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Key Clinical Updates in Hyperthyroidism (Thyrotoxicosis)

The FDA approved the novel PCSK9 inhibitor inclisiran, which uses silencing RNA technology to reduce liver production of PCSK9 protein by approximately 80%. Twice-yearly dosing is novel for lipid-lowering therapy; inclisiran enables new delivery strategies, including in-clinic administration.

Raal FJ et al; ORION-9 Investigators. N Engl J Med. [PMID: 32197277]

Ray KK et al; ORION-10 and ORION-11 Investigators. N Engl J Med. [PMID: 32187462]

Reduction of LDL cholesterol with statins is just one part of a program to reduce the risk of CVD. Other measures—including diet, exercise, smoking cessation, hypertension control, weight loss, diabetes control, and antithrombotic therapy—are also of central importance. For example, exercise (and weight loss) may reduce the LDL cholesterol and increase the HDL. Quitting smoking reduces the effect of other cardiovascular risk factors (such as a high cholesterol level); it may also increase the HDL cholesterol level. Modest alcohol use (1–2 ounces a day) also raises HDL levels and may have a salutary effect on CHD rates.

The use of medications to raise the HDL cholesterol has not been demonstrated to provide additional benefit. For example, cholesteryl ester transfer protein inhibitors are a class of medicines being investigated to raise HDL levels; however, agents in this class have not been shown to be effective in so doing. The addition of niacin to statins has also been carefully studied in the AIM-HIGH study and the HPS2-THRIVE study in patients at high risk for CVD and shown not to produce any further benefit (ie, to decrease parameters of cardiovascular risk).

Pappa  E  et al. Cardioprotective properties of HDL: structural and functional considerations. Curr Med Chem. 2020;27:2964.
[PubMed: 30714519]  
Preiss  D  et al. Lipid-modifying agents, from statins to PCSK9 inhibitors: JACC focus seminar. J Am Coll Cardiol. 2020;75:1945.
[PubMed: 32327106]  
van der Vorst  EPC. High-density lipoproteins and apolipoprotein A1. Subcell Biochem. 2020;94:399.
[PubMed: 32189309]  


Studies of nonhospitalized adults have reported only modest cholesterol-lowering benefits of individual dietary therapies, typically in the range of a 5–10% decrease in LDL cholesterol, and even less over the long term. The effect of diet therapies, however, may be additive; some patients will have striking reductions in LDL cholesterol—up to a 25–30% decrease—whereas others will have clinically important increases. Thus, the results of diet therapy should be assessed about 4 weeks after initiation.

Several nutritional approaches to diet therapy are available. Most Americans eat over 35% of calories as fat, of which 15% is saturated fat. A traditional cholesterol-lowering diet recommends reducing total fat to 25–30% and saturated fat to less than 7% of calories, with complete elimination of trans fats. These diets replace fat, particularly saturated fat, with carbohydrate. Other diet plans, including the Dean Ornish Diet and most vegetarian diets, restrict fat even further. Low-fat, ...

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