Effect of telling patients their "spirometric-lung-age" on smoking cessation in Japanese smokers.

BACKGROUND: Cigarette smoking remains a significant public health problem. However, current treatment programs have not yet succeeded in sufficiently reducing smoking rates. The study aimed to examine whether patients' recognition of "spirometric-lung-age (SLA)" estimated from spirometry data prompts smoking cessation. METHODS: From December 2010 to September 2011, participating smokers were prospectively enrolled into the standardized smoking cessation program (Visits 1-5 for 12 weeks) and assigned single-blindly to either SLA assessment or control groups. The SLA group was informed of the estimated age of their lungs from spirometry analysis and given an opportunity to recognize the difference from their actual chronological age, whereas the control group was not. The primary calculation of outcome was the smoking quit rate on Visit 5, whereas the secondary end-point was the proportion of patients who remained abstinent 1 year later. RESULTS: One hundred and twenty-six Japanese smokers (88 males) participated and were randomly assigned to the SLA group (n=52) or the control group (n=74). The smoking quit rate on Visit 5 was similar in the SLA assessment group and control group (59.6% vs. 41.9%; P=0.0700). However, the proportion of patients who remained abstinent 1 year later was similar in both groups (78.6% vs. 69.0%; P=0.5497). Multivariate logistic regression analysis after adjusting baseline characteristics demonstrated that telling patients their SLA, the use of varenicline, and age were significantly associated with smoking quit rate on Visit 5 whereas only age was associated with remaining abstinent 1 year later. CONCLUSIONS: Telling patients their SLA can become a useful tool prompting smoking cessation among Japanese smokers although other factors such as pharmacotherapy and age also influence the cessation of smoking.

Disease duration and severity impacts on long-term cardiovascular events in Japanese patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) increases the mortality and morbidity of cardiovascular disease (CVD). However, the relationship between RA and the risk of CVD in the Japanese population remains unclear. METHODS AND RESULTS: This study comprised 571 RA patients who were admitted to Juntendo University Hospital from January 1990 to December 2000. Cardiovascular events (CVEs) were defined as cardiac death, acute coronary syndrome (ACS), symptomatic stroke, and congestive heart failure. During follow-up (mean 11.7 ± 5.8 years), 7.5% of the patients died from all causes and 11.0% experienced CVEs. The morbidity of stroke and ACS was 3.6 and 2.5 per 1000 person-years, respectively. The mean RA disease duration at enrolment was significantly longer in patients who experienced CVEs than in those who did not experience CVEs (15.0 ± 12.7 years vs. 10. 8 ± 9.7 years; p = 0.01). Physical disabilities due to RA were more severe in patients who experienced CVEs than in those who did not experience CVEs. Patients with a long RA disease duration showed significantly higher event rates (p = 0.033). Cox proportional hazards analysis identified a longer RA duration as an independent risk factor for CVD (hazard ratio 1.57, 95% CI 1.09-2.30, p = 0.02). CONCLUSION: Japanese RA patients showed a relatively high incidence of CVD, despite the fact that they had few coronary risk factors. The RA disease duration was an independent risk factor for CVEs.

The high molecular weight adiponectin level is associated with the atherogenic lipoprotein profiles in healthy Japanese males.

AIM: Circulating adiponectin comprises high, medium and low molecular weight (HMW, MMW, and LMW) forms. Decreased adiponectin levels have been demonstrated to correlate with the atherogenic lipoprotein profile in patients with metabolic syndrome(MS). However, the associations of these isoforms with the atherogenic lipoprotein profiles in the healthy population remain unclear. METHODS: Apparently healthy male subjects were divided into non-MS(n=132) and MS(n=63) groups. We measured the total, HMW, MMW and LMW adiponectin levels by ELISA, and determined the detailed lipoprotein profiles by high-performance liquid chromatography. RESULTS: The total and HMW adiponectin levels in the MS group were significantly lower than those in the non-MS group(3.8±1.9 vs. 4.9±2.4µg/mL, p＜0.001 and 1.6±1.2 vs. 2.5±1.9µg/mL, p＜0.001, respectively), whereas the MMW and LMW levels did not differ significantly between the groups. The total and HMW adiponectin levels correlated with the atherogenic lipoprotein profiles, including the following: 1) increased cholesterol levels in the small LDL subclasses; 2) decreased cholesterol levels in the larger HDL subclasses; 3) increased triglycerides(TGs) in almost all VLDL and LDL subclasses and 4) decreased TGs in the large HDL and increased TGs in the small HDL subclasses. In addition, a multivariate analysis demonstrated that the HMW adiponectin level was an independent predictor of the small LDL and HDL levels(p=0.02 for both). CONCLUSIONS: The HMW, but not MMW or LMW, adiponectin levels are associated with the typical atherogenic lipoprotein profiles, independent of MS components. Measurement of the HMW adiponectin levels could be useful for identifying the atherogenicity in apparently healthy males.

High hexacosanoic acid levels are associated with coronary artery disease.

AIMS: Levels of saturated very long chain fatty acids (VLCFAs) are associated with coronary risk factors, including metabolic syndrome (MS), atherogenic lipoproteins, and systemic inflammation. However, the relationship between circulating levels of saturated VLCFA and coronary artery disease (CAD) remains unclear. METHOD: We enrolled 100 consecutive CAD patients and 40 age-, gender-, and body mass index (BMI)-matched healthy control subjects. The levels of hexacosanoic acid (C26:0), a VLCFA, in whole blood were measured by gas-liquid chromatography mass spectrometry. RESULTS: C26:0 levels were significantly higher in the CAD group than in the control group (2.42±0.32 vs. 2.27±0.24 µg/ml, P=0.01) and positively correlated with BMI (r=0.23, P=0.008), triglyceride levels (r=0.22, P=0.01), and hypertension (P=0.01). CAD patients with MS showed the highest C26:0 levels adjusted by hematocrit. Furthermore, adjusted C26:0 levels in CAD patients without MS were higher than those in controls (P=0.02), suggesting that C26:0 levels increased with the presence of CAD independent of MS. Our multivariate analysis revealed that high C26:0 levels in whole blood is an independent marker for CAD even after adjustment for age, gender, BMI, lipid profiles, fasting plasma glucose, and blood pressure. CONCLUSION: High C26:0 levels in whole blood may be an independent marker for identifying the risks of CAD.

Effect of cardiac rehabilitation on muscle mass, muscle strength, and exercise tolerance in diabetic patients after coronary artery bypass grafting.

BACKGROUND: The effects of cardiac rehabilitation (CR) on muscle mass, muscle strength, and exercise tolerance in patients with diabetes mellitus (DM) who received CR after coronary artery bypass grafting (CABG) have not been fully elucidated. METHODS: We enrolled 78 consecutive patients who completed a supervised CR for 6 months after CABG (DM group, n=37; non-DM group, n=41). We measured mid-upper arm muscle area (MAMA), handgrip power (HGP), muscle strength of the knee extensor (Ext) and flexor (Flex), and exercise tolerance at the beginning and end of CR. RESULTS: No significant differences in confounding factors, including age, gender, ejection fraction, or number of CR sessions, were observed between the two groups. At the beginning of CR, the levels of Ext muscle strength and peak VO2 were significantly lower in the DM group than in the non-DM group. At the end of CR, significant improvement in the levels of muscle strength, HGP, and exercise tolerance was observed in both groups. However, the levels of Ext muscle strength, HGP, peak VO2, thigh circumference, and MAMA were significantly lower in the DM group than in the non-DM group. In addition, no significant improvement in thigh circumference and MAMA was observed in the DM group. At the end of CR, the levels of thigh circumference and MAMA correlated with Ext and Flex muscle strength as well as with HGP. Percent changes in the levels of Ext muscle strength were significantly correlated with those of MAMA and hemoglobin A1c. CONCLUSIONS: These data suggest that improvement in muscle strength may be influenced by changes in muscle mass and high glucose levels in DM patients undergoing CR after CABG. A CR program, including muscle mass intervention and blood glucose control, may improve deterioration in exercise tolerance in DM patients after CABG.

High levels of very long-chain saturated fatty acid in erythrocytes correlates with atherogenic lipoprotein profiles in subjects with metabolic syndrome.

AIM: Very long chain saturated fatty acid (VLCFA) levels in erythrocytes are associated with metabolic syndrome (MS). However, the relationship between levels of the VLCFA ligonoceric acid (C24:0) in erythrocytes and the atherogenic lipoprotein profiles and inflammatory state in MS remain unclear. METHODS: Based on the International Diabetes Federation (IDF) definition of MS, 195 apparently healthy males were assigned to either an MS group (n=38) or a non-MS group (n=157). Fatty acid composition of erythrocytes was determined by gas liquid chromatography. RESULTS: Erythrocytes from the MS group had a significantly higher level of C24:0 than cells from the non-MS group (4.06±0.48% versus 3.88±0.34%; p=0.03). C24:0 levels were significantly correlated with several components of MS. The C24:0 levels showed a significant negative correlation with LDL and HDL particle size. Multivariate linear regression analysis showed that C24:0 levels were independently correlated with LDL particle size after adjusting for age and each MS criterion. C24:0 levels were also positively correlated with log-transformed high-sensitivity CRP levels (p=0.04). CONCLUSION: C24:0 levels in erythrocytes are associated with specific atherogenic lipoprotein profiles and inflammation status in subjects with MS.

Clinical significance of the measurements of urinary liver-type fatty acid binding protein levels in patients with acute coronary syndrome.

BACKGROUND: Recently, much attention has been focused on cardio-renal interaction. Urinary liver-type fatty acid binding protein (U-L-FABP), which is produced in the proximal tubule by renal hypoxia and oxidative stress, has been identified as a useful marker for diagnosis of acute kidney disease and a predictor of future events in chronic kidney disease. However, the clinical significance of U-L-FABP measurements in patients with acute coronary syndrome (ACS) has not been completely evaluated. METHODS AND RESULTS: This study included 50 consecutive patients with ACS [37 with acute myocardial infarction (AMI) and 13 with unstable angina pectoris (UAP)] and 47 subjects without coronary artery disease (control group). U-L-FABP levels, urinary albumin (U-Alb), and other serum parameters were measured at admission and at 24 h after percutaneous coronary intervention. RESULTS: U-L-FABP levels in patients with AMI were significantly higher (p=0.0019), than in control subjects, while patients with UAP did not exhibit such an increase. U-L-FABP levels at admission were positively correlated with brain natriuretic protein levels (p=0.001) and duration of hospitalization (p=0.025). At follow-up angiography, patients with restenosis had significantly higher U-L-FABP (p=0.047) and U-Alb levels (p<0.0001) than those without restenosis. After a median follow-up of 42 months, U-L-FABP levels at second measurement in patients with major adverse cardiocerebrovascular events (MACCEs) were significantly higher than those in patients without MACCEs (p=0.028). After adjusting for confounding factors, high U-L-FABP levels at second measurement were found to be independent factors for MACCEs (p=0.019). CONCLUSIONS: These data suggest that patients with ACS, especially those with AMI, have high U-L-FABP levels, and that U-L-FABP measurements may be useful in identifying high-risk patients for future cardiovascular events after ACS.

Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between azelnidipine and amlodipine on glucose tolerance and endothelial function--a crossover trial (AGENT).

BACKGROUND: Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice. METHODS: Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT. RESULTS: Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (P < 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both P < 0.05). Serum levels of high-sensitivity C-reactive protein (P = 0.067) and interleukin-6 (P = 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (P = 0.016). CONCLUSIONS: These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension.

Impact of diabetes on muscle mass, muscle strength, and exercise tolerance in patients after coronary artery bypass grafting.

BACKGROUND: The impact of diabetes mellitus (DM) on muscle mass, muscle strength, and exercise tolerance in patients who had undergone coronary artery bypass grafting (CABG) has not been fully elucidated. METHODS: We enrolled 329 consecutive patients who received cardiac rehabilitation (CR) after CABG (DM group, n=178; non-DM group, n=151) and measured lean body weight, mid-upper arm muscle area (MAMA), and handgrip power (HGP) at the beginning of CR. We also performed an isokinetic strength test of the knee extensor (Ext) and flexor (Flex) muscles and a cardiopulmonary exercise testing at the same time. RESULTS: No significant differences in risk factors, including age, gender, number of diseased vessels, or ejection fraction were observed between the 2 groups. The levels of Ext muscle strength, peak oxygen uptake, and anaerobic threshold were significantly lower in the DM group than in the non-DM group (all p<0.05). Both peak oxygen uptake and MAMA correlated with Ext and Flex muscle strength as well as HGP (all p<0.005). The MAMA, HGP, and Ext muscle strength were lower in patients who received insulin therapy than in those who did not. Interestingly, fasting glucose levels significantly and negatively correlated with Ext muscle strength. CONCLUSIONS: These data suggest that DM patients had a lower muscle strength and exercise tolerance than non-DM patients. Moreover, a high glucose level may affect these deteriorations in DM patients after CABG.

Clinical significance of the measurements of plasma N-terminal pro-B-type natriuretic peptide levels in patients with coronary artery disease who have undergone elective drug-eluting stent implantation.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a diagnostic biomarker for patients with congestive heart failure (CHF). However, the clinical significance of measurements of NT-proBNP levels in patients with coronary artery disease (CAD) who have undergone drug-eluting stent (DES) implantation has not been fully elucidated. METHODS AND RESULTS: We recruited 280 patients with documented CAD who were scheduled for elective coronary intervention and also age- and gender-matched 140 healthy subjects. Subjects with acute coronary syndrome, ongoing CHF, and stage IV or V chronic kidney disease were excluded. We measured the plasma NT-proBNP levels and followed the CAD patients who have undergone DES implantation for up to 62 months until occurrence of major adverse cardiovascular events (MACE). Plasma NT-proBNP levels were significantly higher in CAD patients compared to control subjects (p<0.0001). In the CAD group, 25 patients developed MACE and the NT-proBNP levels in the MACE group were significantly higher compared to that in the non-MACE group (p=0.005). After adjusting for the confounding factors, high NT-proBNP levels were observed to be independent factors for CAD (p<0.0001) and MACE (p=0.021). CONCLUSIONS: These results demonstrated that the measurements of NT-proBNP levels may be useful in identifying high-risk subjects among CAD patients who have undergone elective DES implantation.

Effects of fenofibrate on lipid profiles, cholesterol ester transfer activity, and in-stent intimal hyperplasia in patients after elective coronary stenting.

BACKGROUND: The association between modulation of detailed lipoprotein profiles and cholesterol ester transfer (CET) activity by peroxisome proliferator-activated receptor (PPAR)-a agonists in patients with coronary artery disease remains unclear. We assessed lipid profiles, plasma CET activity, and in-stent intimal hyperplasia after fenofibrate treatment in patients who underwent elective coronary stenting. METHODS: Forty-three consecutive patients who underwent elective coronary stenting were randomized to the fenofibrate group (300 mg/day for 25 weeks, n = 22) or the control group (n = 21). At baseline and follow up, CET activity and lipoprotein profiles were measured, and quantitative coronary angiography was performed. RESULTS: In the fenofibrate group, the levels of large very low-density lipoprotein cholesterol, and small low-density lipoprotein (LDL) cholesterol decreased and those of small high-density lipoprotein (HDL) cholesterol increased. Besides, CET activity decreased independent of the effect of fenofibrate on total and LDL cholesterol. The reduction of CET activity significantly correlated with the increase in LDL particle size (r = 0.47, P = 0.03) and the decrease of triglycerides in large HDL subclasses (r = 0.48, P = 0.03). Although there were no significant differences in restenosis parameters between the two groups, low CET activity significantly correlated with the inhibition of neointimal hyperplasia (r = 0.56, P = 0.01). CONCLUSIONS: Fenofibrate inhibited CET activity and thereby improved atherogenic lipoprotein profiles, and reduced intimal hyperplasia after coronary stenting.

Voluntary exercise ameliorates the progression of atherosclerotic lesion formation via anti-inflammatory effects in apolipoprotein E-deficient mice.

AIM: A sedentary lifestyle with insufficient exercise is associated with cardiovascular disease. Previous studies have demonstrated that endurance exercise benefits atherosclerosis and cardiovascular disorders; however, the mechanisms by which physical activity, such as voluntary exercise (Ex), produces these effects are not fully understood. METHODS AND RESULTS: Eight-week-old male apolipoprotein (ApoE)-deficient mice were fed a standard diet (STD) or high fat diet (HFD) for 10 weeks. The HFD+Ex group mice performed Ex on a running wheel for 10 weeks. No significant differences in lipid profiles were observed between the HFD and HFD+Ex groups. Although changes in body and brown adipose tissue weights were comparable between the HFD and HFD+Ex groups, white adipose tissue weight was significantly lower in the HFD+Ex group than in the HFD group. The areas of atherosclerotic lesions in the aortic sinus and thoracoabdominal aorta were significantly reduced in the HFD+Ex group than in the HFD group (p<0.001). There was a strong negative correlation between atherosclerotic areas and the mean running distance per day in the HFD+Ex group (r=-0.90, p=0.01). Endothelial function was significantly preserved in the HFD+Ex group (p<0.05). Serum interleukin-6 and macrophage chemoattractant protein-1 levels were significantly lower and those of adiponectin were significantly higher in the HFD+Ex group than in the HFD group (p<0.05). CONCLUSIONS: These results suggest that Ex ameliorates the progression of endothelial dysfunction and atherosclerotic lesion formation through anti-inflammatory effects, despite continued consumption of HFD.

Single administration of alpha-glucosidase inhibitors on endothelial function and incretin secretion in diabetic patients with coronary artery disease - Juntendo University trial: effects of miglitol on endothelial vascular reactivity in type 2 diabetic patients with coronary heart disease (J-MACH) -.

BACKGROUND: Post-prandial hyperglycemia, hyperlipidemia, and endothelial dysfunction play an important role in the pathogenesis of atherosclerosis. Improvement in post-prandial hyperglycemia on alpha-glucosidase inhibitors (alpha-GIs) is associated with a risk reduction of cardiovascular diseases, but the post-prandial effects of alpha-GIs on endothelial function and incretin secretion in type 2 diabetic patients with coronary artery disease (CAD) remain unclear. METHODS AND RESULTS: The post-prandial effects of a single administration of miglitol and voglibose on endothelial function and changing levels of glucose, insulin, lipids, glucagon-like peptide (GLP)-1, and gastric inhibitory polypeptide (GIP) were compared after a standard meal loading in 11 diabetic patients with CAD, using a placebo-controlled cross-over design. The changing levels of glucose, insulin and triglycerides at 60 min were significantly lower in the miglitol group than in the voglibose and placebo groups (all P<0.01). GLP-1 levels were significantly higher at 120 min (P<0.05) and GIP levels were significantly lower at 30 min and 60 min (P<0.05) in the miglitol group compared to other treatments. The reactive hyperemia duration at 120 min was significantly maintained in the miglitol group compared to the other groups. CONCLUSIONS: A single administration of miglitol significantly improved post-prandial glucose/lipid metabolism, incretin secretion, and endothelial dysfunction in diabetic patients with CAD, suggesting that miglitol may be a useful anti-atherogenic agent (UMIN000002264).

Polyunsaturated fatty acid levels of serum and red blood cells in apparently healthy Japanese subjects living in an urban area.

AIM: We assessed levels of polyunsaturated fatty acid (PUFA) in serum and red blood cells (RBCs) among groups stratified by generation and its clinical significance in Japanese subjects living in an urban area. METHODS: We enrolled 200 apparently healthy Japanese (126 males, mean age: 50.3+/-9.2 years) living in an urban area. Levels of PUFA, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA) in serum and RBCs were measured for each generation (G1 <35y, G2 35y-<45y, G3 45y-<55y, G4 55y-<65y, G5>or=65y). RESULTS: No significant differences in EPA, DHA, AA, or EPA/AA were observed between males and females. After dividing into generations, stepwise increases in EPA and DHA, but not DGLA or AA, were observed in serum (all p<0.0001). EPA/AA ratios were stepwisely increased in serum (mean: G1:0.26, G2:0.29, G3:0.43, G4:0.58, G5:0.68, p<0.0001) and RBCs (mean: G1:0.10, G2:0.09, G3:0.15, G4:0.20, G5:0.23, p<0.0001). Positive correlations of EPA (r=0.83), DHA (r=0.55), DGLA (r=0.54), AA (r=0.29), and EPA/AA (r=0.91) were demonstrated between serum and RBCs. In addition, a significant positive correlation between EPA/AA ratios and insulin sensitivity as well as a negative correlation between those ratios and insulin resistance were observed in subjects with metabolic syndrome. CONCLUSION: Low levels of EPA/AA, which were associated with insulin resistance, were demonstrated in young Japanese adults living in an urban area.

Effects of phase III cardiac rehabilitation on mortality and cardiovascular events in elderly patients with stable coronary artery disease.

BACKGROUND: Cardiac rehabilitation (CR) has numerous benefits, including reduction of mortality and cardiovascular events, in patients with coronary artery disease (CAD). However, the long-term effect of phase III CR in elderly patients with stable CAD is still unknown. METHODS AND RESULTS: The 111 elderly male CAD patients (>or=65 years), including 37 subjects participating in supervised CR for 6 months and 74 age-matched controls, were analyzed. The patients were followed for up to 3,500 days, until the occurrence of death or 1 of the following major adverse cardiovascular events (MACE): cardiovascular death, acute coronary syndrome, refractory angina requiring revascularization, admission for congestive heart failure, or stroke. All-cause mortality tended to be lower in the CR group than in the Control group (14% vs 28%, P=0.081). The MACE incidence was significantly lower in the CR group than in the Control group (30% vs 62%, P=0.001). Multivariate Cox proportional hazard analysis showed that the MACE incidence was significantly lower in the CR group than in the Control group [adjusted hazard ratio 0.43 (95% confidence interval 0.20-0.91), P=0.027]. CONCLUSIONS: Phase III CR has the beneficial effect of reducing cardiovascular events even in elderly patients with stable CAD.

Relationship between exercise tolerance and muscle strength following cardiac rehabilitation: comparison of patients after cardiac surgery and patients with myocardial infarction.

BACKGROUND AND PURPOSE: Previous studies have demonstrated that cardiac rehabilitation (CR) improves exercise tolerance and muscle strength in patients with myocardial infarction (MI) and in patients after cardiac surgery. However, the association between exercise tolerance and muscular strength following CR and the comparison of relationships among various disease categories has not been fully examined. The purpose of the present study was to assess the relationship between exercise tolerance and muscle strength following CR in patients after cardiac surgery and patients with MI. METHODS AND RESULTS: One hundred and four patients who participated in CR for 6 months were enrolled [post-cardiac valve surgery (VALVE), n=28; post-coronary artery bypass grafting (CABG), n=42; post-acute MI, n=34]. The exercise tolerance, thigh/calf circumferences, and muscle strength were measured before and after CR. At the baseline, the thigh circumference was significantly smaller in the VALVE group than in the MI group. There were significant positive correlations between peak VO(2) and muscle torques of the lower muscles in all groups. After 6 months, peak VO(2) and muscle torque were significantly increased in all groups (p<0.001). A positive significant correlation between percent increases in peak VO(2) and muscular strength was observed in the VALVE group (r=0.51, p<0.01), but not in the other groups. In addition, the changes in peak VO(2) and calf circumference after CR were significantly higher in the VALVE group than in the MI group. CONCLUSIONS: These data suggest that exercise intolerance in patients after heart valve surgery may in part depend on decreased muscular strength. Further studies are needed to assess whether the strategy of increasing muscular strength of lower limb by programmed resistance training could be effective for improving exercise intolerance in patients after heart valve surgery and symptomatic patients with heart failure.

Effects of cardiac rehabilitation in patients with metabolic syndrome after coronary artery bypass grafting.

BACKGROUND: Cardiac rehabilitation (CR) has numerous beneficial effects, including the modification of coronary risk factors and improvement of the prognosis, in patients with coronary artery disease (CAD). Limited data are available regarding the effects of CR on the physical status and risk factors in patients with metabolic syndrome (MetS) after coronary artery bypass grafting (CABG). METHODS AND RESULTS: We enrolled 32 patients with MetS after CABG, who participated in a supervised CR program for 6 months. Metabolic parameters, blood chemistry, exercise tolerance, and muscle strength of the thigh were measured before and after CR. After CR: (1) the body mass index, waist circumference, and fat weight significantly decreased; (2) peak V O(2) and anaerobic threshold were significantly increased; (3) isokinetic peak torques of knee extensor and flexor muscles significantly increased; (4) metabolic scoring defined by the number of the modified Adult Treatment Panel criteria of the US National Cholesterol Education Program was significantly improved; (5) serum concentration of high-sensitivity C-reactive protein also significantly decreased. CONCLUSIONS: These results suggest that CR might be useful for patients with MetS after CABG.

Serum levels of remnant lipoprotein cholesterol and oxidized low-density lipoprotein in patients with coronary artery disease.

BACKGROUND: Oxidized low-density lipoprotein (OxLDL) and remnant lipoprotein play a crucial role in the development of atherosclerosis. Recently, a novel method for measuring remnant cholesterol levels (remnant lipoproteins cholesterol homogenous assay: RemL-C) has been established. However, the correlation between OxLDL and remnant lipoprotein, including RemL-C, has not been fully investigated. METHODS: We enrolled 25 consecutive patients with documented coronary artery disease (CAD) and 20 controls. Remnant-like particle cholesterol (RLP-C) and RemL-C were used to determine the levels of remnant lipoprotein cholesterol. Serum levels of malondialdehyde-modified LDL (MDA-LDL) and OxLDL using a monoclonal antibody DLH3 (OxPC) were used to measure the concentration of circulating OxLDL. RESULTS: The CAD group had high levels of fasting glucose and glycosylated hemoglobin (HbA1c), and low levels of high-density lipoprotein cholesterol compared with the control group. Serum levels of total cholesterol or LDL cholesterol were not significantly different between the two groups. The levels of RemL-C (p = 0.035), MDA-LDL (p = 0.018), and MDA-LDL/LDL-C (p = 0.036) in the CAD group were significantly higher than those in the control group. The levels of RLP-C tended to be higher in the CAD group than those in the control group (p = 0.096). Positive correlations were demonstrated between remnant lipoprotein cholesterol and OxLDL (RLP-C and MDA-LDL/LDL-C, r = 0.45, p = 0.0024, RLP-C and OxPC, r = 0.51, p = 0.0005, RemL-C and MDA-LDL/LDL-C, r = 0.42, p = 0.0044, RemL-C and OxPC, r = 0.43, p = 0.0043). Similar trends were observed in non-diabetic subjects and in subjects without metabolic syndrome. Positive correlations were also observed between RLP-C and RemL-C (r = 0.94, p < 0.0001) and between MDA-LDL/LDL-C and OxPC (r = 0.40, p = 0.0074). CONCLUSIONS: These results suggest that the association between high levels of remnant lipoprotein cholesterol and high OxLDL levels might be linked to atherogenesis in patients with CAD.

Enhanced production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in very long chain saturated fatty acid-accumulated macrophages.

BACKGROUND: Deterioration of peroxisomal beta-oxidation activity causes an accumulation of very long chain saturated fatty acids (VLCSFA) in various organs. We have recently reported that the levels of VLCSFA in the plasma and/or membranes of blood cells were significantly higher in patients with metabolic syndrome and in patients with coronary artery disease than the controls. The aim of the present study is to investigate the effect of VLCSFA accumulation on inflammatory and oxidative responses in VLCSFA-accumulated macrophages derived from X-linked adrenoleukodystrophy (X-ALD) protein (ALDP)-deficient mice. RESULTS: Elevated levels of VLCSFA were confirmed in macrophages from ALDP-deficient mice. The levels of nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), intracellular reactive oxygen species (ROS), and pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interluekin-6 (IL-6), and interleukin-12p70 (IL-12p70), were significantly higher in macrophages from ALDP-deficient mice than in those from wild-type mice. The inducible NO synthase (iNOS) mRNA expression also showed an increase in macrophages from ALDP-deficient mice. CONCLUSION: These results suggested that VLCSFA accumulation in macrophages may contribute to the pathogenesis of inflammatory diseases through the enhancement of inflammatory and oxidative responses.

Deletion of the Fc receptors gamma chain preserves endothelial function affected by hypercholesterolaemia in mice fed on a high-fat diet.

AIMS: To clarify the role of Fc receptors (FcR) for immunoglobulin in endothelial dysfunction induced by hypercholesterolaemia, we evaluated the effect of deletion of the FcR gamma chain on endothelium-dependent relaxation and oxidative stress after 10 weeks on a high-fat diet in FcR gamma(-/-) mice compared with that in wild-type mice. METHODS AND RESULTS: Plasma cholesterol levels of those on the high-fat diet were significantly increased compared with those on the normal chow diet in both groups of mice. Endothelium-dependent relaxation of the aortic ring with acetylcholine in wild-type mice was significantly reduced by the high-fat diet (ED(50): 0.22 vs. 0.43 nM, P < 0.002), whereas the relaxation in FcR gamma(-/-) mice was not inhibited (ED(50): 0.22 vs. 0.23 nM, NS). Furthermore, superoxide detection by dihydroethidium-derived fluorescence and immunohistochemical staining of p22phox expression were significantly increased in wild-type mice fed on the high-fat diet, while these oxidative stresses in FcR gamma(-/-) mice were not enhanced by the high-fat diet. Oil Red O-staining showed no significant lipid accumulation at the aortic sinus in both groups of mice. CONCLUSION: This study demonstrates that the deletion of the FcR gamma chain preserves the endothelial function and attenuates oxidative stress affected by hypercholesterolaemia in FcR gamma(-/-) mice. These results indicate that FcR may play the pivotal role in endothelial dysfunction through oxidative stress induced by hypercholesterolaemia.