e2 Arterioscler Thromb Vasc Biol January 2019 lipoprotein remnant particles can penetrate and accumulate in the subendothelial arterial space and induce local and systemic atherogenic responses. Thus, patients with familial dysbetalipoproteinemia (also known as type III hyperlipoproteinemia or remnant removal disease) exhibit markedly accelerated atherosclerosis, despite LDL-C levels being in the normal range. 15 These patients exhibit elevated remnants primarily because of mutations in the APOE (apolipoprotein E) gene, which prevent effective hepatic clearance of the apoE-containing TRLs. Furthermore, increased arterial inflammation, measured as increased arterial 18F-fluorodeoxyglucose uptake, can be seen in patients with familial dysbetalipoproteinemia. 16 Increased 18F-fluorodeoxyglucose uptake is closely associated with inflammatory activation of macrophages, 17 suggesting that remnants cause increased activation of lesional macrophages. The elevated remnant levels result in increased lipid accumulation in circulating monocytes and increased expression of adhesion molecules in these cells, as well as monocytosis, 15 which would all be predicted to increase macrophage accumulation in lesions of atherosclerosis. Thus, a marked increase in remnants results in atherogenic effects both systemically and locally. In patients without known genetic conditions affecting TRL remnant clearance, the role of remnants in ASCVD is more difficult to assess, in part, because remnants are poorly defined and are difficult to measure. One common method of assessing remnant levels is to subtract LDL-C and HDL-C from total cholesterol levels. This method is inexact, especially at high triglyceride levels. Measurements of plasma triglyceride levels, often used as a surrogate of TRLs and remnants, are also an approximation because fasting concentrations of plasma triglycerides correspond to the sum of triglyceride content in nascent VLDL (very low-density lipoprotein) and remnants. Nevertheless, fasting triglyceride levels can predict long-term and short-term cardiovascular risk in patients with acute coronary syndrome who are treated effectively with statins, 18 suggesting that elevated fasting triglycerides, directly or indirectly, contribute to residual risk. Triglyceride content in plasma increases in the postprandial state because of the presence of triglyceride-rich chylomicrons and their remnants. 19 Nonfasting triglycerides are also associated with increased risk of ischemic heart disease and MI20 and with a stepwise higher risk of heart failure. 21 Therefore, in some patients, it is recommended to assess both nonfasting and fasting lipid profiles. 22 A recent article in ATVB highlights the importance of postprandial triglyceride clearance in atherosclerosis in humans. Kurihara et al23 used optical coherence tomography to visualize high-risk atherosclerotic lesions, defined as thin-cap fibroatheroma, and the association with postprandial dyslipidemia after a meal tolerance test in 30 patients with stable coronary artery disease. They demonstrated that thin-cap fibroatheromas are associated with increased levels of remnants after the meal tolerance test, and with elevated baseline apoC-III (apolipoprotein C-III) levels, suggesting baseline abnormalities in TRL clearance in patients with high-risk lesions. In another ATVB article, insulin treatment of diabetic mice was shown to reduce plasma triglycerides and cholesterol and to increase LPL (lipoprotein lipase) activity concomitant with a reduction in atherosclerosis. 24 LPL hydrolyzes triglycerides and promotes uptake of fatty acids into tissues, thereby lowering plasma triglyceride levels. Interestingly, blood …