Hypertriglyceridemia: A Neglected Risk Factor for Ischemic Stroke?

Abstract

Hypertriglyceridemia is caused by defects in triglyceride metabolism and generally manifests as abnormally high plasma triglyceride levels. Although the role of hypertriglyceridemia may not draw as much attention as that of plasma cholesterol in stroke, plasma triglycerides, especially nonfasting triglycerides, are thought to be correlated with the risk of ischemic stroke. Hypertriglyceridemia may increase the risk of ischemic stroke by promoting atherosclerosis and thrombosis and increasing blood viscosity. Moreover, hypertriglyceridemia may have some protective effects in patients who have already suffered a stroke via unclear mechanisms. Therefore, further studies are needed to elucidate the role of hypertriglyceridemia in the development and prognosis of ischemic stroke.

Keywords: Hypertriglyceridemia; Incidence; Ischemic stroke; Prognosis.

Figure 1.

Metabolism of triglycerides [15]. Triglycerides are incorporated into chylomicron (CM) by enterocytes and into very low-density lipoprotein (VLDL) by hepatocytes. Nascent CM has apolipoprotein B48 (apoB48) on its surface, while nascent VLDL has apolipoprotein B100 (apoB100). After interaction with high-density lipoprotein (HDL), these two types of lipoproteins become mature and can be hydrolyzed by lipoprotein lipase (LPL) anchoring to the vascular endothelium. As a result, free fatty acids (FFAs) are released from CM and VLDL and utilized by peripheral tissues, such as adipose tissue, heart, and skeletal muscle. Mature CM and VLDL become remnant particles after continuous interactions with LPL and HDL and are finally taken up by the liver. GPIHBP1, glycosylphosphatidylinositol anchored high-density lipoprotein binding protein 1.

Figure 2.

Mechanisms behind hypertriglyceridemia and ischemic stroke. Hypertriglyceridemia may increase the risk of ischemic stroke by predisposing patients to atherosclerosis, thrombosis, and hyperviscosity. Hypertriglyceridemia predisposes atherosclerosis mainly through the subendothelial deposition of remnant particles (A), toxic effects of triglyceride-rich lipoprotein (TRL) lipolytic products (B), impairment of endothelial function (C), and the establishment of local and systemic inflammation (D). Hypertriglyceridemia leads to increased concentrations and activity of clotting factors VII, VIII, X, and plasminogen activator inhibitor-1 (PAI-1), activation of platelets and higher blood viscosity, which together predict a higher risk of thrombosis. Hypertriglyceridemia represents a higher blood viscosity because of elevated plasma viscosity and altered erythrocyte properties. Hyperviscosity can increase platelet adhesion, protein infiltration to the subendothelial space, and shear stress damage, and impair microcirculation, leading to a higher risk of atherosclerosis, thrombosis, and cerebral ischemia. TG, triglyceride; NF-κB, nuclear factor κB; MAPK, mitogen-activated protein kinase; TLR, Toll-like receptor; SFA, saturated fatty acid; FFA, free fatty acid; oxLipid, oxidized phospholipid; ICAM, intracellular adhesion molecule; ROS, reactive oxygen species; LPL, lipoprotein lipase; CRP, C-reactive protein; sCAM, soluble cell adhesion molecule; SMC, smooth muscle cell.