Relationship between vascular calcification and bone mineral density in the Old-order Amish.

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.

Coronary microvascular functional reserve: quantification of long-term changes with electron-beam CT preliminary results in a porcine model.

PURPOSE: To evaluate the ability of electron-beam computed tomography (CT) to help quantify long-term changes in coronary microvascular functional reserve in a porcine model. MATERIALS AND METHODS: Electron-beam CT-based intramyocardial blood volume and perfusion and Doppler ultrasonography (US)-based intracoronary blood flow were obtained in 13 pigs at baseline and again 3 months later. Measurements were obtained at rest and after the administration of adenosine. The short-term variation during 30 minutes of electron-beam CT measurements was assessed in nine additional pigs. RESULTS: Short-term variation of blood volume and perfusion averaged 8% and 9%, respectively, and was similar for both weight groups at rest and after adenosine administration. At rest, intracoronary blood flow, blood volume, and perfusion remained unchanged from baseline to follow-up. Long-term increases (percentage change with adenosine relative to that at rest) in blood volume and perfusion reserves were consistent with increasing intracoronary blood flow reserves. Despite these long-term changes in intracoronary blood flow, blood volume, and perfusion, the blood volume-to-perfusion relationship suggests a similar blood volume distribution among different microvascular functional components in normal porcine myocardium at both weight groups. CONCLUSION: Electron-beam CT may be of value for quantifying long-term changes in intramyocardial microvascular function.

Evaluation of the coronary venous system using electron beam computed tomography.

New therapeutic strategies in interventional cardiology and electrophysiology involve the coronary veins. This study examines the potential usefulness of electron beam computed tomography to obtain detailed noninvasive definition of the coronary venous anatomy and of arteriovenous relationships. Electron beam computed tomography allows acquisition and three-dimensional reconstruction of tomographic images of the beating heart with high spatial and temporal resolution. Contrast-enhanced, thin-section electron beam computed tomographic coronary arteriographic images of 34 patients (21 men and 13 women, age 60+/-10 years) were analyzed. The visibility of the coronary veins and their spatial relationship to the coronary arteries were assessed qualitatively on two- and three-dimensional displays. The coronary sinus was visible in 91%, the great cardiac vein in 100%, the middle cardiac vein in 88%, at least one vein overlying the lateral surface of the left ventricle in 97%, the anterior interventricular vein in 97%, and the small cardiac vein in 68%. A left marginal and a left posterior vein were seen in 44%, one of the two in 38%, and neither in 3%. The course of the anterior interventricular vein was parallel to the left anterior coronary artery in 79% and a crossover between the two vessels at an obtuse angle occurred in 12%. Contrast-enhanced electron beam computed tomography imaging of the heart noninvasively provides information on the coronary venous system and arteriovenous relationships that may help guide new interventional procedures.

Gender- and age-dependent relationships between the E-selectin S128R polymorphism and coronary artery calcification.

Development and progression of atherosclerosis involves recruitment and binding of circulating leukocytes to areas of inflammation within the vascular endothelium mediated by a diverse array of cellular adhesion molecules. A polymorphism in the endothelial-leukocyte adhesion molecule 1 (E-selectin) gene has been implicated in early-onset, angiographically defined, severe atherosclerotic disease because it profoundly affects ligand recognition and binding specificity, resulting in a significant increase in cellular adhesion. Relationships between the E-selectin S128R polymorphism and coronary artery calcification (CAC), a marker of atherosclerosis detected with noninvasive electron beam computed tomography, were examined in 294 asymptomatic women aged 40--88 years and 314 asymptomatic men aged 30--80 years from the Epidemiology of Coronary Artery Calcification Study. The E-selectin polymorphism was not associated with presence of CAC in men of any age or in women over age 50. In women 50 years of age or younger the E-selectin polymorphism was significantly associated with presence of CAC after adjustment for age, body mass index, systolic blood pressure, ratio of total cholesterol to high-density lipoprotein cholesterol, and smoking. The significant association between E-selectin and CAC in women 50 years of age or younger may suggest that the 128R allele is a risk factor for coronary atherosclerosis in younger asymptomatic women, who typically have lower levels of traditional risk factors and reduced adhesion molecule expression due to the presence of higher levels of endogenous hormones.

Use of a new myocardial centroid for measurement of regional myocardial dysfunction by electron beam computed tomography: comparison with technetium-99m sestamibi infarct size quantification.

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.

Combination of hypercholesterolemia and hypertension augments renal function abnormalities.

Hypercholesterolemia and hypertension are both risk factors for end-stage renal disease. This study was designed to examine whether their coexistence augmented impairment in renal function and redox status. Regional renal hemodynamics and function in response to vasoactive challenges with acetylcholine or sodium nitroprusside were quantified by using electron-beam computed tomography in pigs after 12 weeks of either a normal (n=10) or hypercholesterolemic (n=10) diet, renovascular hypertension (n=7), or combined hypercholesterolemia+hypertension (n=6). The hypercholesterolemic and hypercholesterolemic+hypertensive groups had significantly increased serum cholesterol levels, whereas in the hypertensive and hypercholesterolemic+hypertensive groups, mean arterial pressure was significantly elevated compared with the group fed a normal diet. Basal regional renal perfusion and glomerular filtration rates were similar among the groups. In response to acetylcholine, cortical perfusion increased in normal animals (15.6+/-4.7%, P=0.002) but not in hypercholesterolemic or hypertensive animals (8.0+/-7.4% and 8.2+/-5.9%, respectively; P>0.05). Moreover, in the hypercholesterolemic+hypertensive group, cortical perfusion response was further attenuated (2.5+/-4.8%, P=0.02) and significantly different from the group fed a normal diet (P<0.05). The response to sodium nitroprusside followed a similar pattern, and the impairment was augmented in the hypercholesterolemic+hypertensive group. The functional abnormalities in hypercholesterolemia or hypertension were associated with a decrease in systemic and/or renal tissue levels of oxygen radical scavengers that was again accentuated in hypercholesterolemia+hypertension. These results demonstrate that concurrent hypercholesterolemia and hypertension have a greater detrimental effect on renal perfusion responses compared with hypercholesterolemia or hypertension alone, associated with a marked pro-oxidant shift in redox status. These effects may potentially augment renal functional impairment and play a role in the initiation and progression of renal injury in hypertension and atherosclerosis.

Coronary artery calcification measured at electron-beam CT: agreement in dual scan runs and change over time.

PURPOSE: To use a recently described regression approach to evaluate agreement in the quantity of coronary artery calcification (CAC) with two consecutive acquisitions (dual scan runs) at electron-beam computed tomography (CT) in a quality-control program and to assess the change in CAC quantity over time in an individual. MATERIALS AND METHODS: A total of 1,376 asymptomatic research participants, who were not selected because they were at high risk for coronary artery disease, were examined for the quantity of CAC with dual scan runs at electron-beam CT. With these data, 95% limits of agreement were established and used to evaluate differences between scan runs performed approximately 3.5 years apart in 81 participants. RESULTS: The 95% limits of agreement depended on the mean quantity of CAC in the dual scan runs. Of the 81 participants whose examinations were approximately 3.5 years apart, 59 (73%) had no apparent change in CAC between the two examinations, 21 (26%) had large increases suggesting progression of CAC, and one (1%) had a large decrease suggesting regression of CAC. CONCLUSION: The demonstrated method can be used to evaluate both agreement in dual scan runs and change in quantity of CAC over time.

Minimally invasive evaluation of coronary microvascular function by electron beam computed tomography.

BACKGROUND: We previously demonstrated that in vivo electron-beam computed tomography (EBCT)-based indicator-dilution methods provide an estimate of intramyocardial blood volume (BV) and perfusion (F), which relate as BV=aF+b radicalF, where a characterizes the recruitable (exchange) and b the nonrecruitable (conduit) component of the myocardial microcirculation. In the present study, we compared BV and F with intracoronary Doppler ultrasound-based coronary blood flow (CBF) as a method for detecting and quantifying differential responses of these microvascular components to vasoactive drugs in normal (control) and hypercholesterolemic (HC) pigs. METHODS AND RESULTS: BV and F values were obtained from contrast-enhanced EBCT studies in 14 HC and 14 control pigs. BV, F, and CBF values were obtained at baseline (intracoronary infusion of saline) and after 5 minutes each of intracoronary infusion of adenosine (100 microgram. kg(-1). min(-1)) and nitroglycerin (40 microgram/min). BV and CBF reserves in response to adenosine were attenuated in HC pigs compared with controls (90+/-36% versus 127+/-42%, P<0.03, and 485+/-182% versus 688+/-160%, P<0.01, respectively). The relationship between BV and F showed consistently lower recruitable BV in HC versus control pigs. Nonrecruitable BV reserve in response to adenosine was attenuated in HC compared with controls (77+/-20% versus 135+/-28%, P<0.001). Our findings are consistent with HC-induced impairment of intramyocardial resistance vessel function. CONCLUSIONS: EBCT technology allows minimally invasive evaluation of intramyocardial microcirculatory function and permits assessment of microvascular BV distribution in different functional components. This method may be of value in evaluating the coronary microcirculation in pathophysiological states such as hypercholesterolemia.

Association of fibrinogen with quantity of coronary artery calcification measured by electron beam computed tomography.

Increased plasma fibrinogen concentration is an independent risk factor for cardiovascular disease. Fibrinogen is the main coagulation protein in plasma, a determinant of blood viscosity, and can act as a cofactor for platelet aggregation. In this study of middle-aged men and women, we examined the association between plasma fibrinogen concentration and coronary artery calcification (CAC), a marker of preclinical coronary atherosclerosis. Two hundred twenty-eight participants were selected from the community-based Epidemiology of Coronary Artery Calcification Study, in which CAC was measured noninvasively by electron beam computed tomography. One hundred fourteen participants (57 men) were selected because they had high quantities of CAC; the remaining 114 participants (57 men) were selected because they had no detectable CAC. Logistic regression models were used to investigate the association between plasma fibrinogen concentration and high quantity of CAC. In men, an increase of 1 standard deviation in fibrinogen concentration was associated with a statistically significant odds ratio of 1.6 (95% CI 1.1 to 2.5) for a high quantity of CAC. In women, the corresponding odds ratio was 2.5 (95% CI 1.6 to 4.1). Inferences from sex-specific bivariate logistic models for odds ratios adjusted individually for each coronary risk factor and C-reactive protein were similar to those from the univariate models. In women, there was also a significant interaction between fibrinogen concentration and age. According to the models, younger women with high plasma fibrinogen were more likely to have high quantities of CAC than were younger women with low plasma fibrinogen. The strength of this association was diminished in older women.

Effects of acute and chronic angiotensin receptor blockade on myocardial vascular blood volume and perfusion in a pig model of coronary microembolization.

Based on the reduction of ischemic cardiac events in clinical trials and experimental observations, inhibition of the effects of angiotensin II on coronary microcirculatory function may afford myocardial protection after injury. The immediate effects of intracoronary AT1 receptor blockade with irbesartan were examined in a pig model in the healthy myocardium and in acute ischemia induced by injection of 30-microm microspheres into the left anterior descending coronary artery (LAD). Electron-beam computed tomography was performed for in-vivo quantitative measurements of regional intramyocardial vascular blood volume (V(B)) and perfusion (F(M)), as well as left ventricular ejection fraction (LVEF) and muscle mass. Ratios of V(B) and F(M) in the anterior (LAD-supplied)/ inferior (control) myocardium were generated. At baseline, 0.2 mg/kg irbesartan injected into the LAD increased V(B) and F(M) ratios significantly by 27 +/- 8% and 51 +/- 13%, respectively. After anterior coronary microembolization, V(B) and F(M) ratios were 0.60 +/- 0.05 and 0.51 +/- 0.05, respectively, and were significantly increased by irbesartan (by 24 +/- 10% and by 36 +/- 11%, respectively). After 4 weeks of treatment with oral irbesartan (n = 7) or placebo (n = 7), an improved LVEF (56 +/- 4% v 44 +/- 4%, P = .046) was observed in irbesartan-treated animals, but no difference in LV end-diastolic volumes or muscle mass. Resting V(B) (0.95 +/- 0.06 v 0.76 +/- 0.06; P = .047) and F(M) (0.84 +/- 0.05 v 0.64 +/- 0.04; P = .016) ratios were significantly greater in irbesartan-treated animals. Using adenosine, there was a trend for higher V(B) and F(M) ratios in irbesartan- v placebo-treated animals. Therefore, in a pig model of acute myocardial ischemia, AT1 receptor blockade by irbesartan induced microvascular vasodilation and, ostensibly, conveyed myocardial protection. Long-term treatment with irbesartan resulted in moderate enhancements of resting V(B) and F(M) compared with placebo, suggesting a role for coronary microcirculatory effects of chronic AT1 receptor blockade in preserving LVEF.

Probabilistic model for prediction of angiographically defined obstructive coronary artery disease using electron beam computed tomography calcium score strata.

BACKGROUND: Electron beam CT (EBCT) is an accurate, noninvasive method to detect and quantify coronary artery calcification, a marker of coronary artery disease (CAD). This investigation examined the accuracy of EBCT to detect obstructive CAD (> or =50% stenosis) and determined the optimal strata for quantity of coronary artery calcification to facilitate clinical decision-making. METHODS AND RESULTS: Clinical research patients (n=213) were examined with coronary angiography and EBCT (angiography group), and 765 research participants were examined with only EBCT (nonangiography group). Of the angiography group, 53% had obstructive CAD. After adjustment for verification bias, the estimated sensitivity and specificity for calcium score > or =1 were 97.0% and 72.4%, respectively. Likelihood ratios for strata of calcium score associated with obstructive CAD were calculated in each sex and 2 age groups. Among those > or =50 years old, the same 4 strata of EBCT calcium scores were identified in each sex; likelihood ratios ranged from 0.03 (calcium score 0) to 12.85 (calcium score > or =200). The same 3 strata EBCT calcium scores were identified in each sex among those <50 years old; likelihood ratios ranged from 0.13 (calcium score 0) to 190 (calcium score > or =100). CONCLUSIONS: A calcium score > or =200 among those > or =50 years old and calcium score > or =100 among those <50 years old provided strong evidence that patients of either sex had obstructive CAD. A calcium score of 0 provided strong evidence that patients > or =50 years old did not have obstructive CAD.

[Economic aspects of using electron beam computerized tomography]. / Okonomische Aspekte bei der Anwendung der Elektronenstrahlcomputertomographie.

Electron beam computed tomography (EBCT) allows visualization and quantification of calcium in the coronary arteries. This has been demonstrated to correlate well with the overall plaque burden in the coronary arteries. EBCT is, therefore, well suited for the detection of early stages of coronary atherosclerosis. Especially in asymptomatic patients with several risk factors, staging coronary artery disease by coronary calcium, scanning may allow prognostic assessment and guide preventive and therapeutic interventions. To date, only scant data are available regarding the cost effectiveness and the economic impact of this imaging technique. In this manuscript we compare various methods for the diagnosis of coronary artery disease using a theoretical model and review the results of a prospective trial in our emergency room of coronary calcium scanning in patients with acute chest pain. Using Framingham data and prognostic data from long-term follow-up, we discuss the impact of coronary calcification scanning on primary preventive measures and its economical consequences. EBCT is a promising technique which has created a lot of attention due to its ease of application. It is currently undergoing critical appraisal in the medical literature. Further randomized prospective trials are needed (and underway, i.e., MESA, EDIC, CARDIA II) to better define its value and limitations in the clinical arena.

Measuring leg muscle and fat mass in humans: comparison of CT and dual-energy X-ray absorptiometry.

Dual-energy X-ray absorptiometry (DEXA) is reported to be inferior to computed tomography (CT) to measure changes in appendicular soft tissue composition. We compared CT- and DEXA-measured thigh muscle and fat mass to evaluate the random and systematic discrepancies between these two methods. Thigh skeletal muscle area (single-slice CT) was suboptimally (r(2) = 0.74, P < 0.0001) related to DEXA-measured thigh fat-free mass (FFM). In contrast, thigh muscle and adipose tissue volumes (multislice CT) were highly related to DEXA-measured thigh FFM and fat (both r(2) = 0.96, P < 0.0001). DEXA-measured leg fat was significantly less than multislice-CT-measured leg adipose tissue volume, whereas multislice-CT-measured leg muscle mass was less (P < 0.0001) than DEXA-measured leg FFM. The systematic discrepancies between the two approaches were consistent with the 10-15% nonfat components of adipose tissue. In conclusion, CT and DEXA measures of appendicular soft tissue are highly related. Systematic differences between DEXA and CT likely relate to the underlying principles of the techniques.

Comparison of two different software systems for electron-beam CT-derived quantification of coronary calcification.

OBJECTIVE: The growing interest in coronary calcium quantification by electron-beam CT (EBCT) has led to the development of various software systems for the analysis of EBCT raw data, but it is unknown whether these software systems yield comparable results. METHODS: Two sets of EBCT scans were obtained in 73 asymptomatic patients less than 15 minutes apart. Both scans of each patient were analyzed using two different software systems, the Mayo Clinic software and the AccuImage Scoring System. The authors compared the calcium quantities yielded by the two different software systems, analyzed the interscan variability, and calculated the interobserver variability. Finally, they investigated the influence of the CT density factor inherent in the widely used Agatston score for the quantification of coronary calcium on reproducibility. RESULTS: The mean score determined by the Mayo Clinic software was 14% greater than that determined by the AccuImage system. The mean difference between the two systems was 14% +/- 25%, and the median difference was 3%. The relative mean and the median difference between the two scans of one patient were 15.3% and 6% determined by the AccuImage system and 17% and 6.5% determined by the Mayo Clinic software. The interobserver reliability calculated by the Mayo Clinic software was better than that of the AccuImage system. There was a trend for better reproducibility using calcium area rather than the Agatson score. CONCLUSIONS: Two different scoring systems do not necessarily yield the same result. Calcium quantities were systematically determined to be greater by one system than the other, and there were significant differences with regard to interobserver reliability. Hence, software should be tested with regard to reproducibility data, and the interpretation of calcium quantities should acknowledge which type of software was used.

Independent and incremental value of coronary artery calcium for predicting the extent of angiographic coronary artery disease: comparison with cardiac risk factors and radionuclide perfusion imaging.

OBJECTIVES: The study was done to test the ability to predict the extent of angiographically determined coronary artery disease (CAD) by quantification of coronary calcium using electron-beam computed tomography (EBCT) and to compare it with more conventional parameters for delineating the angiographic extent of CAD, that is, cardiovascular risk factors and radionuclide single-photon emission computed tomography (SPECT). BACKGROUND: The angiographic extent of CAD is a powerful predictor of subsequent events. Use of EBCT may be able to define it by virtue of its ability to determine plaque burden. METHODS: We examined 308 patients presenting with suspected but not previously known CAD who underwent selective coronary angiography. As measures of the angiographic extent of CAD, coronary artery greater even 20 (CAGE > or =20) and CAGE > or =50 scores represented the total number of coronary segments with > or =20% or > or =50% stenoses, respectively. The EBCT-derived total calcium scores were obtained in 291 patients, risk factors as defined by the National Cholesterol Education Program in 239 patients, and SPECT scans in 136 patients. RESULTS: Using multiple linear regression analysis, total calcium scores were better independent predictors of both CAGE > or =20 and CAGE > or =50 scores than either a SPECT-derived radionuclide perfusion score or the risk factors age, male gender and ratio of total/high-density lipoprotein (HDL) cholesterol. The association between EBCT and angiographic scores remained highly significant after excluding the influence of all interrelated risk factors and SPECT variables (r = 0.65; p < 0.001 for CAGE > or =20 scores, r = 0.50; p < 0.001 for CAGE > or =50 scores). CONCLUSIONS: Coronary calcium predicts the angiographic extent of CAD in symptomatic patients and provides independent and incremental information to the more conventional clinical parameters derived from SPECT or risk assessment.

Noninvasive evaluation of a novel swine model of renal artery stenosis.

Intrarenal hemodynamics and excretory function distal to renal artery stenosis are difficult to quantify noninvasively. In this study, a swine model of chronic unilateral renal artery stenosis, achieved by implantation of an intravascular device that leads to a gradual and progressive luminal area narrowing, was developed and evaluated. Bilateral cortical and medullary volumes, blood flows, and segmental tubular dynamics were assessed in the intact kidneys of seven pigs using electron-beam computerized tomography before and 1 mo after implantation of the device. Within 1 mo, a 66% angiographic stenosis was significantly correlated with a 25% increase in BP. The volume and blood flow were markedly lower in the stenotic compared with the contralateral kidney and cortex, while the medulla exhibited minimal changes. In the stenotic kidney, intratubular contrast content has decreased in all nephron segments, especially in the distal tubule, where it correlated with an increase in serum creatinine and stenosis severity. In the contralateral kidney, dilution of proximal tubular fluid correlated with the increase in BP, likely due to pressure-natriuresis. In conclusion, the swine model closely resembles human renovascular hypertension. In the stenotic kidney, the hemodynamic impairment of the cortex is dissociated from the relatively preserved renal medulla, and the earliest effect on excretory function is observed in the distal nephron, where the fall in the amount of fluid reaching that segment is directly proportional to the renal arterial compromise. Electron-beam computerized tomography shows promise to noninvasively quantify, follow-up, and study changes in concurrent, in vivo intrarenal hemodynamics and segmental tubular function in renovascular hypertension.

Measurement of in vivo myocardial microcirculatory function with electron beam CT.

PURPOSE: The purpose of this work was to examine the capability of electron beam CT (EBCT) to characterize responses of recruitable (capillaries and small arterioles) compared with nonrecruitable (small to large arterioles) myocardial microvessels to vasoactive substances. METHOD: Myocardial perfusion (F) and total intramyocardial blood volume (BV) of the anterior cardiac wall were quantitated in 36 pigs, using EBCT and intravenous contrast agent injections, before and after intracoronary administration of either NG-monomethyl-L-arginine (L-NMMA), nitroglycerin, adenosine, or saline. Plotting the relationship of BV and F provided values for the recruitable and nonrecruitable microvascular transit times and BV allotment. RESULTS: Nitroglycerin increased nonrecruitable BV by 84.5+/-7.4%, whereas adenosine increased both recruitable and nonrecruitable microvascular BV (47.1+/-18.9 and 66.0+/-10.9%, respectively). L-NMMA led to a 25.1% decrease only in the recruitable BV. In the control group, no changes were observed. CONCLUSION: Characteristic responses of different-size myocardial microvessels may be inferred with EBCT, which provides a unique opportunity to portray intramyocardial microcirculatory function noninvasively.

Progression of coronary artery calcification: a pilot study.

OBJECTIVE: To describe individual changes in the quantity of coronary artery calcification (CAC) measured by electron beam computed tomography (CT) and determine the rate of change in the quantity of CAC during a 3.5-year period. MATERIAL AND METHODS: Eighty-eight consecutive participants (51 men at least 30 years of age and 37 women at least 40 years of age) from a community-based CAC study were invited for a follow-up examination. Established coronary artery disease risk factors were studied at baseline. CAC score was measured by electron beam CT at baseline and follow-up. RESULTS: Of the 88 invited participants, 82 (93%) returned for a follow-up examination. Considerable variation existed among the participants in the extent of CAC score change. On average, CAC score increased over time by an estimated 24% each year (P<0.05). The relative increase in CAC score over time was significantly lower for older than for younger participants but did not vary significantly by sex. CONCLUSION: The ability to recruit follow-up participants in this pilot study and to detect significant change in CAC score over time provides evidence that electron beam CT is useful for studying progression of CAC in a sample and may be a valuable procedure for assessing the effectiveness of clinical interventions designed to retard progression of coronary atherosclerosis.

An algorithm for noninvasive identification of angiographic three-vessel and/or left main coronary artery disease in symptomatic patients on the basis of cardiac risk and electron-beam computed tomographic calcium scores.

OBJECTIVES: We sought to model an algorithm for noninvasive identification of angiographically obstructive three-vessel and/or left main disease based on conventional cardiac risk assessment and site and extent of coronary calcium determined by electron-beam computed tomography (EBCT). BACKGROUND: Such an algorithm would greatly facilitate clinical triage in symptomatic patients with no previous diagnosis of coronary artery disease (CAD). METHODS: We examined 291 patients with suspected, but not previously diagnosed, CAD who underwent coronary angiography for clinical indications. Cardiac risk factors were determined as defined by the National Cholesterol Education Program. An EBCT scan was performed in all patients, and a coronary calcium score (Agatston method) was computed. Total per-patient calcium scores and separate scores for the major coronary arteries were generated. These scores were also analyzed for localization of coronary calcium in the more distal versus proximal tomographic sections. These parameters and the risk factors were considered for the model described in the following section. RESULTS: Sixty-eight patients (23%) had angiographic three-vessel and/or left main CAD. Multiple logistic regression analysis determined male sex, presence of diabetes and left anterior descending (LAD) and circumflex (LCx) coronary calcium scores, independent from more distal calcium localization, as independent predictors for identification of three-vessel and/or left main CAD. Based on this four variable model, a simple noninvasive index (NI) was constructed as the following: loge(LAD score) + log(e)(LCx score) + 2[if diabetic] + 3[if male]. Receiver operating characteristic curve analysis for this NI yielded an area under the curve of 0.88+/-0.03 (p < 0.0001) for separating patients with, versus without, angiographic three-vessel and/or left main CAD. Various NI cutpoints demonstrated sensitivities from 87-97% and specificities from 46-74%. The NI values >14 increased the probability of angiographic three-vessel and/or left main CAD from 23% (pretest) to 65-100% (posttest), and NI values <10 increased the probability of no three-vessel and/or left main CAD from 77% (pretest) to 95-100% (posttest). CONCLUSIONS: On the basis of a simple algorithm ("noninvasive index"), EBCT calcium scanning in conjunction with risk factor analysis can rule in or rule out angiographically severe disease, i.e., three-vessel and/or left main CAD, in symptomatic patients.

Coronary calcification by electron beam computed tomography and obstructive coronary artery disease: a model for costs and effectiveness of diagnosis as compared with conventional cardiac testing methods.

OBJECTIVES: The purpose of this study was to determine if electron beam computed tomography (EBCT) has potential as a cost-effective approach to diagnosis of obstructive coronary disease. BACKGROUND: Coronary calcification quantified by EBCT is closely related to the extent of atherosclerosis. METHODS: A model based upon published sensitivities (Se)/specificities (Sp) for diagnosis in an ambulatory patient of obstructive coronary disease (> or =50% stenosis) and population prevalence was tested for angiography alone, or treadmill exercise, stress echocardiography, stress thallium or predetermined EBCT calcium score outpoints, followed by angiography if indicated. RESULTS: Total direct testing costs increased in proportion to disease prevalence whereas cost-effectiveness, direct costs/patient diagnosed correctly with disease, decreased as a function of prevalence. Using an EBCT calcium score of 168 (Se/Sp = 71%/90%) provided for the least costly and most cost-effective noninvasive pathway. Calcium scores of 80 (Se/Sp = 84%/84%) and 37 (Se/Sp = 90%/77%) were also cost-effective when prevalence of disease was < or =70%; but results for a >0 calcium score (Se/Sp = 95%/46%) cutpoint were not superior to conventional methods. Calcium score cutpoints of 37, 80 or 168 provided similar or superior overall negative and positive predictive values to conventional noninvasive testing pathways across all prevalence subgroups. CONCLUSIONS: In ambulatory patients evaluated for obstructive coronary disease, a testing pathway utilizing quantification of coronary calcium by EBCT as an initial noninvasive testing approach minimized direct costs, and maximized cost-effectiveness in population groups with low/ moderate disease prevalence (< or =70%); as expected, direct angiography as the first and only test proved most cost-effective in patients with a high prevalence (>70%) of disease.