Familial Combined Hyperlipidemia

This inherited disorder, present in 1/200 persons, can cause different lipoprotein abnormalities in affected individuals, including hypercholesterolemia (elevated LDL), hypertriglyceridemia (elevated triglycerides and VLDL), or both. Atherosclerosis is accelerated. A mixed dyslipidemia (plasma triglycerides 2.3-9.0 mmol/L [200-800 mg/dL], cholesterol levels 5.2-10.3 mmol/L [200-400 mg/dL], and HDL levels <10.3 mmol/L [<40 mg/dL] in men and <12.9 mmol/L [<50 mg/dL] in women) and a family history of hyperlipidemia and/or premature cardiovascular disease suggest the diagnosis of FCHL. Many of these pts also have the metabolic syndrome (Chap. 120 Metabolic Syndrome), and it may be difficult to differentiate familial from secondary causes of hyperlipidemia. All pts should restrict dietary cholesterol and fat and avoid alcohol and oral contraceptives; pts with diabetes should be treated aggressively. An HMG-CoA reductase inhibitor is usually required, and many pts will require a second drug (cholesterol absorption inhibitor, niacin, or fibrate) for optimal control.

Dysbetalipoproteinemia

This rare genetic disorder is associated with homozygosity for an apoprotein variant (apoE2) that has reduced affinity for the LDL receptor. Development of disease requires additional environmental and/or genetic factors. Plasma cholesterol (6.5-13.0 mmol/L [250-500 mg/dL]) and triglycerides (2.8-5.6 mmol/L [250-500 mg/dL]) are increased due to accumulation of VLDL and chylomicron remnant particles. Pts usually present in adulthood with xanthomas and premature coronary and peripheral vascular disease. Cutaneous xanthomas are distinctive, in the form of palmar and tuberoeruptive xanthomas. Triglycerides and cholesterol are both elevated. Diagnosis is established by lipoprotein electrophoresis (showing a broad beta band) or a ratio of VLDL (by ultracentrifugation) to total plasma triglycerides of >0.3. The disorder is associated with accelerated atherosclerosis. Dietary modifications should be instituted, and HMG-CoA reductase inhibitors, fibrates, and/or niacin may be necessary. Comorbidities, such as diabetes mellitus, obesity, or hypothyroidism, should be optimally managed.