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The Triglyceride Issue Revisited: Findings From the Helsinki Heart Study

The Triglyceride Issue Revisited: Findings From the Helsinki Heart Study Abstract Background: In clinical practice, high triglyceride level is recognized as an indicator of increased risk of coronary heart disease (CHD), while most epidemiological studies have shown that triglyceride level is not an independent risk factor for CHD. In an effort to explain this discrepancy we reanalyzed the Helsinki Heart Study data in the light of findings from recent clinical studies related to the insulin resistance syndrome. Methods: The log-linear modeling technique was used to study the pattern of cross-sectional interdependence of triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, low-density lipoprotein cholesterol level, blood pressure, and blood glucose level. The CHD risk associated with different combinations of levels of triglycerides, HDL-C, and blood pressure was assessed via Cox proportional hazards models. Results: Triglycerides occupied a central role in the pattern of associations of the factors studied; in particular, the associations with HDL-C level, blood pressure, and blood glucose level were without threshold values. The prevalence of high triglyceride level plus low HDL-C level was strongly associated with blood pressure and blood glucose level, while the prevalence of low HDL-C level alone was not. Only the subgroup with both high triglyceride and low HDL-C levels showed a substantial CHD risk, while those with low HDL-C levels alone or high triglyceride levels alone showed a marginal risk. Conclusions: Our results suggest that triglycerides play a central mediating role in the occurrence of several CHD risk factors, especially those related to the insulin resistance syndrome. Because of these interdependencies, the question of an independent effect of triglycerides is not relevant, and when assessing CHD risk, triglycerides should be considered jointly with HDL-C.(Arch Intern Med. 1994;154:2714-2720) References 1. Castelli WP. The triglyceride issue . Am Heart J. 1986;112:432-437.Crossref 2. Wilhelmsen L, Wedel H, Tibblin G. Multivariate analysis of risk factors for coronary heart disease . Circulation . 1973;48:950-958.Crossref 3. Lippel K, Tyroler H, Eder H, Gotto A, Vahoung G. Relationship of hypertriglyceridemia to atherosclerosis . Atherosclerosis . 1981;1:406-417. 4. Austin MA. Plasma triglyceride as a risk factor for coronary heart disease: the epidemiologic evidence and beyond . Am J Epidemiol. 1989;129:249-259. 5. Manninen V, Tenkanen L, Koskinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study . Circulation . 1992;85:37-45.Crossref 6. Criqui MH, Heiss G, Cohn R, et al. Plasma triglyceride level and mortality from coronary heart disease . N Engl J Med. 1993;328:1220-1225.Crossref 7. Study Group, European Atherosclerosis Society. The recognition and management of hyperlipidemia in adults . Eur Heart J. 1988;9:571-600. 8. Hamsten A. Hypertriglyceridemia, triglyceride-rich lipoproteins and coronary heart disease . Baillieres Clin Endocrinol Metab. 1990;4:895-922.Crossref 9. Reaven GM. Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension . Diabetes Care . 1991;14:195-202.Crossref 10. Reichl D, Miller NE. Pathophysiology of reverse cholesterol transport . Arteriosclerosis . 1989;9:785-797.Crossref 11. Lamarche B, Despres J-P, Pouliot M-C, et al. Metabolic heterogeneity associated with high plasma triglyceride or low HDL cholesterol levels in men . Arterioscler Thromb. 1993;13:33-40.Crossref 12. Olefsky JM, Farquhar JW, Reaven GM. Reappraisal of the role of insulin in hypertriglyceridemia . Am J Med. 1974;57:551-560.Crossref 13. Krauss RM. The tangled web of coronary risk factors . Am J Med. 1991;90 ( (suppl 2A) ):365-415.Crossref 14. Reaven GM. The role of insulin resistance and hyperinsulinemia in coronary heart disease . Metabolism . 1992;41:16-19.Crossref 15. Mänttäri M, Elo O, Frick MH, et al. The Helsinki Heart Study: basic design and randomization procedure . Eur Heart J. 1987;8( (suppl 1) ):1-29.Crossref 16. Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia . N Engl J Med. 1987; 317:1237-1245.Crossref 17. Manninen V, Elo MO, Frick MH, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study . JAMA . 1988; 260:641-651.Crossref 18. Manninen V, Huttunen JK, Tenkanen L, et al. High-density lipoprotein cholesterol as a risk factor for coronary heart disease in the Helsinki Heart Study . In: Miller NE, ed. High Density Lipoproteins and Atherosclerosis II . Amsterdam, the Netherlands: Exerpta Medica; 1989:35-42. 19. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifugation . Clin Chem. 1972;18:499-502. 20. WHO Expert Committee on Diabetes Mellitus. Second Report . Geneva, Switzerland: World Health Organization; 1980. Technical Report 646. 21. Expert Committee on Cardiovascular Diseases and Hypertension. Hypertension and Coronary Heart Disease: Classification and Criteria for Epidemiological Studies . Geneva, Switzerland: World Health Organization; 1959. Technical Report 168. 22. Dixon WJ, ed. BMDP Statistical Software Manual . Berkeley: University of California Press; 1990. 23. Spratka JM, Norsted SW, Folsom AR, Burke GL, Luepker RV. Life-style factors do not explain racial differences in high-density lipoprotein cholesterol: the Minnesota Heart Survey . Epidemiology . 1992;3:156-163.Crossref 24. Hamsten A, Wiman B, de Faire U, Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction . N Engl J Med. 1985;313:1557-1563.Crossref 25. Meade TW, Mellows S, Brozovic M, et al. Haemostatic function and ischaemic heart disease . Lancet . 1986;2:533-537.Crossref 26. Report of a Meeting of Physicians and Scientists, University College London Medical School. Hypertriglyceridemia and vascular risk . Lancet . 1993;342:781-787.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

The Triglyceride Issue Revisited: Findings From the Helsinki Heart Study

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Publisher
American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1994.00420230107012
Publisher site
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Abstract

Abstract Background: In clinical practice, high triglyceride level is recognized as an indicator of increased risk of coronary heart disease (CHD), while most epidemiological studies have shown that triglyceride level is not an independent risk factor for CHD. In an effort to explain this discrepancy we reanalyzed the Helsinki Heart Study data in the light of findings from recent clinical studies related to the insulin resistance syndrome. Methods: The log-linear modeling technique was used to study the pattern of cross-sectional interdependence of triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, low-density lipoprotein cholesterol level, blood pressure, and blood glucose level. The CHD risk associated with different combinations of levels of triglycerides, HDL-C, and blood pressure was assessed via Cox proportional hazards models. Results: Triglycerides occupied a central role in the pattern of associations of the factors studied; in particular, the associations with HDL-C level, blood pressure, and blood glucose level were without threshold values. The prevalence of high triglyceride level plus low HDL-C level was strongly associated with blood pressure and blood glucose level, while the prevalence of low HDL-C level alone was not. Only the subgroup with both high triglyceride and low HDL-C levels showed a substantial CHD risk, while those with low HDL-C levels alone or high triglyceride levels alone showed a marginal risk. Conclusions: Our results suggest that triglycerides play a central mediating role in the occurrence of several CHD risk factors, especially those related to the insulin resistance syndrome. Because of these interdependencies, the question of an independent effect of triglycerides is not relevant, and when assessing CHD risk, triglycerides should be considered jointly with HDL-C.(Arch Intern Med. 1994;154:2714-2720) References 1. Castelli WP. The triglyceride issue . Am Heart J. 1986;112:432-437.Crossref 2. Wilhelmsen L, Wedel H, Tibblin G. Multivariate analysis of risk factors for coronary heart disease . Circulation . 1973;48:950-958.Crossref 3. Lippel K, Tyroler H, Eder H, Gotto A, Vahoung G. Relationship of hypertriglyceridemia to atherosclerosis . Atherosclerosis . 1981;1:406-417. 4. Austin MA. Plasma triglyceride as a risk factor for coronary heart disease: the epidemiologic evidence and beyond . Am J Epidemiol. 1989;129:249-259. 5. Manninen V, Tenkanen L, Koskinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study . Circulation . 1992;85:37-45.Crossref 6. Criqui MH, Heiss G, Cohn R, et al. Plasma triglyceride level and mortality from coronary heart disease . N Engl J Med. 1993;328:1220-1225.Crossref 7. Study Group, European Atherosclerosis Society. The recognition and management of hyperlipidemia in adults . Eur Heart J. 1988;9:571-600. 8. Hamsten A. Hypertriglyceridemia, triglyceride-rich lipoproteins and coronary heart disease . Baillieres Clin Endocrinol Metab. 1990;4:895-922.Crossref 9. Reaven GM. Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension . Diabetes Care . 1991;14:195-202.Crossref 10. Reichl D, Miller NE. Pathophysiology of reverse cholesterol transport . Arteriosclerosis . 1989;9:785-797.Crossref 11. Lamarche B, Despres J-P, Pouliot M-C, et al. Metabolic heterogeneity associated with high plasma triglyceride or low HDL cholesterol levels in men . Arterioscler Thromb. 1993;13:33-40.Crossref 12. Olefsky JM, Farquhar JW, Reaven GM. Reappraisal of the role of insulin in hypertriglyceridemia . Am J Med. 1974;57:551-560.Crossref 13. Krauss RM. The tangled web of coronary risk factors . Am J Med. 1991;90 ( (suppl 2A) ):365-415.Crossref 14. Reaven GM. The role of insulin resistance and hyperinsulinemia in coronary heart disease . Metabolism . 1992;41:16-19.Crossref 15. Mänttäri M, Elo O, Frick MH, et al. The Helsinki Heart Study: basic design and randomization procedure . Eur Heart J. 1987;8( (suppl 1) ):1-29.Crossref 16. Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia . N Engl J Med. 1987; 317:1237-1245.Crossref 17. Manninen V, Elo MO, Frick MH, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study . JAMA . 1988; 260:641-651.Crossref 18. Manninen V, Huttunen JK, Tenkanen L, et al. High-density lipoprotein cholesterol as a risk factor for coronary heart disease in the Helsinki Heart Study . In: Miller NE, ed. High Density Lipoproteins and Atherosclerosis II . Amsterdam, the Netherlands: Exerpta Medica; 1989:35-42. 19. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifugation . Clin Chem. 1972;18:499-502. 20. WHO Expert Committee on Diabetes Mellitus. Second Report . Geneva, Switzerland: World Health Organization; 1980. Technical Report 646. 21. Expert Committee on Cardiovascular Diseases and Hypertension. Hypertension and Coronary Heart Disease: Classification and Criteria for Epidemiological Studies . Geneva, Switzerland: World Health Organization; 1959. Technical Report 168. 22. Dixon WJ, ed. BMDP Statistical Software Manual . Berkeley: University of California Press; 1990. 23. Spratka JM, Norsted SW, Folsom AR, Burke GL, Luepker RV. Life-style factors do not explain racial differences in high-density lipoprotein cholesterol: the Minnesota Heart Survey . Epidemiology . 1992;3:156-163.Crossref 24. Hamsten A, Wiman B, de Faire U, Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction . N Engl J Med. 1985;313:1557-1563.Crossref 25. Meade TW, Mellows S, Brozovic M, et al. Haemostatic function and ischaemic heart disease . Lancet . 1986;2:533-537.Crossref 26. Report of a Meeting of Physicians and Scientists, University College London Medical School. Hypertriglyceridemia and vascular risk . Lancet . 1993;342:781-787.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Dec 12, 1994

References