Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine, Morioka, Iwate, Japan.
Clin Ther. 2009 Oct;31(10):2113-25. doi: 10.1016/j.clinthera.2009.10.010.
High-molecular-weight (HMW) adiponectin has important antiatherosclerotic properties.
This study compared circulating HMW adiponectin concentrations and other parameters between patients with coronary artery disease (CAD) and participants without CAD. We investigated whether treatment with statins and either telmisartan or enalapril might affect HMW adiponectin and other parameters in patients with CAD. Finally, adiponectin concentrations were compared after 6 months of treatment between CAD patients with versus without cardiac events.
Consecutive patients with stable CAD admitted to our hospital (Iwate Medical University School of Medicine, Iwate, Japan) for percutaneous coronary intervention (PCI) and stent implantation and with no previous treatment with renin-angiotensin system blockers or statins were recruited. Patients with CAD who met all eligibility criteria were randomly assigned using computer-generated numbers in a 1:1 ratio to receive telmisartan (40 mg/d) or enalapril (5 mg/d) for 6 months. In addition, all patients with CAD were treated with atorvastatin (10 mg/d). The patients without CAD received no treatment with telmisartan, enalapril, or atorvastatin. Plasma concentrations of total and HMW adiponectin were measured using a highly sensitive ELISA system before PCI or drug treatment (ie, baseline) and after 6 months of treatment. In addition, high-sensitivity C-reactive protein (hs-CRP) and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. To evaluate cardiac events, follow-up coronary angiography was performed at least 6 months after PCI.
This study included 70 patients with stable CAD (mean [SD] age, 65.8 [10.9] years; male/female ratio, 55/15) and 25 participants with normal results on coronary angiography (non-CAD) (mean age, 63.5 [11.2] years; male/female ratio, 20/5). Baseline concentrations (mean [SD]) of HMW adiponectin were significantly lower in the CAD group than in the non-CAD group (2.0 [0.3] vs 9.2 [0.5] microg/mL; P < 0.01). The ratio of HMW to total adiponectin was also lower in the CAD group than in the non-CAD group (0.37 [0.02] vs 0.53 [0.02]; P < 0.01). Baseline concentrations of HMW adiponectin were negatively correlated with hs-CRP (r = -0.60) and HOMA-IR (r = -0.30) in patients with CAD. After 6 months of treatment, the telmisartan group showed significantly increased HMW adiponectin concentrations and HMW/total adiponectin ratio (HMW, 3.7 [0.7] vs 2.1 [0.5] microg/mL; P < 0.01 vs baseline; HMW/total, 0.44 [0.02] vs 0.39 [0.02]; P < 0.05 vs baseline), whereas HOMA-IR was significantly decreased (2.86 [1.93] vs 3.39 [1.77]; P < 0.05 vs baseline). HOMA-IR at follow-up was significantly lower in the telmisartan group than in the enalapril group (2.86 [1.93] vs 3.64 [1.45]; P < 0.05). In contrast, treatment with enalapril was not associated with any significant changes in total or HMW adiponectin concentrations, HMW/total adiponectin ratio, or HOMA-IR. Both the telmisartan and the enalapril groups showed significant decreases in hs-CRP after 6 months (P < 0.05 vs baseline). After 6 months of treatment with either telmisartan or enalapril, HMW adiponectin concentrations were 0.7 (0.2) microg/mL with cardiac events versus 3.2 (0.4) microg/mL without (P < 0.05); HMW/total concentrations were 0.25 (0.03) with cardiac events versus 0.43 (0.01) without (P < 0.01). In contrast, hs-CRP concentrations were higher in patients with cardiac events than in those without cardiac events (2.42 [0.52] vs 1.86 [0.45] log10 microg/dL; P < 0.01).
This study found that treatment with telmisartan and statins (but not enalapril and statins) was associated with a significant increase in HMW adiponectin concentrations and a decrease in insulin resistance in these patients with CAD.
高分子量（HMW）脂联素具有重要的抗动脉粥样硬化作用。
本研究比较了冠心病（CAD）患者和无 CAD 患者的循环 HMW 脂联素浓度和其他参数。我们调查了他汀类药物和替米沙坦或依那普利联合治疗是否会影响 CAD 患者的 HMW 脂联素和其他参数。最后，比较了 CAD 患者在治疗 6 个月后有心脏事件和无心脏事件者的脂联素浓度。
连续纳入因稳定型 CAD 入住日本岩手医科大学医院行经皮冠状动脉介入治疗（PCI）和支架植入术且此前未接受过肾素-血管紧张素系统阻滞剂或他汀类药物治疗的患者。符合所有入选标准的 CAD 患者随机分为替米沙坦（40 mg/d）或依那普利（5 mg/d）组，治疗 6 个月。此外，所有 CAD 患者均接受阿托伐他汀（10 mg/d）治疗。无 CAD 患者未接受替米沙坦、依那普利或阿托伐他汀治疗。于 PCI 或药物治疗前（即基线）及治疗 6 个月后，采用高度敏感 ELISA 系统检测总脂联素和 HMW 脂联素的血浆浓度。同时，检测高敏 C 反应蛋白（hs-CRP）和稳态模型评估的胰岛素抵抗（HOMA-IR）。至少在 PCI 后 6 个月进行随访冠状动脉造影，以评估心脏事件。
本研究纳入 70 例稳定型 CAD 患者（平均年龄 65.8 [10.9] 岁，男/女比例为 55/15）和 25 例冠状动脉造影正常者（非 CAD，平均年龄 63.5 [11.2] 岁，男/女比例为 20/5）。CAD 组 HMW 脂联素基线浓度（均数 [标准差]）显著低于非 CAD 组（2.0 [0.3] μg/mL 比 9.2 [0.5] μg/mL；P < 0.01）。CAD 组 HMW 与总脂联素比值也低于非 CAD 组（0.37 [0.02] 比 0.53 [0.02]；P < 0.01）。CAD 患者基线 HMW 脂联素浓度与 hs-CRP（r = -0.60）和 HOMA-IR（r = -0.30）呈负相关。替米沙坦组治疗 6 个月后 HMW 脂联素浓度和 HMW/总脂联素比值明显升高（HMW，3.7 [0.7] μg/mL 比 2.1 [0.5] μg/mL；P < 0.01 比基线；HMW/总，0.44 [0.02] 比 0.39 [0.02]；P < 0.05 比基线），而 HOMA-IR 明显降低（2.86 [1.93] μg/mL 比 3.39 [1.77] μg/mL；P < 0.05 比基线）。替米沙坦组随访时的 HOMA-IR 明显低于依那普利组（2.86 [1.93] μg/mL 比 3.64 [1.45] μg/mL；P < 0.05）。相比之下，依那普利治疗与总脂联素或 HMW 脂联素浓度、HMW/总脂联素比值或 HOMA-IR 无显著相关性。替米沙坦和依那普利组治疗 6 个月后 hs-CRP 均明显降低（P < 0.05 比基线）。替米沙坦或依那普利治疗 6 个月后，有心脏事件者的 HMW 脂联素浓度为 0.7（0.2）μg/mL，无心脏事件者为 3.2（0.4）μg/mL（P < 0.05）；有心脏事件者的 HMW/总浓度为 0.25（0.03），无心脏事件者为 0.43（0.01）（P < 0.01）。相反，有心脏事件者的 hs-CRP 浓度明显高于无心脏事件者（2.42 [0.52] log10 μg/dL 比 1.86 [0.45] log10 μg/dL；P < 0.01）。
本研究发现，替米沙坦和他汀类药物（而非依那普利和他汀类药物）治疗可显著增加 CAD 患者的 HMW 脂联素浓度，降低胰岛素抵抗。
