Genest Jacques, Frohlich Jiri, Steiner George
Cardiology Division, McGill University Health Center, Healthy Heart Program, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Am J Cardiol. 2004 Apr 1;93(7):848-53. doi: 10.1016/j.amjcard.2003.12.022.
The Diabetes Atherosclerosis Intervention Study (DAIS) examined the effects of fenofibrate or placebo on the progression of coronary artery disease (CAD) in 418 type 2 diabetic subjects with dyslipidemia. Fenofibrate use was associated with a 6% increase in high-density lipoprotein cholesterol, a 28% decrease in triglycerides, a 5% decrease in low-density lipoprotein cholesterol, and a 55% increase in plasma homocysteine (tHcy). The purpose of the present study was to determine whether this increase in tHcy in the fenofibrate group was associated with CAD progression or with clinical events. The increase in tHcy with fenofibrate (n = 207) was not related to changes in factors known to modulate tHcy levels (serum levels of Vitamin B(12), folate, or renal function). CAD was quantified by angiography at baseline and after a minimum of 3 years of therapy with fenofibrate or placebo. The primary end point was change in mean segment diameter (MSD), minimal lumen diameter, and percent stenosis. Baseline tHcy level was correlated with percent diameter stenosis (r = 0.111, p = 0.028). Baseline, but not end-of-study elevated tHcy levels, decreased the beneficial effect of fenofibrate. Unexpectedly, the final tHcy levels correlated negatively with CAD progression (r = -0.111, p = 0.031) in the overall group. In the fenofibrate group, there was no significant correlation between tHcy and minimal lumen diameter (r = -0.135, p = 0.069), or percent stenosis. An increase in tHcy levels was not correlated with adverse clinical events in the fenofibrate group. This analysis of the the DAIS reveals that the fenofibrate-mediated increase in tHcy levels does not attenuate the beneficial effects of fenofibrate on CAD progression or clinical events.
糖尿病动脉粥样硬化干预研究（DAIS）在418例患有血脂异常的2型糖尿病患者中，研究了非诺贝特或安慰剂对冠状动脉疾病（CAD）进展的影响。使用非诺贝特使高密度脂蛋白胆固醇增加6%，甘油三酯降低28%，低密度脂蛋白胆固醇降低5%，血浆同型半胱氨酸（tHcy）增加55%。本研究的目的是确定非诺贝特组中tHcy的这种增加是否与CAD进展或临床事件相关。非诺贝特组（n = 207）中tHcy的增加与已知调节tHcy水平的因素（维生素B12、叶酸的血清水平或肾功能）的变化无关。在基线时以及使用非诺贝特或安慰剂进行至少3年治疗后，通过血管造影对CAD进行量化。主要终点是平均节段直径（MSD）、最小管腔直径和狭窄百分比的变化。基线tHcy水平与直径狭窄百分比相关（r = 0.111，p = 0.028）。基线时而非研究结束时升高的tHcy水平降低了非诺贝特的有益作用。出乎意料的是，在整个组中，最终tHcy水平与CAD进展呈负相关（r = -0.111，p = 0.031）。在非诺贝特组中，tHcy与最小管腔直径（r = -0.135，p = 0.069）或狭窄百分比之间无显著相关性。非诺贝特组中tHcy水平的升高与不良临床事件无关。对DAIS的这项分析表明，非诺贝特介导的tHcy水平升高不会减弱非诺贝特对CAD进展或临床事件的有益作用。
