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Biomedical subjects

Eric Bruckert

Publications and source records attributed to Eric Bruckert.

At least 19 recordsLinked to original sources
PubMed2006

Blood lipids in brain infarction subtypes.

BACKGROUND: Little is known about the relationship between hypercholesterolaemia and specific aetiological subtypes of brain infarction (BI). METHODS: In a cross-sectional study of 492 pairs of patients with a BI proven by MRI and matched hospital controls, we determined the blood levels of triglycerides, total, HDL and LDL cholesterol, and apolipoprotein A(1) and B, in the same centralized laboratory. We performed aetiological BI subtype classification. RESULTS: Except for triglycerides, the risk of BI increased continuously with the lipid levels, without any heterogeneity between the main BI subtypes or the group on lipid-lowering therapy. The adjusted odds ratio per standard deviation in LDL cholesterol (0.93 mmol/l) was 1.74 (95% confidence interval, 1.02-2.98) in atherothrombotic strokes (n = 109) and 2.71 (95% confidence interval, 1.60-4.55) in lacunar strokes (n = 105). Eighty percent of patients were above the ATP-III guideline threshold LDL cholesterol of 2.59 mmol/l (100 mg/dl), with a major contribution of both atherothrombotic and lacunar stroke subtypes to this group. CONCLUSIONS: These findings suggest that blood lipids, particularly total and LDL cholesterol levels, are associated with all subtypes of BI, and that LDL above 2.59 mmol/l is highly prevalent.

Aged↗
PubMed2006

Cardiovascular risk and rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion.

OBJECTIVE: To develop clinical practice guidelines for the evaluation and management of cardiovascular risk in patients with rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: Recommendations were developed using the evidence-based approach and expert opinion: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing the recommendations; Evidence providing answers to the five questions was sought in the literature; Based on this evidence, recommendations were developed by a panel of experts. RESULTS: The recommendations were as follows: 1) In patients with RA, attention should be given to the risk of cardiovascular disease, which is responsible for an excess burden of morbidity and mortality; 2) It must be recognized that RA may be an independent cardiovascular risk factor. Persistent inflammation is an additional risk factor; 3) The cardiovascular risk should be evaluated, and modifiable risk factors should be corrected; 4) In patients with RA requiring glucocorticoid therapy, the need for cardiovascular risk minimization is among the reasons that mandate the use of the minimal effective dose; 5) It should be recognized that methotrexate may protect against cardiovascular mortality in patients with RA; 6) It should be recognized that TNFalpha antagonists remain contraindicated in patients with RA and severe heart failure. TNFalpha antagonists do not seem to worsen moderate heart failure and may protect against cardiovascular mortality; 7) AFSSAPS recommendations about LDL-cholesterol objectives should be followed, with active RA being counted as a cardiovascular risk factor; 8) In patients with RA, statin therapy should be considered only when cholesterol levels are elevated despite appropriate dietary treatment; 9) RA per se does not indicate aspirin for primary prevention. When aspirin is used for secondary prevention, it should be recognized that concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the antiplatelet effects and increase the gastrointestinal side effects of aspirin therapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Carotid atherosclerosis is not related to past tuberculosis in hypercholesterolemic patients.

BACKGROUND: Tuberculosis is a chronic recurrent infection and inflammation is part of the disease which may remain undiagnosed for months. Furthermore immunization with recombinant heat shock protein-65-rich mycobacterium tuberculosis increased atherogenesis in hypercholesterolemic animal models. OBJECTIVE: To investigate the potential interrelationships between past tuberculosis with carotid and femoral atherosclerosis in hypercholesterolemic patients. DESIGN AND SETTING: Case control study in a university hospital. PATIENTS: Two groups of hypercholesterolemic patient group (n=147) studied in a cardiovascular prevention unit during the same quarter, age (+/-1 year) and sex-matched. The first group presented a history of tuberculosis in the past and the second group never. METHODS: Atherosclerosis was assessed by carotid and femoral external echography. Measurements of maximum plaque diameter were done in longitudinal planes, and the extent of atherosclerosis was graded according to the most severe visible changes on the scanned arteries. RESULTS: The frequency and the distribution of atherosclerosis was similar in the two groups, whatever the arterial site explored, carotid or femoral. None of the clinical and biological studied variables were different between the two groups of patients. CONCLUSION: Past tuberculosis is not associated with increased frequency of atherosclerotic lesions in hypercholesterolemic patients.

Carotid Artery Diseases↗
PubMed2006

Alterations in lipoprotein defense against oxidative stress in metabolic syndrome.

Metabolic syndrome (MetS) is a high-risk condition for premature atherosclerotic vascular disease. Patients with MetS display a lipoprotein profile in which dense low-density lipoproteins (LDL), which are more susceptible to oxidation, predominate. Oxidation of lipoproteins can be attenuated in vivo by enzymatic and nonenzymatic antioxidant defenses, but high-density lipoproteins (HDL) play a key role in the protection of LDL from oxidation. Such activity depends on the presence of apolipoproteins (apoA-I, apoA-II, apoA-IV, apoE) and enzymes (paraoxonase 1, platelet activating factor-acetylhydrolase, lecithin:cholesterol acyltransferase, glutathione peroxidase). The impairment of HDL antioxidative activity in MetS is partly related to an enrichment of small HDL in triglycerides and their depletion in cholesteryl esters, to the replacement of apoA-I by serum amyloid A, and to glycation and oxidation of apoA-I. Therapeutic normalization of the quantity and the quality of HDL particles may constitute a novel approach to attenuate atherosclerosis and cardiovascular risk in MetS.

Atherosclerosis↗
PubMed2006

Use of an indirect effect model to describe the LDL cholesterol-lowering effect by statins in hypercholesterolaemic patients.

Statins are the most commonly prescribed agents for the treatment of hypercholesterolaemia. This is due to their efficacy in reducing low-density lipoprotein cholesterol (LDL) level which is the primary goal of the treatment especially for patients with multiple risk factors or with established coronary heart diseases. The purpose of this study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model that describes the LDL-lowering process in patients with hypercholesterolaemia treated with atorvastatin, fluvastatin or simvastatin. A total of 100 patients were studied retrospectively. They received atorvastatin (n = 57), fluvastatin (n = 26) or simvastatin (n = 17). As no pharmacokinetic data were available, the absorption rate was fixed to 1/h and atorvastatin, simvastatin and fluvastatin elimination half-lives were fixed to 14, 2 and 2.5 h respectively. A total of 309 LDL levels were measured and the data were analysed by nonmem v. The time course of the LDL-lowering effect of statins was described by an indirect-response model with precursor (LDL synthesis, input rate K(in)) and response (circulating LDL, input and output rates K) compartments. The following parameters were estimated: LDL input rate (K(in)) 0.14 +/- 0.015 g/L/day (mean +/- SD); inhibition fraction of K(in) (INH) 0.21 +/- 0.017; and dose producing 50% increase of LDL removal (D50), 26 +/- 7.8, 1.3 +/- 0.48 and 15 +/- 5.25 mg for atorvastatin, simvastatin and fluvastatin, respectively. Gender, bodyweight, age, calories/day, sugar/day, lipids/day, hyperlipidaemia types and waist/hip circumference, renal and hepatic functions had no effect on the pharmacodynamic parameters. The pharmacodynamic parameters for the three statins were accurately estimated. The PK/PD model developed successfully predicted the time course of the LDL-lowering effect of statins.

Adolescent↗
PubMed2006

One third of the variability in HDL-cholesterol level in a large dyslipidaemic population is predicted by age, sex and triglyceridaemia: The Paris La Pitié Study.

OBJECTIVE: The objective of this study was to identify key determinants of high-density lipoprotein-cholesterol (HDL-C) level, including subclinical inflammation and insulin resistance, and to determine the prevalence of a low HDL-C phenotype in dyslipidaemic patients at high cardiovascular risk. METHODS: In a cross-sectional study, we assessed the prevalence of low HDL-C phenotypes in 14 667 dyslipidaemic patients attending our specialised lipid clinic and evaluated the potential relationships between HDL-C level and 16 clinical and biological parameters. RESULTS: In univariate analysis, women exhibited higher plasma concentrations of HDL-C as compared with men. Levels of triglycerides, fasting blood glucose, uric acid, waist circumference, body mass index, high sensitivity C-reactive protein (hs-CRP), insulin resistance (as HOMA-IR index) and smoking were all negatively correlated with HDL-C, whereas age was positively correlated with HDL-C levels. Moderate drinkers (10-30 g/day) displayed higher HDL-C concentrations as compared with abstinent subjects; in contrast, consumption of more than 30 g alcohol/day was associated with a further non-significant elevation of HDL-C levels as compared to moderate drinkers. Multivariate analysis identified eight independent correlates of HDL-C. Age, sex and TG accounted for 37% of variability in HDL-C; modifiable factors including waist circumference, alcohol consumption and smoking, in addition to HOMA-IR and hs-CRP, accounted for an additional 5% of the variability in HDL-C. Using a cut-off of 40 mg/dL (1.03 mmol/L) for men and 50 mg/dL (1.29 mmol/L) for women, 33% and 28% of men and women displayed low levels of HDL-C. CONCLUSION: Eight independent determinants of HDL-C account for 41% of variability in HDL-C in our dyslipidaemic population. Three of them, i.e. age, sex and degree of triglyceridaemia accounted for more than one third of such variability. The high prevalence of low HDL-C phenotypes in dyslipidaemic patients at elevated cardiovascular risk emphasises the need for both lifestyle and pharmacological strategies of intervention to raise HDL-C.

Adult↗
PubMed2005

Elevated serum levels of proinflammatory cytokines and biomarkers of matrix remodeling in never-treated patients with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a common inherited disorder of lipoprotein metabolism, whose origin involves mutations in the gene coding for the low-density lipoprotein receptor protein. Although FH is monogenic, wide variation occurs in the onset and severity of atherosclerosis in these patients. METHODS: Since data on levels of inflammatory proteins and/or active factors in FH patients who have never received lipid-lowering treatment are lacking, serum levels of MMP-3, active MMP-9 and TIMP-1 as well as pro-inflammatory cytokines (TNF-alpha, IL-18) were determined in never-treated homozygous FH Moroccan patients (n=4) and compared to those of heterozygous FH subjects (n=7) and of healthy control subjects (n=5). RESULTS: When compared to controls, homozygous FH patients exhibited levels of active MMP-9 and TIMP-1 (p<0.05), and of both high sensitive-CRP and IL-18 which were significantly elevated (p<0.05 and p<0.01, respectively). In heterozygous FH patients, intermediate values between FH homozygotes and healthy controls were observed for these markers, with the exception of MMP-9 activity whose levels were significantly elevated (p<0.05). Multivariate analysis revealed a positive correlation between apolipoprotein B, TIMP-1 and IL-18 levels, and between hs-CRP and IL-18 (p<0.01). CONCLUSIONS: Although the sample size of this FH group was limited, our data suggest that nontreated homozygous FH patients, and to a lesser degree heterozygous FH patients, exhibit not only a markedly proinflammatory vascular state but also pronounced extracellular matrix remodeling, as reflected by elevated circulating levels of inflammatory cytokines and MMPs.

Adolescent↗
PubMed2005

Comparison of efficacy and safety assessment of fluvastatin in patients <65 years versus > or =65 years of age.

This pooled analysis of 30 completed clinical trials assessed the efficacy and safety of fluvastatin in patients <65 (n = 8,037) and patients > or =65 years of age (n = 3,717). The results demonstrated that in patients > or =65 years of age, lipid changes with fluvastatin therapy are equivalent to or slightly better than those observed in patients <65 years of age. Treatment with fluvastatin produced a significantly lower incidence of major cardiovascular clinical end points (major adverse cardiac events [MACEs]) and an increase in the time to a first MACE in the older population. The incidence of adverse events, particularly those of concern with statin therapy, was similar between the placebo- and fluvastatin-treated patients and between the different age groups. In conclusion, data derived from the pooled analysis with fluvastatin demonstrate that cardiovascular events are reduced in older high-risk patients to a greater extent compared with younger patients. Furthermore, this pooled analysis supports the use of fluvastatin to lower cholesterol levels in older high-risk patients.

Age Factors↗
PubMed2005

Renal disease in cardiovascular disorders: an underrecognized problem.

Chronic renal disease is generally appreciated as a major and rapidly growing health problem. In the United States alone, as many as 19.5 million people may have markers of early renal disease, and more than 660,000 people are expected to require renal replacement therapy by the year 2010. By contrast, the presence and pathological role of renal disease in patients with cardiovascular disease are somewhat underrecognized. Evidence now shows that even minor impairments in renal function, as indicated by measures including glomerular filtration rate and microalbuminuria, are common in cardiovascular disease states and predictive of cardiovascular events. Indeed, microalbuminuria may be a marker of systemic vascular disease rather than kidney dysfunction alone. In patients with hypertension, diabetes, metabolic syndrome, acute coronary syndromes, and stroke, markers of renal disease have proved to be at least as predictive of morbidity and mortality as conventional risk factors. Yet, chart reviews in a variety of clinical settings reflect poor recognition and management of renal disease in at-risk patients. Models for renal protection are based on the control of risk factors, particularly blood pressure, that are associated with renal and cardiovascular outcomes. Screening protocols for markers of renal disease should recognize the potential inaccuracy of serum creatinine concentrations and the preferability of glomerular filtration rate estimates that take age and gender into account. Pilot programs for screening high-risk populations have shown efficacy in detecting renal disease.

Biomarkers↗
PubMed2005

Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study.

OBJECTIVES: To characterize the risk factors, rate of occurrence, onset, nature and impact of mild to moderate muscular symptoms with high-dosage HMG-CoA reductase inhibitor (statin) therapy in general practice. METHODS: The Prédiction du Risque Musculaire en Observationnel (Prediction of Muscular Risk in Observational conditions, PRIMO) survey was an observational study of muscular symptoms in an unselected population of 7924 hyperlipidemic patients receiving high-dosage statin therapy in a usual care, outpatient setting in France. Information on patient demographics, treatment history and muscular symptoms was obtained by questionnaires. RESULTS: Multivariate analysis revealed the strongest predictors for muscular symptoms to be a personal history of muscle pain during lipid-lowering therapy (odds ratio, OR, 10.12, 95% CI 8.23-12.45; P < 0.0001), unexplained cramps (OR 4.14; 95% CI 3.46-4.95; P < 0.0001) and a history of creatine kinase (CK) elevation (OR 2.04; 95% CI 1.55-2.68; P < 0.0001). Overall, muscular symptoms were reported by 832 patients (10.5%), with a median time of onset of 1 month following initiation of statin therapy. Muscular pain prevented even moderate exertion during everyday activities in 315 patients (38%), while 31 (4%) were confined to bed or unable to work. Fluvastatin XL was associated with the lowest rate of muscular symptoms (5.1%) among individual statins. CONCLUSION: PRIMO demonstrated that mild to moderate muscular symptoms with high-dosage statin therapy may be more common and exert a greater impact on everyday lives than previously thought. Knowledge of the risk factors for muscular symptoms will allow identification and improved management of high-risk patients. The risk of muscular symptoms with fluvastatin XL treatment may be lower than with high dosages of other statins.

Aged↗
PubMed2005

Intake of added oils and fats among middle-aged French adults: relationships with educational level and region of residence.

OBJECTIVE: To describe the relative contribution of 10 created food groups to total fat intake in middle-aged subjects. The relationship of added oil and fat intake with region of residence and educational level was also assessed. DESIGN: Cross-sectional study. SUBJECTS/SETTING: Participants of the French Supplémentation en Vitamines et Minéraux Antioxydants study who completed at least six 24-hour dietary records after inclusion into the study (N=6,572). RESULTS: Added oils and fats were the main source of total fat intake. Animal fat and margarine intakes showed a significant inverse association with educational level, whereas oils with monounsaturated fatty acids (MUFA) were positively associated with education level. Animal fat intake was significantly higher in the western and northern parts of France (54.2% and 50.4%) and lower in the Mediterranean Coast (39.0%). A significant inverse gradient was found with oils with polyunsaturated fatty acids or MUFA in the southwest and the Mediterranean Coast compared with the northern part of France. CONCLUSIONS: We showed a north to south gradient for animal fat intake and the opposite for oils with MUFA and polyunsaturated fatty acid in France. This gradient parallels the known disparities for cardiovascular mortality in this country. This should contribute to adapting dietary guidelines for dietary change in a public health perspective.

Alcohol Drinking↗
PubMed2005

Sampling variability of liver biopsy in nonalcoholic fatty liver disease.

BACKGROUND & AIMS: In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH. METHODS: Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 samples collected. The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the kappa reliability test. RESULTS: No features displayed high agreement; substantial agreement was only seen for steatosis grade; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies and lobular inflammation displayed only slight agreement. Overall, the discordance rate for the presence of hepatocyte ballooning was 18%, and ballooning would have been missed in 24% of patients had only 1 biopsy been performed. The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy. Intraobserver variability was systematically lower than sampling variability and therefore could not account for most of the sampling error. CONCLUSIONS: Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma; therefore, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies.

Adult↗
PubMed2005

High prevalence of low HDL-cholesterol in a pan-European survey of 8545 dyslipidaemic patients.

OBJECTIVE: Low HDL-cholesterol is a strong independent cardiovascular risk factor recognized as a therapeutic target in recent guidelines. The Pan-European Survey on HDL-cholesterol collected data on plasma lipid profiles from 8545 dyslipidaemic patients in the care of 1339 specialist physicians in 11 European countries. The main objective was to obtain a reliable estimation of the prevalence of low HDL (< 1.03 mmol/L [< 40 mg/dL] in men; < 1.29 mmol/L [< 50 mg/dL] in women). RESEARCH DESIGN AND METHODS: Eligible patients were aged >or= 18 years and had received diet and exercise plus pharmacologic lipid-modifying treatment for >or= 3 months, or had serum cholesterol >or= 5.18 mmol/L (>or= 200 mg/dL) and/or serum triglycerides >or= 2.03 mmol/L (>or= 180 mg/dL) despite >or= 3 months of diet and exercise. RESULTS: The survey population was overweight (mean body mass index 29.0 kg/m2), with a high prevalence of sedentary lifestyle (68%), type 2 diabetes (45%), hypertension (72%) and coronary heart disease (45%). Lipid-modifying treatment, received by 85% of patients, included lifestyle modification (85%) and/or lipid-lowering drugs (85% received a statin). The prevalence of low HDL-cholesterol despite lipid-modifying treatment was 40% (women) and 33% (men). Very low HDL-cholesterol (< 0.90 mmol/L [< 35 mg/dL]) occurred in 14% of treated patients, with similar prevalence in the subgroup of patients not receiving such treatment. Hypertriglyceridaemia (> 1.69 mmol/L [> 150 mg/dL]) occurred in 57% of men not under lipid-modifying treatment and in 47% of men receiving such treatment; corresponding values in women were 48% and 43%. Both low HDL-cholesterol and hypertriglyceridaemia occurred in 26% of men and 27% of women who were not receiving lipid-modifying treatment and in 21% of men and 25% of women receiving lipid-modifying treatment. CONCLUSIONS: Low HDL-cholesterol and hypertriglyceridaemia are, therefore, common among European patients treated for dyslipidaemia. Clearly, physicians need to focus more of their attention on this major risk factor and to consider adequate treatment when indicated.

Adult↗
PubMed2004

Educational level has a major impact on the representations of cholesterol: a study in 1579 hypercholesterolemic patients.

OBJECTIVE: To determine the specific features of representations of cholesterol and hypercholesterolemia according to the educational level (EL) and gender among hypercholesterolemic (HC) subjects. DESIGN: The knowledge, beliefs and personal opinions of 1579 hypercholesterolemic patients [58% males; 40% low EL; mean age 58.3 (SD = 11.5)], recruited by their general practitioners, were analyzed from the responses to a self-administered questionnaire. RESULTS: In comparison with women, and after adjusting for EL, men were less likely to know the acceptable total cholesterol level (OR = 0.80; P < 0.05), more likely to perceive hypercholesterolemia as not being a serious disorder (OR = 1.33; P < 0.05), mainly due to overweight (OR = 1.74; P < 0.001), modern (OR = 1.41; P < 0.01), and carefree lifestyle (OR = 1.80; P < 0.01), and less able to commit themselves to a therapeutic project (diet is only possible if shared by the spouse or family, OR = 1.25; P < 0.05). In comparison with subjects with a middle/high EL, and after adjusting for gender, the least educated subjects exhibited lower dietary knowledge (P < 0.001) and less right beliefs (the presence of cholesterol in blood is normal, OR = 0.48; P < 0.001), expressed the most misconceptions concerning hypercholesterolemia and its attendant risks (high cholesterol can induce cancer, OR = 1.63, P < 0.01, or rheumatism, OR = 3.64; P < 0.001; it is possible to perceive high cholesterol levels before seeing the results of blood tests, OR = 1.48; P < 0.001), exhibited lower self-efficacy (it is discouraging to know that heredity plays a role in a health problem, OR = 1.42; P < 0.001) and were the least convinced by and motivated for treatment (treatment may be limited in time, OR = 1.32; P < 0.05, dieting is impossible if one has an active lifestyle including eating out, OR = 1.64; P < 0.001). CONCLUSIONS: For distinctive reasons, male gender and low educational level, which are already recognized as cardiovascular risk factors, emerged from our study as limiting patient's personal involvement in the management of hypercholesterolemia. They attest to the need to support educational and informational messages aimed at alerting, convincing and motivating. To heighten the impact of such efforts, it would seem necessary to target specific messages to men and patients with low educational level.

Body Mass Index↗
PubMed2004

Hypothyroidism and cardiovascular disease: role of new risk factors and coagulation parameters.

Hypothyroidism is a common condition and recent epidemiological studies demonstrated that up to 10 percent of subjects may display its subclinical form. Despite the well-known relationship between overt hypothyroidism and cardiovascular disease, few studies demonstrating such a link are available. However, the relationship between hypothyroidism and a variety of cardiovascular risk factors is now well established. Recent data on new cardiovascular risk factors that were shown to be associated with hypotyroidism are reviewed. Haemostatic and fibrinolytic parameters are disturbed differently according to the stage of hypothyroidism. C-reactive protein levels are higher in patients with overt and subclinical hypotyroidism compared to euthyroid patients. In contrast, elevation of homocysteine values was demonstrated only in overt hypothyroidism. Although no randomized controlled trial evaluated the potential benefits of levothyroxine substitution on the risk to suffer major coronary events in patients with subclinical hypothyroidism, there is growing evidence that this disorder is mainly characterized by a high risk of cardiovascular disease.

C-Reactive Protein↗
PubMed2004

Adiponutrin: A new gene regulated by energy balance in human adipose tissue.

Adiponutrin is a newly identified nonsecreted adipocyte protein regulated by changes in energy balance in rodents. We documented the influence of energy balance modification on adiponutrin gene expression in humans. We investigated the mRNA expression in sc adipose tissue of nonobese women and in obese women during 2-d very low-calorie diet (VLCD) and subsequent refeeding as well as before and after a VLCD of 3 wk (21-d VLCD). The adiponutrin mRNA levels of the nonobese and obese women were not different (P > 0.05). Two-day VLCD reduced the average level of adiponutrin mRNA expression by 36% (P = 0.0016), whereas refeeding elevated the mRNA level by 31% (P = 0.004). The 3-wk VLCD caused a dramatic 58% fall of the adiponutrin mRNA expression level (P = 0.001). The mRNA level was negatively correlated with fasting glucose (Rho = -0.62; P < 0.0001), and subjects with high adiponutrin mRNA level had an increased insulin sensitivity. Compared with other adipocyte proteins such as leptin and adiponectin, adiponutrin mRNA did not show correlation with either adiposity indexes or with leptin or adiponectin mRNAs. These results indicate that adiponutrin gene expression in humans is highly regulated by changes in energy balance.

Adipose Tissue↗
PubMed2004

Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity.

A metabolic syndrome (MetS) phenotype is characterized by insulin-resistance, atherogenic dyslipidemia, oxidative stress, and elevated cardiovascular risk and frequently involves subnormal levels of high-density lipoprotein (HDL) cholesterol. We evaluated the capacity of physicochemically distinct HDL subfractions from MetS subjects to protect low-density lipoprotein against oxidative stress.MetS subjects presented an insulin-resistant phenotype, with central obesity and elevation in systolic blood pressure and plasma triglyceride, LDL-cholesterol, apolipoprotein B, glucose, and insulin levels. Systemic oxidative stress, assessed as plasma 8-isoprostanes, was significantly higher (3.7-fold) in MetS subjects (n = 10) compared with nonobese normolipidemic controls (n = 11). In MetS, small, dense HDL3a, 3b, and 3c subfractions possessed significantly lower specific antioxidative activity (up to -23%, on a unit particle mass basis) than their counterparts in controls. In addition, HDL2a and 3a subfractions from MetS patients possessed lower total antioxidative activity (up to -41%, at equivalent plasma concentrations). The attenuated antioxidative activity of small, dense HDL subfractions correlated with systemic oxidative stress and insulin resistance and was associated with HDL particles exhibiting altered physicochemical properties (core triglyceride enrichment and cholesteryl ester depletion). We conclude that antioxidative activity of small, dense HDL subfractions of altered chemical composition is impaired in MetS and associated with elevated oxidative stress and insulin resistance. Induction of selective increase in the circulating concentrations of dense HDL subfractions may represent an innovative therapeutic approach for the attenuation of high cardiovascular risk in MetS.

Adult↗