Three Musketeers for Lowering Cholesterol: Statins, Ezetimibe and Evolocumab

: Coronary heart disease (CHD) is closely related to hypercholesterolemia, and lowering serum cholesterol is currently the most important strategy in reducing CHD. In humans, the serum cholesterol level is determined mainly by three metabolic pathways, namely, dietary cholesterol intake, cholesterol synthesis, and cholesterol degradation in vivo. An intervention that targets the key molecules in the three pathways is an important strategy in lowering serum lipids. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) to reduce lowdensity lipoprotein (LDL) by about 20% to 45%. However, up to 15% of patients cannot tolerate the potential side effects of high statin dosages, and several patients also still do not reach their optimal LDL goals after being treated with statins. Ezetimibe inhibits cholesterol absorption by targeting the Niemann–Pick C1-like 1 protein (NPC1L1), which is related to cholesterol absorption in the intestines. Ezetimibe lowers LDL by about 18% when used alone and by an additional 25% when combined with statin therapy. The proprotein convertase subtilisin/kexin type 9 (PCSK9) increases hepatic LDLR degradation, thereby reducing the liver’s ability to remove LDL, which can lead to hypercholesterolemia. Evolocumab, which is a PCSK9 monoclonal antibody, can reduce LDL from baseline by 53% to 56%. The three drugs exert lipidlowering effects by regulating the three key pathways in lipid metabolism. Combining any with the two other drugs on the basis of statin treatment has improved lipid-lowering effect. Whether the combination of the three musketeers will reduce the side effects of monotherapy and achieve lipid-lowering effect should be studied further in the future.

ANIMAL SPIRITS, ECONOMIC POLICIES AND BUSINESS CYCLES: THE THREE MUSKETEERS OF THE ECONOMIC WORLD

This study quantifies animal spirits by constructing an index using information from major sectors of the economy. The key drivers of the animal spirits are the monetary/fiscal policies and the stage of the business cycle and therefore the effect of these drivers on animal spirits is also estimated. Furthermore, the effect of changes in the animal spirits index is generated to examine which sector is affected the most by animal spirits. In other words, we test whether animal spirits produce asymmetric effects on the economy. Our work suggests a policy change (and a shock/recession) produces dual effects on the economy which are (a) direct effects and (b) indirect effects, which is brought about by animal spirits. Therefore, it is crucial for policymakers to estimate the direct and indirect effects of policy changes as well as shocks/recessions on the economy to gauge the accumulative effect, rendering them more to design effective policies.