Eva V. Chomka

Electron-Beam Tomography Coronary Artery Calcium and Cardiac Events A 37-Month Follow-Up of 5635 Initially Asymptomatic Low- to Intermediate-Risk Adults

Background—Conventional coronary artery disease (CAD) risk factors fail to explain nearly 50% of CAD events. This study examines the association between electron-beam tomography (EBT) coronary artery calcium (CAC) and cardiac events in initially asymptomatic low- to intermediate-risk individuals, with adjustment for the presence of hypercholesterolemia, hypertension, diabetes, and a history of cigarette smoking. Methods and Results—The study was performed in 8855 initially asymptomatic adults 30 to 76 years old (26% women) who self-referred for EBT CAC screening. Conventional CAD risk factors were elicited by use of a questionnaire. After 37±12 months, information on the occurrence of cardiac events was collected and confirmed by use of medical records and death certificates. In men, events (n=192) were associated with the presence of CAC (RR=10.5, P <0.001), diabetes (RR=1.98, P =0.008), and smoking (RR=1.4, P =0.025), whereas in women, events (n=32) were linked to the presence of CAC (RR=2.6, P =0.037) and not risk factors. The presence of CAC provided incremental prognostic information in addition to age and other risk factors. Conclusions—The association between EBT CAC and cardiac events observed in this study of initially asymptomatic, middle-aged, low to intermediate-risk individuals presenting for screening suggests that in this group, knowledge of the presence of EBT CAC provides incremental information in addition to that defined by conventional CAD risk assessment.

Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adults☆

Electron beam tomography (EBT) is a noninvasive method used to detect coronary artery calcium (CAC). Due to the age-associated increase in incidence and magnitude of CAC, interpretation of results can be difficult. The purpose of this study was to develop a set of age- and gender-stratified CAC distributions to serve as standards for the clinical interpretation of EBT scans. Between 1993 and 1999, 35,246 asymptomatic subjects, 30 to 90 years of age, were self-referred for CAC screening using an Imatron EBT scanner. CAC score was calculated based on the number, areas, and peak computed tomographic density for each detected calcific lesion. CAC score in each coronary artery was equal to the sum of all lesions for that artery and the total CAC score was equal to the sum of the score of each artery. Total CAC scores were assigned to a percentile according to age and gender. CAC scores were reported at the 10th, 25th, 50th, 75th, and 90th percentiles for 16 age and/or gender groups. The prevalence of CAC increased with age for men and women. The extent of CAC differed significantly between men and women in the same age group. In summary, this study reports the distribution of CAC score by age and gender. Knowledge of the distribution of CAC, the effect of age on the total CAC score as well as the differences in total CAC scores that exist between men and women of similar age will assist the clinician in interpreting EBT CAC results.

Aprotinin for coronary bypass operations: Efficacy, safety, and influence on early saphenous vein graft patency. A multicenter, randomized, double- blind, placebo-controlled study

The purpose of this study was to evaluate the efficacy and safety of aprotinin in a U.S. population of patients undergoing coronary artery bypass grafting. Early vein graft patency rates were assessed by ultrafast computed tomography. A total of 216 patients at five centers were randomized to receive either high-dose aprotinin or placebo during the operation; 151 patients underwent primary operation, and 65 underwent repeat procedures. Total blood product exposures in the primary group were 2.2 per patient receiving aprotinin as compared with 5.7 per patient receiving placebo (p = 0.010). The repeat group had 0.3 exposures per patient receiving aprotinin as compared with 10.7 per patient receiving placebo (p = < 0.001). Consistent reductions in the percent of patients requiring donor red blood cells and in the number of units of platelets, fresh frozen plasma, and cryoprecipitate required were associated with the use of aprotinin in both primary and repeat groups. Mortality was 5.6% in the aprotinin group and 3.7% in the placebo group (p = 0.517). In the primary group, clinical diagnoses of myocardial infarction were made in 8.9% of patients receiving aprotinin as compared with 5.6% of the patients receiving placebo (p = 0.435). In the repeat group, infarctions occurred in 10.3% of patients receiving aprotinin and 8.3% of patients receiving placebo (p = 1.000). Secondary analysis of electrocardiograms and available enzyme data showed no significant difference in infarction rates between the treatment groups. There was no difference in clinically significant renal dysfunction. The early vein graft patency rates were 92.0% in the aprotinin group and 95.1% in the placebo group (p = 0.248). In this study, aprotinin was effective in reducing bleeding and blood product transfusion rates, and its use was not associated with an increase in complications. An adverse effect on early vein graft patency rates was not demonstrated, but the number of grafts assessed was insufficient for absolute conclusions in this regard.

Detection of calcific deposits in coronary arteries by ultrafast computed tomography and correlation with angiography

Abstract Calcium, when present in coronary arteries, is located in atherosclerotic plaque. 1–3 The presence of radiographically detectable calcium often correlates with the presence of angiographically significant coronary artery disease, particularly in younger populations. 3 The sensitivity and specificity of coronary artery calcium have been compared with coronary arteriography as the gold standard for definition of coronary artery stenosis. Fluoroscopic radiographic imaging methods have been previously used to detect coronary artery calcium. In addition, conventional computed tomography (CT) has been used to identify it, 4,5 and we have utilized ultrafast CT to detect its presence during routine clinical studies. 6 This study was performed to determine the potential clinical utility of ultrafast computed tomography detection of coronary artery calcium as a noninvasive screening tool for the prediction of angiographically significant coronary artery disease.

Reproducibility of the measurement of coronary calcium with ultrafast computed tomography

The differences observed in repeated coronary calcium measurements underscores the importance of considering reproducibility issues when evaluating the significance of serial calcium scores. Furthermore, reproducibility data have important implications for planning intervention trials in which ultrafast computed tomography is used to monitor the evolution of atherosclerotic disease.

Measurement of myocardial blood flow by ultrafast computed tomography.

Myocardial blood flow was analyzed by radioisotope-labeled microspheres and ultrafast computed tomography (CT) in 16 closed-chest, anesthetized dogs. The first set of 10 dogs had CT and microsphere measurements before and after chromonar-induced increases in myocardial blood flow. A second set of six dogs had flows measured at control and during temporary reductions in regional flow produced by balloon cuff occlusion of the left anterior descending coronary artery. All dogs had four-slice, 20-instance CT scans after injection of a medium bolus (0.35 ml/kg) of contrast medium into a femoral vein simultaneous with injection of microspheres into the left atrium. CT myocardial flow was calculated as the change in myocardial CT numbers divided by the area from a blood pool time-density curve. A wide range of myocardial blood flows was produced as determined by microspheres (0 to 6.7 ml/min/g). Global flow of the first set of dogs was shown to have excellent correlation (r = .95, n = 17) for a limited range (.4 less than X less than 1.4 ml/min/g) of flows. Regional flows of these measurements demonstrated less correlation (r = .63, n = 110) but extended the range of flow to 1.7 ml/min/g. At higher flows (greater than 2.5 ml/min/g) the correlation for global and regional flows was not significantly different than zero. Regional ischemic flow correlation extended the linear range of flow to 0 ml/min/g (r = .62, n = 17). These results show that CT can measure myocardial blood flow over a limited but clinically relevant range of flows defined as slightly above normal to ischemic. These results indicate that another preparation of CT flow measurement must be sought for quantification of myocardial perfusion values significantly above normal.

Conventional coronary artery disease risk factors and coronary artery calcium detected by electron beam tomography in 30,908 healthy individuals.

PURPOSE Electron beam tomography (EBT) is a noninvasive measure of coronary artery calcium (CAC), a marker for atherosclerosis. In this study we examined the association between conventional risk factors for coronary artery disease (CAD) and CAC. METHODS EBT CAC screening was performed on 30,908 asymptomatic individuals aged 30 to 90 years. Prior to EBT screening, individuals provided demographic and CAD risk factor information. EBT utilized a C-100 EBT scanner, and the amount of CAC was determined using the Agatston scoring method. RESULTS The results of this study demonstrate that for both men and women, all conventional risk factors were significantly associated with the presence of any detectable CAC, and the mean CAC score increased in proportion to the number of CAD risk factors. In age-adjusted (multivariable) logistic regression analysis, cigarette use, histories of hypercholesterolemia, diabetes, and hypertension were each significantly associated with mild to extensive CAC scores (> or =10.0). CONCLUSION CAD risk factors are associated with higher atherosclerotic plaque burden in both men and women. The odds ratios associated with each risk factor relative to the extent of CAC are similar to those reported for the development of clinical CAD, suggesting the existence of an association between CAC (subclinical disease) and CAD (clinical disease).

Influence of Age and Gender on the Presence of Coronary Calcium Detected by Ultrafast Computed Tomography

OBJECTIVES This study sought to determine the relation between coronary calcification detected with ultrafast computed tomography and lumen narrowing defined with angiography and evaluated whether this relation is influenced by age and gender. BACKGROUND Ultrafast computed tomography has been shown to be a sensitive method for detection of coronary calcification associated with atherosclerotic disease, but the relation between the extent of coronary calcification and degree of lumen narrowing and the possible influence of gender or age, or both, on this relation have not been clarified. METHODS Seventy men and 70 women were studied with ultrafast computed tomography for analysis of coronary calcification and coronary angiography. Coronary atherosclerosis was considered present if any lumen irregularity was noted on angiography, and obstructive coronary artery disease was defined as a lumen diameter narrowing > or = 70%. RESULTS Coronary calcification had a sensitivity of 88% for identification of patients with atherosclerotic disease and 97% for those with obstructive disease, with corresponding specificities of 55% and 41%, respectively. The sensitivity of coronary calcium for detection of atherosclerotic disease in women < 60 years old was 50%, significantly less than the 97% sensitivity in women > 60 years old and the 87% sensitivity in men < 60 years old (p < 0.05 for each comparison). Logistic regression analysis revealed a 1.81-fold increase in the likelihood of detecting coronary calcification in the atherosclerotic lesions of men compared with those in women (95% confidence interval 1.12 to 2.93, p = 0.016) when controlled for age and severity of coronary disease by angiography. CONCLUSIONS Atherosclerotic lesions in women are less likely to have coronary calcium than lesions with a similar degree of lumen narrowing in men. Differences in the pattern of coronary calcification between men and women may provide insight into the gender differences observed in the clinical development of symptomatic coronary artery disease.

Aprotinin for coronary artery bypass grafting: Effect on postoperative renal function

Two hundred sixteen patients undergoing coronary artery bypass graft procedures were randomized to receive either high-dose aprotinin or placebo. Clinically important postoperative renal insufficiency was infrequent, with a single patient (0.9%) from each group requiring dialysis. Although increases in the serum creatinine level occurred postoperatively in more patients who received aprotinin (20/108) than in those given placebo (13/108), the difference between the two groups was not statistically significant (p = 0.186), and the increases were generally small and transient. Likewise, there was no difference between the groups in terms of the incidence of abnormal serum electrolyte levels, blood urea nitrogen levels, or urinalysis findings, or in the frequency of abnormal creatinine clearance rates. Under the conditions described, aprotinin use does not appear to be associated with a significant risk of serious renal toxicity.

Usefulness of Electron Beam Tomography in Adolescents and Young Adults With Heterozygous Familial Hypercholesterolemia

BACKGROUND Because of the success of secondary prevention of coronary events by intense risk factor modification, a more precise measure of atherosclerosis in youth would have great clinical value both in the design of clinical trials for the demonstration of the usefulness of coronary disease prevention early in life and in guiding therapy. Identification of calcium in coronary arteries by electron beam tomography has been associated with severity of atherosclerosis in adults. METHODS AND RESULTS Twenty-nine youths 11 to 23 years old with familial hypercholesterolemia (average LDL cholesterol, 5.95 mmol/L) underwent electron beam tomography as well as comprehensive risk factor assessment with measurement of total cholesterol, triglycerides, HDL cholesterol, lipoprotein (a), apolipoprotein E phenotype, blood pressure, body mass index, and history of tobacco use. Significant coronary calcium was identified in 7 of 29 subjects. Increased body mass index was significantly associated with the presence of coronary calcium (25.3 versus 20.6 kg/m2, P<0.03). No other risk factors were associated with the presence of coronary calcium. CONCLUSIONS Coronary calcium, uncommonly identified before the fourth decade, was found in a significant percentage of adolescents and young adults with familial hypercholesterolemia. Overweight may increase the likelihood of coronary calcium being present in individuals already at high risk.