Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, Graz A-8036, Austria Synlab Academy, Mannheim, Germany.
Eur Heart J. 2015 Jan 1;36(1):31-8. doi: 10.1093/eurheartj/ehu055. Epub 2014 Feb 25.
The aim of the study was to examine whether differences in average diameter of low-density lipoprotein (LDL) particles were associated with total and cardiovascular mortality.
We studied 1643 subjects referred to coronary angiography, who did not receive lipid-lowering drugs. During a median follow-up of 9.9 years, 398 patients died, of these 246 from cardiovascular causes. We calculated average particle diameters of LDL from the composition of LDL obtained by β-quantification. When LDL with intermediate average diameters (16.5-16.8 nm) were used as reference category, the hazard ratios (HRs) adjusted for cardiovascular risk factors for death from any cause were 1.71 (95% CI: 1.31-2.25) and 1.24 (95% CI: 0.95-1.63) in patients with large (>16.8 nm) or small LDL (<16.5 nm), respectively. Adjusted HRs for death from cardiovascular causes were 1.89 (95% CI: 1.32-2.70) and 1.54 (95% CI: 1.06-2.12) in patients with large or small LDL, respectively. Patients with large LDL had higher concentrations of the inflammatory markers interleukin (IL)-6 and C-reactive protein than patients with small or intermediate LDL. Equilibrium density gradient ultracentrifugation revealed characteristic and distinct profiles of LDL particles in persons with large (approximately even distribution of intermediate-density lipoproteins and LDL-1 through LDL-6) intermediate (peak concentration at LDL-4) or small (peak concentration at LDL-6) average LDL particle diameters.
Calculated LDL particle diameters identify patients with different profiles of LDL subfractions. Both large and small LDL diameters are independently associated with increased risk mortality of all causes and, more so, due to cardiovascular causes compared with LDL of intermediate size.
本研究旨在探讨 LDL 颗粒平均直径的差异是否与全因和心血管死亡率相关。
我们研究了 1643 名接受冠状动脉造影检查且未服用降脂药物的患者。在中位随访 9.9 年期间，398 名患者死亡，其中 246 名死于心血管原因。我们通过β定量法获得的 LDL 组成计算 LDL 颗粒的平均直径。当以 LDL 中间平均直径（16.5-16.8nm）作为参考类别时，校正心血管危险因素后，大（>16.8nm）或小（<16.5nm）LDL 患者的全因死亡风险比（HR）分别为 1.71（95%CI：1.31-2.25）和 1.24（95%CI：0.95-1.63）。校正心血管原因死亡的 HR 分别为大（>16.8nm）或小（<16.5nm）LDL 患者的 1.89（95%CI：1.32-2.70）和 1.54（95%CI：1.06-2.12）。大 LDL 患者的炎症标志物白细胞介素（IL）-6 和 C 反应蛋白的浓度高于小或中 LDL 患者。平衡密度梯度超速离心显示大 LDL（中间密度脂蛋白和 LDL-1 至 LDL-6 均匀分布）、中 LDL（LDL-4 峰浓度）和小 LDL（LDL-6 峰浓度）患者的 LDL 颗粒具有特征性和不同的分布。
计算出的 LDL 颗粒直径可识别出具有不同 LDL 亚组分谱的患者。大 LDL 和小 LDL 直径均与全因死亡风险增加独立相关，与中等大小的 LDL 相比，更与心血管原因死亡风险增加相关。
