Laboratory of Atherosclerosis and Vascular Biology, Faculty of Medical Sciences, State University of Campinas, São Paulo, Brazil.
Laboratory of Atherosclerosis and Vascular Biology, Faculty of Medical Sciences, State University of Campinas, São Paulo, Brazil; Department of Cardiology, Brigham and Women's Hospital, Boston, New England, United States.
Nutr Metab Cardiovasc Dis. 2020 Feb 10;30(2):254-264. doi: 10.1016/j.numecd.2019.09.017. Epub 2019 Sep 23.
Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis.
Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect β = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden.
Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.
肥胖相关的高密度脂蛋白（HDL）功能下降，如胆固醇流出能力（CEC），支持了这种脂蛋白功能障碍可能导致肥胖患者动脉粥样硬化形成的观点。我们研究了体重增加是否会影响其他潜在的 HDL 保护作用，并且这些变化甚至可能在肥胖范围内之前就会发生，这是一项横断面分析。
本研究共纳入 899 名无症状个体，进行了横断面研究，包括血脂谱、体重指数（BMI）、生化指标和颈动脉内膜中层厚度（cIMT）的检测。采用超速离心法分离脂蛋白，并对随机选择的亚组（n=101）进行 HDL 理化特性、CEC、抗氧化活性、抗炎活性、HDL 介导的血小板聚集抑制作用的检测。与 BMI 升高相关的 HDL-C 增加与 cIMT 增加呈负相关（交互效应β=-0.054；95%CI -0.0815，-0.0301）。CEC、HDL-C、HDL 大小和 HDL 抗氧化活性与 cIMT 呈负相关。BMI 与 HDL 介导的血小板聚集抑制呈负相关（Spearman's rho -0.157，p<0.03）和 CEC（Spearman's rho -0.32，p<0.001），但令人惊讶的是，它与抗氧化活性呈正相关（Spearman's rho 0.194，p=0.052）。因此，即使在非肥胖、非糖尿病个体中，BMI 的增加也与 HDL 保护功能的广泛变化相关，降低 CEC 并增加抗氧化活性。在这些受试者中，HDL 浓度、大小或功能的降低与动脉粥样硬化负担的增加有关。
我们的研究结果表明，在非肥胖、非糖尿病个体中，BMI 的增加与 HDL 保护功能受损和动脉粥样硬化负担的增加有关。
