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    PCSK9 Inhibitors: A 5-Question Quiz


    Answer B. A heterogeneous group of disorders resulting in elevated serum cholesterol and triglyceride concentrations. (NOT consistent with FH) 

    Familial hypercholesterolemia is transmitted via autosomal dominant inheritance and results mainly in isolated elevated total cholesterol (due to elevated LDL-C) and is less likely to cause elevations in triglyceride (TG) concentration. TGs are more commonly elevated in related disorders of cholesterol homeostasis, such as familial hypertriglyceridemia, familial combined hyperlipidemia and familial dysbetalipoproteinemia. In homozygous familial hypercholesterolemia (HoFH), diagnostic criteria can include genetic analyses and/or clinical scoring systems. Because of its autosomal dominant transmission, a through family history is important. Clinical manifestations include premature CHD, cutaneous manifestations such as tendon xanthomas, widespread atherosclerosis, and early mortality. HeFH, whose prevalence is higher than was previously appreciated, can also result in clinical characteristics such as tendon thickening, xanthelasmas, xanthomas, and corneal arcus. There are three currently accepted resources for diagnosis of FH: the Simon Broom Criteria, the Med Ped Criteria, and the FH Dutch Lipid Clinic Criteria. Although molecular diagnosis is helpful, it is not essential to diagnosis of this condition and early identification and treatment can have a considerable impact on the natural history of the disease.

    Going back to our case…. At age 33, the patient experienced an acute MI. Angiography showed widespread CAD that required the placement of 3 stents. Daily oral drug therapy was initiated for secondary CAD prevention: atorvastatin (80 mg), ezetimibe (10 mg), ramipril (5 mg), clopidogrel (75 mg), bisoprolol (5 mg) and ASA (81 mg). At 6 months after his MI, his serum TC and LDL-C concentrations were 207 and 145 mg/dL, respectively; trial of rosuvastatin 40 mg resulted in slight improvement of his serum TC to 180 mg/dL and LDL-C to 125 mg/dL.

    Is this patient a candidate for PCSK9 inhibitor therapy?  The answer will follow later. First, how much do you know about PCSK9 and inhibition of this enzyme? Test your knowledge below.

    Question 2.

    Payal Kohli, MD
    Payal Kohli, MD, is an attending cardiologist for Kaiser Permanente in Denver, Colorado.


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