The haptoglobin (Hp)2-2 phenotype (~35–40% of people) is associated with increased oxidation and dysfunctional HDL in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL cholesterol and lower triglycerides have not reliably prevented cardiovascular disease in diabetes. We aimed to determine whether the effect of adding fenofibrate versus placebo to simvastatin on the risk of coronary artery disease (CAD) events depends on Hp phenotype in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial.

Cox proportional hazards regression models quantified the relationship between fenofibrate therapy and CAD events in the ACCORD lipid trial in participants with the Hp2-2 phenotype (n = 1,795) separately from those without (n = 3,201).

Fenofibrate therapy successfully lowered the risk of CAD events in participants without the Hp2-2 phenotype (multivariable adjusted hazard ratio 0.74 [95% CI 0.60–0.90] compared with no fenofibrate therapy) but not in participants with the Hp2-2 phenotype (1.16 [0.87–1.56]; P interaction = 0.009). Subgroup analyses revealed that this protective effect of fenofibrate against CAD events among the non–Hp2-2 phenotype group was pronounced in participants with severe dyslipidemia (P interaction = 0.01) and in males (P interaction = 0.02) with an increased CAD risk from fenofibrate treatment observed in females with the Hp2-2 phenotype (P interaction = 0.002).

The effect of fenofibrate added to simvastatin on risk of CAD events depends on Hp phenotype in the ACCORD lipid trial.

结合珠蛋白 (Hp)2-2 表型（约 35-40% 的人）与高血糖症中氧化增加和功能失调的 HDL 相关，这可以解释为什么旨在药理学提高 HDL 胆固醇和降低甘油三酯的药物不能可靠地预防糖尿病患者的心血管疾病. 我们旨在确定在辛伐他汀中添加非诺贝特与安慰剂对冠状动脉疾病 (CAD) 事件风险的影响是否取决于糖尿病心血管风险控制行动 (ACCORD) 脂质试验中的 Hp 表型。

Cox 比例风险回归模型量化了 ACCORD 脂质试验中具有 Hp2-2 表型 ( n = 1,795) 与没有 ( n = 3,201)参与者的非诺贝特治疗与 CAD 事件之间的关系。

非诺贝特治疗成功地降低了无 Hp2-2 表型参与者的 CAD 事件风险（与未接受非诺贝特治疗相比，多变量调整风险比 0.74 [95% CI 0.60-0.90]），但没有 Hp2-2 表型参与者（1.16 [ 0.87–1.56]；P交互作用 = 0.009）。亚组分析显示，在非 Hp2-2 表型组中，非诺贝特对 CAD 事件的这种保护作用在严重血脂异常的参与者（P交互作用 = 0.01）和男性（P交互作用 = 0.02）中显着，非诺贝特的 CAD 风险增加在具有 Hp2-2 表型的女性中观察到治疗（P交互作用 = 0.002）。

非诺贝特联合辛伐他汀对 CAD 事件风险的影响取决于 ACCORD 脂质试验中的 Hp 表型。