Prospective, randomized, single-blind comparison of effects of 6 months of treatment with telmisartan versus enalapril on high-molecular-weight adiponectin concentrations in patients with coronary artery disease.
BACKGROUND
High-molecular-weight (HMW) adiponectin has important antiatherosclerotic properties.


OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Satoh
Mamoru
M
Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine, Morioka, Iwate, Japan. m_satoh@imu.ncvc.go.jp
Tabuchi
Tsuyoshi
T
Minami
Yoshitaka
Y
Takahashi
Yuji
Y
Itoh
Tomonori
T
Nakamura
Motoyuki
M
D052242:Adiponectin / Q000097:blood*; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008970:Molecular Weight; D011446:Prospective Studies; D000077333:Telmisartan
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D004656:Enalapril; D002097:C-Reactive Protein; D000077333:Telmisartan