Page 640 - Basic _ Clinical Pharmacology ( PDFDrive )

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Dyslipidemia

Mary J. Malloy, MD, & John P. Kane, MD, PhD

C ASE STUD Y

A 42-year-old woman has heterozygous familial hyper- so they were discontinued although she did not develop
cholesterolemia (HeFH) but is otherwise well and has no elevated levels of creatine kinase. Her untreated LDL-C is
symptoms of coronary or peripheral vascular disease. A 235 mg/dL and triglycerides 125 mg/dL. Her LDL-C goal
carotid ultrasound was normal. Her mother had a myo- for primary prevention of arteriosclerotic vascular disease
cardial infarction at age 51 and had no known risk factors is in the 70-mg/dL range because of her multiple lipopro-
other than her presumed HeFH. The patient also has ele- tein risk factors and her mother’s history of premature
vated lipoprotein (a) at 2.5 times normal and low HDL-C coronary artery disease. She has no other risk factors and
(43 mg/dL). She developed muscle symptoms with each her diet and exercise habits are excellent. How would you
of 3 statins (atorvastatin, rosuvastatin, and simvastatin) manage this patient?

Plasma lipids are transported in complexes called lipoproteins. of lipoproteins by free radicals creates ligands for these receptors.
Metabolic disorders that involve elevations in any lipoprotein The atheroma grows with the accumulation of foam cells,
species are termed hyperlipoproteinemias or hyperlipidemias. collagen, fibrin, and frequently calcium. Whereas such lesions
Hyperlipemia denotes increased levels of triglycerides. can slowly occlude coronary vessels, clinical symptoms are more
The major clinical sequelae of hyperlipidemias are acute frequently precipitated by rupture of unstable atheromatous
pancreatitis and atherosclerosis. The former occurs in patients plaques, leading to activation of platelets and formation of occlu-
with marked hyperlipemia. Control of triglycerides can prevent sive thrombi.
recurrent attacks of this life-threatening disease. Although treatment of hyperlipidemia can cause slow physical
Atherosclerosis is the leading cause of death for both genders in regression of plaques, the well-documented reduction in acute
the USA and other Western countries. Lipoproteins that contain coronary events that follows vigorous lipid-lowering treatment
apolipoprotein (apo) B-100 convey lipids into the artery wall. is attributable chiefly to mitigation of the inflammatory activity
These are low-density (LDL), intermediate-density (IDL), of macrophages and is evident within 2–3 months after starting
very-low-density (VLDL), and lipoprotein(a) (Lp[a]). Remnant therapy.
lipoproteins formed during the catabolism of chylomicrons that High-density lipoproteins (HDL) exert several antiathero-
contain the B-48 protein (apo B-48) can also enter the artery wall, genic effects. They participate in retrieval of cholesterol from the
contributing to atherosclerosis. artery wall and inhibit the oxidation of atherogenic lipoproteins.
Cellular components in atherosclerotic plaques (atheromas) Low levels of HDL (hypoalphalipoproteinemia) are an indepen-
include foam cells, which are transformed macrophages, and dent risk factor for atherosclerotic disease and thus are a potential
smooth muscle cells filled with cholesteryl esters. These cellular target for intervention.
alterations result from endocytosis of modified lipoproteins via at Cigarette smoking is a major risk factor for coronary disease. It
least four species of scavenger receptors. Chemical modification is associated with reduced levels of HDL, impairment of cholesterol

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