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Changes in IGFBP-2 levels following a one-year lifestyle modification program are independently related to improvements in plasma apo B and LDL apo B levels.
Carter, S, Lemieux, I, Li, Z, Alméras, N, Tremblay, A, Bergeron, J, Poirier, P, Després, JP, Picard, F
Atherosclerosis. 2019;:89-97
Abstract
BACKGROUND AND AIMS Recent transversal studies have associated insulin-like growth factor binding protein (IGFBP)-2 levels with glucose tolerance and parameters of the lipoprotein-lipid profile. Here, we aimed at determining the longitudinal effects of a one-year lifestyle modification program on IGFBP-2 levels and to identify specific metabolic improvements impacted by the changes in IGFBP-2. METHODS 99 middle-aged Caucasian men were involved in a lifestyle modification program consisting in personalized healthy eating and physical activity counseling, combined to elicit a daily 500 kcal deficit. Anthropometric and metabolic parameters as well as circulating IGFBP-2 levels were measured before and after one year of the lifestyle modification program. RESULTS The intervention triggered positive changes in many metabolic parameters and a 43% (p < 0.0001) increase of IGFBP-2 levels. Subjects with the most substantial increases in IGFBP-2 also experienced the most important metabolic improvements. Changes in IGFBP-2 levels (both absolute and relative) were correlated with markers of body fat distribution and lipoprotein-lipid profile, and independently associated with changes in LDL apolipoprotein (apo) B but not VLDL apo B concentrations. Further analyses showed that for similar changes in BMI, waist circumference and visceral adipose tissue volume, large changes in IGFBP-2 levels were required to observe improvements in LDL apo B levels. CONCLUSIONS The 1-year lifestyle modification program was associated with increased IGFBP-2 concentrations. Increases in IGFBP-2 levels were closely associated with reduced LDL apo B concentrations and independently of the modifications in fat mass and insulin sensitivity. Further mechanistic studies are required to assess the effects of IGFBP-2 levels on LDL metabolism.
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Weight loss achieved by bariatric surgery modifies high-density lipoprotein subfractions and low-density lipoprotein oxidation towards atheroprotection.
Coimbra, S, Reis, F, Ferreira, C, Nunes, S, Viana, S, Catarino, A, Rocha-Pereira, P, Belo, L, Monteiro, L, Catarino, C, et al
Clinical biochemistry. 2019;:46-53
Abstract
OBJECTIVES Weight loss achieved by laparoscopic adjustable gastric banding (LAGB) induces an increase in high-density lipoprotein cholesterol (HDLc) but a small effect on low-density lipoprotein (LDL), although changes in their quality (size and composition) are uncertain. Our aim was to study the impact of weight loss, achieved 13-months after LAGB, on inflammation and dyslipidemia, focusing on HDL and LDL subfractions, and oxidized LDL (oxLDL). DESIGN & METHODS We evaluated standard lipid profile, HDL and LDL subfractions, oxLDL, interleukin (IL)-6 and C-reactive protein (CRP), in twenty obese patients, before (T0) and 13-months after LAGB (T1), and in seventeen healthy controls. RESULTS At T1, patients showed lower body weight (12% median weight loss) and anthropometric indices; reduction in TG, atherogenic indices, oxLDL, oxLDL/LDL ratio, CRP and IL-6, and enhancement in HDLc; an increase in large HDL and intermediate HDL subfractions, and a decrease in small HDL subfraction; LDL subfractions were not modified. Percentual change (%Δ) of oxLDL, from T0 to T1, correlated significantly and positively with %Δ of small HDL subfraction and with %Δ of body mass index. CONCLUSIONS Weight loss induced atheroprotective changes on inflammation, and lipid profile, enhancing larger HDL, the more atheroprotective subfraction, reducing the less protective subclass, small HDL, and reducing oxLDL and oxLDL/LDL ratio. Quality of lipoproteins appears useful cardiovascular risk biomarkers, deserving further studies.
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Serum and dietary zinc and copper in Iranian girls.
Gonoodi, K, Moslem, A, Darroudi, S, Ahmadnezhad, M, Mazloum, Z, Tayefi, M, Zadeh, SAT, Eslami, S, Shafiee, M, Khashayarmanesh, Z, et al
Clinical biochemistry. 2018;:25-31
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Abstract
OBJECTIVE Girls with micronutrient deficiencies may have impaired growth and development, and furthermore this may also impact on their childbearing. We have investigated the relationship between serum zinc and copper concentrations, dietary zinc and copper intake and anthropometric and demographic parameters, and cardiovascular risk factors, in 408 girls living in northeastern Iran. METHODS A total of 408 healthy girls, aged 12-18 years old, were included in our study. Serum zinc and copper concentrations were measured by flame atomic absorption (Varian AA240FS) and zinc and copper intake were assessed using a 3-day dietary record. RESULTS There was a weak correlation between serum and dietary zinc intake (r = 0.117, p = 0.018). The correlation between serum and dietary copper approached significance (r = -0.094, p = 0.056). The mean serum zinc and copper concentrations were 14.61 ± 2.71 μmol/L and 19.48 ± 8.01 μmol/L respectively. Height, total cholesterol (TC) and low-density lipoprotein (LDL) were positively correlated with serum copper concentration. Subjects with high serum copper concentrations (>24 μmol/L) were found to have a significantly higher fasting blood glucose (FBG) compared to subjects with normal, or low serum copper concentrations (p = 0.033). Girls who were in the 5th percentile or greater for height were found to have higher serum copper concentrations than girls in other height categories. CONCLUSION There was a weak relationship between dietary and serum concentrations of zinc. Copper status was associated with anthropometric and biochemical parameters, including FBG and lipid profile. Further studies are required to define the role of copper in metabolic health.
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Treatment of HIV infection with a raltegravir-based regimen increases LDL levels, but improves HDL cholesterol efflux capacity.
Funderburg, NT, Xu, D, Playford, MP, Joshi, AA, Andrade, A, Kuritzkes, DR, Lederman, MM, Mehta, NN
Antiviral therapy. 2017;(1):71-75
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BACKGROUND Persons infected with HIV often have altered lipid profiles that may be affected by antiretroviral therapies (ART). Traditional lipid measurements may be insufficient to assess cardiovascular disease (CVD) risk in this population. METHODS We report results from 39 ART-naive participants in a substudy of A5248, a single-arm study of raltegravir, emtricitabine/tenofovir administration. Samples were collected at baseline, 12, 24 and 48 weeks after ART initiation. We performed advanced lipid phenotyping using nuclear magnetic resonance spectroscopy (Liposcience, Raleigh, NC, USA) for lipid particle size and number, and examined high-density lipoprotein (HDL) function measuring reverse cholesterol transport using J774 macrophages. RESULTS We report significant increases in total cholesterol (13 mg/dl; P<0.001) and low-density lipoprotein (LDL; 8 mg/dl; P=0.03), with no change in triglycerides and without an increase in LDL particle number (P>0.1 all time points). HDL levels were increased over baseline levels at all time points (P<0.003), but reached a peak at week 12 and subsequently declined. HDL particle numbers also increased from baseline (P<0.002) and HDL function improved at week 48 (7% increase in efflux capacity; P<0.001). Oxidized LDL (oxLDL) levels decreased by week 12, but rose subsequently, and were not different from baseline at later time points. CONCLUSIONS HDL increases were associated with increases in beneficial HDL particles and HDL cholesterol efflux capacity, which may reduce future CVD events. Persistent inflammation in these HIV+ participants, may be a cause or consequence of oxLDL levels, and may contribute to declining levels of HDL over time. Clinicaltrials.gov NCT00660972.
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Serum oxidized low-density lipoprotein levels are related to cardiometabolic risk and decreased after a weight loss treatment in obese children and adolescents.
Morell-Azanza, L, García-Calzón, S, Rendo-Urteaga, T, Martin-Calvo, N, Chueca, M, Martínez, JA, Azcona-Sanjulián, MC, Marti, A
Pediatric diabetes. 2017;(5):392-398
Abstract
BACKGROUND AND AIMS The oxidation of low-density lipoprotein (LDL) cholesterol particles is an early atherogeninic event. Obese pediatric populations have higher levels of oxidized LDL (oxLDL) than normal weight children. The aim of this study was to evaluate the effect of a weight loss program on the biochemical profile and oxLDL levels in Spanish obese children and adolescents. METHODS Forty obese children (mean age 11 years, 51% boys) followed a 10-week weight loss program. They were dichotomized at the median of body mass index-standard deviation score (BMI-SDS) change, as high (HR) and low responders (LR) after the intervention. The intervention included a moderate energy-restricted diet, nutritional education, and family involvement. Anthropometric and biochemical measurements were performed at the beginning and during the follow up. A cardiometabolic risk score (CMS) was calculated considering metabolic risk factors. RESULTS Higher baseline oxLDL levels were associated with a higher CMS in obese children (P < .001). After the intervention, oxLDL significantly decreased in the HR group. Moreover, a positive correlation between changes in oxLDL and BMI-SDS (r = 0.385, P = .015) was found after the weight loss program. Interestingly, multiple-adjusted regression models showed an association between changes in total cholesterol [B: 0.127, 95% confidence interval (CI): 0.06 to 0.20] and LDL-cholesterol (B: 0.173, 95% CI: 0.08 to 0.26) with changes in oxLDL. CONCLUSIONS Higher baseline oxLDL levels were associated with a higher CMS in obese children. After the weight loss program, a decrease in oxLDL levels was found in HR subjects and the oxLDL levels were associated with BMI-SDS and cholesterol levels.
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Analysis of Lipoprotein Subfractions in 920 Patients With and Without Type 2 Diabetes.
Zhao, X, Zhang, HW, Zhang, Y, Li, S, Xu, RX, Sun, J, Zhu, CG, Wu, NQ, Gao, Y, Guo, YL, et al
Heart, lung & circulation. 2017;(3):211-218
Abstract
BACKGROUND It has been demonstrated that diabetic dyslipidaemia is the chief bridge between diabetes and incremental risk of cardiovascular disease in patients with diabetes. However, the characteristics of lipoprotein subfractions distribution in patients with type 2 diabetes (T2D) have not been fully investigated. The aim of present study was to evaluate the distributions of lipoprotein subfractions in T2D patients. METHODS A total of 920 patients, who have not received lipid-lowering drug treatment previously, were consecutively enrolled in this study. Based on the evidence of diabetes, patients were divided into T2D group (n=204) and non-T2D group (n=716). Both low- and high-density lipoprotein cholesterol (LDL- and HDL-C) subfractions were analysed using the Quantimetrix Lipoprint System. The distributions of lipoprotein subfractions were evaluated in patients with and without T2D. RESULTS Compared with non-T2D individuals, the T2D group manifested significantly lower large HDL-C concentration/HDL subfraction percentage, smaller mean LDL particle size but higher small HDL-C and LDL-C concentrations as well as small HDL and LDL subfraction percentages. Moreover, the data indicated that the small HDL-C/ LDL-C concentrations, the small and large HDL subfraction percentages along with the mean LDL particle size were independently related to the existence of T2D (95% CI=1.009-1.067, p=0.009; 95% CI=0.938-0.983, p=0.001; 95% CI=1.023-1.135, p=0.005; 95% CI= 1.005-1.048, p=0.014; 95% CI=0.940-0.999, p=0.040; respectively) assessed by logistic regression analysis. CONCLUSIONS The present study indicated that the changes of lipid profile in patients with T2D are characterised by abnormal distributions of lipoprotein subfractions apart from clinically atherogenic dyslipidaemia.
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Serum oxidized low-density lipoprotein decreases in response to statin therapy and relates independently to reductions in coronary plaque in patients with HIV.
Nou, E, Lu, MT, Looby, SE, Fitch, KV, Kim, EA, Lee, H, Hoffmann, U, Grinspoon, SK, Lo, J
AIDS (London, England). 2016;(4):583-90
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OBJECTIVE Circulating oxidized low-density lipoprotein (oxLDL) levels are elevated in HIV-infected patients and have been associated with atherosclerosis. Statins have been shown to reduce plaque on coronary computed tomography angiography (cCTA) in HIV-infected individuals. Thus, we investigated the effect of statins on serum oxLDL levels and the relationship between changes in oxLDL and coronary atherosclerosis on cCTA in patients with HIV. DESIGN We previously conducted a 12-month randomized, placebo-controlled trial with atorvastatin in 40 HIV-infected patients on stable antiretroviral therapy with subclinical coronary atherosclerosis and low-density lipoprotein (LDL)-cholesterol less than 130 mg/dl. METHODS In the current analysis, patients underwent cCTA and measurements of serum oxLDL, sCD14, sCD163, lipoprotein phospholipase-A2, and fasting lipids at baseline and end of the study. RESULTS Nineteen patients were randomized to atorvastatin and 21 patients to placebo. Serum oxLDL decreased -22.7% (95% CI -28.7 to -16.7) in the atorvastatin group and increased 7.5% (95% CI -3.3 to 18.4) in the placebo group (P < 0.0001). Change in oxLDL significantly correlated with changes in noncalcified plaque volume, total plaque volume, positively remodeled plaque, and low attenuation plaque. The association between changes in oxLDL and noncalcified plaque volume was independent of the baseline 10-year Framingham risk, LDL, CD4 cell count, and viral load. CONCLUSION Statins lower oxLDL levels in HIV-infected patients, and reductions in oxLDL are related to improvements in coronary atherosclerosis, independent of traditional cardiovascular risk factors. Reductions in oxLDL may be one mechanism through which statins exert beneficial effects on reducing atherosclerosis in HIV-infected individuals.
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Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events.
Mora, S, Buring, JE, Ridker, PM
Circulation. 2014;(5):553-61
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BACKGROUND Low-density lipoprotein cholesterol (LDL-C) is the traditional measure of risk attributable to LDL. Non-high-density lipoprotein cholesterol (NHDL-C), apolipoprotein B (apoB), and LDL particle number (LDL-P) are alternative measures of LDL-related risk. However, the clinical utility of these measures may only become apparent among individuals for whom levels are inconsistent (discordant) with LDL-C. METHODS AND RESULTS LDL-C was measured directly, NHDL-C was calculated, apoB was measured with immunoassay, and LDL-P was measured with nuclear magnetic resonance spectroscopy among 27 533 healthy women (median follow-up 17.2 years; 1070 incident coronary events). Participants were grouped by median LDL-C (121 mg/dL) and each of NHDL-C, apoB, and LDL-P. Discordance was defined as LDL-C greater than or equal to the median and the alternative measure less than the median, or vice versa. Despite high LDL-C correlations with NHDL-C, apoB, and LDL-P (r=0.910, 0.785, and 0.692; all P<0.0001), prevalence of LDL-C discordance as defined by median cut points was 11.6%, 18.9%, and 24.3% for NHDL-C, apoB, and LDL-P, respectively. Among women with LDL-C less than the median, coronary risk was underestimated for women with discordant (greater than or equal to the median) NHDL-C (age-adjusted hazard ratio, 2.92; 95% confidence interval, 2.33-3.67), apoB (2.48, 2.01-3.07), or LDL-P (2.32, 1.88-2.85) compared with women with concordant levels. Conversely, among women with LDL-C greater than or equal to the median, risk was overestimated for women with discordant (less than the median) NHDL-C (0.40, 0.29-0.57), apoB (0.34, 0.26-0.46), or LDL-P (0.42, 0.33-0.53). After multivariable adjustment for potentially mediating factors, including HDL cholesterol and triglycerides, coronary risk remained underestimated or overestimated by ≈20% to 50% for women with discordant levels. CONCLUSIONS For women with discordant LDL-related measures, coronary risk may be underestimated or overestimated when LDL-C alone is used. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00000479.
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Sevelamer does not decrease lipopolysaccharide or soluble CD14 levels but decreases soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol levels in individuals with untreated HIV infection.
Sandler, NG, Zhang, X, Bosch, RJ, Funderburg, NT, Choi, AI, Robinson, JK, Fine, DM, Coombs, RW, Jacobson, JM, Landay, AL, et al
The Journal of infectious diseases. 2014;(10):1549-54
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UNLABELLED Abnormal levels of inflammation are associated with cardiovascular disease and mortality in human immunodeficiency virus (HIV)-infected patients. Microbial translocation, which may cause inflammation, is decreased by sevelamer in patients undergoing hemodialysis. In this single-arm study, we evaluated the effects of 8 weeks of sevelamer therapy on 36 HIV-infected subjects who were not receiving antiretroviral therapy. Sevelamer did not significantly change markers of microbial translocation, inflammation, or T-cell activation. During sevelamer treatment, however, levels of soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol decreased significantly, whereas D-dimer levels increased. Thus, in this study population, sevelamer did not reduce microbial translocation but may have yielded cardiovascular benefits. CLINICAL TRIALS REGISTRATION NCT 01543958.
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Physical activity versus sedentary behavior: associations with lipoprotein particle subclass concentrations in healthy adults.
Aadland, E, Andersen, JR, Anderssen, SA, Kvalheim, OM
PloS one. 2013;(12):e85223
Abstract
BACKGROUND Physical activity (PA) and sedentary behavior (SED) may have independent effects on health and disease. This might be due to PA and SED having distinct effects on lipoprotein metabolism. The aim of this study was to determine associations between lipoprotein subclass particle concentrations (-P) and accelerometer-measured SED and moderate-to-vigorous PA (MVPA) in a sample of healthy adult subjects. METHODS Lipoprotein subclass particle concentrations were determined by proton nuclear magnetic resonance spectroscopy, whereas SED and MVPA were measured using Agtigraph GT1M and GT3X+ accelerometers. We obtained valid data in 73 subjects (30 men and 43 women, age 40.5 ± 10.6 years; body mass index 24.0 ± 2.8). Multiple regression analysis was used to determine associations (partial correlations) with lipoproteins. RESULTS Positive associations were detected between SED and small VLDL-P, large LDL-P and TG (partial r = 0.24 to 0.25, p < .047). Corresponding associations were non-significant for MVPA (partial r = -0.12 to 0.04, p > .355). On the contrary, MVPA was positively associated with large HDL-P, average HDL size, Apo A1 and HDL-cholesterol (partial r = 0.28 to 0.50, p < .027), whereas SED was not (partial r = -0.06 to 0.07, p > .607). CONCLUSION There might be a specific effect of SED versus MVPA on lipoprotein metabolism. However, our results must be interpreted carefully due to possible effect-modification by gender and a low sample size. Thus, our findings should be viewed as preliminary.