Evaluation of subclinical atherosclerosis in individuals with markedly elevated HDL-cholesterol levels

• Grant number: 10/20212-4
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2011 - October 31, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Raul Dias dos Santos Filho
• Grantee: Raul Dias dos Santos Filho
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Antonio Gabriele Laurinavicius ; Viviane Zorzanelli Rocha Giraldez

Abstract

Although low HDL-C is strongly associated with the development of atherosclerotic disease and the current guidelines suggest values above 40mg/dl for men and 50mg/dL for women, there is, to date, no specific guidelines on the ideal HDL-C to be reached, nor on the best way to achieve these levels. This gap is due to the lack of conclusive evidence of cardiovascular protection of markedly elevated HDL-C levels.Hyperalphalipoproteinemia (HALP) is a condition characterized by the presence of markedly elevated HDL-c plasma levels. HALP carriers offer the opportunity to evaluate the impact of isolated increase in HDL-C on cardiovascular risk. It is unclear whether HALP represents an atherogenic or atheroprotective condition. Besides, there is controversy about the role of CETP, whose reduced activity seems to be the most prevalent cause of HALP in cholesterol homeostasis. The elucidation of these points is necessary, given the increasing interest in CETP as a potential therapeutic target for raising HDL-c. To compare the prevalence of subclinical atherosclerosis among patients with HALP and control subjects, correlating these data with measures of function of CETP and HDL itself would contribute to clarifying these points. To the best of our knowledge, Coronary CT has not been applied yet in the study of subclinical coronary atherosclerosis in patients with HALP.Primary Objective:To compare the prevalence of subclinical atherosclerosis, evaluated by coronary computed tomography (calcium score) among patients with HDL-C> 90mg/dL and those with average concentrations of HDL-C (between 40 and 50mg/dL for men and between 50 and 60 mg / dL for women). Secondary objectives: 1 - To evaluate the characteristics and function of HDL-C in these patients by studying the size and electrophoretic mobility of particles and determining the concentrations of apoAI, APOAII and paraoxonase, correlating these characteristics with the presence of subclinical atherosclerosis. 2 - To study the cause of HALP in these patients, by evaluating the role of CETP and hepatic lipase (HL) and correlate these findings with the presence of subclinical atherosclerosis and functional characteristics of HDL-C. Methods: -Population: 100 volunteers will be recruited, without previous manifestation of cardiovascular disease, aged between 45 and 75 and with two or more previous measurements of lipid profile revealing HDL-C greater than or equal to 90mg/dL (HALP group). The control group will consist of 100 volunteers, without previous manifestation of cardiovascular disease, aged between 45 and 75 years and with HDL-C levels between 40 and 50mg/dL for males and between 50 and 60 mg / dL for women. Candidates will be recruited from the outpatient Heart Institute of HC-FMUSP, as the inclusion and exclusion criteria below. Inclusion Criteria: * Age between 45-75 years * HDL-C> 90mg/dL in two or more measurements for the HALP group; HDL-C levels between 40-50 mg / dL (men) or between 50-60 mg / dL (women) for the control group. Exclusion Criteria: * Use of statins *Diabetes mellitus *Alcoholism *Pregnancy *known coronary heart disease *Active liver disease *Contra-indication for the procedure. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LAURINAVICIUS, ANTONIO G.; SANTOS, ITAMAR S.; SANTOS, RAUL D.; BENSENOR, ISABELA M.; CONCEICAO, RAQUEL D.; LOTUFO, PAULO A.. Extremely elevated HDL-cholesterol levels are not associated with increased carotid intima-media thickness: data from ELSA Brasil. JOURNAL OF CLINICAL LIPIDOLOGY, v. 10, n. 4, p. 898-904, AUG 2016. (10/20212-4)