This article was downloaded by: [New York University] On: 06 May 2015, At: 02:10 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of the American College of Nutrition Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uacn20
Vitamin E supplementation, plasma lipids and incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). a
a
a
a
a
a
S J DeMaio , S B King 3rd , N J Lembo , G S Roubin , J A Hearn , H N Bhagavan & D a
S Sgoutas a
Andreas Gruentzig Cardiovascular Center, Department of Internal Medicine (Cardiology), Atlanta, GA. Published online: 02 Sep 2013.
To cite this article: S J DeMaio, S B King 3rd, N J Lembo, G S Roubin, J A Hearn, H N Bhagavan & D S Sgoutas (1992) Vitamin E supplementation, plasma lipids and incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA)., Journal of the American College of Nutrition, 11:1, 68-73, DOI: 10.1080/07315724.1992.10718198 To link to this article: http://dx.doi.org/10.1080/07315724.1992.10718198
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Vitamin £ Supplementation, Plasma Lipids and Incidence of Restenosis After Percutaneous Transluminal Coronary Angioplasty (PTCA) Samuel J. DeMaio, MD, Spencer B. King, III, MD, Nicholas J. Lembo, MD, Gareth S. Roubin, MB, PhD, James A. Hearn, MD, Hemmige N. Bhagavan, PhD, FACN, and Demetrios S. Sgoutas, PhD Andreas Gruentzig Cardiovascular Center, Department of Internal Medicine (Cardiology), Atlanta (S.J.D., S.B.K., N.J.L., G.S.R., J.A.H.), Hoffman-La Roche Ine, Nutley, NJ (H.N.B.), and Department ofPathology and Laboratory Medicine, Emory University School ofMedicine, Atlanta (D.S.S.)
Downloaded by [New York University] at 02:10 06 May 2015
Key words: percutaneous transluminal coronary angioplasty, restenosis, dl-a-tocopherol, vitamin E To test whether a-tocopherol prevents restenosis following percutaneous transluminal coronary angioplasty (PTCA), we enrolled patients in a double-blind, placebo-controlled trial. Patients were randomized after successful PTCA to receive vitamin E in the form of dl-a-tocopherol, 1200 IU/day, orally vs an inactive placebo for 4 months. Patients' blood was analyzed at baseline and at 4 months post-PTCA for differences in plasma lipids, lipoproteins, apolipoproteins, atocopherol, retinol, /3-carotene and lipoperoxide concentrations. One hundred patients completed the protocol. No significant difference was found in any parameter except a-tocopherol level between the vitamin E group and the placebo group, verifying compliance. Follow-up cardiac catheterization was obtained in 83% of the patients receiving placebo and in 86% of the patients receiving dl-a-tocopherol. Including thallium and exercise stress testing, objective information was obtained for practically all the patients receiving dl-a-tocopherol or placebo. Restenosis was defined as the presence of a lesion with >50% stenosis in a previously dilated artery segment and results were analyzed with respect to pre- and postPTCA artery diameter, vessel diameter at follow-up, and restenosis rate. Patients receiving dl-a-tocopherol had a 35.5% restenosis angiographically documented vs 47.5% restenosis in patients receiving the placebo. The overall incidence of restenosis defined by an abnormal angiogram or thallium test or exercise stress test was 34.6% in patients receiving dl-atocopherol and 50% in patients receiving the placebo. This difference (p = 0.06) did not reach significance because of an inadequate sample size.
Abbreviations: CV = coefficient of variation, HDL = high-density lipoproteins, HDL-C = high-density lipoprotein cholesterol, IU = international units, LDL = low-density lipoproteins, Lp(a) = lipoprotein (a), MDA = malonaldehyde, PTCA = percutaneous transluminal coronary angioplasty, SD = standard deviation
INTRODUCTION
suggests that intimai proliferation of migrating smooth muscle cells would be the main cause of restenosis after PTCA. Some other factors which may contribute to reste nosis are: increased shear, platelet adhesion, mural throm bus and spasm. Recently, a potential regulatory function for oxidized lipoproteins has been described [5-7] includ ing regulation of platelet adhesion, production of plateletderived growth factor, and proliferation of smooth muscle cells [6,7]. These findings advanced the hypothesis that antioxidants like vitamin E may prevent proliferation of smooth muscle cells by shielding circulating lipoproteins
Percutaneous transluminal coronary angioplasty (PTCA) [1] has gained increased acceptance as a safe and effective therapy for coronary artery disease. Long-term benefit of coronary angioplasty has been limited in some patients, however, by the recurrence of stenotic lesions [2,3]. Various therapies such as aspirin and other antiplatelet agents have been proposed to decrease such recurrences [4]. The pathophysiologic mechanism of restenosis has been enigmatic so far, but accumulated evidence strongly
Address reprints requests to Demetrios S. Sgoutas, PhD, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.
Journal of the American College of Nutrition, Vol. 11, No. 1, 68-73 (1992) Published by the American College of Nutrition 68
Vitamin E and Coronary Artery Disease from peroxidation and by inhibiting the secretion of factors which stimulate the growth of smooth muscle cells. Re cently, several studies [8-11 ] employing cell cultures, iso lated perfused hearts, and intact animals have tested this hypothesis. The present study was undertaken to prospectively evaluate the effectiveness of vitamin E given in the form of dl-a-tocopherol supplementation in preventing recurrent stenosis in patients who underwent successful PTCA.
MATERIALS AND METHODS
Downloaded by [New York University] at 02:10 06 May 2015
Patients Patients were selected at random and most had char acteristic symptoms or objective clinical evidence of myocardial ischemia based on stress testing data and on spon taneous electrocardiographic T wave changes. The angio graphie procedure was performed by the femoral route using a standard technique described previously [1]. Suc cessful dilatation (20% reduction in stenosis diameter and a final stenosis 50% loss of the initial gain in luminal diameter. If a patient's narrowing of lu minal diameter was 80% before PTCA and 20% immedi ately after PTCA, a subsequent narrowing of >50% in luminal diameter was defined as restenosis. Stenoses were measured in at least two projections using a computerized caliper system (a 2D cinematic viewer and Prodical 1101 programmable digital caliper, Ultrasound Ine, Killingsworth, CT). Diameter stenosis was calculated as the mean of measurements in two or three available projections. For patients with PTCA of multiple lesions, the first stenosis to be dilated (usually the most severe) was analyzed. Pa tients were determined to have clinical restenosis if any of the following tests were positive: angiography, exercise stress test or thallium test. Treadmill stress testing and thallium testing are highly sensitive tests for determining restenosis, particularly in patients who have had multiple stress tests in the past. Methods Coronary arteriograms were reviewed by two independ ent blinded observers and stenoses were measured in two orthogonal views using digital electronic calipers. Plasma and serum were separated within 1-2 hours by low speed centrifugation. Total cholesterol and total triglycérides
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
69
Vitamin E and Coronary Artery Disease Table 1. Baseline Characteristics According to Study Groups Factor
Vitamin E
Placebo
Patients 1 Age2 Sex: male 3 Previous myocardial infarction 3
52 54 ± 8 44(82%) 11(23%)
48 53 ± 9 40(81%) 10(20%)
1
Number of patients in the group. Values are mean ± standard deviation (SD). 3 Number of patients with percentage of total patients in each group in parentheses.
Table 3. PTCA Results According to Study Groups' Diameter stenosis %* Vitamin E
Placebo
68 ± 15 26 ± 10
72 ± 14 22 ± 12
Before PTCA After PTCA
P value
NS NS
1
Values are mean ± SD. NS = nonsignificant at p = 0.05. Statistical significance was assessed by Student's t-test.
Downloaded by [New York University] at 02:10 06 May 2015
2
were determined enzymatically [12,13]. The procedures were standardized according to the guidelines set by the Lipid Research Clinic Program [14]. There was an intraassay and interassay coefficient of variation (CV) of
Journal of the American College of Nutrition Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uacn20
Vitamin E supplementation, plasma lipids and incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). a
a
a
a
a
a
S J DeMaio , S B King 3rd , N J Lembo , G S Roubin , J A Hearn , H N Bhagavan & D a
S Sgoutas a
Andreas Gruentzig Cardiovascular Center, Department of Internal Medicine (Cardiology), Atlanta, GA. Published online: 02 Sep 2013.
To cite this article: S J DeMaio, S B King 3rd, N J Lembo, G S Roubin, J A Hearn, H N Bhagavan & D S Sgoutas (1992) Vitamin E supplementation, plasma lipids and incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA)., Journal of the American College of Nutrition, 11:1, 68-73, DOI: 10.1080/07315724.1992.10718198 To link to this article: http://dx.doi.org/10.1080/07315724.1992.10718198
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Vitamin £ Supplementation, Plasma Lipids and Incidence of Restenosis After Percutaneous Transluminal Coronary Angioplasty (PTCA) Samuel J. DeMaio, MD, Spencer B. King, III, MD, Nicholas J. Lembo, MD, Gareth S. Roubin, MB, PhD, James A. Hearn, MD, Hemmige N. Bhagavan, PhD, FACN, and Demetrios S. Sgoutas, PhD Andreas Gruentzig Cardiovascular Center, Department of Internal Medicine (Cardiology), Atlanta (S.J.D., S.B.K., N.J.L., G.S.R., J.A.H.), Hoffman-La Roche Ine, Nutley, NJ (H.N.B.), and Department ofPathology and Laboratory Medicine, Emory University School ofMedicine, Atlanta (D.S.S.)
Downloaded by [New York University] at 02:10 06 May 2015
Key words: percutaneous transluminal coronary angioplasty, restenosis, dl-a-tocopherol, vitamin E To test whether a-tocopherol prevents restenosis following percutaneous transluminal coronary angioplasty (PTCA), we enrolled patients in a double-blind, placebo-controlled trial. Patients were randomized after successful PTCA to receive vitamin E in the form of dl-a-tocopherol, 1200 IU/day, orally vs an inactive placebo for 4 months. Patients' blood was analyzed at baseline and at 4 months post-PTCA for differences in plasma lipids, lipoproteins, apolipoproteins, atocopherol, retinol, /3-carotene and lipoperoxide concentrations. One hundred patients completed the protocol. No significant difference was found in any parameter except a-tocopherol level between the vitamin E group and the placebo group, verifying compliance. Follow-up cardiac catheterization was obtained in 83% of the patients receiving placebo and in 86% of the patients receiving dl-a-tocopherol. Including thallium and exercise stress testing, objective information was obtained for practically all the patients receiving dl-a-tocopherol or placebo. Restenosis was defined as the presence of a lesion with >50% stenosis in a previously dilated artery segment and results were analyzed with respect to pre- and postPTCA artery diameter, vessel diameter at follow-up, and restenosis rate. Patients receiving dl-a-tocopherol had a 35.5% restenosis angiographically documented vs 47.5% restenosis in patients receiving the placebo. The overall incidence of restenosis defined by an abnormal angiogram or thallium test or exercise stress test was 34.6% in patients receiving dl-atocopherol and 50% in patients receiving the placebo. This difference (p = 0.06) did not reach significance because of an inadequate sample size.
Abbreviations: CV = coefficient of variation, HDL = high-density lipoproteins, HDL-C = high-density lipoprotein cholesterol, IU = international units, LDL = low-density lipoproteins, Lp(a) = lipoprotein (a), MDA = malonaldehyde, PTCA = percutaneous transluminal coronary angioplasty, SD = standard deviation
INTRODUCTION
suggests that intimai proliferation of migrating smooth muscle cells would be the main cause of restenosis after PTCA. Some other factors which may contribute to reste nosis are: increased shear, platelet adhesion, mural throm bus and spasm. Recently, a potential regulatory function for oxidized lipoproteins has been described [5-7] includ ing regulation of platelet adhesion, production of plateletderived growth factor, and proliferation of smooth muscle cells [6,7]. These findings advanced the hypothesis that antioxidants like vitamin E may prevent proliferation of smooth muscle cells by shielding circulating lipoproteins
Percutaneous transluminal coronary angioplasty (PTCA) [1] has gained increased acceptance as a safe and effective therapy for coronary artery disease. Long-term benefit of coronary angioplasty has been limited in some patients, however, by the recurrence of stenotic lesions [2,3]. Various therapies such as aspirin and other antiplatelet agents have been proposed to decrease such recurrences [4]. The pathophysiologic mechanism of restenosis has been enigmatic so far, but accumulated evidence strongly
Address reprints requests to Demetrios S. Sgoutas, PhD, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.
Journal of the American College of Nutrition, Vol. 11, No. 1, 68-73 (1992) Published by the American College of Nutrition 68
Vitamin E and Coronary Artery Disease from peroxidation and by inhibiting the secretion of factors which stimulate the growth of smooth muscle cells. Re cently, several studies [8-11 ] employing cell cultures, iso lated perfused hearts, and intact animals have tested this hypothesis. The present study was undertaken to prospectively evaluate the effectiveness of vitamin E given in the form of dl-a-tocopherol supplementation in preventing recurrent stenosis in patients who underwent successful PTCA.
MATERIALS AND METHODS
Downloaded by [New York University] at 02:10 06 May 2015
Patients Patients were selected at random and most had char acteristic symptoms or objective clinical evidence of myocardial ischemia based on stress testing data and on spon taneous electrocardiographic T wave changes. The angio graphie procedure was performed by the femoral route using a standard technique described previously [1]. Suc cessful dilatation (20% reduction in stenosis diameter and a final stenosis 50% loss of the initial gain in luminal diameter. If a patient's narrowing of lu minal diameter was 80% before PTCA and 20% immedi ately after PTCA, a subsequent narrowing of >50% in luminal diameter was defined as restenosis. Stenoses were measured in at least two projections using a computerized caliper system (a 2D cinematic viewer and Prodical 1101 programmable digital caliper, Ultrasound Ine, Killingsworth, CT). Diameter stenosis was calculated as the mean of measurements in two or three available projections. For patients with PTCA of multiple lesions, the first stenosis to be dilated (usually the most severe) was analyzed. Pa tients were determined to have clinical restenosis if any of the following tests were positive: angiography, exercise stress test or thallium test. Treadmill stress testing and thallium testing are highly sensitive tests for determining restenosis, particularly in patients who have had multiple stress tests in the past. Methods Coronary arteriograms were reviewed by two independ ent blinded observers and stenoses were measured in two orthogonal views using digital electronic calipers. Plasma and serum were separated within 1-2 hours by low speed centrifugation. Total cholesterol and total triglycérides
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
69
Vitamin E and Coronary Artery Disease Table 1. Baseline Characteristics According to Study Groups Factor
Vitamin E
Placebo
Patients 1 Age2 Sex: male 3 Previous myocardial infarction 3
52 54 ± 8 44(82%) 11(23%)
48 53 ± 9 40(81%) 10(20%)
1
Number of patients in the group. Values are mean ± standard deviation (SD). 3 Number of patients with percentage of total patients in each group in parentheses.
Table 3. PTCA Results According to Study Groups' Diameter stenosis %* Vitamin E
Placebo
68 ± 15 26 ± 10
72 ± 14 22 ± 12
Before PTCA After PTCA
P value
NS NS
1
Values are mean ± SD. NS = nonsignificant at p = 0.05. Statistical significance was assessed by Student's t-test.
Downloaded by [New York University] at 02:10 06 May 2015
2
were determined enzymatically [12,13]. The procedures were standardized according to the guidelines set by the Lipid Research Clinic Program [14]. There was an intraassay and interassay coefficient of variation (CV) of
