Weiyi Tang

Coronary Calcium Does Not Accurately Predict Near-Term Future Coronary Events in High-Risk Adults

BACKGROUND Prognostic risk models have had limited success in predicting coronary events in subjects with multiple risk factors. We and others have proposed an alternative approach using radiographically detectable coronary calcium. We evaluated and compared the predictive value of these 2 approaches for determining coronary event risk in asymptomatic adults with multiple coronary risk factors. In addition, we assessed the predictive value of a risk model that included calcium score and cardiac risk-factor data. METHODS AND RESULTS We recruited 1196 asymptomatic high-coronary-risk subjects who then underwent risk-factor assessment and cardiac electron-beam CT (EBCT) scanning and were followed up for 41 months with a 99% success rate. We applied the Framingham model and our data-derived risk model to determine the 3-year likelihood of a coronary event. The mean age of our cohort was 66 years, and mean 3-year Framingham risk was 3.3+/-3.6%. Sixty-eight percent (818 subjects) had detectable coronary calcium. There were 17 coronary deaths (1.4%) and 29 nonfatal infarctions (2. 4%). The receiver operating characteristic (ROC) curve areas calculated from the Framingham model, our data-derived risk model, and the calcium score were 0.69+/-0.05, 0.68+/-0.05, and 0.64+/-0.05, respectively (P=NS). When calcium score was included as a variable in the data-derived model, the ROC area did not change significantly (0.68+/-0.05 to 0.71+/-0.04; P=NS). CONCLUSIONS Neither risk-factor assessment nor EBCT calcium is an accurate event predictor in high-risk asymptomatic adults. EBCT calcium score does not add significant incremental information to risk factors, and its use in clinical screening is not justified at this time.

Prognostic significance of cardiac cinefluoroscopy for coronary calcific deposits in asymptomatic high risk subjects

OBJECTIVES This research investigated the prognostic significance of radiographically detectable coronary calcific deposits. BACKGROUND Coronary calcific deposits are almost always associated with coronary atherosclerosis. We investigated the association between fluoroscopically determined coronary calcium and coronary heart disease end points at 1 year of follow-up. METHODS This prospective population-based cohort study was conducted in the suburbs of Los Angeles. Fourteen hundred sixty-one asymptomatic adults with an estimated > or = 10% risk of having a coronary heart disease event within 8 years underwent cardiac cinefluoroscopy for assessment of coronary calcium at initiation of the study. Clinical status including angina, documented myocardial infarction, myocardial revascularization and death from coronary heart disease were determined after 1 year. RESULTS The prevalence of calcific deposits was high (47%). A follow-up examination at 1 year was successfully completed in 99.9% of subjects. Six subjects (0.4%) had died from coronary heart disease and 9 (0.6%) had had a nonfatal myocardial infarction. Thirty-seven subjects (2.5%) reported angina pectoris, and 13 (0.9%) had undergone myocardial revascularization. Fifty-three subjects had at least one event during the 1-year period. Radiographically detectable calcium was associated with the presence of at least one of these end points, with a risk ratio of 2.7 (confidence limits 1.4, 4.6). The presence of coronary calcium was an independent predictor of at least one end point when controlling for age, gender and risk factors. However, three deaths due to coronary heart disease and two nonfatal myocardial infarctions occurred in subjects without detectable coronary calcium. CONCLUSIONS The presence of coronary calcific deposits incurs an increased risk of coronary heart disease events in asymptomatic high risk subjects at 1 year. This increased risk is independent of that incurred by standard risk factors.

Does coronary artery screening by electron beam computed tomography motivate potentially beneficial lifestyle behaviors

We evaluated the extent to which cardiovascular risk-reducing behaviors are initiated as a result of knowledge of newly detected coronary artery disease, based on test results from noninvasive electron beam computed tomography (EBCT). A total of 703 men and women, aged 28 to 84 years, asymptomatic and without prior coronary disease, who had a baseline EBCT coronary artery scan and basic medical history and risk factor information completed a follow-up survey questioning them about health behaviors undertaken since their scan. Baseline calcium scores were significantly higher in those who subsequently reported consulting with a physician, or reported new hospitalization, coronary revascularization, beginning aspirin usage, blood pressure medications, cholesterol-lowering therapy, decreasing dietary fat, losing weight, beginning vitamin E, and under more worry (all p <0.01). Other factors, including reducing time worked, obtaining life insurance, losing employment, increased work absenteeism, increasing exercise, or stopping smoking were not associated with coronary calcium. In logistic regression, after adjusting for age, gender, pre-existing high cholesterol, high blood pressure, cigarette smoking, and a positive family history of coronary disease, the natural log of total calcium score remained associated with new aspirin usage, new cholesterol medication, consulting with a physician, losing weight, decreasing dietary fat, new coronary revascularization (all p <0.01), but also new hospitalization (p <0.05) and increased worry (p <0.001). The results suggest that potentially important risk-reducing behaviors may be reinforced by the knowledge of a positive coronary artery scan, independent of preexisting coronary risk factor status.

Ethnic Origin and Serum Levels of 1α,25-Dihydroxyvitamin D3 Are Independent Predictors of Coronary Calcium Mass Measured by Electron-Beam Computed Tomography

BACKGROUND Blacks have been found to have lower amounts of coronary calcium as well as higher levels of the osteoregulatory steroid 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] than whites. We sought to determine if racial differences in coronary calcium mass could be explained by differences in serum levels of 1,25(OH)2D3. METHODS AND RESULTS We evaluated standard coronary risk factors, quantified coronary calcium mass with electron-beam computed tomography (EBCT), and measured serum 1,25(OH)2D3 with radioimmunoassay in 283 high-risk subjects (51 [180%] black, 232 [82%] white). Black subjects had lower masses of coronary calcium than whites (14 versus 47 mg; P=.003). Serum 1,25(OH)2D3 levels were slightly higher in blacks (41 versus 38 pg/mL; P=.05). Log 1,25(OH)2D3 levels were inversely proportional to log-transformed calcium mass (r=-.19; P=.001) in both races. Multivariate linear regression demonstrated that both black race (P=.02) and 1,25(OH)2D3 levels (P=.007) contributed inversely and independently to coronary calcium mass. However, an interaction term of racex1,25(OH)2D3 did not significantly contribute to coronary calcium mass, indicating that other undetermined factors in addition to 1,25(OH)2D3 are responsible for ethnic differences in coronary calcium mass. CONCLUSIONS Both black race and serum levels of 1,25(OH)2D3 are independent negative determinants of coronary calcium mass. Nevertheless, diminished amounts of coronary calcium in blacks are not accounted for by higher 1,25(OH)2D3 levels.

Racial differences in coronary calcium prevalence among high-risk adults

A total of 1,461 asymptomatic high-risk adult subjects were studied with digital subtraction fluoroscopy and conventional cinefluoroscopy to detect coronary calcium. Ethnicity and risk factor data were recorded. No subject had a history or electrocardiographic evidence of prior myocardial infarction. The prevalence of coronary calcium by digital subtraction fluoroscopy was high (58%). Substantial ethnic differences in prevalence were noted: 36% of African American subjects, 60% of Caucasian subjects, and 60% of Asian American subjects had definite radiographic evidence of coronary calcium. The difference in prevalence between African American and other subjects was significant (p < 0.0001) by chi-square test for all 3 races. These differences persisted in the unsubtracted cinefluoroscopic images (p < 0.0001) and after controlling for age, gender, and other risk factors (p = 0.003). After 20 +/- 11 months of follow-up, African Americans had more coronary artery disease events (13%) than Caucasians (6%) or Asian Americans (5%) (p = 0.04). Thus, African Americans have a significantly lower prevalence of coronary calcium than do Caucasians or Asian Americans. Based on the follow-up results, these differences in prevalence are not explained by differences in coronary artery disease risk.

ACCURACY OF QUANTIFYING CORONARY HYDROXYAPATITE WITH ELECTRON BEAM TOMOGRAPHY

RATIONALE AND OBJECTIVES. The electron beam tomography coronary calcium score continues to be used without experimental validation. To determine its accuracy, a series of experiments was performed. METHODS.A chest phantom model was constructed with coronary arteries represented by cylindrical holes containing hydroxyapatite granules embedded in a gelatin matrix to simulate coronary arteries. Experiments were performed to determine the relationship between the mass of hydroxyapatite in each of these arteries, the coronary calcium score currently used in coronary screening, and an alternative method of estimating mass from the images. The model was scanned with equal amounts of hydroxyapatite in each artery: 1) when the cylindrical heart was rotated 36 degrees 10 times between scans, and 2) when the particle diameters varied from 0.1 mm to 4 mm. The scores were calculated, and a subtraction algorithm was applied to estimate the exact mass of hydroxyapatite in each artery. RESULTS. The hydroxyapatite scores varied by 42% with position and by 1.54 X 106% with particle diameter. The estimated masses from the subtraction algorithm were more stable with position and particle size, with maximum percent errors of 10% and 14% for position and particle size, respectively. CONCLUSIONS.These results suggest that the coronary calcium score is invalid, and that more precise and clinically relevant methods, such as the arterial summation method, should be rigorously tested in clinical studies.

Prevalence of fluoroscopic coronary calcific deposits in high-risk asymptomatic persons☆

Coronary calcific deposits are always associated with coronary atherosclerosis. Sensitive radiographic technology can detect coronary calcium before atherosclerosis becomes symptomatic. A total of 1461 asymptomatic high-risk adult subjects were studied with digital subtraction fluoroscopy to detect coronary calcium. Risk factor data were recorded including age, sex, family history, smoking history, diabetes history, body mass index, systolic blood pressure, left ventricular hypertrophy on ECG, total serum cholesterol level, high-density lipoprotein (HDL) cholesterol, and total cholesterol/HDL ratio. Digital subtraction fluoroscopy in the left anterior oblique projection was performed in all subjects. The prevalence of calcific deposits in at least one major coronary artery was high (58.3%). Eleven percent had coronary calcium in all three major arteries. Multivariate logistic regression analysis showed significant correlations (p < 0.05) between the prevalence of coronary calcium and age, smoking history (relative risk = 1.30), diabetes history (relative risk = 1.24), and family history (relative risk = 1.26). In older subjects (at least 65 years of age), smoking and serum lipoproteins assumed greater importance as contributors to coronary calcium, whereas in younger subjects a history of diabetes was more significant. Coronary calcific deposits are prevalent in high-risk asymptomatic subjects. Their occurrence is closely related to most known risk factors.

Coronary heart disease deaths and infarctions in people with little or no coronary calcium

Measurement of coronary artery calcium with electronbeam computed tomography (EBCT) has been proposed to identify people with subclinical atherosclerosis. A study in patients undergoing coronary angiography showed that a calcium score of 159 on EBCT is the optimal cutpoint to discriminate those with obstructive coronary disease (at least one lesion with angiographic stenosis severity >80%) from those without. Despite conflicting results from prospective investigations assessing the prognostic capabilities of EBCT calcium scanning, it has been suggested that a negative EBCT scan virtually rules out obstructive coronary stenosis and indicates low risk of a coronary event. Can a patient with an EBCT calcium score of less than 160 confidently be told they are at little or no risk of a coronary event? We assessed coronary risk factors and measured coronary calcium with EBCT in 1196 symptomless people with at least one coronary risk factor but no previous history of coronary disease. We then noted the occurrence of coronary events (death due to coronary heart disease and non-fatal myocardial infarction) over 41 months. All events were verified by a blinded adjudication committee based upon examination of hospital records. Over 99% of individuals were followed up. The mean risk of infarction or coronary death within 3 years was 3·3%, based on risk-factor assessment performed at the time of EBCT scanning and calculations with the Framingham algorithm. Median calcium score was 44, with a minimum of 0 and a maximum of 4576. Two-thirds had some detectable calcium. Individuals were divided into equal tertiles of 398 each on the basis of calcium score, and the number of events in each tertile compared. There were 46 patents with coronary events: 17 with coronary heart disease death and 35 with myocardial infarction (four fatal and 29 non-fatal). Patients in higher tertiles of calcium score were more likely to suffer infarctions and the combined endpoint of death or infarction (p=0·003 and 0·002, respectively, table). 24 of the 46 patients with coronary events—52% (nine of 17 coronary heart disease deaths [53%] and 14 of 33 infarctions [42%])—were in the two lowest tertiles of calcium score, all of whom had calcium scores of 152 or less. The sensitivity and specificity of a calcium score of 0 for predicting coronary heart disease death or myocardial infarctions were 87% and 32%; those of a score of 151 were 52% and 67%. We conclude that, in symptomless people with risk factors for coronary disease, half of those suffering events have calcium scores less than 152. Therefore, an EBCT scan with a calcium score less than 152 does not indicate low-risk of a subsequent infarction or coronary heart disease death.

In vitro atherosclerotic plaque and calcium quantitation by intravascular ultrasound and electron-beam computed tomography

The purpose of this investigation was to compare the accuracy of intravascular ultrasound (IVUS) and electron-beam computed tomography (EBCT) in quantitating human atherosclerotic plaque and calcium. In experiment 1, 12 human atherosclerotic arterial segments were obtained at autopsy and imaged by using IVUS and EBCT. The plaque from each arterial segment was dissected and a volume measurement of the dissected plaque was obtained by water displacement. The plaque from each arterial segment was ashed at 700 degrees F, and the weight of the remaining ashes was used as an estimate of the calcium mass. In experiment II, 11 calcified arterial segments were obtained at autopsy and imaged by using IVUS at one site along the artery. A corresponding histologic cross section stained with Massons trichrome was prepared. In experiment I, the mean plaque volume measured by water displacement was 165.3 +/- 118.4 microliters. The mean plaque volume calculated by IVUS was 166.1 +/- 114.4 microliters and correlated closely with that by water displacement (r = 0.98, p < 0.0001). The mean calcium mass measured by ashing was 19.4 +/- 15.8 mg. The mean calculated calcium mass by EBCT was 19.9 mg and correlated closely with that by ashing (r=0.98, p<0.001). The mean calculated calcium volume by IVUS was 18.6 +/- 11.2 microliters and correlated linearly with the calcium mass by ashing (r = 0.87, p < 0.0003). In experiment II, the mean cross-sectional area of the calcified matrix was 1.71 +/- 0.66 mm2 by histologic examination compared with 1.44 +/- 0.66 mm2 by IVUS. There was a good correlation between the calcified cross-sectional area by histologic examination and IVUS (r = 0.76, p < 0.007); however, IVUS may underestimate the amount of calcium present depending on the intralesional calcium morphologic characteristics. In conclusion, IVUS accurately quantitates atherosclerotic plaque volume as well as the cross-sectional area and volume of intralesional calcium, especially if the calcium is localized at the base of the plaque. IVUS underestimates the amount of calcium present because of signal drop-off when the calcium is too thick for the ultrasound to completely penetrate. In comparison, EBCT accurately quantitates calcium mass regardless of the intralesional calcium morphologic characteristics; however, EBCT does not accurately quantitate plaque volume and will miss noncalcified atherosclerotic lesions.

REPRODUCIBILITY OF DIGITAL SUBTRACTION FLUOROSCOPIC READINGS FOR CORONARY ARTERY CALCIFICATION

RATIONALE AND OBJECTIVESDigital subtraction fluoroscopy, an inexpensive screening test for coronary atherosclerosis, is highly sensitive in detecting coronary calcifications. However, no previous study has reported interobserver agreement for this test. METHODSSix hundred and thirty-one subjects underwent digital subtraction fluoroscopy in the 60° left anterior oblique projection. Images were acquired with pulsed fluoroscopy at 15 frames per second. An averaged mask was subtracted from successive images. These fluoroscopic images were stored on a digital disk and replayed in cine loop format. An observer, blinded to clinical information, read the fluoroscopic studies for the presence of calcium in the left main-left anterior descending artery, circumflex artery, and right coronary artery. The images were then stored on digital tape and reread by a second blinded observer. RESULTSThe percentages of interobserver agreement regarding the presence and absence of calcium in left main-left anterior descending, circumflex, and right coronary arteries, were 91.9%, 92.9%, and 92.2%, respectively. The overall kappa values, which are 0.85, 0.77, and 0.82 in left main-left anterior descending, circumflex, and right coronary arteries, respectively, show a highly significant level of agreement (P < .0001). CONCLUSIONDigital subtraction fluoroscopy is a reliable screening test for coronary calcifications.