Hypertriglyceridemic Subjects Research Articles

Gene–gene interactions among PPARα/δ/γ polymorphisms for hypertriglyceridemia in Chinese Han population

The peroxisome proliferator-activated receptors (PPARs)-α,-β/δ and -γ are the ligand-activated transcription factors that function as the master regulators of glucose, fatty acid and lipoprotein metabolism, energy balance, cell proliferation and differentiation, inflammation and atherosclerosis. This study examined the main effects of both single-locus and multilocus interactions among genetic variants in Chinese Han individuals to test the hypothesis that PPAR-α/δ/γ polymorphisms may contribute to the etiology of hypertriglyceridemia independently and/or through such complex interactions. We genotyped 9 single nucleotide polymorphisms for PPAR-α/δ/γ. Participants were recruited from the Prevention of MetS and Multi-metabolic Disorders in Jiangsu Province of China Study. 820 subjects (474 non-hypertriglyceridemia subjects, 346 hypertriglyceridemia subjects) were randomly selected. Single-locus analyses showed that after adjusted for age, sex, smoking, alcohol consumption, body mass index, waist circumference and fasting glucose, rs1800206, rs9794, rs3856806 and rs1805192 were significantly associated with hypertriglyceridemia, the OR (95% CI) were 4.43(3.08–6.37), 1.49(1.10–2.02), 1.56(1.16–2.08), 2.43(1.80–3.29), respectively. Further, generalized multifactor dimensionality reduction method analysis showed that two-to-six-locus and eight-locus models were significant (p<0.05), which indicated a potential gene–gene interaction among PPAR-α/δ/γ polymorphisms. The results suggest that PPAR-α/δ/γ polymorphisms may contribute to the risk of hypertriglyceridemia independently and/or in an interactive manner.

Genetic Variation in theOX40L/OX40System and Plasma Lipid and Lipoprotein Levels in a Chinese Hypertriglyceridemic Population

To investigate the variations of OX40 (tumor necrosis factor receptor superfamily, member 4) and its ligand OX40L genes and their relationships with serum lipids and apolipoproteins (apo) levels in Chinese healthy individuals and patients with endogenous hypertriglyceridemia (HTG) in the Chengdu area. The genotypes and allele frequencies of the rs3850641 and rs17568 polymorphisms in the OX40L and OX40 genes were assayed by polymerase chain reaction and restriction fragment length polymorphism. In the case-control study, which included 126 HTG subjects and 206 normal control subjects, the frequencies of the G allele at the rs3850641 site and the G allele at the rs17568 site in the patients were similar to those observed in the controls. In the HTG group, subjects with G allele carriers of the rs3850641 site had lower serum high-density lipoprotein cholesterol and apo AI levels as compared to those of genotype AA. In the case group, subjects with G allele carriers of the rs17568 site had higher serum low-density lipoprotein cholesterol (LDL-C) levels, while controls had lower serum total serum cholesterol and LDL-C levels. These results suggest that the rs3850641 and rs17568 polymorphisms in the OX40L and OX40 genes are associated with some of the lipid and lipoprotein variations in subjects with endogenous HTG and/or in the general population of Han Chinese.

Effects of EPA supplementation on plasma fatty acids composition in hypertriglyceridemic subjects with FABP2 and PPARα genotypes

BackgroundFatty acid binding protein 2 (FABP2) and peroxisome proliferator-activated receptor α (PPARα) are involved in cellular uptake and metabolism of fatty acids. Polymorphism of FABP2 and PPARα may influence plasma levels of fatty acids in those who take supplemental eicosapentaenoic acid (EPA). The purpose of this study was to study the potential associations between the Ala54/Thr polymorphism in FABP2 protein and the Leu162/Val in exon 5 and G/C in intron 7 of PPARα with plasma fatty acids composition after EPA supplementation.MethodsTwenty three FABP2 Ala54 and twenty three Thr54 carriers with hypertriglyceridemia were enrolled in this study. Participants took 2 g of pure EPA daily for 8 wks. Plasma fatty acids composition was determined and changes from the baseline were measured.ResultsAlthough EPA supplementation increased the level of plasma EPA and ω-3 fatty acids in both carriers of FABP2 and PPARα genes, these effects were more pronounced in Thr54 and Val162 carriers. EPA supplementation decreased the level of some n-6 fatty acids such as arachidonic acid.ConclusionEPA consumption has more favorable effects on blood n-3 fatty acids and can change the level of plasma n-3 fatty acids, particularly EPA. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for preventing cardiovascular diseases. Finally, diets and micronutrient recommendations should be individualized for high risk people.

PS18 - 84. Expression of the complement system is upregulated in subcutaneous adipocytes from non-obese hypertriglyceridemic subjects and is associated with local insulin resistance

Dysfunctional adipose tissue plays an important role in the etiology of cardiometabolic disorders such as dyslipidaemia, the metabolic syndrome and type 2 diabetes.

Up-Regulation of the Complement System in Subcutaneous Adipocytes from Nonobese, Hypertriglyceridemic Subjects Is Associated with Adipocyte Insulin Resistance

Dysfunctional adipose tissue plays an important role in the etiology of the metabolic syndrome, type 2 diabetes, and dyslipidemia. However, the molecular mechanisms underlying adipocyte dysfunction are incompletely understood. The aim of the study was to identify differentially regulated pathways in sc adipocytes of dyslipidemic subjects. Whole-genome expression profiling was conducted on sc adipocytes from a discovery group of nine marginally overweight subjects with familial combined hyperlipidemia (FCHL) and nine controls of comparable body sizes as well as two independent confirmation groups. In this study, FCHL served as a model of familial insulin resistance and dyslipidemia, in the absence of frank obesity. Functional analyses and gene set enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes or a custom pathway database identified the complement system and complement regulators as one of the top up-regulated pathways in FCHL [false discovery rate (FDR) < 1E-30]. Higher adipocyte complement expression in FCHL was confirmed in the appropriate confirmation group. Higher complement gene expression was associated with lower adipocyte insulin receptor substrate-1 expression as marker of adipocyte insulin resistance, independent of age, sex, or disease status, and this association was corroborated in the two confirmation groups. Additionally, complement gene expression was associated with triglycerides in the discovery set and with triglycerides and/or waist circumference in the confirmation groups. Complement pathway up-regulation did not appear to be driven by hypertriglyceridemia because a 40% pharmacological reduction in triglycerides did not affect complement expression. These findings point to an up-regulation of a complement-related transcriptome in sc adipocytes under metabolically stressed conditions, even in the absence of overt obesity. Such up-regulation may subsequently influence downstream processes, including macrophage infiltration into adipose tissue and adipocyte insulin resistance.

Expression of the complement system is upregulated in subcutaneous adipocytes from non-obese hypertriglyceridemic subjects and is associated with local insulin resistance

Expression of the complement system is upregulated in subcutaneous adipocytes from non-obese hypertriglyceridemic subjects and is associated with local insulin resistance

Quantitative evaluation of the structure and function of the common carotid artery in hypertriglyceridemic subjects using ultrasound radiofrequency-data technology

Assessment of the properties of blood-vessel walls by ultrasound radiofrequency (RF)-data technology is an innovative technique. We quantitatively evaluated the intima-media thickness (IMT) and arterial elasticity of the common carotid artery (CCA) in asymptomatic subjects with hypertriglyceridemia (HTG) using RF-data technology.Thirty HTG subjects and 30 matched controls were enrolled in the study. The common carotid arterial systolic diameter, diastolic diameter, IMT, carotid distensibility (CD), local pulse wave velocity (PWVβ), and stiffness (β) were compared between the two groups, as was the correlation between triglyceride level and the parameters mentioned above.The HTG group had significantly higher values of CCA-IMT compared with the control group (p<0.001). There were significant differences between the HTG group and controls in terms of higher values of PWVβ and β, and lower values of CD (all p<0.05). No difference was observed in terms of the systolic and diastolic diameter of the CCA (p>0.05). The level of triglycerides had significant positive correlations with CCA-IMT (r=0.493, p<0.001), whereas significant correlations with CD, PWVβ, and β were not observed in the HTG group.Ultrasound RF-data technology can be used to non-invasively and quantitatively detect the change in the structure and function of the CCA in asymptomatic HTG subjects for evaluating preclinical atherosclerosis.

Prehypertension in dyslipidemic individuals; relationship to metabolic parameters and intima-media thickness

Like hypertension, prehypertension is associated with cardiovascular disease. The aim of this study was to evaluate: a) the prevalence of prehypertension/hypertension in individuals with various dyslipidemic phenotypes; b) the relation between blood pressure (BP) and other risk factors for atherosclerosis; c) atherogenic potential of prehypertension by the assessment of intima-media thickness of the arteria carotis communis (IMT). 667 clinically asymptomatic subjects were divided into four dyslipidemic phenotypes (DLP) according to apolipoprotein B (apoB) and triglycerides (TG): DLP1 (n=198, normo-apoB/normo-TG), DLP2 (n=179, normo-apoB/hyper-TG), DLP3 (n=87, hyper-apoB/normo-TG), DLP4 (n=203, hyper-apoB/hyper-TG). DLP1 served as a control group. There was significantly higher prevalence of prehypertension and hypertension in subjects with dyslipidemia (DLP2 43.0%, 41.3%; DLP3 42.5%, 29.9%; DLP4 42.4%, 47.8%) than in normolipidemic individuals (DLP1 32.8%, 20.2%). Systolic and diastolic blood pressure (SBP + DBP) correlated with age, total cholesterol, TG, non-HDL-cholesterol, body mass index and waist circumference; SBP additionally with C-peptide, fasting glycemia; DBP additionally with apoB, homeostasis model assessment (HOMA) and plasminogen activator inhibitor-1. The IMT of hypertensive and of prehypertensive subjects was higher than that of subjects with normal BP in all DLPs. The prevalence of prehypertension was higher in all dyslipidemic patients. The common prevalence of prehypertension/hypertension was highest in the hypertriglyceridemic subjects. Prehypertensive and hypertensive patients had higher IMT than normotensive individuals in all DLPs.

Abstract P220: The Effect of Diet-Induced Weight Loss on HDL Functionality in Individuals with Metabolic Syndrome: Investigating Alteration of the Initial Step in Reverse Cholesterol Transport as a Function of Plasma Lipoprotein Composition

The prevalence of metabolic syndrome (MetS) with obesity-linked diabetes continues to increase globally and is associated with atherogenic dyslipidemia characterized by high triglycerides (TG), small, dense low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C) levels. HDL orchestrates the reverse cholesterol transport (RCT) process, initiated by macrophage cholesterol efflux (MCE). The traditional hypothesis is that individuals with dyslipidemia have impaired RCT that leads to atherogenesis. However, a recent study showed that one metric of HDL function, macrophage cholesterol efflux (MCE) to diluted patient plasma, inversely correlated with atherosclerotic burden, independent of plasma HDL-C levels. Moreover, cholesterol efflux from ABCA1-upregulated macrophage cell lines to sera of diabetic hypertriglyceridemic subjects is enhanced compared to normolipidemic (NL) controls. The effect of weight loss on MCE in obese individuals with MetS is unknown. The purpose of this study is to evaluate MCE in obese individuals with MetS as a function of plasma dyslipidemia, and to determine the effect of weight loss on the RCT process. We measured the rate of MCE from human monocytic leukemia THP1 cells to plasma of NL controls (n=24) and obese MetS (n=24) patients before and after 4 to 6 weeks of very low calorie, diet-induced weight loss. Weight loss in the MetS patients was significant, averaged 21.3 lbs, with concurrent significant decreases in TG, apoB, TC, LDL-C and non-HDL-C. Measures of insulin resistance, systolic blood pressure and kidney function improved with weight loss. HDL-C was not significantly altered, but apoA-I decreased with weight loss. MCE to plasma of obese MetS patients was higher than MCE to control plasma ((7.44 + 1.36) % vs (6.39 + 1.23) %, p=0.0069). MCE to plasma of obese MetS patients significantly decreased after weight loss (6.23 + 1.69) %, comparable to control values. MCE was strongly correlated to apoB levels (r 2 = 0.13 - 0.38), consistent with apoB lipoprotein function as a cholesterol sink. This was confirmed by size exclusion chromatography analysis of the distribution of effluxed cholesterol among plasma lipoproteins in 1 control and 2 Mets patients. In conclusion, obese patients with MetS demonstrate increased MCE, a measure of HDL function, compared to NL controls, which significantly decreases in response to diet-induced weight loss, concurrent with a reduction in triglyceride and apoB levels. These results suggest that the high apoB lipoprotein levels in MetS pateints facilitate MCE, and may at least partially compensate for the low HDL-C to promote RCT in these patients.

Very Low Density Lipoprotein Metabolism in Patients with Chronic Kidney Disease

Background: Hypertriglyceridemia is a common metabolic complication of chronic kidney disease (CKD) and an important risk factor for coronary heart disease in this patient population. The mechanisms responsible for the development of hypertriglyceridemia in subjects with CKD are not clear. Methods: We studied very low density lipoprotein triglyceride (VLDL-TG) and VLDL-apolipoprotein B-100 (VLDL-apoB-100) kinetics in vivo in 6 subjects with non-dialysis-dependent CKD (CKD-ND), 6 subjects with CKD treated with peritoneal dialysis (CKD-PD) and 24 sex-, age- and body mass index-matched control subjects with normal renal function (12 control subjects each matched with the CKD-ND and CKD-PD group, respectively). Results: The secretion rates of VLDL-TG and VLDL-apoB-100 into plasma were not different between CKD-ND or CKD-PD and their respective control groups. The mean residence times of VLDL-TG and VLDL-apoB-100 in plasma, which represents the time VLDL-TG and VLDL-apoB-100 spend in the circulation after secretion by the liver, tended to be greater in subjects with CKD-ND than in control subjects (222 ± 38 vs. 143 ± 21 min, p = 0.07, and 352 ± 102 vs. 200 ± 20 min, p = 0.06, respectively) and were about two-fold greater in subjects with CKD-PD compared with their control group (248 ± 51 vs. 143 ± 21 min and 526 ± 116 vs. 182 ± 16 min, respectively; both p ≤ 0.01). Conclusion: Impaired plasma clearance of VLDL-TG and VLDL-apoB-100 is the major abnormality associated with hypertriglyceridemia in patients with either CKD-ND or CKD-PD.

Can Purified Omega-3 Polyunsaturated Fatty Acids Supplementation Act Blood Pressure Levels in Untreated Normal-High Blood Pressure Subjects with Hypertriglyceridemia?

Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) from fish and fish oils appear to protect against coronary heart disease: their dietary intake is in fact inversely associated with cardiovascular disease morbidity/mortality in population studies. Recent evidence suggests that at least a part of this protective effect is mediated by a relatively small but significant decrease in blood pressure (BP) level. In fact, omega-3 PUFAs exhibit wide-ranging biological actions that include regulating both vasomotor tone and renal sodium excretion, partly competing with omega-6 PUFAs for common metabolic enzymes and thereby decreasing the production of vasoconstrictor rather than vasodilator and anti-inflammatory eicosanoids. PUFAs also reduce angiotensin-converting enzyme (ACE) activity, angiotensin II formation. We retrospectively evaluated the long-term effect of a omega-3 PUFAs supplementation on the blood pressure level of 91 hypertriglyceridemic subjects with untreated normal-high blood pressure that were prescribed a 3 grams omega-3 PUFAs supplementation in order to improve their plasma lipid pattern. After 24 months of treatment, systolic blood pressure (SBP) meanly decreased by 2.6 +/- 2.5 mmHg (p = 0.001) and diastolic blood pressure (DBP) by 1.4 +/- 3.1 mmHg (p < 0.001), while basal heart rate decreased by 4.1 +/- 4.6 bpm (p < 0.001). Both SBP and DBP reduction were significantly related to the baseline SBP (p < 0.001) and DBP (p < 0.001), respectively. Diastolic blood pressure change was also inversely related to the patient’s age (p = 0.004). No significant difference was perceived in the metabolic syndrome subgroup. In our retrospective study, highly purified omega-3 PUFAs long-term supplementation is associated with a significant reduction in SBP, DBP, and basal heart rate in hypertriglyceridemic patients with normal-high blood pressure. The main determinants of the omega-3 PUFAs anti-hypertensive effect appear to be the basal blood pressure level and age. Future research will clarify if omega-3 PUFAs supplementation could improve the antihypertensive action of specific blood pressure lowering drug classes and of statins.

Atherogenic alterations in hypertriglyceridemic patients would not depend on insulin resistance

Background and aimsSeveral studies have been carried out to characterize the different alterations associated with hypertriglyceridemia (HTG) and to identify this dyslipemia as an independent risk factor for cardiovascular disease (CVD). HTG is frequently, but not always, associated with insulin resistance (IR). The present study was aimed to evaluate if the alterations observed in biomarkers of CVD were similar in HTG states independently of IR. MethodsHTG was defined as triglycerides ≥1.69mmol/l and IR as HOMA-IR ≥3.1. HTG-IR patients (n=15) were compared with HTG subjects without IR (WIR) (n=15) and with normotriglyceridemic (NTG)-WIR individuals (n=30). ResultsBoth HTG groups shared the increment in VLDL-C and non-HDL-C, HDL enrichment in triglycerides and depletion in phospholipids, the decrease in adiponectin concentration, and the increase in CETP activity. HDL-C and VCAM-1 levels were altered only in HTG-IR patients in comparison with the other groups, while oxidized LDL was only higher in HTG-IR than the control group. Multiple regression analysis identified triglycerides as the independent predictor of HDL-C, CETP activity and oxidized LDL levels. ConclusionThe increase in triglycerides is the major determinant factor of the atherogenic modifications observed, while IR would be an amplifier factor.

Healthy Lifestyle Behaviors and Triglycerides

Healthy Lifestyle Behaviors and Triglycerides

Apolipoprotein B100 is a better treatment target than calculated LDL and non-HDL cholesterol in statin-treated patients

Clinical trials have shown that apolipoprotein B100 (apoB) is better than calculated low-density lipoprotein cholesterol (c-LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) as a target for statin treatment. However, there are no published reports of how well these targets are reached in patients with more severe hyperlipidaemias than represented in trials, as seen in lipid clinics. We audited 195 patients attending a tertiary centre lipid clinic, who had been treated with a statin for more than one year. We measured total cholesterol, HDL-cholesterol (HDL-C) and triglyceride and from these calculated LDL-cholesterol (LDL-C) and non-HDL-C. We determined the average measured apoB values, at critical target values of LDL-C and non-HDL-C, by linear regression and compared them with values of apoB considered equivalent to these cholesterol indexes by expert groups. We also assessed the number of patients, both before and after treatment, in whom c-LDL-C and non-HDL-C could not be calculated due to hypertriglyceridaemia. At the LDL-C target of 2.6 mmol L(-1) and the non-HDL-C target of 3.4 mmol L(-1), the measured apoB values were significantly higher than consensus apoB target values. The difference was most marked for c-LDL-C in hypertriglyceridaemic subjects and for non-HDL-C in patients without hypertriglyceridaemia. A similar pattern was seen using centile-derived consensus values but the differences were accentuated because this approach generates lower equivalent consensus apoB values. ApoB offers a more consistent treatment target independent of hypertriglyceridaemia and would obviate technical problems related to high triglycerides.

Dual Metabolic Defects Are Required to Produce Hypertriglyceridemia in Obese Subjects

Obesity increases the risk of cardiovascular disease and premature death. However, not all obese subjects develop the metabolic abnormalities associated with obesity. The aim of this study was to clarify the mechanisms that induce dyslipidemia in obese subjects. Stable isotope tracers were used to elucidate the pathophysiology of the dyslipidemia in hypertriglyceridemic (n=14) and normotriglyceridemic (n=14) obese men (with comparable body mass index and visceral fat volume) and in normotriglyceridemic nonobese men (n=10). Liver fat was determined using proton magnetic resonance spectroscopy, and subcutaneous abdominal and visceral fat were measured by magnetic resonance imaging. Serum triglycerides in obese subjects were increased by the combination of increased secretion and severely impaired clearance of triglyceride-rich very-low-density lipoprotein(1) particles. Furthermore, increased liver and subcutaneous abdominal fat were linked to increased secretion of very-low-density lipoprotein 1 particles, whereas increased plasma levels of apolipoprotein C-III were associated with impaired clearance in obese hypertriglyceridemic subjects. Dual metabolic defects are required to produce hypertriglyceridemia in obese subjects with similar levels of visceral adiposity. The results emphasize the clinical importance of assessing hypertriglyceridemic waist in obese subjects to identify subjects at high cardiometabolic risk.

Hemostatic effects of bezafibrate and ω-3 fatty acids in isolated hypertriglyceridemic patients

This study aimed to compare the effects of ω-3 fatty acids and fibrate treatment on plasma levels and activities of hemostatic risk factors on glucose and lipid metabolism in subjects with isolated hypertriglyceridemia. Seventy-three subjects with elevated triglyceride levels were allocated into one of the following treatment options: bezafibrate (200mg twice daily), ω-3 fatty acids (1g twice daily) or placebo. Plasma lipids, glucose homeostasis markers (fasting and 2-h post-glucose load plasma glucose levels and HOMA), as well as plasma levels/activities of fibrinogen, factor VII and PAI-1 were determined at baseline, on the day of randomization, and after 4 and 12 weeks of the treatment. Not only did bezafibrate improve plasma lipids, but it also increased glucose sensitivity and tended to reduce post-glucose loads of plasma glucose. Except for the reduction in plasma triglycerides, ω-3 fatty acids produced no effect on the lipid profile and insulin sensitivity. Both treatment options reduced, to similar extents, plasma levels of fibrinogen and PAI-1 and factor VII coagulant activity. Our study indicates that, although fibrates exhibit more-pronounced metabolic effects than do ω-3 fatty acids, both these treatment options are equipotent in producing a complex beneficial effect on hemostasis in isolated hypertriglyceridemic subjects.

Triglycerides and Cardiovascular Disease

A long-standing association exists between elevated triglyceride levels and cardiovascular disease* (CVD).1,2 However, the extent to which triglycerides directly promote CVD or represent a biomarker of risk has been debated for 3 decades.3 To this end, 2 National Institutes of Health consensus conferences evaluated the evidentiary role of triglycerides in cardiovascular risk assessment and provided therapeutic recommendations for hypertriglyceridemic states.4,5 Since 1993, additional insights have been made vis-a-vis the atherogenicity of triglyceride-rich lipoproteins (TRLs; ie, chylomicrons and very low-density lipoproteins), genetic and metabolic regulators of triglyceride metabolism, and classification and treatment of hypertriglyceridemia. It is especially disconcerting that in the United States, mean triglyceride levels have risen since 1976, in concert with the growing epidemic of obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM).6,7 In contrast, mean low-density lipoprotein cholesterol (LDL-C) levels have receded.7 Therefore, the purpose of this scientific statement is to update clinicians on the increasingly crucial role of triglycerides in the evaluation and management of CVD risk and highlight approaches aimed at minimizing the adverse public health–related consequences associated with hypertriglyceridemic states. This statement will complement recent American Heart Association scientific statements on childhood and adolescent obesity8 and dietary sugar intake9 by emphasizing effective lifestyle strategies designed to lower triglyceride levels and improve overall cardiometabolic health. It is not intended to serve as a specific guideline but will be of value to the Adult Treatment Panel IV (ATP IV) of the National Cholesterol Education Program, from which evidence-based guidelines will ensue. Topics to be addressed include epidemiology and CVD risk, ethnic and racial differences, metabolic determinants, genetic and family determinants, risk factor correlates, and effects related to nutrition, physical activity, and lipid medications. In the United States, the National Health and …

Cardiovascular disease in recent onset diabetes mellitus

Diabetes is associated with a marked increased risk of atherosclerotic vascular disorders, including coronary, cerebrovascular, and peripheral artery disease. Cardiovascular disease (CVD) could account for disabilities and high mortality rates in patients with diabetes. Conventional risk factors, including hyperlipidemia, hypertension, smoking, obesity, lack of exercise, and a positive family history, contribute similarly to macrovascular complications in type 2 diabetic patients and non-diabetic subjects. The levels of these factors in diabetic patients are certainly increased, but not enough to explain the exaggerated risk for macrovascular complications in the diabetic population. Furthermore, recently, macrovascular complications of diabetes have been shown to start before the onset of diabetes. Indeed, several clinical studies have confirmed the increased risk of CVD in patients with impaired glucose tolerance (IGT). Since insulin resistance-related postprandial metabolic derangements are thought to play a central role in the development and progression of CVD in patients with IGT, amelioration of postprandial metabolic disturbance is a therapeutic target for the prevention of CVD in these high-risk patients. Therefore, in this paper, we review the molecular mechanisms for the increased risk of CVD in recent onset diabetes mellitus, especially focusing on postprandial dysmetabolism. We also discuss here the potential therapeutic strategies that specially target the mechanisms responsible for vascular alterations in diabetes.

Hipertrigliceridemia, esteatosis hepática y riesgo cardiovascular

Objectives Nonalcoholic fatty liver disease (NAFLD) has been associated with both hypertriglyceridemia and an increased risk of cardiovascular complications. The aim of our study was to assess factors related to the presence of NAFLD in patients with hypertriglyceridemia and to calculate their Framingham score risk. Patients and methods A total of 1.394 subjects (mean age 50.3 ± 12.4 years, 74.1% male) participating in the Hypertriglyceridemia Register of the Spanish Society of Arteriosclerosis were studied. Hypertriglyceridemia was considered as a triglyceride concentration ≥200 mg/dL confirmed on two different occasions. Liver steatosis was diagnosed by ultrasound. NAFLD was defined as the presence of steatosis in patients who were moderate alcohol consumers or abstainers. Results Of the 649 subjects included in the final sample, 321 (49.5%) had NAFLD. As expected, liver enzymes were higher in this population. The presence of NAFLD was associated with a higher body mass index (p < 0.001), increased waist circumference (p < 0.001) and a higher prevalence of metabolic syndrome (p < 0.001). No differences in triglyceride concentration or in the prevalence of diabetes were found between subjects with and without NAFLD. A Framingham risk score above 20% was observed in 52.4% of the participants, with no differences in relation to NAFLD status. Conclusions Hypertriglyceridemic subjects with NAFLD have a higher prevalence of obesity, mainly abdominal, and metabolic syndrome. The estimated cardiovascular risk in this population is very high but does not differ according to the presence of NAFLD.

Short-term fenofibrate treatment reduces elevated plasma Lp-PLA 2 mass and sVCAM-1 levels in a subcohort of hypertriglyceridemic GOLDN participants

High levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with inflammation, atherosclerosis, and coronary heart disease events. In addition, Lp-PLA(2) has been linked to classical markers of endothelial activation, including soluble vascular cell adhesion molecule-1 (sVCAM-1). Although treatment with fenofibrate reduces Lp-PLA(2) mass, it is unclear whether fenofibrate reduces sVCAM-1 levels or whether an association exists between any changes observed in Lp-PLA(2) and sVCAM-1. Concentrations of Lp-PLA(2) mass and sVCAM-1 levels were measured in plasma at baseline and after 3 weeks of fenofibrate treatment (160 mg/d) in 96 hypertriglyceridemic participants of the Genetics of Lipid-lowering Drugs and Diet Network study. Lp-PLA(2) and sVCAM-1 were stratified by tertiles as determined by baseline levels of the respective target. Fenofibrate treatment resulted in a 30.1% mean increase in Lp-PLA(2) mass (P = 0.0003) and a 14.7% mean increase in sVCAM-1 levels (P = 0.0096) but only in tertile1 of either target. In contrast, Lp-PLA(2) mass was reduced by 35.3% (P < 0.0001) in tertile 3. Soluble VCAM-1 levels were significantly reduced by 7.74% (P = 0.0109) and 17.2% (P < 0.0001) in tertiles 2 and 3, respectively. No associations were observed between Lp-PLA(2) and sVCAM-1 at baseline or post-treatment. In conclusion, fenofibrate treatment in hypertriglyceridemic subjects reduced the levels of Lp-PLA(2) mass and sVCAM-1, but only in those with elevated baseline levels of these biomarkers. The greatest reductions in Lp-PLA(2) levels were observed in individuals with Lp-PLA(2) concentrations indicative of increased cardiovascular disease risk (>200 ng/mL).