Comparison of medically versus surgically treated acute type a aortic dissection in patients <80 years old versus patients ≥80 years old.

Although recent progress in emergency surgery has resulted in an increase in the indication for older patients with acute type A aortic dissection (AAD), some patients remain who cannot undergo surgical treatment and little is known about the prognosis of patients with AAD who receive medical treatment, especially in elderly patients. Of the 82 patients with AAD who were admitted to our institution, 48 received medical therapy only. We retrospectively reviewed their clinical data and analyzed the prognostic value of the clinical characteristics in both younger and older patients. The in-hospital and 1-year mortality were significantly lower in the patients who underwent surgical treatment than in those who received medical treatment (6% vs 65%, p <0.001; 8% vs 73%, p <0.001, respectively). Of the patients with medical treatment, the in-hospital and 1-year mortality rate in the younger (<80 years old, n = 27) and older (≥80 years old, n = 21) groups was 70% and 80% and 57% and 65%, respectively. For the younger group, the presence of an open false lumen was significantly associated with in-hospital mortality (89% vs 50%, p = 0.044). In contrast, in the older group, a lower serum albumin level (3.4 ± 0.3 vs 4.0 ± 0.5 g/dl, p = 0.010) and the incidence of an open false lumen (83% vs 33%, p = 0.032) were significantly associated with in-hospital mortality. In conclusion, in addition to an open false lumen as a risk factor, a lower serum albumin level is an important prognostic factor in older patients with AAD.

Does N-acetylcysteine reduce the incidence of contrast-induced nephropathy and clinical events in patients undergoing primary angioplasty for acute myocardial infarction?

OBJECTIVES: We examined oral N-acetylcysteine effects on contrast-induced nephropathy (CIN) and clinical events in patients undergoing primary angioplasty for acute myocardial infarction. BACKGROUND: Recent studies have reported that N-acetylcysteine reduces CIN and improves the clinical outcome in patients undergoing primary angioplasty. However, additional investigations are warranted to further support these findings. METHODS: We randomly assigned 76 patients undergoing primary angioplasty into two groups: 38 patients were assigned to N-acetylcysteine (NAC, 705 mg orally administration before and 12, 24, 36 hours after primary angioplasty), and 38 patients to placebo. CIN was defined as an increase in the serum creatinine concentration of 25 percent or more from baseline value within the 72-hour period after primary angioplasty. RESULTS: CIN occurred in 7 patients (9.2%). In the NAC group, the incidence of CIN tended to be lower than in the placebo group (NAC; 2/38; 5.3% vs. Placebo; 5/38; 13.2%, p=0.21). The composite endpoints such as death, acute renal failure requiring temporary renal replacement therapy, or need for mechanical ventilation did not occur in either group. CONCLUSION: While N-acetylcysteine might have the possibility to reduce the incidence of contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction, the in-hospital mortality and morbidity were not significantly different between the two groups.

The prognostic value of treadmill exercise testing in very elderly patients: heart rate recovery as a predictor of mortality in octogenarians.

AIMS: Several treadmill exercise testing prognostic parameters have been identified in various populations. However, despite the widespread use of treadmill exercise testing, the prognostic value in very elderly patients has not been well characterized. The aim of this study was to assess the results of treadmill exercise testing in octogenarians, and to examine various parameters in order to identify a prognostic marker of mortality. METHODS AND RESULTS: This study included 97 consecutive octogenarians (age, 81.1 ± 1.8 years; 66% male) who were referred for treadmill exercise testing. During the follow-up period (2.6 ± 1.6 years), all-cause death occurred in 20 patients (21%). Univariate Cox proportional hazard regression analysis showed that abnormal heart rate recovery (HRR) (defined as a decreased heart rate of ≤ 18 beats per minute after peak exercise) [hazard ratio (HR), 2.82; 95% confidence interval (CI), 1.06-7.47; P = 0.037] and ischaemic ST-segment change (HR, 2.56; 95% CI, 1.01-6.46; P = 0.047) were significantly associated with all-cause mortality. After adjusting for age and sex, multivariate Cox proportional hazard analysis showed that abnormal HRR was the only independent predictor of all-cause death (HR, 2.86; 95% CI, 1.01-8.11; P = 0.048). CONCLUSION: Attenuated HRR is a significant prognostic marker for all-cause death among octogenarians. The results may provide helpful support for risk stratification in clinical practice.

Upregulation of renal eNOS by high-sodium diet facilitates hypertension in doxorubicin-treated rats through enhanced oxidative stress.

It is known that renal nitric oxide (NO) is an important controller of urinary sodium excretion. A defect in the kidney's NO system could cause salt-sensitive hypertension. Since it has been demonstrated that doxorubicin binds to the reductase domain of endothelial NO synthase (eNOS) and generates superoxide in vitro, we tested our hypothesis that a high-sodium diet would upregulate the expression of eNOS and enhance oxidative stress in the kidney of doxorubicin-treated rats, resulting in a facilitation of hypertension. At 4 weeks after treatment with doxorubicin in Sprague-Dawley rats, the systolic blood pressure significantly increased only in the high-sodium diet group. The expressions of eNOS protein in the renal cortex and medulla were significantly higher in high-sodium groups than in normal-sodium groups, regardless of doxorubicin treatment. In rats treated with doxorubicin, a biomarker of oxidative damage 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunohistological staining of renal tissues showed strong staining of the proximal and distal tubules. In particular, rats with doxorubicin in the high-sodium diet group demonstrated a significant increase in urinary exertion of 8-OHdG as well as more prominently stained tubules against 8-OHdG antibody, but markedly lower urinary NO(x) excretion than in rats without doxorubicin, even than in the untreated, low-sodium group. In conclusion, these results indicate that the oxidative stress induced by doxorubicin impairs NO production in the kidney. As such, doxorubicin treatment appears to contribute to the development of salt-sensitive hypertension through reductive activation of upregulated eNOS by a high-sodium diet instead of NO production.

Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC.

Fenofibrate improves endothelial function by lipid-lowering and anti-inflammatory effects. Additionally, fenofibrate has been demonstrated to upregulate endothelial nitric oxide synthase (eNOS). AMP-activated protein kinase (AMPK) has been reported to phosphorylate eNOS at Ser-1177 and stimulate vascular endothelium-derived nitric oxide (NO) production. We report here that fenofibrate activates AMPK and increases eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with fenofibrate increased the phosphorylation of AMPK and acetyl-CoA carboxylase. Fenofibrate simultaneously increased eNOS phosphorylation and NO production. Inhibitors of protein kinase A and phosphatidylinositol 3-kinase failed to suppress the fenofibrate-induced eNOS phosphorylation. Neither bezafibrate nor WY-14643 activated AMPK in HUVEC. Furthermore, fenofibrate activated AMPK without requiring any transcriptional activities. These results indicate that fenofibrate stimulates eNOS phosphorylation and NO production through AMPK activation, which is suggested to be a novel characteristic of this agonist and unrelated to its effects on peroxisome proliferator-activated receptor alpha.

Inverse correlation between soluble CD40 ligand and soluble CD40 is absent in patients with unstable angina.

The CD40/CD40 ligand (CD40L) system mediates inflammatory processes important in atherogenesis and plaque instability. The expression of CD40L on activated T cells was suppressed by soluble CD40 (sCD40) in vitro. However, the relationship between soluble CD40L (sCD40L) and sCD40 in unstable angina (UA) is still unknown. Thirty-seven consecutive patients with recent chest pain or discomfort were recruited. Patients with both Braunwald's class IB-IIIB and with coronary stenosis (or stenoses) of >75% were assigned to the UA group (n = 19, aged 67.2 +/- 8.2 years), and the rest to the control group (n = 18, aged 63.4 +/- 8.7 years). The serum levels of sCD40L and sCD40, and the plasma levels of matrix metalloproteinase (MMP)-9, were measured by enzyme-linked immunosorbent assays. A significantly inverse correlation between sCD40L and sCD40 was shown in the controls (r = -0.72, P = 0.0007), but was absent in the UA group (r = -0.16, P not significant), although there was no statistical significance between these groups in terms of serum levels of sCD40L or sCD40. The difference of the regression slopes of these regression lines was statistically significant (P < 0.01). Additionally, there was a significant correlation between sCD40 and plasma levels of MMP-9 in the patients with and without UA (r = 0.58, P = 0.0096), but no significant correlation between sCD40L and MMP-9 levels (r = 0.00, P not significant). The balance between CD40 and CD40L may be lost in patients with UA. Soluble CD40 expression may also be related to MMP-9 expression in atherosclerotic tissues.

Dietary fish oil attenuates cardiac hypertrophy in lipotoxic cardiomyopathy due to systemic carnitine deficiency.

OBJECTIVE: 1,2-Diacylglycerol (DAG), a lipid second messenger that activates protein kinase C (PKC), is increased with a distinct fatty acid composition in the heart of the juvenile visceral steatosis (JVS) mouse, which develops pathological cardiac hypertrophy with lipid accumulation induced by the perturbation of fatty acid beta-oxidation due to systemic carnitine deficiency. Fish oil (FO) may exert its beneficial effects on the cardiomyopathy in JVS mice by modifying the molecular species composition of myocardial DAG. To test this hypothesis, we investigated the effects of dietary FO on the hypertrophied hearts in JVS mice. METHODS: Both control and JVS mice were fed a FO diet (containing 10% FO) or a standard diet from 4 weeks of age. RESULTS: At 8 weeks of age, the ventricular-to-body weight ratio in JVS mice was 2.7-fold higher than that in controls (9.9 +/- 0.1 vs. 3.7 +/- 0.1 mg/g, P < 0.01) and was reduced by dietary FO (7.7 +/- 0.1 mg/g, P < 0.01 vs. JVS mice). In JVS mice, myocardial DAG levels were elevated by 2.3-fold with a distinct fatty acid composition with increases in C18:1n-7,9 and C18:2n-6 fatty acids compared with controls; dietary FO had no effects on the total DAG levels but significantly altered the fatty acid composition of DAG with reduction of both fatty acid species. Immunoblot analysis showed that dietary FO prevented the membrane translocation of cardiac PKCs alpha, beta2, and epsilon in JVS mice. Dietary FO did not affect the plasma and myocardial total carnitine levels in JVS mice. Furthermore, dietary FO significantly improved the progressive left ventricular dysfunction and survival rate in JVS mice. CONCLUSIONS: Dietary FO may attenuate cardiac hypertrophy with improvements in cardiac function and survival in JVS mice via modification of the molecular species composition of myocardial DAG and the consequent inhibition of PKC redistribution. These results suggest the implication of the molecular species composition of DAG in the pathogenesis of lipotoxic cardiomyopathy due to perturbations of fatty acid beta-oxidation.