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Background PCSK9 inhibition with alirocumab significantly reduced LDL-C levels in trials of up to 78 weeks' duration in patients with heterozygous familial hypercholesterolemia (HeFH). We report results from 3 years of an ongoing open-label treatment extension ( NCT01576484 ) to a 12-week double-blind trial in HeFH patients ( NCT01266876 ). Methods Patients who completed the parent study and were receiving stable daily statin ± ezetimibe could enter the open-label extension, where they received alirocumab 150 mg every 2 weeks (Q2W) subcutaneously (n = 58). The primary endpoint was safety (treatment-emergent adverse events, TEAEs). Efficacy endpoints included the percentage change in LDL-C from baseline at Week 24. Safety and efficacy data were available up to Weeks 156 and 148, respectively. Results Mean baseline LDL-C was 150.7 mg/dL (3.9 mmol/L), despite all patients being on a statin (76% on high-intensity statin; 72% also receiving ezetimibe). Over 156 weeks, 54 (93.1%) patients experienced a TEAE, 12 (20.7%) experienced a serious TEAE, and two (3.4%) discontinued due to a TEAE. Injection site reactions occurred in 21 (36.2%) patients. Mean (SD) reduction in LDL-C from baseline to Week 24 was 65.4 (21.1)%, with reductions maintained through 148 weeks (Week 148 reduction: 56.0 [23.8]%). Mean apolipoprotein B reduction was 50.9% and median lipoprotein (a) reduction was 22.5% at Week 24 (46.1% and 25.6% at Week 148, respectively). Conclusions Open-label treatment for 3 years with alirocumab 150 mg Q2W, administered with background statin ± ezetimibe, was generally well-tolerated and had a safety profile comparable with that seen in the overall alirocumab clinical trial program. Alirocumab provided significant, sustained LDL-C reductions. [ABSTRACT FROM AUTHOR]

Abstract: The French part of the continental shelf of the Bay of Biscay (northeast Atlantic) is the habitat of an anchovy (Engraulis encrasicolus L.) population of scientific interest because of its economic importance and the trend towards greater interannual fluctuations in its abundance, particularly as a consequence of variations in recruitment. Each year a 1-month survey of this population and its pelagic environment is undertaken. Among the descriptors of ecosystem function characterized, mesozooplankton aspartate transcarbamylase (ATC) activity is measured with the goal of defining overall productivity of the mesozooplankton communities. Diverse physical forcing factors are responsible for the enhancement of productivity in the Bay of Biscay, and their respective influences vary at interannual scales. We present the results of ATC activity measurements carried out within the anchovy habitat during six consecutive breeding seasons (from 2000 to 2005). A strong correlation was found between mean ATC activity and variations in interannual biomass for the anchovy population (R =0.928; p <0.01). During the study period the anchovy population collapsed, and a particularly low level of ATC activity in the mesozooplankton preceded this event 1 year earlier. Conversely, an increase in anchovy abundance in the year following the collapse was preceded by a return to substantially higher levels of ATC activity. We hypothesize that this relationship may be robust and generally applicable. We speculate on the environmental descriptors necessary to confirm this result, in view of its potential application to the monitoring of this valuable fish population in the Bay of Biscay. [Copyright &y& Elsevier]

Fishermen have long observed the sudden change of shoaling behaviour of small pelagic fish following a strong wind event. The phenomenon was thereafter confirmed by fisheries scientists using acoustic tools. In this study, we report our observations made with acoustics to measure disorganization of the previously observed spatial distribution and shape of shoals that occurred after a wind event. The measurements were made during a fisheries research cruise in the Bay of Biscay (NE Atlantic) aimed at determining (1) small pelagic fish species abundance and (2) the individual nutritional state of anchovies (Engraulis encrasicolus L.) via evaluation of their RNA/DNA ratio. A spatial fine-scale study was conducted in two of the main breeding areas for anchovy, one located near the plume of a large river (haline stratification) and the other in an open sea location over the continental shelf break (thermal stratification). After a strong wind event, a change of the spatial and bathymetric distribution of the fish community, including anchovy, was observed in the open sea area, whereas no effect was detected in the near shore area. The RNA/DNA ratios determined in anchovy white muscles were quite similar in both areas before the wind event. Afterwards, they remained unchanged near the shore but were significantly reduced in the open sea location. This difference can be explained by the disparity in the strength of the stratification (i.e. haline versus thermal), but a change in the species composition of the fish community may also have played a role. [ABSTRACT FROM AUTHOR]

Abstract: The study examines the spatial variations over the French continental shelf of the southern Bay of Biscay (North-East Atlantic) in the nutritional condition of anchovy (Engraulis encrasicolus L.) larvae which was estimated through their DNA/C index. The same cruise yielded quantitative estimates of two metabolic descriptors of the functioning of mesozooplanktonic communities, the enzymes pyruvate kinase (PK) and trypsin, for the first time evaluated simultaneously. The aim was to appraise quality and quantity of matter assimilated by the mesozooplankton and to specify whether the main components of prey ingested by copepods are principally carbohydrates, through PK activity, or protein, under the action of the digestive endopeptidase trypsin. The larval DNA/C index was significantly correlated with PK specific activity but not with trypsin specific activity in the mesozooplankton. This is consistent with previous data on concomitant variations, although on quite different scales, in mesozooplankton PK activity and the larval DNA/C index. [Copyright &y& Elsevier]

Abstract: A fisheries research cruise conducted in 2000 offered a first opportunity to take simultaneous measurements of the activities of three enzymes in mesozooplankton samples collected at a regional scale over the continental shelf of the Bay of Biscay in the NE Atlantic, with the aim of characterizing main aspects of the functioning of the biotic environment of small pelagic fish populations. The activity of the digestive endopeptidase trypsin was selected to characterize the assimilation rate of proteins, whereas pyruvate kinase (PK) was chosen as an indicator of carbohydrate assimilation and aspartate transcarbamylase (ATC) provided an overall assessment of mesozooplankton productivity. The Bay of Biscay region is subject to various strong physical driving forces that directly affect the primary structure of the pelagic food web. On our cruise, the phytoplankton biomass distribution reflected these different physical influences: diatoms dominated the nutrient-enriched coastal water; picoplankton dominated the northern-central part where nutrients were depleted; and nanoplankton were abundant at the shelf break where internal waves provided an input of nutrients. These and other results (on bacteria, particulate organic carbon distribution, among others) illustrate the differences that exist in the microbial food webs of different sectors of the bay. The living matter produced was characterized by the quality and quantity of the smallest prey items that were available to higher trophic levels. Variations in mesozooplankton enzyme activities may agree well not only with classically expected results, but also present unexpected special features: high ATC specific activities were measured around the mouth of the Gironde, in the nutrient-rich desalted water of the plume, but surprisingly not in front of the Loire river. PK specific activities reflected preponderantly the balance between phytoplankton cells sizes and the related bacterial abundance resulting from nutrient limitation (mainly P), that induces varying carbohydrates production potential. Trypsin specific activities were moderately variable, except in a restricted area where a highly abundant protein content characterized the particulate matter and in the plume of water flowing out of the Gironde. It is concluded that the presented approach of the metabolism of mesozooplankton communities may provide novel views on crucial processes occurring at the mesoscale, which fits in generally well with the scales of ecological factors mostly influential on small pelagic fish populations. [Copyright &y& Elsevier]

Abstract: Pyruvate kinase (PK) activity measurements are used to assess the role of carbohydrates in global feeding of mesozooplankton communities inhabiting an estuary plume. As a consequence of a remarkably low freshwater discharge rate, the sea surface layers of the area under estuarine influence showed a very moderate salinity fall and a nearly total depletion in nitrates, whereas higher levels of these nutrients were found in deeper, more saline, layers. Small-scale PK activity variations in mesozooplankton appear to be closely correlated to nitrate integration values within the water column. The results were analysed in comparison with literature reports. The study produced a coherent overall interpretation, which strongly supports the reliability of this new biochemical tool in detecting assimilation of trace carbohydrates in the diet of mesozooplankton. [Copyright &y& Elsevier]

A major spawning ground of the European anchovy (Engraulis encrasicolus) population in the Bay of Biscay is located near the mouth of the Gironde estuary. Variations in the river discharge affect the supply of nutrients to the coastal marine area encompassing anchovy spawning grounds. Two “Pegase” cruises (May–June 1997 and 1998) observed two contrasting situations: with and without a superficial layer of less saline water. Two new nutritional indices were used to assess potential effects (1) on carbohydrate assimilation rates by zooplankton estimated via pyruvate kinase (PK) activity measurements and (2) on nutritional condition of the anchovy larvae measured with the DNA/C index. Both indices indicated a much poorer situation in 1997 compared to 1998. Results of this study implicate river outflow rate as a potential factor influencing larval anchovy condition and perhaps to some extent recruitment variability. [Copyright &y& Elsevier]

This purpose of this study was to investigate how plasma C-reactive protein (CRP), a nonspecific acute-phase reactant, modulates the risk of coronary heart disease (CHD) associated with the small, dense, low-density lipoprotein (LDL) phenotype. LDL particle size and plasma CRP were measured in the Quebec Cardiovascular Study cohort of 2,025 men free of CHD at baseline, among whom 103 had a first CHD event during a 5-year follow-up period. Plasma CRP levels were measured using the Behring Latex-Enhanced (highly sensitive) CRP assay. LDL particle size phenotype was characterized using 2% to 16% polyacrylamide gradient gel electrophoresis. There were weak but significant associations between plasma CRP levels and features of LDL size, such as the proportion of LDL with a diameter <255 A˚ (r = 0.09, p <0.001) and LDL peak particle size (r = −0.09, p <0.001). Variations in plasma CRP levels modulated the risk of CHD associated with small LDL peak particle size (relative risk 4.3 vs 2.5 in men with high vs low plasma CRP levels, respectively) and with an elevated proportion of LDL <255 A˚ (relative risk 6.6 vs 3.0). Thus, increased plasma CRP levels further elevate the risk of CHD associated with having small, dense LDL particles. [Copyright &y& Elsevier]

Examines the association between elevated plasma c-reactive protein (CRP) levels and risk for future ischemic heart disease (IHD) in men in Quebec. Measurement of the baseline plasma levels using a highly sensitive assay; Ability of CRP level to predict short-term but not long-term risk for IHD; Evidence of a time-to-event dependency in the elderly.

Discusses a study which found that low-density lipoprotein is not the best indicator of a risk of coronoary events. Findings which suggest that plasma apolipoprotein B is an excellent indicator of risk; Correlation between high cholesterol and the risk of coronary disease; Proposal of modifications to the clinical practice of diagnosis and treatment of lipids.

Examines the effect on phospholipid association of deletion of central alpha-helices in human apolipoprotein. Ability of mutants to form reconstituted apoA-I containing lipoproteins; Involvement of amphipathic alpha-helices within residues in interactions.

Lanthanide dodecyl sulfates, LnDSx, are remarkably effective to catalyze the reaction of diepoxides with diamines in the liquid and solid states, a key reaction in the formation of epoxy thermosets. Among all lanthanides, the lanthanum complex LaNa(DS)4(H2O)2 is the most active, allowing a decrease of 60 kJ mol−1 of the activation energy between polyethylene imine and limonene dioxide, a biobased epoxy monomer. [ABSTRACT FROM AUTHOR]

Introduction: This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries. Methods: This retrospective and prospective observational study enrolled patients initiated on evolocumab during August 2017 to July 2019 at 49 sites across Canada, Mexico, Colombia, Saudi Arabia and Kuwait. Medical records data were extracted within 6 months prior to (baseline) and every 3 months for 12 months post evolocumab initiation and reported as available. Results: A total of 578 patients were enrolled (40.1% female, median age 60 [interquartile range (IQR) 51–68] years); 83.7% had atherosclerotic cardiovascular disease and/or familial hypercholesterolemia. Median low-density lipoprotein cholesterol (LDL-C) at baseline was 3.4 (IQR 2.7–4.2) mmol/L (131.5 [IQR 104.4–162.4] mg/dL), with 75.6% of patients receiving a statin (59.2% high intensity). Compared to baseline, the median lowest LDL-C was reduced by 70.2% and remained stable over 12 months of treatment. Guideline-recommended LDL-C thresholds < 1.8, < 1.4 and < 1.0 mmol/L (< 70, < 55 and < 40 mg/dL) were achieved by 75.3%, 63.6% and 47.4% of patients. LDL-C outcomes were consistent across high- and very high-risk patients. Background lipid-lowering therapy remained relatively stable. No serious treatment-emergent adverse events were reported, and persistence to evolocumab was 90.2% at 12 months. Conclusion: These findings provide real-world evidence that evolocumab use is in accordance with its international guideline-recommended place in dyslipidemia therapy, as well as confirmation of its effectiveness and safety in a heterogeneous population. Evolocumab can address a healthcare gap in the management of dyslipidemia by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background and aims: Statin-associated muscle symptoms (SAMS) are frequently reported. Nevertheless, few data on objective measures of muscle function are available. Recent data suggesting an important nocebo effect with statin use could confound such effects. The objective was to assess if subjective and objective measures of muscle function improve after drug withdrawal in SAMS reporters. Methods: Patients (59 men, 33 women, 50.3±9.6 yrs.) in primary cardiovascular prevention composed three cohorts: statin users with (SAMS, n = 61) or without symptoms (No SAMS, n = 15), and controls (n = 16) (registered at clinicaltrials.gov, NCT01493648). Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (Fhg) were measured using isokinetic and handheld dynamometers, respectively. A 10-point visual analogue scale (VAS) was used to self-assess SAMS intensity. Measures were taken before and after two months of withdrawal. Results: Following withdrawal, repeated-measures analyses show improvements for the entire cohort in Eext, Efle, Ffle, Pext and Pfle (range +7.2 to +13.3%, all p≤0.02). Post-hoc analyses show these changes to occur notably in SAMS (+8.8 to +16.6%), concurrent with a decrease in subjective perception of effects in SAMS (VAS, from 5.09 to 1.85). Fhg was also improved in SAMS (+4.0 to +6.2%) when compared to No SAMS (-1.7 to -4.2%) (all p = 0.02). Conclusions: Whether suffering from "true" SAMS or nocebo, those who reported SAMS had modest but relevant improvements in muscle function concurrent with a decrease in subjective symptoms intensity after drug withdrawal. Greater attention by clinicians to muscle function in frail statin users appears warranted. Trial registration: This study is registered in clinicaltrials.gov (NCT01493648). [ABSTRACT FROM AUTHOR]

Background and aims Maximizing the acute reduction of LDL-cholesterol (C) and lipoprotein (a) (Lp(a)) concentrations in patients with homozygous familial hypercholesterolemia (HoFH) is the main goal of lipoprotein apheresis (LA). The objective of this study was to examine how the pre-LA serum TG concentrations influence the efficacy of LA to acutely reduce LDL-C and Lp(a) concentrations in HoFH patients. Methods Data from 1761 LA treatments of HoFH patients (n = 10) and compound heterozygous patients (n = 5) collected between 2008 and 2016 were analyzed. These data included the pre- and post-LA concentrations of LDL-C, TGs and Lp(a); volume of filtered plasma; type of LA system used (dextran sulfate adsorption (DSA) or heparin-induced extracorporeal LDL precipitation (HELP)); and interval between treatments. Results A significant association between the pre-LA TG concentrations and acute LA-induced reduction in LDL-C, modified by the type of LA system used, was observed ( p pre-LA TG quartile*LA system  = .04). Using the DSA system, the acute reduction of the LDL-C concentrations was attenuated by 3.9% when the pre-LA TG concentrations were >2.09 mmol/L vs. ≤0.93 mmol/L (highest vs. lowest quartiles: −59.4% vs. −63.3%, p  = .007). Using the HELP system, no significant difference was observed in the reduction of LDL-C between the highest and the lowest quartiles of serum TGs (−65.8% vs. −66.4%, p  = .9). No association was observed between pre-LA TG concentrations and acute LA-induced decrease in Lp(a) ( p  = .2). Conclusions The efficacy of LA is inversely associated with pre-LA TG concentrations in HoFH patients who used the DSA system instead of the HELP system. [ABSTRACT FROM AUTHOR]

Background and aims In previous phase III studies, the PCSK9 monoclonal antibody alirocumab was administered at doses of 75 or 150 mg every 2 weeks (Q2W). CHOICE I (NCT01926782) evaluated 300 mg every 4 weeks (Q4W) in patients on either maximally tolerated statin or no statin, both ± other lipid-lowering therapies. Methods CHOICE I included patients with hypercholesterolemia at moderate-to-very-high cardiovascular risk. Patients were randomized to alirocumab 300 mg Q4W, 75 mg Q2W (calibrator arm), or placebo for 48 weeks, with dose adjustment for either alirocumab arm to 150 mg Q2W at Week (W) 12 if at W8 LDL-C levels were >70/100 mg/dL (1.8/2.6 mmol/L) depending on cardiovascular risk or LDL-C reduction was <30% from baseline. Co-primary endpoints were percent LDL-C change from baseline to W24, and to time-averaged LDL-C over W21–24. Results Approximately two-thirds of randomized patients were receiving statins. At W12, 14.7% (no statin) and 19.3% (statin) of patients receiving alirocumab 300 mg Q4W required dose adjustment. At W24, significant LDL-C reductions from baseline were observed with alirocumab 300 mg Q4W: mean differences were −52.7% (no statin; placebo: –0.3%) and −58.8% (statin; placebo: –0.1%). Average LDL-C reductions from baseline to W21–24 were also significantly greater with alirocumab 300 mg Q4W vs. placebo in patients not receiving (−56.9% vs. –1.6%) and receiving statin (−65.8% vs. –0.8%). Treatment-emergent adverse event rates ranged from 61.1 to 75.0% (placebo) and 71.5 to 78.1% (alirocumab 300 mg Q4W). Conclusions Alirocumab 300 mg Q4W is a viable additional treatment option in patients requiring LDL-C-lowering. [ABSTRACT FROM AUTHOR]

The article presents the study which examines the extent to which the low-density lipoprotein (LDLR) genotype modulates the rebound after lipoprotein apheresis (LA) in LDL-cholesterol and lipoprotein A concentrations in patients with hypercholesterolemia (HoFH). Details on the method of the study, in which data on all consecutive LA treatments with HoFH were collected, are offered.

Batchhydrogenolysis of concentrated glycerol has been conductedover different Cu/ZnO-based catalysts prepared by the coprecipitationmethod. The catalysts were characterized by X-ray diffraction, H2temperature-programmed reduction, and the N2Otitration technique of measurement of the metallic Cu surface area.Results show that the reaction system is affected by hydrogen pressure,temperature, glycerol concentration, and the surface area of metalliccopper. Our results tend to show that the reaction scheme is morecomplicated than the commonly accepted dehydration–hydrogenationmechanism. Tests conducted with varying hydrogen pressure indicatethat the mechanism may begin with the dehydrogenation of glycerolto glyceraldehyde. Tests conducted with varying water content tendto show that high water content favors ethylene glycol (EG) formation.The selectivity to 1,2-propanediol (12PG) versus ethylene glycol isa function of the relative reaction rates where the glyceraldehydecan react to either yield 12PG or go through a retro-Claisen routeto yield EG. Finally, multiple catalytic tests conducted with a constantamount of copper surface area show that, according to the Madon–Boudartcriterion, the catalytic system is heavily hampered by transport phenomenalimitations. [ABSTRACT FROM AUTHOR]

Objective We examined the obesity phenotype most strongly associated with increased plasma concentrations of sTNFR2, and compared which of the two markers, TNF-α or sTNFR2, better predicts indices of plasma glucose-insulin homeostasis. Design, patients and measurements Plasma sTNFR2 levels were measured in a sample of 287 healthy nondiabetic men [age: 43·9 ± 8·0 years (mean ± SD)], covering a wide range of adiposity values (BMI: 29·0 ± 4·4 kg/m2; waist girth: 100·0 ± 11·7 cm). Results Plasma sTNFR2 levels correlated positively and significantly with BMI ( r = 0·36; P < 0·0001), fat mass ( r = 0·42; P < 0·0001), waist girth ( r = 0·38; P < 0·0001) as well as with visceral ( r = 0·37; P < 0·0001) and subcutaneous adipose tissue (AT) ( r = 0·40; P < 0·0001) areas measured by computed tomography. Two subgroups ( n = 27 in each group) of overweight men (BMI ≥25 kg/m2) were individually matched for similar BMI values, but with markedly different levels of visceral AT (< or ≥130 cm2) and then compared with a control group of 46 lean subjects (with both BMI <25 kg/m2 and visceral AT <130 cm2). This analysis revealed that men characterized by high levels of visceral AT had significantly higher concentrations of sTNFR2 compared with obese men with low visceral AT (1861 ± 457 pg/ml vs. 1722 ± 400; P < 0·05) and with lean controls (1570 ± 291 pg/ml; P < 0·001). Whereas subjects classified across tertiles of TNF-α levels showed no difference in glucose tolerance and insulin levels, subjects in the upper tertile of plasma sTNFR2 levels were characterized with the highest plasma insulin concentrations during the OGTT and had the highest area under the curve of insulin concentrations. Conclusions These results indicate that sTNFR2 levels are more closely related to abdominal AT accumulation than to total adiposity. Furthermore, plasma concentrations of sTNFR2 are independently related to plasma glucose-insulin homeostasis beyond the known contribution of visceral adiposity. [ABSTRACT FROM AUTHOR]

Abstract: We tested the hypothesis that elevated plasma interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen concentrations are independent risk factors and interact in increasing the long-term risk of ischemic heart disease (IHD) in men. A total of 1982 IHD-free men from the Quebec Cardiovascular Study were followed over a period of 13 years during which 210 first fatal IHD events and non-fatal myocardial infarctions were recorded. Increased CRP levels (4th versus 1st quartile) were not associated with an increased risk of IHD after adjustment for non-lipid risk factors (age, body mass index, systolic blood pressure, diabetes, smoking and medication use at baseline), lipid risk factors (LDL and HDL cholesterol and triglyceride levels) and for IL-6 and fibrinogen (RR=0.70, 95% CI=0.43–1.13). High plasma IL-6 levels (4th versus 1st quartile) were associated with a 70% greater risk of IHD independent of confounding risk factors and of the other 2 inflammatory markers (RR=1.71, 95% CI=1.07–2.75). The relationship between high fibrinogen levels (4th versus 1st quartile) and IHD risk was borderline significant in multivariate analyses (RR=1.53, 95% CI=0.97–2.43). An inflammation score based on plasma IL-6 and fibrinogen levels improved the IHD risk predictive value of a multivariate model of traditional risk factors (p =0.03). Including plasma CRP levels into the inflammatory score provided no additional predictive value. In conclusion, elevated plasma IL-6 concentrations are more strongly related to IHD risk than CRP and fibrinogen. An inflammation score based on high plasma IL-6 and fibrinogen levels used in combination with traditional risk factors may improve our ability to adequately identify high risk individuals. [Copyright &y& Elsevier]

Background: HMG-CoA reductase inhibitors (statins) are commonly used in medicine to control blood lipid disorder. Large clinical trials have demonstrated that statins greatly reduces cardiovascular-related morbidity and mortality in patients with and without coronary artery disease. Also, the use of HMG-CoA reductase inhibitors has been reported to have immunosuppressive effects. Case presentation: We describe an unusual case of regression of vitiligo in a patient treated with high dose simvastatin. The relation between simvastatin and regression of vitiligo in this case report may be related to the autoimmune pathophysiology of the disease. Conclusion: This unexpected beneficial impact provides another scientific credence to the hypothesis that immune mechanisms play a role in the development of vitiligo and that the use of statins as immuno-modulator could be of use not only for treatment relative to organ transplant but in other pathologies such as vitiligo. [ABSTRACT FROM AUTHOR]

An atherogenic dyslipidemia, characterized by increased plasma triglyceride and apolipoprotein (apo) B levels, low HDL-cholesterol concentrations and the development of small, dense LDL particles has been associated with the presence of abdominal-visceral obesity. Visceral obesity is also associated with a hypercoagulate state and elevated concentrations of procoagulant factors such as factor VII. Moreover, it is known that some genetic variants in the gene encoding factor VII alter its activity and concentration, and consequently these variants may have an impact on atherosclerosis development. The objective of this study was to verify whether the factor VII R353Q polymorphism contributes to predict the risk of an atherogenic dyslipidemia in absence and in the presence of visceral obesity. A sample of 299 French-Canadian men, selected in order to cover a wide range of body fatness values, participated in this study. We observed that the R353 allele was more commonly observed among men characterized by apo B levels below 1.09 g/l than among men with apo B levels greater or above this threshold value (allele frequency of 92.1 vs 85.4%, χ[sup 2]=6.18, P=0.01). Multivariate analyses further showed that the genotype R353/R353 was associated with a lower risk to exhibit atherogenic concentrations of total-apo B (≥1.09 g/l) and LDL apo B (≥0.95 g/l) before (odds ratio:0.47, 95%CI=0.27–0.90, P=0.02; odds ratio:0.46, 95%CI=0.25–0.85, P=0.01, respectively) and after adjustments for age and visceral AT (odds ratio:0.49, 95%CI=0.24–0.91, P=0.02; odds ratio:0.44, 95%CI=0.23-0.85, P=0.01, respectively). When the two genotype groups were further divided on the basis of visceral adipose tissue (AT) accumulation using a cutoff point of 130 cm[sup 2], we observed that R353/R353 homozygotes with low visceral AT were characterized by a more favorable lipoprotein-lipid profile, mainly lower total-cholesterol, total-apo B, and LDL-apo B levels compared with R353/R353 homozygotes with high levels of visceral AT. In contrast, irrespective of obesity, plasma lipid levels among carriers of the Q353 allele were similar to those of viscerally obese men homozygous for the R353 allele. In conclusion, results of the present study suggest that the factor VII R353 allele is associated with lower concentrations of plasma apo B levels. However, the presence of visceral obesity abolishes this effect. Further studies will be necessary to confirm this association and the mechanism involved. [ABSTRACT FROM AUTHOR]

A low plasma HDL-cholesterol concentration is an important risk factor for coronary heart disease (CHD) and is often accompanied by increased triglyceride concentrations. Women have generally higher HDL-cholesterol and lower triglyceride concentrations and concomitantly are at lower risk of CHD than men. As HDL particle size is a new and potentially important marker of CHD risk, we have examined the potential gender difference in HDL particle size, assessed by nondenaturing 4–30% polyacrylamide gradient gel electrophoresis, in a sample of men (n=231) and women (n=183). Overall, men were characterized by a less favorable lipoprotein–lipid profile, which was accompanied by smaller HDL particle size compared to women. However, when men and women were matched for HDL particle size and compared for their metabolic profile, it was found that both genders were characterized by similar plasma lipoprotein–lipid profile despite the fact that women were characterized by higher levels of total body fat but lower waist girth than men. In summary, HDL particle size is a strong marker of the gender-related difference in the determination of the metabolic risk profile. [Copyright &y& Elsevier]

Background: Evolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known.Methods: We conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia. Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter (3.4 mmol per liter) or more and a triglyceride level of 400 mg per deciliter (4.5 mmol per liter) or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo. The primary end point was the percent change in LDL cholesterol level from baseline to week 24; key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24.Results: A total of 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean percent change from baseline in LDL cholesterol level was -44.5% in the evolocumab group and -6.2% in the placebo group, for a difference of -38.3 percentage points (P<0.001). The absolute change in the LDL cholesterol level was -77.5 mg per deciliter (-2.0 mmol per liter) in the evolocumab group and -9.0 mg per deciliter (-0.2 mmol per liter) in the placebo group, for a difference of -68.6 mg per deciliter (-1.8 mmol per liter) (P<0.001). Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups.Conclusions: In this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables. (Funded by Amgen; HAUSER-RCT ClinicalTrials.gov number, NCT02392559.). [ABSTRACT FROM AUTHOR]

Homozygous familial hypercholesterolemia (HoFH) is an orphan disease, most often caused by bi-allelic mutations of the LDLR gene. Patients with HoFH have elevated LDL-C levels >13 mmol/L, tendinous xanthomata and severe, premature atherosclerotic cardiovascular disease (ASCVD). Untreated, most HoFH patients die of ASCVD in youth. New therapeutic modalities include lomitapide, an inhibitor of microsomal triglyceride transfer protein that lowers hepatic LDL-C production. We have recently identified 79 Canadian patients with HoFH. Here, we describe our experience with lomitapide in the province of Quebec, a geographic area known to have a high prevalence of HoFH. This is a retrospective case series of 12 HoFH patients followed at three lipidology centers in the province of Quebec. Mean age of the patients was 44 ± 18 years; age at time of HoFH diagnosis ranged from 2 to 59 years. All patients were on a statin and ezetimibe 10 mg/day and five patients were treated with LDL apheresis. Treatment with lomitapide reduced LDL-C levels by 38% (intention-to-treat). Intolerable gastrointestinal side effects were observed in 3/12 patients and were the main reason for treatment discontinuation. Three patients tolerated lomitapide at doses ranging between 5 and 30 mg/day without major side effects. Downwards drug titration was necessary in the 6 remaining patients because of gastrointestinal side effects (n = 5) and elevated liver enzymes (n = 1), and 2 of them finally discontinued treatment. Lomitapide may be used to further decrease LDL-C in HoFH patients; gastrointestinal side effects and hepatic toxicity may limit adherence. Image 1 • Homozygous familial hypercholesterolemia (HoFH) is a rare lipoprotein disease. • HoFH is associated with severe, premature atherosclerotic cardiovascular disease. • Lomitapide treatment in HoFH reduced LDL-C levels by 38%. • Side effects and discontinuation of treatment were observed in 42% of patients. [ABSTRACT FROM AUTHOR]

• Highly ordered Co substituted mesoporous SBA-16 was prepared via postgrafting technique using cobalt acetylacetonate. • High loading of low coordination Co(II) finely dispersed on SBA-16 silica was obtained by a facile impregnation method. • Co/SBA-16 catalysts with excellent stability and reusability exhibited high yield in aerobic epoxidation of limonene under very mild conditions. • Ethylacetate has been found as the greenest and the most active solvent in this reaction. • The reaction conditions were systematically investigated and optimized using a statistical experimental design. Cobalt substituted mesoporous SBA-16 catalysts, made by post grafting technique using directly cobalt acetylacetonate as the precursor was prepared. High loading of cobalt finely dispersed on SBA-16 silica was obtained. The Co/SBA-16 catalysts exhibited high conversion and selectivity in epoxidation of limonene towards limonene epoxides with molecular oxygen as the most desirable oxidant and isobutyraldehyde as co-reagent under very mild conditions in the presence of the green solvent ethylacetate. A variety of characterization techniques such as nitrogen physisorption, XRD, DR-UV–vis, XPS, TEM indicates that the proposed impregnation procedure is a highly tunable and reproducible strategy to disperse transition metals in mesoporous silica materials. The unique pore structure of Co/SBA-16 catalysts could be beneficial for the epoxidation of bulky alkene molecules. The reaction conditions were systematically investigated using a statistical experimental design. Repeated catalytic tests showed no remarkable difference in the activity of fresh and recycled catalysts over three process cycles. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: Low-attenuation muscle (LAM) area at mid-thigh, a computed tomography (CT)–derived index of intramuscular lipids, is associated with insulin resistance, obesity, and type 2 diabetes. The present study aimed at testing the hypothesis that changes in LAM area in trunk muscles from a single abdominal scan could provide relevant information to evaluate the effects of a lifestyle intervention without the use of a mid-thigh CT scan. Methods: Cardiometabolic risk variables, including waist circumference, lipoprotein–lipid profile, glucose tolerance, and cardiorespiratory fitness, were assessed in a sample of 102 dyslipidemic viscerally obese men at baseline and after a 1-yr lifestyle intervention. Abdominal (L4–L5) and mid-thigh CT scans were performed and abdominal muscles classified as psoas and core muscles. Scans were segmented to calculate muscle areas, LAM areas, and mean attenuation values. Results: All muscle groups showed a decrease in LAM areas (P < 0.0001) in response to the lifestyle intervention. Changes in LAM areas were significantly associated with changes in triglycerides, high-density lipoprotein (HDL) cholesterol, cholesterol/HDL cholesterol ratio and log triglycerides/HDL cholesterol ratio (mid-thigh, 0.20 ≤ | r | ≤ 0.29; psoas, 0.28 ≤ | r | ≤ 0.38; core, 0.29 ≤ | r | ≤ 0.34, P < 0.05). Changes in core LAM area were significantly associated with changes in 2-h glucose levels, glucose area measured during the oral glucose tolerance test and homeostasis model assessment of insulin resistance (0.21 ≤ r ≤ 0.34, P < 0.05). Stepwise regression analyses showed that changes in LAM psoas area were associated with changes in HDL cholesterol and the cholesterol/HDL cholesterol ratio independently from changes in visceral adiposity. Conclusions: Changes in trunk LAM areas are useful indices of changes in mid-thigh LAM area observed with a 1-yr lifestyle intervention. Thus, an additional mid-thigh scan is not necessary to evaluate muscle lipid content by CT when an abdominal CT scan is available. [ABSTRACT FROM AUTHOR]

Objective: To determine whether vitamin D3 supplementation improves insulin sensitivity, using the hyperinsulinemiceuglycemic clamp. Design: This single-centre, double-blind, placebo-controlled trial randomised 96 participants at high risk of diabetes or with newly diagnosed type 2 diabetes to vitamin D3 5000 IU daily or placebo for 6 months. Methods: We assessed at baseline and 6 months: (1) primary aim: periphe ral insulin sensitivity (M-value using a 2-h hyperinsulinemic-euglycemic clamp); (2) secondary aims: other insulin sensitivity (HOMA2%S, Matsuda) and insulin secretion (insulinogenic index, C-peptide area under the curve, HOMA2-B) indices using a 2-h oral glucose tolerance test (OGTT); β-cell function (disposition index: M-value × insulinogenic index); fasting and 2-h glucose post OGTT; HbA1c; anthropometry. Results: Baseline characteristics were similar between groups (% or mea n ± s.d.): women 38.5%; age 58.7 ± 9.4 years; BMI 32.2 ± 4.1 kg/m2; prediabetes 35.8%; diabetes 20.0%; 25-hydroxyvitamin D (25(OH )D) 51.1 ± 14.2 nmol/L. At 6 months, mean 25(OH)D reached 127.6 ± 26.3 nmol/L and 51.8 ± 16.5 nmol/L in the treatment and placebo groups, respectively (P < 0.001). A beneficial effect of vitamin D3 compared with placebo was observed on M-value (mean change (95% CI): 0.92 (0.24-1.59) vs −0.03 (−0.73 to 0.67); P = 0.009) and disposition index (mean change (95% CI): 267.0 (−343.4 to 877.4) vs −55.5 (−696.3 to 585.3); P = 0.039) after 6 months. No effect was seen on other outcomes. Conclusions: In individuals at high risk of diabetes or with newly diagnosed type 2 diabetes, vitamin D supplementation for 6 months significantly increased peripheral insulin sensitivity and β-cell function, suggesting that it may slow metabolic deterioration in this population. [ABSTRACT FROM AUTHOR]

The origins of the Surface Water and Ocean Topography (SWOT) mission date back to the mid-1970s with the launch of GOES-3 and SEASAT. These missions were then followed in 1992 by the Topex-Poseidon satellite, then by Jason-1 (2001), OSTM/Jason-2 (2008), and Jason 3 (2016), a series of joint satellite missions between NASA and CNES with a goal to monitor global ocean circulation. The proposed new SWOT mission will provide 120-km-wide swath interferometric coverage with a 20-km-wide gap at the nadir. The SWOT measurements will consist of water surface elevations and water surface slopes covering nearly all of the earth's land surface at least once every 21 days. In 2010, NASA invited the Canadian Space Agency to contribute, and Canadian scientists welcomed the invitation to join the SWOT Science Definition Team and contribute to the experiments. The Canadian segment of the mission is known as the "SWOT-C" project. The SWOT satellite mission will provide unique opportunities in the Canadian context for water managers in both the public domain and in the private sector. This paper provides an overview of recent scientific progress by the SWOT-C Terrestrial Hydrology team, outlining current plans and progress towards applications and calibration post-launch. [ABSTRACT FROM AUTHOR]

Cholesterol efflux capacities (CECs) are negatively associated with cardiovascular disease risk, irrespective of plasma high-density lipoprotein (HDL) cholesterol levels. Whether interventions targeting lifestyle improve HDL-CECs is unknown. Our objective was to determine whether improving dietary quality and increasing physical activity levels improves HDL-CECs in men with abdominal obesity and dyslipidemia. Our study sample included men (48 ± 8.5 yr) with an elevated waist circumference (≥90 cm) associated with dyslipidemia (triglycerides ≥1.69 and/or HDL cholesterol <1.03 mmol/l); 113 men completed a 1-yr intervention, consisting of a healthy eating and physical activity/exercise program, and 32 were included in a control group. An oral lipid tolerance test (OLTT) was performed in a subsample of 28 men who completed the intervention, and blood was collected every 2 h for 8 h. HDL-CECs were measured using [3H]cholesterol-labeled J774 macrophages and HepG2 hepatocytes. The lifestyle modification program led to an overall improvement in the cardiometabolic risk profile, increases in J774-HDL-CEC by 14.1% (+0.88 ± 1.09%, P < 0.0001), HepG2-HDL-CEC by 3.4% (+0.17 ± 0.75%, P = 0.01), and HDL cholesterol and apolipoprotein A-1 levels (13.5%, P < 0.0001 and 14.9%, P < 0.0001, respectively). J774-HDL-CECs and HepG2-HDL-CECs did not change in the control group. The best predictor for changes in HDL-CEC was apolipoprotein A-1 level. The lifestyle modification program also improved HDL-CEC response in postprandial lipemia during an OLTT. HDL-CEC did not change during the OLTT. Our results suggest that increasing physical activity levels and improving diet quality can have a positive impact on both HDL quantity and quality in men with abdominal obesity and dyslipidemia. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Familial hypercholesterolemia (FH) is under-diagnosed and under-treated in most of the world, including Canada. National registries play a key role in identifying patients with FH, understanding gaps in care, and advancing the science of FH to better treat these patients. Methods FH Canada has established a national registry across 19 academic sites acting as "hubs" in Canada to increase awareness and access to standard-of-care therapies. Results To-date, more than 3000 patients with FH have been entered into a secure, web-based database. Early outcomes of this initiative include a greater understanding of treatment gaps for patients with FH in Canada, the development of a new, simplified Canadian definition of FH, and tools to aid in the diagnosis of FH, including imputation of baseline levels of LDL cholesterol. Conclusions As the national registry expands in size and scope, further learning will emerge with ultimate benefit for the diagnosis and treatment of FH in Canada. Highlights • FH Canada has established a national registry across 19 academic sites acting as "hubs" in Canada. • To-date, more than 3000 patients with FH have been entered into a secure, web-based database. • Early outcomes of this initiative include a greater understanding of treatment gaps for patients with FH in Canada. • FH Canada has developed a new, simplified Canadian definition of FH, and tools to aid in the diagnosis of FH. [ABSTRACT FROM AUTHOR]

The relationship between circulating estrogen levels and cardiometabolic risk factors such as insulin resistance is unclear in postmenopausal women. High estradiol (E2) levels have been reported to predict increased risk of type 2 diabetes in this population. We aimed to examine associations among estrogen levels, adiposity measurements, and cardiometabolic risk variables including insulin resistance in postmenopausal women. One hundred-one healthy participants (mean ± SD: age 57 ± 4 yr, BMI 27.9 ± 4.8 kg/m2) were included in the analysis. Fifteen plasma steroids or metabolites were measured by liquid chromatography-tandem mass spectrometry. Insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp. Body composition and fat distribution were determined with hydrostatic weighing and computed tomography, respectively. Blood lipids and circulating cytokines were also measured. Circulating E2 was positively correlated with all adiposity indexes ( r = 0.62 to 0.42, P < 0.0001) except waist-to-hip ratio. E2 was positively correlated with VLDL-cholesterol, plasma-, VLDL-, and HDL-triglyceride levels ( r = 0.31 to 0.24, P < 0.02) as well as with hs-CRP and IL-6 ( r = 0.52 and 0.29, P < 0.005) and negatively with HDL-cholesterol, adiponectin, and insulin sensitivity ( r = -0.36 to -0.20, P < 0.02). With adjustments for percent body fat, correlations between E2 and metabolic risk variables were no longer significant. Similar results were observed for circulating estrone (E1) and estrone-sulfate (E1-S) levels. In conclusion, circulating estrogen concentrations are proportional to adipose mass in postmenopausal women, although they remain in the low range. Insulin resistance as well as altered blood lipids and cytokines are observed when circulating estrogen levels are high within that range, but these differences are explained by concomitant variation in total adiposity. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported high plasma concentrations of both intestinal apolipoprotein (apo) B- 48-containing lipoproteins and PCSK9 in subjects with familial hypercholesterolemia (FH). However, the extent to which LDL receptor deficiency and PCSK9 levels influence plasma apoB-48 concentrations in humans remains to be fully characterized. The objective of the study was to assess the independent association between FH, PCSK9 concentrations and plasma apoB-48 levels in a large cohort of genetically defined FH heterozygotes (HeFH) and homozygotes (HoFH). Methods: A total of 118 HeFH, 6 HoFH, and 117 controls were included in the study. Plasma PCSK9 and apoB-48 concentrations were measured in the fasting state. Results: Plasma PCSK9 and apoB-48 levels were higher in FH subjects compared with controls (PCSK9: HoFH: 642. 6 ± 246.9 vs. HeFH: 324.9 ± 119.8 vs. controls: 194.5 ± 65.9 ng/mL, P < 0.0001; apoB-48: HoFH: 14.71 ± 4.36 vs. HeFH: 6.55 ± 4.24 vs. controls: 3.03 ± 2.07 μg/mL; P < 0.0001). There were no correlations between apoB-48 and PCSK9 plasma levels in both controls (ρ = 0.06, P = 0.5) and HeFH subjects (ρ = 0.07, P = 0.4). Multiple linear regression analysis showed that the FH status was the only independent factor associated with apoB-48 levels, contributing to 28.7% of the variance (P < 0.0001). Conclusions: These data indicate that the elevation in plasma apoB-48 levels associated with FH is independent of PCSK9 levels. [ABSTRACT FROM AUTHOR]

Our objective was to examine the respective contributions of changes in visceral adiposity, subcutaneous adiposity, liver fat, and cardiorespiratory fitness (CRF) to the improvements in cardiometabolic risk markers in response to a 3-yr healthy eating/physical activity lifestyle intervention. Ninety-four out of 144 viscerally obese healthy men completed a 3-yr lifestyle intervention. Body weight, body composition, and fat distribution were assessed by anthropometry and DEXA/computed tomography. CRF, adipokines, lipoprotein/lipid profile, and 75 g of oral glucose tolerance were assessed. CRF and visceral and subcutaneous adiposity significantly improved over the 3-yr intervention, with a nadir in year 1 and a partial regain in year 3. Liver fat (estimated by insulin hepatic extraction) stabilized from year 1 to year 3, whereas HOMA-IR, ISI-Matsuda index, and adiponectin continued to improve. Multivariate analysis revealed that both visceral adiposity and estimated liver fat reductions contributed to the improved ISI-Matsuda index observed over 3 yr (r2 = 0.28, P < 0.001). Three-year changes in fat mass and CRF were independently associated with changes in visceral fat (adjusted r2 = 0.40, P < 0.001), whereas only changes in CRF were associated with changes in estimated liver fat (adjusted r2 = 0.18, P < 0.001). A long-term (3 yr) healthy eating/physical activity intervention in men improves several cardiometabolic risk markers over the long term (3 yr) despite a partial body weight regain observed between year 1 and year 3. The improvement in CRF contributes to visceral and estimated liver fat losses over the long term, which in turn explain the benefits of the lifestyle intervention on cardiometabolic risk profile. [ABSTRACT FROM AUTHOR]

Background Present guidelines emphasise the importance of low concentrations of LDL cholesterol (LDL-C) in patients with familial hypercholesterolaemia. In most patients with the disease, however, these concentrations are not achieved with present treatments, so additional treatment is therefore warranted. Inhibition of cholesteryl ester transfer protein has been shown to reduce LDL-C concentrations in addition to regular statin treatment in patients with hypercholesterolaemia or at high risk of cardiovascular disease. We aimed to investigate the safety and efficacy of anacetrapib, a cholesteryl ester transfer protein inhibitor, in patients with heterozygous familial hypercholesterolaemia. Methods In this multicentre, randomised, double-blind, placebo-controlled, phase 3 study, patients aged 18–80 years with a genotype-confirmed or clinical diagnosis of heterozygous familial hypercholesterolaemia, on optimum lipid-lowering treatment for at least 6 weeks, and with an LDL-C concentration of 2·59 mmol/L or higher without cardiovascular disease or 1·81 mmol/L or higher with cardiovascular disease from 26 lipid clinics across nine countries were eligible. We randomly allocated participants with a computer-generated allocation schedule (2:1; block size of six; no stratification) to oral anacetrapib 100 mg or placebo for 52 weeks, with a 12 week post-treatment follow-up afterwards. We masked patients, care providers, and those assessing outcomes to treatment groups throughout the study. The primary outcome was percentage change from baseline in LDL-C concentration. We did analysis using a constrained longitudinal repeated measures model. This trial is registered with ClinicalTrials.gov, number NCT01524289. Findings Between Feb 10, 2012, and Feb 12, 2014, we randomly allocated 204 patients to anacetrapib and 102 to placebo. One patient in the anacetrapib group did not receive the drug. At week 52, anacetrapib reduced mean LDL-C concentration from 3·3 mmol/L (SD 0·8) to 2·1 mmol/L (0·8; percentage change 36·0% [95% CI −39·5 to −32·5] compared with an increase with placebo from 3·4 mmol/L (1·2) to 3·5 mmol/L (1·6; percentage change 3·7% [–1·2 to 8·6], with a difference in percentage change between anacetrapib and placebo of −39·7% (95% CI −45·7 to −33·7; p<0·0001). The number of cardiovascular events was increased in patients given anacetrapib compared with those given placebo (4 [2%] of 203 vs none [0%] of 102; p=0·1544), but the proportion with adverse events leading to discontinuation was similar (12 [6%] of 203 vs five [5%] of 102). Interpretation In patients with heterozygous familial hypercholesterolaemia, treatment with anacetrapib for 1 year was well tolerated and resulted in substantial reductions in LDL-C concentration. Whether this change leads to a reduction of cardiovascular events will be answered in an outcome study. INSET: Panel: Research in context.. [ABSTRACT FROM AUTHOR]

The article presents a study that assessed the efficacy of alirocumab, a monoloclonal antibody for proprotein convertase subtilisinkexin type 9, in reducing low-density lipoprotein cholesterol levels in patients receiving statin therapy. The study reveals higher rates of injection-site reactions, myalgia, neurocognitive events and ophthalmologic events in patients administered with alirocumab and lower rate of major adverse cardiovascular events including death from myocardial infarction.

Objective : To assess whether plasma IGFBP-2 is independently associated with components of the lipoprotein-lipid profile and to suggest a cutoff value that could identify subjects with the features of the metabolic syndrome. Methods : In this cross-sectional study, 379 Caucasian men from the general population and covering a wide range of BMI were recruited through the media. Subjects with type 2 diabetes, BMI values > 40 kg/m 2 , or taking medication targeting glucose or lipid metabolism or blood pressure were excluded. Anthropometric data were collected and plasma IGFBP-2 concentrations, glucose tolerance and an extensive plasma lipid profile were determined after an overnight fast. Results : Subjects with low IGFBP-2 levels were characterized by increased fat mass ( p < 0.0001), impaired insulin sensitivity ( p < 0.0001) and higher plasma triglyceride (TG) levels ( p < 0.0001). When divided into 6 quantiles, only subjects with the highest IGFBP-2 levels (>221.5 ng/mL) did not meet the NCEP ATP III criteria for the clinical diagnosis of the metabolic syndrome. In addition, circulating IGFBP-2 levels were significantly associated with VLDL-TG ( r = −0.51, p < 0.0001) and HDL-C ( r = −0.27, p < 0.0001) levels. After adjustments, plasma IGFBP-2 was found to be independently associated with VLDL-TG levels but not with HDL-C concentrations. Conclusions : In our cohort, IGFBP-2 levels <221.5 ng/mL are incrementally associated with a detrimental plasma lipoprotein-lipid profile. After adjustment for covariates, IGFBP-2 remained independently associated with VLDL-TG but not HDL-C levels. This study supports further investigations in other populations and validation of IGFBP-2 as a biomarker of early dyslipidemia. [ABSTRACT FROM AUTHOR]

Objectives Studies performed in rodents have suggested a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in insulin resistance and impaired body fat distribution. Our objective was to examine the relationships between markers of adiposity and insulin resistance and plasma PCSK9 levels in humans. In addition, we explored the effect of a one-year lifestyle modification program on plasma PCSK9 levels in abdominally obese, dyslipidemic men. Methods Plasma PCSK9 levels were measured by ELISA in 175 abdominally obese, dyslipidemic sedentary men. Of these abdominally obese men, 117 non-diabetic individuals completed a one-year lifestyle modification program aiming at increasing cardiorespiratory fitness levels and improving nutritional quality. Results We found no association between plasma PCSK9 levels and body mass index, waist circumference, fat and fat-free mass, or visceral and subcutaneous adipose tissue measured by computed tomography. Compared to men with the lowest PCSK9 levels (bottom tertile), those with the highest PCSK9 levels (top tertile) had the most detrimental lipoprotein-lipid profile including lower LDL particle size (253.6 ± 4.0 vs. 251.6 ± 4.0 Å, p < 0.05) and higher apolipoprotein C-III levels (36.8 ± 10.6 vs. 32.3 ± 32.3, p < 0.05). These men were also characterized by higher HOMA-IR indices (6.78 ± 3.01 vs. 5.54 ± 2.91, p < 0.05). After one year, study participants lost on average 6.7 ± 4.6 kg ( p < 0.0001). Plasma PCSK9 decreased by 9.2 ± 53.7 ng/ml (3.8%, p = 0.07). Conclusions Plasma PCSK9 levels are not associated with body fat distribution indices, modestly associated with markers of insulin resistance and LDL particle size and are slightly affected by a lifestyle modification program in abdominally obese men. [ABSTRACT FROM AUTHOR]