Kim Daniel Seung, Li Yatong K, Bell Griffith A, Burt Amber A, Vaisar Tomas, Hutchins Patrick M, Furlong Clement E, Otvos James D, Polak Joseph F, Arnan Martinson Kweku, Kaufman Joel D, McClelland Robyn L, Longstreth W T, Jarvik Gail P
Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA Department of Biostatistics, University of Washington School of Public Health, Seattle, WA.
Department of Biostatistics, University of Washington School of Public Health, Seattle, WA.
J Am Heart Assoc. 2016 May 20;5(5):e002977. doi: 10.1161/JAHA.115.002977.
Recent studies have failed to establish a causal relationship between high-density lipoprotein cholesterol levels (HDL-C) and cardiovascular disease (CVD), shifting focus to other HDL measures. We previously reported that smaller/denser HDL levels are protective against cerebrovascular disease. This study sought to determine which of small+medium HDL particle concentration (HDL-P) or large HDL-P was more strongly associated with carotid intima-media thickening (cIMT) in an ethnically diverse cohort.
In cross-sectional analyses of participants from the Multi Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of nuclear magnetic resonance spectroscopy-measured small+medium versus large HDL-P with cIMT measured in the common and internal carotid arteries, through linear regression. After adjustment for CVD confounders, low-density lipoprotein cholesterol (LDL-C), HDL-C, and small+medium HDL-P remained significantly and inversely associated with common (coefficient=-1.46 μm; P=0.00037; n=6512) and internal cIMT (coefficient=-3.82 μm; P=0.0051; n=6418) after Bonferroni correction for 4 independent tests (threshold for significance=0.0125; α=0.05/4). Large HDL-P was significantly and inversely associated with both cIMT outcomes before HDL-C adjustment; however, after adjustment for HDL-C, the association of large HDL-P with both common (coefficient=1.55 μm; P=0.30; n=6512) and internal cIMT (coefficient=4.84 μm; P=0.33; n=6418) was attenuated. In a separate sample of 126 men, small/medium HDL-P was more strongly correlated with paraoxonase 1 activity (rp=0.32; P=0.00023) as compared to both total HDL-P (rp=0.27; P=0.0024) and large HDL-P (rp=0.02; P=0.41) measures.
Small+medium HDL-P is significantly and inversely correlated with cIMT measurements. Correlation of small+medium HDL-P with cardioprotective paraoxonase 1 activity may reflect a functional aspect of HDL responsible for this finding.
近期研究未能证实高密度脂蛋白胆固醇水平（HDL-C）与心血管疾病（CVD）之间存在因果关系，研究重点遂转向其他HDL指标。我们之前报道过，较小/较致密的HDL水平可预防脑血管疾病。本研究旨在确定在一个种族多样化队列中，小+中HDL颗粒浓度（HDL-P）和大HDL-P哪一个与颈动脉内膜中层厚度（cIMT）的关联更强。
在动脉粥样硬化多族裔研究（MESA）参与者的横断面分析中，我们通过线性回归评估了核磁共振波谱法测量的小+中HDL-P与大HDL-P和颈总动脉及颈内动脉cIMT之间的关联。在对CVD混杂因素、低密度脂蛋白胆固醇（LDL-C）、HDL-C进行校正后，经过4次独立检验的Bonferroni校正（显著性阈值=0.0125；α=0.05/4），小+中HDL-P与颈总动脉（系数=-1.46μm；P=0.00037；n=6512）和颈内动脉cIMT（系数=-3.82μm；P=0.0051；n=6418）仍显著负相关。在对HDL-C进行校正之前，大HDL-P与两个cIMT结果均显著负相关；然而，在对HDL-C进行校正后，大HDL-P与颈总动脉（系数=1.55μm；P=0.30；n=6512）和颈内动脉cIMT（系数=4.84μm；P=0.33；n=6418）的关联减弱。在一个包含126名男性的独立样本中，与总HDL-P（rp=0.27；P=0.0024）和大HDL-P（rp=0.02；P=0.41）指标相比，小/中HDL-P与对氧磷酶1活性的相关性更强（rp=0.32；P=0.00023）。
小+中HDL-P与cIMT测量值显著负相关。小+中HDL-P与具有心脏保护作用的对氧磷酶1活性之间存在相关性，这可能反映了导致这一结果的HDL的功能特性。
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