Abnormal Circadian Blood Pressure Profile as a Prognostic Marker in Patients with Nonischemic Dilated Cardiomyopathy.

OBJECTIVES: An abnormal circadian blood pressure (BP) profile is considered a risk factor for cardiovascular disease. However, its significance in heart failure patients with nonischemic etiology is unknown. Herein, we investigated the prognostic value of a circadian BP profile in patients with nonischemic dilated cardiomyopathy (NIDCM). METHODS: We enrolled 114 NIDCM patients (76 males, mean age 53.1 years). The percent nighttime BP fall (%NBPF) was defined using ambulatory BP monitoring as a percent decrease in mean systolic BP in nighttime from daytime. All patients were divided into three groups: dipper (%NBPF ≥10), non-dipper (0 ≤ %NBPF < 10), and riser (%NBPF <0). RESULTS: Riser patients had the highest serum creatinine levels (dipper, 0.78 ± 0.20 mg/dl; non-dipper, 0.85 ± 0.21 mg/dl; riser, 0.99 ± 0.23 mg/dl; p = 0.006). In survival analysis, riser patients had the highest cumulative cardiac-related deaths (log-rank, p = 0.001), which was an independent predictor of cardiac-related deaths (hazard ratio, 12.6; 95% confidence interval, 1.76-253; p = 0.01). Multivariate analysis revealed that the norepinephrine level at 24-hour collected urine (24 h U-NE) and the serum creatinine level were independent determinants of %NBPF (adjusted R2 = 0.20; 24 h U-NE, p = 0.0001; serum creatinine, p = 0.04). CONCLUSIONS: The riser profile was associated with poor prognosis of NIDCM, which may reflect impaired sympathetic nervous system activity. Evaluating the circadian BP profile may be useful for risk stratification in NIDCM patients.

[Assessment of cardiac contractile reserve].

Left ventricular (LV) function is usually measured by imaging modalities such as echocardiography under static conditions in patients with dilated cardiomyopathy (DCM). However, some studies have reported that LV contractile function at rest is not reliable for assessment of the reversibility of LV contraction. Therefore, it is important to evaluate LV functional response under dynamic conditions by use of pharmacological as well as exercise stress (contractile reserve). In our studies, LVdP/dtmax was measured at rest and under dobutamine stress using a pigtail catheter with a high-fidelity micromanometer placed into the left ventricle in DCM patients. deltaVdP/dtmax as an index of myocardial contractile reserve was defined as the percentage increase in LVdP/dtmax induced by dobutamine infusion. Firstly, deltaLVdP/dtmax was correlated with peak oxygen consumption by cardiopulmonary exercise testing. In addition, impaired deltaLVdP/dtmax was associated with unfavorable prognosis. Secondly, reduced deltaLVdP/dtmax was associated with an increased washout rate evaluated by myocardial 123I-MIBG and 99mTc-MIBI scintigraphy. Finally, this residual contractile reserve was related to molecular remodeling caused by overactivation of the sympathetic nerve system in DCM patients. This review focused on the current status of contractile reserve with our findings, including procedures for evaluating contractile reserve, clinical implications, and molecular biological significance.

Atorvastatin prevents ischemic limb loss in type 2 diabetes: role of p53.

AIM: Diabetic peripheral artery disease (PAD) is prone to be aggressive and recent reports have demonstrated that p53 accumulation may be responsible for impaired wound healing in diabetes. Statins has been demonstrated to facilitate p53 degradation by activating its specific ubiquitin ligase, MDM2. The aim of this study was to determine whether atorvastatin (ATR) improves the outcome of diabetic PAD through MDM2-mediated reduction of p53. METHODS: Male KK/Ay mice (9 weeks old) were treated with ATR (2 mg/kg/day p.o.) or vehicle for 2 weeks and subjected to ischemic hindlimb operation to generate a diabetic PAD model. Incidences of amputation and changes of p53/MDM2 signaling in each ischemic limb were assessed 2 weeks after the operation (at 13 weeks of age). Effects of ATR on the insulin resistance of age-matched (13-week-old) and unoperated KK/Ay mice were assessed by the glucose tolerance test, circulating adiponectin concentration, and changes in insulin signaling (IRS-1/Akt phosphorylation). RESULTS: In intact KK/Ay, ATR treatment mitigated insulin resistance without affecting cholesterol levels. All diabetic PAD models exhibited autoamputation (100%); however, ATR treatment partially restored the limb loss (41.7%). The p53 expression level in the ischemic limb of ATR-treated KK/Ay was significantly decreased and MDM2 phosphorylation level was markedly increased in tandem with the activation of Akt. Hypoxia mimetic iron chelator deferroxamine promoted p53 accumulation in H9c2 myoblast cells by suppressing the Akt/MDM2 pathway, which was restored by ATR. CONCLUSIONS: ATR was found to restore ischemic limb loss in diabetes by augmenting p53 degradation through direct activation of the Akt/MDM2 pathway in skeletal muscle.