ABC | Volume 110, Nº4, April 2018

Original Article Is Lipid Accumulation Product Associated with an Atherogenic Lipoprotein Profile in Brazilian Subjects? Flavia De Conti Cartolano, 1 Caroline Pappiani, 1 Maria Camila Prupper de Freitas, 1 Antonio M. Figueiredo Neto, 2 Antônio Augusto Ferreira Carioca, 1 Nágila Raquel Teixeira Damasceno 1 Faculdade de Saúde Publica da Universidade de São Paulo; 1 Instituto de Física da Universidade de São Paulo, 2 São Paulo, SP – Brazil Mailing Address: Nágila Raquel Teixeira Damasceno • Faculdade de Saúde Pública. Avenida Doutor Arnaldo, 715. Postal Code 01246-904. São Paulo, SP - Brazil E-mail: nagila@usp.br Manuscript received March 21, 2017, revised manuscript September 18, 2017, accepted November 09, 2017 DOI: 10.5935/abc.20180054 Abstract Background: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. Objective: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. Methods: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APOAI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference [cm] -58) × (triglycerides [mmol/L] ) for women and (waist circumference [cm] -65) × (triglycerides [mmol/L] ) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05. Results: LAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables. Conclusion: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders. (Arq Bras Cardiol. 2018; 110(4):339-347) Keywords: Cardiovascular Diseases; Lipoproteins, HDL; Lipoproteins, LDL; Insulin Resistance; Dyslipidemias; Adults; Risk Factors. Introduction Cardiovascular disease (CVD) is the leading cause of premature morbidity and mortality worldwide, compromising significant private and government resources. 1 Public policy programs are focused on prevention and modification in traditional risk factors (hypertension, dyslipidemia, smoking, and diabetes mellitus ), which are the basis of all models of cardiovascular risk prediction. Nevertheless, identification of new risk factors and/or markers for CVD is important to better understand some clinical events that cannot be explained by classical risk factors. These new biomarkers involve measurable biochemical parameters in serum or plasma, however, cholesterol associated with high-density lipoprotein (HDL-C) and low‑density lipoprotein (LDL-C) remain the main lipoproteins monitored to estimate cardiovascular risk in adults. 2 Currently, biomarkers associated with functionality and structure of lipoproteins – such as their size (small, intermediate, large and phenotypes A and B) – antioxidants (tocopherols, carotenoids), apolipoproteins (Apo B, AI, CII, J, F) and enzymes (Lp-PLA 2 , ACAT) have been investigated. 3-5 Particularly, small dense LDL have been extensively described by its proatherogenic properties. This particle migrates to the subendothelial space more easily, recruits and activates macrophages, causing their transformation into foam cells and generating fatty streak, a hallmark of atherosclerosis. 4 Contrary to the well-established atherogenic mechanisms of LDL, functional role of HDL size remains controversial. Small HDL species are described as more antioxidant, anti-inflammatory and more capable to promote cellular cholesterol efflux. 6 In opposite, Woudberg et al. showed that obesity was associated with reduced large HDL subclasses. 7 Many of these biomarkers are expensive, require methods technically sophisticated and show limited use in primary health care and prevention of diseases. 339