Chapter 181: Hypercholesterolemia and Hypertriglyceridemia

Hyperlipoproteinemia is characterized by hypercholesterolemia, isolated hypertriglyceridemia, or both. Genetic causes of hyperlipoproteinemia are summarized in Table 181-1. Diabetes mellitus, obesity, ethanol consumption, oral contraceptives, glucocorticoids, renal disease, hepatic disease, and hypothyroidism can cause secondary hyperlipoproteinemias or worsen underlying hyperlipoproteinemic states.

TABLE 181-1: Primary Hyperlipoproteinemias Caused by Known Single-Gene Mutations
GENETIC DISORDERPROTEIN (GENE) DEFECTLIPOPROTEINS ELEVATEDCLINICAL FINDINGSGENETIC TRANSMISSIONESTIMATED INCIDENCE
Hypertriglyceridemia
Lipoprotein lipase deficiencyLPL (LPL)Chylomicrons, VLDLEruptive xanthomas, hepatosplenomegaly, pancreatitisAR∼1/1,000,000
Familial apoC-II deficiencyApoC-II (APOC2)Chylomicrons, VLDLEruptive xanthomas, hepatosplenomegaly, pancreatitisAR<1/1,000,000
ApoA-V deficiencyApoA-V (APOA5)Chylomicrons, VLDLEruptive xanthomas, hepatosplenomegaly, pancreatitisAR<1/1,000,000
GPIHBP1 deficiencyGPIHBP1ChylomicronsEruptive xanthomas, pancreatitisAR<1/1,000,000
Combined hyperlipidemia
Familial hepatic lipase deficiencyHepatic lipase (LIPC)VLDL remnants, HDLPancreatitis, CHDAR<1/1,000,000
Familial dysbetalipoproteinemiaApoE (APOE)Chylomicron remnants, VLDL remnantsPalmar and tuberoeruptive xanthomas, CHD, PVDAR∼1/10,000
Hypercholesterolemia
Familial hypercholesterolemiaLDL receptor (LDLR)LDLTendon xanthomas, CHDAD∼1/250 to 1/500
Familial defective apoB-100ApoB-100 (APOB)LDLTendon xanthomas, CHDAD<∼1/1500
Autosomal dominant hypercholesterolemia, type 3PCSK9 (PCSK9)LDLTendon xanthomas, CHDAD<1/1,000,000
Autosomal recessive hypercholesterolemiaARH (LDLRAP)LDLTendon xanthomas, CHDAR<1/1,000,000
SitosterolemiaABCG5 or ABCG8LDLTendon xanthomas, CHDAR<1/1,000,000
Abbreviations: AD, autosomal dominant; apo, apolipoprotein; AR, autosomal recessive; ARH, autosomal recessive hypercholesterolemia; CHD, coronary heart disease; LDL, low-density lipoprotein; LPL, lipoprotein lipase; PVD, peripheral vascular disease; VLDL, very-low density lipoprotein.

Standard lipoprotein analysis assesses total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Both LDL and HDL cholesterol levels are temporarily decreased for several weeks after myocardial infarction or acute inflammatory states, but can be accurately measured if blood is obtained within 8 h of the event.

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