Association Between HDL Functions and Atherosclerotic Burden in Healthy Individuals

NCT ID: NCT02106013

Last Updated: 2014-04-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 101 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2014-03-31

Brief Summary

This is a study of HDL function in healthy individuals classified in three groups according to their HDL-cholesterol levels (Low HDL-C, Intermediate HDl-C and High HDL-C), with the purpose of investigating which characteristics of the HDL particle might be associated to atherosclerotic burden, characterized by carotid intima-media thickness above 1mm.

Detailed Description

Selection: Study participants are initially selected trough the evaluation of consecutive lipid profiles from individuals who spontaneously seek governmental primary care centers of the city of Campinas, Sao Paulo, Brazil. Telephone-based screening interviews are performed, followed by in-person clinical evaluation and blood exams.

Biochemical analyses: Glucose, triglycerides, HDL-C and c-reactive protein (CRP) are measured in an automated Modular® Analytics Evo (Roche Diagnostics, Burgess Hill, West Sussex, UK), using Roche Diagnostics® reagents (Mannheim, Germany). LDL-cholesterol is calculated by the Friedewald formula. Serum insulin levels are measured using ELISA (Millipore, Massachusetts, USA). The Homeostasis Model Assessment (HOMA) Calculator version 2.2 (University of Oxford, UK) is used to estimate insulin sensitivity. Apolipoproteins A-I and B-100 and lipoprotein (a) are determined by nephelometry in an automated system and reagents from Dade-Behring® (Marburg, Germany).

Carotid artery ultrasound: Carotid artery atherosclerosis is estimated by using high-resolution B-mode ultrasound, at the posterior wall of the common carotid artery.

Lipoprotein isolation: HDL from each study participant is isolated from plasma, through ultracentrifugation (Beckman Coulter Inc., Palo Alto, USA).

HDL chemical composition: Using commercially available enzymatic kits, HDL content of total proteins, total cholesterol, free cholesterol, phospholipids, triglycerides and apolipoprotein A-I are measured. Cholesteryl ester (CE) is calculated as the difference between total cholesterol and free cholesterol times 1.67. HDL molar concentration is estimated based on particle total mass and molecular weight.

HDL physical-chemical characterization: HDL particle size is determined using dynamic light scattering, and zeta potential using laser Doppler micro-electrophoresis.

Determination of proteins involved in HDL metabolism: Cholesteryl ester transfer protein, phospholipids transfer protein, lipoprotein lipase, hepatic lipase and lecithin:cholesterol acyl transferase activities are determined trough radiometric exogenous assays.

HDL functions: Cholesterol efflux capacity, antioxidant activity, susceptibility to oxidation, anti-inflammatory activity and platelet aggregation inhibition are measured using straightforward and consolidated methodologies.

Statistical Analyses: Differences between groups are evaluated using ANOVA or Kruskal-Wallis, with Bonferroni's post-hoc multiple comparison analysis, according to variable distribution. Chi-Square is used to compare categorical data. Analysis of covariance (ANCOVA) adjusted for confounding variables is also used, after checking variables with histograms, normality plots, and residual scatter plots that tested for linearity, normality, and variance. Pearson's correlation test is used to assess the relationships between variables. A two-sided p-value of 0.05 is considered significant.

Conditions

Low HDL Cholesterol

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Low HDL-C

Study participants with HDL-C levels below the 10th percentile (HDL-C ≤32 mg/dL)

No interventions assigned to this group

Intermediate HDL-C

Study participants with HDL-C levels between 40th and 60th percentiles (40≤HDL-C≤67 mg/dL)

No interventions assigned to this group

High HDL-C

Study participants with HDL-C levels above the 90th percentile (HDL-C ≥78mg/dL)

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• glucose <100 mg/dL
• Urea <71 mg/dL
• Creatinine < 1.20 mg/dL
• Uric acid <7.0 mg/dL
• Alanine aminotransferase <50 U/L
• Aspartate aminotransferase < 33 U/L
• Gamma-glutamyl transferase <71 U/L
• Alkaline phosphatase <129 U/L
• Thyroid stimulating hormone between 0.41 and 4.50 μUI/mL
• Free thyroxin between 0.9 and 1.8 ng/dL

Exclusion Criteria

• Symptomatic cardiovascular disease
• LDL-cholesterol ≥130 mg/dL
• Triglycerides ≥150 mg/dL
• Metabolic syndrome
• BMI ≥ 30 kg/m2
• Smoking habit
• Daily intake of alcohol >14g
• Regular use of medical treatments

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

Conselho Nacional de Desenvolvimento Científico e Tecnológico

OTHER_GOV

Sponsor Role: collaborator

University of Campinas, Brazil

OTHER

Sponsor Role: lead

Responsible Party

Andrei Carvalho Sposito

Professor of Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrei C Sposito, PhD MD

Role: PRINCIPAL_INVESTIGATOR

University of Campinas, Brazil

Locations

State University of Campinas

Campinas, São Paulo, Brazil

Countries

Brazil

Other Identifiers

BHS2

Identifier Type: -

Identifier Source: org_study_id