极低密度脂蛋白胆固醇与胆固醇吸收和合成标志物的关联性研究

Association between very low density lipoprotein cholesterol and cholesterol absorption/synthesis markers in patients with moderate and high risk of coronary heart disease

目的通过评价极低密度脂蛋白胆固醇（VLDL-C）水平与胆固醇吸收和合成标志物水平及其变化的关联性，探索降低VLDL-C的有效方法。方法从2008年10月到2009年6月在河南省和山西省两家医院心内科，连续人选363例从未服用过他汀药物的冠心病中高危患者，基线时测定患者体内VLDL-C水平和胆固醇吸收、合成标志物水平，并进行统一的问卷调查和体格检查，期间给予患者阿托伐他汀20mg／d对血脂进行干预，共持续4周，试验结束时再次测定VLDL．C和胆固醇吸收、合成标志物的水平。分析时按胆固醇吸收、合成标志物水平或降低幅度三分位进行分组及交叉分组，采用协方差分析方法调整年龄和性别后比较在不同胆固醇吸收和合成状态下患者VLDL-C的水平及其变化情况。并采用偏相关分析方法和多元线性回归的方法分析VLDL-C的水平与胆固醇吸收、合成标志物的关联性。结果（1）363例患者中最终共283例患者纳入统计分析，平均年龄为（55．43±9．01）岁，VLDL-C基线水平为1．06（0．65，1．86）mmol／L，胆固醇吸收标志物菜油固醇为6．01（3．78，9．45）mg／L，合成标志物7-烯胆烷醇为13．46（8．30，21．07）mg／L。（2）偏相关分析和多元回归结果均显示VLDL-C基线水平与胆固醇吸收标志物菜油固醇水平呈正相关（r=0．153，P〈0．05），但与胆固醇合成标志物7一烯胆烷醇的相关性无统计学意义（r：0．182，P=0．173）。在不同的胆固醇吸收、合成状态下随着基线菜油固醇水平的升高，VLDL-C基线水平呈现明显的上升趋势（趋势性检验P=0．035）。（3）经4周阿托伐他汀干预后，VLDL．C下降了38．0％，VLDL-C的降幅与菜油固醇的降幅呈明显正相关（r=0．331，P〈0．001），随着菜油固醇下降幅度的增加，VLDL-C的下降幅度亦呈现明显增加的趋势（趋势性检验P=0．032），而VLDL-C变化与7一烯胆烷醇变化的相关性则无统计学意义（趋势性检验P=0．798）。结论VLDL-C水平与胆固醇吸收标志物有明显的相关性，为进一步研究胆固醇吸收抑制剂是否可以更有效降低VLDL-C水平提供了初步的假设。

Objective To evaluate the association between very low density lipoprotein cholesterol （VLDL-C） and cholesterol absorption and synthesis markers in patients with moderate and high risk of coronary heart disease. Methods A total 363 statin-naive patients with moderate and high risk of coronary heart disease were consecutively recruited from two hospitals in Shanxi and Henan provinces between October 2008 and June 2009. A standard questionnaire and physical examination were performed at baseline.Atorvastatin （20 mg/day） was administered to patients for 4 weeks. Venous blood samples after an overnight fast were collected before and after treatment for measuring VLDL-C and cholesterol absorption and synthesis markers. In qualitative analyses, the baseline level of cholesterol absorption and synthesis markers and their reduction after atorvastatin treatment were categorized into 3 tertile groups. Results （ 1 ） Of 363 patients, 283 patients with mean age of （55.43 ± 9.01 ）years old with complete data were finally analyzed. The median level of baseline VLDL-C was 1.06 （0. 65, 1.86） mmol/L. The median level of baseline cholesterol absorption marker （ Campesterol ） and cholesterol synthesis marker （Lathosterol） was 6.01 （ 3.78,9.45 ） mg/L and 13.46 （8.30,21.07） mg/L, respectively. （2） Partial correlation analysis and multiple regression showed the baseline level of VLDL-C was positively correlated with Campesterol （r = 0. 153, P 〈 0. 05） but not with Lathosterol（ r = 0. 182, P = 0. 173 ）. Furthermore, baseline VLDL-C level significantly increased with tertile of the baseline level of Campesterol in the qualitative analyses（ P for trend = 0. 035 ）. （3） Mean reduction in VLDL-C levels was 38.0% after g weeks atorvastatin treatment. VLDL-C reduction was positively correlated with Campesterol reduction （ r = 0. 331, P 〈 0. 001 ）. VLDL-C reduction significantly increased with the tertile of Campesterol reduction （P for trend = 0. 032）. But this trend was not observed between VLDL-C level and Lathosterol （P for trend = 0. 798 ）. Conclusion The level of VLDL-C was closely related to cholesterol absorption marker, and further studies are needed to validate if inhibitor of cholesterol absorption （for example by Ezetimibe） could bring about more effective VLDL-C lowering effect in this patient cohort.