Management of dyslipidemia in adults - includes patient information

Author: Syed M. Ahmed, John F. Donnelly
Date: May 1, 1998

Dyslipidemias are disorders of lipoprotein metabolism, including lipoprotein overproduction or deficiency. These disorders may be manifested by elevation of the serum total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride concentrations, and a decrease in the high-density lipoprotein (HDL) cholesterol concentration.

Epidemiologic, angiographic and post-mortem studies have documented a causal relationship between elevated serum cholesterol levels and the genesis of coronary heart disease. Angiographic studies show that aggressive cholesterol reduction by a variety of methods, as opposed to dietary modifications alone, results in increased rates of plaque regression and stabilization.[1] Treatment with cholesterol-lowering drugs appears to be accompanied by a reduction in the lipid content of atherosclerotic plaques, thereby making them more stable and less prone to rupture.[2,3] The Scandinavian Simvastatin Survival Study[4] demonstrated a 30 percent reduction in total mortality in simvastatin-treated patients with coronary heart disease as compared with patients not receiving this agent. In a primary prevention trial,[5] patients treated with pravastatin showed a 26 percent reduction in LDL cholesterol levels and a 31 percent reduction in coronary events (nonfatal myocardial infarction or death from coronary heart disease) as compared with the placebo group.

Even after recognizing the controversies surrounding cholesterol screening and therapy,[6,7] most experts emphasize the importance of treating hypercholesterolemia.[8-10] While guidelines for treating dyslipidemias may lack uniformity, much common ground exists for the management of dyslipidemias.[11] The recommendations in this article are primarily based on the guidelines from the National Cholesterol Education Program (NCEP).[12]

Diagnosis and Classification

Secondary causes of dyslipidemia include hypothyroidism and a genetic predisposition, such as autosomal dominant familial hypercholesterolemia (Table 1).[13] Triglyceride elevation may occur in association with diabetes mellitus, alcoholism, obesity and hypothyroidism. Dyslipidemias have been traditionally classified in accordance with the elevated lipoprotein classes (Table 2).[14] Currently, genetic dyslipidemias are classified as familial hypercholesterolemia, familial combined hyperlipidemia and polygenic: hypercholesterolemia.

TABLE 1Selected Causes of Secondary DyslipidemiaIncreased LDL cholesterol levelDiabetes mellitusHypothyroidismNephrotic syndromeObstructive liver diseaseDrugsAnabolic steroidsProgestinsBeta-adrenergic blockers (without intrinsic sympathomimetic action)ThiazidesIncreased triglyceride levelAlcoholismDiabetes mellitusHypothyroidismObesityRenal insufficiencyDrugsBeta-adrenergic blockers (without intrinsic sympathomimetic action)Bile acid-binding resinsEstrogensTiclopidine (Ticlid)Decreased HDL cholesterol levelCigarette smokingDiabetes mellitusHypertriglyceridemiaMenopauseObesityPuberty (in males)UremiaDrugsAnabolic steroidsBeta-adrenergic blockers (without intrinsic sympathomimetic action)Progestins

LDL = low-density lipoprotein; HDL = high-density lipoprotein.

Adapted with permission from Schaefer EJ. Diagnosis and management of lipoprotein disorders. In: Rifkind BM, ed. Drug treatment of hyperlipidemia. New York: Dekker 1991:17-52.

TABLE 2Fredrickson Classification of the Dyslipidemias(*)Legends forA = 2 arrow upB = 3 arrow upC = 4 arrow upPhenotype Lipoprotein(s) elevated Serum cholesterol levelI Chylomicrons Normal to [arrow up]IIa LDL 2 arrow upIIb LDL and VLDL 2 arrow upIII IDL 2 arrow upIV VLDL Normal to [arrow up]V VLDL and chylomicrons Normal to [arrow up]Phenotype Serum triglyceride level AtherogenicityI 4 arrow up None seenIIa Normal +++IIb 2 arrow up +++III 3 arrow up +++IV 2 arrow up +V 4 arrow up +

LDL low-density lipoprotein; IDL intermediate-density lipoprotein; VLDL = very-low-density lipoprotein; HDL high-density lipoprotein; [arrow up] mildly increased; 2 arrow up = moderately increased; 3 arrow up = severely increased; 4 arrow up = very severely increased; + mild to moderate atherogenicity; +++ = severe atherogenicity.

(*)--HDL cholesterol levels are not considered in the Fredrickson classification.

Adapted from Fredrickson DS, Levy RI, Lees RS. Fat transport in lipoproteins--an integrated approach to mechanisms and disorders. N Engl J Med 1967;276:34-42, 94-103, 148-56, 215-25,273-81.

The NCEP guidelines, however, are based on clinical cut points that indicate relative risk for coronary heart disease. Included in the guidelines is the general recommendation that total cholesterol and HDL cholesterol levels be measured every five years beginning at age 20 in patients who do not have coronary heart disease or other atherosclerotic disease. Both of these measurements may be obtained in the nonfasting state. The results of these measurements and the presence of other risk factors for coronary heart disease may demand a more comprehensive lipoprotein analysis (Table 3).[12]

TABLE 3 Coronary Heart Disease Risk Based on Risk Factors Other Than the LDL Level

Positive risk factorsMale [is greater than or equal to] 45 yearsFemale [is greater than or equal to] 55 years or postmenopausal without estrogen replacement therapyFamily history of premature coronary heart disease (definite myocardial infarction or sudden death before age 55 in father or other male first-degree relative or before age 65 in mother or other female first-degree relative)Current cigarette smokingHypertension (blood pressure [is greater than or equal to] 140/90 mm Hg or patient is receiving antihypertensive drug therapy)HDL cholesterol level <35 mg per dL (<0.90 mmol per L)Diabetes mellitusNegative risk factor(*)High HDL cholesterol level ([is greater than or equal to] 60 mgper dL [[is greater than or equal to] 1.60 mmol per L])

LDL = low-density lipoprotein; HDL = high-density lipoprotein.

(*)--Subtract one positive risk factor if negative risk factor is present

Adapted from National Cholesterol Education Program. Second report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (adult treatment panel II). Bethesda, Md.: National Cholesterol Education Program, National Institutes of Health, National Heart, Lung, and Blood Institute, 1993; DHSS publication no. (NIH) 93-3095:5.

The LDL cholesterol level can be measured directly or can be calculated by using the Friedwald formula (measurement is expressed in milligrams per deciliter):

LDL = total cholesterol - HDL - (triglyceride/5)

This formula cannot be used when the triglyceride level is greater than 400 mg per dL (4.50 mmol per L) or when patients have type III hyperlipoproteinemia.

While cholesterol levels are classified into desirable, borderline high-risk and high-risk categories (Table 4),[12] decisions regarding the treatment of hypercholesterolemia are based on the LDL cholesterol level and the presence or absence of other risk factors for coronary heart disease. Two or three fasting LDL measurements must be averaged to classify the patient's risk.

TABLE 4 Risk classification of Hypercholesterolemia in Patients Without Coronary Heart Disease

Classification Total cholesterol levelDesirable 200 mg per dL (5.15 mmol per L)Borderline 200 to 239 mg per dL high risk (5.15 to 6.20 mmol per L)High risk [is greater than or equal to] 240 mg per dL ([is greater than or equal to] 6.20 mmol per L)Classification LDL cholesterol levelDesirable < 130 mg per dL (<3.35 mmol per L)Borderline 130 to 159 mg per dL high risk (3.35 to 4. 10 mmol per L)High risk 160 mg per dL ([is greater than or equal to] 4.15 mmol per L)Classification HDL cholesterol levelDesirable [is greater than or equal to] 60 mg per dL ([is greater than or equal to] 1.55 mmol per L)Borderline 35 to 59 mg per dL high risk (0.90 to 1.55 mmol per L)High risk < 35 mg per dL (< 0.90 mmol per L)

LDL = low-density lipoprotein; HDL = high-density lipoprotein.

[34.] Bostorn AG, Cupples LA, Jenner JL, Ordovas JIM, Seman LJ, Wilson PW, et al. Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study JAMA 1996;276:544-8.

[35.] Chapman MJ, Huby T, Nigon F, Thillet J. Lipoprotein (a): implication in atherothrombosis. Atherosclerosis 1994;110(Suppl):S69-75.

[36.] Kinlay S, Dobson AJ, Heger RF, McElduff P, Alexander H, Dickeson J. Risk of primary and recurrent acute myocardial infarction from lipoprotein (a) in men and women. J Am Coll Cardiol 1996;28:870-5.

[37.] Darling GM, Johns JA, McCloud PI, Davis SR. Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women. N Engl J Med 1997;337:595-601.

[38.] Grodstein F, Stamper MJ, Colditz GA, Willett WC, Manson JE, Joffe M, et al. Postmenopausal hormone therapy and mortality. N Engl J Med 1997; 336:1769-75.

[39.] Davidson MH, Testolin LM, Maki KC, von Duvillard 5, Drennan KB. A comparison of estrogen replacement, pravastatin, and combined treatment for the management of hypercholesterolemia in postmenopausal women. Arch Intern Med 1997; 157:1186-92.

[40.] Keller C. LDL-apheresis: results of long-term treatment and vascular outcome. Atherosclerosis 1991; 86:1-8.

[41.] Buchwald H, Varco RL, Matts JP, Long JM, Fitch LL, Campbell GS, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of Hyperlipidemias (POSCH), N Engl J Med 1990;323:946-55.

Each year members of a different medical faculty prepare articles for "Practical Therapeutics." This series is coordinated by the Department of Family Medicine at Wright State University School of Medicine, Dayton, Ohio. Guest editors of the series are Cynthia G. Olsen, M.D., and Gordon S. Walbroehl, M.D.

SYED M. AHMED, M.D., M.P.H., DR.P.H., is an assistant professor of family medicine at Wright State University School of Medicine and the Miami Valley Hospital family medicine residency program, both in Dayton, Ohio. He is a graduate of Sir. Salimullah Medical College, Dhaka University, Dhaka. He completed a residency and fellowship in family medicine at Baylor College of Medicine, Houston. He obtained both a masters degree and a doctorate in public health from the University of Texas School of Public Health, Houston.

MARK E. CLASEN, M.D., PH.D., is chairman of the Department of Family Medicine at Wright State University School of Medicine. He completed a residency in family medicine at the University of Mississippi Medical Center, Jackson. He has a certificate of added qualification in geriatrics. He is also president of University Medical Services Association, Dayton, Ohio.

JOHN F. DONNELLY, M.D., is associate professor in the Department of Family Medicine at Wright State University School of Medicine. He received a medical degree from the University of Texas-Houston Medical School and completed a residency in family medicine at Memorial Hospital Family Practice Residency Program in Houston.

Address correspondence to Syed M. Ahmed, M.D., M.P.H., Dr.P.H., Department of Family Medicine, East Dayton Health Center 2132 E Third St., Dayton, OH 45403. Reprints are not available from the authors.

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