Yadon Arad

Prediction of coronary events with electron beam computed tomography.

OBJECTIVES We sought to determine the prognostic accuracy of electron beam computed tomographic (EBCT) scanning of the coronary arteries at three to four years. BACKGROUND Coronary artery calcium scores determined by EBCT correlate with the severity of coronary artery disease. However, previous reports of the prognostic accuracy of EBCT scanning for coronary events in asymptomatic individuals are conflicting. METHODS Asymptomatic men and women undergoing coronary EBCT completed initial and follow-up evaluations, which included past medical history, the Rose angina questionnaire and interim cardiovascular events. Reported coronary events (death, nonfatal myocardial infarction [MI] and revascularization procedures) were confirmed without knowledge of the scan results. RESULTS Information was obtained in 1,172 (99.6%) of 1,177 eligible subjects (baseline age 53 +/- 11 years, 71% men). During an average follow-up of 3.6 years, 39 subjects sustained coronary events: three coronary deaths, 15 nonfatal MIs and 21 coronary artery revascularization procedures. The mean coronary artery calcium score was 764 +/- 935 among subjects with events as compared with 135 +/- 432 among those without events (p < 0.0001). For the prediction of all coronary events and of nonfatal MIs and deaths, the areas under the receiver-operator characteristics curve were 0.84 and 0.86, respectively, and a coronary calcium score > or =160 was associated with odds ratios of 15.8 and 22.2, respectively. The odds ratios for all events remained high (14.3 to 20.2) after adjustment for self-reported cardiovascular risk factors. CONCLUSIONS In asymptomatic adults, EBCT of the coronary arteries predicts coronary death and nonfatal MI and the need for revascularization procedures.

Continuous Probabilistic Prediction of Angiographically Significant Coronary Artery Disease Using Electron Beam Tomography

Background—We sought to incorporate electron beam tomography–derived calcium scores in a model for prediction of angiographically significant coronary artery disease (CAD). Such a model could greatly facilitate clinical triage in symptomatic patients with no known CAD. Methods and Results—We examined 1851 patients with suspected CAD who underwent coronary angiography for clinical indications. An electron beam tomographic scan was performed in all patients. Total per-patient calcium scores and separate scores for the major coronary arteries were added to logistic regression models to calculate a posterior probability of the severity and extent of angiographic disease. These models were designed to be continuous, adjusted for age and sex, corrected for verification bias, and independently validated in terms of their incremental diagnostic accuracy. The overall sensitivity was 95%, and specificity was 66% for coronary calcium to predict obstructive disease on angiography. With calcium scores >20, >80, and >100, the sensitivity to predict stenosis decreased to 90%, 79%, and 76%, whereas the specificity increased to 58%, 72%, and 75%, respectively. The logistic regression model exhibited excellent discrimination (receiver operating characteristic curve area, 0.842±0.023) and calibration (&khgr;2 goodness of fit, 8.95;P =0.442). Conclusions—Electron beam tomographic calcium scanning provides incremental and independent power in predicting the severity and extent of angiographically significant CAD in symptomatic patients, in conjunction with pretest probability of disease. This algorithm is most useful when applied to an intermediate-risk population.

Comparison of electron beam computed tomography scanning and conventional risk factor assessment for the prediction of angiographic coronary artery disease

OBJECTIVE To determine whether electron beam computed tomography (CT) adds to conventional risk factor assessment in the prediction of angiographic coronary artery disease. BACKGROUND Electron beam CT scanning can be used to predict the severity of coronary atherosclerosis, but whether it does so independently of conventional risk factors is unclear. METHODS Electron beam CT scans were performed and conventional risk factors were measured in 290 men and women undergoing coronary arteriography for clinical indications. The association of the electron beam CT-derived coronary artery calcium score and conventional risk factors with the presence and severity of angiographically defined coronary atherosclerosis was analyzed by logistic regression and receiver-operator characteristics analysis. RESULTS Age, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol and the coronary calcium score were significantly and independently associated with the presence of any coronary disease and obstructive coronary disease. In association with any coronary disease, odds ratios for age, the ratio of total cholesterol to HDL cholesterol and calcium score, highest quartile vs. lowest quartile, were 6.01 (95% confidence interval 2.87 to 12.56), 3.14 (1.56 to 6.31) and 94.08 (21.06 to 420.12), respectively. For obstructive coronary disease, highest quartile vs. lowest quartile, the respective odds ratios for age, the ratio of total cholesterol to HDL and calcium score were 3.86 (1.86 to 8.00), 4.11 (1.98 to 8.52) and 34.12 (12.67 to 91.86). Male gender was also significantly associated with any coronary disease (odds ratio 2.19, p=0.04) and obstructive coronary disease (odds ratio 2.07, p=0.04). Cigarette smoking was significantly associated with any coronary disease (odds ratio=2.74, p=0.004), and diabetes was significantly associated with obstructive disease (odds ratio 3.16, p=0.01). After adjustment for the coronary calcium score and other risk factors, it was determined that triglycerides, family history and hypertension were not significantly associated with any disease state. A coronary calcium score >80 (Agatston method) was associated with an increased likelihood of any coronary disease regardless of the number of risk factors, and a coronary calcium score > or = 170 was associated with an increased likelihood of obstructive coronary disease regardless of the number of risk factors (p < 0.001). CONCLUSIONS Electron beam CT scanning offers improved discrimination over conventional risk factors in the identification of persons with any angiographic coronary disease or angiographic obstructive coronary disease.

Dehydroepiandrosterone feeding prevents aortic fatty streak formation and cholesterol accumulation in cholesterol-fed rabbit.

The concentration of dehydroepiandrosterone sutfate (DHEA-S) In human plasma Is higher than any other steroid. Recent evidence has suggested an Inverse relationship between plasma DHEA levels and the development of coronary atherosclerosis In humans. We used the cholesterol-fed rabbit model to Investigate whether DHEA feeding would diminish aortic fatty streak formation in this model. Fifteen New Zealand White rabbits were fed rabbit chow supplemented with 0.5% cholesterol (wt/ wt). Seven animals were, In addition, fed DHEA, 0.5% of diet (wt/wt). Animals were sacrificed after 2 months, and the aortic Involvement with fatty streaks was evaluated by computerized planimetry of Sudan IV-stalned aortas and by chemical analysis of aortic wall llpfds. Compared to controls, DHEA-fed animals had similar plasma levels of total, very low density llpoproteln (VLDL), low density llpoproteln (LDL), and high density llpoproteln (HDL) cholesterol, cortlcolds, and estrogens. DHEA-fed animals had higher plasma levels of total, VLDL, and LDL trlglycerldes and lower HDL trlglycerlde8 than did controls. DHEA feeding resulted In 30% and 40%, respectively, inhibition of fatty streak formation by chemical analysis and planimetry. We conclude that DHEA feeding Inhibits the development of aortic fatty streaks in cholesterol-fed rabbits, Independent of changes in plasma total and LDL cholesterol levels or DHEA conversion to estrogens or cortlcolds.

Effects of Lovastatin Therapy on Very-Low-Density Lipoprotein Triglyceride Metabolism in Subjects With Combined Hyperlipidemia: Evidence for Reduced Assembly and Secretion of Triglyceride-Rich Lipoproteins

We have previously reported decreased production rates of the major apolipoprotein B (apoB)-containing lipoproteins, very-low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) in patients with combined hyperlipidemia (CHL) during treatment with lovastatin. In the present study, we determined the effects of lovastatin therapy on VLDL triglyceride (TG) metabolism. Plasma VLDL turnover was determined in six CHL patients, before and during lovastatin therapy. 3H-triglyceride-glycerol-specific activity data derived from injection of 3H-glycerol were analyzed by compartmental modeling. The effects of lovastatin on VLDL TG metabolism were compared with those previously determined on VLDL apoB metabolism in these subjects. Lovastatin therapy was associated with decreased concentrations of VLDL TG in five of six patients and decreased VLDL apoB concentrations in all six. VLDL TG production rates (PR) decreased in five patients, with the mean for the group decreasing from 14.1 +/- 7.1 to 10.3 +/- 4.0 mg/kg/h (P less than .05). VLDL apoB PR also decreased in five patients, with the mean decreasing from 21.8 +/- 20.3 to 12.2 +/- 9.0 mg/kg/d (P = .11). Changes in VLDL TG concentrations during lovastatin treatment were correlated with changes in VLDL apoB concentrations (r = .74, P = .09) and in VLDL TG PR (r = .91, P = .01). Changes in VLDL TG PR were also related to changes in VLDL apoB PR (r = .62, P = NS). There were no consistent changes in the fractional catabolic rates of either VLDL TG or VLDL apoB during lovastatin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of thoracic aortic and aortic valve calcium to coronary artery calcium and risk assessment

Aortic calcium, aortic valve calcium (AVC), and coronary artery calcium (CAC) have been associated with cardiovascular event risk. We examined the prevalence of thoracic aortic calcium (TAC) and AVC in relation to the presence and extent of CAC, cardiovascular risk factors, and estimated risk of coronary heart disease (CHD). In 2,740 persons without known CHD aged 20 to 79 years, CAC was assessed by electron beam- or multidetector-computed tomography. We determined the prevalence of TAC and AVC in relation to CAC, CHD risk factors, and predicted 10-year risk of CHD. A close correspondence of TAC and AVC was observed with CAC. TAC and AVC increased with age; by the eighth decade of life, the prevalence of TAC was similar to that of CAC (>80%), and 36% of men and 24% of women had AVC. Age, male gender, and low-density lipoprotein cholesterol were directly related to the likelihood of CAC, TAC, and AVC; higher diastolic blood pressure and cigarette smoking additionally predicted CAC. Body mass index and higher systolic and lower diastolic blood pressures were also related to TAC, and higher body mass index and lower diastolic blood pressure were related to AVC. Calculated risk of CHD increased with the presence of AVC and TAC across levels of CAC. TAC and AVC provided incremental value over CAC in association with the 10-year calculated risk of CHD. If longitudinal studies show an incremental value of aortic and aortic valve calcium over that of CAC for prediction of cardiovascular events, future guidelines for risk assessment incorporating CAC assessment may additionally incorporate the measurement of aortic and/or aortic valve calcium.

Serum concentration of calcium, 1,25 vitamin D and parathyroid hormone are not correlated with coronary calcifications. An electron beam computed tomography study.

BackgroundThe amount of coronary artery calcification, measured using electron beam computed tomography, is correlated with the volume of coronary artery atherosclerotic plaque, the severity of stenosis by angiography, and with the likelihood of future cardiovascular events. The deposition of calcium in atherosclerotic plaques may also be influenced by determinants of calcium metabolism, thus contributing to the variance of the relation between coronary artery calcification and extent of atherosclerosis. Our objective was to determine whether this variance could be explained by differences in the parameters of calcium metabolism. Design and methodsWe measured serum concentrations of calcium, 1,25(OH)2 vitamin D and parathyroid hormone (PTH) in 50 subjects undergoing angiography for clinical indications, and evaluated the correlations between these concentrations and calcium deposition in the coronary arteries, and the ratio of calcium deposition to extent of atherosclerosis using coronary angiography. Results and conclusionsSerum concentrations of calcium 1,25(OH)2 vitamin D and PTH were not correlated with coronary calcification or the ratio of coronary calcification to the extent of coronary stenosis. We conclude that, in subjects undergoing coronary angiography, the variance of the relationship between coronary atherosclerosis and coronary calcium is not a result of differences in serum concentrations of calcium, 1,25(OH)2 vitamin D or PTH. Coronary Artery Dis 9:513–518

Correlations between vascular calcification and atherosclerosis: a comparative electron beam CT study of the coronary and carotid arteries.

PURPOSE Electron beam CT (EBCT)-derived coronary artery calcium scores correlate with the extent of atherosclerosis, but there is a substantial variance about the general relationship between coronary calcification and coronary atherosclerosis. The relationship between calcification and atherosclerosis may also differ in various arteries. This study was designed to evaluate whether the relation between carotid artery intima-media thickness (IMT) and carotid artery calcium could be used as a correction factor to improve the correlation between coronary calcification and coronary atherosclerosis. METHOD We measured atherosclerosis in the coronary and carotid arteries by angiography and ultrasonography, respectively, and quantified coronary and carotid calcium deposition with EBCT in 50 subjects. The correlation between the findings in the carotid and coronary arteries was investigated. RESULTS Coronary artery calcium score correlated with coronary angiography and with carotid calcium score. Coronary stenosis correlated with carotid IMT. There was no meaningful correlation of carotid IMT and carotid calcium. CONCLUSION There is an intraindividual variation in the relationship of plaque mass to calcification among different vessels. The relation between carotid artery calcification and carotid IMT is not predictive of the relation between coronary artery calcification and coronary obstruction.

Rationale and design of the St. Francis Heart Study: a randomized clinical trial of atorvastatin plus antioxidants in asymptomatic persons with elevated coronary calcification.

Early detection of asymptomatic subjects who are at risk for future cardiovascular events may allow for earlier medical treatment in order to prevent disease progression and future events. Electron-beam computed tomography accurately identifies people with increased coronary calcification, which is correlated with increased coronary plaque mass, increased likelihood of obstructive coronary disease, and increased likelihood of future cardiovascular events. The St. Francis Heart Study is a single-center combination study of men and women 50-70 years old that includes a natural history study of the relation between calcium scores and cardiovascular events (n = 5582), the association of calcium scores with traditional and nontraditional coronary disease risk factors (n = 1160), and a randomized clinical trial designed to assess the benefit of combination treatment with atorvastatin, vitamin C, and vitamin E, as compared to placebos, in subjects with elevated age- and gender-adjusted coronary calcification (n = 1007). Mean follow-up duration will be 4 years. The study is proceeding on schedule with anticipated completion by August 2002. It should provide important information regarding the benefits of treating asymptomatic men and women who have elevated coronary artery calcium, using cholesterol reduction and antioxidant therapy. The article describes the design of the St. Francis Heart Study.

Predictive Value of EBCT Scanning

To the Editor: Secci and colleagues are to be commended for the integrity required to question the accuracy of electron-beam CT (EBCT) scanning as a screening test for coronary disease,1 particularly when at least one member of the group had anticipated that the method would prove successful. However, their conclusion that the amount of coronary calcification fails to predict nonfatal myocardial infarction (MI) and coronary death is at odds with their own and other data and is probably the result of a critical flaw in the design of the South Bay Heart Watch. In the larger cohort of 1461 South Bay Heart Watch subjects, the risk of nonfatal myocardial infarction and coronary death has been proportional to the number of calcified coronary arteries as determined by fluoroscopy.2 The fact that there is a threshold for the detection of coronary calcification by any method (and, in the case of a method as insensitive as fluoroscopy, a rather high threshold3 ) implies first, that the greater the number of calcified vessels, the higher the coronary calcium score and second, that the sample of 326 high-risk subjects was too small to confirm what was already demonstrated in the larger study. Two other studies4 5 of EBCT scanning in less-selected populations have reported unprecedented accuracy of the EBCT-derived coronary calcium score in the prediction of nonfatal MI and coronary death. When pooled with data from the South Bay Heart Watch, these studies yield odds ratios of 4.7 to 9.5 for nonfatal MI and coronary death for subjects with calcium scores in the upper third versus the lower two thirds of the population ( P <0.001). These findings are consistent with autopsy evidence of calcification of the coronary arteries in victims of sudden cardiac death and fatal MI,6 as well as …