Triglycerides and Coronary Heart Disease: Implications of Recent Clinical Trials
Abstract
This paper reviews the clinical trial data that offer insight into the question of whether, and in what groups of people, triglycerides might be an appropriate therapeutic target for the primary or secondary prevention of atherosclerotic cardiovascular disease. Two angiographic trials (the Lopid Coronary Angiography Trial and the Bezafibrate Coronary Atherosclerosis Intervention Trial) and three clinical endpoint trials (the Helsinki Heart Study, the Bezafibrate Infarction Prevention Study, and the VA HDL Intervention Trial) are reviewed. Hypertriglyceridemia per se is probably not an appropriate therapeutic target for the prevention of atherosclerotic cardiovascular disease because it is a poor marker of atherogenic risk and because there have been no clinical trials that have directly addressed the question of whether lowering the triglyceride level reduces the number of clinical events. The studies reviewed here, however, suggest that patients with established coronary heart disease and a high triglyceride level, in association with either a low high-density lipoprotein-cholesterol level or perhaps other features of the metabolic syndrome, such as obesity, diabetes, or hypertension, may benefit from fibrate therapy. For patients without established coronary heart disease, it is reasonable to consider hypertriglyceridemia as a risk marker prompting the aggressive treatment of other risk factors such as hypertension, diabetes, high low-density lipoprotein-cholesterol, and obesity.
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For patients with established type 2 diabetes, clinical trials confirm that treating dyslipidemia and hypertension reduces cardiovascular risk.
“For patients with established type 2 diabetes mellitus, clinical trials confirm a reduction in cardiovascular risk from treatment of dyslipidemia 161-163,179 -181 and hypertension.91”
From Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (2005) · cites this paper as [162]
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Grundy, S. M., Cleeman, J. I., Daniels, S. R., Donato, K. A., Eckel, R. H., Franklin, B. A., Gordon, D. J., Krauss, R. M., Savage, P. J., Smith, S. C., et al. (2005) · Circulation · doi:10.1161/circulationaha.105.169404 · Cited by 11,961 · see citing works
Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Circulation · doi:10.1161/01.cir.0000133317.49796.0e · Cited by 6,902 · see citing works
Eckel, R. H., Alberti, K., Grundy, S. M., & Zimmet, P. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61794-3 · Cited by 6,283 · see citing works
Grundy, S. M., Brewer, H. B., Cleeman, J. I., Smith, S. C., & Lenfant, C. (2004) · Circulation · doi:10.1161/01.cir.0000111245.75752.c6 · Cited by 5,982 · see citing works
Eckel, R. H., Grundy, S. M., & Zimmet, P. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66378-7 · Cited by 5,566 · see citing works
Grundy, S. M., Cleeman, J. I., Bairey Merz, C. N., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.07.001 · Cited by 1,550 · see citing works
Grundy, S. M. (2010) · Springer eBooks · doi:10.1007/978-1-4419-5839-6_1 · Cited by 1,225 · see citing works
Definition of Metabolic Syndrome
Grundy, S. M., Brewer, H. B., Cleeman, J. I., Smith, S. C., & Lenfant, C. J. M. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000111245.75752.c6 · Cited by 718 · see citing works
Diagnosis and management of the metabolic syndrome
Grundy, S. M., Cleeman, J. I., Daniels, S. R., Donato, K. A., Eckel, R. H., Franklin, B. A., Gordon, D. J., Krauss, R. M., Savage, P. J., Smith, S. C., et al. (2005) · Current Opinion in Cardiology · doi:10.1097/01.hco.0000200416.65370.a0 · Cited by 434 · see citing works
The effects of antipsychotic therapy on serum lipids: a comprehensive review
Meyer, J. M., & Koro, C. E. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.01.014 · Cited by 407 · see citing works
“Observational studies using case-control methods and most prospective cohort studies have consistently shown a strong association of increased TG levels with CHD (Austin, 1999; Jeppesen et al., 1998; Rubins, 2000).”
MethodGrundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000133317.49796.0e · Cited by 195 · see citing works
Willner, E. L., Tow, B., Buhman, K. K., Wilson, M. D., Sanan, D. A., Rudel, L. L., & Farese, R. V. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0336398100 · Cited by 181 · see citing works
Wolfrum, C., & Stoffel, M. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.001 · Cited by 165 · see citing works
Lipolysis of triglyceride-rich lipoproteins, vascular inflammation, and atherosclerosis
Schwartz, E. A., & Reaven, P. D. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.09.021 · Cited by 130 · see citing works
Peroxisome proliferator-activated receptor agonists, hyperlipidaemia, and atherosclerosis
Vosper, H., Khoudoli, G. A., Graham, T. L., & Palmer, C. N. A. (2002) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00232-2 · Cited by 95 · see citing works
Srivastava, R. A. K., Jahagirdar, R., Azhar, S., Sharma, S., & Bisgaier, C. L. (2006) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-005-9053-y · Cited by 94 · see citing works
“Epidemiological evidences suggest a strong link between obesity and the development of type 2 diabetes leading to abnormalities in lipid metabolism and predisposition to CVD complications [3, 8].”
BackgroundCardio Metabolic Syndrome: A Global Epidemic
Kelli, H. M., & Kassas, I. (2015) · Journal of Diabetes & Metabolism · doi:10.4172/2155-6156.1000513 · Cited by 70 · see citing works
“North America ranked lower than Western Europe in cholesterol levels [52].”
BackgroundMetabolic Issues With Atypical Antipsychotics in Primary Care
Kabinoff, G. S., Toalson, P. A., Healey, K. M., McGuire, H. C., & Hay, D. P. (2003) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.v05n0103 · Cited by 67 · see citing works
Abdel‐Aziz, A. A. ‐., El‐Azab, A. S., Attia, S. M., et al. (2011) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2011.07.002 · Cited by 65 · see citing works
Wagner, K., Tomasch, R., & Elmadfa, I. (2001) · European Journal of Nutrition · doi:10.1007/s003940170004 · Cited by 62 · see citing works
Matzno, S., Yasuda, S., Juman, S., Yamamoto, Y., Nagareya-Ishida, N., Nakabayashi, T., Matsuyama, K., & Tazuya-Murayama, K. (2005) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.57.11.0014 · Cited by 59 · see citing works
“Several clinical studies alerted to the massive rhabdomyolysis and life threatening hyperkalaemia in a patient administered the combination of cerivastatin and gemfibrozil (Rubins 2000; Hendriks et al 2001; Shek & Ferrill 2001; Marsa-Carretero et al 2002).”
BackgroundLi, Y., Zhang, D., He, Y., Chen, C., Song, C., Zhao, Y., Bai, Y., Wang, Y., Pu, J., Chen, J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-15737-3 · Cited by 54 · see citing works
Alanazi, M. M., Almehizia, A. A., Bakheit, A. H. H., et al. (2018) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2018.12.001 · Cited by 54 · see citing works
“The biological activities of N-substituted phthalimides is well established (Cullen, 2000; Krauss,1998; Rubins, 2000; Rubins and Robins, 2000).”
Peroxisome proliferator-activated receptors: are they involved in atherosclerosis progression?
Puddu, P., Puddu, G. M., & Muscari, A. (2003) · International Journal of Cardiology · doi:10.1016/s0167-5273(02)00565-x · Cited by 47 · see citing works
Beyond LDL-C – The Importance of Raising HDL-C
Wierzbicki, A. S., & Mikhailidis, D. P. (2002) · Current Medical Research and Opinion · doi:10.1185/030079902125000165 · Cited by 47 · see citing works
The dilemma of the metabolic syndrome in children and adolescents: disease or distraction?
Jones, K. L. (2006) · Pediatric Diabetes · doi:10.1111/j.1399-5448.2006.00212.x · Cited by 45 · see citing works
“Fibrates are effective drugs for reducing hypertriglyceridemia and cardiovascular risk (63).”
BackgroundSanada, M., Tsuda, M., Kodama, I., Sakashita, T., Nakagawa, H., & Ohama, K. (2004) · Menopause The Journal of The North American Menopause Society · doi:10.1097/01.gme.0000094211.15096.b4 · Cited by 38 · see citing works
“cholesterol;(12) predominance of potentially atherogenic, small, dense, LDL particles;(13) resistance to insulin-mediated, glucose uptake;(14) and predispositions to coagulation abnormalities,(15) and hypertension.(16) The WHI finding that estrogen plus progestin does not confer benefit for preventing CHD among women…”
ResultWierzbicki, A. S., Clarke, R. E., Viljoen, A., & Mikhailidis, D. P. (2012) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e328353adc1 · Cited by 37 · see citing works
“All these studies showed that CVD event rates were greater in patients with higher baseline triglyceride and lower HDL-C levels [51].”
BackgroundEwart, H. S., Cole, L., Kralovec, J. A., Layton, H., Curtis, J. M., Wright, J. L. C., & Murphy, M. (2002) · Journal of Nutrition · doi:10.1093/jn/132.6.1149 · Cited by 37 · see citing works
Free fatty acid metabolism during fenofibrate treatment of the metabolic syndrome
Vega, G. L. (2003) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(03)00170-x · Cited by 37 · see citing works
Prevalence of metabolic syndrome and cardiovascular disease in a hypertriglyceridemic population
Ascaso, J. F., Millán, J., Mateo‐Gállego, R., Ruiz, A., Tembra, M. S., Borrallo, R. M., Zambón, D., González‐Santos, P., Peres-de-Juan, M., & Ros, E. (2011) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2010.12.011 · Cited by 34 · see citing works
“Hypertriglyceridemia has also been considered by others [7,8] as an independent factor for cardiovascular risk.”
Síndrome metabólico: una mirada interdisciplinaria
Barrera, M. D. P., Pinilla, A. E., Cortés, É., Mora, G., & Rodríguez, M. N. (2008) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 25 · see citing works
Hypolipidemic therapy for the metabolic syndrome
Cignarella, A., Bellosta, S., Corsini, A., & Bolego, C. (2006) · Pharmacological Research · doi:10.1016/j.phrs.2006.03.012 · Cited by 27 · see citing works
Zhong, Z., Liu, J., Zhang, Q., Zhong, W., Li, B., Li, C., Liu, Z., Yang, M., & Zhao, P. (2019) · Medicine · doi:10.1097/md.0000000000014309 · Cited by 25 · see citing works
Alcohol Use and Prognosis in Patients With Coronary Heart Disease
Mukamal, K. J. (2003) · Preventive Cardiology · doi:10.1111/j.1520-037x.2003.01333.x · Cited by 23 · see citing works
Genetics and Prevention: A New Look at High-Density Lipoprotein Cholesterol
Genest, J. J. (2002) · Cardiology in Review · doi:10.1097/00045415-200201000-00011 · Cited by 22 · see citing works
“The disorder is highly heterogeneous and likely results from several genes, with a strong environmental influence (33).”
BackgroundUpdate on perioperative evaluation and management of cardiac disease in vascular surgery patients
Krupski, W. C. (2002) · Journal of Vascular Surgery · doi:10.1067/mva.2002.129647 · Cited by 22 · see citing works
The Metabolic Syndrome and Cardiometabolic Risk: Scope of the Problem and Current Standard of Care
Lender, D., & Clough, S. S. (2006) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.26.5part2.3s · Cited by 19 · see citing works
Luo, J. J., Chang, H., Chang, S., Chou, T., Chen, C., Shih, T., & Huang, C.-C. (2003) · Journal of Occupational and Environmental Medicine · doi:10.1097/00043764-200301000-00015 · Cited by 18 · see citing works
Interplay between proteins and metabolic syndrome–A review
Miglani, N., & Bains, K. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2014.938259 · Cited by 16 · see citing works
“Clinical trials confirm a reduction in cardiovascular risk from treatment of dyslipidemia (Ballantyne et al., 2001; Rubins, 2000; Rubins et al., 2002; Goldberg et al., 1998; Haffner et al., 1999; Collins et al., 2003) and hypertension (Chobanian et al., 2003).”
BackgroundMahajan, R., Gupta, K., & Kapoor, V. (2010) · International Journal of Pharmacology · doi:10.3923/ijp.2010.338.345 · Cited by 14 · see citing works
Audit of monitoring of the parameters of metabolic syndrome in patients on clozapine
Tully, J., Sim, C., Hemani, R., et al. (2012) · The Psychiatrist · doi:10.1192/pb.bp.111.037994 · Cited by 13 · see citing works
“18 Fibrates have been shown to reduce end-points of cardiovascular disease in patients with atherogenic dyslipidaemia and metabolic syndrome 19 and may serve as an important adjunct in overweight patients with elevated triglyceride and low high-density lipoprotein cholesterol.”
Managing cardiovascular risk in patients with metabolic syndrome
Bassand, J. (2006) · Clinical cornerstone · doi:10.1016/s1098-3597(06)80003-7 · Cited by 13 · see citing works
The metabolic syndrome: An exercise in utility or futility?
SADIKOT, S. M., & Misra, A. (2007) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2006.11.001 · Cited by 12 · see citing works
Assessment of Compliance with Lipid Guidelines in an Academic Medical Center
Schwiesow, S. J., Nappi, J. M., & Ragucci, K. R. (2005) · Annals of Pharmacotherapy · doi:10.1345/aph.1g303 · Cited by 11 · see citing works
“Of the 287 patients who were included in the study, 69% (199) wereprescribed a statin, 3% (9)a fibrate,”
BackgroundEpidemiology of Coronary Heart Disease in the Elderly
Vokonas, P., & Kannel, W. B. (2008) · Fundamental and clinical cardiology · doi:10.3109/9781420061710.008 · Cited by 12 · see citing works
Enhancing the treatment of metabolic syndrome with integrative medicine
Wang, W. (2013) · Journal of Chinese Integrative Medicine · doi:10.3736/jintegrmed2013033 · Cited by 9 · see citing works
Modulation of Lipoprotein Metabolism by Antisense Technology: Preclinical Drug Discovery Methodology
Crooke, R. M., & Graham, M. J. (2013) · Methods in molecular biology · doi:10.1007/978-1-60327-369-5_14 · Cited by 9 · see citing works
La cintura hipertrigliceridémica
Ascaso, J. F. (2005) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/s0214-9168(05)73357-x · Cited by 7 · see citing works
Valor de la dislipemia en el conjunto de los factores de riesgo cardiovascular
Barrios, V., & Escobar, C. (2011) · Revista Española de Cardiología Suplementos · doi:10.1016/s1131-3587(11)70012-7 · Cited by 6 · see citing works
Kapinová, A., Kubatka, P., Kružliak, P., et al. (2015) · Biologia · doi:10.1515/biolog-2015-0025 · Cited by 4 · see citing works
Mohan, V. K., & George, M. (2021) · Current Research in Nutrition and Food Science Journal · doi:10.12944/crnfsj.9.3.01 · Cited by 4 · see citing works
Recomendaciones específicas para el manejo del paciente con síndrome metabólico
Medina, L. V., Jiménez, M. L., & Carretero, R. G. (2007) · Hipertensión y Riesgo Vascular · doi:10.1016/s1889-1837(07)71859-7 · Cited by 2 · see citing works
Perón, J. M. R., González, S. R. M., Cabrera, E. B. A., et al. (2002) · Revista cubana de medicina militar · Cited by 3 · see citing works
Recomendaciones específicas para el manejo del paciente con síndrome metabólico
Medina, L. V., Jiménez, M. L., & Carretero, R. G. (2007) · Hipertensión · doi:10.1016/s0212-8241(07)72441-6 · Cited by 2 · see citing works
Role of PPARs in the Pathogenesis of the Metabolic Syndrome
Medina‐Gómez, G., Gray, S. L., & Vidal‐Puig, A. (2005) · Elsevier eBooks · doi:10.1016/b978-84-8174-892-5.50015-2 · Cited by 2 · see citing works
Síndrome metabólico: ¿cómo diagnosticarlo y cómo tratarlo?
Ascaso, J. F., & Carmena, R. (2006) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/s0214-9168(06)73706-8 · Cited by 1 · see citing works
patients on clozapine Audit of monitoring of the parameters of metabolic syndrome in
Tully, J., Sim, C., Hemani, R., et al. (2014) · Cited by 1 · see citing works
Cytochrome P450: Another Player in the Myocardial Infarction Game?
Sunder‐Plaßmann, R. (2006) · Advances in clinical chemistry · doi:10.1016/s0065-2423(06)43008-0 · Cited by 1 · see citing works
Okwuosa, T. M. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-502-6_11
Atherosclerosis and Antihyperlipidemic Agents
Gad, L. M. (2012) · InTech eBooks · doi:10.5772/38881
Therapie von Fettstoffwechselstörungen, Harnsäurediathese bzw. Gicht
Krappweis, J. (2003) · Springer eBooks · doi:10.1007/978-3-662-09397-9_19
Mahtab, H., Mahmud, R. S., Pervin, K., et al. (2012) · BIRDEM Medical Journal · doi:10.3329/birdem.v2i1.12354
Smith, C. S., Spertus, J. A., Franklin, B. A., Gordon, D. J., Krauss, R. M., Savage, P. J., Grundy, S. M., Cleeman, J. I., Daniels, S. R., & Donato, K. A. (2006)
A REVIEW ON METABOLIC SYNDOME: BIOCHEMICAL INVESTIGATIONS
Khalil, S. S., Ahmed, A. I., Mohammed, N. A., El-Naggar, A. A., Ali, H. A., Al-Saadawy, H. A., & Ahmad, K. R. E. (2018) · Slovenian Veterinary Research · doi:10.26873/svr-670-2018
“Also, fibrates used to relieve the symptoms of athe rogenic, dyslipidaemia and enhance CVD diseases (110,111).”
BackgroundCHRONIC INTERACTION BETWEEN METFORMIN AND MELOXICAM IN MICE
Al-Rekabi, F. M. K. (2019) · Asian Journal of Pharmaceutical and Clinical Research · doi:10.22159/ajpcr.2019.v12i2.29947
“Measurement of TG and total blood cholesterol is important in the diagnosis and management of hyperlipidemia, hypertriglyceridemia refers to high TG levels in the blood [45,46].”
BackgroundSchaarschmidt, W. (2010) · Qucosa (Saxon State and University Library Dresden)
Therapie von Fettstoffwechselstörungen, Harnsäurediathese bzw. Gicht
Schindler, C. (2006) · Springer eBooks · doi:10.1007/3-540-29812-6_18
Management of Cholesterol Disorders
Grundy, S. M. (2007) · Springer eBooks · doi:10.1007/978-1-84628-715-2_131
- Authors
- Rubins, H. B.
- Venue
- European Journal of Cardiovascular Risk
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-10
- Volume
- 7
- Issue
- 5
- Pages
- 339-345
- ISSN
- 1741-8267 (ISSN-L)
- 1741-8275
- OpenAlex
- W1952202554
- Cited by
- 69
- References
- 0
- Citations by year
- 2021: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 4
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Cardiovascular Prevention & Rehabilitation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Office of Research and Development
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- triglycerides, hypertriglyceridemia, coronary artery disease, atherosclerotic cardiovascular disease, fibrate therapy, bezafibrate, Helsinki Heart Study, HDL cholesterol, metabolic syndrome, cardiovascular risk markers, primary prevention, secondary prevention
- MeSH terms
- Aged, Hypolipidemic Agents, Bezafibrate, Coronary Artery Disease, Female, Humans, Male, Middle Aged, Prognosis, Triglycerides, Hypertriglyceridemia, Gemfibrozil, Treatment Outcome, Controlled Clinical Trials as Topic
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