Usefulness of lipoprotein ratios in assessing carotid atherosclerosis in Japanese type 2 diabetic patients

ObjectiveIt is indicated that total/HDL cholesterol and LDL/HDL cholesterol ratios have more predictive power for cardiovascular disease compared to classic lipid parameters. However, there have been few reports about the usefulness of these indices for the assessment of early stage atherosclerosis in Japanese type 2 diabetic subjects.MethodsWe examined the relation between various lipid parameters and carotid atherosclerosis in 934 type 2 diabetic subjects without apparent atherosclerotic diseases (males, 71.7%; age, 59.6 ± 10.5 years (mean ± SD)). Serum concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), and triglyceride were measured. LDL cholesterol (LDL-C) level was calculated using the Friedewald formula. The presence of carotid plaque and intima-media thickness (IMT) were evaluated by ultrasonography.ResultsA stepwise multivariate regression analysis demonstrated that HDL-C (β = ?0.110, p < 0.001), TC/HDL-C (β = 0.132, p < 0.001) and LDL-C/HDL-C ratios (β = 0.132, p < 0.001) were independent determinants of IMT even after adjustment of other conventional risk factors. However, there was no significant correlation between IMT and TC, triglyceride, LDL-C, and non-HDL-C levels. TC/HDL-C and LDL-C/HDL-C ratios and non-HDL-C levels were significantly higher, but HDL-C levels were significantly lower in patients with carotid plaque than those without it (p < 0.05). There was no significant difference between the groups regarding TC, LDL-C, and triglyceride levels. Furthermore, TC/HDL-C (OR; 1.34, p < 0.001) and LDL-C/HDL-C (OR; 1.54, p < 0.001) ratios showed a positive and linear relationship with the prevalence of carotid plaque, whether covariates were adjusted or not.ConclusionsTC/HDL-C and LDL-C/HDL-C ratios are useful as a tool to assess the risk of early stage atherosclerosis in Japanese type 2 diabetic patients.     

Normal weight obese (NWO) women: an evaluation of a candidate new syndrome

Background and aimsObesity, an independent risk factor for cardiovascular disease (CVD), has been associated with the early development of coronary atherosclerosis in adolescents and young men. A subset of metabolically obese but normal weight individuals was identified, with potentially increased risks for development of the metabolic syndrome despite their normal body mass index. We determined the relationship among body fat distribution and selected CVD risk factors to distinguish normal weight obese from controls with normal metabolic profiles.Methods and resultsWe analysed anthropometric variables, body composition by DXA, RMR by indirect calorimetry and bioumoral variables of 74 clinically healthy Caucasian Italian women. Significant differences were observed in the biochemical HDL-chol values between NWO and controls and pre-obese-obese. Significant correlations were found among cardiovascular risk indexes, LEAN of the right part of the trunk and TC/HDL (R = −0.69, p < 0.001) and LDL/HDL (R = −0.72, p < 0.001), and LEAN and RMR (R = 0.44, p = 0.022) of NWO women.ConclusionsIn normal weight obese women the cardiovascular risk indexes are related to metabolic variables and to body fat mass distribution. NWO individuals showed a relationship between the decrease in LEAN of the left leg and an increase in CVD risk factors. We suggest that LEAN distribution seems to be a potential predictor of CVD.     

Postprandial modulation of serum paraoxonase activity and concentration in diabetic and non-diabetic subjects

ObjectivesTo analyse the HDL associated anti-oxidant enzyme paraoxonase-1, during postprandial hyperlipaemia.Methods and resultsType 2 diabetic patients (n = 72), glucose intolerant patients (n = 10) and controls (n = 38) consumed a high fat:high carbohydrate meal. Blood samples were collected up to 4 h and analysed for lipids and paraoxonase-1. In vitro studies examined HDL function with respect to the enzyme. There were significant postprandial increases in serum triglycerides. Paraoxonase-1 activity decreased significantly throughout the postprandial phase. Concentrations of the enzyme initially decreased significantly, but returned to fasting concentrations at 4 h. Specific activities were significantly lower at 4 h, compared to fasting. The decrease in specific activity was linked to the dynamic phase of postprandial lipoprotein metabolism. Apo AI limited loss of paraoxonase-1. HDL isolated after being subjected to postprandial conditions in vitro had reduced capacity to associate with and stabilise PON1.ConclusionsPostprandial hyperlipaemia was associated with changes to serum paraoxonase-1, consistent with a reduced anti-oxidant potential of HDL. No differences were observed between diabetic and non-diabetic patients, suggesting that the effect was linked to postprandial hyperlipaemia. Modifications to paraoxonase-1 could contribute to increased risk of vascular disease associated with postprandial lipaemia, particularly in diabetic patients, who are already deficient in serum paraoxonase-1.     

Plasma proprotein convertase subtilisin-kexin type 9 does not change during 24h insulin infusion in healthy subjects and type 2 diabetic patients

PurposeProprotein convertase subtilisin–kexin type 9 (PCSK9) promotes low density lipoprotein (LDL) receptor degradation, thereby providing a key pathway for LDL metabolism. PCSK9 mRNA expression may be upregulated by insulin in murine models. Here we examined effects of exogenous hyperinsulinemia on plasma PCSK9 levels in humans without and with type 2 diabetes mellitus.MethodsA 24 h moderately hyperinsulinemic glucose clamp (30 mU/kg/h) was performed in 8 healthy men and 8 male type 2 diabetic patients. Plasma PCSK9 was measured using a sandwich enzyme-linked immunosorbent assay.ResultsPlasma LDL cholesterol and apolipoprotein B were lowered by insulin in healthy subjects and diabetic patients (P < 0.01 for all), whereas triglycerides were also decreased in healthy subjects (P < 0.01). Plasma PCSK9 levels remained unchanged in healthy subjects (median (interquartile range) change, ?23 (?63 to 25) %, P = 0.50) and in diabetic patients (change, 4 (?17 to 44) %, P = 0.20). Individual absolute and relative changes in LDL cholesterol, apolipoprotein B and triglycerides after 24 h of insulin were unrelated to changes in PCSK9 (P > 0.15 for all).ConclusionPlasma PCSK9 levels are not increased by exposure to moderate 24 h hyperinsulinemia in healthy and type 2 diabetic individuals.     

Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia

BackgroundOmega-3 fatty acids and fenofibrate are both used to treat patients with hypertriglyceridemia. However, a head-to-head comparison of the lipoprotein and metabolic effects of these two medicines has not been published.MethodsThis was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Fifty patients in each group were given placebo, omega-3 fatty acids 2 g (most commonly used dosage in Korean patients), or fenofibrate 160 mg, respectively daily for 2 months.ResultsOmega-3 fatty acids therapy decreased triglycerides by 21% and triglycerides/HDL cholesterol and improved flow-mediated dilation (P < 0.01), however, did not significantly change insulin, plasma adiponectin levels, and insulin sensitivity (determined by QUICKI) relative to baseline measurements. Fenofibrate therapy decreased total cholesterol, triglycerides by 29%, and triglycerides/HDL-cholesterol (all P < 0.01) and improved flow-mediated dilation when compared with baseline. When compared with placebo and omega-3 fatty acids, fenofibrate therapy decreased non-HDL cholesterol (P < 0.001) and triglycerides/HDL cholesterol (P = 0.016) while increasing HDL cholesterol (P < 0.001) and apolipoprotein AI (P = 0.001). Of note, when compared with omega-3 fatty acids, fenofibrate therapy decreased fasting insulin (P = 0.023) and increased plasma adiponectin (P = 0.002) and insulin sensitivity (P = 0.015).ConclusionsOmega-3 fatty acids and fenofibrate therapy promoted similar changes in triglycerides and endothelium-dependent dilation. However, fenofibrate therapy had substantially better effects on lipoprotein and metabolic profiles in patients with hypertriglyceridemia.     

Homocysteine is a determinant of ApoA-I and both are associated with ankle brachial index, in an ambulatory elderly population

ObjectiveThe ankle brachial index (ABI) is an indicator of lower extremity peripheral arterial disease (PAD) and a predictor of atherothrombosis. ApoA-I and HDL are associated with PAD, in humans. Homocysteine influences the liver expression of ApoA-I and decreases its blood level and HDL in genetic mice models. We aimed therefore to evaluate whether homocysteine and its nutritional determinants, folate and vitamin B12 are associated with ABI by influencing HDL metabolism, in an ambulatory elderly population.Methods667 elderly volunteers from rural Sicily were assessed for ABI, homocysteine and its determinants, lipid markers and other predictors of PAD. HDL size was assessed in 15 sera in upper and lower quartiles of Hcy distribution.ResultsIn multivariate analysis, ApoA-I and homocysteine were two predictors of ABI (β-coefficient = 2.86, P < 0.004 and β-coefficient = ?3.41, P < 0.001, respectively). Homocysteine correlated negatively with ApoA-I (R = ?0.147, P < 0.001) and with HDL-Cholesterol (R = ?0.113, P = 0.003). The associations of homocysteine, vitamin B12 and methylmalonic acid with ApoA-I and HDL2a particles and that of homocysteine with increased small size HDL3c suggested mechanisms related with impaired synthesis of ApoA-I and HDL and abnormal maturation of HDL particles.ConclusionThe influence of homocysteine on ApoA-I and HDL metabolism provides new insights on its role on vascular diseases, at a cross-point between atherosclerosis and atherothrombosis.     

Glycated apolipoprotein B and myocardial infarction

AimsTo evaluate the association of serum concentrations of glycated apolipoprotein B (ApoBg) with the incidence of myocardial infarction (MI) in subjects with and without diabetes.MethodsThe design is a nested case-control study. The cohort included 5632 subjects over 50 years of age attending the clinical laboratories of a small geographic area in southern Italy. After five years, 4563 subjects were traced and 103 had developed MI. We sampled from the cohort two controls for each incident case of MI, frequency matched for sex and diabetes. ApoBg was measured using a monoclonal antibody. Logistic regression was used for statistical analysis of the data.ResultsApoBg at baseline was higher in subjects who developed myocardial infarction than in controls in both non-diabetic and diabetic subjects (t test, P = 0.009 and P = 0.05 respectively). MI odds ratio in the third tertile of ApoBg was 2.01 (95 % CI 0.93–4.33) in non-diabetic and 2.88 (0.85–9.68) in diabetic subjects (chi-square test for trend; non-diabetics P = 0.03, diabetics P = 0.06). Serum triglycerides, cholesterol, HDL and LDL cholesterol, glucose and insulin were not associated with MI (P > 0.10).ConclusionApoBg at baseline is directly associated with the development of MI in the following five years in both diabetic and non-diabetic individuals.     

Visit-to-visit variability in systolic blood pressure is correlated with diabetic nephropathy and atherosclerosis in patients with type 2 diabetes

ObjectiveRecent studies make remarks on the effect of variability in systolic blood pressure (SBP) on the development of cardiovascular disease. The aim of this study was to investigate the relationship between the variability in SBP and the degree of diabetic nephropathy and atherosclerosis in patients with type 2 diabetes.MethodsWe measured SBP in 422 consecutive patients with type 2 diabetes at every visit during a year, and we calculated the coefficient of variation (CV) of SBP. Then, we evaluated relationships of variability of SBP to degree of urinary albumin excretion (UAE), which is a useful marker for cardiovascular disease as well as diabetic nephropathy, ankle-brachial index (ABI) and pulse wave velocity (PWV).ResultsCV of SBP positively correlated with log UAE (r = 0.210, P < 0.0001) or PWV (r = 0.409, P < 0.0001), whereas CV of SBP inversely correlated with ABI (r = ?0.098, P = 0.0463). Multiple regression analysis demonstrated that CV of SBP independently correlated with log UAE (β = 0.149, P = 0.0072), PWV (β = 0.337, P < 0.0001) or ABI (β = ?0.162, P = 0.0101).ConclusionsNot only average SBP but also variability in SBP is correlated with diabetic nephropathy and atherosclerosis in patients with type 2 diabetes.     

Di-oleoyl phosphatidylcholine (PC-18:1) stimulates paraoxonase 1 (PON1) enzymatic and biological activities: in vitro and in vivo studies

ObjectiveParaoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme which possess anti-atherogenic properties. Our aim was to analyze the effect of HDL phospholipids on HDL-associated paraoxonase (PON1) catalytic and biological activities.Methods and resultsIn HDL isolated from di-oleoyl-phosphatidylcholine (PC-18:1)-enriched serum, HDL–PC-18:1 levels, as well as PON1 lactonase, arylesterase and paraoxonase activities were increased by 23%, 35%, 47% and 63%, respectively, as compared to control HDL (p < 0.01). Furthermore, PON1 contribution to HDL-mediated cholesterol efflux from J774A.1 macrophages was higher in PC-18:1-enriched HDL in comparison to control HDL.In vivo olive oil consumption by Balb C mice increased HDL phospholipids/protein (30%), and HDL–PON1 arylesterase (150%) and lactonase (94%) activities (p < 0.01). Furthermore, in the olive oil-treated mice PON1 contribution to HDL-mediated macrophage cholesterol efflux was higher by 100%, in comparison to placebo mouse HDL (p < 0.01). Similarly, olive oil consumption by healthy subjects increased HDL–PC-18:1 levels, HDL–PON1 arylesterase (88%), lactonase (52%), paraoxonase (140%) activities and PON1 stimulatory effect on HDL-mediated cholesterol efflux (53%) as compared to HDL before treatment (p < 0.01).PC-18:1 stimulatory effect on recombinant PON1 mutant (lacks 20 amino acids at the N-terminal region) paraoxonase and lactonase activities was lower by 56% and 57%, respectively, in comparison to its effect on wild type PON1 (p < 0.01).ConclusionIntervention to increase PON1 activities by HDL enrichment with PC-18:1 could be proven as a beneficial anti-atherogenic therapy.     

Thoracic aortic calcification and coronary heart disease events: the multi-ethnic study of atherosclerosis (MESA)

ObjectiveTo assess the relationship of lipoprotein subfractions to coronary heart disease (CHD).MethodsProspective 29.1-year follow-up of 1905 men measured for lipoprotein mass concentrations by analytic ultracentrifugation between 1954 and 1957. Vital status was determined for 97.2% of the cohort. Blinded physician medical record and death certificate review confirmed 179 CHD deaths. Follow-up questionnaires identified 182 nonfatal myocardial infarctions and 93 revascularization procedures from 1346 (98.3%) of the surviving cohort and from the next-of-kin of 153 men who died.ResultsWhen adjusted for age, total incident CHD was inversely related to HDL2-mass (P = 0.0001) and HDL3-mass (P = 0.02), and concordantly related to LDL-mass (P < 10^?11), IDL-mass (P < 10^?7), and small (P < 10^?7) and large VLDL-mass concentrations (P = 0.003). The hazard reduction per mg/dl of HDL was greater for HDL2-mass than HDL3-mass (P = 0.04). The lowest quartiles of both HDL2-mass (P = 0.007) and HDL3-mass (P = 0.001) independently predicted total incident CHD when adjusted for traditional risk factors. Risk for premature CHD (≤65 years old) was significantly greater in men within the lowest HDL2 (P = 0.03) and HDL3 quartiles (P = 0.04) and having higher LDL-mass concentrations (P = 0.001). Serum cholesterol's relationship to incident CHD (P < 10^?8) was accounted for by adjustment for LDL-mass concentrations (adjusted P = 0.90).ConclusionsLipoprotein subfractions differ in their relationship to CHD.     

Relationship of plasma apolipoprotein M with proprotein convertase subtilisin-kexin type 9 levels in non-diabetic subjects

PurposeApolipoprotein M (apoM) retards atherosclerosis development in murine models, and may be regulated by pathways involved in LDL metabolism. Proprotein convertase subtilisin–kexin type 9 (PCSK9) plays a key role in LDL receptor processing. We determined the extent to which plasma apoM is related to PCSK9 levels in subjects with varying degrees of obesity.MethodsWe sought correlations between plasma apoM and PCSK9, measured using recently developed ELISAs, in 79 non-diabetic subjects.ResultsApoM and PCSK9 levels were both correlated positively with total cholesterol, non-HDL cholesterol, LDL cholesterol and apoB (P < 0.05 to P < 0.001). ApoM correlated positively with PCSK9 in lean individuals (n = 37, r = 0.337, P = 0.041), but not in overweight subjects (n = 32, r = 0.125, P = 0.50) and in obese subjects (n = 10, r = ?0.055, P = 0.88).ConclusionsThe PCSK9 pathway may contribute to plasma apoM regulation in humans. The influence of PCSK9 on circulating apoM appears to be modified by adiposity.     

Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati subjects classified with the metabolic syndrome

Background and aimsCarbohydrate restriction (CR) has been shown to improve dyslipidemias associated with metabolic syndrome (MetS). We evaluated the effects of CR on lipoprotein subfractions and apolipoproteins in Emirati adults classified with the MetS.Methods and results39 subjects (15 men/24 women) were randomly allocated to a CR diet [20–25% energy from carbohydrate (CHO)] for 12 wk (CRD group) or a combination treatment consisting of CRD for 6 wk followed by the American Heart Association diet (50–55% CHO, AHA group) for an additional 6 wk. All subjects reduced body weight, LDL cholesterol and triglycerides (P < 0.01). At baseline all subjects had low concentrations of medium VLDL and total HDL particles associated with the very low plasma triglycerides and HDL cholesterol in this population. After 12 wk, the large VLDL subfraction was decreased over time for subjects in the CRD group (P < 0.01) while these changes were not observed in those subjects who changed to the AHA diet. The number of medium and small LDL particles decreased for all subjects rendering a less atherogenic lipoprotein profile. In agreement with these results, a significant decrease in apolipoprotein (apo) B was observed (P < 0.01). The medium HDL subfraction and apo A-II, which can be considered pro-atherogenic, were also decreased over time in the CRD group only.ConclusionsThese results suggest that weight loss favorably affects lipoprotein metabolism and that the CRD had a better effect on atherogenic VLDL and HDL than the low fat diet recommended by AHA.     

Pancreatic β-cell function relates positively to HDL functionality in well-controlled type 2 diabetes mellitus

BackgroundHigh density lipoproteins (HDLs) have been implicated in glucose homeostasis. Among subjects with normal fasting glucose (NFG), impaired fasting glucose (IFG) and Type 2 diabetes mellitus (T2DM) we tested whether pancreatic β-cell function relates to HDL functionality, as determined by HDL anti-oxidative capacity and cellular cholesterol efflux to plasma.Subjects and methodsHDL anti-oxidative capacity (inhibition of LDL oxidation in vitro), cellular cholesterol efflux (the ability of plasma to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single human donor), glucose and insulin were determined in fasting plasma samples from 37 subjects with NFG, 36 with IFG and 22 with T2DM (no glucose lowering drug or insulin treatment; HbA1c 6.0 ± 1.0%). Homeostasis model assessment was used to estimate pancreatic β-cell function (HOMA-β) and insulin resistance (HOMAir).ResultsHOMA-β was lowest, whereas HOMAir was highest in T2DM (P < 0.01 and P < 0.001 vs. NFG). HDL anti-oxidative capacity and cellular cholesterol efflux did not differ significantly according to glucose tolerance category. In univariate analysis and after controlling for HOMAir both HDL anti-oxidative capacity (P < 0.05) and cellular cholesterol efflux (P < 0.01) were positively correlated with HOMA-β in T2DM, but not in NFG and IFG. In age-, sex- and HOMAir-adjusted analyses, T2DM status interacted positively with HDL anti-oxidative capacity (P = 0.001) and cellular cholesterol efflux (P = 0.042) on HOMA-β. HbA1c interacted similarly with HDL functionality measures on HOMA-β.ConclusionsPancreatic β-cell function relates to pathophysiologically relevant measures of HDL function in T2DM, but not in NFG and IFG. Better HDL functionality may contribute to maintenance of β-cell function in subjects with well-controlled T2DM.     

Components of the metabolic syndrome, but not the metabolic syndrome per se, are associated with aortic distensibility

Background and aimReduction in aortic distensibility occurs early in the atherosclerosis process and carries a poor prognosis. Metabolic syndrome is common and it is associated with increased cardiovascular mortality. The aim of this cross-sectional study was to investigate the association between metabolic syndrome and aortic distensibility.Methods and resultsA total of 135 subjects without diabetes were studied. Metabolic syndrome was diagnosed using the NCEP-ATP-III criteria. Aortic distensibility was assessed non-invasively by ultrasonography. Multivariate analysis, after controlling for the components of the metabolic syndrome, and, additionally, for body mass index, pulse pressure, presence of coronary artery disease, use of statins and use of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, demonstrated an independent association between aortic distensibility and age (p < 0.001), systolic blood pressure, (p = 0.02), diastolic blood pressure (p = 0.005), and history of hypertension (p < 0.001), but not metabolic syndrome status. Moreover, there was a suggestive association with albumin-to-creatinine ratio (p = 0.06).ConclusionsMetabolic syndrome per se is not associated with reduction in aortic distensibility. From the components of the metabolic syndrome, only blood pressure is a strong predictor of aortic distensibility. In addition, ageing and higher values of albumin-to-creatinine ratio are also associated with low aortic distensibility.     

Inter-relationship between low-density lipoprotein phenotype and carotid intima-media thickness in North Indian type 2 diabetic subjects

AimsDiabetic dyslipidemia is characterized by a preponderance of small dense LDL which is highly atherogenic. The aim of this study was to examine the interrelationship between LDL Phenotype and atherosclerosis; to determine the factors determining LDL phenotype; and evaluate LDLc:apo-B ratio as a surrogate for the assessment of LDL phenotype in a group of North Indian Type 2 diabetic subjects.Methods285 diabetic subjects attending the outpatient Endocrine Clinic were subjected to detailed anthropometry and fasting serum lipid and apo-B was measured. The carotid intima-media thickness (IMT) was determined using a high resolution B-mode Ultrasonography. LDLc:apo-B ratio was taken as a surrogate index for LDL size.Results29.5% patients with normal triglyceride levels and 52.1% patients with normal LDLc levels showed the presence of small dense LDL or Phenotype B as estimated by the LDL cholesterol/apo-B ratio. The mean IMT in Phenotype B group was higher (0.88 mm vs. 0.68 mm). Triglycerides was the most important predictor variable predicting carotid IMT (R² = 0.15, β = 0.376) as well as LDL phenotype B (R² = 0.28, β = 0.561).ConclusionsTriglycerides and HDLc contribute independently to the variability in LDL particle size, and LDL particle size was associated with preclinical atherosclerosis as determined by carotid IMT in North Indian Type 2 diabetic subjects. LDL cholesterol/apo-B ratio serves as an easy clinical tool to determine the elevated small dense LDL.     

Systemic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk

ObjectiveIn recent years high sensitive C-reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) were recognized as risk factors for cardiovascular disease (CVD). The aim of the present study was to investigate the relationship between these vascular and systemic markers of low-grade inflammation and traditional risk factors, the metabolic syndrome (MetS) or insulin resistance (IR).Methods and resultsIn 137 adults (41–78 years) with at least 2 risk factors for atherosclerosis the following parameters were determined: hsCRP, sVCAM-1, sICAM-1, PAI-1, fibrinogen, waist circumference (WC), blood pressure, Body Mass Index (BMI), fasting serum glucose (FSG), insulin, triglycerides (TG), total cholesterol (TC), LDL, and HDL. The presence or absence of MetS according to the AHA/NHLBI Scientific Statement criteria was assessed. IR was defined using the homeostasis model (HOMA-IR). Subjects with MetS had significantly higher values of hsCRP, sICAM-1, sVCAM-1, PAI-1, fibrinogen (each P < 0.05) and lower HDL-levels (P < 0.05) compared with subjects without MetS. Similar results were found using HOMA-IR-quartiles. Subjects in the bottom quartile (HOMA-IR ≤ 1.32) had significantly lower levels of hsCRP, sVCAM-1, sICAM-1, and PAI-1 (each P < 0.05) than subjects in the top quartile (HOMA-IR ≥ 5.03). HDL was significantly higher (P < 0.05) in subjects in the lowest quartile versus those in the highest quartile. Incidentally we found no significant differences in total and LDL cholesterol among MetS, HOMA, and traditional CVD risk factor groups, respectively.ConclusionSystemic and vascular markers of inflammation showed significant associations with IR and the MetS and may be incorporated into traditional CVD risk prediction models. Such models should be established and validated in forthcoming large scale prospective studies on CVD risk.     

LDL and HDL subclasses in acute ischemic stroke: Prediction of risk and short-term mortality

ObjectiveSmall, dense low-density lipoprotein (sdLDL) and small-sized high-density lipoprotein (HDL) particles are established risk factors for ischemic heart disease. However, their clinical significance for acute ischemic stroke (AIS) is uncertain. This study evaluates associations of LDL and HDL particle sizes and subclasses with AIS risk and short-term mortality after AIS.MethodsTwo hundred AIS patients hospitalised for first-in-a-lifetime stroke and 162 apparently healthy controls were included in the study. LDL and HDL particles were separated by gradient gel electrophoresis and serum lipid parameters were measured by standard laboratory methods. Baseline characteristics of LDL and HDL particles were evaluated for the prediction of AIS and short-term mortality after AIS.ResultsAIS patients had significantly more LDL III and IVb, but less LDL I and II particles. They also had significantly smaller HDL size, more HDL 3a, 3b and 3c and less HDL 2b subclasses. The relative content of both sdLDL and small-sized HDL particles was significantly increased in patients (P < 0.001 and P < 0.001, respectively). In addition, sdLDL was significantly higher in AIS fatalities (n = 25) compared with survivors (n = 175, P < 0.05). Increased sdLDL was a significant predictor of AIS (OR = 4.31; P < 0.001) and in-hospital mortality after AIS (OR = 5.50; P < 0.05). The observed relationships persisted after adjustment for conventional risk factors.ConclusionsAIS is associated with adverse distributions of LDL and HDL subclasses. In addition, short-term mortality after AIS is associated with increased sdLDL particles. Our results indicate that sdLDL is an independent predictor of both AIS onset and consecutive short-term mortality.     

Switching fibrate to statin in type 2 diabetic patients: Consequences on lipid profile

Interest of statins in terms of morbid-mortality reduction in primary and secondary prevention in type 2 diabetic patients has broadly been proven in recent studies, while evidence for fibrates preventive effect is considerably weaker. HMGCoA reductase inhibitors are known to decrease low density lipoprotein cholesterol (LDL C) in a greater extension than triglycerides (TG). In type 2 diabetic patients, the dyslipidemic profile is commonly associated with reduced high-density lipoproteins (HDL C), increased TG and normal or mildly elevated LDL C.Patients and methodsType 2 diabetic outpatients (n = 45) treated with fibrate with or without history of cardiovascular disease were included. Mean age was 57.7 ± 13.2 yr, sex ratio was 16/39 (F/M), and BMI was 29.3 ± 4.4 kg/m². Non-inclusion criteria were TG ≥ 3.5 g/L and intolerance to statins or a combined lowering lipid therapy. Serum lipid profile, HbA_1c and creatin kinase (CK) were assessed under treatment with fibrate, then after a 3-month wash-out period, and after a 6-month treatment with a low dose of atorvastatin (10 mg/day).ResultsAfter a 3-month wash-out period, total cholesterol (TC) was 1.98 ± 0.31 g/L (m ± SD), TG 1.63 ± 1.09 g/L, HDL C 0.46 ± 0.12 g/L, and LDL C 1.22 ± 0.31 g/L. Comparing lipid profile with atorvastatin vs fibrate, we observed a significant decrease in TC and LDL C (1.56 vs 1.79 g/L P = 0.001, and 0.84 vs 1.09 g/L, P = 0.001, respectively). No significant difference between treatments was observed for TG (1.35 vs 1.17 g/L, P = 0.06), and HDL C (0.44 vs 0.48 g/L, P = 0.15). When treated with atorvastatin, 90% of patients achieved a LDL C < 1 g/L, compared to 51% when treated with fibrate (P = 0.001). HbA_1c remained about 7.6 ± 1.5%, and CK in the normal range.ConclusionIn well-controlled type 2 diabetic patients previously treated with fibrate, short-term (6 months) treatment with low-dose atorvastatin (10 mg/day) improves TC and LDL C levels, without any alteration in TG and HDL C levels.     

Relationship between total oxidant status and severity of diabetic nephropathy in type 2 diabetic patients

Background and aimData on oxidative stress in type 2 diabetic patients with diabetic nephropathy is scant. The objective of this study was to investigate possible associations between total oxidant status (TOS) and the severity of diabetic nephropathy in type 2 diabetic patients by using a novel automated measurement method.Methods and resultsThirty-six patients with diabetic nephropathy (group 1), 25 diabetic patients without nephropathy (group 2) and 30 controls (group 3) were enrolled. Serum total antioxidant capacity (TAC), TOS levels and oxidative stress index (OSI) were determined. The severity of the disease was determined with microalbuminuria levels. TAC was lower, while TOS and OSI were higher in group 1 than in group 3 (P < 0.01, P < 0.001, P < 0.001; respectively). There were no statistically significant differences between group 2 and group 3 with respect to TAC, TOS and OSI (all P > 0.05). Group 1 had higher TOS and OSI than group 2 (both P < 0.05), but there was no statistically significant difference with respect to TAC. Significant correlations were observed between microalbuminuria levels, and TAC, TOS and OSI levels (r = −0.616, P < 0.001; r = 0.488, P < 0.01; r = 0.567, P < 0.001; respectively).ConclusionOur results suggest that oxidative stress is increased in patients with diabetic nephropathy compared to diabetic patients without nephropathy and this increase seems to be related to the severity of microalbuminuria levels.     

The effect of a novel intergenic polymorphism (rs11774572) on HDL-cholesterol concentrations depends on TaqIB polymorphism in the cholesterol ester transfer protein gene

Background and aimsSeveral genes have been shown to individually affect plasma lipoprotein metabolism in humans. Studies on gene–gene interactions could offer more insight into how genes affect lipid metabolism and may be useful in predicting lipid concentrations. We tested for gene–gene interactions between TaqIB SNP in the cholesterol ester transfer protein (CETP) and three novel single nucleotide polymorphisms (SNPs), namely rs11774572, rs7819412 and rs6995374 for their effect on metabolic syndrome (MetS) components and related traits.Methods and resultsThe aforementioned SNPs were genotyped in 1002 subjects who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Lipids were measured by standard procedures and lipoprotein subfractions, by proton nuclear magnetic resonance spectroscopy. Polymorphism rs11774572 was significantly associated with MetS (P = 0.020), mainly driven by the association of the C allele with lower HDL-C (P = 0.043) and higher triglycerides (P = 0.049) and insulin (P = 0.040) concentrations than TT subjects. A significant interaction between SNPs rs11774572 and CETP-TaqIB SNPs was found for HDL-C concentrations (P = 0.006) and for HDL (P = 0.008) and LDL particle sizes (P = 0.009), small LDL (P = 0.004), and VLDL concentrations (P = 0.021), in which TT homozygotes displayed higher HDL-C concentrations and for HDL and LDL particle sizes, and lower small LDL and VLDL concentrations than C carriers, if they were CETP B2 allele carriers (P values ranging from <0.001 to 0.001).ConclusionsThe rs11774572 polymorphism may play a role in the dyslipidemia that characterizes MetS. The interaction between rs11774572 and CETP-TaqIB SNPs on HDL-C concentrations provides some insights into the underlying mechanisms.