Candesartan improves impaired endothelial function in the human coronary artery.

BACKGROUND: Endothelial dysfunction is closely related to cardiovascular events. Several studies have documented that angiotensin II type 1 receptor blockers (ARB) improve peripheral endothelial dysfunction. However, the effect of ARB on coronary endothelial function remains elusive. The purpose of this study was to ascertain the beneficial effects of ARB on human coronary artery endothelial function. METHODS AND RESULTS: Twenty-seven patients were randomly assigned to either the candesartan group (n=14) or the control group (n=13) and followed for 12 months. Coronary blood flow velocity was measured in the left anterior descending artery without stenosis using an intracoronary Doppler-tipped guide-wire. We evaluated coronary endothelial function as the coronary blood flow velocity reserve (CFR), which was defined as the percent change in the coronary blood flow velocity after an intracoronary acetylcholine infusion. At baseline, the CFR in both groups was below 300%, implying that these patients had endothelial dysfunction. After treatment with candesartan for 6 months, the CFR increased significantly from 199 ± 20 to 337 ± 27% (P<0.001), whereas the CFR did not change in the control group (194 ± 32 vs. 185 ± 41%, P=0.52). During 12 months of observation, the cardiovascular event-free survival rate of the patients with an increased CFR was significantly greater than the rate in patients with a decreased CFR (P=0.02). Moreover, the cardiovascular event-free survival rate was greater in the candesartan group than in the control group (P=0.04). CONCLUSION: Our results suggest that candesartan improves coronary endothelial dysfunction of human coronary arteries and may prevent cardiac events.

Effect of pioglitazone on left ventricular diastolic function and fibrosis of type III collagen in type 2 diabetic patients.

BACKGROUND: Myocardial fibrosis is the major factor that regulates left ventricular (LV) diastolic function. Pioglitazone, an anti-diabetic drug, is reported to improve the LV diastolic function in diabetic patients, but its influence on myocardial fibrosis has not been clarified. We evaluated the effect of pioglitazone on LV diastolic function and myocardial fibrosis in type 2 diabetic (T2DM) patients. METHODS AND RESULTS: Fifteen T2DM patients were enrolled in the ON group, and the parameters were examined before and after pioglitazone administration (15-30 mg/day) for 6 months. Twenty-four T2DM patients were assigned to the OFF group, and the parameters were examined before and 6 months after cessation of pioglitazone. We measured echocardiographic parameters such as early diastolic mitral annular velocity (E') and plasma concentration of aminoterminal propeptide of procollagen type III (PIIIP), a marker of myocardial fibrosis. In the ON group, pioglitazone significantly increased E' (6.04+/-1.70 cm/s vs. 6.51+/-1.64 cm/s, p<0.01) and decreased PIIIP (0.553+/-0.056 U/ml vs. 0.517+/-0.072 U/ml, p<0.05). There was a significant negative correlation between the change in PIIIP and the change in E' (r=-0.424, p=0.046). On the other hand, E' was significantly decreased (5.69+/-1.34 cm/s vs. 4.97+/-1.20 cm/s, p<0.01) in the OFF group. PIIIP was not significantly changed in the OFF group, but there was a significant negative correlation between the change in PIIIP and the change in E' (r=-0.374, p=0.035). CONCLUSION: Six months of pioglitazone administration suppressed the synthesis of type III collagen, and this was associated with improved LV diastolic function in T2DM patients. Cessation of pioglitazone weakened the suppression of the synthesis of type III collagen, which in turn seemed to be associated with worse LV diastolic function.

Usefulness of plasma BNP levels as a marker of left ventricular wall stress in obese individuals.

Plasma brain natriuretic peptide (BNP) level is known to reflect left ventricular wall stress (LVWS). Recent studies have shown that obese individuals have lower BNP levels. However, the usefulness of BNP level as a marker of LVWS in obese individuals remains unclear. This study examined whether BNP reflects LVWS even in obese individuals.This study enrolled 136 hospital inpatients who had suffered chronic heart failure (NYHA class I or II), or who had undergone a thorough examination for angina pectoris. On the basis of body mass index (BMI), we divided the inpatients into nonobese (< 25) and obese (> or = 25) groups. All BNP measurements, cardiac catheterizations, and echocardiographic examinations were carried out within 24 hours. Although no significant differences were found between the two groups in the hemodynamic parameters examined, including end-diastolic LVWS (LV-EDWS) and end-systolic LVWS (LV-ESWS), BNP levels were significantly lower in the obese group compared to the nonobese group. In the nonobese group, a definite correlation between LV-EDWS or LV-ESWS and BNP (r = 0.43, r = 0.46, respectively) was observed, whereas no correlation was found between LV-EDWS or LV-ESWS and BNP in the obese group (r = -0.09, r = 0.06, respectively). To explore the mechanism for suppressed BNP levels in obese individuals, the correlation of BNP with biochemical markers was analyzed. Statistical significance was found only between adiponectin and BNP (r = 0.44), implying that BNP or adiponectin might influence the plasma levels of the other.In conclusion, BNP levels cannot be used as a marker of LVWS in obese individuals.

[Assessment of left ventricular diastolic function with pioglitazone in type 2 diabetic patients].

OBJECTIVES: This study investigated the effect of pioglitazone, an insulin sensitizer, on left ventricular diastolic function in type 2 diabetic patients. METHODS: Various echocardiographic parameters such as left ventricular ejection fraction, transmitral E/A ratio (E/A), deceleration time of E, isovolumetric relaxation time and left ventricular Tei index were measured. A total of 59 patients were enrolled in the ON-group, and the parameters were examined before and after pioglitazone administration (15-30 mg/day) for 6 months, and 9 patients in the OFF-group, and the parameters were examined before and 6 months after cessation of pioglitazone. RESULTS: Average age of subjects was 61.5 years with an age range from 45 to 79 years. Left ventricular ejection fraction and brain natriuretic peptide were not significantly changed both in the ON-group and in the OFF-group. Pioglitazone significantly increased E/A (0.91 +/- 0.23 vs 0.99 +/- 0.24, p < 0.01)and decreased deceleration time of E (233.9 +/- 58.6 vs 209.9 +/- 38.3 msec, p < 0.01), isovolumetric relaxation time(91.5 +/- 13.6 vs 76.0 +/- 12.1 msec, p < 0.01)and left ventricular Tei index (0.38 +/- 0.11 vs 0.35 +/- 0.09, p < 0.01) in the ON-group. On the other hand, E/A (1.08 +/- 0.35 vs 0.88 +/- 0.20, p < 0.01) was significantly decreased and left ventricular Tei index (0.28 +/- 0.11 vs 0.33 +/- 0.11, p < 0.01) was significantly increased in the OFF-group. CONCLUSIONS: Pioglitazone administration improves and cessation worsens left ventricular diastolic function.