Abdominal aortic diameter and vascular atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVES: To gain insight into early mechanisms of aortic widening, we examined associations between the diameter of the abdominal aorta (AD) and cardiovascular disease (CVD) risk factors and biomarkers, as well as measures of subclinical atherosclerosis, in a multi-ethnic population. DESIGN: Cross-sectional cohort. METHODS: A total of 1926 participants (mean age 62, 50% women) underwent chest and abdomen scanning by computed tomography, ultrasound of the carotid arteries, and CVD risk factor assessment. AD was measured 5 cm above and at the bifurcation. RESULTS: In a model containing traditional CVD risk factors, biomarkers and ethnicity, only age (standardized ß = 0.97), male sex (ß = 1.88), body surface area (standardized ß = 0.92), current smoking (ß = 0.42), D-dimer levels (ß = 0.19) and hypertension (ß = 0.53) were independently and significantly associated with increasing AD (in mm) at the bifurcation; use of cholesterol-lowering medications predicted smaller AD (ß = -0.70) (P < 0.01 for all). These findings were similar for AD 5 cm above the bifurcation with one exception: compared to Caucasian-Americans, Americans of Chinese, African and Hispanic descent had significantly smaller AD 5 cm above the bifurcation (ß's = -0.59, -0.49, and -0.52, respectively, all P < 0.01), whereas AD at the bifurcation did not differ by ethnicity. Physical activity, alcohol consumption, diabetes and levels of IL-6, CRP and homocysteine were not independently associated with AD. Higher aortic and coronary artery calcium burden, but not common carotid artery intima-media thickness, were independently, but modestly (ß = 0.11 to 0.19), associated with larger AD. CONCLUSIONS: Incremental widening of the aortic diameter shared some, but not all, risk factors for occlusive vascular disease.

Association of obesity and atrial fibrillation among middle-aged and elderly Chinese.

OBJECTIVE: To examine the associations between body mass index (BMI), waist circumference (WC) and risk of atrial fibrillation (AF) in Chinese adults. DESIGN, SUBJECTS AND MEASUREMENTS: A cross-sectional study was conducted to explore the association between obesity and atrial fibrillation among 18,615 Chinese (10,370 females) aged 35 years and above in 2004. AF was defined by electrocardiography and history. Obesity was classified by BMI and WC, including overweight (BMI: 24.0-27.9 kg m(-2); WC: 85.0-94.9 cm for men and 80.0-89.9 cm for women) and obesity (BMI: > or = 28.0 kg m(-2); WC: > or = 95 cm for men and > or = 90 cm for women), according to the Chinese Guidelines on Prevention and Treatment of Obesity in Adults. Multivariable logistic regression was used to analyze the association between obesity and AF. RESULTS: Age- and sex-adjusted prevalence of AF (n=194) was higher with increased BMI, with 0.9% for normal, 1.1% for overweight and 1.6% for obese (P(trend)<0.01) Chinese. Compared with normal BMI, multivariable-adjusted odds ratios (ORs) were 1.2 (95% confidence interval (CI): 0.8-1.7) for overweight BMI and 1.8 (95% CI: 1.2-2.8) for obese BMI (P(trend)<0.01). After excluding known secondary AF (valvular, postoperative and hyperthyroid) and unclassified AF, the corresponding multivariable-adjusted ORs were 1.4 (95% CI: 0.9-2.2) and 2.2 (95% CI: 1.3-3.7) (P (trend)<0.01). The same trends were observed for WC. Multivariable-adjusted OR was 2.6 (95% CI: 1.4-4.6) for participants with both BMI and WC obesity and 1.7 (95% CI: 1.0-2.9) for participants with both BMI and WC overweight in comparison with those with both BMI and WC in the normal range. CONCLUSION: Obesity, either defined by BMI or WC, was significantly associated with AF among middle-aged and elderly Chinese.

Validation of thoracic quantitative computed tomography as a method to measure bone mineral density.

The purpose of this study was to measure precision of thoracic quantitative computed tomography (QCT) bone mineral density (BMD) and correlation to lumbar spine QCT bone density. We measured the reproducibility of thoracic QCT; two consecutive thoracic QCT scans of the T9, T10, and T11 vertebrae were performed on 95 subjects (49 females, 46 males; mean age, 62.5 years) undergoing coronary scanning. In order to correlate the thoracic to standard lumbar measurement, the subjects also underwent a lumbar QCT scan of the L1, L2, and L3 vertebrae as part of an abdominal aortic scanning study. The variation of thoracic BMD was assessed in different ethnic subgroups. Consecutive thoracic QCT measurements showed good agreement (r=0.98; RMS CV=5.78%). Thoracic bone density was significantly higher than lumbar bone density results (paired t-test, P=0.003), but the two methods correlated well (r=0.86). The regression equation for the relationship between lumbar (X) and thoracic (Y) QCT was Y=0.87X + 22.97. The standard error of estimate was 19.0 mg/cm3. Thoracic QCT from coronary calcium thoracic scans is able to measure BMD with rescan precision and regression errors that are small compared to the biologic variability in the population. Given the relatively small precision error and the reasonable correlation to lumbar BMD, an ancillary assessment of thoracic BMD in a cardiac scan is likely to be a useful assessment of bone mineral status in the general population.

Coronary artery calcium evaluation by electron beam computed tomography and its relation to new cardiovascular events.

Electron beam computed tomography is widely used to screen for coronary artery calcium (CAC). We evaluated the relation of CAC to future cardiovascular disease events in 926 asymptomatic persons (735 men and 191 women, mean age 54 years) who underwent a baseline electron beam computed tomographic scan. All subjects included in this report returned a follow-up questionnaire 2 to 4 years (mean 3.3) after scanning, inquiring about myocardial infarction, stroke, and revascularizations. Sixty percent of men and 40% of women had a positive scan at baseline. Twenty-eight cardiovascular events occurred and were confirmed by blinded medical record review. The presence of CAC (a total calcium score of >0) and increasing score quartiles were related to the occurrence of new myocardial infarction (p <0.05), revascularizations (p <0.001), and total cardiovascular events (p <0.001). Those with scores at or above the median (score of 5) had a relative risk of 4.5 (p <0.01) for new events. From Cox regression models, adjusted for age, gender, and coronary risk factors, the relative risks for those with scores of 81 to 270 and -271 (compared with 0) for cardiovascular events were 4.5 (p <0.05) and 8.8 (p <0.001), respectively. These data support previous reports showing CAC to be a modest predictor of future cardiovascular events.

Prognostic value of coronary electron-beam computed tomography for coronary heart disease events in asymptomatic populations.

The predictive ability of electron-beam computed tomography (EBCT) for coronary heart disease outcomes, particularly hard coronary outcomes (myocardial infarction or death), has been questioned in asymptomatic populations. Our objective was to synthesize data on the use of EBCT for determining cardiovascular prognosis in asymptomatic populations. Studies were identified using standard systematic review methods. The outcome of interest was relative risk for myocardial infarction or sudden death, and combined events including revascularization. Nine articles met the inclusion criteria, of which 5 were of independent studies. Using meta-analytic techniques to synthesize prognostic data, there was an increased risk (summary risk ratio 8.7, 95% confidence interval 2.7 to 28.1) of a combined outcome of nonfatal myocardial infarction or death or revascularization if the calcium score was above a median score. Similarly, there was an increased risk for hard events: myocardial infarction or death (summary risk ratio 4.2, 95% confidence interval 1.6 to 11.3). However, there was significant heterogeneity in the studies' quality and patient populations. Although EBCT appears to predict combined and hard coronary outcomes similarly in high risk, asymptomatic populations, these results should be interpreted with caution. Further study is needed on the incremental value of EBCT over conventional risk prediction before this test is used in screening asymptomatic populations.

Screening for occult coronary artery disease with radiographic detection of coronary calcification.

Coronary atherosclerosis is ubiquitous among adults, yet many afflicted persons will suffer no coronary events. Atherosclerotic plaque formation in the coronary arteries is a dynamic process, and the onset of a coronary event is often unheralded, sudden, and lethal. In addition, it is known that the amount of calcification in the coronary arteries correlates with the amount of atherosclerosis in different persons and, to a lesser degree, in segments of the coronary tree in the same person. Radiographic imaging methods, including fluoroscopy, electron-beam computed tomography, and helical computed tomography, can detect coronary calcium and seem to be able to diagnose coronary atherosclerosis. However, data on the relationship between quantity of coronary calcium and event likelihood are limited. Thus, the diagnostic value and, particularly, the prognostic value of calcium detection are controversial and may be applicable only to certain subgroups of patients.

Alcohol consumption, coronary calcium, and coronary heart disease events.

This study was performed to determine if alcohol intake was associated with reduced coronary risk in a high-risk asymptomatic population, and whether this effect was independent of coronary risk factors and coronary calcium. In 1,196 asymptomatic subjects with coronary risk factors, we assessed alcohol consumption history, performed risk factor measurements, and quantified coronary calcium with electron beam computed tomography. These subjects were then followed for a mean of 41 months, and coronary events (myocardial infarction or coronary death) were noted. Significant inverse predictors of coronary events included alcohol use and serum high-density lipoprotein cholesterol level. Direct predictors of events were history of systemic hypertension, smoking, diabetes mellitus, serum cholesterol, and coronary calcium score. Subjects with coronary calcium were 3.1 times more likely to suffer a coronary event than those without calcium (95% confidence interval [CI] limits 1.3 to 7.2). Subjects who drank alcohol had a relative risk of 0.3 (95% CI limits 0.2 to 0.6) for developing coronary events. After controlling for age, gender, and other risk factors with logistic regression, these differences in relative risk persisted (relative risk 0.58; 95% CI limits 0.41 to 0.82). Alcohol consumption is a significant inverse predictor of coronary events, comparable in magnitude to standard risk factors and to radiographically measured coronary calcium. This effect is independent of coronary risk factors and coronary calcium.

Racial differences in the significance of coronary calcium in asymptomatic black and white subjects with coronary risk factors.

OBJECTIVES: To compare the significance of a specific feature of coronary atherosclerosis--coronary calcium--in asymptomatic black and white subjects with coronary risk factors. BACKGROUND: The natural history and clinical evolution of coronary atherosclerosis differs between blacks and whites. Differences in the underlying pathobiology of atherosclerosis may be one determinant of the ethnic variability in the clinical manifestation of coronary atherosclerosis. METHODS: In 1,375 high-risk but asymptomatic subjects (93 blacks [6.8%] and 1,282 whites [93.2%]) with at least one risk factor but no prior evidence of coronary disease, we assessed coronary risk factors, calculated Framingham risk of a coronary event and evaluated coronary calcium with digital subtraction fluoroscopy. We then followed these subjects clinically for 70 +/- 13 months, noting the occurrence of the following coronary events: death due to coronary heart disease (CHD); myocardial infarction (MI); angina pectoris; and performance of coronary bypass or angioplasty. RESULTS: Risk factor profiles were similar in black and white subjects (6-year Framingham risk 15 +/- 7% in blacks, 14 +/- 8% in whites [NS]). Coronary calcium was present in 59.9% of white subjects but only 35.5% of black subjects (p = 0.0001). Nevertheless, after 70 months of follow-up, more blacks than whites (22 blacks [23.7%] vs. 190 whites [14.8%]; p = 0.04) suffered one of the following end points: CHD death, MI, angina or revascularization. The age, gender and coronary risk-adjusted odds ratio of black race for at least one event was 2.16 (95% CI 1.34 to 3.48). CONCLUSIONS: Despite having a lowered prevalence of coronary calcium than high risk whites, high risk blacks suffer more CHD events. Coronary calcium therefore does not carry the same pathobiologic significance in blacks that it does in whites, consistent with the concept that there are specific racial differences in the natural history of CHD and its evolution into clinically manifest events.

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.

Coronary calcium: the good, the bad, and the uncertain.

BACKGROUND: Coronary calcium deposits have been widely regarded to result from a passive process of encrustation or adsorption of mineral onto advanced, complex atherosclerotic lesions. Increasing interest has focused on noninvasive radiologic detection of these calcium deposits as a diagnostic and prognostic adjunct to clinical evaluation of coronary artery disease, particularly with the use of newer, high-resolution imaging techniques such as electron beam computed tomography. METHODS AND RESULTS: We reviewed the literature on coronary calcium and its relation to pathologic atherosclerosis, angiographic stenoses,and clinical events. Clinical calcium detection studies have demonstrated an association between coronary calcium and both extent of coronary artery disease and risk of adverse events. These studies have in the past tended to reinforce the perception that calcific deposits result from a passive mineralization process, signify advanced coronary artery disease, and foreshadow future coronary events. CONCLUSIONS: Recent pathologic, genetic, clinical, and biochemical evidence reviewed in this article suggests that coronary calcium deposits are a manifestation of a complex, organized, and regulated process similar in many respects to new bone formation and may not be a reliable indicator of either the extent of coronary disease or the risk of a future event. These studies also suggest that atherosclerosis and calcific deposits may be distinct pathologic entities that frequently occur together and are related to each other in ways that are poorly understood.

Coronary calcium and standard risk factors in symptomatic patients referred for coronary angiography.

OBJECTIVES: The purpose of this study was to compare quantitative estimates of coronary calcification with traditional coronary risk factors to determine their independent predictive power for the diagnosis of obstructive angiographic coronary artery disease in symptomatic patients. METHODS: Three hundred sixty-eight symptomatic patients underwent coronary angiography and electron beam computed tomography at four different centers between April 1989 and December 1993. A blinded cardiologist interpreted the electron beam computed tomograms. Coronary risk factors were obtained in all 368 patients. Both bivariate and multivariate analyses were used to investigate the relation between risk factors and angiographic disease. RESULTS: One hundred fifty-eight patients (43%) had angiographically obstructive coronary artery disease (>50% luminal stenosis) and 297 (81%) had coronary calcification. At the bivariate level, only male sex and log-transformed coronary calcification were predictive of angiographic disease (p = 0.008, p = 0.001). By multivariate analysis, only male sex and coronary calcification were predictive (p = 0.001, p = 0.001). Sixty-four of the 71 patients without coronary calcification did not have disease, yielding a negative predictive value of 90%. Receiver operating characteristic curve analysis showed that the amount of coronary calcium was a significantly better discriminator of disease than were the other risk factors. CONCLUSIONS: Coronary calcification is a stronger predictor of angiographic coronary artery disease in symptomatic patients undergoing angiography than are standard risk factors.

Exercise tolerance in asymptomatic elderly men with fluoroscopically detected coronary artery calcification.

STUDY OBJECTIVE: 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. DESIGN: This study was designed to address whether elderly asymptomatic men, selected because they have CAC, have reduced exercise tolerance due to functionally significant CAD. PARTICIPANTS AND SETTING: 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. METHODS AND RESULTS: 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. CONCLUSION: Significant CAC in asymptomatic men over age 50 does not signify exercise limitation due to CAD.

Ethnic origin and serum levels of 1alpha,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.

Active serum vitamin D levels are inversely correlated with coronary calcification.

BACKGROUND: Arterial calcification is a common feature of atherosclerosis, occurring in >90% of angiographically significant lesions. Recent evidence from this and other studies suggests that development of atherosclerotic calcification is similar to osteogenesis; thus, we undertook the current investigation on the potential role of osteoregulatory factors in arterial calcification. METHODS AND RESULTS: We studied two human populations (173 subjects) at high and moderate risk for coronary heart disease and assessed them for associations between vascular calcification and serum levels of the osteoregulatory molecules osteocalcin, parathyroid hormone, and 1alpha,25-dihydroxyvitamin D3 (1,25-vitamin D). Our results revealed that 1,25-vitamin D levels are inversely correlated with the extent of vascular calcification in both groups. No correlations were found between extent of calcification and levels of osteocalcin or parathyroid hormone. CONCLUSIONS: These data suggest a possible role for vitamin D in the development of vascular calcification. Vitamin D is also known to be important in bone mineralization; thus, 1,25-vitamin D may be one factor to explain the long observed association between osteoporosis and vascular calcification.

Electron beam computed tomographic coronary calcium as a predictor of coronary events: comparison of two protocols.

BACKGROUND: We assessed the accuracy of two electron beam computed tomography (EBCT) protocols for predicting coronary events. METHODS AND RESULTS: In 1994, 24 months after enrollment in a longitudinal study, 326 high-risk adults underwent both 3- and 6-mm image-slice thickness EBCT scanning and were followed up for 32.0+/-4.0 additional months. Events were defined as either coronary death, myocardial infarction, or revascularization. We monitored these subjects for the 32-month postscanning period with yearly phone calls and acquisition of records for all hospital admissions. At the time of scanning, 11 subjects (3%) had already suffered 12 events (5 infarctions and 7 revascularizations) during the 24-month prescanning period. During the postscanning period, 18 subjects (6%) suffered 23 events (5 coronary deaths, 6 infarctions, and 12 revascularizations). Thus, 28 subjects (9%) suffered 35 events. Calcium quantities calculated for both protocols, performed on the same subjects, were sorted in ascending order and divided into equal quartiles. When revascularizations were included, there was a significant trend toward higher frequencies of events with increasing calcium quantity (P<.01). However, coronary death and infarction were not significantly more frequent in higher quartiles. These relationships were preserved in the subjects without prior events at the time of scanning. CONCLUSIONS: Calcium quantities from the 3-mm and the more reproducible 6-mm scanning are equally accurate for predicting events. Coronary calcium amount appears to be a weak predictor of coronary death and infarction. Its predictive accuracy is superior for predicting revascularization.