Curr Treat Options Cardiovasc Med. 2000 Apr;2(2):173-187. doi: 10.1007/s11936-000-0010-5.
Hypercholesterolemia and Dyslipidemia.
Current treatment options in cardiovascular medicine
Superko
Affiliations
Affiliations
- Berkeley HeartLab, Inc., 1875 South Grant Street, Suite 700, San Mateo, CA 94402, USA.
PMID: 11096522
DOI: 10.1007/s11936-000-0010-5
Abstract
Disorders of cholesterol and lipoprotein metabolism are at the heart of atherosclerosis and coronary artery disease (CAD). CAD, however, is a metabolic disorder that involves a complex interaction between genetic susceptibility and environmental conditions. Despite considerable success in the treatment of hypercholesterolemia, atherosclerosis remains the leading cause of death in most Western countries. Although cholesterol-lowering trials have revealed a 25% to 30% reduction in clinical events, most patients continue to have events even when treated successfully with cholesterol-lowering medications (Fig. 1). This less-than-optimal result is partly because atherosclerosis is a multifactorial disease. Although disorders of lipoprotein metabolism are found in more than 80% of patients with CAD, these disorders are very heterogeneous, and single-drug therapy aimed at one disorder should not be expected to improve the disease status in most patients. Metabolic treatment still requires identification and treatment of patients with high cholesterol levels, but the focus has shifted to identifying high-risk patients in groups previously thought to be low risk, or to identifying disorders coexistent with high cholesterol levels that are not corrected by standard cholesterol-lowering medications (Table 1). The ability to detect high-risk CAD traits, which are often inherited, and to predict response to treatment has substantially improved in the past few years. These improvements allow identification of metabolic subgroups of patients, which can alter risk prediction and response to specific treatments. Sophisticated laboratory methods permit physicians to apply this knowledge to patient care and to enter a new era of CAD risk factor detection and treatment. These advances allow for a more scientific approach than did the previously standard epidemiologic risk factors and routine blood lipid profiles. The current state-of-the-art method of diagnosing and treating lipoprotein disorders has progressed beyond the standard "lipid profile," which includes total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol along with fasting triglyceride levels. Incorporating aspects of the atherogenic lipid profile (ALP), LDL subclass distribution, HDL subclass distribution, apo E isoforms, and lipoprotein (a) provides the interested clinician with the tools to create a more detailed and accurate diagnosis of lipoprotein disorders. Sophisticated laboratory tests are available to clinicians through technology transfer programs, as exemplified by the Lawrence Berkeley National Laboratory/Berkeley HeartLab collaboration, and allow clinicians access to research-quality laboratory tools. This has significant clinical relevance because the presence of these disorders guides treatment specific to the disorder(s). Appropriate treatment is more beneficial in subgroups exhibiting the disorder that the therapy is most likely to correct. A single drug or lifestyle therapy is no longer appropriate for all patients. The treatment must match the disorder.
References
- N Engl J Med. 1995 Nov 16;333(20):1301-7 - PubMed
- J Intern Med. 1989 Oct;226(4):271-6 - PubMed
- Artery. 1991;18(6):315-25 - PubMed
- Am J Cardiol. 1998 Nov 5;82(9A):34Q-46Q - PubMed
- J Clin Invest. 1983 Sep;72(3):743-7 - PubMed
- Circulation. 1996 Nov 1;94(9):2146-53 - PubMed
- Circulation. 1995 Feb 15;91(4):948-50 - PubMed
- JAMA. 1992 Jun 24;267(24):3326-9 - PubMed
- Arterioscler Thromb. 1991 Jan-Feb;11(1):174-82 - PubMed
- J Clin Invest. 1987 Apr;79(4):1110-9 - PubMed
- Arteriosclerosis. 1989 Jan-Feb;9(1 Suppl):I8-13 - PubMed
- Arterioscler Thromb. 1993 Aug;13(8):1139-58 - PubMed
- Arterioscler Thromb. 1994 Nov;14 (11):1730-6 - PubMed
- N Engl J Med. 1996 Oct 3;335(14):1001-9 - PubMed
- Am J Cardiol. 1984 Aug 27;54(5):20C-26C - PubMed
- Arteriosclerosis. 1988 Jan-Feb;8(1):1-21 - PubMed
- Arterioscler Thromb. 1991 Nov-Dec;11(6):1737-44 - PubMed
- Arteriosclerosis. 1989 May-Jun;9(3):335-44 - PubMed
- JAMA. 1997 Nov 12;278(18):1509-15 - PubMed
- Pediatr Res. 1993 Nov;34(5):670-4 - PubMed
- Proc Natl Acad Sci U S A. 1989 Jan;86(2):587-91 - PubMed
- Clin Chem. 1990 Jan;36(1):20-3 - PubMed
- J Clin Invest. 1986 Sep;78(3):815-21 - PubMed
- Am J Med. 1993 Jan;94(1):7-12 - PubMed
- Arterioscler Thromb. 1994 Feb;14(2):275-81 - PubMed
- Curr Opin Lipidol. 1996 Dec;7(6):363-8 - PubMed
- Science. 1981 Feb 6;211(4482):584-6 - PubMed
- Arterioscler Thromb. 1993 Dec;13(12):1728-37 - PubMed
- Int J Epidemiol. 1986 Mar;15(1):51-5 - PubMed
- Mol Cell Biochem. 1992 Aug 18;113(2):141-9 - PubMed
- FASEB J. 1995 Jun;9(9):768-76 - PubMed
- J Clin Invest. 1990 Jun;85(6):1709-15 - PubMed
- J Lipid Res. 1986 Mar;27(3):326-33 - PubMed
- Clin Chim Acta. 1981 Jul 18;114(1):45-52 - PubMed
- Arterioscler Thromb. 1993 Apr;13(4):579-89 - PubMed
- Am J Cardiol. 1994 Jun 1;73(15):1037-40 - PubMed
- Med Clin North Am. 1982 Mar;66(2):375-402 - PubMed
- Science. 1988 Apr 29;240(4852):622-30 - PubMed
- Am J Cardiol. 1998 Feb 26;81(4A):52B-59B - PubMed
- Arterioscler Thromb. 1994 Oct;14(10):1586-93 - PubMed
- JAMA. 1994 Apr 6;271(13):999-1003 - PubMed
- Circulation. 1996 Nov 15;94(10):2351-4 - PubMed
- J Clin Invest. 1973 Jul;52(7):1544-68 - PubMed
- JAMA. 1988 Jun 24;259(24):3579-86 - PubMed
- Circulation. 1997 Jan 7;95(1):69-75 - PubMed
- Curr Opin Cardiol. 1995 Jul;10(4):347-54 - PubMed
- Circulation. 1986 Oct;74(4):758-65 - PubMed
- Am J Med. 1994 Oct;97(4):323-31 - PubMed
- Int J Epidemiol. 1989;18(3 Suppl 1):S1-230 - PubMed
- J Clin Invest. 1987 Dec;80(6):1571-7 - PubMed
- Circulation. 1989 Nov;80(5):1313-9 - PubMed
- JAMA. 1995 Dec 13;274(22):1771-4 - PubMed
- Atherosclerosis. 1985 Nov;57(2-3):293-301 - PubMed
- Lancet. 1994 Nov 19;344(8934):1383-9 - PubMed
- Proc Natl Acad Sci U S A. 1980 Jan;77(1):604-8 - PubMed
- Science. 1993 Aug 13;261(5123):921-3 - PubMed
- Circulation. 1982 Dec;66(6):1176-8 - PubMed
- JAMA. 1984 Jan 20;251(3):351-64 - PubMed
- Diabetes. 1988 Dec;37(12):1595-607 - PubMed
- Metabolism. 1993 Nov;42(11):1461-7 - PubMed
- Circulation. 1966 Oct;34(4):679-97 - PubMed
- Metabolism. 1991 Feb;40(2):217-21 - PubMed
- Am Heart J. 1987 Feb;113(2 Pt 2):589-97 - PubMed
- Circulation. 1974 Mar;49(3):476-88 - PubMed
- JAMA. 1990 Dec 19;264(23 ):3007-12 - PubMed
- Curr Opin Lipidol. 1994 Oct;5(5):339-49 - PubMed
- Lancet. 1991 Jan 26;337(8735):203-4 - PubMed
- N Engl J Med. 1986 Mar 13;314(11):671-7 - PubMed
Publication Types