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.

Gadolinium pharmacokinetics of chronic myocardial infarcts: Implications for late gadolinium-enhanced infarct imaging.

PURPOSE: To monitor gadolinium pharmacokinetics in the hearts of patients with chronic myocardial infarcts and to determine the variability of contrast agent concentrations and accuracy of infarct detection over an hour time period. MATERIALS AND METHODS: Twenty-five patients with chronic myocardial infarcts were examined. T1 measurements were performed every 2 minutes using an inversion recovery CINE balanced steady-state free precession technique. Paired differences in T1 values over time for the discrimination between the left ventricular (LV) bloodpool, viable, and infarct myocardium were statistically evaluated. The average change per 1, 5, and 10 minutes of the inversion time parameter for optimal nulling of viable myocardium was calculated. Receiver operator characteristic (ROC) curve analysis was performed to compare the performance of late gadolinium-enhanced infarct imaging at increasing delays after contrast agent administration. RESULTS: Significantly different T1 values were reached after 10 minutes between the LV bloodpool, infarcted, and viable myocardium. The T1 difference between myocardial infarcts and the LV bloodpool increased over time, while the difference between viable myocardium and the LV bloodpool decreased. ROC curve analysis showed a decrease in performance of a fixed T1 value to discriminate between the LV bloodpool and viable myocardium over time, while there was a marked increase in the discrimination between the LV bloodpool and infarcted myocardium. CONCLUSION: The ability to discriminate between infarcted myocardium and the LV bloodpool improves with an increasing delay after contrast agent administration while discrimination between viable myocardium and the LV bloodpool decreases.

Myocardial fat deposition after left ventricular myocardial infarction: assessment by using MR water-fat separation imaging.

PURPOSE: To prospectively investigate the prevalence of fat deposition in chronic myocardial infarction (MI) by using magnetic resonance (MR) fat-water separation imaging with sampling of the entire left ventricular (LV) myocardium. A subsidiary aim was to determine the relationship between LV fat deposition and scar characteristics, as well as regional and global cardiac functional parameters. MATERIALS AND METHODS: Twenty-five patients with LV MI were evaluated in this prospective institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study after they provided written informed consent. A 1.5-T MR system was used to perform volumetric cine, fat-sensitive, and late gadolinium-enhanced (LGE) infarct imaging. Water-fat separation was performed by using a three-point Dixon reconstruction from in- and opposed-phase black-blood gradient-echo images. Fat deposition location was compared with LGE infarct imaging by using a 17-segment model. Global and regional functional variables, LGE volumes, and fat deposition were compared by using the Pearson correlation, Student t test, and multiple regression. RESULTS: A fat deposition prevalence of 68% was found in areas of chronic MI. The patients with fat deposition had larger infarctions (30.0 mL +/- 15.1 [standard deviation] vs 14.8 mL +/- 6.1; P = .002), decreased wall thickening (2.3% +/- 20.0 vs 37.8% +/- 34.4; P = .003), and impaired endocardial wall motion (2.9 mm +/- 2.0 vs 5.8 mm +/- 2.6; P = .007). The volume of fat deposition was correlated with infarct volume, LV ejection fraction, LV end-diastolic volume index, and LV end-systolic volume index. CONCLUSION: There is a high prevalence of fat deposition in healed MI. It is associated with post-infarction characteristics including infarct volume, LV mass, wall thickness, wall thickening, and wall motion.

T1-weighted magnetic resonance imaging shows fatty deposition after myocardial infarction.

Pathologic studies have shown an increased lipid content in areas of myocardial infarction (MI). We sought to show the ability of precontrast T1-weighted MRI to noninvasively detect fat deposition in MI and show its association with infarct age. Thirty-two patients with MI were studied. Precontrast inversion-recovery (IR) cine steady-state free precession (SSFP) imaging was used to generate both fat- and muscle-nulled images to locate areas of fat deposition in the left ventricular (LV) myocardium. Postcontrast delayed hyperenhanced (DHE) imaging was also performed. Image contrast in regions of MI on precontrast images and postcontrast DHE images was measured. The association of image contrast with infarct age was determined by means of correlations and Student's t-test. We found a significant association between infarct age and image contrast in both fat- and muscle-nulled images. Precontrast T1-weighted MRI is a promising method for detecting myocardial fat deposition in chronic MI, and can be used to assess myocardial infarct age.

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.