Increased Serum Heat Shock Protein 27 Antibody Titers and Prooxidant-Antioxidant Balance in Patients with Beta-Thalassemia Major

Objective: Determination of the serum heat shock protein 27 (Hsp27) antibody titers and prooxidant-antioxidant balance (PAB) in patients with thalassemia as markers of cell and oxidative stress, respectively. Methods: Serum PAB and anti-Hsp27 antibody titers were measured in 140 patients with thalassemia major and 140 sex- and age-matched healthy volunteers. Results: A significantly higher serum PAB value was observed in patients in comparison to controls. In the patient group, anti-Hsp27 antibody titers were significantly higher than for the control group (p < 0.001). We found a weak negative correlation between anti-Hsp27 antibody concentrations and the PAB (p = 0.03), but these values were not correlated with serum superoxide dismutase activity in the thalassemic patients. Conclusions: Increased levels of serum PAB and Hsp27 antibodies may be involved in the pathological consequences of β-thalassemia major and may contribute to the development of endothelial injury.     

Arterial disease in lupus and secondary antiphospholipid syndrome: association with anti-beta2-glycoprotein I antibodies but not with antibodies against oxidized low-density lipoprotein

The prevalence and clinical significance of antibodies against beta2- glycoprotein I (anti-beta2GPI) and antibodies against oxidized low- density lipoprotein (anti-ox-LDL) were evaluated as potential indicators of arterial disease in patients with systemic lupus erythematosus (SLE) and SLE with secondary antiphospholipid syndrome (APS). IgG anti-beta2GPI and IgG anti-ox-LDL were measured by enzyme- linked immunosorbent assay (ELISA) in serum samples from 118 patients with SLE, including 40 with secondary APS. IgG anti-beta2GPI were positive in 17% (20/118) of SLE patients. The presence and titres of IgG anti-beta2GPI were strongly associated with a history of arterial thrombosis. Haemolytic anaemia was also significantly associated with the presence of IgG anti-beta2GPI. The prevalence of IgG anti-ox-LDL was 53% (63/118), but there was no association with arterial thrombosis. No correlation between the values of anti-ox-LDL and those of anti-beta2GPI was found. These results suggest that IgG anti- beta2GPI could be a marker for arterial thrombosis in SLE patients, while IgG anti-ox-LDL were not associated with arterial disease in this group of lupus patients.      

Association of seropositivity for antibody to Chlamydia-specific lipopolysaccharide and coronary artery disease in Japanese men

Recent studies suggest an association between Chlamydia pneumoniae infection and coronary artery disease (CAD). To examine this relationship in Japanese men, serum IgA and IgG antibodies to Chlamydia-specific lipopolysaccharide were measured by enzyme-linked immunosorbent assay in 507 patients with CAD and 200 age-matched controls. CAD patients were divided into (1) 269 patients with myocardial infarction (MI) and (2) 238 patients with chronic coronary heart disease (CCHD). Compared with the control group, the CAD group did not differ in the prevalences of both antibodies (IgA: 23.7 vs 18.0%, p=0.10; IgG: 52.7 vs 51.0%, p=0.6). The index of IgG antibody was not significantly different between CAD and control groups (median 1.19 vs 1.18, p=0.3), whereas the index of IgA antibody was significantly higher in CAD than control group (median 0.60 vs 0.46, p<0.0001). Compared with the control group, the MI group had a significantly higher prevalence of IgA antibody (28.6 vs 18.0%, p=0.007); however, there was no difference in the prevalence of IgG antibody (58.0 vs 51.0%, p=0.13). The CCHD group did not differ in the prevalences of both antibodies (IgA: 18.1 vs 18.0%, p=0.9; IgG: 45.6 vs 51.0%, p=0.2). After the adjustment for coronary risk factors, odds ratios (ORs) of seropositive antibodies for CAD were 1.59 [95% confidence interval (CI): 0.88-2.87, p=0.12] for IgA seropositivity and 0.92 (95%CI: 0.58-1.47, p=0.7) for IgG seropositivity in all cases. In the MI and control groups, ORs of seropositive antibodies for MI were 2.67 (95%CI: 1.32-5.38, p=0.007) for IgA seropositivity, and 1.36 (95%CI: 0.79-2.36, p=0.2) for IgG seropositivity. This study discovered that IgA antibody to Chlamydia was significantly associated with CAD, especially with MI, in Japanese Men and the findings suggest that chronic infection of Chlamydia may be linked to the pathogenesis of MI.     

Seropositivity against Chlamydia pneumoniae in patients with coronary atherosclerosis

BACKGROUND: Results of therapy in patients with unstable coronary syndromes with antibiotics directed against Chlamydia pneumoniae have been variable, perhaps due to the heterogeneity of patients in these trials. HYPOTHESIS: The aim of the present study was to correlate the severity of coronary artery disease (CAD) with seropositivity against C. pneumoniae prospectively. METHODS: We measured the frequency of seropositivity (IgG levels > or = 1/64 and IgA levels > or = 1/16 against Chlamydia pneumoniae) in 110 patients with CAD and in 49 controls. RESULTS: As expected, traditional CAD risk factors were seen more often in patients with CAD than in controls. Mean values of total cholesterol (184 +/- 52 and 166 +/- 44 mg/dl, respectively) and triglyceride (143 +/- 60 and 112 +/- 63 mg/dl, respectively) in serum were significantly higher in patients with CAD than in controls (both p < 0.04). There were no significant differences between the two groups in serum high-density lipoprotein cholesterol (34 +/- 13 and 32 +/- 14 mg/dl, respectively) and lipoprotein (a) (Lp(a):241 +/- 247 and 223 +/- 263 mg/l, respectively) levels. The rate of IgG seropositivity was 52% (28/54) in patients with stable CAD, 41% (23/56) in patients with unstable CAD, and 35% in controls (p = NS). The rate of IgA seropositivity was 25% (14/54) in patients with stable CAD, 12% (6/49) in patients with unstable angina, and 12% (6/49) in controls (all p = NS). CONCLUSIONS: Only a small percentage of patients with CAD demonstrate seropositivity against Chlamydia pneumoniae. Antibiotic therapy in these selected patients, but not in the remaining patients, may be considered rational. These considerations may underlie the failure to see consistent benefits of antibiotic therapy in patients with CAD.     

Effect of low-dose (1 mg/day) pitavastatin on left ventricular diastolic function and albuminuria in patients with hyperlipidemia

The aim of the present study was to evaluate the factors that modulate the protective action of statins on cardiorenal function, regardless of the lipid-lowering effect. To treat abnormal serum lipid profiles, low-dose pitavastatin (1.0 mg/day) was administered to 65 hyperlipidemic patients. The exclusion criteria included left ventricular ejection fraction <40% and apparent renal disease. Age- and gender-matched patients with hyperlipidemia (n = 40) served as the controls. After 12 to 16 weeks of pitavastatin treatment, pitavastatin had decreased low-density lipoprotein cholesterol (from 143.5 ± 31.4 to 98.2 ± 19.4 mg/dl, p <0.01), triglycerides (from 157.7 ± 57.2 to 140.5 ± 60.7 mg/dl, p <0.01), E/e' (from 10.8 ± 6.2 to 9.0 ± 4.5, p <0.05), a parameter of left ventricular diastolic function, and albuminuria (from 47.6 ± 55.9 to 28.5 ± 40.0 mg/g creatinine, p <0.01). Furthermore, pitavastatin decreased serum transforming growth factor-β1 (from 709 ± 242 to 550 ± 299 pg/ml, p <0.01), urinary 8-hydroxy-2'-deoxyguanosine (from 6.6 ± 4.1 to 5.0 ± 3.1 μg/g creatinine, p <0.01), an oxidative stress marker, and increased urinary nitrate and nitrite (from 22.5 ± 14.6 to 29.4 ± 27.6 nmol/g creatinine, p <0.05). No such changes were observed in the controls. Multiple regression analysis in the pitavastatin group revealed the effect of pitavastatin on cardiorenal function was associated with suppression of oxidative stress, but not on low-density lipoprotein cholesterol reduction. In conclusion, pitavastatin decreases E/e' and albuminuria, which is associated with suppression of oxidative stress.     

Association between serum paraoxonase activity and oxidative stress in acute coronary syndromes

OBJECTIVE: The oxidation of low-density lipoprotein (LDL) is believed to have a central role in atherogenesis. Under oxidative stress not only LDL, but all other serum lipids are exposed to oxidation. High-density lipoprotein (HDL)-associated paraoxonase (PON1) was shown to inhibit LDL and HDL oxidation. We investigated the relationship between PON1 and oxidative stress in acute myocardial infarction and unstable angina in a comparative fashion. METHODS AND RESULTS: Activities of PON1, concentrations of malondialdehyde (MDA), lipids and lipoproteins were measured in patients (38 subjects with acute myocardial infarction and 33 subjects with unstable angina pectoris) and in age- and sex-matched controls (32 subjects). Serum PONI activity was significantly lower in patients than in controls (p < 0.001). Patients had significantly increased serum MDA concentrations (p < 0.001) and there were strong negative correlations (p < 0.001) between serum PON1 and MDA levels in the acute myocardial infarction group (r = -0.673), in the unstable angina pectoris group (r = -0.868) and in healthy controls (r = -0.778). Serum HDL-cholesterol (HDL-C) concentrations were lower in patients than controls (p < 0.05). No correlation was observed between PON1 and HDL-C levels in patients or controls. Apo A I concentrations were significantly lower in the patient groups (p < 0.01), but were insignificant between patients with AMI and UAP. Apo A-I and PON1 levels did not show any correlation. Apo B concentrations were lowest in the healthy controls, higher in the UAPgroup and highest in the AMI group (p < 0.001). In the acute myocardial infarction group LDL/apo B ratio was lower than in healthy controls and in the UAP group, suggesting smaller LDL particle size. CONCLUSIONS: Results of this study indicate that lower serum PON1 activity is associated with oxidative stress and the activity of PON1 is not related to HDL-cholesterol.     

Autoantibody against peroxiredoxin I, an antioxidant enzyme, in patients with systemic sclerosis: possible association with oxidative stress

OBJECTIVES: To determine the prevalence and clinical correlation of autoantibody to peroxiredoxin (Prx) I, an antioxidant enzyme, in patients with systemic sclerosis (SSc). METHODS: Serum samples from SSc patients (n = 70) and healthy controls (n = 23) were examined by ELISA using human recombinant Prx I. The presence of anti-Prx I antibody was further evaluated by immunoblotting analysis. To determine the functional relevance of anti-Prx I antibody in vivo, we assessed whether anti-Prx I antibody was able to inhibit Prx I enzymatic activity using yeast thioredoxin reductase system. RESULTS: IgG anti-Prx I antibody levels in SSc patients were significantly higher than healthy controls and this autoantibody was detected in 33% of SSc patients. The presence of IgG anti-Prx I antibody was associated with longer disease duration, more frequent presence of pulmonary fibrosis, heart involvement, and anti-topoisomerase I antibody and increased levels of serum immunoglobulin and erythrocyte sedimentation rates. IgG anti-Prx I antibody levels also correlated positively with renal vascular damage and negatively with pulmonary function tests. Furthermore, anti-Prx I antibody levels correlated positively with serum levels of 8-isoprostane, a marker of oxidative stress. Immunoblotting analysis confirmed the presence of anti-Prx I antibody. Remarkably, Prx I enzymatic activity was inhibited by IgG isolated from SSc sera containing IgG anti-Prx I antibody. CONCLUSIONS: These results suggest that elevated IgG anti-Prx I autoantibody is associated with the disease severity of SSc and that anti-PrxI antibody may enhance the oxidative stress by inhibiting Prx I enzymatic activity.     

Usefulness of anti-oxidized LDL antibody determination for assessment of clinical control in patients with heart failure

BACKGROUND: It has been suggested that oxidative stress may play a role in the pathogenesis of heart failure, this may have potential implications for therapeutic strategies. However, measures of oxidative stress are subject to confounding inaccuracies. IgG antibodies to oxidized LDL reflect exposure to the lipoprotein over an extended period and may thus mirror oxidative stress over a prolonged time frame. Therefore, we tested the hypothesis that anti-oxLDL antibodies correlate with the control of heart failure (HF), as manifested by hospital admissions for cardiac dysfunction. METHODS: One hundred and two consecutive patients attending the HF clinic with either systolic or diastolic HF were enrolled and the quality of clinical control was evaluated by assessing hospital admissions over the year prior to index determination of the oxidative stress marker. Antibodies to oxLDL were determined by ELISA and pro-BNP levels were also measured. RESULTS: Most patients (mean age 71.5 years) had systolic HF; mean NYHA functional class was 2.7 and mean left ventricular ejection fraction was 39.7%. Anti-oxLDL antibodies, but not pro-BNP, correlated significantly with mean NYHA score (averaged from all clinic visits in the year prior to blood testing), and with hospital admissions over the year prior to blood testing. Mean IgG anti-oxLDL antibody levels in patients with hospital admissions were 3.4 times higher than those in subjects not hospitalized over the previous year. CONCLUSION: IgG anti-oxLDL antibody levels correlate with the severity of HF.     

Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women

OBJECTIVES: The purpose of the study was to investigate whether cholesterol metabolism is associated with coronary artery disease (CAD) in postmenopausal women. BACKGROUND: Although hypercholesterolemia, a predominant risk factor of CAD, is related to cholesterol metabolism, the association between cholesterol metabolism and CAD is not well known. METHODS: In addition to conventional coronary risk factors, fasting serum squalene, delta8-cholestenol, desmosterol, lathosterol (indicators of cholesterol synthesis), cholestanol, campesterol and sitosterol (indicators of cholesterol absorption) were measured in 48 50- to 55-year-old consecutive women with angiographically verified CAD and in 61 age-matched healthy controls. RESULTS: The coronary patients had elevated ratios of squalene (p < 0.001), desmosterol (p = 0.005), campesterol (p = 0.028) and sitosterol (p = 0.022) to cholesterol, but had lower respective lathosterol value (p = 0.041) compared with the controls, despite similar serum cholesterol levels. Adjusted for age, body mass index, family history of CAD, smoking, hypertension, serum triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol level and glycosylated hemoglobin A1c% (GHbA1c), the ratios of squalene (odds ratio, 1.36; 95% confidence interval, 1.17 to 1.57), lathosterol (0.98; 0.97 to 0.99), campesterol (1.01; 1.00 to 1.01) and sitosterol (1.01; 1.00 to 1.03) were significantly associated with the risk of CAD. In addition, family history of CAD and GHbA1c% were also independently related to the presence of CAD. CONCLUSIONS: The results suggest that women with elevated ratios of serum squalene, campesterol and sitosterol to cholesterol and low respective lathosterol values have enhanced risk for CAD. Thus, enhanced absorption and reduced synthesis of cholesterol may be related to coronary atherosclerosis.     

Association of paraoxonase-1 activity and concentration with angiographic severity and extent of coronary artery disease.

OBJECTIVES: The goal of this study was to examine the association between paraoxonase-1 (PON1) activity and concentration and the severity and extent of coronary artery disease (CAD). BACKGROUND: Paraoxonase-1, a high-density lipoprotein-associated enzyme, is proposed to have an antiatherogenic effect by protecting low-density lipoproteins against oxidation. METHODS: We studied PON1 activity and concentration in 107 patients with known or suspected CAD referred for cardiac catheterization. Based on visual estimation of coronary angiograms, subjects were classified as having no or mild CAD (<50% stenosis) and significant CAD (> or =50% stenosis). Quantitative coronary angiography (QCA) was used to estimate the indexes of severity, extent, and overall atheroma burden of CAD. RESULTS: We found lower values of PON1 activity and concentration (p = 0.003 and p = 0.016, respectively) in the group with significant CAD as compared with the group with no or mild CAD. The PON1 activity was significantly inversely correlated with CAD severity (r = -0.364, p < 0.001), extent (r = -0.221, p = 0.022), and atheroma burden (r = -0.277, p = 0.004). Similarly, PON1 concentration correlated with CAD severity (r = -0.306, p = 0.001) and atheroma burden (r = -0.229, p = 0.017). In multiple regression analysis, gender and PON1 activity were significant determinants of the severity of CAD independently of age, hypertension, smoking, abnormal glucose regulation, and high-density lipoprotein cholesterol. CONCLUSIONS: Our results indicate that PON1 activity and concentration are lower in subjects with significant CAD, and that there is a significant relationship between PON1 activity and concentration and CAD assessed by QCA.     

Prevalence of atrial arrhythmia in 48 hypertensive patients: research of predictive criteria]

We studied atrial arrhythmias during a continue prospective work in 48 hypertensive patients referred to the OMS criteria. Hypertension was confirmed by a blood pressure ambulatory monitoring and stress testing blood pressure trend. All cardiovascular drugs were stopped at admission. Patients with associated valvular or coronary artery disease were excluded from analysis. In all patients, we realized a twelve lead-ECG, stress testing, 24 hour Holter monitoring, a blood pressure ambulatory monitoring, two-dimensional echocardiography with Doppler study and cardiac radio-nuclide angiography with diastolic function study. Atrial arrhythmias were considered significant if more than 100 premature atrial beats (PAB) and/or more than three successive PAB were present during Holter monitoring. Significant atrial arrhythmias were found in 39.5% of patients (group II, n = 19), not significant in 60.5% of patients (group I, n = 29). The duration of hypertension was longer in group II (140 vs 66 months, p < 0.05). There was no difference between the two populations considering left atrial size or blood pressure level. Furthermore, we were surprised to find a normal E/A ratio on mitral Doppler recording in patients with atrial arrhythmias (1.23 vs 0.9; p < 0.05). Others diastolic parameters didn't significantly differ. Left ventricular mass index was similar in the two groups but patients with atrial arrhythmias had more asymmetric hypertrophy (1.23 vs 1.13 septum/posterior wall ratio: p < 0.05). Conclusion: atrial arrhythmias in our study seem to be more dependent from duration of HTA and left ventricular asymmetric structure than from left atrial size.(ABSTRACT TRUNCATED AT 250 WORDS)     

High remnant lipoprotein levels in patients with variant angina

BACKGROUND: Dyslipidemia with increased oxidative stress but without elevation of low-density lipoprotein cholesterol has been recently implicated in the pathogenesis of coronary vasospasm. HYPOTHESIS: Disordered triglyceride-rich lipoprotein metabolism may be linked to the genesis of coronary artery spasm. METHODS: Both serum remnant lipoprotein (RLP) and alpha-tocopherol levels were determined in 18 patients with the active stage of variant angina (VA), in 16 patients with the inactive stage of variant angina (IVA), and in 19 control subjects (CONTROL). RESULTS: The RLP levels were significantly (p < 0.05) higher in VA (6.4 +/- 2.7 mg/dl) than in IVA (4.4 +/- 1.5 mg/dl). In contrast, alpha-tocopherol levels were significantly lower in VA than that in CONTROL. Serum trigyceride levels were not significantly different among the study groups, although serum high-density lipoprotein cholesterol levels were significantly lower in VA than in CONTROL. Smoking was significantly (p < 0.05) more prevalent in VA (72%) than in IVA (25%) and CONTROL (37%). Serum RLP levels correlated positively with triglyceride levels (R = 0.73) and correlated inversely with alpha-tocopherol levels (R = -0.31) significantly in all study subjects. CONCLUSIONS: Patients with active stage of variant angina had higher RLP levels than inactive patients with variant angina and lower alpha-tocopherol levels than control subjects. Disordered triglyceride-rich lipoprotein metabolism with increased oxidative stress appears to be linked to the activity of coronary vasospasm, suggesting a possible role in its pathogenesis.     

Anti-cardiolipin antibodies and endothelial function in patients with coronary artery disease

Endothelial dysfunction is considered an important marker in atherosclerosis, having a prognostic value. Antiphospholipid antibodies are considered prothrombotic and have recently been reported to be associated also with atherosclerosis. This study was conducted to investigate a possible association of endothelial dysfunction with various antiphospholipid autoantibodies in healthy subjects and patients with cardiovascular disease. In a single-center, prospective study, 2 groups were included. The study group included patients with cardiovascular diseases (coronary disease and/or cerebrovascular disease) and healthy subjects without apparent heart disease who were referred to the endothelial function laboratory for the assessment of endothelial function. Flow-mediated dilatation, which indicates endothelial function, and nitroglycerin-mediated vasodilatation, which indicates smooth-muscle function, were measured. The 2 groups were evaluated for autoantibodies, including anticardiolipin (aCL; immunoglobulin G [IgG], immunoglobulin M [IgM], and immunoglobulin A [IgA]), antinuclear antibody, anti-beta2-glycoprotein I (IgG, IgM, and IgA), and oxidized low-density lipoprotein. One hundred seven subjects were included in the study: 45 patients (42%) and 62 healthy controls (58%). Flow-mediated dilatation was significantly lower in patients compared with healthy controls (8.0 +/- 9.5% vs 8.0 +/- 13.5%, p = 0.012). In addition, nitroglycerin-mediated vasodilatation was nonsignificantly lower in patients than in healthy controls (8.0 +/- 13.4% vs 11.0 +/- 16.7%, p = 0.084). The mean levels of anti-beta2-glycoprotein I (IgG, IgM, and IgA), aCL (IgM and IgA), antinuclear antibody, and oxidized low-density lipoprotein were not different between groups. However, the mean level of IgG aCL was significantly higher in patients than in healthy controls. In conclusion, in accordance with previous reports of an association between aCL and atherosclerosis, patients with cardiovascular disease had endothelial dysfunction and elevated levels of aCL.     

Isolated type 2 diabetes mellitus causes myocardial dysfunction that becomes worse in the presence of cardiovascular diseases: results of the myocardial doppler in diabetes (MYDID) study 1

AIMS: Patients with type 2 diabetes mellitus (DM) often suffer disproportionately and have a worse outcome when burdened with cardiovascular complications compared with those without DM. A specific heart muscle disease reportedly caused by DM per se may explain this. We sought to investigate whether an echo Doppler diagnosis of such a myocardial disease is clinically relevant in DM with or without coexistent coronary artery disease (CAD) and/or hypertension (HTN). SUBJECTS AND METHODS: Two hundred subjects (127 males, 73 females, 56 +/- 10 years) including controls (n = 23), patients with HTN (n = 20), CAD (n = 35), uncomplicated DM (n = 59), DM+HTN (n = 27), DM+CAD (n = 16) and DM+CAD+HTN (n = 20) underwent tissue Doppler-enhanced dobutamine stress echocardiography. Myocardial function was assessed by measuring left ventricular myocardial peak systolic velocity (PSV) and early diastolic velocity at rest and during peak stress, besides measurements of standard Doppler variables. RESULTS: Average left ventricular PSV at rest was significantly lower in CAD (4.7 +/- 1.5) compared with controls (5.7 +/- 1.2) and in DM+CAD+HTN (4.6 +/- 1.4) compared with DM (5.6 +/- 1.3; all p < 0.05). During peak stress, lower PSV persisted in CAD (9.5 +/- 3.1) and DM+CAD+HTN (8.1 +/- 2.7), while appearing de novo in DM (11.3 +/- 2.6) and HTN (11.0 +/- 2.3) unlike in the controls (12.5 +/- 2.5; all p < 0.001). When pooled together, DM subjects with CAD and/or HTN or both had significantly lower PSV (9.1 +/- 2.7) than those without (10.0 +/- 2.8; p < 0.001). Early diastolic velocity response was equally lower in both groups compared with the controls. CONCLUSION: The results suggest that dobutamine stress unmasks myocardial functional disturbances caused by uncomplicated DM. The discrete disturbances become quantitatively more pronounced in the presence of coexistent cardiovascular diseases.     

Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis

AIMS: Factors responsible for the progression of non-alcoholic fatty liver disease (NAFLD) to more severe liver injury are poorly understood. In the present study, we investigated the association between immune reactions triggered by oxidative stress and stage of NAFLD. METHODS: Titres of IgG against human serum albumin adducted with malondialdehyde (MDA-HSA) or arachidonic acid hydroperoxide (AAHP) and against oxidised cardiolipin (Ox-CL) were measured in 167 NAFLD patients with steatosis only (n = 79), steatohepatitis (n = 74), or steatosis plus cirrhosis (n = 14), and in 59 age and sex matched controls. RESULTS: Circulating IgG against lipid peroxidation products was significantly higher (p<0.001) in NAFLD patients than in controls. Oxidative stress dependent immune responses were not associated with obesity, type 2 diabetes, or with serum cholesterol, ferritin, or aminotransferase levels. Titres of lipid peroxidation related antibodies were also independent of the extent of steatosis and were similarly distributed in patients with and without necroinflammation. In contrast, the same antibodies were significantly increased in patients with advanced fibrosis or cirrhosis. Logistic regression analysis confirmed that anti-MDA antibodies were independently associated with progression of NALFD and that NAFLD patients with titres of anti-MDA-HSA antibodies above the control threshold value had a threefold (relative risk 2.82 (95% confidence interval 1.35-5.90); p = 0.007) higher risk of having advanced fibrosis/cirrhosis than patients whose antibody titres were within the control range. CONCLUSIONS: These results indicate that the presence of immune reactions triggered by oxidative stress can be an independent predictor of progression of NAFLD to advanced fibrosis.     

Right and left ventricular function and pulmonary artery pressure in patients with bronchiectasis

BACKGROUND: Bronchiectasis may have deleterious effects on cardiac function secondary to pulmonary hypertension (PH). This study was designed to assess cardiac function and determine the prevalence of PH in patients with cystic and cylindrical bronchiectasis. METHODS: A cross-sectional study of patients with bronchiectasis diagnosed by CT scan was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia between December 2005 and January 2007. Pulmonary function tests were performed, arterial blood gas measurements were made, and cardiac function and systolic pulmonary artery pressure (SPAP) were assessed by echocardiography. RESULTS: Of 94 patients (31% men, n = 29), 62 patients (66%) had cystic bronchiectasis and 32 patients (34%) had cylindrical bronchiectasis. Right ventricular (RV) systolic dysfunction was observed in 12 patients (12.8%), left ventricular (LV) systolic dysfunction was observed in 3 patients (3.3%), and LV diastolic dysfunction was observed in 11 patients (11.7%); all had cystic bronchiectasis. RV dimensions were significantly greater in the cystic bronchiectasis group, and were positively correlated with SPAP (p < 0.0001) and negatively correlated with Pao2 (p < 0.016). Other hemodynamic variables were not different between groups. PH in 31 patients (32.9%) was significantly greater in patients with cystic bronchiectasis compared with cylindrical bronchiectasis (p = 0.04). In cystic bronchiectasis, SPAP was positively correlated with Paco2 (p = 0.001), and inversely correlated with Pao2 (p = 0.03), diffusion capacity of the lung for carbon monoxide percentage (p = 0.02), and FEV1 (p = 0.02). CONCLUSIONS: RV systolic dysfunction and PH were more common than LV systolic dysfunction in bronchiectatic patients. LV diastolic dysfunction was mainly seen in severe PH. We recommend detailed assessment of cardiac function, particularly LV diastolic function, in patients with bronchiectasis.     

“Supranormal” Cardiac Function in Athletes Related to Better Arterial and Endothelial Function

Objective: Athlete's heart is associated with left ventricular (LV) hypertrophy (LVH), and “supranormal” cardiac function, suggesting that this is a physiological process. Hypertrophy alone cannot explain increase in cardiac function, therefore, other mechanisms, such as better ventriculo‐arterial coupling might be involved. Methods: We studied 60 male (21 ± 3 years) subjects: 27 endurance athletes, and a control group of 33 age‐matched sedentary subjects. We assessed global systolic and diastolic LV function, short‐ and long‐axis myocardial velocities, arterial structure and function and ventriculo‐arterial coupling, endothelial function by flow‐mediated dilatation, and amino‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and biological markers of myocardial fibrosis and of oxidative stress. Results: Athletes had “supranormal” LV longitudinal function (12.4 ± 1.0 vs 10.1 ± 1.4 cm/s for longitudinal systolic velocity, and 17.4 ± 2.6 vs 15.1 ± 2.4 cm/s for longitudinal early diastolic velocity, both P < 0.01), whereas ejection fraction and short‐axis function were similar to controls. Meanwhile, they had better endothelial function (16.7 ± 7.0 vs 13.3 ± 5.3%, P < 0.05) and lower arterial stiffness (pulse wave velocity 7.1 ± 0.6 vs 8.8 ± 1.1 m/s, P = 0.0001), related to lower oxidative stress (0.259 ± 0.71 vs 0.428 ± 0.88 nmol/mL, P = 0.0001), with improved ventriculo‐arterial coupling (37.1 ± 21.5 vs 15.5 ± 13.4 mmHg.m/s³× 10³, P = 0.0001). NT‐proBNP and markers of myocardial fibrosis were not different from controls. LV longitudinal function was directly related to ventriculo‐arterial coupling, and inversely related to arterial stiffness and to oxidative stress. Conclusions: “Supranormal” cardiac function in athletes is due to better endothelial and arterial function, related to lower oxidative stress, with optimized ventriculo‐arterial coupling; athlete's heart is purely a physiological phenomenon, associated with “supranormal” cardiac function, and there are no markers of myocardial fibrosis. (Echocardiography 2010;27:659‐667)     

Right ventricular diastolic dysfunction and the acute effects of sildenafil in pulmonary hypertension patients

AIMS: This study investigated whether right ventricular (RV) diastolic function is impaired in pulmonary hypertension (PH) patients, and whether it is related to RV mass and afterload. In addition, the effects of an acute reduction of RV afterload by the oral intake of sildenafil were studied. Finally, we assessed whether diastolic function is related to cardiac parameters of disease severity. METHODS AND RESULTS: Twenty-five PH patients and 11 control subjects were studied. Right-heart catheterization and N-terminal pro-brain natriuretic peptide (NT-proBNP) sampling were performed in patients. MRI measured RV ejection fraction, mass, and diastolic function. Isovolumic relaxation time (IVRT), normalized early peak filling rate (E), atrium-induced peak filling rate (A), and E/A ratio described diastolic function. Compared to control subjects, patients had prolonged mean (+/- SD) IVRT (133.5 +/- 53.2 vs 29.3 +/- 20.8 ms, respectively; p < 0.001), decreased E (3.0 +/- 1.6 vs 6.4 +/- 2.5 s(-1), respectively; p < 0.001) and E/A ratio (1.1 +/- 0.7 vs 5.3 +/- 4.9, respectively; p < 0.001), and increased A (3.0 +/- 1.4 vs 1.5 +/- 0.9 s(-1), respectively; p = 0.001). IVRT was related to RV mass (r(25) = 0.56; p = 0.005) and pulmonary vascular resistance (r(25) = 0.74; p < 0.0001). Sildenafil therapy reduced RV afterload and improved RV diastolic and systolic function. IVRT was correlated with NT-proBNP level (r = 0.70; p < 0.001), and was inversely related to cardiac index (r = -0.70; p < 0.001) and RV ejection fraction (r = -0.69; p < 0.001). CONCLUSION: In PH patients, RV diastolic dysfunction is related to RV mass and afterload. RV diastolic function improves by reducing afterload. The correlations between diastolic function and prognostic parameters showed that diastolic function is most impaired in patients with severe disease.     

心绞痛、心肌梗死患者血清胆红素浓度分析

目的：探讨血清总胆红素浓度与冠心病的关系。方法：检测115例冠心病心绞痛,心肌梗死患及75例非冠心病病人血清总胆红素浓度,分析冠心病与胆红素水平的关系。结果：冠心病心绞痛,心肌梗死患血清总胆红素浓度明显低于非冠心病组（P＜0．05）,血清总胆红素与总胆固醇,低密度脂蛋白胆固醇,载脂蛋白B水平呈负相关,结论：低胆红素血症可能是冠心病危险因子之一,胆红素对血脂代谢有影响。     

Comparison of remnant-like lipoprotein particles in postmenopausal women with and without coronary artery disease and in men with coronary artery disease

It is known that hypertriglyceridemia is a risk factor of coronary artery disease (CAD) in postmenopausal women. This study prospectively examined whether remnant lipoprotein, an atherogenic triglyceride-rich lipoprotein, may have a significant risk and prognostic values in postmenopausal women with angiographically verified CAD. Remnant-like lipoprotein particles cholesterol (RLP cholesterol) levels in fasting serum were measured in 134 consecutive postmenopausal women with (n = 56) or without (n = 78) CAD by an immunoseparation method. The women with CAD were followed for ≤24 months until occurrence of the following clinical coronary events: readmission or coronary revascularization due to recurrent or refractory angina pectoris, nonfatal myocardial infarction, and cardiac death. Multivariate logistic regression analysis showed that high RLP cholesterol levels (>5.7 mg/dl cholesterol; 90th percentile of the distribution of RLP cholesterol levels in controls) were a significant risk factor for the presence of CAD independent of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and other traditional risk factors. Kaplan-Meier analysis demonstrated that women with CAD and higher RLP cholesterol levels had a significantly higher probability of developing coronary events (p <0.001). In multivariate Cox hazard analysis, high RLP cholesterol levels as well as diabetes and hypercholesterolemia were a significant predictor of future coronary events independent of other risk factors in women with CAD (odds ratio 9.7, 95% confidence intervals 1.3 to 20.3, P = 0.02). In conclusion, increased levels of RLP cholesterol are a significant and independent risk factor of CAD and predict future coronary events in postmenopausal women with CAD.