Measurement of thoracic bone mineral density with quantitative CT.

PURPOSE: To create standard thoracic bone mineral density (BMD) values for patients undergoing cardiac computed tomography (CT) by using thoracic quantitative CT and to compare these BMDs (in a subpopulation) with those obtained by using lumbar spine quantitative CT. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant study. A total of 9585 asymptomatic subjects (mean age, 56 years; age range, 30-90 years) who underwent coronary artery calcium scanning, including 4131 women, were examined. Patients with vertebral deformities or fractures were excluded. Six hundred forty-four subjects (322 of whom were female) also underwent lumbar quantitative CT. The mean thoracic vertebral BMDs for both sexes were reported separately in a subgroup of subjects aged 30 years and in 29 age-based subgroups in 2-year intervals from ages 30 to 90 years. The formulas used to calculate the female T score (T(f)) and the male T score (T(m)) on the basis of thoracic quantitative CT measurements were as follows: T(f) = (BMD(im) - 222)/36, and T(m) = (BMD(im) - 215)/33, where BMD(im) is the individual mean BMD. Comparisons between thoracic quantitative CT and lumbar quantitative CT measurements, as well as analyses of intraobserver, interobserver, and interscan variability, were performed. RESULTS: The young-subgroup mean BMD was 221.9 mg/mL ± 36.2 (standard deviation) for the female subjects and 215.2 mg/mL ± 33.2 for the male subjects. The mean thoracic BMDs for the female and male subjects were found to be 20.7% higher and 17.0% higher, respectively, than the values measured with lumbar quantitative CT (P < .001 for both comparisons). A significant positive association between the thoracic and lumbar quantitative CT measurements (r > 0.85, P < .001) was found. Intraobserver, interobserver, and interscan variabilities in thoracic quantitative CT measurements were 2.5%, 2.6%, and 2.8%, respectively. CONCLUSION: There was a significant association between the mean thoracic and lumbar BMDs. Therefore, standard derived measurements (young-subgroup BMD ± standard deviation) based on these data can be used with thoracic CT images to estimate the bone mineral status.

Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: a randomized clinical trial.

OBJECTIVES: Previous studies demonstrated that aged garlic extract reduces multiple cardiovascular risk factors. This study was designed to assess whether aged garlic extract therapy with supplements (AGE+S) favorably affects inflammatory and oxidation biomarkers, vascular function and progression of atherosclerosis as compared to placebo. METHODS: In this placebo-controlled, double-blind, randomized trial (conducted 2005-2007), 65 intermediate risk patients (age 60+/-9 years, 79% male) were treated with a placebo capsule or a capsule containing aged garlic extract (250 mg) plus Vitamin B12 (100 microg), folic acid (300 microg), Vitamin B6 (12.5 mg) and l-arginine (100 mg) given daily for a 1 year. All patients underwent coronary artery calcium scanning (CAC), temperature rebound (TR) as an index of vascular reactivity using Digital Thermal Monitoring (DTM), and measurement of lipid profile, autoantibodies to malondialdehyde (MDA)-LDL, apoB-immune complexes, oxidized phospholipids (OxPL) on apolipoprotein B-100 (OxPL/apoB), lipoprotein (a) [Lp (a)], C-reactive protein (CRP), homocysteine were measured at baseline and 12 months. CAC progression was defined as an increase in CAC>15% per year and an increase in TR above baseline was considered a favorable response. RESULTS: At 1 year, CAC progression was significantly lower and TR significantly higher in the AGE+S compared to the placebo group after adjustment of cardiovascular risk factors (p<0.05). Total cholesterol, LDL-C, homocysteine, IgG and IgM autoantibodies to MDA-LDL and apoB-immune complexes were decreased, whereas HDL, OxPL/apoB, and Lp (a) were significantly increased in AGE+S to placebo. CONCLUSION: AGE+S is associated with a favorable improvement in oxidative biomarkers, vascular function, and reduced progression of atherosclerosis.

Normal thoracic aorta diameter on cardiac computed tomography in healthy asymptomatic adults: impact of age and gender.

RATIONALE AND OBJECTIVES: To establish the normal criterion of ascending aortic diameter (AAOD) measured by 64 multidetector computed tomography (MDCT) and electron beam computed tomography (EBT) based on gender and age. MATERIALS AND METHODS: A total of 1442 consecutive subjects who were referred for evaluation of possible coronary artery disease underwent coronary computed tomographic (CT) angiography (CTA) and coronary artery calcium scanning (CACS) (55 + 11 years, 65% male) without known coronary heart disease, hypertension, chronic pulmonary and renal disease, diabetes, and severe aortic calcification. The AAOD aortic diameter, descending aortic diameter (DAOD), pulmonary artery (PAD), and chest anteroposterior diameter (CAPD), posterior border of the sternal bone to the anterior border of the spine, were measured at the slice level of mid-right pulmonary artery using end systolic trigger imaging. The volume of four chambers, ejection fraction of left ventricle, and cardiac output were measured in 56% of the patients. Patients' demographic information, age, gender, weight, height, and body surface area were recorded. The mean value and age-specific and gender-adjusted upper normal limits (mean +/- 2 standard deviation) were calculated. The linear correlation analysis was done between AAOD and all parameters. The reproducibility, wall thickness, and difference between end-systole and end-diastole were calculated. RESULTS: AAOD has significant linear association with age, gender, DAOD, and pulmonary artery diameter (P < .05). There is no significant correlation between AAOD and body surface area, four-chamber volume, left ventricular ejection fraction, cardiac output, and CAPD. The mean intraluminal AAOD was 31.1 +/- 3.9 and 33.6 +/- 4.1 mm in females and males, respectively. The upper normal limits (mean +/- 2 standard deviations) of intraluminal AAOD, were 35.6, 38.3, and 40 mm for females and 37.8, 40.5, and 42.6 mm for males in age groups 20-40, 41-60, and older than 60 years, respectively. Intraluminal aortic diameters should parallel echocardiography and invasive angiography. Traditional cross-sectional imaging (with CT and magnetic resonance imaging) includes the vessel wall. The mean total AAOD was 33.5 and 36.0 mm in females and males, respectively. The upper normal limits (mean +/- 2 standard deviations) of intraluminal AAOD were 38.0, 40.7 and 42.4 mm for females and 40.2, 42.9, and 45.0 mm for males in age group 20 to 40, 41 to 60, and older than 60 years, respectively. The inter- and intraobserver, scanner, and repeated measurement variabilities were low (r value >0.91, P < .001, coefficient variation <3.2%). AAOD was 1.7 mm smaller in end-diastole than end-systole (P < .001). CONCLUSIONS: The AAOD increases with age and male gender. Gender-specific and age-adjusted normal values for aortic diameters are necessary to differentiate pathologic atherosclerotic changes in the ascending aorta. Use of intraluminal or total aortic diameter values depends on the comparison study employed.

All-cause mortality by age and gender based on coronary artery calcium scores.

AIMS: Although coronary artery calcium (CAC) has been established as a robust tool for predicting total mortality during intermediate follow-up, less is known about the long-term predictive value of CAC. METHODS AND RESULTS: This study included 13 092 asymptomatic patients without known cardiovascular disease who underwent a clinically indicated CAC scan. CAC was categorized as an Agatson score of 0, 1-99, 100-399, and ≥400. We used multivariable Cox proportional hazards to calculate adjusted hazard ratios (HRs) for mortality stratified by age (younger, intermediate, or older) and gender. The mean age of participants was 58 ± 11 years and 67% were men. During a median follow-up of 11.0 ± 3.2 years, there were 522 deaths (4.0%). Compared with CAC = 0, increasing CAC was associated with higher mortality rate: 1-99 [HR: 1.5, 95% confidence interval (95% CI): 1.1-2.1]; 100-399 (HR: 1.8, 95% CI: 1.3-2.5); ≥400 (HR: 2.6, 95% CI: 1.9-3.6). Relative risk according to CAC category did not differ between genders. The strongest associations between CAC and mortality were observed for young and intermediate age participants. Nonetheless, the mortality rate of the older patients with CAC = 0 was far lower than that of the general US population. CAC was more predictive of long-term (15 years) than intermediate-term (5 years) mortality for men [receiver operator characteristics (ROC): 0.723 vs. 0.702] and women (ROC: 0.69 vs. 0.65). CONCLUSION: CAC is strongly associated with the long-term risk of mortality in young- and middle-aged men and women. In older patients, the long-term risk stratification of CAC is lower, due principally to increased mortality rate in patients with low calcium scores; however, even in the older patients, those with absent or low CAC are at a significantly lower risk of mortality compared with the general population.

Cost-effectiveness of multidetector computed tomography compared with myocardial perfusion imaging as gatekeeper to invasive coronary angiography in asymptomatic firefighters with positive treadmill tests.

BACKGROUND: In a prospective evaluation of 3950 Los Angeles County firefighters who underwent wellness/fitness examinations, 495 firefighters had abnormal treadmill tests and were referred for cardiology evaluation. Cost of the traditional myocardial perfusion imaging (MPI) followed by invasive coronary angiography (ICA) was compared with a method incorporating 64-slice multidetector computed tomography (MDCT) with coronary calcium score (CCS) followed by computed tomographic angiography (CTA) and ICA as indicated. OBJECTIVE: We compared the costs of 2 methods of predicting coronary artery disease (CAD) by ICA among asymptomatic patients with positive treadmill tests. METHODS: A decision-analytic framework was used to compare the net direct costs of CAD diagnosis associated with MDCT versus MPI. In the MDCT arm, all received CCS followed by CTA for those with calcium scores>10 and ICA for those with > or =50% stenosis on CTA. For the MPI arm, results were estimated from prior years' experience, in which firefighters with abnormal treadmill results were referred to ICA. RESULTS: Of 495 firefighters, 131 (26.9%) had abnormal CCS and went to CTA; 40 (8.1%) had > or =50% stenosis on CTA and went to ICA. According to prior years' experience with MPI, 146 (29.5%) would have shown abnormalities requiring ICA. Average cost was $1376/person for MPI versus $503/person for CCS with or without CTA as gatekeeper. All sensitivity analyses showed lower costs for the MDCT pathway compared with MPI. CONCLUSION: In this firefighter population, the cost of ICA-confirmed diagnosis of CAD is substantially lower with MDCT as gatekeeper than with MPI.

Prognostic value of number and site of calcified coronary lesions compared with the total score.

OBJECTIVES: This study sought to evaluate the long-term prognostic value of the number and sites of calcified coronary lesions and to compare the accuracy of number of calcified lesions with the extent of total calcium score. BACKGROUND: There is a strong relationship between mortality and total coronary artery calcium (CAC) score. It is not known whether the number of calcified lesions or their location influences outcome. METHODS: A total of 14,759 asymptomatic patients were referred for evaluation of CAC scanning using electron beam tomography. Univariable and multivariable Cox proportional hazards models were developed to estimate time to all-cause mortality at, on average, 6.8 years (n = 281). RESULTS: Risk-adjusted annual mortality was 0.19% (95% confidence interval 0.18% to 0.21%) for patients without any calcified lesions. For patients with >20 lesions, annual risk-adjusted mortality exceeded 2% per year. Mortality rates were significantly higher for left main lesions as compared to other coronary arteries with annual mortality rates of 1.3%, 2.1%, 9.2%, and 13.6% for 1 to 2, 3 to 5, and > or =6 lesions, respectively (p < 0.0001). For left main CAC scores of 0 to 10, 11 to 100, 101 to 399, and 400 to 999, annual risk-adjusted mortality was 0.33%, 0.81%, 1.73%, and 7.71%, respectively (p < 0.0001). All 4 patients with a CAC score of > or =1,000 in the left main died during follow-up. However, patients with more frequent calcified lesions also had higher CAC scores. Specifically, > or =81% of patients with >10 calcified lesions also had a CAC score > or =100. With exception, for patients with CAC scores > or =1,000, annual mortality was dramatically higher at 3.0% to 4.5% for those with 1 to 5 calcified lesions as compared with 1.1% to 2.0% for those with 6 or more lesions (p < 0.0001). CONCLUSIONS: We report that mortality rates increased proportionally with the number of calcified lesions. Although predictive information is contained in the number of calcified lesions, its added statistical value is minimal. With exception, patients with frequent lesions in the left main or those with a few large calcified lesions have a particularly high mortality risk.

Coronary calcium progression rates with a zero initial score by electron beam tomography.

BACKGROUND: A review of existing literature shows that for individuals with initial coronary calcium scores (CCS) of zero it would be reasonable to consider follow-up scanning no sooner than 3 years from the initial evaluation, however the data is very limited. In this study, we sought to determine the rate of new calcifications in patients initially presenting with a zero initial score on electron beam tomography (EBT). METHODS AND RESULTS: We evaluated 710 physician-referred participants (253 women and 448 men, mean age=56+/-9 years [range=29 to 93]) with no coronary artery calcium (CAC) at baseline electron beam tomography (EBT) scan. The participants underwent a follow-up scan at least 12 months apart. In our study, 248 (35%) were followed for 1-3 years, 256 (36%) for 3-5 years and 204 (29%) for >5 years, respectively. Overall, more than half of the individuals (62%) did not develop any CAC (score remained zero) in the interim period, whereas only 2% had CAC progression >50 during the follow-up. The overall median (interquartile range) and mean+/-S.D. change/year in these individuals was 0 (0-0.8) and 1+/-3, respectively. Only 11 (2%) had CAC progression/year of 11-50, whereas 3 (1%) had CAC change/year >50. It is interesting to note that even among individuals with long-term follow-up (>5 years), very few individuals (2%) had CAC progression >50. Individuals with follow-up 3-5 years did not have a significantly higher odds ratio for CAC change >10 (p=0.17) as compared to the reference group (follow-up of 1-3 years). All the other individuals who had a longer follow-up (>5 years) had a significantly higher likelihood of CAC progression >10 (OR=6.6, 95% CI=2.6-16.9, p<0.0001) compared to the reference group. CONCLUSION: In individuals with no detectable coronary calcium on an initial EBT scan, a repeat scan can be recommended no sooner than 5 years.

Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients.

OBJECTIVES: The purpose of this study was to develop risk-adjusted multivariable models that include risk factors and coronary artery calcium (CAC) scores measured with electron-beam tomography in asymptomatic patients for the prediction of all-cause mortality. BACKGROUND: Several smaller studies have documented the efficacy of CAC testing for assessment of cardiovascular risk. Larger studies with longer follow-up will lend strength to the hypothesis that CAC testing will improve outcomes, cost-effectiveness, and safety of primary prevention efforts. METHODS: We used an observational outcome study of a cohort of 25,253 consecutive, asymptomatic individuals referred by their primary physician for CAC scanning to assess cardiovascular risk. Multivariable Cox proportional hazards models were developed to predict all-cause mortality. Risk-adjusted models incorporated traditional risk factors for coronary disease and CAC scores. RESULTS: The frequency of CAC scores was 44%, 14%, 20%, 13%, 6%, and 4% for scores of 0, 1 to 10, 11 to 100, 101 to 400, 401 to 1,000, and >1,000, respectively. During a mean follow-up of 6.8 +/- 3 years, the death rate was 2% (510 deaths). The CAC was an independent predictor of mortality in a multivariable model controlling for age, gender, ethnicity, and cardiac risk factors (model chi-square = 2,017, p < 0.0001). The addition of CAC to traditional risk factors increased the concordance index significantly (0.61 for risk factors vs. 0.81 for the CAC score, p < 0.0001). Risk-adjusted relative risk ratios for CAC were 2.2-, 4.5-, 6.4-, 9.2-, 10.4-, and 12.5-fold for scores of 11 to 100, 101 to 299, 300 to 399, 400 to 699, 700 to 999, and >1,000, respectively (p < 0.0001), when compared with a score of 0. Ten-year survival (after adjustment for risk factors, including age) was 99.4% for a CAC score of 0 and worsened to 87.8% for a score of >1,000 (p < 0.0001). CONCLUSIONS: This large observational data series shows that CAC provides independent incremental information in addition to traditional risk factors in the prediction of all-cause mortality.

Ethnic differences in the prognostic value of coronary artery calcification for all-cause mortality.

OBJECTIVES: The purpose of this study was to evaluate the prognostic value of coronary artery calcium (CAC), a known marker of subclinical atherosclerosis, in a large, ethnically diverse cohort of 14,812 patients for the prediction of all-cause mortality. BACKGROUND: Disparities in case fatality rates for heart disease among ethnic groups are well known. In 2001, rates of death from heart disease were 30% higher among African Americans (AA) than non-Hispanic whites (NHW). Some of this variability may be due to differing pathophysiological mechanisms and effects of underlying atherosclerosis. METHODS: Ten-year death rates from all causes (total deaths = 505) were compared using risk-adjusted Cox proportional hazards models in AA (n = 637), Hispanic (HS, n = 1,334), Asian (AS, n = 1,065), and NHW (n = 11,776) populations. RESULTS: Ethnic minority patients were generally younger (0.3 to 4 years), more often persons with diabetes (p < 0.0001), hypertensive (p < 0.0001), and female (p < 0.0001). The prevalence of CAC scores > or =100 was highest in NHW (31%) and lowest for HS (18%) (p < 0.0001). Overall survival was 96%, 93%, and 92% for AS, NHW, and HS, respectively, as compared with 83% for AA (p < 0.0001). When comparing prognosis by CAC scores in ethnic minorities as compared with NHW, relative risk ratios were highest for AA with CAC scores > or =400 exceeding 16.1 (p < 0.0001). Hispanics with CAC scores > or =400 had relative risk ratios from 7.9 to 9.0, whereas AS with CAC scores > or =1,000 had relative risk ratios 6.6-fold higher than NHW (p < 0.0001). CONCLUSIONS: Consistent with population evidence, AA with increasing burden of subclinical coronary artery disease were the highest-risk ethnic minority population. These data support a growing body of evidence noting substantial differences in cardiovascular risk by ethnicity.

Inhibiting progression of coronary calcification using Aged Garlic Extract in patients receiving statin therapy: a preliminary study.

BACKGROUND: Aged Garlic Extract (AGE) reduces multiple cardiovascular risk factors, including blood pressure, cholesterol, platelet aggregation and adhesion, while stimulating nitric oxide generation in endothelial cells. However, no study has evaluated the ability of AGE to inhibit vascular calcification, a marker of plaque formation in human coronary arteries. OBJECTIVE: To assess the efficacy of Aged Garlic Extract (AGE) on changing the rate of atherosclerosis progression as compared to placebo. DESIGN: A placebo-controlled, double-blind, randomized pilot study to determine whether the atherosclerotic plaque burden detected by electron beam tomography (EBT) will change at a different rate under the influence of AGE as compared to placebo. Twenty-three patients were enrolled, and 19 patients completed the study protocol. AGE 4 ml or the equivalent amount of placebo was given to subjects. Duration of the study was 1 year. S-allylcysteine (SAC), one of the active compound of AGE, was measured in the blood as a compliance marker. RESULTS: The mean change of the calcium score (volumetric method) for the AGE group (n = 9) was 7.5 +/- 9.4% over 1 year. The placebo group (n = 10) demonstrated an average increase in calcium scores of 22.2 +/- 18.5%, significantly greater than the treated cohort (P = 0.046). There were no significant differences in individual cholesterol parameters or C reactive protein between the groups. In patients randomized to AGE, there was a nonsignificant trend for improving cholesterol/high-density lipoprotein ratio (P = 0.07) and homocysteine level (P = 0.08). CONCLUSIONS: This small pilot study indicates the potential ability of AGE to inhibit the rate of progression of coronary calcification, as compared to placebo over 1 year. Should these findings be extended and confirmed in larger studies, garlic may prove useful for patients who are at high risk of future cardiovascular events.