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CLINICAL RESEARCH: HEART FAILURE/TRANSPLANTATION

Glucose intolerance, as reflected by hemoglobin a_1c level, is associated with the incidence and severity of transplant coronary artery disease

Tomoko Kato, MD, PhD^*, Michael C. Y. Chan, MD, FRCPC, FACC^*, Shao-Zhou Gao, MD^*, John S. Schroeder, MD^*, Mitsuhiro Yokota, MD, PhD, FACC, Toyoaki Murohara, MD, PhD, Mitsunori Iwase, MD, PhD, FACC, Akiko Noda, PhD, Sharon A. Hunt, MD, FACC^* and Hannah A. Valantine, MD, MRCP, FACC^*,*

^* Department of Cardiology, Stanford University, Stanford, California, USA
Cardiovascular Division, Department of Clinical Pathophysiology, Nagoya, Japan
Department of Cardiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan
Nagoya University School of Health Sciences, Nagoya, Japan

Manuscript received December 3, 2002; revised manuscript received June 10, 2003, accepted August 26, 2003.

^* Reprint requests and correspondence: Dr. Hannah A. Valantine, Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Falk CVRC, Stanford, California 94305-5406, USA.
hvalantine{at}stanford.edu

OBJECTIVES: The possible effect of plasma hemoglobin A_1c (HbA_1c) on the development of transplant coronary artery disease (TxCAD) was investigated.

BACKGROUND: Glucose intolerance is implicated as a risk factor for TxCAD. However, a relationship between HbA_1c and TxCAD has not been demonstrated.

METHODS: Plasma HbA_1c was measured in 151 adult patients undergoing routine annual coronary angiography at a mean period of 4.1 years after heart transplantation. Intracoronary ultrasound (ICUS) was also performed in 42 patients. Transplant CAD was graded by angiography as none, mild (stenosis in any vessel 30%), moderate (31% to 69%), or severe (70%) and was defined by ICUS as a mean intimal thickness (MIT) 0.3 mm in any coronary artery segment. The association between TxCAD and established risk factors was examined.

RESULTS: Plasma HbA_1c increased with the angiographic grade of TxCAD (5.6%, 5.8%, 6.4%, and 6.2% for none, mild, moderate, and severe disease, respectively; p < 0.05 for none vs. moderate or severe) and correlated with disease severity (r = 0.24, p < 0.05). The HbA_1c level was higher in patients with MIT 0.3 mm than in those with MIT <0.3 mm (6.4% vs. 5.7%, p < 0.05). Multivariate logistic regression analysis identified HbA_1c as an independent predictor of TxCAD, as detected by angiography or ICUS (odds ratios 1.9 and 2.4, 95% confidence intervals 1.5 to 6.3 [p = 0.010] and 1.3 to 4.2 [p < 0.005], respectively).

CONCLUSIONS: Persistent glucose intolerance, as reflected by plasma HbA_1c, is associated with the occurrence of TxCAD and may play an important role in its pathogenesis.

Abbreviations and Acronyms   BMI = body mass index   CMV = cytomegalovirus   DM = diabetes mellitus   HbA1c = hemoglobin A1c   HDL = high-density lipoprotein   ICUS = intracoronary ultrasound   ISHLT = International Society for Heart and Lung Transplantation   LDL = low-density lipoprotein   MIT = mean intimal thickness   TxCAD = transplant coronary artery disease

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