title: Coronary microvascular function is independently associated with left ventricular filling pressure in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  Left ventricular (LV) diastolic dysfunction is known as an early marker of myocardial alterations in patients with diabetes. Because microvascular disease has been regarded as an important cause of heart failure or diastolic dysfunction in diabetic patients, we tested the hypothesis that coronary flow reserve (CFR), which reflects coronary microvascular function, is associated with LV diastolic dysfunction in patients with type 2 diabetes.
  
  
  METHODS
  We studied asymptomatic patients with type 2 diabetes but without overt heart failure. Transthoracic Doppler echocardiography was performed that included pulsed tissue Doppler of the mitral annulus and CFR of the left anterior descending artery (induced by adenosine 0.14 mg/kg/min). The ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/e') was used as a surrogate marker of diastolic function. We also evaluated renal function, lipid profile, parameters of glycemic control and other clinical characteristics to determine their association with E/e'. Patients with LV ejection fraction <50%, atrial fibrillation, valvular disease, regional wall motion abnormality, renal failure (serum creatinine >2.0 mg/dl) or type 1 diabetes were excluded. Patients with a CFR <2.0 were also excluded based on the suspicion of significant coronary artery stenosis.
  
  
  RESULTS
  We included 67 asymptomatic patients with type 2 diabetes and 14 non-diabetic controls in the final study population. In univariate analysis, age, presence of hypertension, LV mass index, estimated glomerular filtration rate and CFR were significantly associated with E/e'. Multivariate analysis indicated that both LV mass index and CFR were independently associated with E/e'. In contrast, there were no significant associations between parameters of glycemic control and E/e'.
  
  
  CONCLUSIONS
  CFR was associated with LV filling pressure in patients with type 2 diabetes. This result suggests a possible link between coronary microvascular disease and LV diastolic function in these subjects.
authors.affiliation: Department of Cardiology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. dqh07724@nifty.ne.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawata
authors.affiliation: Department of Cardiology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. daimon@muf.biglobe.ne.jp.
authors.forename: Masao
authors.initials: M
authors.lastname: Daimon
authors.affiliation: Department of Cardiology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. smiyaza@juntendo.ac.jp.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: Department of Cardiology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. richikaw@juntendo.ac.jp.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Ichikawa
authors.affiliation: Department of Cardiology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. marumasa@juntendo.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Maruyama
authors.affiliation: Department of Cardiology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. sjchiang1117@seed.net.tw.
authors.forename: Shuo-Ju
authors.initials: SJ
authors.lastname: Chiang
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan. itochina@juntendo.ac.jp.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Ito
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan. fumihiko@juntendo.ac.jp.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan. hwatada@juntendo.ac.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
authors.affiliation: Department of Cardiology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. daida@juntendo.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Daida
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000175:diagnosis; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D058065:Diabetic Cardiomyopathies / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D018619:Echocardiography, Doppler, Pulsed; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation; D055806:Microvessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D016277:Ventricular Function, Left; D017725:Ventricular Pressure