MRI has been shown to have the potential to define plaque composition ex vivo or in the aorta, but studies of the heart arteries are so far very limited. Widespread utilization of noninvasive plaque imaging requires that the studies be done consistently and reproducibly. The training of the interpreting physicians is of paramount concern.

Aim: sudden coronary death (SCD) in older individuals is generally associated with extensive coronary atherosclerosis, although it may be the first manifestation of ischaemic heart disease. In younger age-groups, SCD may occur in the presence of less severe disease. We sought to (1) examine the extent of coronary atherosclerosis in young victims of SCD compared with age- and sex-matched controls, (2) analyse the composition of atherosclerotic plaques in these patients, (3) identify the predominant mechanism of SCD, and (4) evaluate the possibility of detecting this mechanism on the basis of morphologic plaque features, in particular presence and amount of lipid accumulation and calcific deposits., Methods and Results: coronary arteries were obtained at autopsy from 28 victims of SCD under age 50 with no prior clinical manifestation of ischaemic heart disease (IHD) and no myocardial scar formation and from 16 age- and sex-matched subjects dying of noncardiac causes out of hospital. Sections of all available major coronary arteries were cut in 5-mm intervals to yield a total of 1357 histologic sections, which were analysed using digitised planimetry. Victims of SCD had significantly more major coronary arteries per subject with luminal area narrowing > or = 75% than controls (on average, 2.1 vs. 0.2). Plaque area per histologic section was 5.1 +/- 2.1 mm(2) in SCD cases and 2.0 +/- 0.9 mm(2) in controls (P < 0.001). The major constituent of all plaques was fibrous tissue. Lipid core area per section was 0.49 +/- 0.59 mm(2) in SCD cases and 0.004 +/- 0.01 mm(2) in controls (P < 0.001), and calcified plaque area was 0.18 +/- 0.19 mm(2) in SCD cases and 0.02 +/- 0.05 mm(2) in controls (P < 0.001), both defining significant differences between SCD cases and controls. Arterial thrombosis, most often with underlying plaque rupture was the mechanism of SCD in > 80% of the cases. Considering histologic sections with > or = 50 and with > or = 75% area stenosis, plaque rupture was independently predicted by lipid core area. Calcific deposits were a frequent feature of plaque rupture but were only associated with it in univariate analysis., Conclusions: the extent and severity of coronary atherosclerosis in young victims of SCD as the first manifestation of IHD was substantially greater than in age-and sex-matched controls and comparable with that previously reported in SCD cases with a broader age range. Lipid core and calcified plaque areas provided for excellent separation between the two groups, which may have implications for identifying persons at increased risk for SCD by non invasive visualisation and assessment of the coronary arteries.

Rationale and Objectives: The study compared the performance of conventional endocardial and epicardial centroid algorithms with the new "myocardial" centroid algorithm in patients with anterior myocardial infarction. "Floating" endocardial or epicardial centroid algorithms, commonly used in tomographic imaging methods to assess regional motion, may misrepresent left ventricular regional myocardial function in the presence of markedly asymmetric left ventricular contraction., Methods: A new centroid algorithm based on regional myocardial mass distribution was tested in 29 patients with a first anterior myocardial infarction and was compared with conventional centroid algorithms. Direct comparisons in 60 equal sectors at one midventricular level per patient were performed between electron beam computed tomography and technetium-99m sestamibi single-photon emission computed tomography. The thresholds of regional myocardial function used to define infarction were varied for regional ejection fraction from 20% to 40% and for regional wall thickening from 0 to 4 mm. Regression and Bland-Altman analysis were used to compare infarct size by regional myocardial function with infarct size by sestamibi single-photon emission computed tomography., Results: The new myocardial centroid showed the least shift toward infarcted myocardium from diastole to systole and had the highest amplitudes of the measurement curves for regional ejection fraction and regional wall thickening. The optimal regional myocardial function thresholds for each centroid algorithm for regional ejection fraction were endocardial, 30% (R = 0.62; mean difference to sestamibi, -0.5% +/- 22.1% tomographic infarct size points); epicardial, 30% (R = 0.79; mean difference, 2.2% +/- 13.1% tomographic infarct size points); and new myocardial, 25% (R = 0.88; mean difference, -0.6% +/- 9.5% tomographic infarct size points). The optimal thresholds for regional wall thickening were endocardial, 1 mm (R = 0.70; mean difference, -2.2% +/- 14.3% tomographic infarct size points); epicardial, 1 mm (R = 0.78; mean difference, -4.6% +/- 12.7% tomographic infarct size points); and new myocardial, 2 mm (R = 0.71; mean difference, 2.1% +/- 14.1% tomographic infarct size points). The best agreement (R = 0.88) between electron beam computed tomography infarct size and sestamibi single-photon emission computed tomography infarct size was achieved with regional ejection fraction and the new myocardial centroid algorithm., Conclusions: In asymmetrically contracting left ventricles, the new myocardial centroid algorithm is superior to conventional methods for tomographic analysis of regional myocardial function.