ABC | Volume 110, Nº4, April 2018

Original Article Cartolano et al LAP and lipoprotein size Arq Bras Cardiol. 2018; 110(4):339-347 Figure 1 – Percentages of large, intermediate, and small HDL (high density lipoprotein) particles, according to the LAP (lipid accumulation protein) tertiles. A) Adjusted by sex, age, smoking, statin, fibrate, and hypoglycemic drugs. B) Men, adjusted by age, smoking, statin, fibrate, and hypoglycemic drugs (n = 132). C) Women, adjusted by age, smoking, statin, fibrate, and hypoglycemic drugs (n = 219). i: Larger HDL. ii: Intermediate HDL. iii: Small HDL. Data are presented as mean and 95% confidence interval. Comparative analysis was performed using the linear trend test. LAP tertiles: T1 ≤ 45.5; 45.5 < T2 ≤ 80.3; T3 > 80.3. HDL – high-density lipoprotein, LAP: lipid accumulation product, % - percentage. Comparison between groups was performed by ANOVA or Kruskal-Wallis and multiple comparisons by Tukey test. * versus T1, § versus T2. Significance level adopted for all analysis p < 0.05. A B C i 40 35 30 25 20 40 35 30 25 20 40 45 50 55 15 20 25 30 15 10 20 25 30 15 10 20 25 30 40 45 50 55 40 45 50 55 40 35 30 25 20 % ii iii % % iii % iii % ii % ii % i % i % T1 T2 T3 T1 T2 T3 T1 T2 T3 T1 T2 T3 T1 T2 T3 T1 T2 T3 T1 T2 T3 T1 T2 T3 T1 T2 T3 p < 0.001 p < 0.001 p < 0.001 p < 0.001 p < 0.001 p = 0.001 p < 0.001 p < 0.001 p < 0.001 Large HDL Intermediate HDL Small HDL LAPTercile LAPTercile LAPTercile *§ *§ *§ *§ *§ *§ * * * * * * * * * * suggested that small HDL particle size is associated with several features of the metabolic syndrome and risk of CAD. 34 Our results showed a negative relationship of LAP with larger HDL and a positive relationship with smaller HDL particles. This profile is in agreement with the increased concentrations of HDL-C levels in subjects with lower LAP, although no correlation was found between LAP and Apo A1. Together with the LDL results, it reinforces the role of LAP as a surrogate marker for atherogenic lipoprotein subfractions. In addition, our findings also showed a positive linear trend between NEFA values and LAP. Epidemiological studies have reported an association between NEFA and the risk of diabetes mellitus. 35,36 Increased concentrations of NEFA in individuals with visceral obesity contribute to the development of various disorders such as peripheral insulin resistance, dyslipidemia, and β -cell apoptosis. 37 Our data showedNEFAvalues similar toor higher than the values reported in the literature. 38,39 This is compatiblewith the increased values also observed for glucose, insulin andHOMA‑IR, independent of sex in our study. Linear trends between LAP and fasting glucose, insulin and HOMA-IR confirm that this index is associated with multiple glucose- and cardiovascular-related dysfunctions. Previously, Sambataro et al. 40 showed that insulin sensitivity is not limited to dysfunction of fasting glucose and insulin and that lipidmetabolismmay affect this sensitivity. Therefore, the ability of LAP to simultaneously identify changes in glucose and lipid metabolism can expand the clinical relevance of this index. This study had some limitations. The most significant one is that this study was conducted only in individuals with at least one cardiovascular risk factor, i.e., hypertension, diabetes mellitus or dyslipidemia. This suggests that the association found here might not be valid for health people. On the other hand, unfortunately, early diagnosis of dyslipidemia and changes in glucose metabolism are common events in young adults. Thus, more individuals would benefit from the inclusion of LAP in screening and monitoring of cardiovascular risk. Second limitation is the evaluation of previous cardiovascular events by clinical data and changes in the ECG. Although it is known that these data do not necessarily reflect the absence of coronary disease, in clinical practice, individuals are not submitted to complementary tests, such as provocation test to detect myocardial ischemia, if the initial evaluation indicates low cardiovascular risk. In screening protocols, ECG, in combination 344