Smoking status and endothelial function in Japanese men.

It is established that smoking is a major risk factor of atherosclerosis. Endothelial dysfunction occurs in the initial step in the pathogenesis of atherosclerosis and plays a critical role in the development of atherosclerosis. The purpose of this study was to evaluate the association between smoking status and endothelial function in detail in men. We measured flow-mediated vasodilation (FMD) in 2209 Japanese men including 1181 men who had never smoked and 1028 current smokers. All of the participants were divided into five groups by smoking pack-years: never smoker group (= 0), light smoker group (> 0 to 10), moderate smoker group (> 10 to 20), heavy smoker group (> 20 to 30) and excessive smoker group (> 30). FMD significantly decreased in relation to pack-years (6.6 ± 3.4% in the never smoker group, 6.8 ± 3.0% in the light smoker group, 6.5 ± 2.9% in the moderate smoker group, 5.9 ± 2.9% in the heavy smoker group, and 4.9 ± 2.7% in the excessive smoker group; P < 0.001). After adjustment for age (≥ 65 years), body mass index, systolic blood pressure, low-density lipoprotein cholesterol, glucose, and year of recruitment, FMD was significantly smaller in the excessive smoker group than in the never smoker group as a reference group (OR 1.95, 95% CI 1.42 to 2.67; P < 0.001). These findings suggest that FMD decreases with an increase in the number of cigarettes smoked and that excessive smoking is associated with endothelial dysfunction. Cigarette smoking is harmful to vascular function in men who are heavy smokers.

Relationship between cell number and clinical outcomes of autologous bone-marrow mononuclear cell implantation in critical limb ischemia.

Cell therapy using intramuscular injections of autologous bone-marrow mononuclear cells (BM-MNCs) improves clinical symptoms and can prevent limb amputation in atherosclerotic peripheral arterial disease (PAD) patients with critical limb ischemia (CLI). The purpose of this study was to evaluate the effects of the number of implanted BM-MNCs on clinical outcomes in atherosclerotic PAD patients with CLI who underwent cell therapy. This study was a retrospective observational study with median follow-up period of 13.5 years (range, 6.8-15.5 years) from BM-MNC implantation procedure. The mean number of implanted cells was 1.2 ± 0.7 × 109 per limb. There was no significant difference in number of BM-MNCs implanted between the no major amputation group and major amputation group (1.1 ± 0.7 × 109 vs. 1.5 ± 0.8 × 109 per limb, P = 0.138). There was also no significant difference in number of BM-MNCs implanted between the no death group and death group (1.5 ± 0.9 × 109 vs. 1.8 ± 0.8 × 109 per patient, P = 0.404). Differences in the number of BM-MNCs (mean number, 1.2 ± 0.7 × 109 per limb) for cell therapy did not alter the major amputation-free survival rate or mortality rate in atherosclerotic PAD patients with CLI. A large number of BM-MNCs will not improve limb salvage outcome or mortality.

A Comparison of Adrenalectomy and Eplerenone on Vascular Function in Patients with Aldosterone-producing Adenoma.

CONTEXT: It remains unclear whether adrenalectomy has more beneficial effects than treatment with a mineralocorticoid receptor antagonist on vascular function in patients with aldosterone-producing adenoma (APA). OBJECTIVE: The aim of this study was to compare the effects of adrenalectomy and treatment with eplerenone on vascular function in patients with APA. DESIGN, SETTING, AND PATIENTS: Flow-mediated vasodilation (FMD), as an index of endothelium-dependent vasodilation, and nitroglycerine-induced vasodilation (NID), as an index of endothelium-independent vasodilation, were measured to assess vascular function before and after a 3-month treatment with eplerenone and at 3 months after adrenalectomy in 23 patients with APA. RESULTS: Flow-mediated vasodilation and NID after adrenalectomy were significantly higher than those before treatment with eplerenone (5.4 ± 2.6% vs 2.7 ± 1.9% and 14.8 ± 4.7% vs 9.6 ± 4.6%, P < 0.01, respectively) and those after treatment with eplerenone (5.4 ± 2.6% vs 3.1 ± 2.3% and 14.8 ± 4.7% vs 11.0 ± 5.3%, P < 0.01 and P = 0.03, respectively), while treatment with eplerenone did not alter FMD and NID compared with those before treatment with eplerenone. After adrenalectomy, the increase in FMD and NID were significantly correlated with a decrease in plasma aldosterone concentration and a decrease in the aldosterone-renin ratio. There were no significant relationships between FMD and changes in other parameters or between NID and changes in other parameters. CONCLUSIONS: Adrenalectomy, but not treatment with eplerenone, improved vascular function in patients with APA. Adrenalectomy may be more effective than treatment with eplerenone for reducing the incidence of future cardiovascular events in patients with APA. Clinical Trial Information: URL for the clinical trial: http://UMIN; Registration Number for the clinical trial: UMIN000003409.

Long-Term Clinical Outcomes of Autologous Bone Marrow Mononuclear Cell Implantation in Patients With Severe Thromboangiitis Obliterans.

BACKGROUND: Patients with severe Buerger disease, also known as thromboangiitis obliterans (TAO), are at risk of major limb amputation. It has been shown that autologous bone marrow mononuclear cell (BM-MNC) implantation improves the condition of critical limb ischemia in TAO patients. This study was conducted to further clarify the long-term (>10 years) results of autologous BM-MNC implantation in patients with TAO.Methods and Results:An observational study was conducted of the long-term results of BM-MNC implantation in 47 lower limbs of 27 patients with TAO. The mean (±SD) follow-up period was 12.0±8.6 years. There was no major amputation event up to 10 years of follow-up in patients treated with BM-MNC implantation. The overall amputation-free survival rates were significantly higher in patients who underwent BM-MNC implantation than in internal controls and historical controls. There was no significant difference in amputation-free survival rates between the historical and internal controls. There was also no significant difference in overall survival between patients who underwent BM-MNC implantation and the historical controls. CONCLUSIONS: BM-MNC transplantation successfully prevented major limb amputation over a period of >10 years in patients with severe TAO who had no other therapeutic options.

Review of the Long-term Effects of Autologous Bone-Marrow Mononuclear Cell Implantation on Clinical Outcomes in Patients with Critical Limb Ischemia.

Critical limb ischemia (CLI) is associated with a high risk of limb amputation. It has been shown that cell therapy is safe and has beneficial effects on ischemic clinical symptoms in patients with CLI. The aim of this study was to further investigate the outcomes of intramuscular injection of autologous bone-marrow mononuclear cells (BM-MNCs) in a long-term follow-up period in atherosclerotic peripheral arterial disease (PAD) patients who have no optional therapy. This study was a retrospective and observational study that was carried out to evaluate long-term clinical outcomes in 42 lower limbs of 30 patients with atherosclerotic PAD who underwent BM-MNC implantation. The median follow-up period was 9.25 (range, 6-16) years. The overall amputation-free rates were 73.0% at 5 years after BM-MNC implantation and 70.4% at 10 years in patients with atherosclerotic PAD. The overall amputation-free rates at 5 years and at 10 years after implantation of BM-MNCs were significantly higher in atherosclerotic PAD patients than in internal controls and historical controls. There were no significant differences in amputation rates between the internal control group and historical control group. The rate of overall survival was not significantly different between the BM-MNC implantation group and the historical control group. Implantation of autologous BM-MNCs is feasible for a long-term follow-up period in patients with CLI who have no optional therapy.

Eplerenone improves endothelial function and arterial stiffness and inhibits Rho-associated kinase activity in patients with idiopathic hyperaldosteronism: a pilot study.

OBJECTIVE: Primary aldosteronism is one of the most common cause of secondary hypertension. It is well known that the incidence of cardiovascular events is higher in patients with primary aldosteronism than in patients with essential hypertension. In a previous study, we showed that aldosterone-producing adenoma is associated with vascular function and structure. The aim of this study was to evaluate the effects of eplerenone on vascular function in the macrovasculature and microvasculature, arterial stiffness and Rho-associated kinase (ROCK) activity in patients with idiopathic hyperaldosteronism (IHA). METHODS: Vascular function, including reactive hyperemia index (RHI), flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID), arterial stiffness including brachial-ankle pulse wave velocity (baPWV) and brachial intima-media thickness (IMT) and ROCK activity in peripheral leukocytes were measured before and after 12 weeks of treatment with eplerenone in 50 patients with IHA. RESULTS: After 12 weeks, eplerenone decreased the aldosterone renin ratio but did not alter SBP and DBP. Eplerenone treatment increased log RHI from 0.56 ±â€Š0.25 to 0.69 ±â€Š0.25 (P < 0.01) and NID from 12.8 ±â€Š5.8 to 14.9 ±â€Š6.9% (P = 0.02) and it decreased baPWV from 1540 ±â€Š263 to 1505 ±â€Š281 (P = 0.04) and ROCK activity from 1.20 ±â€Š0.54 to 0.89 ±â€Š0.42 (P < 0.01), whereas there was no significant change in FMD (increase from 4.6 ±â€Š3.4 to 4.6 ±â€Š3.6%, P = 0.99) or brachial IMT (decrease from 0.28 ±â€Š0.07 to 0.28 ±â€Š0.04 mm, P = 0.14). CONCLUSION: Eplerenone improves microvascular endothelial function, vascular smooth muscle function, arterial stiffness and ROCK activity in patients with IHA. CLINICAL TRIAL REGISTRATION INFORMATION: URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409.

Microvascular endothelial function is impaired in patients with idiopathic hyperaldosteronism.

The aims were to evaluate the relationship between idiopathic hyperaldosteronism (IHA) and grade of vascular function in the macrovasculature and microvasculature. Vascular function, including reactive hyperemia index (RIH), flow-mediated vasodilation (FMD), and nitroglycerine-induced vasodilation (NID) were evaluated in 52 patients with IHA, 53 patients with aldosterone-producing adenoma (APA), and 52 age-, sex-, and blood pressure-matched patients with essential hypertension (EHT). Log RHI was lower in the IHA and APA groups than in the EHT group (0.54 ± 0.25 and 0.55 ± 0.23 versus 0.79 ± 0.28; P < 0.01, respectively). FMD was lower in the APA group than in the EHT group (3.4 ± 2.1% versus 4.8 ± 2.8%; P = 0.02), whereas there was no significant difference in FMD between the IHA and the APA and EHT groups. NID was lower in the APA group than in the EHT group (10.0 ± 4.5% versus 12.5 ± 5.7%; P = 0.03), whereas there was no significant difference in NID between the IHA, APA, and EHT groups. Multiple regression analysis revealed an association of log RHI with plasma aldosterone concentration (t = -2.24; P = 0.03) and an association of FMD with plasma aldosterone concentration (t = -3.07; P < 0.01). Microvascular endothelial function was impaired in patients with IHA compared with that in patients with EHT.

Who is the operator, that is the question: a multicentre study of catheter ablation of atrial fibrillation.

AIMS: A worldwide survey reported that the success rate of atrial fibrillation (AF) ablation was higher in high-volume centers compared with low-volume centers. We tested whether the procedure volume of each operator was associated with the outcome of AF ablation in high-volume centres. METHODS AND RESULTS: We studied 471 patients with paroxysmal AF who underwent pulmonary vein (PV) isolation for the first time in three cardiovascular centers where the annual AF ablation volume was >100 procedures. We classified a total of 10 primary operators according to their operation volume on the basis of ACC/AHA/ACP CLINICAL COMPETENCE STATEMENT; high-volume operator (≥50 cases/year, N = 3) or low-volume operator (<50 cases/year, N = 7). The patients included were dichotomized according to the annual operation volume of their attending physician. The endpoints were the freedom from AF recurrence 1 year after the ablation, major complications including thromboembolisms, massive bleeding or death, and the procedural duration. RESULTS: A complete isolation of the four PVs was achieved in 99.1%. The freedom from AF recurrence was more common in patients treated by high-volume operators than those treated by low-volume operators (165/216 [76.4%] vs. 160/255 [62.8%]; P = 0.001). A high-volume operator was the only independent predictor of the freedom from AF recurrence (hazard ratio 1.73, 95% confidence interval 1.23-2.48; P = 0.002). The patients treated by high-volume operators were less likely to have major complications (1.4% vs. 7.8%; P = 0.001), and had a shorter procedural duration (139.9 ± 25.3 vs. 149.3 ± 27.1 min; P = 0.03). CONCLUSIONS: Operator proficiency may predict the outcome after AF ablation even in high-volume centres.

The assembly of the FtsZ ring at the mid-chloroplast division site depends on a balance between the activities of AtMinE1 and ARC11/AtMinD1.

Chloroplast division comprises a sequence of events that facilitate symmetric binary fission and that involve prokaryotic-like stromal division factors such as tubulin-like GTPase FtsZ and the division site regulator MinD. In Arabidopsis, a nuclear-encoded prokaryotic MinE homolog, AtMinE1, has been characterized in terms of its effects on a dividing or terminal chloroplast state in a limited series of leaf tissues. However, the relationship between AtMinE1 expression and chloroplast phenotype remains to be fully elucidated. Here, we demonstrate that a T-DNA insertion mutation in AtMinE1 results in a severe inhibition of chloroplast division, producing motile dots and short filaments of FtsZ. In AtMinE1 sense (overexpressor) plants, dividing chloroplasts possess either single or multiple FtsZ rings located at random intervals and showing constriction depth, mainly along the chloroplast polarity axis. The AtMinE1 sense plants displayed equivalent chloroplast phenotypes to arc11, a loss-of-function mutant of AtMinD1 which forms replicating mini-chloroplasts. Furthermore, a certain population of FtsZ rings formed within developing chloroplasts failed to initiate or progress the membrane constriction of chloroplasts and consequentially to complete chloroplast fission in both AtMinE1 sense and arc11/atminD1 plants. Our present data thus demonstrate that the chloroplast division site placement involves a balance between the opposing activities of AtMinE1 and AtMinD1, which acts to prevent FtsZ ring formation anywhere outside of the mid-chloroplast. In addition, the imbalance caused by an AtMinE1 dominance causes multiple, non-synchronous division events at the single chloroplast level, as well as division arrest, which becomes apparent as the chloroplasts mature, in spite of the presence of FtsZ rings.