Hypertriglyceridemia is a prevalent risk factor for cardiovascular disease (CVD) and increasingly important in the setting of current obesity and insulin resistance epidemics. High triglyceride (TG) levels are markers for several types of atherogenic lipoproteins. Patients who have hypertriglyceridemia may be at significant risk for CVD even if low-density lipoprotein cholesterol levels are at goal, and therefore warrant treatment that optimizes diet, reduces overweight, and promotes regular exercise. High-risk patients with hypertriglyceridemia, such as those with diabetes, CVD, or metabolic syndrome, may benefit from additional drug treatment aside from a statin to address other lipid abnormalities. In this discussion, we review the role of hypertriglyceridemia and its associated atherogenic lipoproteins in the pathogenesis of atherosclerosis, the relevance of a high TG level as a predictor of CVD, the cardiovascular outcomes from TG-lowering intervention trials, and the current guidelines for treating hypertriglyceridemia.

with an elevated risk of coronary heart disease (CHD) ( 1-5 ). However, evidence from randomized clinical trials that studied drugs that increased HDL-C has not been consistent with the hypothesis that HDL protects against CHD. In large-scale trials of novel cholesteryl ester transfer protein inhibitors, CHD incidence was not reduced despite substantial increases in HDL-C levels ( 6-8 ); trials of estrogen replacement therapy in postmenopausal women did not confi rm a protective effect on CHD despite increases in HDL-C ( 9-11 ); and two recent trials of niacin also failed to show reduction in CHD risk, although the increases in HDL-C were modest ( 12, 13 ). Furthermore, some genetic variation that is associated with high HDL-C concentration is not associated with reduced CHD ( 14 ). This raises questions regarding the effi cacy of HDL-C elevation, in general, as a strategy for CHD prevention.Accumulating evidence indicates that protein composition of HDL may be relevant to the risk of CHD ( 15-17 ). ApoE and apoC-III are found on the surface of both triglyceride-rich lipoproteins (TRLs) and . The concentration of apoE in HDL is an independent predictor of recurrent coronary events ( 15 ). More recently, a proteomic analysis showed greater apoE enrichment in small-size HDL (HDL3) in subjects with established coronary artery disease than in normal controls ( 16 ). Similarly, HDL containing apoC-III independently predicts increased risk of an initial coronary event in separate cohorts of men and women ( 17 ), and a high ratio of apoC-III to apoA-I in HDL predicts recurrent coronary events ( 15 ).Abstract Human HDLs have highly heterogeneous composition. Plasma concentrations of HDL with apoC-III and of apoE in HDL predict higher incidence of coronary heart disease (CHD). The concentrations of HDL-apoA-I containing apoE, apoC-III, or both and their distribution across HDL sizes are unknown. We studied 20 normal weight and 20 obese subjects matched by age, gender, and race. Plasma HDL was separated by sequential immunoaffi nity chromatography (anti-apoA-I, anti-apoC-III, anti-apoE), followed by nondenaturing-gel electrophoresis. Mean HDL-cholesterol concentrations in normal weight and obese subjects were 65 and 50 mg/dl ( P = 0.009), and total apoA-I concentrations were 119 and 118 mg/dl, respectively. HDL without apoE or apoC-III was the most prevalent HDL type representing 89% of apoA-I concentration in normal weight and 77% in obese ( P = 0.01) individuals; HDL with apoE-only was 5% versus 8% ( P = 0.1); HDL with apoC-III-only was 4% versus 10% ( P = 0.009); and HDL with apoE and apoC-III was 1.5% versus 4.6% ( P = 0.004). Concentrations of apoE and apoC-III in HDL were 1.5-2× higher in obese subjects ( P р 0.004). HDL with apoE or apoC-III occurred in all sizes among groups. Obese subjects had higher prevalence of HDL containing apoE or apoC-III, subfractions associated with CHD, whereas normal weight subjects had higher prevalence of HDL without apoE or apoC-III, subfractions with protective association against ...

The variety of symptoms observed in patients with neurocysticercosis (NCC) is associated with the generation of reactive species by inflammatory cells. Reactive species can damage the cell membrane, inducing lipid peroxidation (LP) and giving rise to genotoxic free radicals. In this study we investigated the presence of LP products in cerebrospinal fluid (CSF) and the frequency of DNA damage in peripheral lymphocytes from 25 patients with NCC. Patients with NCC showed higher LP levels compared to controls (n=7), especially patients presenting with severe symptoms. There was a significant correlation between LP and the inflammatory response (Spearman's correlation coefficient 0.75, P<0.01). The presence of free radicals in the central nervous system (CNS) may favour the development of severe clinical symptoms, even in patients under anti-inflammatory treatment but with a poor response. DNA damage correlated with the presence of LP and with symptom severity (correlation coefficient 0.30, P<0.05, and 0.54, P<0.01, respectively). These results demonstrate the generation of oxidative damage in the CNS of patients with NCC, which may be responsible for the severity of the symptoms. LP determination in the CSF of patients with NCC could be used to determine the inflammatory reaction developed.

Human high-density lipoprotein (HDL) particles are highly heterogeneous in composition, and in relation to coronary heart disease (CHD). Specifically, HDL containing apoC-III predicts increased incidence of CHD, whereas HDL that does not contain apoC-III predicts decreased CHD incidence. Recently, we found that obese subjects had a higher concentration of HDL with apoC-III and a lower concentration of HDL without apoC-III than normal weight controls. However, the effects of weight loss on HDL with or without apoC-III are not known. We studied 39 obese participants (mean BMI of 34) in a weight-loss trial assigned to a high fat 40%/high protein 25%/low carbohydrate 35% diet for 2 years. We chose this diet group because HDL-cholesterol (-C) levels increased the most compared to the other diet groups with more carbohydrate and less fat. Participants with at least 8% loss of initial body weight at 2 years were assigned to the weight loss group (n=21), while those without a change in weight comprised the no-weight loss group (n=18). Subjects were matched by age (mean 51 years), gender, and race. HDL without apoC-III and HDL with apoC-III were separated from plasma by sequentially using anti-apoA-I and anti-apoC-III immunoaffinity chromatography. For both groups, the mean baseline HDL-C and total plasma apoA-I concentrations were 48 and 119mg/dL, respectively. Weight loss increased HDL-C concentration by an average of 25% (p<0.01 for changes between groups), and total apoA-I by 9% (p<0.02). In the weight-loss group, mean apoA-I concentrations of HDL without apoC-III increased by12% (from 99 to 111 mg/dL) compared to a decrease of 6% in the no-weight loss group (from 107 to 101mg/dL) (p<0.02). The apoA-I concentration of HDL with apoC-III, 15 mg/dL, remained unchanged. In conclusion , moderate weight loss selectively increased the concentration of HDL without apoC-III, the predominant HDL type that predicts reduced incidence of CHD. In contrast, weight loss did not affect HDL with apoC-III, an HDL type associated with increased CHD risk. This represents a partial normalization of HDL subtypes by moderate weight loss. This effect on HDL subpopulations defined by absence of apoC-III suggests a novel mechanism by which weight loss may reduce cardiovascular disease risk.