Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Abstract

The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG. Initial experience with en ezetimibe/fibrates combination seems promising. The recently released IMPROVE-IT Trial is the first to prove that adding a non-statin drug (ezetimibe) to a statin lowers the risk of future CV events. In conclusion, the classical clinical paradigm of lipids-modifying treatment should be changed and high TG should be recognized as an important target for therapy in their own right. Hypertriglyceridemia should be treated.

Increased plasma dipeptidyl peptidase-4 activities are associated with high prevalence of subclinical atherosclerosis in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study

“…TG, as far as is currently known, is not directly atherogenic but represent an important biomarker of CVD risk because of its association with atherogenic remnant particles and apo C-III, a proatherogenic protein found on all classes of the plasma lipoproteins [31]. A recent review suggested that TG may also stimulated atherogenesis by other mechanisms, which included the production of proinflammatory cytokines, fibrinogen and coagulation factors and impairment of fibrinolysis [32]. In our study, we did find a significant increase in TG levels in subjects with subclinical atherosclerosis, but the precise role of TG in the pathogenesis of atherosclerosis remains to be elucidated.…”

“…The HDL cholesterol hypothesis is gradually being replaced by the HDL function hypothesis [34]. HDL cholesterol might be a marker of cardiovascular health but is non-causal in the atherogenesis [32,34]. Currently LDL is considered as the major atherogenic lipoprotein [32], it is a heterogeneous class of particles and accumulating evidence suggests that different LDL subfractions vary in their risk profile [35].…”

“…In our study, we did find a significant increase in TG levels in subjects with subclinical atherosclerosis, but the precise role of TG in the pathogenesis of atherosclerosis remains to be elucidated. HDL has long been regarded as the good" lipoprotein because epidemiological and clinical studies M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 12 have identified an inverse association between HDL concentration and CV disease [32]. The most important antiatherogenic function of HDL is reverse cholesterol transport [33].…”

Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease

“…With regards to the association of higher T with lower TG in community-dwelling men (Group A), this may be mediated via the relationship between higher T and more favourable body composition [30,31]. High TG has been associated with reduced HDL, increased small dense LDL, production of proinflammatory cytokines, endothelial dysfunction, and thereby with increased cardiovascular risk [32].…”

The Association between Cardiovascular Risk and Elevated Triglycerides

“…The result of 29 prospective studies analysis showed that patients in the highest versus the lowest tertile of triglyceride had an odds ratio of 1.72 for CHD (95% CI, 1.56-1.90). (7,12) In patients with very high triglyceride levels and patients with familial chylomicronemia syndrome the risk for atherosclerosis is attenuated, maybe since their plasma lipoprotein particles are too large to enter into the arterial intima. Nevertheless, there are many indications that there is an increased risk of CV disease in the marked or severe HTG as well.…”