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Atherogenic subfractions of lipoproteins in the treatment of metabolic syndrome by physical activity and diet - the RESOLVE trial.

ABSTRACT: We aimed to comprehensively evaluate lipoprotein profile including lipid particle size following a lifestyle intervention in metabolic syndrome (MetS) volunteers and to assess the associations between lipoprotein subfractions and carotid-intima-media-thickness (CIMT) - a surrogate indicator of atherogenesis.100 participants (50-70 years) from the RESOLVE trial, underwent a one-year follow-up beginning with a three-week residential program combining high exercise volume (15-20 h/week), restrictive diet (-500 kcal/day), and education. For baseline references, 40 aged-matched healthy controls were recruited. Independent associations between subfractions of lipoproteins and CIMT were evaluated using a generalized estimating equations model accounting for variation in correlations between repeated measures. The lipoprotein subfractions profile was assessed using Lipoprint® electrophoresis allowing to separate: the very low-density lipoprotein (VLDL) fraction, then the intermediate-density lipoprotein (IDL) C, B and A, the low-density lipoprotein (LDL) with subfractions 1 and 2 as large LDL and subfractions 3 to 7 as small dense LDL (sdLDL), and the high density lipoprotein (HDL) subfractions categorized into large, intermediate, and small HDL. Apolipoproteins A1 and B were also measured.78 participants completed the program. At baseline, apolipoproteins B/A1, VLDL, sdLDL and small HDL were higher in MetS than in healthy controls; IDL, LDL size, large and intermediate HDL were lower. Despite time-related regains during the follow-up, lipoprotein subfractions traditionally involved in cardiovascular risk, such as sdLDL, improved immediately after the residential program with values closest to those of healthy controls. CIMT improved throughout the lifestyle intervention. Using a generalized estimating equations model, none of the subfractions of lipoproteins nor apolipoproteins were linked to CIMT.Lipoprotein subfractions traditionally involved in CVR, decreased after the 3-week residential program. During a 12 month follow-up, the time-related regains remained closer to the values of healthy controls than they were at baseline. CIMT improved throughout the lifestyle intervention. However, we failed to demonstrate a link between some lipoprotein subfractions and the atherogenicity directly measured from the wall thickness of arteries (CIMT). Further investigations are required to explore the atherogenicity of lipoprotein subfractions.NCT00917917.

SUBMITTER: Dutheil F

PROVIDER: S-EPMC4115215 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Atherogenic subfractions of lipoproteins in the treatment of metabolic syndrome by physical activity and diet - the RESOLVE trial.

Dutheil Frédéric F Walther Guillaume G Chapier Robert R Mnatzaganian George G Lesourd Bruno B Naughton Geraldine G Verney Julien J Fogli Anne A Sapin Vincent V Duclos Martine M Vinet Agnès A Obert Philippe P Courteix Daniel D Lac Gérard G

Lipids in health and disease 20140711

<h4>Background</h4>We aimed to comprehensively evaluate lipoprotein profile including lipid particle size following a lifestyle intervention in metabolic syndrome (MetS) volunteers and to assess the associations between lipoprotein subfractions and carotid-intima-media-thickness (CIMT) - a surrogate indicator of atherogenesis.<h4>Methods</h4>100 participants (50-70 years) from the RESOLVE trial, underwent a one-year follow-up beginning with a three-week residential program combining high exercis ...[more]

PMID: 25015177

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Project description:Treatment of the metabolic syndrome in adults is generally approached with diet and physical activity. The influence of diet and physical activity on cardiometabolic outcomes in children has not been clearly established.The main objective of this study was to test the hypothesis that the distribution of energy from fat and carbohydrate in addition to limited time spent engaging in physical activity would contribute to the prevalence of the metabolic syndrome and its components in a multiethnic pediatric population.Observational, cross-sectional study. Diet was assessed by two 24-hour recalls, physical activity by accelerometry, body composition by dual-energy absorptiometry, and glucose and lipid levels using fasting sera.Presence of metabolic syndrome and its components.202 African-American (n=79), white (n=68), or Hispanic (n=55) healthy children aged 7 to 12 years.The contribution of diet and physical activity to the metabolic syndrome and its components were assessed by logistic regression and multiple linear regression analyses.Prevalence of the metabolic syndrome in the total sample was 8.4%, with Hispanics more likely than whites and African Americans to meet the criteria. A greater intake of energy from carbohydrate was related to a greater waist circumference and higher concentrations of triglyceride and glucose particularly apparent within the African-American sample (P<0.05). Fat intake was associated with a lower waist circumference (P<0.05) and with lower concentrations of triglyceride (P<0.05) and glucose (P<0.001) in the total sample. Greater moderate/hard physical activity was associated with higher high-density lipoprotein cholesterol concentrations in whites (P<0.05). Increased sedentary behavior was related to greater glucose concentration in whites and Hispanics (P<0.05 for both).Diet composition was more closely related to the components of the metabolic syndrome than was physical activity, with carbohydrate intake being adversely related to waist circumference, triglyceride levels, and glucose levels. Furthermore, relationships among diet and metabolic syndrome outcomes were stronger among African-American children, suggesting that nutrition interventions in this group may be particularly beneficial.

Project description:Randomized controlled trials (RCTs) show that decreases in low-density lipoprotein cholesterol (LDL-C) by the use of statins cause a significant reduction in the development of cardiovascular disease (CVD). However, one of our previous studies showed that, among eight RCTs that investigated the effect of statins vs. a placebo on CVD development, 56-79% of patients had residual CVD risk after the trials. In three RCTs that investigated the effect of a high dose vs. a usual dose of statins on CVD development, 78-87% of patients in the high-dose statin arms still had residual CVD risk. The risk of CVD development remains even when statins are used to strongly reduce LDL-C, and this type of risk is now regarded as statin residual CVD risk. Our study shows that elevated triglyceride (TG) levels, reduced high-density lipoprotein cholesterol (HDL-C), and the existence of obesity/insulin resistance and diabetes may be important metabolic factors that determine statin residual CVD risk. Here, we discuss atherogenic lipoproteins that were not investigated in such RCTs, such as lipoprotein (a) (Lp(a)), remnant lipoproteins, malondialdehyde-modified LDL (MDA-LDL), and small-dense LDL (Sd-LDL). Lp(a) is under strong genetic control by apolipoprotein (a), which is an LPA gene locus. Variations in the LPA gene account for 91% of the variability in the plasma concentration of Lp(a). A meta-analysis showed that genetic variations at the LPA locus are associated with CVD events during statin therapy, independent of the extent of LDL lowering, providing support for exploring strategies targeting circulating concentrations of Lp(a) to reduce CVD events in patients receiving statins. Remnant lipoproteins and small-dense LDL are highly associated with high TG levels, low HDL-C, and obesity/insulin resistance. MDA-LDL is a representative form of oxidized LDL and plays important roles in the formation and development of the primary lesions of atherosclerosis. MDA-LDL levels were higher in CVD patients and diabetic patients than in the control subjects. Furthermore, we demonstrated the atherogenic properties of such lipoproteins and their association with CVD as well as therapeutic approaches.

Project description:Purpose:One cause of metabolic syndrome (MetS) is inactivity. This study analyzed the prevalence of MetS due to causes of activity limitation (AL) in adults over 40 years old. Paticipants and Methods:Participants included 2885 people aged 40-79 (1198 men and 1687 women) who completed the Korean National Health and Nutrition Survey (KNHANES) conducted between 2013 and 2017. They were divided into two groups based on age: the middle age group (MA) included 1148 total participants, 515 men and 633 women from 40-59 years old; the older age group (OA) included 1737 total participants, 683 men and 1054 women from 60-79 years old. MetS was diagnosed according to the Third Report of the National Cholesterol Education Program and the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATP III). Logistic regression was conducted to calculate the odds ratio for MetS prevalence. Results:The prevalence of MetS in people with AL increased 1.432-fold in the MA men group, 1.511-fold in the OA men group, 1.546-fold in the MA women group, and 1.565-fold in the OA women group. There were several causes of AL; people with physical activity for diabetes mellitus and hypertension increased MetS prevalence in both sexes and all age groups: MA men group (OR=3.216, 95% CI=1.852-7.354, P=0.034), MA women group (OR=2.159, 95% CI=1.854-5.346, P=0.032), OA men group (OR=3.200, 95% CI=1.235-7.841, P=0.009), and OA women group (OR=3.444, 95% CI=1.310-6.627, P=0.008). Also, mental problems in the MA men group (OR=2.284, 95% CI=1.591-4.986, P=0.012) and OA men group (OR=1.149, 95% CI=1.017-2.941, P=0.012), and musculoskeletal problems in the MA women group (OR=1.784, 95% CI=1.102-2.902, P=0.021) and OA women group (OR=1.459, 95% CI=1.054-1.993, P=0.004) increased the prevalence. Conclusion:The prevalence of MetS due to activity limitation was increased in MA and OA groups. Activity limitation increased the MetS prevalence from 1.4- to 1.5-times, Therefore, to prevent metabolic syndrome, physical activity should be increased, and guidelines should be presented according to the activity limitation causes, age, and sex.

Project description:Erectile dysfunction (ED), impaired arterial elasticity, elevated resting heart rate as well as increased levels of oxidized LDL and fibrinogen associate with future cardiovascular events. Physical activity is crucial in the prevention of cardiovascular diseases (CVD), while metabolic syndrome (MetS) comprises an increased risk for CVD events. The aim of this study was to assess whether markers of subclinical atherosclerosis are associated with the presence of ED and MetS, and whether physical activity is protective of ED.57 MetS (51.3 ± 8.0 years) and 48 physically active (PhA) (51.1 ± 8.1 years) subjects participated in the study. ED was assessed by the International Index of Erectile Function (IIEF) questionnaire, arterial elasticity by a radial artery tonometer (HDI/PulseWave™ CR-2000) and circulating oxLDL by a capture ELISA immunoassay. Fibrinogen and lipids were assessed by validated methods. The calculation of mean daily energy expenditure of physical exercise was based on a structured questionnaire.ED was more often present among MetS compared to PhA subjects, 63.2% and 27.1%, respectively (p < 0.001). Regular physical exercise at the level of > 400 kcal/day was protective of ED (OR 0.12, 95% CI 0.017-0.778, p = 0.027), whereas increased fibrinogen (OR 4.67, 95% CI 1.171-18.627, p = 0.029) and elevated resting heart rate (OR 1.07, 95% CI 1.003-1.138, p = 0.04) were independently associated with the presence of ED. In addition, large arterial elasticity (ml/mmHgx10) was lower among MetS compared to PhA subjects (16.6 ± 4.0 vs. 19.6 ± 4.2, p < 0.001), as well as among ED compared to non-ED subjects (16.7 ± 4.6 vs. 19.0 ± 3.9, p = 0.008). Fibrinogen and resting heart rate were highest and large arterial elasticity lowest among subjects with both MetS and ED.Markers of subclinical atherosclerosis associated with the presence of ED and were most evident among subjects with both MetS and ED. Thus, especially MetS patients presenting with ED should be considered at high risk for CVD events. Physical activity, on its part, seems to be protective of ED.ClinicalTrials.gov NCT01119404.

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Atherogenic subfractions of lipoproteins in the treatment of metabolic syndrome by physical activity and diet - the RESOLVE trial.

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Atherogenic subfractions of lipoproteins in the treatment of metabolic syndrome by physical activity and diet - the RESOLVE trial.

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