Treatment of Asymptomatic Adults With Elevated Coronary Calcium Scores With Atorvastatin, Vitamin C, and Vitamin E: The St. Francis Heart Study Randomized Clinical Trial

Department of Research, St. Francis Hospital, Roslyn, New York 11576, USA.
Journal of the American College of Cardiology (Impact Factor: 15.34). 07/2005; 46(1):166-72. DOI: 10.1016/j.jacc.2005.02.089
Source: PubMed

ABSTRACT We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease (ASCVD) events.
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.
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.
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]).
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.

  • Journal of Nuclear Cardiology 03/2008; 15(2):162-9. DOI:10.1016/j.nuclcard.2008.01.009 · 2.65 Impact Factor
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    ABSTRACT: Imaging of vascular calcification is increasingly used for cardiovascular screening purposes in asymptomatic patients. Coronary and aortic calcium deposits in the vascular wall have been shown to be related to atherosclerotic plaque burden. New imaging techniques with electron beam computed tomography (EBCT) and multi-slice computed tomography (MSCT), to measure the calcium content in the coronary arteries, are promising methods for clinical risk assessment. However, the rising costs of these emerging cardiac imaging techniques and the radiation exposure involved demand a more critical evaluation of already existing and less expensive technology. In this thesis we have investigated whether arterial calcifications that are frequently seen on mammograms may serve as a screening tool for atherosclerotic risk assessment in women. The simultaneous use of mammograms for screening on breast cancer and atherosclerotic disease could be very cost-effective. Based on our findings in two different populations of women we can now conclude that the major determinants of medial calcification in the breast arteries are age, diabetes, previous pregnancies and lactation after pregnancy. The mechanisms of BAC are comparable to the medial calcification that is seen in the peripheral vessels of diabetics and in patients with end stage renal disease (ESRD). In diabetics, hyperglycaemia is an important determinant for medial sclerosis and not the classic CHD risk factors. High glucose can induce proliferation of VSMC into calcifying cells, but other metabolic stimuli in patients with diabetes, like hyperinsulinemia and glycoxidation products, can also promote the calcifying process. In patients with ESRD the uptake of calcium by VSMC is multifactorial and enhanced by elevated extracellular calcium- and phosphate levels, secondary hyperparathyreoidism and uremic toxins. The wide-spread use of calcium containing oral phosphate binders, to prevent uremic dystrophy, further promote the calcifying process. The alterated mineral metabolism during pregnancy and lactation is presumably the most important causative factor in the occurrence of BAC. Pregnancy is associated with major changes in the calcium metabolism to meet the high requirements for foetal growth and for breast-milk production. Some biochemical proteins of bone resorption and formation (e.g. osteocalcin, bone morphogenic protein) are elevated in the first months of lactation and are also found in calcified vascular tissues. We assume that when calcium is more available in the (breast) circulation, like during pregnancy and lactation, vascular smooth muscle cells can become activated and promote mineralization. Another common factor in the enhancement of vascular calcification in pregnant women and patients with ESRD may be caused by elevated levels of parathyroid hormone-related protein (PTHrP). PTHrP is expressed in a variety of bone and vascular tissues and causes hypercalcaemia. The production of PTHrP by the lactating mammary gland may be an explanation for the association of BAC with breastfeeding.
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    ABSTRACT: To study changes in breast artery calcifications (BAC) over time and its relation with coronary heart disease (CHD) risk factors. Breast arterial calcifications were studied at baseline and after five years follow-up in 453 women participating in the Raloxifene Use for The Heart (RUTH) study. All mammograms were scored by two observers. With logistic regression analysis the independent effect of risk factors on the progression of BAC was evaluated. BAC was present in 94 of 453 (21%) women at baseline and in 116 of 453 (26%) women after 5.0±1.04 years. Progression of BAC was seen in 44 of 453 (10%) women. In 22 participants (5%) BAC was not present at baseline, while in 22 participants (5%) the severity of BAC merely changed from grade 1 to grade 2 calcification. Age was significantly associated with progression of BAC (OR 1.09, 95% CI 1.03 to 1.14). Multivariate regression analysis with adjustment for age and the duration of follow-up showed no association between CHD risk factors and the progression of BAC. Lipid-lowering drugs protected for progression (adjusted OR 0.5, 95% CI 0.22 to 0.98). The strongest determinant in the progression of BAC was BAC at baseline (adjusted OR 4.2, 95% CI 2.10 to 8.27). Progression of BAC is not associated with CHD risk factors, but with increasing age and BAC at baseline. Lipid-lowering drugs protect against progression of BAC.
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