To illustrate the heterogeneity that exists among various dyslipidemias, some of the different primary (inherited) and secondary disorders associated with each lipoprotein phenotype are outlined in Table 27-1. Major apolipoproteins associated with chylomicrons and very low density lipoproteins (VLDL) are B, C, and E; with low-density lipoproteins (LDL), B; and with high-density lipoproteins (HDL), A-I and A-II.
Causes of secondary hyperlipidemia must be sought and treated. Secondary hypercholesterolemia may be associated with hypothyroidism, nephrotic syndrome, obstructive liver disease, acute intermittent porphyria, pregnancy, anorexia nervosa, and certain drugs (such as thiazide diuretics, retinoids, glucocorticoids, cyclosporine, progestins, and androgens). Secondary hypertriglyceridemia may result from diabetes mellitus, obesity, alcohol intake, excess intake of refined sugars, chronic renal failure, myocardial infarction, infections (bacterial, viral), systemic lupus erythematosus, dysglobulinemia, glycogen storage disease (type I), lipodystrophy, nephrotic syndrome, bulimia, autoimmune disorders, pregnancy, and certain drugs (such as beta-adrenergic blockers, retinoids, and estrogens). The most common causes of secondary combined hyperlipidemia include hypothyroidism, nephrotic syndrome, chronic renal failure, liver disease, Werner’s syndrome, acromegaly, and certain drugs such as thiazide diuretics, glucocorticoids, and retinoids.
Blood lipid abnormalities (particularly elevated levels of LDL cholesterol [LDL-C]; low levels of HDL, HDL2, and HDL cholesterol [HDL-C]; and high levels of fasting triglycerides), which contribute to craniocervical atherosclerosis, are important risk factors for ischemic stroke (more in Western societies than in Asian populations). There is also limited evidence of an inverse association between serum cholesterol values and the risk for intracerebral hemorrhage or subarachnoid hemorrhage. Correction of these and other lipid abnormalities that lead to atherosclerosis is expected to be beneficial primarily for the prevention of atherosclerotic ischemic stroke.
Therapy for lipid disorders must be individualized and includes dietary changes (the basic and preferred initial step for most patients), maintenance of ideal body weight, aerobic exercise, and pharmacologic agents. Current guidelines1 recommend initiation of moderate- or high-intensity statin therapy for: (1) individuals with clinical atherosclerotic cardiovascular disease (ASCVD) such as coronary heart disease (CHD) and stroke; (2) individuals with primary elevation of LDL-C greater than or equal to 190 mg per dL; (3) individuals 40 to 75 years of age with diabetes and an LDL-C 70 to 189 mg per dL without clinical ASCVD; and (4) individuals without clinical ASCVD or diabetes who are 40 to 75 years of age with LDL-C 70 to 189 mg per dL and a 10-year ASCVD risk greater than or equal to 7.7%, as determined by the Pooled Cohort Risk Assessment Equations.2,3 In the Heart Outcomes Prevention Evaluation-3 trial, lipid-lowering therapy with statin (rosuvastatin 10 mg a day) in individuals (men ≥55 years; women ≥65 years) without established cardiovascular disease (CVD) who had at least one CVD risk factor (elevated waist-to-hip ratio, history of low HDL-C, current or recent tobacco use, dyslipidemia, family history of premature coronary artery disease, or mild renal dysfunction) led to a reduction in CVD events (reduction from 4.8% to 3.7% during a median follow-up of 5.6 years).4
TABLE 27-1 Classification of Primary and Secondary Blood Lipid Disorders
