{"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&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"],"_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}]}}