Cholesterol Remnants, Triglyceride-Rich Lipoproteins and Cardiovascular Risk

Abstract

Randomized clinical trials with statins and other lipid-lowering drugs have shown the presence of a "residual cardiovascular risk" in those treated to "target" for LDL-cholesterol. This risk is mainly associated to lipid components other than LDL and in particular to remnant cholesterol (RC) and to lipoproteins rich in triglycerides in fasting and non-fasting conditions. During fasting, RCs correspond to the cholesterol content of the VLDL and their partially depleted triglyceride remnant containing apoB-100. Conversely, in non-fasting conditions, RCs include also cholesterol present in chylomicrons containing apoB-48. Therefore, RCs refer to total plasma cholesterol minus HDL-cholesterol and LDL-cholesterol, that is, all the cholesterol present in the VLDL, chylomicrons and in their remnants. A large body of experimental and clinical data suggests a major role of RCs in the development of atherosclerosis. In fact, RCs easily pass the arterial wall and bind to the connective matrix stimulating the progression of smooth muscle cells and the proliferation of resident macrophages. RCs are a causal risk factor for cardiovascular events. Fasting and non-fasting RCs are equivalent for predicting vascular events. Further studies on drugs effect on RC levels and clinical trials to evaluate the efficacy of RC reduction on cardiovascular events are needed.

Keywords: atherosclerosis; remnant cholesterol; residual cardiovascular risk; triglyceride-rich lipoprotein.

Figure 1

Remnants of cholesterol and atherosclerosis: During the post-prandial period, enterocytes produce chylomicrons which are released into the circulation via the intestinal lymphatic system. In the liver, regardless of meals, hepatocytes synthesize and release VLDL into the general circulation. Circulating and tissue lipoprotein lipases (LPL) hydrolyse VLDL and chylomicron triglycerides, transforming them into VLDL/IDL remnants and chylomicron remnants, respectively. Due to their small size, remnants easily penetrate the arterial wall and accumulate in the sub-endothelium causing inflammation, foam cells formation, platelet activation and oxidative stress leading to plaque progression.