Which one of the following drug mechanisms of action is true?
Ezetimibe inhibits intestinal uptake of dietary and biliary cholesterol without affecting the absorption of fat-soluble nutrients. Statins reduce synthesis of cholesterol in the liver by competitively inhibiting HMG-CoA reductase activity. The reduction in intracellular cholesterol concentration induces LDL receptor expression on the hepatocyte cell surface which results in extraction of LDL-C from the blood. Cholestyramine is a bile acid sequestrant. Gemfibrozil is a fibrate and an agonist of PPAR-α.
A patient is not achieving target LDL-C on high-dose statin alone.
Which combination with statin is not recommended?
Combination of statins with fibrates may enhance the risk for myopathy. The risk is highest with gemfibrozil, and the combination should be avoided. The risk appears to be small with other fibrates. Colesevelam is a newer bile acid sequestrant.
Which one of the following agents will have the greatest LDL-C-lowering effect?
Statins have the greatest effect on LDL-C followed by bile acid sequestrants and then fibrates (which have a greater effect on triglycerides): rosuvatatin > atorvastatin > simvastatin > pravastatin.
A 20-year-old man is referred with tendon xanthomas and an LDL-C of 13 mmol/L.
What is the likely diagnosis?
The presence of tendon xanthomata is virtually diagnostic of FH. LDL-C concentrations >13mmol/L in adults is suggestive of a clinical diagnosis of homozygous FH, and DNA testing would be appropriate
A 33-year-old man attends clinic with a total cholesterol of 7.8 (LDL-C 5.1). He has no evidence of premature atherosclerosis or clinical xanthomata/xanthelasma. He volunteers that two uncles on the maternal side had heart attacks in their forties.
According to the Simon Broome criteria:
Simon Broome criteria are used to make a diagnosis of FH in an index individual. In an adult, TC >7.5 (LDL-C >4.9) is suggestive of FH when associated with a family history of premature CV disease (or definitive family history of TC > 7.5). A definite diagnosis is made in the presence of tendon xanthoma (including in a family member) or DNA mutation (LDL-R, apo B-100, or PCSK9).
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