High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort.
High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort.
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DOI：
10.1016/j.atherosclerosis.2016.01.012
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发表时间：
2016-03
期刊：
影响因子：
5.3
通讯作者：
Kraus WE
中科院分区：
文献类型：
--
作者：
McGarrah RW;Craig DM;Haynes C;Dowdy ZE;Shah SH;Kraus WE
最近，提高 HDL 胆固醇 (HDL-C) 的疗法在预防心血管疾病 (CVD) 事件方面的失败，削弱了人们对 HDL-C 在临床风险评估中的作用的兴趣。新数据表明，HDL 的动脉粥样硬化保护特性取决于 HDL-C 未反映的特定 HDL 颗粒特性。本研究的目的是确定 HDL 颗粒浓度 (HDL-P) 和 HDL 亚类与高危心血管人群死亡率的关联，并检查这些参数在死亡风险判别和重新分类模型中的临床效用。使用核磁共振波谱，我们测量了参加 CATHGEN 冠状动脉导管插入术生物样本库的 3972 名个体的 HDL-P 和 HDL 亚类；在稳健的临床模型中测试与全因死亡率的关联；并检查了 HDL 亚类在增量死亡风险区分和重新分类中的效用。平均随访八年，29.6% 的人死亡。在针对 10 个 CVD 危险因素进行调整的多变量模型中，HDL-P [HR，0.71 (0.67-0.76)，p= 1.3e-24] 与死亡率的负相关性强于 HDL-C [HR 0.93 (0.87-0.99)，p=0.02]。 HDL 尺寸越大，风险越大，而中小尺寸 HDL 颗粒 (MS-HDL-P) 的总和则风险较小。此外，HDL-P 水平与死亡率的强烈负相关完全是由 MS-HDL-P 造成的。调整 MS-HDL-P 后，HDL-C 与死亡率无关。将 MS-HDL-P 添加到 GRACE 风险评分中可显着改善风险辨别和风险重新分类。 HDL-P 和较小的 HDL 亚类是高风险 CVD 人群中残余死亡风险和 HDL-C 增量的独立标志。在高危人群的风险分层和 HDL 靶向治疗的未来开发中应考虑这些措施。
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.