Long-term all-cause mortality among asymptomatic individuals with 80th percentile of coronary calcium score based on age and gender in the St. Francis Heart Study.

OBJECTIVES: High coronary artery calcium score (CAC) is a significant risk factor for cardiovascular morbidity and mortality. We investigated the long-term outcome of subjects with elevated CAC. METHODS: We studied 1005 participants of The St. Francis Heart Study who were asymptomatic and apparently healthy and had CAC scores at 80th percentile or higher for age and gender. They were randomized to receive atorvastatin 20 mg daily or placebo for up to 5 years. We used an as-treated study design accounting for cross-overs at the end of the original trial. All-cause mortality risk was assessed using adjusted hazard ratios. RESULTS: Mean age was 59 ± 6 years and 26% (N = 263) were female. After 17 ± 3 years follow-up 176 subjects died. High CAC at baseline was associated with increased mortality risk with adjusted hazard ratio for logarithmic transformed CAC at 1.33 and 95% confidence interval 1.06-1.68. The mortality risk associated with CAC was similar between the group with high-sensitivity CRP ≥2 and <2 mg/dL. Those with a family history of premature coronary artery disease exhibited a higher mortality risk in association with high CAC with an adjusted hazard ratio 1.51 (1.09, 2.09). CONCLUSION: Elevated CAC is an independent risk for long-term all-cause mortality. The screening of CAC score in addition to identifying conventional risk factors can differentiate asymptomatic individuals with and without increased long-term mortality risk.

Collective impact of conventional cardiovascular risk factors and coronary calcium score on clinical outcomes with or without statin therapy: The St Francis Heart Study.

BACKGROUND AND AIMS: The efficacy of statin therapy remains unknown in patients eligible for statin therapy with and without elevated coronary calcium score (CAC). The study sought to evaluate how cardiovascular risk factors, expressed in terms of statin eligibility for primary prevention, and CAC modify clinical outcomes with and without statin therapy. METHODS: We conducted a post-hoc analysis of the St. Francis Heart Study treatment trial, a double-blind, placebo-controlled randomized controlled trial of atorvastatin (20 mg), vitamin C (1 g), and vitamin E (1000 U) daily, versus placebos in 990 asymptomatic individuals with CAC ≥ 80th percentile for age and gender. Primary cardiovascular outcomes included non-fatal myocardial infarction or coronary death, coronary revascularization, stroke, and peripheral arterial revascularization. We further stratified the treatment and placebo groups by eligibility (eligible when statin indicated) for statin therapy based on 2013 ACC/AHA guidelines and based on CAC categories. RESULTS: After a median follow-up of 4.8 years, cardiovascular events had occurred in 3.9% of the statin treated but not eligible, 4.6% of the untreated and not eligible, 8.9% of the treated and eligible and 13.4% of the untreated and eligible groups, respectively (p<0.001). Low CAC (<100) occurred infrequently in statin eligible subjects (≤4%) and was associated with low 10-year event rate (<1 per 100 person-years). In contrast, high CAC (>300) occurred frequently in more than 35% of the statin not eligible subjects and was associated with a high 10-year event rate (≥17 per 100 person-years). Risk prediction improved significantly when both clinical risk profile and CAC score were combined (net reclassification index p = 0.002). CONCLUSIONS: Under the current statin treatment guidelines a small number of statin eligible subjects with low CAC might not benefit from statin therapy within 5 years. However, the statin not eligible subjects with high CAC have high event rate attributing to loss of opportunity for effective primary prevention.

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.

High dose and long-term statin therapy accelerate coronary artery calcification.

BACKGROUND: In randomized clinical trials statins and placebo treated patients showed the same degree of coronary artery calcium (CAC) progression. We reanalyzed data from two clinical trials to further investigate the time and dose dependent effects of statins on CAC. Additionally, we investigated whether CAC progression was associated with incident cardiovascular events. METHODS AND RESULTS: Data were pooled from two clinical trials: St. Francis Heart Study (SFHS) (419 and 432 patients treated with placebo and 20 mg atorvastatin daily, respectively) and EBEAT Study (164 and 179 patients respectively treated with 10 mg and 80 mg atorvastatin daily). CAC scores were assessed at baseline, 2 years and 4-6 years in SFHS; in EBEAT they were measured at baseline and 12 months. After a short-term follow-up (12 to 24 months) placebo and low dose atorvastatin showed a similar CAC increase, although 80 mg/daily atorvastatin increased CAC an additional 12-14% over placebo (p<0.001). In the long-term, atorvastatin caused a greater progression of CAC compared to placebo (additional 1.1%, p=0.04). In SFHS 42 cardiovascular events occurred after the second CT scan. The baseline and progression of CAC were greater in patients with events. However, only baseline CAC and family history of premature cardiovascular disease but not CAC progression were independent predictors of events. CONCLUSIONS: Despite a greater CAC increase with high dose and long-term statin therapy, events did not occur more frequently in statin treated patients. This suggests that CAC growth under treatment with statins represents plaque repair rather than continuing plaque expansion.

Abdominal aortic calcium, coronary artery calcium, and cardiovascular morbidity and mortality in the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To evaluate the predictive value of abdominal aortic calcium (AAC) for incident cardiovascular disease (CVD) independent of coronary artery calcium (CAC). APPROACH AND RESULTS: We evaluated the association of AAC with CVD in 1974 men and women aged 45 to 84 years randomly selected from the Multi-Ethnic Study of Atherosclerosis participants who had complete AAC and CAC data from computed tomographic scans. AAC and CAC were each divided into following 3 percentile categories: 0 to 50th, 51st to 75th, and 76th to 100th. During a mean of 5.5 years of follow-up, there were 50 hard coronary heart disease events, 83 hard CVD events, 30 fatal CVD events, and 105 total deaths. In multivariable-adjusted Cox models including both AAC and CAC, comparing the fourth quartile with the ≤ 50th percentile, AAC and CAC were each significantly and independently predictive of hard coronary heart disease and hard CVD, with hazard ratios ranging from 2.4 to 4.4. For CVD mortality, the hazard ratio was highly significant for the fourth quartile of AAC, 5.9 (P=0.01), whereas the association for the fourth quartile of CAC (hazard ratio, 2.1) was not significant. For total mortality, the fourth quartile hazard ratio for AAC was 2.7 (P=0.001), and for CAC, it was 1.9, P=0.04. Area under the receiver operating characteristic curve analyses showed improvement for both AAC and CAC separately, although improvement was greater with CAC for hard coronary heart disease and hard CVD, and greater with AAC for CVD mortality and total mortality. Sensitivity analyses defining AAC and CAC as continuous variables mirrored these results. CONCLUSIONS: AAC and CAC predicted hard coronary heart disease and hard CVD events independent of one another. Only AAC was independently related to CVD mortality, and AAC showed a stronger association than CAC with total mortality.

The natural history of coronary calcification: a meta-analysis from St Francis and EBEAT trials.

BACKGROUND AND AIM: Coronary artery calcium score (CACs) is an established quantitative tool for assessing subclinical atherosclerosis. The aim of this study was to assess in a meta-analysis model the natural history and reproducibility of CACs measurements obtained from St Francis and EBEAT trials. METHODS: We analysed data from 649 individuals: 443 on placebo with 2 year follow-up from St Francis trial (Study A) and 209 on 10 mg atorvastatin with 1 year follow-up of EBEAT trial (Study B). Total CACs and that in the left coronary artery (LCA) branches, left main stem (LMS), left anterior descending (LAD), left circumflex (Cx) and right coronary artery (RCA) were analysed. In view of the wide CACs spectrum, data were logarithmically transformed before the analyses and mixed model analysis was used to evaluate the change of CACs over time. RESULTS: The overall agreement between the two measurements was fairly good, showing a small but significant increase in CAC: 68% of the group as a whole presented an increase in CACs, 23% of the cohort had negligible change in CACs of <10% irrespective of the baseline CACs; and the remaining 10% showed a fall in CACs. Both studies showed similar patterns. The analysis of individual coronary arteries showed significantly higher variability of measurements in the RCA than in the LCA. Males had higher baseline CACs than females, but the rate of progression was not different between genders, irrespectively of age and baseline score. CONCLUSION: The natural history of CACs was overtime progression in the majority of subjects, irrespective of gender. The higher variability in RCA measurements could be related to the low baseline CACs or exaggerated movement of the right side atrioventricular ring, whereas those for LCA branches are influenced by the branch allocation of the CACs. Large changes to and from zero, might be related to technical limitations.

Progression of coronary calcium and incident coronary heart disease events: MESA (Multi-Ethnic Study of Atherosclerosis).

OBJECTIVES: The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events. BACKGROUND: CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. METHODS: We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. RESULTS: A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression. CONCLUSIONS: Progression of CAC is associated with an increased risk for future hard and total CHD events.

Metabolic syndrome, diabetes, and incidence and progression of coronary calcium: the Multiethnic Study of Atherosclerosis study.

OBJECTIVES: This study sought to examine and compare the incidence and progression of coronary artery calcium (CAC) among persons with metabolic syndrome (MetS) and diabetes mellitus (DM) versus those with neither condition. BACKGROUND: MetS and DM are associated with subclinical atherosclerosis as evidenced by CAC. METHODS: The MESA (Multiethnic Study of Atherosclerosis) included 6,814 African American, Asian, Caucasian, and Hispanic adults 45 to 84 years of age, who were free of cardiovascular disease at baseline. Of these, 5,662 subjects (51% women, mean age 61.0 ± 10.3 years) received baseline and follow-up (mean 2.4 years) cardiac computed tomography scans. We compared the incidence of CAC in 2,927 subjects without CAC at baseline and progression of CAC in 2,735 subjects with CAC at baseline in those with MetS without DM (25.2%), DM without MetS (3.5%), or both DM and MetS (9.0%) to incidence and progression in subjects with neither MetS nor DM (58%). Progression of CAC was also examined in relation to coronary heart disease events over an additional 4.9 years. RESULTS: Relative to those with neither MetS nor DM, adjusted relative risks (95% confidence intervals [CI]) for incident CAC were 1.7 (95% CI: 1.4 to 2.0), 1.9 (95% CI: 1.4 to 2.4), and 1.8 (95% CI: 1.4 to 2.2) (all p < 0.01), and absolute differences in mean progression (volume score) were 7.8 (95% CI: 4.0 to 11.6; p < 0.01), 11.6 (95% CI: 2.7 to 20.5; p < 0.05), and 22.6 (95% CI: 17.2 to 27.9; p < 0.01) for those with MetS without DM, DM without MetS, and both DM and MetS, respectively. Similar findings were seen in analysis using Agatston calcium score. In addition, progression predicted coronary heart disease events in those with MetS without DM (adjusted hazard ratio: 4.1, 95% CI: 2.0 to 8.5, p < 0.01) and DM (adjusted hazard ratio: 4.9 [95% CI: 1.3 to 18.4], p < 0.05) among those in the highest tertile of CAC increase versus no increase. CONCLUSIONS: Individuals with MetS and DM have a greater incidence and absolute progression of CAC compared with individuals without these conditions, with progression also predicting coronary heart disease events in those with MetS and DM.

Asymptomatic individuals with a positive family history for premature coronary artery disease and elevated coronary calcium scores benefit from statin treatment: a post hoc analysis from the St. Francis Heart Study.

OBJECTIVES: The goal of this study was to evaluate whether individuals with a positive family history for premature coronary artery disease (CAD) and coronary calcium scoring (CCS) above the 80th percentile might benefit from preventive treatment. BACKGROUND: First-degree relatives of patients with premature CAD have an increased risk for cardiovascular disease (CVD), whereas events are poorly predicted in these individuals. Surrogate markers, such as CCS, might refine risk scoring. Nevertheless, the outcome of the St. Francis Heart trial, which investigated the effect of atorvastatin 20 mg/day in asymptomatic individuals with CCS above the 80th percentile, did not reach statistical significance. METHODS: We performed a post hoc analysis on the database of the St. Francis trial to assess efficacy of treatment with atorvastatin 20 mg/day in those with CCS above the 80th percentile and presence (n = 543) or absence (n = 462) of a positive family history for premature CAD. All participants received aspirin 81 mg/day. Primary outcome included coronary death, myocardial infarction, coronary revascularization, stroke, and arterial surgery. RESULTS: A total of 1,005 individuals, with a mean age of 59.0 ± 5.9 years and a median absolute CCS of 370 Agatston units (interquartile range: 183 to 662) participated in the trial. After a follow-up of 4.3 (interquartile range: 3.5 to 4.5) years, 7.2% of the treated individuals with a positive family history had a cardiovascular event versus 12.5% of the placebo group (hazard ratio [HR]: 0.55; 95% confidence intervals [CI]: 0.31 to 0.97; p = 0.040). This is comparable with a number needed to treat of 18.9. In individuals without a family history, events were minimally reduced: 6.6% in the treated versus 6.8% in the placebo group (HR: 1.04; 95% CI: 0.51 to 2.13; p = 0.912). CONCLUSIONS: The combination of a positive family history and CCS above the 80th percentile identifies a subgroup within the primary prevention population that receives greater benefit from statin treatment than the population at large. These results have important implications for future guidelines concerning individuals with a positive family history for premature CAD.

Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is defined as the spectrum of benign fatty liver to necroinflammation and fibrosis. Its prevalence has been found to be as high as 39%. It is estimated that up to 15% of those affected will go on to have progressive liver disease. Currently, there is no proven therapy for NAFLD. In this study, we aim to determine whether statin therapy may be an effective treatment for NAFLD and identify independent predictors of NAFLD. METHODS: In all, 1,005 men and women, aged 50-70 years were randomized to receive either a daily combination of atorvastatin 20 mg, vitamin C 1 g, and vitamin E 1,000 IU vs. matching placebo, as part of the St Francis Heart Study randomized clinical trial. Liver to spleen (LS) ratios were calculated on 455 subjects with available computed tomography scans performed at baseline and follow-up to determine NAFLD prevalence. Baseline and final LS ratios were compared within treatment groups, and results were compared between the treatment and placebo groups using univariate and multivariate analyses. Mean duration of follow-up was 3.6 years. RESULTS: There were 80 patients with NAFLD at baseline. We identified baseline triglyceride levels (odds ratio (OR)=1.003, P<0.001) and body mass index (OR=0.10, P<0.001) as independent correlates of NAFLD. Treatment with atorvastatin combined with vitamins E and C significantly reduced the odds of NAFLD at the end of follow-up, 70 vs. 34% (OR=0.29, P<0.001). CONCLUSIONS: In conclusion, atorvastatin 20 mg combined with vitamins C and E is effective in reducing the odds of having hepatic steatosis by 71% in healthy individuals with NAFLD at baseline after 4 years of active therapy.

Coronary artery calcium score and risk classification for coronary heart disease prediction.

CONTEXT: The coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear. OBJECTIVE: To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk. DESIGN, SETTING, AND PARTICIPANTS: CACS was measured by computed tomography in 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident CHD were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement and compared the distribution of risk using model 2 vs model 1. MAIN OUTCOME MEASURES: Incident CHD events. RESULTS: During a median of 5.8 years of follow-up among a final cohort of 5878, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% confidence interval, 0.16-0.34; P < .001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2. CONCLUSION: In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.

Coronary calcium coverage score: determination, correlates, and predictive accuracy in the Multi-Ethnic Study of Atherosclerosis.

PURPOSE: To develop a new calcium score for use with unenhanced cardiac computed tomography (CT) that can be used to define the percentage of coronary arteries affected by calcium and to correlate this score with risk factors and cardiovascular events. MATERIALS AND METHODS: Institutional review boards at all participating centers approved this HIPAA-compliant study, and all participants gave written informed consent. Calcium coverage score (CCS), which represents the percentage of coronary arteries affected by calcific plaque, was calculated for 3252 participants in the Multi-Ethnic Study of Atherosclerosis in whom calcific plaque was detected with CT. Quasi-Poisson models were used to estimate associations (assessed by using t tests with robust standard errors) between CCS and risk factors. Associations between the CCS, Agatston, and calcium mass scores (hereafter, mass scores) and outcomes were estimated and assessed by using Cox proportional hazards models with Wald tests. The predictive ability of these models was assessed by using area under the receiver operating characteristic curves and bootstrap t tests. RESULTS: After adjustments were made for age, race, ethnicity, and sex in the quasi-Poisson model, CCS was associated with hypertension, dyslipidemia, and diabetes (P < .001 for all diseases). After adjustments for age and sex, a twofold increase in CCS was associated with a 52% (95% confidence interval: 34%, 72%) increase in risk for any coronary heart disease (CHD) event. When Agatston or mass scores were included with CCS in a Cox model for prediction of CHD events, neither Agatston score nor mass score was a significant predictor, whereas CCS remained significantly associated with CHD events. Although receiver operating characteristic curves suggested that there was a difference between CCS score and Agatston and mass scores in prediction of a cardiac event, no differences in prediction of hard cardiac events (myocardial infarction, death) were found. CONCLUSION: Both spatial distribution and amount of calcified plaque contribute to risk for CHD.

Coronary calcium as a predictor of coronary events in four racial or ethnic groups.

BACKGROUND: In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. METHODS: We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. RESULTS: There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. CONCLUSIONS: The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected.

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.

Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: There is substantial evidence that coronary calcification, a marker for the presence and quantity of coronary atherosclerosis, is higher in US whites than blacks; however, there have been no large population-based studies comparing coronary calcification among US ethnic groups. METHODS AND RESULTS: Using computed tomography, we measured coronary calcification in 6814 white, black, Hispanic, and Chinese men and women aged 45 to 84 years with no clinical cardiovascular disease who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). The prevalence of coronary calcification (Agatston score >0) in these 4 ethnic groups was 70.4%, 52.1%, 56.5%, and 59.2%, respectively, in men (P<0.001) and 44.6%, 36.5%, 34.9%, and 41.9%, respectively, (P<0.001) in women. After adjustment for age, education, lipids, body mass index, smoking, diabetes, hypertension, treatment for hypercholesterolemia, gender, and scanning center, compared with whites, the relative risks for having coronary calcification were 0.78 (95% CI 0.74 to 0.82) in blacks, 0.85 (95% CI 0.79 to 0.91) in Hispanics, and 0.92 (95% CI 0.85 to 0.99) in Chinese. After similar adjustments, the amount of coronary calcification among those with an Agatston score >0 was greatest among whites, followed by Chinese (77% that of whites; 95% CI 62% to 96%), Hispanics (74%; 95% CI 61% to 90%), and blacks (69%; 95% CI 59% to 80%). CONCLUSIONS: We observed ethnic differences in the presence and quantity of coronary calcification that were not explained by coronary risk factors. Identification of the mechanism underlying these differences would further our understanding of the pathophysiology of coronary calcification and its clinical significance. Data on the predictive value of coronary calcium in different ethnic groups are needed.

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.