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Prostacyclin synthesis in heart transplant recipients
The Top 10 Reasons Cardiologists and Other Physicians Are Not Interested in Lipids
Editor in Chief, William Clifford Roberts’ piece, “Getting Cardiologists Interested in Lipids,” was most informative (The American Journal ofCardiology 1993;72:744-745).His David Letterman style list-Top Reasons Cardiologists Are Not Interested in Lipids-was particularly outstanding. As a general internist, I’m in the group ranked slightly below cardiologists in understanding the importance of cholesterol in the development of atherosclerosis, as noted by national studies.l I offer 2 additional reasonswhy cardiologists, internists, and physicians, in general, involved in treating problems related to atherosclerosis have not received with a great deal of enthusiasm the recommendationsof theNational Cholesterol Education Program (NCEP) expert panel. The NCEP 1988 report2 listed risk factors for coronary artery disease. One risk factor was noted to be cigarette smoking (currently smoke >lO cigarettes/day).As early as 1904,studies found that cigarette smokers had a considerably higher incidence of peripheral vascular disease than nonsmokers and in 1958 a major study linked smoking to coronary artery disease.3,4In 1987Willet et al5 observed that even “the lightest smokers (l-4 cigarettes per day) had a significant elevated risk of coronary artery disease,relative risk equals 2.4.” It continues to be a point of interest to me how the NCEP arrived at the conclusion that a significant risk factor for the development of coronary artery disease is smoking at a level currently >lO cigarettes/day. The 1993 study6 has corrected this to reflect that current cigarette smoking at any level is a significant risk. The meansby which this correction was accomplished is
not clarified in the 1993report in the text and there are no references. The second reason why I think physicians, in general, have not been more actively involved in helping their patients learn more about the role of cholesterol in atherosclerosis relates to the fact that the nationwide program of the American Medical Association (the Fat/Cholesterol Education Program) has the sameincorrect information regarding cigarette smoking that the NCEP report of 1988 contained. The brochures that the American Medical Association has provided to hand out to patients has continued to include this incorrect information regarding cigarette smoking as a risk factor through the December 1991printing. The handout entitled, “What You Should Know About High Blood Cholesterol,” was funded as recently as December 1991 by Fleischman’s margarine and Egg Beaters, both products of Nabisco FoodsCompany, a division of R.J. Reynolds Company, which for many years has been known as R.J. Reynolds Tobacco Company. I have received no more recent copies of “What You Should Know About High Blood Cholesterol” than that of December 1991. Has R.J. Reynolds/Nabisco Foods Co. decided to drop sponsorship of the American Medical Association’s cholesterol education program? James H. Lutschg, MD Baton Rouge, Louisiana
1.5November 1993 1. SchuckeiB, Wittes JT, Cutler JA, Bailey K, Mackintosh DR, Gordon DJ, Haines CM, Mattson ME, Goor RS, Rifkind BM. Change in physician pcrspective on cholesterol and heart disease. Results from two national surveys. JAMA 1987;258:3521-3531. 2. The Expert Panel. Report of the national cholesterol education program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Arch Intern Med 1988:148:3ti9. 3. Read RC. Systemic’effects of smoking. Am J Surg 1984:14X:70&71 I. 4. Hammond EC, Horn D. Smoking and death ratereport on forty-four months of follow-up of 187,783 men. I. Total mortality. JAMA 1958;166: 1159-264. 5. Willet W, Green A, Stampfer M, Speizer FE, Colditz GA, Rosner B, Monson RR, Statson W, Hennekens CH. Relative and absolute excess risks of coronay heart disease among women who smoke cigarettes. N En,@J Med 1987;317:1303-1309.
6. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Edncation Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). JAMA 1993;269: 3015-3023.
Prostacyclin Synthesis in Heart Transplant Recipients
I was interested in the recent paper by Bordet et al,l which asserted that systemic prostacyclin synthesis is decreasedby about 60% in heart transplantrecipients. This conclusion was based on measurementsof the principal urinary metaboliteof prostacyclin, 2,3-dinor-6-oxo-prostaglandin F WWlp. However, this urinary metabolite represents only a small fraction of total systemicprostacyclin production. Fitzgerald et al2 found that of prostacyclin infused intravenously in healthy subjects, only 6.8% appearedin the urine as 2,3-dinor-6-oxo-PGFlp. Cyclosporine or other aspectsof the transplant regimen could alter the pathways of prostacyclin metabolism and decrease the percentage of systemic prostacyclin recovered as its 2,3-d& nor-6-oxo-PGF,p metabolite.No data are available to validate the use of this metabolite in the transplant population. The authors could validate their use of 2,3-dinor-6-oxo-PGF,p by measuring urinary excretion of this compound in several transplant recipients and control subjectsduring an infusion of prostacyclin. Without such studies, the data do not support the conclusion that systemic prostacyclin synthesis is reduced in heart transplant recipients. David
E. Johnston,
MD
Boston, Massachusetts 4 November 1993 1. Bordet J-C, de Lorgeril M, Dnrbin S, Boissonnat P, Renaud S, Dnreau G, Dechavanne M. Systemic but not renal production of prostacyclin is highly reduced in cyclosporit-treated heart transplant recipients. Am J Cardiol 1993;72:486 487. 2. Fitzgerald GA, Brash AR, Falardeau P, Oates JA. Estimated rate of prostacyclin secretion into the circulation of normal man. J Clin Invest 1981;68:1272
1276.
Letters (from the United States) concerning a particular article in the Journal must be received within 2 months of the article’s publication, and should be limited (with rare exceptions) to 2 double-spaced typewritten pages. Two copies must be submitted.
READERS’COMMENTS 1139
Editor in Chief, William Clifford Roberts’ piece, “Getting Cardiologists Interested in Lipids,” was most informative (The American Journal ofCardiology 1993;72:744-745).His David Letterman style list-Top Reasons Cardiologists Are Not Interested in Lipids-was particularly outstanding. As a general internist, I’m in the group ranked slightly below cardiologists in understanding the importance of cholesterol in the development of atherosclerosis, as noted by national studies.l I offer 2 additional reasonswhy cardiologists, internists, and physicians, in general, involved in treating problems related to atherosclerosis have not received with a great deal of enthusiasm the recommendationsof theNational Cholesterol Education Program (NCEP) expert panel. The NCEP 1988 report2 listed risk factors for coronary artery disease. One risk factor was noted to be cigarette smoking (currently smoke >lO cigarettes/day).As early as 1904,studies found that cigarette smokers had a considerably higher incidence of peripheral vascular disease than nonsmokers and in 1958 a major study linked smoking to coronary artery disease.3,4In 1987Willet et al5 observed that even “the lightest smokers (l-4 cigarettes per day) had a significant elevated risk of coronary artery disease,relative risk equals 2.4.” It continues to be a point of interest to me how the NCEP arrived at the conclusion that a significant risk factor for the development of coronary artery disease is smoking at a level currently >lO cigarettes/day. The 1993 study6 has corrected this to reflect that current cigarette smoking at any level is a significant risk. The meansby which this correction was accomplished is
not clarified in the 1993report in the text and there are no references. The second reason why I think physicians, in general, have not been more actively involved in helping their patients learn more about the role of cholesterol in atherosclerosis relates to the fact that the nationwide program of the American Medical Association (the Fat/Cholesterol Education Program) has the sameincorrect information regarding cigarette smoking that the NCEP report of 1988 contained. The brochures that the American Medical Association has provided to hand out to patients has continued to include this incorrect information regarding cigarette smoking as a risk factor through the December 1991printing. The handout entitled, “What You Should Know About High Blood Cholesterol,” was funded as recently as December 1991 by Fleischman’s margarine and Egg Beaters, both products of Nabisco FoodsCompany, a division of R.J. Reynolds Company, which for many years has been known as R.J. Reynolds Tobacco Company. I have received no more recent copies of “What You Should Know About High Blood Cholesterol” than that of December 1991. Has R.J. Reynolds/Nabisco Foods Co. decided to drop sponsorship of the American Medical Association’s cholesterol education program? James H. Lutschg, MD Baton Rouge, Louisiana
1.5November 1993 1. SchuckeiB, Wittes JT, Cutler JA, Bailey K, Mackintosh DR, Gordon DJ, Haines CM, Mattson ME, Goor RS, Rifkind BM. Change in physician pcrspective on cholesterol and heart disease. Results from two national surveys. JAMA 1987;258:3521-3531. 2. The Expert Panel. Report of the national cholesterol education program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Arch Intern Med 1988:148:3ti9. 3. Read RC. Systemic’effects of smoking. Am J Surg 1984:14X:70&71 I. 4. Hammond EC, Horn D. Smoking and death ratereport on forty-four months of follow-up of 187,783 men. I. Total mortality. JAMA 1958;166: 1159-264. 5. Willet W, Green A, Stampfer M, Speizer FE, Colditz GA, Rosner B, Monson RR, Statson W, Hennekens CH. Relative and absolute excess risks of coronay heart disease among women who smoke cigarettes. N En,@J Med 1987;317:1303-1309.
6. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Edncation Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). JAMA 1993;269: 3015-3023.
Prostacyclin Synthesis in Heart Transplant Recipients
I was interested in the recent paper by Bordet et al,l which asserted that systemic prostacyclin synthesis is decreasedby about 60% in heart transplantrecipients. This conclusion was based on measurementsof the principal urinary metaboliteof prostacyclin, 2,3-dinor-6-oxo-prostaglandin F WWlp. However, this urinary metabolite represents only a small fraction of total systemicprostacyclin production. Fitzgerald et al2 found that of prostacyclin infused intravenously in healthy subjects, only 6.8% appearedin the urine as 2,3-dinor-6-oxo-PGFlp. Cyclosporine or other aspectsof the transplant regimen could alter the pathways of prostacyclin metabolism and decrease the percentage of systemic prostacyclin recovered as its 2,3-d& nor-6-oxo-PGF,p metabolite.No data are available to validate the use of this metabolite in the transplant population. The authors could validate their use of 2,3-dinor-6-oxo-PGF,p by measuring urinary excretion of this compound in several transplant recipients and control subjectsduring an infusion of prostacyclin. Without such studies, the data do not support the conclusion that systemic prostacyclin synthesis is reduced in heart transplant recipients. David
E. Johnston,
MD
Boston, Massachusetts 4 November 1993 1. Bordet J-C, de Lorgeril M, Dnrbin S, Boissonnat P, Renaud S, Dnreau G, Dechavanne M. Systemic but not renal production of prostacyclin is highly reduced in cyclosporit-treated heart transplant recipients. Am J Cardiol 1993;72:486 487. 2. Fitzgerald GA, Brash AR, Falardeau P, Oates JA. Estimated rate of prostacyclin secretion into the circulation of normal man. J Clin Invest 1981;68:1272
1276.
Letters (from the United States) concerning a particular article in the Journal must be received within 2 months of the article’s publication, and should be limited (with rare exceptions) to 2 double-spaced typewritten pages. Two copies must be submitted.
READERS’COMMENTS 1139