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Increased plasma homocysteine is an independent predictor of new coronary events in older persons
1. Serruys P, Jaegere P, Kiemeneki F, Macaya C, Rutch W, Heyndrickx G, Emenuelsson H, Marco J, Legrand W, Materne P. A comparison of balloon expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331:489 – 495. 2. Savage MP, Douglas SS, Fischman DL. Stent placement compared with balloon angioplasty for obstructed coronary bypass grafts. N Engl J Med 1997; 337:740 –747. 3. Lefkovits J, Holmes RD, Califf RM, Safian RD, Pieper K, Keeler G, Topol EJ, Predictors and sequelae of distal embolization during saphenous vein graft intervention from the CAVEAT-II trial. Circulation 1995;92:734 –740. 4. Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King SB III, Loop FD, Peterson KL, Reevers TJ, Williams DO, Winters WL. Guidelines for percutaneous transluminal coronary angioplasty: a report of the American College of Cardiology/American Heart Association Task Force on assessment of diagnostic and therapeutic cardiovascular procedures. Circulation 1988;78:486 –502. 5. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, Francis CK, Hillis D, Ludbrook P, for the TIMI Investigators. Thrombolysis in Myocardial Infarction (TIMI) Trial. Phase I: a comparison between intravenous tissue-plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 1987;76:142–154. 6. Cohen J. Statistical Power Analysis for the Behavioral Sciences, 2nd ed. Hillsdale, NJ: Lawrence Erlbaum, 1988.
7. Elsner M, Auch-Schwelk W, Britten M, Walter DH, Schachinger V, Zeiher AM. Coronary stent grafts covered by polytetrafluoroethylene membrane. Am J Cardiol 1999;84:335–338. 8. Gurbel PA, Criado FJ, Curnutte EA, Patten P, Secada-Lovio J. Percutaneous revascularization of an extensively diseased saphenous vein graft with a saphenous vein-covered Palmaz stent. Cathet Cardiovasc Diagn 1997;40:75– 78. 9. Stephanadis C, Toutouzas K, Vlachopoulos C, Tsiamis E, Kallikazaros I, Stratos C, Vavuranakis M, Toutouzas P. Percutaneous implantation of autologous vein graft stent for treatment of coronary artery disease. Lancet 1995;345:1509 – 1512. 10. Von Biegelen C, Haude M, Herrmann J, Altmann C, Klinkhart W, Welge D, Wieneke H, Baumgart D, Sack S, Erbel. Early clinical experience with the implantation of a novel synthetic coronary stent graft. Cathet Cardiovasc Intervent 1999;47:496 –503. 11. Kong TQJ, Davidson CJ, Mayers SN, Tanke JT, Parker MA, Bonow RO. Prognostic implication of creatine-kinase elevation following elective coronary artery interventions. JAMA 1997;277:461– 466. 12. Abdemeguid AE, Whitlow PL, Sapp SK, Ellis SG, Topol EJ. Long-term outcome of transient, uncomplicated in-laboratory coronary artery closure. Circulation 1995;91:2733–2741.
Increased Plasma Homocysteine Is an Independent Predictor of New Coronary Events in Older Persons Wilbert S. Aronow, lasma homocysteine has been demonstrated to be a risk factor for coronary artery disease (CAD). P However, not all prospective studies support an associ1–7
ation between elevated plasma homocysteine levels and CAD. 8,9 We previously reported an association between plasma homocysteine level and CAD in 153 older men and 347 older women. 7 We are now reporting on 31month follow-up data showing that plasma homocysteine is an independent risk factor for new coronary events in these 500 older persons. •••
We reported that high plasma homocysteine levels and low plasma folate and vitamin B12 levels were associated with a higher prevalence of CAD in 153 men and 347 women, mean age 81 ⫾ 9 years (range 60 to 99), in a long-term health care facility.7 We investigated, in a prospective study, the association of plasma homocysteine, folate, and vitamin B12 levels and other risk factors with the incidence of new coronary events in these 500 older men and women. Fasting plasma homocysteine, folate, and vitamin B12 levels were determined as described previously.7 Other risk factors investigated were prior CAD, current cigarette smoking, hypertension, diabetes mellitus, fasting serum total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides, and obesity. Prior CAD was diagnosed if the person had a documented clinical history of myocardial infarction From Hebrew Hospital Home, Bronx, New York, and the Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York; and the Division of Clinical Epidemiology, University of Texas Medical School at Houston, Houston, Texas. Dr. Aronow’s address is: Hebrew Hospital Home, 801 Co-op City Boulevard, Bronx, New York 10475. Manuscript received December 20, 1999; revised manuscript received and accepted February 10, 2000.
346
©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 August 1, 2000
MD,
and Chul Ahn,
PhD
TABLE I Association of Risk Factors With New Coronary Events in Older Persons
Variable Age (yrs) Homocysteine (mol/L) Vitamin B12 (ng/L)) Folate (g/L) Total cholesterol (mg/L) HDL cholesterol (mg/L) Triglycerides (mg/L) Men Women Prior myocardial infarction or angina pectoris Smoking Systemic hypertension Diabetes mellitus Obesity
New Coronary No New Events Coronary Events (n ⫽ 194) (n ⫽ 306) p Value 82 16.8 457 7.5 204 37 127 64 130 128
⫾9 ⫾ 4.6 ⫾ 140 ⫾ 2.7 ⫾ 30 ⫾8 ⫾ 62 (33%) (67%) (66%)
81 12.8 562 9.4 191 47 113 89 217 91
54 150 100 29
(28%) (77%) (52%) (15%)
16 122 53 24
⫾9 ⫾ 3.9 ⫾ 153 ⫾ 3.1 ⫾ 26 ⫾ 11 ⫾ 47 (29%) (71%) (30%)
0.083 ⬍0.0001 ⬍0.0001 ⬍0.0001 0.0001 0.0001 0.005 0.356 ⬍0.0001
(5%) ⬍0.0001 (40%) ⬍0.0001 (17%) ⬍0.0001 (8%) 0.012
or electrocardiographic evidence of Q-wave myocardial infarction (n ⫽ 214) or typical angina pectoris without previous myocardial infarction (n ⫽ 5). Two of the 5 persons with typical angina pectoris without myocardial infarction also had coronary revascularization. Hypertension was diagnosed according to the criteria of the Sixth Joint National Committee (JNC VI) Report on the Detection, Evaluation, and Treatment of Hypertension.10 Diabetes mellitus was diagnosed according to the American Diabetic Association’s new criteria.11 The weight and height of each person were correlated with the average height-weight table for persons aged 65 to 94 years.12 A person was considered obese if he or she was ⱖ20% above ideal body weight. 0002-9149/00/$–see front matter PII S0002-9149(00)00931-0
hypertension, diabetes mellitus, and obesity. Stepwise Cox regression analysis showed that significant in95% Confidence dependent predictors of new coroIntervals nary events in older persons were 1.021–1.062 age (risk ratio ⫽ 1.041), plasma ho1.044–1.103 mocysteine (risk ratio ⫽ 1.073), cur1.798–3.542 rent cigarette smoking (risk ratio ⫽ 1.419–2.910 2.524), systemic hypertension (risk 1.461–2.800 ratio ⫽ 2.032), diabetes mellitus 1.008–1.019 (risk ratio ⫽ 2.022), serum total cho0.907–0.942 lesterol (risk ratio ⫽ 1.013), serum HDL cholesterol (risk ratio ⫽ 0.925), and serum triglycerides (risk 1.001–1.007 ratio ⫽ 1.004). Plasma homocysteine was a significant independent predictor of new coronary events in older persons with prior CAD (risk ratio ⫽ 1.068) and in older persons without prior CAD (risk ratio ⫽ 1.106).
TABLE II Prognostic Variables for New Coronary Events in Older Persons and Their Regression Coefficients in the Stepwise Cox Regression Model Variable Age Homocysteine Smoking Systemic hypertension Diabetes mellitus Total cholesterol High-density lipoprotein cholesterol Triglycerides
Regression Coefficient
SE
p Value
Risk Ratio
0.0405 0.0702 0.9257 0.7090
0.0100 0.0140 0.1729 0.1832
0.0001 0.0001 0.0001 0.0001
1.041 1.073 2.524 2.032
0.7043 0.0134 ⫺0.0783
0.1661 0.0028 0.0097
0.0001 0.0001 0.0001
2.022 1.013 0.925
0.0037
0.0016
0.0218
1.004
Persons were followed for the incidence of new coronary events. New coronary events were diagnosed if the person developed documented nonfatal or fatal myocardial infarction or sudden cardiac death. Myocardial infarction was diagnosed as previously described.13 Sudden cardiac death was defined as an unexpected cardiac death in a person with heart disease found dead within 1 hour of being clinically stable.14 The senior investigator reviewed all coronary events with the attending physician. The follow-up period was from the time the baseline data were obtained until the time of new coronary events, death from any cause, or the cutoff date for analysis of data. The mean follow-up period was 31 ⫾ 9 months (range 1 to 36). For analyses comparing persons with and without new coronary events, chi-square tests were used for dichotomous variables and Student’s t tests for continuous variables (Table I). The stepwise Cox regression model was used to identify significant independent predictors of new coronary events (Table II). New coronary events developed in 194 of 500 persons (39%). Table I shows the association of risk factors with new coronary events in 500 older persons and lists levels of statistical significance. Table II shows significant independent risk factors for new coronary events in older persons by the stepwise Cox regression model. The stepwise Cox regression model also showed that plasma homocysteine was a significant independent risk factor for new coronary events in older persons with prior CAD (p ⫽ 0.0014; risk ratio ⫽ 1.068; 95% confidence intervals 1.026 to 1.112), and in older persons without prior CAD (p ⫽ 0.0003; risk ratio ⫽ 1.106; 95% confidence intervals 1.047 to 1.168). •••
Plasma homocysteine has been demonstrated to be a risk factor for CAD.1–7 However, not all prospective studies support an association between elevated plasma homocysteine levels and CAD.8,9 Univariate analysis of the data from the present prospective study showed that risk factors for new coronary events in older persons were elevated plasma homocysteine, total cholesterol, and triglyceride levels, low plasma vitamin B12, folate, and HDL cholesterol levels, prior CAD, current cigarette smoking,
Although increased plasma homocysteine was found to be an independent risk factor for new coronary events in older persons with and without prior CAD in the present prospective study, treating increased plasma homocysteine levels to reduce the risk of coronary events must be considered experimental pending the results of on-going interventional studies. Other modifiable risk factors must be treated. 1. Boushey CJ, Beresford SAA, Omenn GS, Motulsky AG. A quantitative
assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995;274:1049 –1057. 2. Genest JJ Jr, McNamara JR, Salem DN, Wilson PWF, Schaefer EJ, Malinow MR. Plasma homocyst(e)ine levels in men with premature coronary artery disease. J Am Coll Cardiol 1990;16:1114 –1119. 3. Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, Tishler PV, Hennekens CH. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992;268:877– 881. 4. Robinson K, Mayer EL, Miller DP, Green R, van Lente F, Gupta A, KottkeMarchant K, Savon SR, Selhub J, Nissen SE, Kutner M, Topol EJ, Jacobsen DW. Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent reversible risk factors for coronary artery disease. Circulation 1995;92:2825– 2830. 5. Dalery K, Lussier-Cacan S, Selhub J, Davignon J, Latour Y, Genest J Jr. Homocysteine and coronary artery disease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate, and folate. Am J Cardiol 1995;75: 1107–1111. 6. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996;27:517–527. 7. Aronow WS, Ahn C. Association between plasma homocysteine and coronary artery disease in older persons. Am J Cardiol 1997;80:1216 –1218. 8. Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases. A statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1999;99:178 –182. 9. Amsterdam EA. Homocysteine and atherosclerosis update. Prev Cardiol 1999;4:129. 10. Joint National Committee. The Sixth Report of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med 1997;157:2413–2444. 11. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997;20:1183–1197. 12. Master AM, Lasser RP, Beckman G. Tables of average weight and height of Americans aged 65 to 94 years: relationship of weight and height to survival. JAMA 1960;172:658 – 662. 13. Aronow WS. Prevalence of presenting symptoms of recognized acute myocardial infarction and of unrecognized healed myocardial infarction in elderly patients. Am J Cardiol 1987;60:1182. 14. Roberts WC. Sudden cardiac death: definitions and causes. Am J Cardiol 1986;57:1410 –1413.
BRIEF REPORTS
347
7. Elsner M, Auch-Schwelk W, Britten M, Walter DH, Schachinger V, Zeiher AM. Coronary stent grafts covered by polytetrafluoroethylene membrane. Am J Cardiol 1999;84:335–338. 8. Gurbel PA, Criado FJ, Curnutte EA, Patten P, Secada-Lovio J. Percutaneous revascularization of an extensively diseased saphenous vein graft with a saphenous vein-covered Palmaz stent. Cathet Cardiovasc Diagn 1997;40:75– 78. 9. Stephanadis C, Toutouzas K, Vlachopoulos C, Tsiamis E, Kallikazaros I, Stratos C, Vavuranakis M, Toutouzas P. Percutaneous implantation of autologous vein graft stent for treatment of coronary artery disease. Lancet 1995;345:1509 – 1512. 10. Von Biegelen C, Haude M, Herrmann J, Altmann C, Klinkhart W, Welge D, Wieneke H, Baumgart D, Sack S, Erbel. Early clinical experience with the implantation of a novel synthetic coronary stent graft. Cathet Cardiovasc Intervent 1999;47:496 –503. 11. Kong TQJ, Davidson CJ, Mayers SN, Tanke JT, Parker MA, Bonow RO. Prognostic implication of creatine-kinase elevation following elective coronary artery interventions. JAMA 1997;277:461– 466. 12. Abdemeguid AE, Whitlow PL, Sapp SK, Ellis SG, Topol EJ. Long-term outcome of transient, uncomplicated in-laboratory coronary artery closure. Circulation 1995;91:2733–2741.
Increased Plasma Homocysteine Is an Independent Predictor of New Coronary Events in Older Persons Wilbert S. Aronow, lasma homocysteine has been demonstrated to be a risk factor for coronary artery disease (CAD). P However, not all prospective studies support an associ1–7
ation between elevated plasma homocysteine levels and CAD. 8,9 We previously reported an association between plasma homocysteine level and CAD in 153 older men and 347 older women. 7 We are now reporting on 31month follow-up data showing that plasma homocysteine is an independent risk factor for new coronary events in these 500 older persons. •••
We reported that high plasma homocysteine levels and low plasma folate and vitamin B12 levels were associated with a higher prevalence of CAD in 153 men and 347 women, mean age 81 ⫾ 9 years (range 60 to 99), in a long-term health care facility.7 We investigated, in a prospective study, the association of plasma homocysteine, folate, and vitamin B12 levels and other risk factors with the incidence of new coronary events in these 500 older men and women. Fasting plasma homocysteine, folate, and vitamin B12 levels were determined as described previously.7 Other risk factors investigated were prior CAD, current cigarette smoking, hypertension, diabetes mellitus, fasting serum total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides, and obesity. Prior CAD was diagnosed if the person had a documented clinical history of myocardial infarction From Hebrew Hospital Home, Bronx, New York, and the Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York; and the Division of Clinical Epidemiology, University of Texas Medical School at Houston, Houston, Texas. Dr. Aronow’s address is: Hebrew Hospital Home, 801 Co-op City Boulevard, Bronx, New York 10475. Manuscript received December 20, 1999; revised manuscript received and accepted February 10, 2000.
346
©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 August 1, 2000
MD,
and Chul Ahn,
PhD
TABLE I Association of Risk Factors With New Coronary Events in Older Persons
Variable Age (yrs) Homocysteine (mol/L) Vitamin B12 (ng/L)) Folate (g/L) Total cholesterol (mg/L) HDL cholesterol (mg/L) Triglycerides (mg/L) Men Women Prior myocardial infarction or angina pectoris Smoking Systemic hypertension Diabetes mellitus Obesity
New Coronary No New Events Coronary Events (n ⫽ 194) (n ⫽ 306) p Value 82 16.8 457 7.5 204 37 127 64 130 128
⫾9 ⫾ 4.6 ⫾ 140 ⫾ 2.7 ⫾ 30 ⫾8 ⫾ 62 (33%) (67%) (66%)
81 12.8 562 9.4 191 47 113 89 217 91
54 150 100 29
(28%) (77%) (52%) (15%)
16 122 53 24
⫾9 ⫾ 3.9 ⫾ 153 ⫾ 3.1 ⫾ 26 ⫾ 11 ⫾ 47 (29%) (71%) (30%)
0.083 ⬍0.0001 ⬍0.0001 ⬍0.0001 0.0001 0.0001 0.005 0.356 ⬍0.0001
(5%) ⬍0.0001 (40%) ⬍0.0001 (17%) ⬍0.0001 (8%) 0.012
or electrocardiographic evidence of Q-wave myocardial infarction (n ⫽ 214) or typical angina pectoris without previous myocardial infarction (n ⫽ 5). Two of the 5 persons with typical angina pectoris without myocardial infarction also had coronary revascularization. Hypertension was diagnosed according to the criteria of the Sixth Joint National Committee (JNC VI) Report on the Detection, Evaluation, and Treatment of Hypertension.10 Diabetes mellitus was diagnosed according to the American Diabetic Association’s new criteria.11 The weight and height of each person were correlated with the average height-weight table for persons aged 65 to 94 years.12 A person was considered obese if he or she was ⱖ20% above ideal body weight. 0002-9149/00/$–see front matter PII S0002-9149(00)00931-0
hypertension, diabetes mellitus, and obesity. Stepwise Cox regression analysis showed that significant in95% Confidence dependent predictors of new coroIntervals nary events in older persons were 1.021–1.062 age (risk ratio ⫽ 1.041), plasma ho1.044–1.103 mocysteine (risk ratio ⫽ 1.073), cur1.798–3.542 rent cigarette smoking (risk ratio ⫽ 1.419–2.910 2.524), systemic hypertension (risk 1.461–2.800 ratio ⫽ 2.032), diabetes mellitus 1.008–1.019 (risk ratio ⫽ 2.022), serum total cho0.907–0.942 lesterol (risk ratio ⫽ 1.013), serum HDL cholesterol (risk ratio ⫽ 0.925), and serum triglycerides (risk 1.001–1.007 ratio ⫽ 1.004). Plasma homocysteine was a significant independent predictor of new coronary events in older persons with prior CAD (risk ratio ⫽ 1.068) and in older persons without prior CAD (risk ratio ⫽ 1.106).
TABLE II Prognostic Variables for New Coronary Events in Older Persons and Their Regression Coefficients in the Stepwise Cox Regression Model Variable Age Homocysteine Smoking Systemic hypertension Diabetes mellitus Total cholesterol High-density lipoprotein cholesterol Triglycerides
Regression Coefficient
SE
p Value
Risk Ratio
0.0405 0.0702 0.9257 0.7090
0.0100 0.0140 0.1729 0.1832
0.0001 0.0001 0.0001 0.0001
1.041 1.073 2.524 2.032
0.7043 0.0134 ⫺0.0783
0.1661 0.0028 0.0097
0.0001 0.0001 0.0001
2.022 1.013 0.925
0.0037
0.0016
0.0218
1.004
Persons were followed for the incidence of new coronary events. New coronary events were diagnosed if the person developed documented nonfatal or fatal myocardial infarction or sudden cardiac death. Myocardial infarction was diagnosed as previously described.13 Sudden cardiac death was defined as an unexpected cardiac death in a person with heart disease found dead within 1 hour of being clinically stable.14 The senior investigator reviewed all coronary events with the attending physician. The follow-up period was from the time the baseline data were obtained until the time of new coronary events, death from any cause, or the cutoff date for analysis of data. The mean follow-up period was 31 ⫾ 9 months (range 1 to 36). For analyses comparing persons with and without new coronary events, chi-square tests were used for dichotomous variables and Student’s t tests for continuous variables (Table I). The stepwise Cox regression model was used to identify significant independent predictors of new coronary events (Table II). New coronary events developed in 194 of 500 persons (39%). Table I shows the association of risk factors with new coronary events in 500 older persons and lists levels of statistical significance. Table II shows significant independent risk factors for new coronary events in older persons by the stepwise Cox regression model. The stepwise Cox regression model also showed that plasma homocysteine was a significant independent risk factor for new coronary events in older persons with prior CAD (p ⫽ 0.0014; risk ratio ⫽ 1.068; 95% confidence intervals 1.026 to 1.112), and in older persons without prior CAD (p ⫽ 0.0003; risk ratio ⫽ 1.106; 95% confidence intervals 1.047 to 1.168). •••
Plasma homocysteine has been demonstrated to be a risk factor for CAD.1–7 However, not all prospective studies support an association between elevated plasma homocysteine levels and CAD.8,9 Univariate analysis of the data from the present prospective study showed that risk factors for new coronary events in older persons were elevated plasma homocysteine, total cholesterol, and triglyceride levels, low plasma vitamin B12, folate, and HDL cholesterol levels, prior CAD, current cigarette smoking,
Although increased plasma homocysteine was found to be an independent risk factor for new coronary events in older persons with and without prior CAD in the present prospective study, treating increased plasma homocysteine levels to reduce the risk of coronary events must be considered experimental pending the results of on-going interventional studies. Other modifiable risk factors must be treated. 1. Boushey CJ, Beresford SAA, Omenn GS, Motulsky AG. A quantitative
assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995;274:1049 –1057. 2. Genest JJ Jr, McNamara JR, Salem DN, Wilson PWF, Schaefer EJ, Malinow MR. Plasma homocyst(e)ine levels in men with premature coronary artery disease. J Am Coll Cardiol 1990;16:1114 –1119. 3. Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, Tishler PV, Hennekens CH. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992;268:877– 881. 4. Robinson K, Mayer EL, Miller DP, Green R, van Lente F, Gupta A, KottkeMarchant K, Savon SR, Selhub J, Nissen SE, Kutner M, Topol EJ, Jacobsen DW. Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent reversible risk factors for coronary artery disease. Circulation 1995;92:2825– 2830. 5. Dalery K, Lussier-Cacan S, Selhub J, Davignon J, Latour Y, Genest J Jr. Homocysteine and coronary artery disease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate, and folate. Am J Cardiol 1995;75: 1107–1111. 6. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996;27:517–527. 7. Aronow WS, Ahn C. Association between plasma homocysteine and coronary artery disease in older persons. Am J Cardiol 1997;80:1216 –1218. 8. Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases. A statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1999;99:178 –182. 9. Amsterdam EA. Homocysteine and atherosclerosis update. Prev Cardiol 1999;4:129. 10. Joint National Committee. The Sixth Report of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med 1997;157:2413–2444. 11. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997;20:1183–1197. 12. Master AM, Lasser RP, Beckman G. Tables of average weight and height of Americans aged 65 to 94 years: relationship of weight and height to survival. JAMA 1960;172:658 – 662. 13. Aronow WS. Prevalence of presenting symptoms of recognized acute myocardial infarction and of unrecognized healed myocardial infarction in elderly patients. Am J Cardiol 1987;60:1182. 14. Roberts WC. Sudden cardiac death: definitions and causes. Am J Cardiol 1986;57:1410 –1413.
BRIEF REPORTS
347