{"id":4422564,"date":"2025-01-12T05:51:00","date_gmt":"2025-01-12T11:51:00","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/hypercholesterolemia\/"},"modified":"2025-01-12T05:56:31","modified_gmt":"2025-01-12T11:56:31","slug":"hypercholesterolemia","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/hypercholesterolemia\/","title":{"rendered":"Hypercholesterolemia"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">HYPERCHOLESTEROLEMIA<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Definition and Importance<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cholesterol<\/strong>: Essential for cell membrane function; precursor of steroid hormones.<\/li>\n\n\n\n<li><strong>Hypercholesterolemia<\/strong>: Elevated levels of low-density lipoprotein (LDL) cholesterol.\n<ul class=\"wp-block-list\">\n<li>Increases risk for atherosclerosis \u2192 can lead to <strong>coronary heart disease (CHD)<\/strong>, cerebrovascular disease, and peripheral vascular disease.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">NCEP Guidelines for LDL Cholesterol<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>National Heart, Lung, and Blood Institute<\/strong> issued three guidelines (1988, 1993, 2002).<\/li>\n\n\n\n<li><strong>Third Report<\/strong> (ATP III) of the <strong>National Cholesterol Education Program (NCEP)<\/strong> sets cutoffs:\n<ul class=\"wp-block-list\">\n<li><strong>LDL &lt;100 mg\/dL<\/strong> = optimal.<\/li>\n\n\n\n<li>Higher LDL \u2192 higher CHD risk.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Risk factors<\/strong> (e.g., smoking, hypertension, low high-density lipoprotein [HDL], family history of premature CHD, age \u226545 [men] or \u226555 [women]) modify LDL goal.\n<ul class=\"wp-block-list\">\n<li>CHD or risk equivalent (e.g., diabetes) \u2192 LDL goal &lt;100 mg\/dL.<\/li>\n\n\n\n<li>\u22652 risk factors \u2192 LDL goal &lt;130 mg\/dL.<\/li>\n\n\n\n<li>0\u20131 risk factor \u2192 LDL goal &lt;160 mg\/dL.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>Updated guidelines (NCEP ATP IV) expected in fall 2011 may modify these targets.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Etiology of High LDL Cholesterol<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Dietary factors<\/strong>: Diets high in saturated fats and cholesterol \u2191 blood cholesterol.<\/li>\n\n\n\n<li><strong>LDL receptor <\/strong><a href=\"https:\/\/myendoconsult.com\/learn\/cholesterol-synthesis-pathway\/\"  data-wpil-monitor-id=\"280\">pathway is primary regulator of serum cholesterol<\/a>:\n<ul class=\"wp-block-list\">\n<li>LDL receptors on cell surfaces bind apolipoproteins (apo) B100 and E \u2192 clearance of LDL, chylomicron remnants, very low-density lipoproteins (VLDL), etc.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Familial Hypercholesterolemia (FH)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Autosomal dominant<\/strong> disorder.<\/li>\n\n\n\n<li>Mutations in <strong>LDL receptor<\/strong> gene \u2192 decreased or defective LDL receptors.\n<ul class=\"wp-block-list\">\n<li>\u2192 \u2191 plasma <a href=\"https:\/\/myendoconsult.com\/learn\/what-is-ldl-cholesterol\/\"  data-wpil-monitor-id=\"281\">LDL cholesterol<\/a> (3\u20136\u00d7 reference range).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>Clinical findings:\n<ul class=\"wp-block-list\">\n<li><strong>Premature CHD<\/strong>.<\/li>\n\n\n\n<li>Tendon xanthomas, xanthelasma.<\/li>\n\n\n\n<li>Homozygotes more severely affected than heterozygotes.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Familial Defective apo B100<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Mutations in <strong>apo B100<\/strong> gene \u2192 defective LDL binding to LDL receptor.<\/li>\n\n\n\n<li>Phenotype mirrors FH (\u2191 LDL cholesterol, premature CHD, tendon xanthomas).<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Familial Hyperapobetalipoproteinemia and Familial Combined Hyperlipidemia<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Autosomal dominant<\/strong> inheritance with <strong>yet unknown<\/strong> genetic defects.<\/li>\n\n\n\n<li>Characterized by:\n<ul class=\"wp-block-list\">\n<li>\u2191 plasma LDL cholesterol and\/or \u2191 triglycerides.<\/li>\n\n\n\n<li>Possibly low HDL.<\/li>\n\n\n\n<li>Associated with obesity, hyperuricemia, fasting hyperglycemia.<\/li>\n\n\n\n<li>No xanthomas typically.<\/li>\n\n\n\n<li>Increased risk of <strong>premature CHD<\/strong>.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Hypercholesterolemic Xanthomatosis<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Cutaneous and Tendinous Xanthomas<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Occur when <strong>LDL cholesterol<\/strong> is markedly elevated.<\/li>\n\n\n\n<li><strong>Macrophages<\/strong> take up LDL in nonsaturable manner \u2192 become foam cells.<\/li>\n\n\n\n<li><strong>Xanthelasma<\/strong>: Usually on eyelids, accompanied by <strong>arcus corneae<\/strong> in persons &lt;40.<\/li>\n\n\n\n<li><strong>Tuberous xanthomas<\/strong>: Elbows, knees, buttocks (often irritated by clothing).<\/li>\n\n\n\n<li><strong>Tendinous xanthomas<\/strong>: Found in tendon tissue (extensor tendons of hands, Achilles, patellar).<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Atherosclerosis<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>High LDL \u2192 formation of <strong>foam cells<\/strong>, fatty streaks, atheromatous plaques in arteries.<\/li>\n\n\n\n<li>Leads to early-onset CHD if untreated.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Specific Monogenic Causes<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Familial Hypercholesterolemia (FH)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Defect<\/strong>: Mutations in LDL receptor gene.<\/li>\n\n\n\n<li>Types of molecular mutations:\n<ul class=\"wp-block-list\">\n<li>\u2193 LDL receptor synthesis.<\/li>\n\n\n\n<li>\u2193 transport of receptor to membrane.<\/li>\n\n\n\n<li>Defective LDL-receptor binding.<\/li>\n\n\n\n<li>Defect in receptor internalization.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Heterozygous FH<\/strong> (1 in 500 persons):\n<ul class=\"wp-block-list\">\n<li>Plasma total cholesterol >300 mg\/dL, LDL >250 mg\/dL.<\/li>\n\n\n\n<li>Tendon xanthomas in ~75% of patients.<\/li>\n\n\n\n<li>Premature CHD, often before 45 years.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Homozygous FH<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Plasma total cholesterol 600\u20131000 mg\/dL, LDL ~550\u2013950 mg\/dL.<\/li>\n\n\n\n<li>Tuberous xanthomas in early childhood (&lt;6 years).<\/li>\n\n\n\n<li>Aortic valve involvement in ~50%.<\/li>\n\n\n\n<li>Extremely high risk of myocardial infarction before age 20 if untreated.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\">Treatment of FH<\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Heterozygous FH<\/strong>: Low-cholesterol diet + pharmacotherapy (statins, bile acid sequestrants, cholesterol-absorption inhibitors).<\/li>\n\n\n\n<li><strong>Homozygous FH<\/strong>: More resistant to standard therapies; often require <strong>LDL apheresis<\/strong> every 1\u20133 weeks to remove LDL from circulation.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Familial Defective apo B100<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mutation<\/strong>: Single point mutation in apo B100 gene \u2192 poor LDL receptor binding.<\/li>\n\n\n\n<li>Presentation mimics heterozygous FH:\n<ul class=\"wp-block-list\">\n<li>\u2191 LDL, tendon xanthomas, premature CHD.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>Usually less severe than FH, but clinically indistinguishable.<\/li>\n\n\n\n<li><strong>Treatment<\/strong>: Similar to heterozygous FH.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Other Causes of Tendon Xanthomas with Elevated or Normal LDL<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Sitosterolemia<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Autosomal recessive<\/strong>; defective adenosine triphosphate\u2013binding cassette (G5, G8).<\/li>\n\n\n\n<li>Excess absorption of dietary <strong>plant sterols<\/strong> \u2192 elevated plant sterols in plasma\/tissues.<\/li>\n\n\n\n<li>Tendon xanthomas, premature CHD.<\/li>\n\n\n\n<li>LDL also elevated.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Cerebrotendinous Xanthomatosis (CTX)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Autosomal recessive<\/strong>; deficiency of <strong>27-hydroxylase<\/strong> (CYP27A1 mutation).<\/li>\n\n\n\n<li>Abnormal bile acid synthesis \u2192 <strong>cholesterol\/cholestanol<\/strong> accumulation in tissues.<\/li>\n\n\n\n<li>Normal plasma lipids.<\/li>\n\n\n\n<li>Tendon xanthomas + <strong>neurologic manifestations<\/strong> (cerebellar ataxia, pyramidal tract signs).<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>HYPERCHOLESTEROLEMIA Definition and Importance NCEP Guidelines for LDL Cholesterol Etiology of High LDL Cholesterol Familial Hypercholesterolemia (FH) Familial Defective apo B100 Familial Hyperapobetalipoproteinemia and Familial Combined Hyperlipidemia Hypercholesterolemic Xanthomatosis Cutaneous and Tendinous Xanthomas Atherosclerosis Specific Monogenic Causes Familial Hypercholesterolemia (FH) Treatment of FH Familial Defective apo B100 Other Causes of Tendon Xanthomas with Elevated or [&hellip;]<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[688],"class_list":["post-4422564","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-lipid-metabolism","post-wrapper","thrv_wrapper"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422564","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":3,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422564\/revisions"}],"predecessor-version":[{"id":4422567,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422564\/revisions\/4422567"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422564"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422564"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}