Pioglitazone improves left ventricular diastolic function in patients with essential hypertension.
BACKGROUND
Left ventricular (LV) hypertrophy and diastolic dysfunction, which are common cardiac consequences of hypertension, are modified by insulin resistance. The present study assessed the hypothesis that primary treatment of insulin resistance may reverse such cardiac changes in hypertensive patients.


METHODS
A total of 30 patients with essential hypertension were enrolled in this study. In echocardiographic examinations, LV mass index, the peak velocity ratio of early diastolic to atrial filling (E/A), and the E-wave deceleration time (DcT) were determined. Insulin sensitivity test with steady-state plasma glucose (SSPG) method, oral glucose tolerance test, and blood samplings for measurement of adiponectin and matrix metalloproteinase (MMP)-2 were also performed. Six months after treatment with pioglitazone (30 mg/day), an insulin sensitizer, these examinations were repeated.


RESULTS
Pioglitazone significantly increased E/A and decreased DcT, without a change in LV mass index. These improvements in diastolic properties were much greater in subjects with a marked (>or==3.3 mmol/L) decrease in SSPG (n=11) than the others (n=19), although the decrease in glucose levels did not differ between the two groups. In addition, the changes in E/A and DcT were closely correlated with the decrease in SSPG. Pioglitazone treatment significantly elevated plasma adiponectin and MMP-2 levels, and the increase in MMP-2 was positively correlated with the increase in adiponectin.


CONCLUSIONS
The present findings demonstrate that pioglitazone improves LV diastolic function without LV mass regression in hypertensive patients in proportion to the amelioration of insulin resistance. These findings suggest that increased adiponectin and MMP may be involved in the beneficial effect of pioglitazone on diastolic function.
Horio
Takeshi
T
Division of Hypertension and Nephrology, Department of Medicine, National Cardiovascular Center, Suita, Japan. thorio@ri.ncvc.go.jp
Suzuki
Masaaki
M
Suzuki
Kazutaka
K
Takamisawa
Itaru
I
Hiuge
Aki
A
Kamide
Kei
K
Takiuchi
Shin
S
Iwashima
Yoshio
Y
Kihara
Shinji
S
Funahashi
Tohru
T
Yoshimasa
Yasunao
Y
Kawano
Yuhei
Y
D052242:Adiponectin; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003971:Diastole; D004452:Echocardiography; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects*
D052242:Adiponectin; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D045162:Thiazolidinediones; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D000077205:Pioglitazone