Significant Coronary Artery Calcification Research Articles

Different manifestations of coronary artery disease by stress SPECT myocardial perfusion imaging, coronary calcium scoring, and multislice CT coronary angiography in asymptomatic patients with type 2 diabetes mellitus

We sought to assess prospectively the evidence for silent coronary artery disease (CAD) in asymptomatic patients with type 2 diabetes mellitus by stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging, coronary artery calcium (CAC) scoring, and multislice computed tomographic (MSCT) coronary angiography. One hundred asymptomatic patients (aged 30 to 72 years) with type 2 diabetes mellitus and one or more risk factors for CAD were prospectively recruited from an outpatient diabetes clinic. All patients underwent adenosine technetium-99m sestamibi SPECT imaging, CAC scoring, and 64-slice MSCT coronary angiography. Twenty-three patients (23%) had abnormal stress SPECT imaging, consistent with inducible myocardial ischemia, whereas 60 patients (60%) had positive CAC scoring (18 patients [18%] with significant CAC >401), and 70 patients (70%) had abnormal MSCT coronary angiography (24 patients [24%] with significant, >or=50% stenosis). Of 77 patients with normal SPECT, 44 had a positive CAC score (10 patients [13%] >401), and 54 showed CAD on MSCT angiography (16 patients [21%] with >or=50% stenosis). Of 23 patients with an abnormal SPECT, 16 patients had a positive CAC score (8 patients [35%] >401), and 16 patients had CAD on MSCT angiography (8 patients [35%] with >or=50% stenosis). Overall, 17 patients (17%) had more than 2 significantly abnormal diagnostic test results, and 5 patients had three tests with significantly abnormal results. In this cohort of asymptomatic patients with type 2 diabetes mellitus, different modalities visualized different aspects of silent coronary atherosclerosis. Anatomic evidence of coronary atherosclerosis (CAC and MSCT) occurred more frequently than functional evidence (stress SPECT). However, clinically significant manifestations of CAD were observed in about one-quarter to one-fifth of patients by each modality, either separately or combined. The relative prognostic value of each modality needs to be determined by a follow-up of this cohort.

Abstract 2755: Insulin Resistance and Coronary Artery Calcification measured by Electron Beam Tomography

Background: Elevation in the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) has been suggested as a marker of insulin resistance (IR), conferring an increased risk of atherosclerosis in these patients. The association between TG/HDL-C and coronary artery calcification (CAC) measured by computed tomography has yet to be established. The goal of this study was to examine the relationship between IR, as determined by TG/HDL-C ≥ 3.5, and significant CAC (absolute score ≥ 100). Methods: Fasting lipid levels, homocysteine, C reactive protein and lipoprotein (a) levels of 336 asymptomatic individuals, who also underwent electron beam tomography (EBT), were measured. Results: The mean age of participants was 55 ±10 years. 71.7% were male. 37.4% had hypertension, 52.5% had hypercholesterolemia, 12.4% had diabetes mellitus (DM) and 52.5% had family history of premature CHD. Individuals with IR had higher significant CAC (≥100) than those without IR (70% vs. 27%, P=0.0001). After adjustment for age, gender, hypertension, hypercholesterolemia and DM, multivariate regression analysis demonstrated that individuals with IR had more significant CAC (odds ratio 2.1, 95% CI=1.1–3.9, p=0.01). Further sub-analysis revealed that individuals with IR had significantly higher lipoprotein (a) (Lp(a)) than those without IR (odds ratio 1.31, 95% CI=1.09-.16, p=0.03). No significant differences in C-reactive protein (CRP) and homocysteine were found between the two groups. Conclusion: Insulin resistance, as measured by TG/HDL-C ≥ 3.5, was associated with a significantly higher incidence of accelerated atherosclerosis on EBT (absolute CAC score ≥ 100), independent of age, gender and conventional risk factors. IR was also significantly associated with elevated levels of Lp(a). Further studies regarding the clinical significance of insulin resistance and elevated CAC score, as well as its association with Lp(a), may be warranted.

Severe coronary artery calcifications are associated with ischemia in patients undergoing medical therapy

The role of coronary artery calcification (CAC) detection in individuals undergoing medical therapy is controversial. These patients frequently exhibit an artificially low clinical suspicion for obstructive heart disease. Whether detection of CAC adds value to their assessment is unknown. We conducted a cross-sectional analysis of 703 adequately treated individuals who had CAC scoring with electron beam computed tomography and myocardial perfusion imaging within 6 months. We assessed the association of risk factor analysis and CAC scoring with myocardial perfusion imaging abnormalities. Univariate associations between ischemia and male gender, low high-density lipoprotein, high body mass index, diabetes, and CAC score were noted. Despite reasonable control of blood pressure and low-density lipoprotein, the prevalence of inducible ischemia was 0.8%, 4.8%, 5.7%, 8.0%, and 15.1% across CAC scores of 0 to 10, 11 to 100, 101 to 400, 401 to 1000, and greater than 1000, respectively (P < .001 for trend). Logistic regression analysis demonstrated that, after adjustment for risk factors, the odds of ischemia was 3.0 (95% confidence interval, 1.5-5.7) in individuals with CAC scores greater than 400 compared with those with CAC scores of 400 or less. The presence of a CAC score greater than 400 is associated with ischemia in a population receiving good medical therapy. The detection of significant CAC in these individuals warrants additional evaluation for ischemia.

New Technology for Noninvasive Evaluation of Coronary Artery Disease

Cardiac computed tomography (CT) and positron emission tomography (PET) are emerging as powerful noninvasive imaging tools for the evaluation of atherosclerosis in patients with known or suspected coronary artery disease (CAD). Unlike invasive coronary angiography, CT coronary angiography (CTA) not only assesses disease within the coronary lumen but can also provide direct qualitative and quantitative information about nonobstructive atherosclerotic plaque burden within the vessel wall. Thus, it is possible that CTA-based patient evaluation may provide more clinically relevant information on which to base risk assessments compared with conventional “lumenography.” On the other hand, PET is rapidly growing as a powerful and efficient alternative to conventional single-photon emission CT (SPECT) imaging to evaluate regional myocardial perfusion and metabolism in patients with CAD. In addition, PET scanners are now being converted to hybrid PET/CT devices, which, in the setting of CAD, offer the potential for a comprehensive noninvasive cardiac evaluation of anatomy and function. This review will discuss current and potential future applications of cardiovascular CT, PET, and hybrid PET/CT, with a particular focus on ischemic heart disease. The information provided by noninvasive imaging generally falls into 1 of 3 categories: myocardial perfusion, left ventricular (LV) function, or coronary artery anatomy. The clinical utility, value, and role of a noninvasive modality are based on 2 test characteristics: What type of information is provided (eg, stress perfusion, stress and/or rest LV function, coronary anatomy), and what is the accuracy of the information provided. For example, SPECT and PET both provide stress and rest perfusion information, but the latter will be a superior clinical tool if the imaging data better represent the actual defect size and are subject to less artifact. The advantage of PET over SPECT will be further enhanced, as will be discussed later, if it provides additional clinically relevant information not …

Racial differences in coronary artery calcification are not attributed to differences in lipoprotein particle sizes: The Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) Study

Lipoprotein particle levels and size distributions differ by race. As a group, blacks have less coronary artery calcification (CAC) than whites. We evaluated whether racial differences in CAC are explained by differences in lipoprotein levels and particle sizes. A total of 721 blacks and 988 whites underwent measurement of fasting lipoprotein levels and particle sizes. There were 608 subjects who had CAC quantified by electron beam computed tomography. Distributions and interrelationships among lipoprotein levels, particle sizes, and CAC were evaluated by race and sex. Blacks had nominally higher adjusted high-density lipoprotein cholesterol levels (men, 51 vs 50 mg/dL; women, 63 vs 61 mg/dL; P = .05), lower intermediate-density lipoprotein cholesterol levels (women only, 17 vs 18 mg/dL; P = .02), and significantly lower triglyceride levels (men, 116 vs 138 mg/dL; women, 103 vs 136 mg/dL; P < .0001) than whites. Adjusted small dense low-density lipoprotein 3 particle levels were significantly lower (P < .0001) in black men (47 vs 53 mg/dL) and black women (43 vs 48 mg/dL) compared with white men and women, respectively. Black race was associated with a 48% lower adjusted odds of moderate or significant CAC (odds ratio, 0.52; 95% confidence interval, 0.34-0.80). However, this strong association between race and CAC was independent of lipoprotein levels and particle sizes. Blacks have less CAC and more favorable lipoprotein profiles than whites. Racial differences in CAC are not attributable to differences in lipoprotein particle sizes. Future studies of mechanisms of race-related differences in CAC may enhance understanding of the pathophysiology of racial differences in cardiovascular disease.

The Relationship Between Plasma Osteoprotegerin Levels and Coronary Artery Calcification in Uncomplicated Type 2 Diabetic Subjects

This study sought to prospectively evaluate the relationship between plasma osteoprotegerin (OPG), inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], coronary artery calcification (CAC), and cardiovascular events in patients with type 2 diabetes. Arterial calcification is a prominent feature of atherosclerosis and is associated with an increased risk of cardiovascular events. Osteoprotegerin is a cytokine that has recently been implicated in the regulation of vascular calcification. A total of 510 type 2 diabetic patients (53 +/- 8 years; 61% male) free of symptoms of cardiovascular disease were evaluated by CAC imaging. Risk factors, hs-CRP, IL-6, and OPG levels were measured. Patients were followed up for cardiovascular events (cardiac death, myocardial infarction, acute coronary syndrome, late revascularization, and nonhemorrhagic stroke). Significant CAC (>10 Agatston units) was seen in 236 patients (46.3%); OPG was significantly elevated in patients with increased CAC. In multivariable analyses, OPG retained a strong association with elevated CAC scores after adjustment for age, gender, and other risk factors (odds ratio = 2.84, 95% confidence interval 2.2 to 3.67; p < 0.01). Sixteen cardiovascular events occurred during a mean follow-up of 18 +/- 5 months. The waist-to-hip ratio, United Kingdom Prospective Diabetes Study (UKPDS) risk score, OPG level, and CAC score were significant predictors of time to cardiovascular events in a univariate Cox proportional hazards model. In the multivariate model, the CAC score was the only independent predictor of adverse events. Levels of hs-CRP and IL-6 were related to neither the extent of CAC nor short-term events. A high proportion of asymptomatic diabetic patients have significant subclinical atherosclerosis. Of the biomarkers studied, only OPG predicted both subclinical disease and near-term cardiovascular events. Therefore, measurement of OPG merits further investigation as a simple test for identifying high-risk type 2 diabetic patients.

Risk stratification in uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy

To determine the prevalence and clinical predictors of subclinical atherosclerosis and myocardial ischaemia in uncomplicated type 2 diabetes and assess their relationship to short-term outcome. Established risk factors and coronary artery calcium (CAC) scores were prospectively measured in 510 asymptomatic type 2 diabetic subjects (mean age 53+/-8 years, 61% males) without prior cardiovascular disease. Myocardial perfusion scintigraphy (MPS) was performed in all subjects with CAC > 100 Agatston units (AU) (n=127), and a random sample of the remaining patients with CAC < or = 100 AU (n=53). Significant CAC (> 10 AU) was found in 46.3%. Twenty events occurred (two coronary deaths, nine non-fatal myocardial infarctions, three acute coronary syndromes, three non-haemorrhagic strokes, and three late revascularisations) during a median follow-up of 2.2 years (25th-75th percentile = 1.9-2.5 years). The age, systolic blood pressure, the duration of diabetes, United Kingdom Prospective Diabetes Study risk score, CAC score, and extent of myocardial perfusion abnormality were significant predictors of time to cardiovascular events in a univariable Cox proportional hazard model. No cardiac events or perfusion abnormalities occurred in subjects with CAC < or = 10 AU up until 2 years of follow-up. CAC and MPS findings were synergistic for the prediction of short-term cardiovascular events. Subclinical atherosclerosis, measured by CAC imaging, is superior to the established cardiovascular risk factors for predicting silent myocardial ischaemia and short-term outcome. Further studies evaluating the impact of CAC imaging on clinical outcomes and its cost effectiveness are warranted.

Soluble interleukin-2 receptor as a marker for progression of coronary artery calcification in type 1 diabetes

Introduction Soluble interleukin-2 receptor (sIL2r), a marker of T cell activation, is elevated in inflammatory processes, such as rheumatoid arthritis, hepatitis and neoplasm. We explored a potential association between plasma sIL2r levels and progression of coronary artery calcification (CAC), a marker for subclinical atherosclerosis, in a prospectively followed cohort of type 1 diabetic and non-diabetic subjects, aged 20–59 years, with no history of coronary artery disease. Materials and methods CAC progression was assessed by electron beam tomography over 2.6 years (range 1.6–3.2). Plasma sIL2r levels were measured in a nested case–control substudy of 98 subjects (67 diabetic, 31 non-diabetic) with and 173 subjects (84 diabetic, 89 non-diabetic) without significant CAC progression. Log-transformed sIL2r levels were analyzed by conditional logistic regression to compare subjects with and without significant CAC progression. Results SIL2r was a significant predictor for CAC progression after adjusting for presence of baseline CAC, age, gender, diabetes status, baseline calcium volume score and adiponectin (OR 1.99, 95% CI 1.09–3.61, p = 0.02 for a doubling of sIL2r level). Addition of BMI, LDL, HDL, hypertension, smoking status, HbA1c, CRP, fibrinogen, homocysteine and PAI-1 to regression models weakened but did not remove sIL2r as a predictor of CAC progression. There was no indication that this effect was different by diabetes status ( p = 0.6 for diabetes–sIL2r interaction). Discussion Elevated plasma sIL2r is associated with CAC progression independent of traditional coronary artery disease risk factors in type 1 diabetic and non-diabetic young adults. SIL2r should be considered as a novel marker of inflammation leading to coronary artery disease.

Framingham risk equation underestimates subclinical atherosclerosis risk in asymptomatic women

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 ≤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 ≥100 and CAC ≥400 were seen in 10 and 3% of women, respectively. Overall, 20% of women had age-gender derived ≥75th percentile CAC. According to FRE, the majority (84%) of women with significant CAC ≥75th percentile were classified as low-risk. Approximately half (45%) of low-risk women with ≥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.

Low Plasma Adiponectin Levels Predict Progression of Coronary Artery Calcification

Circulating adiponectin levels are lower in men than in women and lower in advanced coronary artery disease, obesity, and type 2 but not type 1 diabetes. However, it is not known whether low adiponectin levels predict development of atherosclerosis independently of other cardiovascular risk factors. Progression of coronary artery calcification (CAC) over an average of 2.6 years (range, 1.6 to 3.3) was assessed in a cohort of patients with type 1 diabetes and nondiabetic subjects 19 to 59 years of age. In this nested case-control substudy, plasma adiponectin levels were measured in 101 cases with significant CAC progression and in 205 controls. Controls were oversampled on the basis of age, gender, diabetes status, and presence of baseline CAC. In conditional logistic regression adjusted for baseline CAC volume and other significant predictors of CAC progression, adiponectin levels were inversely related to progression of CAC in diabetic (OR, 0.47; 95% CI, 0.24 to 0.94) and nondiabetic (OR, 0.15; 95% CI, 0.05 to 0.40 for a doubling in adiponectin levels) subjects. Adjustment for additional cardiovascular risk factors did not change this association. In conditional logistic regression models by quartiles of plasma adiponectin levels, the probability value for trend was statistically significant for all participants (P<0.001) and nondiabetic participants (P<0.001) and was borderline for type 1 diabetics (P=0.08). Low plasma adiponectin levels are associated with progression of CAC in type 1 diabetic and nondiabetic subjects independently of other cardiovascular risk factors.

Coronary and aortic calcifications in patients new to dialysis

Vascular calcification has been associated with all cause and cardiovascular mortality in patients with end-stage kidney disease (ESRD). Whether vascular calcification is present in persons with advanced chronic kidney disease starting dialysis or develops in patients on dialysis is unknown. The purpose of this study was to examine the prevalence of vascular and coronary calcification in patients new to hemodialysis. A total of 129 subjects new to dialysis were evaluated using electron beam computed tomography. The primary outcome was the presence and extent of coronary artery, aortic, and valvular calcification. Forty-three percent of subjects had no significant coronary artery calcification (total score </= 30) and 27% had no detectable aortic calcification. Thirty-four percent had coronary artery scores that placed them above the 90th percentile for age and sex. Coronary artery calcification was significantly associated with a history of coronary artery disease and atherosclerotic vascular disease (ASVD) whereas aortic calcification was significantly associated with ASVD. Age (p < 0.0001), pulse pressure (p = 0.004), diabetes mellitus (p = 0.009), and a history of smoking (p = 0.026) were independently associated with the extent of coronary artery calcification. Age (p < 0.0001) and pulse pressure (p = 0.0003) were independently associated with the extent of aortic calcification. A large fraction of patients new to hemodialysis had no evidence of coronary artery or aortic calcification. Coupled with the extensive vascular calcification reported by others in prevalent dialysis patients these findings suggest that dialysis-specific factors contribute to calcific vascular disease in ESRD.

Study 1: unexpected high incidence of coronary artery disease and abnormal platelet reactivity in long-term pediatric kidney transplant recipients

L ong-term outcomes of children who undergo renal transplantation are unknown. However, as they enter adulthood, many will have risk factors for developing coronary artery disease (CAD). Certain noninvasive tests may detect early CAD. Electron-beam computed tomography (EBCT) can measure the amount of coronary artery calcification (CAC), which correlates with the presence of atherosclerotic CAD. In addition, abnormal platelet function has been linked to increased risk for atherogenesis and CAD. The purpose of this study was to determine the incidence of CAD by using EBCT in adults who underwent renal transplantation as children and determine whether presence of accelerated atherogenesis is associated with enhanced platelet reactivity. Eight pediatric kidney transplant recipients with good long-term allograft function ( 10 years) underwent evaluation by EBCT. The CAC score was determined by standardized technique. Platelet reactivity was assessed by measures of dense granule secretory rate, metabolic content, and spontaneous microaggregate formation. Results were compared with those in age-matched controls. The mean age at transplantation was 14 years (range, 10-16). Mean age at evaluation was 45 years (range, 23-48). Mean follow-up in this group was 17 years (range, 10-23). All received cyclosporine-based immunosuppression. Seven had 2 or more clinical risk factors for CAD. All were asymptomatic at the time of evaluation. Seven out of 8 patients had significant CAC detected on EBCT. When compared with ageand gender-matched controls, study patients had CAC scores 99% (n 4), 95% to 99% (n 2), and 75% to 95% (n 1). Platelets from those with CAC were significantly more likely to form microaggregates after mild stimulation compared with those without CAC (P .02). Also, they were more likely to form microaggregates (P .03), had slower dense granule secretion (P .04), and had lower metabolic stores (P .03) compared with controls. Conclusion: The incidence of CAC by EBCT in long-term pediatric kidney transplant recipients is much higher than expected compared with the general population. Besides clinical risk factors, it appears that platelets from these patients are more reactive, which may place them at further increased risk for thrombotic complications of atherosclerosis. Our data suggest that measures to decrease risk factors for CAD should be undertaken as children approach young adulthood. From the William J. von Liebig Transplant Center, Mayo Clinic; and the Department of Radiology; and Division of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. © 2004 Elsevier Inc. All rights reserved. 0955-470X/04/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.006

The metabolic syndrome, diabetes, and subclinicalatherosclerosis assessed by coronary calcium

ObjectivesWe compared the prevalence and extent of coronary artery calcium (CAC) among persons with the metabolic syndrome (MetS), diabetes, and neither condition. BackgroundThe prevalence and extent of CAC has not been compared among those with MetS, diabetes, or neither condition. MethodsOf 1,823 persons (36% female) age 20 to 79 years who had screening for CAC by computed tomography, 279 had MetS, 150 had diabetes, and the remainder (n = 1,394) had neither condition. Metabolic syndrome was defined with ≥3 of the following: body mass index ≥30 kg/m2; high-density lipoprotein cholesterol <40 mg/dl if male or <50 mg/dl if female; triglycerides ≥150 mg/dl; blood pressure ≥130/85 mm Hg or on treatment; or fasting glucose 110 to 125 mg/dl. The prevalence and odds of any and significant (≥75th percentile) CAC among these groups and by number of MetS risk factors were determined. ResultsThose with neither MetS nor diabetes, MetS, or diabetes had a prevalence of CAC of 53.5%, 58.8%, and 75.3% (p < 0.001), respectively, among men and 37.6%, 50.8%, and 52.6% (p < 0.001), respectively, among women. Coronary artery calcium increased by the number (0 to 5) of MetS risk factors (from 34.0% to 58.3%) (p < 0.001). Forty-one percent of subjects with MetS had either a >20% 10-year risk of CHD or CAC ≥75th percentile for age and gender. Risk factor-adjusted odds for the presence of CAC were 1.40 (95% confidence interval [CI] 1.05 to 1.87) among those with MetS and 1.67 (95% CI 1.12 to 2.50) among those with diabetes, versus those with neither condition. ConclusionsThose with MetS or diabetes have an increased likelihood of CAC compared with those having neither condition.

Electron Beam Computed Tomography for Assessment of Coronary Artery Disease in HIV-Infected Men Receiving Antiretroviral Therapy

Hyperlipidemia has been seen in patients receiving protease inhibitorbased antiretroviral therapy, prompting concern that such patients are at risk for accelerated coronary artery disease (CAD). To assess the risk of CAD in antiretroviraltreated HIV-infected men, we quantified coronary artery calcium (CAC), a sensitive and established marker of subclinical CAD, using electron beam computed tomography (EBCT) of coronary vessels. Sixty HIV-infected men who met the following criteria (cases) were enrolled in the study: age of 40 years or older; naive to antiretroviral therapy or use of a stable antiretroviral regimen for ≥6 months (mean duration, 25.9 months; 41 patients were receiving protease inhibitor therapy); and no known CAD or no use of lipid-lowering agents. EBCT-derived CAC scores, serum lipid levels, history of antiretroviral therapy, and risk factors for CAD were obtained. Each case was compared with three age-, sex-, and race-matched HIV-negative controls randomly selected from a database including >9000 patients who had undergone EBCT. We determined differences in the proportion of cases and controls with CAC scores of >0 (detectable calcium) and clinically significant CAC for age range. There were no statistically significant differences between the number of cases and controls with detectable CAC (33% and 39%, respectively) and clinically significant CAC (18% and 17%, respectively). This study suggests that the rate of coronary atherosclerosis among HIV-infected patients who receive short-term antiretroviral therapy with or without protease inhibitors is not higher than that among age-, sex-, and racematched HIV-negative controls. These results need to be confirmed in larger long-term studies, with controls well matched for coronary risk factors.

Electron beam computed tomography for assessment of coronary artery disease in HIV-infected men receiving antiretroviral therapy.

Hyperlipidemia has been seen in patients receiving protease inhibitor-based antiretroviral therapy, prompting concern that such patients are at risk for accelerated coronary artery disease (CAD). To assess the risk of CAD in antiretroviral-treated HIV-infected men, we quantified coronary artery calcium (CAC), a sensitive and established marker of subclinical CAD, using electron beam computed tomography (EBCT) of coronary vessels. Sixty HIV-infected men who met the following criteria (cases) were enrolled in the study: age of 40 years or older; naive to antiretroviral therapy or use of a stable antiretroviral regimen for >or=6 months (mean duration, 25.9 months; 41 patients were receiving protease inhibitor therapy); and no known CAD or no use of lipid-lowering agents. EBCT-derived CAC scores, serum lipid levels, history of antiretroviral therapy, and risk factors for CAD were obtained. Each case was compared with three age-, sex-, and race-matched HIV-negative controls randomly selected from a database including >9000 patients who had undergone EBCT. We determined differences in the proportion of cases and controls with CAC scores of >0 (detectable calcium) and clinically significant CAC for age range. There were no statistically significant differences between the number of cases and controls with detectable CAC (33% and 39%, respectively) and clinically significant CAC (18% and 17%, respectively). This study suggests that the rate of coronary atherosclerosis among HIV-infected patients who receive short-term antiretroviral therapy with or without protease inhibitors is not higher than that among age-, sex-, and race-matched HIV-negative controls. These results need to be confirmed in larger long-term studies, with controls well matched for coronary risk factors.

Total antioxidant status and coronary artery calcification in type 1 diabetes.

Type 1 diabetes is associated with a high risk of coronary heart disease (CHD), despite the absence of dyslipidemia. Oxidative modification may render LDLs more atherogenic. We aimed to assess antioxidant status in type 1 diabetes and its association with coronary artery calcification (CAC). Total antioxidant status (TAS) of serum was measured using the Trolox equivalent antioxidant capacity assay in 48 type 1 diabetic and 25 nondiabetic subjects. The presence of CAC was assessed in the diabetic subjects using electron beam computed tomography. TAS was reduced in type 1 diabetic subjects compared with nondiabetic subjects (Mann-Whitney U test, P < 0.0001). There were associations between TAS and HbA(1c) (r = -0.43; P = 0.0026) and duration of diabetes (r = -0.35; P = 0.0157). Significant CAC was considered present if the Agatston score was >10. The diabetic subjects with significant CAC were older (P < 0.0001); had longer duration of diabetes (P = 0.0002); were more likely to have high blood pressure (P = 0.040); had higher total cholesterol concentration (P = 0.039), serum creatinine concentration (P = 0.003), and urinary albumin-to-creatinine ratio (P = 0.022); and had lower serum TAS (P = 0.018) compared with those without significant calcification. In logistic regression with CAC as the dependent variable, TAS was entered as a predictor, and the effects on its predictive value of adding other explanatory variables in bivariate analyses were assessed. The power of TAS to predict CAC was independent of many of the traditional CHD risk factors. Whereas TAS as a predictor was no longer statistically significant when age or duration of diabetes were entered into the model, the odds ratio for a TAS concentration above the median value predicting significant CAC only increased from 0.19 to 0.26 and 0.32, respectively. TAS is reduced in type 1 diabetes and is associated with the presence of CAC.

Stent deployment in calcified lesions: Can we overcome calcific restraint with high‐pressure balloon inflations?

Although significant coronary artery (CA) calcification is believed to affect stent deployment, the exact impact on stent deployment after high-pressure balloon inflations is unknown. Intracoronary intravascular examination (ICUS) was performed in 27 moderate-severe calcified CA lesions before and after stent implantation. In case of unsatisfactory results (in-stent area < 90%, minimal in-stent diameter/maximal in-stent diameter < 0.8), further inflations up to 20 atm guided by ICUS were applied. Initially, stent expansion was adequate in 10 stents (37%) and symmetric in 19 (70%). After inflation at 20 atm, stents with adequate expansion increased to 16 (59%, P = 0.0036), but stents with symmetry decreased to 13 (48%, P = 0.0045). Stent expansion was inversely correlated to the arc of calcium (r = -0.8, P < 0.0001). There were five patients with clinical restenosis at 6 months (18%). Increases in stent lumen area with high-pressure balloon inflations in moderate-severe calcified CA lesions are at the expense of symmetry. This may affect clinical restenosis. Cathet Cardiovasc Intervent 2001;52:164–172. © 2001 Wiley-Liss, Inc.

Increased prevalence of significant coronary artery calcification in patients with diabetes.

Coronary artery disease is the major cause of morbidity and mortality in patients with diabetes. Detection of coronary artery disease before the first myocardial infarction and before anginal symptoms will allow for strategies designed to reduce the cardiovascular event rate in this group of patients. Electron beam-computed tomography (EBCT) is a noninvasive technology for evaluating the extent of coronary artery atherosclerosis that relies on the detection of coronary artery calcium (CAC). We used EBCT to detect significant coronary artery atherosclerosis in diabetic patients without symptoms of heart disease. We used EBCT to evaluate calcium in the coronary arteries of 139 consecutive diabetic patients scanned over a 20-month period. The CAC scores in this group were compared with a randomly selected nondiabetic control group and a control group that was selected to match a number of established cardiovascular risk factors. Patients with diabetes had a significant increase in the prevalence of CAC scores > or =400 (25.9%) compared with the randomly selected (7.2%) and matched (14.4%) nondiabetic control groups. Scores in this range have been reported to be highly predictive for abnormal stress myocardial perfusion tomography and subsequent coronary events. Our results, therefore, indicate a substantial prevalence of significant coronary artery disease in an asymptomatic diabetic patient population compared with nondiabetic control subjects. They also suggest that EBCT may be a useful approach for selecting a group of diabetic subjects who would benefit most from additional evaluation for subclinical coronary artery disease.

Stent deployment in calcified lesions: Can we overcome calcific restraint with high-pressure balloon inflations?

Although significant coronary artery (CA) calcification is believed to affect stent deployment, the exact impact on stent deployment after high-pressure balloon inflations is unknown. Intracoronary intravascular examination (ICUS) was performed in 27 moderate-severe calcified CA lesions before and after stent implantation. In case of unsatisfactory results (in-stent area < 90%, minimal in-stent diameter/maximal in-stent diameter < 0.8), further inflations up to 20 atm guided by ICUS were applied. Initially, stent expansion was adequate in 10 stents (37%) and symmetric in 19 (70%). After inflation at 20 atm, stents with adequate expansion increased to 16 (59%, P = 0.0036), but stents with symmetry decreased to 13 (48%, P = 0.0045). Stent expansion was inversely correlated to the arc of calcium (r = -0.8, P < 0.0001). There were five patients with clinical restenosis at 6 months (18%). Increases in stent lumen area with high-pressure balloon inflations in moderate-severe calcified CA lesions are at the expense of symmetry. This may affect clinical restenosis.

Exercise Tolerance in Asymptomatic Elderly Men With Fluoroscopically Detected Coronary Artery Calcification

The value of detecting coronary artery calcification (CAC), by cardiac imaging, for the diagnosis of coronary artery disease (CAD) in asymptomatic middle-aged men has been demonstrated. However, the incidence of CAC increases with age. The functional significance of CAC remains unknown in asymptomatic elderly men. The purpose of this study is to explore whether CAC in asymptomatic aging men signifies the presence of cardiovascular dysfunction during exercise. This study was designed to address whether elderly asymptomatic men, selected because they have CAC, have reduced exercise tolerance due to functionally significant CAD. Thirty-eight asymptomatic male volunteers (ages 50 to 75 years, mean [+/-SD] 64+/-7 years) with a normal resting ECG and at least one coronary risk factor, in a population study. Nineteen subjects had CAC detected by digital subtraction fluoroscopy in at least two major coronary arteries, and 19 subjects had no identifiable CAC. Each subject underwent a symptom-limited incremental exercise test with 12-lead ECG monitoring and respiratory gas analysis. Four indexes of exercise oxygen transport were evaluated: peak oxygen uptake (VO2), lactic acidosis threshold, peak VO2/heart rate ratio, and VO2 relative to a work rate increase. Eleven of 38 subjects (28%) were found to have reduced oxygen transport, which was defined as an abnormal reduction in more than two of the above four indexes of oxygen transport. Five of the 11 subjects with reduced oxygen transport had CAC, and 6 subjects did not (not significant). Only one subject with CAC had exercise ST depression. Significant CAC in asymptomatic men over age 50 does not signify exercise limitation due to CAD.