George T. Kondos

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

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

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

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

Coronary Calcium Predicts Events Better With Absolute Calcium Scores Than Age-Sex-Race/Ethnicity Percentiles: MESA (Multi-Ethnic Study of Atherosclerosis)

OBJECTIVES In this study, we aimed to establish whether age-sex-specific percentiles of coronary artery calcium (CAC) predict cardiovascular outcomes better than the actual (absolute) CAC score. BACKGROUND The presence and extent of CAC correlates with the overall magnitude of coronary atherosclerotic plaque burden and with the development of subsequent coronary events. METHODS MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 asymptomatic participants followed for coronary heart disease (CHD) events including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death. Time to incident CHD was modeled with Cox regression, and we compared models with percentiles based on age, sex, and/or race/ethnicity to categories commonly used (0, 1 to 100, 101 to 400, 400+ Agatston units). RESULTS There were 163 (2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in terms of age- and sex-specific percentiles had significantly lower area under the receiver-operating characteristic curve (AUC) than when using absolute scores (women: AUC 0.73 versus 0.76, p = 0.044; men: AUC 0.73 versus 0.77, p < 0.001). Akaikes information criterion indicated better model fit with the overall score. Both methods robustly predicted events (>90th percentile associated with a hazard ratio [HR] of 16.4, 95% confidence interval [CI]: 9.30 to 28.9, and score >400 associated with HR of 20.6, 95% CI: 11.8 to 36.0). Within groups based on age-, sex-, and race/ethnicity-specific percentiles there remains a clear trend of increasing risk across levels of the absolute CAC groups. In contrast, once absolute CAC category is fixed, there is no increasing trend across levels of age-, sex-, and race/ethnicity-specific categories. Patients with low absolute scores are low-risk, regardless of age-, sex-, and race/ethnicity-specific percentile rank. Persons with an absolute CAC score of >400 are high risk, regardless of percentile rank. CONCLUSIONS Using absolute CAC in standard groups performed better than age-, sex-, and race/ethnicity-specific percentiles in terms of model fit and discrimination. We recommend using cut points based on the absolute CAC amount, and the common CAC cut points of 100 and 400 seem to perform well.

Cardiovascular events with absent or minimal coronary calcification: The Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND Elevated coronary artery calcium (CAC) is a marker for increase risk of coronary heart disease (CHD). Although most CHD events occur among individuals with advanced CAC, CHD can also occur in individuals with little or no calcified plaque. In this study, we sought to evaluate the characteristics associated with incident CHD events in the setting of minimal (score <or=10) or absent CAC (score of zero). METHODS Asymptomatic participants in the MESA (N = 6,809) were followed for occurrence of all CHD events (including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death) and hard CHD events (myocardial infarction or CHD death). Time to incident CHD was modeled using age-and gender-adjusted Cox regression. RESULTS The final study population consisted of 3,923 MESA asymptomatic participants (mean age 58 +/- 9 years, 39% males) who had CAC scores of 0 to 10. Overall, no detectable CAC was seen in 3415 individuals, whereas 508 had CAC scores of 1 to 10. During follow-up (median 4.1 years), there were 16 incident hard events and 28 all CHD events in individuals with absent or minimal CAC. In age-, gender-, race-, and CHD risk factor-adjusted analysis, minimal CAC (1-10) was associated with an estimated 3-fold greater risk of a hard CHD event (HR 3.23, 95% CI 1.17-8.95) or of all CHD event (HR 3.66, 95% CI 1.71-7.85) compared to those with CAC = 0. Former smoking (HR 3.57, 95% CI 1.08-11.77), current smoking (HR 4.93, 95% CI 1.20-20.30), and diabetes (HR 3.09, 95% CI 1.07-8.93) were significant risk factors for events in those with CAC = 0. CONCLUSION Asymptomatic persons with absent or minimal CAC are at very low risk of future cardiovascular events. Individuals with minimal CAC (1-10) were significantly increased to 3-fold increased risk for incident CHD events relative to those with CAC scores of zero.

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

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

Determination of left ventricular ejection fraction by visual estimation during real-time two-dimensional echocardiography

It has been shown that the measured reduction in the cross-sectional area of the left ventricle (LV), as viewed in the short axis, closely approximates its ejection fraction (EF). We assessed the reliability of using two-dimensional echocardiography (2DE) to visually estimate the EF during real-time viewing, without the need of digitizers, planimetry, or calculations. Twenty-five adult hospitalized patients with either suspected or known cardiac disease were evaluated prospectively. Each patient also had gated nuclear angiography during the same admission, and 14 had cardiac catheterization with left ventriculography. The EF was determined by 2DE using a visual estimate of the percent area reduction of the LV cavity in the short-axis view at the level of the papillary muscles. All 2 DE studies were read by two or more blinded reviewers, with a value for the EF to the nearest 2.5% determined by consensus. These values correlated closely to the values determined in all 25 patients with gated nuclear angiography (r = 0.927) and the 14 patients who had left ventriculography (r = 0.935). We believe that this method of visually estimating the LVEF will enable echocardiographers to easily use 2 DE for a reliable and instantaneous assessment of ventricular function, without the need of sophisticated analytical equipment.

Ability of the no-reflow phenomenon during an acute myocardial infarction to predict left ventricular dysfunction at one-month follow-up

Despite angiographically successful opening of an infarct-related vessel within a 6-hour time frame, some patients do not recover left ventricular regional wall function in the infarct zone after an acute myocardial infarction (AMI). Recent evidence suggests that this finding is due to the no-reflow phenomenon, or failure to recover tissue perfusion despite patient epicardial arteries. We performed myocardial contrast echocardiography to assess tissue perfusion before and after opening of an infarct-related artery. Coronary angiograms, regional wall motion scoring, and myocardial contrast enhancement were graded by 3 observers. Of 24 patients with AMI, 7 (29%) failed to recover tissue perfusion in > or = 1 region of myocardium. Of 106 regions subtended by the infarct-related artery, 16 (15%), 43 (41%), and 47 (44%) regions had no-reflow, partial, or normal flow, respectively, after arterial patency was established. There was a spectrum of reperfusion patterns ranging from no-reflow to normal perfusion. One-month follow-up angiographic and myocardial contrast echocardiographic studies were performed in 12 of the 24 patients. At 1 month, all segments of myocardium that had immediate normal perfusion had regained normal wall motion. In contrast, 17 segments that had partial or no-reflow were identified. Of these 17, 3 regained normal function, 10 segments were hypokinetic, and 4 segments were akinetic. We conclude that myocardial contrast echocardiography can be used to identify the no-reflow phenomenon in up to 29% of patients with AMI. Additionally, we found that the immediate-reflow pattern can predict degree of left ventricular dysfunction at 1-month follow-up.

Increased High-Density Lipoprotein Cholesterol Predicts the Pioglitazone-Mediated Reduction of Carotid Intima-Media Thickness Progression in Patients With Type 2 Diabetes Mellitus

Background— Measurement of carotid intima-media thickness (CIMT) has been validated as a measure of atherosclerosis and as a predictor of future cardiovascular events. Compared with glimepiride, pioglitazone has been shown to slow the progression of atherosclerosis measured by CIMT in patients with type 2 diabetes mellitus. Methods and Results— We evaluated individual cardiovascular risk factors as predictors of the change in CIMT produced by pioglitazone treatment by determining whether their addition to a baseline model resulted in loss of significance for the treatment effect on CIMT. Pioglitazone treatment led to improvement in levels of multiple cardiovascular risk markers, including high-sensitivity C-reactive protein, apolipoprotein B, apolipoprotein A1, high-density lipoprotein (HDL) cholesterol, triglyceride, insulin, and free fatty acid. At 24 weeks, there were significant differences in HDL cholesterol, triglyceride, total cholesterol, low-density lipoprotein cholesterol, insulin, body mass index, hip circumference, and high-sensitivity C-reactive protein between the pioglitazone and glimepiride treatment groups. After adjustment for 24-week on-treatment values of cardiovascular risk factors, only inclusion of the changes in HDL cholesterol and insulin significantly impacted the magnitude and significance of the treatment effect on CIMT. Furthermore, irrespective of treatment assignment, increased HDL cholesterol at 24 weeks was a significant predictor of reduced CIMT progression at 72 weeks. Conclusions— The beneficial effect of pioglitazone on HDL cholesterol at 24 weeks predicted its beneficial effect for reducing CIMT progression at 72 weeks. Changes in HDL cholesterol at 24 weeks, irrespective of treatment, predicted less progression of CIMT at 72 weeks. These results suggest that suppression of atherosclerosis with pioglitazone therapy is linked to its ability to raise HDL cholesterol.

The prevalence of coronary artery calcium among diabetic individuals without known coronary artery disease

OBJECTIVES We sought to examine the age and gender distribution of coronary artery calcium (CAC) by diabetes status in a large cohort of asymptomatic individuals. BACKGROUND Among individuals with diabetes, coronary artery disease (CAD) is a major cause of morbidity and mortality. Electron-beam tomography (EBT) quantifies CAC, a marker for atherosclerosis. METHODS Screening for CAC by EBT was performed in 30,904 asymptomatic individuals stratified by their self-reported diabetes status, gender, and age. The distribution of CAC across the strata and the association between diabetes and CAC were examined. RESULTS Compared with nondiabetic individuals (n = 29,829), those with diabetes (n = 1,075) had higher median CAC scores across all but two age groups (women 40 to 44 years old and men and women > or =70 years old). Overall, the likelihood of having a CAC score in the highest age/gender quartile was 70% greater for diabetic individuals than for their nondiabetic counterparts. CONCLUSIONS Younger diabetic individuals appear to have calcified plaque burden comparable to that of older individuals without diabetes. These findings call for future research to determine if EBT-CAC screening has an incremental value over the current CAD risk assessment of individuals with diabetes.

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

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