Cholesterol and Coronary Heart Disease: Predicting Risks by Levels and Ratios

Kinosian, Bruce; Glick, Henry; Garland, Gonzalo

doi:10.7326/0003-4819-121-9-199411010-00002

Cited by 519Lipoproteins and Cardiovascular HealthHealth Promotion and Cardiovascular PreventionDiabetes, Cardiovascular Risks, and Lipoproteins

Cholesterol and Coronary Heart Disease: Predicting Risks by Levels and Ratios

Kinosian, Bruce, Glick, Henry, Garland, Gonzalo·1994·Annals of Internal Medicine

DOI 10.7326/0003-4819-121-9-199411010-00002

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Abstract

OBJECTIVE: Comparison of four measures of cholesterol for predicting men and women who will develop coronary heart disease within 8 to 10 years. DESIGN: Cohort study. PATIENTS: 1898 men who received placebo (the placebo group of the Lipid Research Clinics [LRC] Coronary Primary Prevention Trial [CPPT]), 1025 men and 1442 women who participated in the 1970-1971 Framingham Heart Study biennial examination, and 1911 men and 1767 women without coronary heart disease who were from the LRC Population Prevalence Study. MEASUREMENTS: Total cholesterol, low-density lipoprotein (LDL) cholesterol, ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, and the ratio of LDL to HDL. Outcomes were coronary heart disease in the CPPT and Framingham studies and death from coronary heart disease in the Prevalence Study. RESULTS: Independent information in the total cholesterol/HDL ratio added risk-discriminating ability to total cholesterol and LDL cholesterol measures (P < 0.02), but the reverse was not true. Among women, a high-risk threshold of 5.6 for the total cholesterol/HDL ratio identified a 0% to 15% larger group at 25% to 45% greater risk in the Prevalence and Framingham studies, respectively, than did current guidelines. Among men in the same studies, a risk threshold of 6.4 for the total cholesterol/HDL ratio identified a 69% to 95% larger group at 2% to 14% greater risk than did LDL cholesterol levels alone. Eight-year likelihood ratios for coronary heart disease ranged from 0.32 to 3.11 in men and from 0.59 to 2.98 in women for total cholesterol/HDL ratios (grouped from < 3 to > or = 9). CONCLUSIONS: The total cholesterol/HDL ratio is a superior measure of risk for coronary heart disease compared with either total cholesterol or LDL cholesterol levels. Current practice guidelines could be more efficient if risk stratification was based on this ratio rather than primarily on the LDL cholesterol level.

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The LDL/HDL ratio is used to predict Coronary Heart Disease (CHD), with a higher ratio indicating a higher risk of CHD.
“The LDL/HDL ratio is used to predict Coronary Heart Disease (CHD), with a higher ratio indicating a higher risk of CHD [69].”
From Analysis of early effects of human APOE isoforms on Alzheimer’s disease and type III hyperlipoproteinemia pathways using knock-in rat models with humanized APP and APOE (2024) · cites this paper as [69]

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Background
Acute metabolic responses to a 24-h ultra-marathon race in male amateur runners
Waśkiewicz‬, Z., Kłapcińska, B., Sadowska‐Krępa, E., Czuba, M., Kempa, K., Kimsa, E., & Gerasimuk, D. (2011) · European Journal of Applied Physiology · doi:10.1007/s00421-011-2135-5 · Cited by 117 · see citing works
“It should be stressed that not only concentrations of TG, total cholesterol and its fractions as the independent risk factors, but also the common cholesterol ratios (TC/HDL, LDL/HDL, and TG/HDL), which are considered better predictors of future coronary heart disease (Natarajan et al. 2003; Kinosian et al. 1994; Grov…”
Metabolic benefits 24 months after replacing a protease inhibitor with abacavir, efavirenz or nevirapine
Fisac, C., Fumero, E., Crespo, M., et al. (2005) · AIDS · doi:10.1097/01.aids.0000171405.46113.bf · Cited by 116 · see citing works
“In an analysis of three major epidemiological studies, neither TC nor low density lipoprotein cholesterol levels conveyed additional information when the ratio was used to predict coronary heart disease [26].”
Method
Supplementation of n-3 fatty acids during pregnancy and lactation reduces maternal plasma lipid levels and provides DHA to the infants
Helland, I. B., Saugstad, O. D., Saarem, K., van Houwelingen, A. C., Nylander, G., & Drevon, C. A. (2006) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767050600738396 · Cited by 114 · see citing works
“This ratio may be a predictor of cardiovascular disease [41].”
Background
Efficacy and safety of rosiglitazone plus metformin in Mexicans with type 2 diabetes
Gomez-Perez, F. J., Fanghänel‐Salmón, G., Barbosa, J. A., Montes‐Villarreal, J., Berry, R. A., Warsi, G. M., & Gould, E. M. (2002) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.264 · Cited by 113 · see citing works
Effects of rosuvastatin versus atorvastatin, simvastatin, and pravastatin on non-high-density lipoprotein cholesterol, apolipoproteins, and lipid ratios in patients with hypercholesterolemia: additional results from the STELLAR trial
JONES, P., Hunninghake, D. B., Ferdinand, K. C., Stein, E., Gold, A., Caplan, R. J., & Blasetto, J. W. (2004) · Clinical Therapeutics · doi:10.1016/j.clinthera.2004.09.006 · Cited by 111 · see citing works
Dyslipidemia and abdominal obesity
Paccaud, F. M., Schlüter-Fasmeyer, V., Wietlisbach, V., & Bovet, P. (2000) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(99)00184-5 · Cited by 109 · see citing works
“As far as blood lipid levels are concerned, it is increasingly recognized that the ratio of total cholesterol (TC) to highdensity lipoprotein (HDL) ratio better predicts the occurrence of CVD events than measurements of total cholesterol or HDL alone [5,6].”
Background
Low HDL-cholesterol with normal triglyceride levels is the most common lipid pattern in West Africans and African Americans with Metabolic Syndrome: Implications for cardiovascular disease prevention
Sumner, A. E., Zhou, J., Doumatey, A. P., Imoisili, O. E., Amoah, A. G. B., Acheampong, J. W., Oli, J., Johnson, T., Adebamowo, C., & Rotimi, C. N. (2010) · Global Heart · doi:10.1016/j.cvdpc.2010.07.003 · Cited by 109 · see citing works
“An elevated T-CHOL/ HDL-C ratio is a marker of cardiovascular disease risk, which increases substantially when the ratio is above five [33].”
Background
Elevated high-density lipoprotein cholesterol and cardiovascular mortality in maintenance hemodialysis patients
Moradi, H., Streja, E., Kashyap, M. L., Vaziri, N. D., Fonarow, G. C., & Kalantar‐Zadeh, K. (2014) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfu022 · Cited by 109 · see citing works
Effect of intensive lipid‐lowering therapy on cardiovascular outcome in patients with and those without inflammatory joint disease
Semb, A. G., Kvien, T. K., DeMicco, D. A., Fayyad, R. S., Wun, C., LaRosa, J. C., Betteridge, J. D., Pedersen, T. R., & Holme, I. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34524 · Cited by 108 · see citing works
Is inequality at the heart of it? Cross-country associations of income inequality with cardiovascular diseases and risk factors
Kim, D. J., Kawachi, I. I., Hoorn, S. V., & Ezzati, M. (2008) · Social Science & Medicine · doi:10.1016/j.socscimed.2007.12.030 · Cited by 109 · see citing works
Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients
Catapano, A. L., Davidson, M. H., Ballantyne, C. M., Brady, W. E., Gazzara, R. A., Tomassini, J. E., & Tershakovec, A. M. (2006) · Current Medical Research and Opinion · doi:10.1185/030079906x132721 · Cited by 107 · see citing works
Preventive Medicine and Screening in Older Adults
Goldberg, T. H., & Chavin, S. I. (1997) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1997.tb00952.x · Cited by 105 · see citing works
Effects of margarine compared with those of butter on blood lipid profiles related to cardiovascular disease risk factors in normolipemic adults fed controlled diets
Judd, J. T., Baer, D. J., Clevidence, B. A., Muesing, R. A., Clevidence, B. A., Chen, S. C., Weststrate, J. A., Clevidence, B. A., Meijer, G. W., Janet, W., et al. (1998) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/68.4.768 · Cited by 105 · see citing works
“Changes in the ratios of total or LDL cholesterol to HDL cholesterol may be better predictors of risk for cardiovascular disease than are changes in LDL cholesterol alone (43, 44).”
Background
Changes in lipid profile during infliximab and corticosteroid treatment in rheumatoid arthritis
Peters, M. J. L., Vis, M., van Halm, V. P., Wolbink, G., Voskuyl, A. E., Lems, W. F., Dijkmans, B. A. C., Twisk, J. W. R., Koning, M. H. M. T. D., van de Stadt, R. J., et al. (2007) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2006.059691 · Cited by 104 · see citing works
Plant-Based Nutrition: Exploring Health Benefits for Atherosclerosis, Chronic Diseases, and Metabolic Syndrome—A Comprehensive Review
Peña-Jorquera, H., Cid-Jofré, V., Landaeta-Díaz, L., Petermann-Rocha, F., Martorell, M., Zbinden-Foncea, H., Ferrari, G., Jorquera-Aguilera, C., & Cristi-Montero, C. (2023) · Nutrients · doi:10.3390/nu15143244 · Cited by 103 · see citing works
“An earlier study has supported this and indicated that T/H-r is a superior measure of risk for coronary heart disease compared with either total cholesterol or LDL cholesterol levels [306].”
Result
Association of Apo E Polymorphism With Plasma Lipid Levels in a Multiethnic Elderly Population
Pablos-Méndez, A., Mayeux, R. P., Ngai, C. I., Shea, S., & Berglund, L. (1997) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.17.12.3534 · Cited by 101 · see citing works
Obesity, Body Fat Distribution, and Coronary Artery Disease
Brochu, M., Poehlman, É. T., & Ades, P. A. (2000) · Journal of Cardiopulmonary Rehabilitation · doi:10.1097/00008483-200003000-00003 · Cited by 97 · see citing works
Microalgal docosahexaenoic acid decreases plasma triacylglycerol in normolipidaemic vegetarians: a randomised trial.
Geppert, J., Kraft, V., Demmelmair, H., & Koletzko, B. (2006) · British Journal of Nutrition · doi:10.1079/bjn20051720 · Cited by 96 · see citing works
“…cholesterol, LDL cholesterol:HDL cholesterol and TG:HDL cholesterol ratios were of particular interest as by some authors they are considered superior predictors of CHD compared with total and LDL cholesterol levels (Grover et al. 1994, 1995; Kinosian et al. 1994, 1995; Gaziano et al. 1997).”
Background
A 12-Wk Egg Intervention Increases Serum Zeaxanthin and Macular Pigment Optical Density in Women
Wenzel, A. J., Gerweck, C., Barbato, D., Nicolosi, R. J., Handelman, G. J., & Curran‐Celentano, J. (2006) · Journal of Nutrition · doi:10.1093/jn/136.10.2568 · Cited by 93 · see citing works
“Total cholesterol was divided by HDL-C to yield a ratio (TC:HDL-C) associated with heart disease risk (13).”
Background
Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia
Jenkins, D. J. A., Chiavaroli, L., Wong, J. M. W., Kendall, C., Lewis, G. F., Vidgen, E., Connelly, P. W., Leiter, L. A., Josse, R. G., & Lamarche, B. (2010) · Canadian Medical Association Journal · doi:10.1503/cmaj.092128 · Cited by 92 · see citing works
Balance of Unsaturated Fatty Acids Is Important to a Cholesterol-Lowering Diet: Comparison of Mid-Oleic Sunflower Oil and Olive Oil on Cardiovascular Disease Risk Factors
Binkoski, A. E., Kris-Etherton, P. M., Wilson, T. A., Mountain, M. L., & Nicolosi, R. J. (2005) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2005.04.009 · Cited by 91 · see citing works
Individuals with high total cholesterol/hdl cholesterol ratios are insulin resistant
Jeppesen, Facchini, & Reaven (1998) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1998.00301.x · Cited by 89 · see citing works
Fibrinogen, coagulation factor VII, tissue plasminogen activator, plasminogen activator inhibitor-1, and lipid as cardiovascular risk factors in chronic hemodialysis and continuous ambulatory peritoneal dialysis patients
Tomura, S., Nakamura, Y., Doi, M., Ando, R., Ida, T., Chida, Y., Ootsuka, S., Shinoda, T., Yanagi, H., Tsuchiya, S., et al. (1996) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(96)90523-5 · Cited by 88 · see citing works
Studies on antidyslipidemic effects of Morinda citrifolia (Noni) fruit, leaves and root extracts
Mandukhail, S. R., Aziz, N., & Gilani, A. H. (2010) · Lipids in Health and Disease · doi:10.1186/1476-511x-9-88 · Cited by 87 · see citing works
“Antioxidants are known to effectively prevent this kind of damage [28].”
Background
High-Density Lipoprotein Cholesterol and Coronary Heart Disease
Young, C. E., Karas, R. H., & Kuvin, J. T. (2004) · Cardiology in Review · doi:10.1097/01.crd.0000097140.29929.8a · Cited by 84 · see citing works
“Other observational studies have shown that the total cholesterol to HDL ratio is highly predictive of CHD risk, conveying predictive power beyond that of individual LDL, HDL, or total cholesterol measurements.(13) In 1988, Gordon et al.”
Background
Lipid and apolipoprotein ratios: association with coronary artery disease and effects of rosuvastatin compared with atorvastatin, pravastatin, and simvastatin
Rader, D. J., Davidson, M. H., Caplan, R. J., & Pears, J. S. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(03)00005-5 · Cited by 84 · see citing works
Lipid disorders in antiretroviral-naive patients treated with lopinavir/ritonavir-based HAART: frequency, characterization and risk factors
Montes, M., Pulido, F., Barrós, C., et al. (2005) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dki063 · Cited by 81 · see citing works
“5 to define a group at high risk of coronary heart disease.(4)”
Background
Maximizing the Cost-effectiveness of Lipid-Lowering Therapy
Jacobson, T. A., Schein, J. R., Williamson, A., & Ballantyne, C. M. (1998) · Archives of Internal Medicine · doi:10.1001/archinte.158.18.1977 · Cited by 78 · see citing works
“Although the NCEP guidelines have been useful for their simplicity and as a policy tool to delineate the levels of LDL-C requiring treatment given the number of CHD risk factors, many investigators have advocated more efficient ways to assess the absolute CHD risk, which often require an improved weighting of traditio…”
Method
HDL protein composition alters from proatherogenic into less atherogenic and proinflammatory in rheumatoid arthritis patients responding to rituximab
Raterman, H. G., Levels, H., Voskuyl, A. E., Lems, W. F., Dijkmans, B. A. C., & Nurmohamed, M. T. (2012) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2011-201228 · Cited by 80 · see citing works
Metabolic effects of implantable steroid contraceptives for women
Dorflinger, L. J. (2002) · Contraception · doi:10.1016/s0010-7824(01)00290-6 · Cited by 78 · see citing works
The new pathophysiology of coronary artery disease
Castelli, W. P. (1998) · The American Journal of Cardiology · doi:10.1016/s0002-9149(98)00729-2 · Cited by 76 · see citing works
Role of Fibric Acid Derivatives in the Management of Risk Factors for Coronary Heart Disease
Després, J., Lemieux, I., & Robins, S. J. (2004) · Drugs · doi:10.2165/00003495-200464190-00003 · Cited by 76 · see citing works
Apolipoprotein A-I versus HDL cholesterol in the prediction of risk for myocardial infarction and stroke
Walldius, G., & Jungner, I. (2007) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e3281bd8849 · Cited by 76 · see citing works
Effectiveness of a Lifestyle Physical Activity Versus a Structured Exercise Intervention in Older Adults
Roie, E. V., Delecluse, C., Opdenacker, J., Bock, K. D., Kennis, E., & Boen, F. (2010) · Journal of Aging and Physical Activity · doi:10.1123/japa.18.3.335 · Cited by 75 · see citing works
“Kinosian, Glick, and Garland (1994) found that total-cholesterol:HDL ratio is a better measure of risk for coronary heart disease than either total cholesterol or LDL cholesterol.”
Background
Differences in dyslipidemia between American and Italian women with polycystic ovary syndrome
Essah, P. A., Nestler, J. E., & Carmina, E. (2008) · Journal of Endocrinological Investigation · doi:10.1007/bf03345564 · Cited by 74 · see citing works

Stratifying the patient at risk from coronary disease: New insights from the framingham heart study
Levy, D. A., Wilson, P. W. F., Anderson, K. M., & Castelli, W. P. (1990) · American Heart Journal · doi:10.1016/s0002-8703(05)80050-x · Cited by 157 · see citing works
Thrombogenic Risk Factors for Cardiovascular Disease in Dialysis Patients
Culleton, B. F., & Wilson, P. W. F. (1999) · Seminars in Dialysis · doi:10.1046/j.1525-139x.1999.00002.x · Cited by 12 · see citing works
State of the art coronary heart disease risk estimations based on the Framingham heart study.
Reissigová, J., & Tomečková, M. (2005) · PubMed · Cited by 7 · see citing works
Hypertension and Cardiovascular Disease: Contributions of the Framingham Heart Study
Franklin, S. S., & Wong, N. D. (2013) · Global Heart · doi:10.1016/j.gheart.2012.12.004 · Cited by 224 · see citing works
Serum Uric Acid and Cardiovascular Disease Risk
Culleton, B. F., Larson, M. G., & Levy, D. A. (2000) · Annals of Internal Medicine · doi:10.7326/0003-4819-132-7-200004040-00016

Authors: Kinosian, B., Glick, H., & Garland, G.
Affiliations: Philadelphia VA Medical Center (US)
Corresponding author: Kinosian, Bruce
ORCID: Kinosian, Bruce
Venue: Annals of Internal Medicine
Publisher: American College of Physicians
Published: 1994-11-01
Volume: 121
Issue: 9
Pages: 641-647
ISSN: 0003-4819 (ISSN-L)
1539-3704
DOI: 10.7326/0003-4819-121-9-199411010-00002
OpenAlex: W2081535404
Cited by: 519
References: 0
Citations by year: 2026: 8 · 2025: 10 · 2024: 13 · 2023: 14 · 2022: 15 · 2021: 13 · 2020: 13 · 2019: 10 · 2018: 19 · 2017: 11 · 2016: 4 · 2015: 20 · 2014: 21 · 2013: 18 · 2012: 27
FWCI: 16.95
Type: journal article
Language: en
Open access: closed
Licence: www.acpjournals.org/journal/aim/text-and-data-mining (tdm)
Locations: Annals of Internal Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r29ag009837-01)
National Institute on Aging (NIA R29-AG09837-03)
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Health Promotion and Cardiovascular Prevention
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: coronary artery disease, TC/HDL-C ratio, LDL cholesterol, total cholesterol, risk prediction, risk stratification, risk thresholds, sex differences, likelihood ratios, Framingham Heart Study
MeSH terms: Adult, Aged, Cholesterol, Coronary Disease, Female, Humans, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Predictive Value of Tests, Cohort Studies, Logistic Models

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Cholesterol and Coronary Heart Disease: Predicting Risks by Levels and Ratios

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