Treatment of Lipid Abnormalities

74 Treatment of Lipid Abnormalities



Ross J. Simpson, Jr., Sidney C. Smith, Jr.


For most individuals at risk of coronary heart disease (CHD), elevated serum lipid levels are a dominant modifiable risk factor. Lipid levels can be modified by several types of interventions—appropriate dietary, exercise, and drug programs to lower key components of serum lipid levels—which together represent the most important strategies for reducing an individual’s risk for CHD. This chapter reviews mechanisms by which key blood lipid components can be altered favorably.


Low-density lipoprotein cholesterol (LDL-C) levels are strongly associated with atherosclerosis and CHD events. The lowering of LDL-C levels with drug and diet therapies is consistently related to a reduction in CHD events. The Heart Protection Study demonstrated that, among patients with known cardiovascular disease, regardless of the initial cholesterol value, the lowering of LDL-C with simvastatin, an inhibitor of the enzyme HMG-CoA reductase (which, as part of the mevalonate pathway, controls the rate of cholesterol synthesis), substantially lowers the risk for subsequent CHD events. The Heart Protection Study reaffirmed the primary importance of reducing LDL-C levels in individuals at high risk for CHD events and provided strong evidence that LDL-C reduction should remain the focus of preventive efforts.


High-density lipoprotein cholesterol (HDL-C) levels are influenced by diet, exercise, alcohol, exogenous estrogens, obesity, smoking, diabetes, and certain drugs (e.g., diuretics and anabolic steroids). Of these factors, exercise, estrogens, and alcohol are known to increase HDL-C. However, it should be emphasized that for both estrogens and alcohol, the primary evidence suggesting a benefit in reducing cardiac risk is epidemiologic, and neither is recommended for prevention. Estrogen administration in postmenopausal women has been studied extensively, and currently estrogen is not recommended as a primary or secondary prevention measure for atherosclerotic cardiovascular disease. The cardiovascular benefits of alcohol have been demonstrated in surveys of individuals only among those whose alcohol consumption is in the range of 1 to 3 ounces per day. Initiation of alcohol consumption to reduce cardiovascular risk is not recommended because of the potential for alcohol abuse.


Although a strong inverse relationship exists between HDL-C levels and CHD risk, clinical evidence is not adequate to support the primary use of therapies to increase HDL-C to reduce CHD events independent of lowering LDL-C or triglyceride levels. Moreover, the results of therapy with drugs that raise HDL-C levels often are not as consistent as are the results of drug therapies used to lower LDL-C levels. In the absence of compelling data from large populations of both sexes, the National Cholesterol Education Program (NCEP) recommends that treatment of HDL-C not be the primary therapeutic strategy, but instead that the initial focus be on reducing LDL-C. Increased HDL-C remains a secondary goal. Although recent studies were done on small numbers of individuals using various strategies to increase HDL-C, large randomized clinical trials are needed to ascertain whether therapies that raise HDL-C levels are useful as a primary strategy for CHD prevention.


Triglycerides are important plasma lipids found in varying concentrations in all plasma lipoproteins. The relationship between plasma triglycerides and CHD is debated. Moderately elevated triglycerides are often found in nephrotic syndrome, metabolic syndrome, diabetes, and hypothyroidism. Although triglyceride levels seem to be associated with CHD, there is only limited evidence that lowering triglyceride levels has a protective effect in terms of CHD events. Therapies to lower triglyceride levels are well established and include treatment of the underlying diseases, such as diabetes, reduction of the dietary intake of simple carbohydrates, weight loss, alcohol avoidance, and increased exercise. In patients with diabetes, control of diabetes with a hemoglobin A1C goal of less than 7% should be the first therapeutic strategy. Very high levels of triglycerides (>500 mg/dL) are associated with the development of pancreatitis and eruptive xanthomas and should be treated intensively with therapy targeted to lower triglycerides for these indications.



Diagnostic Approach


Lipids are commonly measured by β quantification: total cholesterol, triglycerides, and HDL-C levels are measured directly; LDL-C levels are estimated by the Friedewald equation (LDL-C = total cholesterol − HDL-C − [triglycerides/5]). The LDL-C measurement is useful for monitoring lipid therapy and for assessing a patient’s risk for a CHD event. In general, as with the other lipid profile components, measurement of LDL-C on a single occasion is not a basis for therapeutic intervention. For patients for whom long-term therapy is indicated, two fasting measurements of the lipoprotein profile, taken at least 1 week apart, should be obtained.


Direct measurement of LDL-C levels, particle size, and particle density can be accomplished by ultracentrifugation, gradient gel electrophoresis, and MRI methods. While measurement of lipoprotein (a) and other lipid fractions may provide additional information on the lipid lipoprotein characteristics, detailed clinical studies that indicate the usefulness of drugs that target these individual lipid components have yet to be reported. In many patients, it is useful to measure these components to further assess risk and occasionally to guide therapy. However, the primary focus is still on lowering LDL-C through drug therapy, diet, and exercise.


Lipid management requires the assessment of the patient’s short-term (10-year) risk for CHD events. The therapy and specific goals are then based on the patient’s absolute risk for a CHD event. The NCEP Adult Treatment Panel III recommends that patients with established coronary disease, diabetes, carotid artery disease, or lower extremity arterial disease be considered to be in the highest risk group (10-year risk >20%). Increasingly, metabolic syndrome and diabetes are becoming dominant cardiovascular risk factors, as the incidence of obesity in the United States and industrialized countries continues to increase (Fig. 74-1; see also Chapter 61). In the absence of such disease, patients’ global risk should be determined by the Framingham risk equation. Global risk is considered high if the 10-year risk is greater than 20%. The global risk of patients in the intermediate-risk (10-year risk of 10%–20%) and low-risk (10-year risk <10%) groups should be considered in light of the presence or absence of major CHD risk factors. The most important CHD risk factors are age (≥45 years for men, ≥55 years for women), a history of premature CHD in a first-degree relative, current cigarette smoking, the presence of hypertension, and HDL-C below 40 mg/dL. Patients with two or more major risk factors in addition to high LDL-C are considered to be at intermediate risk. Patients with one major risk factor in addition to high LDL-C are considered to be at low risk. Using the Framingham risk equation, the 20-year probability of the development of a CHD event can be estimated for patients with two or more risk factors. When the number of risk factors is 0 to 1, the Framingham scoring is not needed (see Chapter 11).


image

Figure 74-1 Metabolic syndrome.


CHD, coronary heart disease; HDL-C, high-density lipoprotein cholesterol; IGT, impaired glucose tolerance; LDL-C, low-density lipoprotein cholesterol; NIDDM, non–insulin-dependent diabetes mellitus; VLDL-C, very-low-density lipoprotein cholesterol.



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Jun 12, 2016 | Posted by in CARDIOLOGY | Comments Off on Treatment of Lipid Abnormalities

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