Coronary artery calcification score as tool for risk assessment among families with premature coronary artery disease.

INTRODUCTION: There is discussion about incorporating a family history (FamHis) of premature coronary artery disease (CAD) in risk score algorithms. However, FamHis provides information on individual risk. Coronary artery calcification score (CACS) is a metric of atherosclerosis that may determine the individual risk within families at high risk of premature CAD. METHODS: In asymptomatic individuals (n = 704), we assessed the association between FamHis of CAD and elevated CACS. To assess the predictive value of CACS in individuals with a FamHis of CAD, we performed a post-hoc analysis on the St. Francis Heart Study (n = 834). We assessed, in a case control design, the risk of future CAD in individuals with a FamHis of CAD and either CACS >80th percentile or no CACS at all. RESULTS: Individuals with a FamHis for CAD had an increased risk for elevated CACS (adjusted odds ratio (OR) 2.23 (95% CI 1.48-3.36); p < 0.05), compared to those without a FamHis. In the prospective study (3.5 years follow-up), the event rate equally low in those with a positive FamHis and a negative FamHis (0% vs. 1%), if they had a CAC of 0. However, in those with CACS >80(th) percentile, a FamHis of CAD doubled the CAD event rate (positive FamHis 12.5% vs. negative FamHis 6.8%; adjusted HR 2.08 (95% CI 1.09-3.87; p < 0.05). CONCLUSION: CAC scoring leads to risk discrimination among those with a positive FamHis for premature CAD. These results support testing CAC score in asymptomatic individuals with a positive FamHis to identify a high risk population.

Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study.

OBJECTIVES: The purpose of this study was to determine the prognostic accuracy of electron beam computed tomographic (CT) scanning of the coronary arteries and the relationship of coronary calcification to standard coronary disease risk factors and C-reactive protein (CRP) in the prediction of atherosclerotic cardiovascular disease (ASCVD) events in apparently healthy middle-age persons. BACKGROUND: As a screening test for coronary artery disease (CAD), electron beam CT scanning remains controversial. METHODS: In a prospective, population-based study, 4,903 asymptomatic persons age 50 to 70 years underwent electron beam CT scanning of the coronary arteries. RESULTS: At 4.3 years, follow-up was available in 4,613 participants (94%), and 119 had sustained at least one ASCVD event. Subjects with ASCVD events had higher baseline coronary calcium scores (median [interquartile range], Agatston method) than those without events: 384 (127, 800) versus 10 (0, 86) (p < 0.0001). For coronary calcium score threshold > or = 100 versus < 100, relative risk (95% confidence interval) was 9.6 (6.7 to 13.9) for all ASCVD events, 11.1 (7.3 to 16.7) for all CAD events, and 9.2 (4.9 to 17.3) for non-fatal myocardial infarction and death. The coronary calcium score predicted CAD events independently of standard risk factors and CRP (p = 0.004), was superior to the Framingham risk index in the prediction of events (area under the receiver-operating characteristic curve of 0.79 +/- 0.03 vs. 0.69 +/- 0.03, p = 0.0006), and enhanced stratification of those falling into the Framingham categories of low, intermediate, and high risk (p < 0.0001). CONCLUSIONS: The electron beam CT coronary calcium score predicts CAD events independent of standard risk factors, more accurately than standard risk factors and CRP, and refines Framingham risk stratification.

Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial.

OBJECTIVES: We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease (ASCVD) events. BACKGROUND: The electron beam computed tomography-derived coronary calcium score predicts coronary disease events. Small, uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events, but controlled, scientific demonstration of these effects is lacking. METHODS: We conducted a double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg daily, vitamin C 1 g daily, and vitamin E (alpha-tocopherol) 1,000 U daily, versus matching placebos in 1,005 asymptomatic, apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender. All study participants also received aspirin 81 mg daily. Mean duration of treatment was 4.3 years. RESULTS: Treatment reduced total cholesterol by 26.5% to 30.4% (p < 0.0001), low-density lipoprotein cholesterol by 39.1% to 43.4% (p < 0.0001), and triglycerides by 11.2% to 17.0% (p < or = 0.02) but had no effect (p = 0.80) on progression of coronary calcium score (Agatston method). Treatment also failed to significantly reduce the primary end point, a composite of all ASCVD events (6.9% vs. 9.9%, p = 0.08). Event rates were related to baseline calcium score (pre-specified analysis) and may have been reduced in a subgroup of participants with baseline calcium score >400 (8.7% vs. 15.0%, p = 0.046 [not a pre-specified analysis]). CONCLUSIONS: Treatment with alpha-tocopherol, vitamin C, and low doses of atorvastatin (20 mg once daily) did not affect the progression of coronary calcification. Treatment may have reduced ASCVD events, especially in subjects with calcium scores >400, but these effects did not achieve conventional levels of statistical significance.

Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study.

Calcified coronary artery plaque, measured at cardiac computed tomography (CT), is a predictor of cardiovascular disease and may play an increasing role in cardiovascular disease risk assessment. The Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA) study of the National Heart, Lung, and Blood Institute are population-based studies in which calcified coronary artery plaque was measured with electron-beam and multi-detector row CT and a standardized protocol in 6814 (MESA) and 3044 (CARDIA study) participants. The studies were approved by the appropriate institutional review board from the study site or agency, and written informed consent was obtained from each participant. Participation in the CT examination was high, image quality was good, and agreement for the presence of calcified plaque was high (kappa = 0.92, MESA; kappa = 0.77, CARDIA study). Extremely high agreement was observed between and within CT image analysts for the presence (kappa > 0.90, all) and amount (intraclass correlation coefficients, >0.99) of calcified plaque. Measurement of calcified coronary artery plaque with cardiac CT is well accepted by participants and can be implemented with consistently high-quality results with a standardized protocol and trained personnel. If predictive value of calcified coronary artery plaque for cardiovascular events proves sufficient to justify screening a segment of the population, then a standardized cardiac CT protocol is feasible and will provide reproducible results for health care providers and the public.

Relation of thoracic aortic and aortic valve calcium to coronary artery calcium and risk assessment.

Aortic calcium, aortic valve calcium (AVC), and coronary artery calcium (CAC) have been associated with cardiovascular event risk. We examined the prevalence of thoracic aortic calcium (TAC) and AVC in relation to the presence and extent of CAC, cardiovascular risk factors, and estimated risk of coronary heart disease (CHD). In 2,740 persons without known CHD aged 20 to 79 years, CAC was assessed by electron beam- or multidetector-computed tomography. We determined the prevalence of TAC and AVC in relation to CAC, CHD risk factors, and predicted 10-year risk of CHD. A close correspondence of TAC and AVC was observed with CAC. TAC and AVC increased with age; by the eighth decade of life, the prevalence of TAC was similar to that of CAC (>80%), and 36% of men and 24% of women had AVC. Age, male gender, and low-density lipoprotein cholesterol were directly related to the likelihood of CAC, TAC, and AVC; higher diastolic blood pressure and cigarette smoking additionally predicted CAC. Body mass index and higher systolic and lower diastolic blood pressures were also related to TAC, and higher body mass index and lower diastolic blood pressure were related to AVC. Calculated risk of CHD increased with the presence of AVC and TAC across levels of CAC. TAC and AVC provided incremental value over CAC in association with the 10-year calculated risk of CHD. If longitudinal studies show an incremental value of aortic and aortic valve calcium over that of CAC for prediction of cardiovascular events, future guidelines for risk assessment incorporating CAC assessment may additionally incorporate the measurement of aortic and/or aortic valve calcium.

Beyond traditional risk factor analysis for coronary artery disease: the case for coronary artery calcium assessment with electron beam computed tomography.

Coronary artery disease is often asymptomatic, leading to inefficient detection. Although coronary artery disease is associated with multiple risk factors, better methods for detection are needed. The quantity of coronary artery calcium as detected with electron beam computed tomography is indicative of plaque mass, and the likelihood of coronary obstruction and future coronary events is independent of other risk factors. Screening for coronary artery disease with electron beam computed tomography offers a complimentary way of detecting early atherosclerosis in asymptomatic patients.

Continuous probabilistic prediction of angiographically significant coronary artery disease using electron beam tomography.

BACKGROUND: We sought to incorporate electron beam tomography-derived calcium scores in a model for prediction of angiographically significant coronary artery disease (CAD). Such a model could greatly facilitate clinical triage in symptomatic patients with no known CAD. METHODS AND RESULTS: We examined 1851 patients with suspected CAD who underwent coronary angiography for clinical indications. An electron beam tomographic scan was performed in all patients. Total per-patient calcium scores and separate scores for the major coronary arteries were added to logistic regression models to calculate a posterior probability of the severity and extent of angiographic disease. These models were designed to be continuous, adjusted for age and sex, corrected for verification bias, and independently validated in terms of their incremental diagnostic accuracy. The overall sensitivity was 95%, and specificity was 66% for coronary calcium to predict obstructive disease on angiography. With calcium scores >20, >80, and >100, the sensitivity to predict stenosis decreased to 90%, 79%, and 76%, whereas the specificity increased to 58%, 72%, and 75%, respectively. The logistic regression model exhibited excellent discrimination (receiver operating characteristic curve area, 0.842+/-0.023) and calibration (chi2 goodness of fit, 8.95; P=0.442). CONCLUSIONS: Electron beam tomographic calcium scanning provides incremental and independent power in predicting the severity and extent of angiographically significant CAD in symptomatic patients, in conjunction with pretest probability of disease. This algorithm is most useful when applied to an intermediate-risk population.