Bilirubin and Epigenetic Modifications in Metabolic and Immunometabolic Disorders.

Bilirubin is the main waste product of heme catabolism. At high concentrations, bilirubin may cause toxicity, especially in the brain, kidney, and erythrocytes. Membrane and mitochondrial dysfunction, oxidative stress, apoptosis, necrosis, endoplasmic reticulum stress, excitotoxicity, inflammation, and epigenetic modifications are the main mechanisms of toxicity triggered by bilirubin in susceptible organs. Many studies have shown that there is an interaction between bilirubin and epigenetic modifications in metabolic and immune diseases. In this review, we first outline the toxicity mediated by bilirubin and then summarize the current knowledge linking bilirubin and epigenetic modifications in metabolic and immunometabolic disorders.

Comparison of Serum Total IgA Levels in Severe and Mild COVID-19 Patients and Control Group.

BACKGROUND: The present study aimed to compare serum total IgA levels between severe and mild COVID-19 patients' groups and the control group. METHODS: In this cross-sectional study, 216 definite severe COVID-19 patients (as the inpatient group), 183 subjects with positive specific COVID-19 IgG with mild or no symptoms as the (outpatient group), and 203 healthy subjects with negative specific serology, as the control group were investigated. The cases' laboratory data were collected, and thereafter, statistical tests, including independent samples t test, ANOVA test, and post hoc test, were performed using SPSS software version 22. RESULT: The mean ± SD of IgA in all the included subjects was 2.23 ± 0.78 (g/L). According to the obtained results, there were statistically significant changes in IgA among the three study groups (P value < 0.05). This difference was significant between both outpatient and inpatient groups (P value < 0.05). The mean ± SD of serum IgG in all the subjects was calculated as 15.83 ± 5.73 (g/L). A strong statistically significant change was also seen in IgG among all three groups (P value < 0.001). Of note, there was a significant negative correlation between IgG and IgA total titers of the outpatient group (P value = 0.011*r = - 0.188). CONCLUSION: It was shown that the total serum IgA and IgG levels are significantly associated with the severity of COVID-19 infection. As well, we found that total serum IgA and IgG are associated with the severity of illness. Since a low level of IgA is asymptomatic and high frequent in Iran and other countries, we suggest the evaluation of serum IgA levels in high-risk people and strengthening immune system in subjects with a low level of IgA, in order to reduce the rate of death. In this regard, oral or nasal mucosal vaccines in combination with parenteral vaccination are recommended due to increasing immunity versus COVID-19 by further secretion of the IgA antibody and preventing virus transmission.

Epidemiology, Sociodemographic Factors and Comorbidity for Allergic Rhinitis, Asthma, and Rhinosinusitis Among 15 to 65-year-Old Iranian Patients.

Background: It is well established that upper and lower airways are often clumped together when diagnosing and treating a disease. This study was designed to determine the prevalence of upper and lower airway diseases and to assess the effect of sociodemographic factors on the prevalence and the comorbidity of these disorders. Methods: This cross-sectional population-based study included patients with ages ranging between 15 to 65 years, who were referred to allergy outpatient clinics in various provinces of Iran from April to September 2020. A modified global Allergy and Asthma European Network (GA2LEN) screening questionnaire was filled out by local allergists of the 12 selected provinces in Iran. Information about the patients and sociodemographic factors was also recorded. Statistical analysis was done by univariate statistical analyses and multiple logistic regressions in SPSS software Version 26. Results: Out of 4988 recruited patients, 1078 (21.6%) had the symptoms of allergic rhinitis (AR) and 285 (5.7%) met the criteria of asthma. The prevalence of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) was 21.6 % and 22%, respectively. The highest prevalence of AR and ARS was in Tehran with the arateof of 33.9% each. Asthma was more prevalent in Khuzestan (14.2%) and CRS in Baluchestan (57.5%). Our analysis showed that the patients with asthma were most likely to have other allergic diseases as well-CRS (OR = 4.8; 95% CI, 2.02- 5.82), AR (OR= 2.5, 95% CI, 2.10-3), ARS (OR = 1.8; 95% CI, 2.10-3), followed by eczema (OR = 1.4; 95% CI, 1.13-1.67).We found that those individuals with CRS were most likely to have painkiller hypersensitivity (OR= 2.1; 95% CI, 1.21-3.83). Furthermore, smoking has been found more than 1.5 folds in patients with ARS. After adjusting variables, there was no correlation between education, occupation, and ethnicity with the studied diseases. Conclusion: Rhinosinusitis is a common condition among Iranian patients. This study confirmed that inflammation of the upper and lower airways can occur simultaneously. Gender, education, occupation, and ethnicity were found to be irrelevant in the development of either AR, asthma, ARS, or CRS.

Olfactory Dysfunction in Patients Infected with 2019 Novel Coronavirus.

INTRODUCTION: The current study aimed at investigating the occurrence and features of olfactory dysfunction in patients with confirmed coronavirus disease 2019 (COVID-19) infection. MATERIALS AND METHODS: Patients with laboratory and clinically confirmed COVID-19 infection were enrolled in this longitudinal study. They were managed in either the inpatient or outpatient setting. The demographic, clinical, and outcome data were retrieved from patients' medical records. Olfactory dysfunction features, including the onset pattern, duration, and recovery time were investigated. The visual analog scale (VAS) was utilized as a self-rating subjective measurement of olfactory function. RESULTS: According to the results, the mean age of the patients (n=502) was obtained at 46.8±18.5 years; moreover, 52.4% and 47.6% of cases were female and male, respectively. It was also revealed that 35.4% and 64.5% of the subjects were outpatients and hospitalized, respectively. Based on the findings, 178 (38.4%) subjects had olfactory dysfunction. The mean values of VAS in hyposmic patients were estimated at 2.5±2.5, 8.3 ±2.1, and 9.4±1.6 at the first evaluation, in 2 weeks, and after 1 month of follow-up (P<0.001). The onset of olfactory dysfunction was more suddenly (58.7%). The majority of cases experienced olfactory dysfunction at the same time as other symptoms 72(51.1%). Based on the results, 0.4% of subjects infected with COVID-19 had olfactory dysfunction as an isolated symptom. The olfactory dysfunction was recovered after 2 weeks in 18 (25.3%) anosmic and 37(46.8%) hyposmic patients. CONCLUSION: Olfactory dysfunction seemed to be an important symptom of COVID-19 infection. The occurrence of this disturbance as a transient self-limited condition was significantly higher among female subjects.

Association between serum Vitamin E concentrations and the presence of Metabolic Syndrome: A population-based cohort study.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of clinical and metabolic features that include central obesity, dyslipidemia, hypertension and impaired glucose tolerance. These features are accompanied by increased oxidative stress and impaired antioxidant defenses. Vitamin E is a major factor in the non-enzymatic antioxidant defenses. The aim of present study was to investigate the association between serum levels of vitamin E and the presence of MetS and its components in a sample population of Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study. METHODS: This cross-sectional study was carried out in 128 subjects with MetS and 235 subjects without MetS. MetS was defined according to the International-Diabetes-Federation criteria. Serum levels of vitamin E were measured using the HPLC method. Anthropometric and biochemical parameters were measured using standard protocols.  Results. MetS patients had significantly lower serum levels of vitamin E (Vit E), Vit E/Total cholesterol (TC), and Vit E/ (TC+triglyceride(TG)) compared to the control group (P < 0.05).  Vit E/ (TG+TC) was also significantly lower in diabetics or those with elevated levels of high sensitive C-reactive protein (hs-CRP). Additionally, there was a significant association between Vit E/ (TG + Total Cho) and the number of components of the metabolic syndrome (p= 0.02) Conclusions. There is a significant inverse association between indices of Vit E status and the presence of MetS. Moreover, a significantly lower Vit E/ (TC+TG) was observed along with individuals with increasing numbers of components of the MetS.

Evaluation of Growth Differentiation Factor-15 in Patients with or without Coronary Artery Disease.

BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a distant member of the transforming growth factor-beta cytokine superfamily expressed in human atherosclerotic plaque macrophages. In this study, we sought to compare GDF-15 between patients with coronary artery disease and control group. METHODS: In this cross-sectional study, 176 subjects were enrolled, consisted of 88 coronary artery disease patients (CAD group) and 88 non-CAD participants (control group. Clinical and demographic data, comprising of family history of CAD, history, and lifestyle factors, hypertension, diabetes, and some blood parameters (e.g. glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)), triglyceride, high-sensitivity C-reactive protein (hs-CRP)). RESULTS: Mean age of the patients was 55.5±11.1 years (age range: 28-80 years). Of all the participants, 91 (51.7%) were male and 85 (48.3%) female. Hs-CRP, LDL-C, and GDF-15 levels were significantly higher in the CAD patients (P=0.091, P=0.008, and P<0.001, respectively). Total cholesterol, hematocrit, and hemoglobin were significantly higher in the controls (P=0.002, P=0.011, and P=0.055, respectively). The area under the receiver operating characteristic curve yielded the satisfactory result of 0.9 (95% CI, 0.8-0.9; P<0.001). The optimum cut-off value of GDF-15 was 1233 ng/L with 71% specificity and 71% sensitivity for CAD diagnosis. CONCLUSION: These data suggest that serum GDF-15 might be useful in prediction of CAD.

Serum vitamin E as a significant prognostic factor in patients with dyslipidemia disorders.

OBJECTIVES: Obesity and overweight are among the main causes of cardiovascular disease (CVD) mortality. Dyslipidemia, fatty liver index, is strongly related to CVD. Vitamin E as an antioxidant protects the hepatic cells against oxidative stress and prevents fatty liver disease. The aim of the current study is to evaluate the relationship between anthropometric parameters and fasted lipid profile with serum vitamin E levels. STUDY DESIGN: A randomized trial was designed based on data from the Mashhad stroke and heart atherosclerotic disorders (MASHAD: 2010-2020). METHODS: 363 CVD subjects (173 males and 190 females) was selected at random, among 9704 subjects in three regions of Mashhad, northeast of Iran to investigate the specific correlations among their serum vitamin E, lipid profile (TG, HDL-C, LDL-C and TC), and anthropometric features (height, weight, BMI, hip and waist circumferences. RESULT: The results indicated the significant relationships between vitamin E, and fasting serum lipid profile in subjects. Serum vitamin E was negatively correlated to TC, TG, and LDL-C and positively related to HDL-C. Also, statistically negative correlations were found between vitamin E and anthropometric parameters (weight, waist and hip circumference, middle Arm, and Systolic Blood Pressure). Moreover, vitamin E ratios such as vitamin E/(TC + TG) and vitamin E/TC values as standardized vitamin E, had significant negative correlation with BMI, the whole of anthropometric parameters, and dyslipidemia risk factors including TC, TG and LDL-C. CONCLUSION: We found that vitamin E profile was significantly lower in the dyslipidemia subjects. It is generally suggested that vitamin E monitoring might be used as a useful prognostic and therapeutic agent in dyslipidemia disorder.

Malondialdehyde-Modified LDL IgG Antibody Levels and Indices of Cardiac Function in Valvular Heart and Coronary Artery Disease Patients.

OBJECTIVE: To compare the changes in anti-malondialdehyde-modified low-density lipoprotein (MDA-LDL) IgG levels among patients undergoing off-pump and on-pump coronary artery bypass grafting (CABG) or valvuloplasty. SUBJECTS AND METHODS: A total of 38, 39 and 34 patients who underwent off-pump CABG, on-pump CABG and valvuloplasty, respectively, were enrolled in this study. Serum anti-MDA-LDL IgG values were measured 24 h before and after the operative procedures and at discharge. Echocardiography was also done before surgery and before discharge. The results were compared with values from 50 healthy controls. RESULTS: In all patients, a reduction in antibody titers was observed post-operatively. However, the decrease was significant only in the off-pump CABG - before surgery: 42.33 (25.83-58.51), after surgery: 30.86 (16.36-51.33) and at discharge: 10.96 (6.82-23.57; p = 0.027). There was a significant positive association between anti-MDA-LDL IgG levels and ejection fraction (r = 0.248, p = 0.036) and a negative association with E/E', a marker of pulmonary capillary wedge pressure, in the coronary patients (r = -0.345, p = 0.012), but no significant associations were found in patients with valvular heart disease. CONCLUSIONS: Serum anti-MDA-LDL IgG levels were associated with cardiac function indices in coronary patients undergoing CABG.

Comparison of cardiac rehabilitation programs combined with relaxation and meditation techniques on reduction of depression and anxiety of cardiovascular patients.

Cardiovascular disease (CVD) is a major cause of death in developed countries. Most cardiac rehabilitation programs include psychological interventions. The aim of this study was to determine the effectiveness of rehabilitation techniques in cardiac patients including psychological-physical interventions such as Meditation and Relaxation. We enrolled 45 patients with CVD and depression. The patients were allocated to 3 groups (Relaxation, Meditation and Control). There was a significant reduction on depression, systolic blood pressure and heart rate in the Meditation group compared with the control group. Our findings suggest that meditation techniques have better outcomes in cardiac patients for improving depression, reduction of systolic and diastolic blood pressure, and heart rate than relaxation techniques.

The Effects of Panax Ginseng on Lipid Profile, Pro-oxidant: Antioxidant Status and High-sensitivity C Reactive Protein Levels in Hyperlipidemic Patients in Iran.

BACKGROUND: Because of the conflicting results from previous studies regarding the efficacy of ginseng on lipid profile and anti-inflammatory and anti-proliferative activities of its components, we aimed to evaluate the effects of Panax ginseng on lipid profile, pro-oxidant - anti-oxidant status and high-sensitivity C reactive protein (hs-CRP) levels. METHODS: Forty Iranian hyperlipidemic patients were randomly assigned to placebo (n = 20) or control (n = 20) groups in this double-blind randomized controlled trial. The ginseng or placebo was taken two capsules twice a day for 8 weeks. Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fasting blood glucose, serum creatinine and hs-CRP levels and pro-oxidant - anti-oxidant balance (PAB) were estimated before and after intervention. RESULTS: There were no significant differences between the two groups with respect to changes in serum TG, LDL-C, HDL-C, and TC/HDL-C levels. Nor were there significant differences between the two groups with respect to changes in hs-CRP level and PAB from baseline to week 8. CONCLUSIONS: Our study demonstrates that ginseng does not have significant effects on lipid profile, Hs-CRP level and PAB. Further clinical studies, with a larger sample size, more prolonged period of therapy are needed to investigate the therapeutic effects of ginseng.

Prooxidant-antioxidant balance and cardiac function in patients with cardiovascular disease following cardiac surgery.

BACKGROUND AND AIM OF THE STUDY: Cardiopulmonary bypass (CPB) is used during on-pump coronary artery bypass grafting (CABG) and heart valvular replacement surgery, and is associated with the induction of oxidative stress. The aim of the study was to assess the association between indices of cardiac function and prooxidant-antioxidant balance (PAB) values in patients undergoing valve replacement surgery and on-or off-pump CABG. METHODS: Data were obtained from 44, 33, and 41 patients undergoing off-pump CABG, on-pump CABG, and valve replacement surgery, respectively. The PAB values were measured 24 h before and after the operative procedure, and at the time of discharge. Echocardiography was performed before surgery and before discharge. RESULTS: The changes in E/E', end-diastolic volume, end-systolic volume, left ventricular diastolic and systolic diameter were significantly related to baseline PAB values. In the valve replacement group, neither baseline nor changes in PAB values were associated with echocardiographic measurements. Also, neither off-pump nor on-pump CABG were significantly different in inducing oxidative stress (p = 0.596). When PAB values were measured in CABG patients, there was a significant difference in values between the three time points (p = 0.013). In the valve replacement group, PAB values were not significantly different between the preoperative and postoperative samples. CONCLUSION: The inverse association between the level of oxidative stress and cardiac function measurement may indicate that high levels of oxidative stress may be a predictor of the deterioration of cardiac function in CABG patients. However, in valvular heart disease patients the serum PAB value was not associated with changes in cardiac function. Levels of oxidative stress, as assessed by the PAB assay, were not significantly different for patients undergoing surgery with or without CPB.

Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial.

Dyslipidemia is a leading risk factor for cardiovascular disease and is also a common feature of obesity. Curcumin is a bioactive phytochemical with well-known antioxidant, anti-inflammatory, and cardioprotective properties. The present study investigated the hypolipidemic activity of curcumin in obese individuals. Participants (n = 30) were treated with curcuminoids (1 g/day), or placebo in a randomized, double-blind, placebo-controlled, crossover trial. Serum concentrations of total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, together with anthropometric parameters and high-sensitivity C-reactive protein were measured before and after each treatment period. Anthropometric parameters including weight, BMI, waist circumference, hip circumference, arm circumference, and body fat remained statistically unchanged by the end of trial (p > 0.05). As for the lipid profile parameters, serum triglycerides were significantly reduced following curcumin supplementation (p = 0.009). However, curcuminoids were not found to affect serum levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (p > 0.05). In summary, the findings of the present study indicated that curcuminoid supplementation (1 g/day for 30 days) leads to a significant reduction in serum triglycerides concentrations but do not have a significant influence on other lipid profile parameters as well as body mass index and body fat.

Changes in small dense low-density lipoprotein levels following acute coronary syndrome.

Low-density lipoprotein (LDL), especially small dense LDL (sdLDL), plays a role in atherogenesis. We compared baseline sdLDL levels between healthy controls and patients with acute coronary syndrome (ACS). Blood samples were taken from patients diagnosed with myocardial infarction ([MI] n = 104) and unstable angina ([UA] n = 100). Both sdLDL and high-sensitivity C-reactive protein (hsCRP) levels were determined on admission and in the next 24 hours after the onset of symptoms. Baseline concentration of sdLDL was significantly higher in patients presenting with ACS than controls (P < .05). In the 24 hours following ACS, the sdLDL levels decreased insignificantly in both groups of patients with ACS (P > .05). The changes in sdLDL values were not significantly different between MI and UA participants (P > .05). Patients with ACS have higher concentration of sdLDL compared with the controls.

Changes in anti-heat shock protein 27 antibody and C-reactive protein levels following cardiac surgery and their association with cardiac function in patients with cardiovascular disease.

The relationship between serum anti-heat shock protein (Hsp)27 antibody and high sensitive C-reactive protein (hs-CRP) levels and indices of cardiac function were investigated in patients undergoing coronary artery bypass grafting (CABG) or heart valve replacement. The changes in anti-Hsp27 antibody titers and hs-CRP levels were compared among patients undergoing off-pump and on-pump CABG or valvular heart replacement. Fifty-three patients underwent off-pump, on-pump CABG, and heart valvular replacement in each group. Serum anti-Hsp27 titers and hs-CRP values were measured 24 h before and after the operation and at discharge. Echocardiography was performed before surgery and before discharge. The results were compared with values from 83 healthy controls. hs-CRP levels increased and anti-Hsp27 antibody decreased following surgery (P < 0.001 and P < 0.05, respectively), although these changes were independent of operative procedure (P = 0.361 and P = 0.120, respectively). Anti-Hsp27 antibody levels were higher at the time of discharge (P = 0.016). Only in coronary patients were anti-Hsp27 antibody levels negatively associated with E/E' (r = -0.268, P = 0.022), a marker of pulmonary capillary wedge pressure. In conclusions, anti-Hsp27 antibody levels are associated with indices of cardiac function in coronary patients. Cardiopulmonary bypass had no significant effect on the induction of changes in anti-Hsp27 levels. Moreover, anti-Hsp27 antibody levels fell in all groups postoperatively; this may be due to the formation of immune complexes of antigen-antibody, and antibody levels were higher at the time of discharge.

Prooxidant-antioxidant balance and antioxidized LDL antibody level values and cardiac function in patients with coronary artery disease.

OBJECTIVES: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). METHODS: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. RESULTS: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). CONCLUSION: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.

Anti-heat shock protein 27 titers and oxidative stress levels are elevated in patients with valvular heart disease.

We studied the immune responses to heat shock protein (Hsp)-27 and pro-oxidant-antioxidant balance (PAB) values in patients with valvular heart disease, but free of angiographically evident coronary artery disease (CAD). Patients who were candidates for valvuloplasty surgery and 30 healthy matched controls were recruited. The anti-Hsp-27 antibody titers were 0.35 ± 0.04 absorbency units (AU) in the valvuloplasty group, being significantly higher than for the controls (0.11 ± 0.02 AU; P < .05). The PAB values were significantly higher in cases (134.67 ± 13.69 Hamidi-Koliakos(HK) unit) when compared with controls (49.78 ± 6.75 HK unit; P < .05). In cases, the ejection fraction was inversely correlated with anti-Hsp-27 antibody (P < .05) but was not significantly related to PAB values (P > .05). Based on the echocardiographic findings, the patients had no evident heart failure, but the high levels of anti-Hsp-27 and PAB values in patients with valvular heart disease may indicate that these variables can be used as markers of heart failure. However, a longitudinal study is required to confirm this hypothesis.

Prooxidant-anti-oxidant balance is not associated with extent of coronary artery disease.

OBJECTIVE: We have measured the pro-oxidant-antioxidant-balance (PAB) levels in patients with defined coronary artery disease (CAD) and compared them with concentrations in healthy subjects. DESIGN AND METHODS: Based on angiography results, 400 patients with stable CAD were divided into CAD- and CAD+, this being further subcategorized into groups with single-, double- and triple-vessel disease (VD). RESULTS: The mean PAB values in the healthy subjects, was significantly lower than for other groups (P<0.001). In CAD- patients, PAB levels were 123.2 ± 43.9, which was not statistically different compared to groups with SVD, 2VD and 3VD (P>0.05). In the CAD+ group, PAB values in 1VD, 2VD and 3VD were not significantly different among patients with SVD, 2VD and 3VD (P>0.05). CONCLUSIONS: In conclusion, we found higher levels of oxidative stress in CAD+ patients compared to healthy subjects. The oxidation level was not related to measures of the extent of CAD such as number of stenosed vessels.

Simvastatin therapy reduces prooxidant-antioxidant balance: results of a placebo-controlled cross-over trial.

Oxidative stress is thought to play an important role in atherogenesis. The statin group of cholesterol-lowering drugs have been shown to reduce cardiovascular events and possess antioxidant properties. We aimed to assess the effects of simvastatin on a novel measure of prooxidant-antioxidant balance (PAB) in dyslipidemic patients. The PAB assay can measure the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby giving a redox index. We treated 102 dyslipidemic individuals with simvastatin, or a placebo in a double-blind, cross-over, placebo-controlled trial. PAB values were measured before and after each treatment period. Seventy-seven subjects completed the study. We found that statin therapy was associated with a significant reduction in PAB values (P < 0.001). This effect appeared to be independent of the cholesterol-lowering effects of statins. We conclude that serum PAB values are decreased by simvastatin therapy. Regarding previous reports on the elevation of PAB in conditions associated with oxidative stress, the PAB assay, along with other markers of oxidative stress, may be applied to estimate the extent of oxidative stress in patients, assessment of the antioxidative efficacy of medication such as statins and perhaps also for the identification of those individuals who need antioxidant therapy.

Simvastatin treatment reduces heat shock protein 60, 65, and 70 antibody titers in dyslipidemic patients: A randomized, double-blind, placebo-controlled, cross-over trial.

OBJECTIVE: This study aimed to evaluate the effects of statin therapy on serum levels of antibodies to several specific heat shock proteins (HSPs) in dyslipidemic patients. DESIGN AND METHODS: Participants (n=102) were treated with simvastatin (40mg/day), or placebo in a randomized, double-blind, placebo-controlled, cross-over trial. Anti-HSP60, 65, 70, and hs-CRP levels were measured before and after each treatment period. Seventy-seven subjects completed the study. RESULTS: Treatment with simvastatin was associated with significant reductions in serum anti-HSP60, 65, and 70 titers in the dyslipidemic patients (10%, 14%, and 15% decrease, respectively) (p<0.001). There have been previous reports of reductions in serum CRP with statin treatment, and although median CRP levels were 9% lower on simvastatin treatment, this did not achieve statistical significance. CONCLUSION: While it is unclear whether HSP antibodies are directly involved in atherogenesis, our findings suggest that simvastatin inhibits autoimmune responses that may contribute to the development of cardiovascular disease.