Nakagami Tomoko, Nishimura Rimei, Sone Hirohito, Tajima Naoko
Diabetes Center, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
J Cardiovasc Pharmacol Ther. 2015 Mar;20(2):169-73. doi: 10.1177/1074248414537706. Epub 2014 Jun 6.
While triglycerides (TGs) and diabetes increase the risk of cardiovascular disease (CVD), their combined effects have not been quantified. We explored the combined effect of elevated TGs and glucose on CVD in a post hoc analysis of the large-scale Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study.
In the MEGA Study, 8214 patients with mild to moderate hypercholesterolemia were randomly allocated to the diet alone group or diet plus pravastatin group and followed for 5 years. Of those, 7832 patients included in the intention-to-treat analysis were stratified into 4 groups: abnormal fasting glucose (AFG) plus high TGs, high TGs alone, AFG alone, and normal fasting glucose plus normal TGs (reference). Cox proportional hazard models were used to compare the incidence of and mortality from CVD in the 4 groups.
Incidence of CVD and coronary heart disease was significantly higher in the groups with AFG alone (hazard ratio [HR], 2.02 and 3.38; P < .01, respectively) and AFG plus high TGs (HR, 2.87 and 3.87; P < .01, respectively) than the reference group. A similar relation was found in models adjusting for high-density lipoprotein cholesterol (HDL-C). Although the incidence of cerebral infarction was significantly higher only in the group with AFG plus high TGs (HR, 2.16; P = .01), it was marginally significantly higher than the reference group after adjustment for HDL-C (HR, 1.86; P = .06). Diet plus pravastatin treatment reduced the risk of cerebral infarction by 66% in the group with AFG plus high TGs (P = .03).
Our findings contribute to the formulation of the hypothesis that patients with hypercholesterolemia having AFG plus high TGs have an increased risk of cerebral infarction. These are compatible with the result from the main study that patients with hypercholesterolemia randomized to diet plus pravastatin had a reduced risk of cerebral infarction.
虽然甘油三酯（TGs）和糖尿病会增加心血管疾病（CVD）的风险，但其联合作用尚未得到量化。我们在一项针对日本成年原发性预防组高胆固醇管理大规模研究（MEGA研究）的事后分析中，探讨了TGs升高与血糖升高对CVD的联合作用。
在MEGA研究中，8214例轻度至中度高胆固醇血症患者被随机分配至单纯饮食组或饮食加普伐他汀组，并随访5年。其中，纳入意向性分析的7832例患者被分为4组：空腹血糖异常（AFG）加TGs升高、单纯TGs升高、单纯AFG以及空腹血糖正常加TGs正常（参照组）。采用Cox比例风险模型比较4组中CVD的发病率和死亡率。
单纯AFG组（风险比[HR]分别为2.02和3.38；P均<0.01）以及AFG加TGs升高组（HR分别为2.87和3.87；P均<0.01）的CVD和冠心病发病率显著高于参照组。在调整高密度脂蛋白胆固醇（HDL-C）的模型中也发现了类似关系。虽然仅AFG加TGs升高组的脑梗死发病率显著更高（HR为2.16；P = 0.01），但在调整HDL-C后略高于参照组（HR为1.86；P = 0.06）。饮食加普伐他汀治疗使AFG加TGs升高组的脑梗死风险降低了66%（P = 0.03）。
我们的研究结果有助于形成这样的假设，即患有高胆固醇血症且AFG加TGs升高的患者脑梗死风险增加。这些结果与主要研究中随机接受饮食加普伐他汀治疗的高胆固醇血症患者脑梗死风险降低的结果相符。
