Abstract
Plasma low density lipoprotein (LDL) plays a central role in atherogenesis, and elevated
levels of LDL are associated with an increased risk of coronary heart disease (CHD).
Studies have now revealed that LDL is structurally heterogeneous, based on its size
and density. Patients with combined hyperlipidemia exhibit a lipid profile — the so-called
atherogenic lipoprotein phenotype — that is associated with elevated triglyceride
levels, low levels of high density lipoprotein and a preponderance of atherogenic,
small, dense LDL particles. Such individuals are at an increased risk of CHD events,
regardless of their total LDL circulating mass. Evidence suggests that when plasma
triglycerides exceed a critical threshold of approximately 133 mg/dl (1.5 mmol/l),
this favours the formation of small, dense LDL from larger, less dense species. Lipid-lowering
agents that are capable of lowering triglyceride levels below this threshold value
will cause a shift to a less dense and, therefore, less atherogenic LDL profile. This
effect has been demonstrated for the HMG-CoA reductase inhibitor atorvastatin which,
in addition to its ability to markedly decrease the total LDL circulating mass, can
also shift the LDL profile towards less dense, larger species. This suggests that
atorvastatin may also affect the atherogenic lipoprotein phenotype found in patients
with combined hyperlipidemia.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to International Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study.J Am Med Assoc. 1986; 256: 2835-2838
- The serum lipoprotein transport system in health, metabolic disorders, atherosclerosis and coronary artery disease.Plasma. 1954; 2: 413
- Heterogeneity of plasma low density lipoprotein manifestations of the physiologic phenomenon in man.Metabolism. 1983; 32: 283
- Detection and quantitation of LDL subfractions.Curr Opin Lipidol. 1992; 3: 377-383
- Low density lipoprotein subfractions and relationships to other risk factors for coronary artery disease in healthy individuals.Arteriosclerosis. 1989; 9: 604-613
- Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk.Atherosclerosis. 1994; 106: 241-253
- Lipoprotein heterogeneity and apolipoprotein B metabolism.Arterioscler Thromb Vasc Biol. 1997; 17: 3542-3556
- Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk.Circulation. 1990; 82: 495-506
- Low density lipoprotein particle size and coronary artery disease.Arterioscler Thromb. 1992; 12: 187-195
- Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfractions in normolipemic men and women.Arterioscler Thromb Vasc Biol. 1995; 15: 1839-1848
- Insulin resistance and hyperinsulinemia in individuals with small, dense, low density lipoprotein particles.J Clin Invest. 1993; 92: 141-146
- Fasting and postprandial determinants for the occurrence of small, dense LDL species in non-insulin dependent diabetic patients with and without hypertriglyceridemia: the involvement of insulin, insulin precursor species and insulin resistance.Atherosclerosis. 1995; 113: 273-287
- Effect of hepatic lipase on LDL in normal men and those with coronary artery disease.Arterioscler Thromb. 1993; 13: 147-153
- Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans.Atherosclerosis. 1996; 124: 261-271
- Different effects of nicotinic acid in subjects with different LDL subclass patterns.Atherosclerosis. 1992; 95: 69-76
- Effects of ciprofibrate on LDL metabolism in man.Atherosclerosis. 1994; 108: 137-148
- Fenofibrate reduces cholesteryl ester transfer from HDL to VLDL and normalises the atherogenic, dense LDL profile in combined hyperlipidemia.Arterioscler Thromb Vasc Biol. 1996; 16: 763-772
- Effects of simvastatin on apoB metabolism and LDL subfraction distribution.Arterioscler Thromb. 1993; 13: 170-189
- A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia.Am J Cardiol. 1997; 80: 39-44
- For the CURVES investigators. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin and fluvastatin in patients with hypercholesterolemia (the CURVES study).Am J Cardiol. 1998; 81: 582-587
Caslake MJ, Forster LF, Stewart G, Roger E, Shepherd J, Packard CJ, Effects of atorvastatin and simvastatin on the LDL subfraction profile in combined hyperlipidemia. Abstract presented at the International Congress on Vascular Disease Prevention, 4–8 May 1998, Glasgow, UK.
Article info
Publication history
Accepted:
June 28,
1999
Identification
Copyright
© 2000 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
