McGarrah Robert W, Craig Damian M, Haynes Carol, Dowdy Z Elaine, Shah Svati H, Kraus William E
Division of Cardiology, Department of Medicine, Durham, NC, USA; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
Atherosclerosis. 2016 Mar;246:229-35. doi: 10.1016/j.atherosclerosis.2016.01.012. Epub 2016 Jan 11.
Recent failures of HDL cholesterol (HDL-C)-raising therapies to prevent cardiovascular disease (CVD) events have tempered the interest in the role of HDL-C in clinical risk assessment. Emerging data suggest that the atheroprotective properties of HDL depend on specific HDL particle characteristics not reflected by HDL-C. The purpose of this study was to determine the association of HDL particle concentration (HDL-P) and HDL subclasses with mortality in a high-risk cardiovascular population and to examine the clinical utility of these parameters in mortality risk discrimination and reclassification models.
Using nuclear magnetic resonance spectroscopy, we measured HDL-P and HDL subclasses in 3972 individuals enrolled in the CATHGEN coronary catheterization biorepository; tested for association with all-cause mortality in robust clinical models; and examined the utility of HDL subclasses in incremental mortality risk discrimination and reclassification.
Over an average follow-up of eight years, 29.6% of the individuals died. In a multivariable model adjusted for ten CVD risk factors, HDL-P [HR, 0.71 (0.67-0.76), p = 1.3e-24] had a stronger inverse association with mortality than did HDL-C [HR 0.93 (0.87-0.99), p = 0.02]. Larger HDL size conferred greater risk and the sum of medium- and small-size HDL particles (MS-HDL-P) conferred less risk. Furthermore, the strong inverse relation of HDL-P levels with mortality was accounted for entirely by MS-HDL-P; HDL-C was not associated with mortality after adjustment for MS-HDL-P. Addition of MS-HDL-P to the GRACE Risk Score significantly improved risk discrimination and risk reclassification.
HDL-P and smaller HDL subclasses were independent markers of residual mortality risk and incremental to HDL-C in a high-risk CVD population. These measures should be considered in risk stratification and future development of HDL-targeted therapies in high-risk populations.
近期升高高密度脂蛋白胆固醇(HDL-C)的疗法未能预防心血管疾病(CVD)事件,这降低了人们对HDL-C在临床风险评估中作用的兴趣。新出现的数据表明,HDL的抗动脉粥样硬化特性取决于HDL-C未反映出的特定HDL颗粒特征。本研究的目的是确定在高危心血管人群中HDL颗粒浓度(HDL-P)和HDL亚类与死亡率之间的关联,并检验这些参数在死亡率风险判别和重新分类模型中的临床效用。
我们使用核磁共振波谱法,测量了CATHGEN冠状动脉造影生物样本库中3972名个体的HDL-P和HDL亚类;在稳健的临床模型中测试其与全因死亡率的关联;并检验HDL亚类在增加死亡率风险判别和重新分类方面的效用。
在平均八年的随访期内,29.6%的个体死亡。在针对10种CVD风险因素进行调整的多变量模型中,HDL-P[风险比(HR),0.71(0.67 - 0.76),p = 1.3×10⁻²⁴]与死亡率的负相关比HDL-C[HR 0.93(0.87 - 0.99),p = 0.02]更强。较大的HDL大小带来更大风险,而中、小尺寸HDL颗粒总和(MS-HDL-P)带来的风险较小。此外,HDL-P水平与死亡率的强负相关完全由MS-HDL-P解释;在对MS-HDL-P进行调整后,HDL-C与死亡率无关。将MS-HDL-P添加到GRACE风险评分中可显著改善风险判别和风险重新分类。
在高危CVD人群中,HDL-P和较小的HDL亚类是残余死亡风险的独立标志物,且相对于HDL-C具有增量价值。在高危人群的风险分层以及未来针对HDL的治疗开发中应考虑这些指标。