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CASE STUDY
A 52-year-old woman was told at age 19 that her “cholesterol” was elevated. Diet and exercise were advised, but she had gained weight, she did no regular exercise, and her diet was high in fat and simple CHO. At her first visit, her direct LDL was 155 mg/dL, triglycerides 458, and HDL 40. Her Lp(a) was not elevated. BMI 30, A1c 6.4, free T4 normal, and ALT about twice the normal. She had no symptoms of coronary or peripheral vascular disease, but a coronary calcium score was greater than zero. Physical examination was normal aside from her obesity that was mostly abdominal. Specific dietary and exercise advice were given. Her mother has T2D and is overweight. Her father survived an MI at age 47. He had no apparent risk factors other than “high cholesterol.” Both parents take a statin. At the end of the visit, 20 mg of rosuvastatin and marine omega 3 fatty acids were prescribed. The patient returned after 3 months. She had lost 6 pounds, was fully compliant with diet, and was gradually increasing her exercise. Her LDL was 97, triglycerides 340, HDL 45, A1c 5.8, and ALT unchanged. How would you manage this patient?
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Plasma lipids are transported in complexes called lipoproteins. Metabolic disorders that involve elevations in any lipoprotein species are termed hyperlipoproteinemia or hyperlipidemia. Hyperlipemia denotes increased levels of triglycerides.
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The major clinical sequelae of hyperlipidemia are acute pancreatitis and atherosclerosis. The former occurs in patients with marked hyperlipemia. Control of triglycerides can prevent recurrent attacks of this life-threatening disease.
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Atherosclerosis is the leading cause of death for both genders in the USA and other Western countries. Lipoproteins that contain apolipoprotein (apo) B-100 convey lipids into the artery wall. These are low-density (LDL), intermediate-density (IDL), very-low-density (VLDL), and lipoprotein(a) (Lp[a]). Remnant lipoproteins formed during the catabolism of chylomicrons that contain the B-48 protein (apo B-48) can also enter the artery wall, contributing to atherosclerosis.
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Cellular components in atherosclerotic plaques (atheromas) include foam cells, which are transformed macrophages, and smooth muscle cells filled with cholesteryl esters. These cellular alterations result from endocytosis of modified lipoproteins via at least four species of scavenger receptors. Chemical modifications of lipoproteins by free radicals create ligands for these receptors. The atheroma grows with the accumulation of foam cells, collagen, fibrin, and calcium. Whereas such lesions can slowly occlude coronary vessels, clinical symptoms are more frequently precipitated by rupture of unstable atheromatous plaques, leading to activation of platelets and formation of occlusive thrombi.
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Although treatment of hyperlipidemia can cause slow physical regression of plaques, the well-documented reduction in acute coronary events that follows vigorous lipid-lowering treatment is attributable chiefly to mitigation of the inflammatory activity of macrophages and is evident within 2–3 months after starting therapy.
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High-density lipoproteins (HDL) exert several antiatherogenic effects. They participate in retrieval of cholesterol ...