Atherogenic Risk Markers Research Articles

The triglyceride-glucose index as an indicator of latent atherogenicity of the plasma lipid profile in healthy men with normolipidaemia

ABSTRACT Objectives The triglyceride-glucose (TyG) index is a novel diagnostic marker for various metabolic and cardiovascular diseases. However, little is known about the association of the TyG index with plasma atherogenicity, especially with its latent forms. The aim of this study was to assess the potential of the use of the TyG index as a marker of atherogenic risk. Methods A total of 202 men with normolipidaemia, aged 20–60 years, were enrolled in this study. Fasting biochemical parameters were measured. The TyG index was calculated as ln[triglyceride(mg/dL)×glucose(mg/dL)]/2. The diagnostic ability of the TyG index for detecting atherogenic risk was tested by receiver operating characteristic (ROC) curve analysis. Results A substantial portion of normolipidaemic men had deviations from the reference values for the indices calculated using apolipoproteins. Unfavorable values for the apolipoprotein (apo) B/apoA-I ratio, low-density lipoprotein cholesterol/apoB (LDL-C/apoB) ratio, and the atherogenic index (ATH index) were observed in 32.7%, 31.7%, and 14.4% of men, respectively. The results of ROC curve analysis showed that the TyG index had good diagnostic ability for identifying unfavorable apolipoprotein indices in normolipidaemic men. Conclusions Thus, the TyG index can be a valuable additional marker for assessing latent atherogenic risk; it can provide useful information for the diagnosis and treatment of early atherosclerosis.

Relationship between thyroid function and lipid atherogenic profile in pediatric patients with multisystem inflammatory syndrome associated with COVID-19.

Concurrent alterations in the metabolic profile and thyroid dysfunction, including non-thyroidal illness syndrome (NTIS) has been reported in multisystem inflammatory syndrome in children (MIS-C). Considering the influence of thyroid hormones (TH) on lipid metabolism, we explored the relationship between thyroid function and the atherogenic lipid profile in children with MIS-C at admission and during a 12-month follow-up. we considered children admitted for MIS-C. Total and HDL cholesterol, triglycerides (TG), fasting plasma glucose, fasting plasma insulin as well as free T3 (FT3), free T4 (FT4), and TSH were assessed at diagnosis within 24 h of admission and during follow-up. TG/HDL ratio, no-HDL/HDL ratio and atherogenic index of plasma was also considered as atherogenic risk markers. we monitored 56 children. On admission, pathological levels of FT3, FT4, TSH, TG, TC, HDL, TG/HDL ratio, no-HDL/HDL ratio, and AIP were detected. Correlation analyses revealed associations between FT3, FT4, and lipid markers and TSH with TG. During monitoring, while complete restoration of TH balance was achieved at 12 months, some patients still exhibited an altered lipid profile, without correlation between thyroid function and lipid markers. we supported a relationship between thyroid function and an atherogenic lipid profile in children with MIS-C. This may result from interactions between adaptive and innate metabolic responses and genetic predisposition. Elucidating the relationship between TH and metabolic pathways during infections could help identify new biomarkers to prevent acute and fatal outcomes, improving patient prognosis and protecting long-term health.

Dyslipidaemia & oxidative stress in patients of psoriasis: Emerging cardiovascular risk factors

Background & objectives:Psoriasis is a recurrent hyper-proliferative skin disease which is often associated with free radical generation, abnormal lipid metabolism and increased inflammatory secretion that induce cardiovascular risk in these patients. The present study was intended to evaluate serum lipids, lipoprotein and oxidants-antioxidants status and to establish their relationship with atherogenic risk markers [oxidized low-density lipoprotein (oxLDL) and high-sensitivity C-reactive protein (hsCRP)] in patients with psoriasis.Methods:The study was conducted on 150 psoriasis patients and 150 age- and sex-matched healthy controls. Overnight fasting blood samples were obtained for lipids, lipoproteins, lipid oxidation and peroxidation products [oxLDL, malondialdehyde (MDA)], antioxidant enzymes [reduced glutathione (GSH) and total antioxidant status] levels and hsCRP estimations.Results:The mean levels of atherogenic lipids [total cholesterol (P<0.001), triacylglycerol (P<0.01)], lipid peroxidation products (P<0.001) and oxLDL and hsCRP (P<0.001) levels in patients with psoriasis were found to be significantly higher than those of healthy controls. On the other hand, ferric-reducing ability of plasma (FRAP, P<0.001) and antioxidant enzyme activities (reduced GSH, P<0.01) were significantly lower when compared to healthy controls. The plasma oxLDL was positively correlated to LDL cholesterol (P<0.001) and MDA (P<0.001) and negatively associated with antioxidant status in these patients. Serum MDA, FRAP and oxLDL were correlated with risk of atherosclerosis in the patients with psoriasis; however, no significant association was found between reduced GSH and hsCRP.Interpretation & conclusions:The study results suggest that LDL oxidation and reactive oxygen species in addition to inflammatory markers may play a pivotal role in inducing atherosclerosis in patients of psoriasis.

Iatrogenic hyperinsulinemia in type 1 diabetes: Its effect on atherogenic risk markers

AimsInsulin is lipogenic and may invoke inflammation. We wished to determine if well controlled human and mice with type 1 diabetes had iatrogenic hyperinsulinemia as an explanation for the increased rate of coronary artery disease (CAD) in type 1 diabetes. MethodsType 1 diabetic subjects with HbA1C less than 7.0% had plasma insulin measured before and one hour after a Boost® challenge and a dose of subcutaneously administered insulin. These levels were compared with non-diabetic humans. Plasma insulin levels in well controlled NOD mice with type 1 diabetes were measured 3h and 17h after their usual dose of insulin. Hepatic cholesterol-relevant CAD and inflammation markers were measured in the NOD mice. ResultMarked iatrogenic hyperinsulinemia was observed in patients at levels of approximately two times higher than in non-diabetic controls. Similar findings were present in the NOD mice. Hepatic CAD risk markers were increased by insulin, but did not exceed normal expression levels in non-diabetic mice with lower insulin. In contrast, insulin-mediated stimulation of pro-inflammatory mediators TNF-α and IL-1β remained significantly higher in hyperinsulinemic NOD than non-diabetic mice. ConclusionOptimal insulin therapy in mice and humans with type 1 diabetes causes iatrogenic hyperinsulinemia and subsequently promotes pro-inflammatory macrophage response independent of hepatic cholesterol-relevant CAD markers. The tight glycemic control in type 1 diabetes may thus increase the risk for atherogenesis via inflammation.

Negatively charged low-density lipoprotein is associated with atherogenic risk in hypertensive patients

Negatively charged low-density lipoprotein (LDL), generated via multiple processes such as oxidation, acetylation, or glycosylation, plays a key role in the initiation and progression of atherosclerosis and related diseases. Anion-exchange high-performance liquid chromatography (AE-HPLC) can subfractionate LDL into LDL-1, LDL-2, and LDL-3 based on LDL particle charge, but the clinical significance of LDL subfractions has not yet been elucidated. The aim of this study was to determine the clinical significance of these fractions with particular regard to atherogenic risk in hypertensive patients. Ninety-eight patients with essential hypertension (age 67.0 ± 10.7 years; 54 males) were enrolled in the present study. The relationships between LDL subfractions and atherogenic risk factors, including lipid profiles, blood pressure and plasma 8-isoprostane as a marker of oxidative stress, were examined. LDL-1 levels were significantly and negatively correlated with body mass index (r = -0.384, p < 0.001), systolic blood pressure (r = -0.457, p < 0.001), non-high-density lipoprotein cholesterol levels (r = -0.457, p < 0.001) and 8-isoprostane levels (r = -0.415, p < 0.001). LDL-3, which is the most negatively charged fraction of total LDL, was significantly and positively correlated with these parameters (r = 0.267, 0.481, 0.357, and 0.337, respectively). LDL-1 levels were significantly lower (p < 0.001), and LDL-2 and LDL-3 levels were significantly higher (each p < 0.001) in patients with poorly controlled hypertension than in patients with well-controlled hypertension. In addition, an increase in the total number of traditional risk factors at time of study participation, but not previous diagnosis, was associated with a decrease in LDL-1 levels and increases in LDL-2 and LDL-3 levels. These data suggest that LDL subfractions are associated with multiple atherogenic risk factors and that treatment to modify these risk factors could result in changes in LDL subfraction levels. In conclusion, LDL subfractions isolated by AE-HPLC may represent a marker of atherogenic risk in patients with hypertension.

Increased plasma glycated low-density lipoprotein concentrations in diabetes: a marker of atherogenic risk.

Nonenzymatic glycation of apolipoprotein B in the low-density lipoprotein (LDL) complex has been considered a proatherogenic modification contributory to the increased susceptibility of patients with diabetes to atherosclerosis. We postulated that glycated LDL concentrations might be associated with other markers of cardiovascular disease. To explore this hypothesis, we measured glycated LDL concentrations by a monospecific immunoassay in 50 patients with type 1 and 100 patients with type 2 diabetes and examined relationships with the amount of albumin excretion and the serum cholesterol and triglyercide concentrations. Plasma glycated LDL showed a significant positive correlation (r = 0.325; P < 0.001) with urinary albumin excretion that was higher in type 1 (r = 0.463) than in type 2 (r = 0.245) patients. The mean glycated LDL concentration progressively increased with increasing albumin excretion when patients were subcategorized into groups of normoalbuminuria, low (</=100 microg/mg of creatinine), and high (101-300 microg/mg) microalbuminuria, and proteinuria. Glycated LDL also correlated positively and significantly with cholesterol (r = 0.578) and triglyceride (r = 0.350) concentrations. The significant correlations in this cross-sectional analysis between glycated LDL and urinary albumin excretion, an index of cardiovascular mortality, and cholesterol and triglyceride concentrations, traditional markers of risk for cardiovascular disease, support the hypothesis that an elevated level of glycated LDL represents an atherogenic risk factor in patients with diabetes.

Lipid atherogenic risk markers can be more favourably influenced by the cis-9,trans-11-octadecadienoate isomer than a conjugated linoleic acid mixture or fish oil in hamsters.

The aim of our present study was to compare the efficiency of conjugated linoleic acids (CLA) and fish oil in modulating atherogenic risk markers. Adult male hamsters were given a cholesterol-rich diet (0.6 g/kg) for 8 weeks; the diet was supplemented with 5 g cis-9,trans-11-CLA isomer/kg, 12 g CLA mixture (CLA-mix)/kg, 12 g fish oil/kg or 12 g fish oil+12 g CLA-mix/kg. The plasma cholesterol status was improved only with the cis-9,trans-11-CLA (HDL-cholesterol and HDL-cholesterol:LDL-cholesterol ratio, P<0.05), but was of borderline significance for CLA-mix (HDL-cholesterol:LDL-cholesterol ratio, P=0.06), with an increase (33-40 %) in the liver lipoprotein receptors (scavenger receptor-type I and LDL ApoB/E receptor) and HDL-binding protein 2 (P<0.05). A 100 % pigment gallstones incidence and a slight insulin resistance (homeostatic model assessment index) were observed in the CLA-mix-fed hamsters (P=-0.031). In comparison, fish-oil feeding alone improved merely the scavenger receptor-type I and HDL-binding protein 2 liver status and faeces sterol output. For most of our present observations, the concomitant intake of fish oil and CLA-mix gave dominant effects that were exclusive and specific to one or the other oil. In conclusion, part of the beneficial effects of CLA in the present study can be ascribed to the cis-9,trans-11-isomer, and these did not generally overlap with those of fish oil. In addition, the CLA-mix effects are clearly affected by the marine (n-3) fatty acids.

Plasma matrix metalloproteinases, low density lipoprotein oxidisability and soluble adhesion molecules after a glucose load in Type 2 diabetes

BackgroundAcute hyperglycaemia is an independent cardiovascular risk factor in Type 2 diabetes which may be mediated through increased oxidative damage to plasma low density lipoprotein, and in vitro, high glucose concentrations promote proatherogenic adhesion molecule expression and matrix metalloproteinase expression.MethodsWe examined these atherogenic risk markers in 21 subjects with Type 2 diabetes and 20 controls during an oral 75 g glucose tolerance test. Plasma soluble adhesion molecule concentrations [E-selectin, VCAM-1 and ICAM-1], plasma matrix metalloproteinases [MMP-3 and 9] and plasma LDL oxidisability were measured at 30 minute intervals.ResultsIn the diabetes group, the concentrations of all plasma soluble adhesion molecules fell promptly [all p < 0.0001] related principally to glycaemic excursions, but such changes also occurred in the control group. Plasma MMP-3 and -9 concentrations were lower [p < 0.05], and LDL oxidisability greater [p < 0.01] in the diabetes group but did not change in either group. There was a direct relationship between plasma MMP-9 and s ICAM-1 in the controls [r = 0.62; p = 0.006] perhaps suggesting a functional relationship between s ICAM-1 shedding and MMP-9.ConclusionsA glucose load leads to a rapid fall in plasma soluble adhesion molecule concentrations in Type 2 diabetes and controls, perhaps reflecting reduced generation of soluble from membrane forms during enhanced leukocyte – endothelial adhesion or increased hepatic clearance, without changes in plasma matrix metalloproteinase concentrations or low density lipoprotein oxidisability. These in vivo findings are in contrast with in vitro data.

Impact on lipoprotein profile after long-term testosterone replacement in hypogonadal men.

Testosterone serum levels may influence the lipoprotein metabolism and possibly atherogenic risk. Our aim was to investigate the effects of long-term testosterone supplementation in hypogonadal men on multiple lipoprotein markers. 18 Hypogonadal men were studied before and after 3, 6, and 18 (n = 7) months of treatment with testosterone enanthate. During treatment, serum testosterone and estradiol increased, reaching normal levels (p < 0.0001 and 0.003, respectively). This was associated with a decrease in HDL cholesterol (from 1.40 +/- 0.10 mmol/l to 1.22 +/- 0.08 mmol/l, p < 0.001) after six months at the expense of HDL2 cholesterol (p < 0.01), as well as apoprotein A1 (from 139 +/- 3.4 mg/dl to 126 +/- 3.0 mg/dl, p < 0.005). Hepatic lipase activity increased (p < 0.05) and correlated positively with testosterone (r = 0.56, p < 0.02) and negatively with HDL cholesterol (r = - 0.58, p < 0.02). Total and LDL cholesterol, triglycerides, and apoprotein B did not increase. Among the seven patients who completed 18 months of treatment, triglycerides, total cholesterol, LDL and HDL cholesterol, as well as total cholesterol/HDL cholesterol ratio values did not differ from baseline while apoprotein A1 (p < 0.03) and HDL cholesterol (p < 0.015) remained decreased and hepatic lipase unchanged. Restoration of testosterone levels in hypogonadal men in this study did not reveal unfavorable changes based on total cholesterol/HDL cholesterol and LDL cholesterol/apoprotein B ratios, which are both atherogenic risk markers. Whether the changes in light of lipoprotein metabolism will adversely influence cardiovascular risk over time remains to be determined.

Triglycerides and coronary heart disease: implications of recent clinical trials.

This paper reviews the clinical trial data that offer insight into the question of whether, and in what groups of people, triglycerides might be an appropriate therapeutic target for the primary or secondary prevention of atherosclerotic cardiovascular disease. Two angiographic trials (the Lopid Coronary Angiography Trial and the Bezafibrate Coronary Atherosclerosis Intervention Trial) and three clinical endpoint trials (the Helsinki Heart Study, the Bezafibrate Infarction Prevention Study, and the VA HDL Intervention Trial) are reviewed. Hypertriglyceridemia per se is probably not an appropriate therapeutic target for the prevention of atherosclerotic cardiovascular disease because it is a poor marker of atherogenic risk and because there have been no clinical trials that have directly addressed the question of whether lowering the triglyceride level reduces the number of clinical events. The studies reviewed here, however, suggest that patients with established coronary heart disease and a high triglyceride level, in association with either a low high-density lipoprotein-cholesterol level or perhaps other features of the metabolic syndrome, such as obesity, diabetes, or hypertension, may benefit from fibrate therapy. For patients without established coronary heart disease, it is reasonable to consider hypertriglyceridemia as a risk marker prompting the aggressive treatment of other risk factors such as hypertension, diabetes, high low-density lipoprotein-cholesterol, and obesity.

Low-density lipoprotein particle size is not a discriminating marker for atherogenic risk in male offspring of parents with early coronary artery disease

The aim of this study was to assess the importance of low-density lipoprotein (LDL) particle size as a marker of atherogenic risk in male offspring of a parent with early coronary artery disease (CAD) before the age of 60 years. CAD-positive (CAD +) offspring were recruited into two groups based on age, 15 to 30 years (In = 20) and 31 to 45 years in = 41), and matched to CAD-negative (CAD −) offspring by age and body mass index (BMI) (n = 20 and 21 per group). LDL peak particle diameter was assessed by polyacrylamide gradient gel electrophoresis. There was no significant difference in LDL peak particle diameter between CAD + and CAD − offspring (26.2 ± 0.1 v 26.2 ± 0.1 nm, mean ± SE). There was also no difference between CAD + offspring and CAD offspring when comparisons were made within their own age group (26.5 ± 0.1 nm in younger CAD + offspring v 26.2 ± 0.1 nm in younger CAD − offspring, and 26.0 ± 0.1 nm in older CAD + offspring v 26.1 ± 0.2 nm in older CAD − offspring. Peak particle diameter was significantly greater in younger CAD + offspring than in older CAD + offspring (26.5 ± 0.1 v 26.0 ± 0.1 nm, P < .05). We conclude that small LDL particle size is not a discriminating marker for early atherogenic risk, and that measurement of LDL particle size has limited value in the assessment of coronary risk, at least in the age ranges we studied.