The study of the serum level of IL-4, TGF-ß, IFN-γ, and IL-6 in overweight patients with and without diabetes mellitus and hypertension.

BACKGROUND: Obesity increases the risk of diabetes mellitus (DM) and hypertension. We aimed to analyze the serum levels of cytokines that have relevance to the pathologies including, interleukin-4 (IL-4), transforming growth factor-ß (TGF-ß), interferon-γ (IFN-γ), and IL-6 cytokines of overweight men with DM and/or hypertension. METHODS: The study collected serum from 164 men. The sample population contained, 54 overweight men without DM or hypertension (control [CTL] group), 36 men with both DM and hypertension (DH group), 20 men with DM but no hypertension (D group), and 54 had hypertension without DM (H). RESULTS: The main results showed that the concentration of IFN-γ in the DH group was significantly higher than the D, H, and CTL groups, IL-6 in DH and D groups was significantly lower than the CTL group. The serum level of TGF-ß and IL-4 cytokines did not show any significant differences across the four groups. Serum levels of IL-6 were also significantly lower in untreated patients in D group than controls and in DH when compared with H groups. CONCLUSION: In conclusion, it appears that the proinflammatory and anti-inflammatory cytokines either play a significant role in the pathogenesis of hypertension and DM or serve as markers for these pathologies. Accordingly, increased serum levels of IFN-γ may participate in the pathogenesis of hypertension in the diabetic patients and decreased IL-6 is associated with type 2 DM.

Role of maternal interleukin-8 (IL-8) in normal-term birth in the human.

Cytokines are the main factors involved in the normal functions of the placenta and delivery process. The aim of this project was to compare serum levels of interleukin-8 (IL-8), IL-6, tumour necrosis factor α (TNF-α) and transforming growth factor ß (TGF-ß) in term and prolonged-pregnancy mothers and their neonates. This study was performed on 240 participants including 60 term and prolonged-pregnancy neonates and their corresponding mothers. Serum levels of IL-8, IL-6, TNF-α and TGF-ß were evaluated by the enzyme-linked immunosorbent assay technique. The results revealed that IL-8 serum levels were significantly lower in the prolonged-pregnancy mothers and their neonates when compared with term mothers and their neonates. Data analysis also revealed a negative correlation between TGF-ß and age of prolonged-pregnancy mothers. A poor positive correlation between IL-6 and head circumference of term neonates was also observed. IL-8 may play crucial roles in the process of on-time delivery and age may significantly affect TGF-ß production in prolonged-pregnancy mothers. Pro-inflammatory cytokines, such as IL-6, can also be considered as main factors involved in fetal growth.

Comparison of serum levels of IL-6, IL-8, TGF-ß and TNF-α in coronary artery diseases, stable angina and participants with normal coronary artery.

Cytokines, which typically regulate the immune responses, play a role in cardiovascular diseases such as coronary artery diseases (CAD) and ischemic heart diseases (IHD). The aims of this study were to evaluate serum levels of IL-6, IL-8, TGF-ß and TNF-α in patients with or without CAD, as well as stable angina, and to assess the effects of drug administration on the serum levels of these cytokines. Serum levels of the cytokines were analyzed in the three groups: patients with acute coronary syndrome, stable angina and participants with normal coronary arteries as controls. Cohort study of the patients showed that Nitrocontin was the only drug used in a significantly different pattern between the groups where it was used less frequently in patients with stable angina compared to the acute coronary syndrome or control groups. Serum levels of the evaluated cytokines were not different neither between the studied groups nor between the groups with variable Gensini scores. However, IL-8 in controls that were not engaged in regular exercise was higher than the controls performing regular exercise. In the stable angina group, TNF-α in non-smokers was higher than the smokers. It was revealed that serum levels of pro-inflammatory cytokines are not associated with atherosclerosis and stable angina in patients from the South-East of Iran. However, suppressed expression of TGF-ß, may increase the risk of CAD. Exercise can reduce the risk of CAD through downregulation of pro-inflammatory cytokines.

Vitamin B12 in Association with Antipsychotic Drugs Can Modulate the Expression of Pro-/Anti-Inflammatory Cytokines in Alzheimer Disease Patients.

INTRODUCTION: Patients with Alzheimer disease (AD) suffer from psychotic symptoms including pain. The current antipsychotic drugs confer limited effectiveness, and hence new strategies are being designed to decrease pain in order to increase antipsychological effectiveness. Vitamin B12 is a safe supplementary drug to decrease pain. Additionally, cytokines participate in the pathogenesis of immune-related diseases such as AD. Thus, the main aim of this clinical trial study was to determine the effects of treatment with risperidone and quetiapine, as antipsychotic drugs, with and without vitamin B12 on the psychotic symptoms of AD patients and the expression of IL-6, IL-8, tumor growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, and endothelin (ET)-1). MATERIAL AND METHODS: Serum levels of IL-6, IL-8, TGF-ß, TNF-α, and ET-1 were evaluated in the following groups: healthy controls, nonpsychotic AD patients, psychotic AD patients, psychotic AD patients under treatment with risperidone, psychotic AD patients under treatment with risperidone plus vitamin B12, psychotic AD patients under treatment with quetiapine, and psychotic AD patients under treatment with quetiapine plus vitamin B12. RESULTS: Treatment with antipsychotic drugs plus vitamin B12 led to a decreased expression of IL-8 and TNF-α and an increased expression of TGF-ß. Vitamin B12 in association with quetiapine reduced the pain in psychotic AD patients. DISCUSSION: Proinflammatory cytokines play important roles in the pathogenesis of psychosis in AD patients. Antipsychotic drugs plus vitamin B12 can reduce and induce the expression of proinflammatory and anti-inflammatory cytokines to improve psychotic symptoms in AD patients.

Comparison of polymerization shrinkage of a new bulk-fill flowable composite with other composites: An in vitro study.

OBJECTIVE: Since composites still face a critical problem called polymerization shrinkage and bulk-fill composites have reported acceptable results for this issue, this study aims to assess the polymerization shrinkage of a new bulk-fill flowable composite (G-aenial bulk injectable [GBI]) and compare it to other bulk-fill and conventional composites. MATERIALS AND METHODS: In this in vitro study, 25 composite discs were fabricated using three bulk-fill and two conventional composites. They were bonded to a microscopic slide and were covered by a coverslip. This assembly was transferred to a linear variable differential transformer and composite samples were cured from underneath the slides. Dimensional changes formed in composite samples were recorded. Data were analyzed using analysis of variance followed by post hoc Tukey's and Dunnett's tests. RESULTS: The groups were significantly different regarding polymerization shrinkage. G-aenial bulk injectable and G-aenial universal flo showed significantly higher polymerization shrinkage than other composites at 30, 60, and 1800 s after light irradiation, while X-tra fil and Filtek Z250 showed the lowest polymerization shrinkage at the aforementioned time points. CONCLUSION: According to the results, the new composite had polymerization shrinkage similar to the conventional one. Bulk-fill composites reported similar or lower shrinkage to conventional composites.

Opium consumption and coronary atherosclerosis in diabetic patients: a propensity score-matched study.

There is a traditional belief among Eastern people that opium may have ameliorating effects on cardiovascular risk factors, especially diabetes; thus, it is widely used among diabetic patients. We attempted to investigate the association of opium consumption with coronary artery disease (CAD) in diabetic patients. A cross-sectional study was conducted on diabetic patients undergoing coronary angiography in our center. Out of 1925 diabetic patients included in the study, 228 were opium users, and the remaining 1697 non-opium users were used as a pool of potential comparators. Propensity scores were used to match the 228 opium consumers with 228 matched comparators for age, sex, and smoking status. The Gensini score and extent score were respectively used to assess the angiographic severity and extent of CAD. The mean Gensini score (86.9 ± 62.7 vs. 59.6 ± 43.4, p < 0.0001) and extent score (7.1 ± 2.9 vs. 5.9 ± 2.9, p < 0.0001) were significantly higher in opium user diabetic patients than in non-opium users. After adjustment for potential confounders, a dose-response relationship was observed between dose of opium and the Gensini score ( ß = 0.27, p = 0.04). There were no significant differences between the routes of opium administration (inhalation vs. oral) regarding the severity and extent of CAD. In conclusion, exposure to opium in diabetic patients may be positively associated with the risk of CAD, and with the angiographically determined severity and extent of the disease. Furthermore, dosage of opium consumption may correlate with severity of CAD.

DMFT of the First Permanent Molars, dmft and Related Factors among All First-Grade Primary School Students in Rafsanjan Urban Area.

STATEMENT OF THE PROBLEM: Dental caries is the most common chronic childhood disorders throughout the world. The dmft (decayed, missing, and filled primary teeth) and DMFT (decayed, missing, and filled permanent teeth) are some of the most important epidemiological indices in dentistry. Evaluation of these two indicators in the population can help in future planning of healthcare programs to improve oral health status. PURPOSE: The aim of this study was to evaluate these indicators and the related factors in first-grade primary school students in Rafsanjan urban area to determine their present status, which might be helpful for future health care planning. MATERIALS AND METHOD: In this cross-sectional study, DMFT index of first permanent molar and dmft were evaluated by census method on 2031 first-grade primary school students in Rafsanjan urban area in 2018 (May-June). Dental examination was done using a mirror and probe under natural light according to World Health Organization criteria. The data were then analyzed using independent two-sample t-test, one-way ANOVA, Tukey's multiple comparisons test, Kolmogorov-Smirnov nonparametric test and Leven's test in SPSS version 21 software. RESULTS: The mean and standard deviation of dmft index and DMFT index of first permanent molar were 6.37 ± 3.40 and 0.30 ± 0.72, respectively. The proportion of caries free students was 4.1%. A significant association was found between the values of these indices and school type, the level of education of parents, parental occupation, family size, and frequency of brushing and the use of floss (p < 0.05). However, there was no significant association between these two indices with gender (p= 0.347 and p= 0.593, respectively). CONCLUSION: The results of this study showed high prevalence of caries in first-grade primary school students in Rafsanjan. Therefore, to improve this situation, more attention is needed for proper oral health program planning and education of families concerning oral hygiene and dental preventive measures.

Predictors of One-Year Retention in Methadone Maintenance Treatment (MMT) in Iran, Rafsanjan.

BACKGROUND: Retention in treatment is a key factor to the success of methadone maintenance treatment (MMT) and considered an important measure in evaluation of treatment effectiveness. OBJECTIVES: This study aimed to investigate the retention rate and predictors of retention in MMT in Rafsanjan. PATIENTS AND METHODS: This was a historical cohort study. A total of 1396 patients admitted between March 2011 and March 2012 in 16 MMT clinics (13 private and 3 state clinics) in Rafsanjan, entered the study and their retention rate was examined for one year. The patients' data abstracted from their medical records using checklists and collected by clinics' staff. Data analyses were performed using SPSS 15.0 and SAS 9.1. Kaplan-Meier method and Cox proportional hazards model were used to determine the retention rate and identify predictors of retention, respectively. RESULTS: The mean age of 1396 patients was 37.65 ± 10.77 years and most patients were men (93.8%). The mean and median of retention duration were 193.22 ± 3.83 and 153 ± 9.54 days, respectively. Three-month and one-year retention rates were 66.0% and 34.4%, respectively. Predictor variables of one-year retention in Cox proportional hazards model were high methadone dosage, polysubstance abuse and treatment under state clinics. CONCLUSIONS: In this study, retention rate was lower compared to previous studies from other countries. The results suggested that program related factors are better predictors of retention than individual related ones.

Opium addiction as an independent risk factor for coronary microvascular dysfunction: A case-control study of 250 consecutive patients with slow-flow angina.

BACKGROUND: Approximately 20% to 30% of patients who undergo coronary angiography for assessment of typical cardiac chest pain display microvascular coronary dysfunction (MCD). This study aimed to determine potential relationships between baseline clinical characteristics and likelihood of MCD diagnosis in a large group of patients with stable angina symptoms, positive exercise test and angiographic ally normal epicardial coronary arteries. MATERIAL AND METHODS: This cross-sectional study included 250 Iranian with documented evidence of cardiac ischemia on exercise testing, class I or II indication for coronary angiography, and either: (1) angiographically normal coronary arteries and diagnosis of MCD with slow-flow phenomenon, or (2) normal angiogram and no evidence of MCD. All patients completed a questionnaire designed to capture key data including clinical demographics, past medical history, and social factors. Data was evaluated using single and multivariable logistic regression models to identify potential individual patient factors that might help to predict a diagnosis of MCD. RESULTS: 125 (11.2% of total) patients were subsequently diagnosed with MCD. 125 consecutive control subjects were selected for comparison. The mean age was similar among the two groups (52.38 vs. 53.26%, p=ns), but there was a higher proportion of men in the study group compared to control (42.4 vs. 27.2%, p=0.012). No significant relationships were observed between traditional cardiovascular risk factors (diabetes, hypertension, and dyslipidemia) or body mass index (BMI), and likelihood of MCD diagnosis. However, opium addiction was found to be an independent predictor of MCD on single and multivariable logistic regression model (OR=3.575, 95%CI: 1.418-9.016; p=0.0069). CONCLUSIONS: We observed a significant relationship between opium addiction and microvascular angina. This novel finding provides a potential mechanistic insight into the pathogenesis of MCD with slow-flow phenomenon.

The Association Between C424c/A Polymorphism Within the IL-25 Gene and Multiple Sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a common autoimmune system disease which affects the central nervous system. It has been documented that interleukin-25 (IL-25) plays key roles in suppressing Th1 responses, which is increased during MS. OBJECTIVES: The aim of this study was to investigate the c424C/A polymorphism within the IL-25 gene in MS patients in comparison to healthy controls. PATIENTS AND METHODS: In this case-control study, 74 patients with MS and 75 healthy controls were selected. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used in order to determine c424C/A polymorphism within the IL-25 gene. RESULTS: The results showed that there was no statistical significant difference in distribution of genotype (AA, AC and CC) and allele (A and C) frequencies between MS patients and healthy controls (P = 0.901 and P = 0.728, respectively). CONCLUSIONS: In conclusion, it appears that the c424C/A polymorphism within the IL-25 gene has no significant relationship with MS, and this polymorphism is probably not associated with MS complications, its onset and gender distribution.

Atorvastatin, Losartan and Captopril Lead to Upregulation of TGF-ß, and Downregulation of IL-6 in Coronary Artery Disease and Hypertension.

INTRODUCTION: Coronary artery disease (CAD) and hypertension are the main reasons of ischemic heart diseases (IHDs). Cytokines as the small glycoproteins are the main arm of immune system and manipulate all of the cardiovascular diseases. The aim of the current study was to examine the effects of treatment of hypertension and CAD on serum levels of IL-6, IL-8, TGF-ß and TNF-α. MATERIAL AND METHODS: This interventional study was performed on the patients with hypertension without CAD (group 1), hypertension and CAD (group 2), CAD but not hypertension (group 3) and without hypertension and CAD as controls (group 4). The patients received routine treatment for hypertension and CAD. Serum levels of IL-6, IL-8, TGF-ß and TNF-α were analyzed in the groups treated with various drugs, using ELISA technique. RESULTS: With regard to the medications, Atorvastatin, Losartan and Captopril were administered more in patients (groups 1, 2 and 3) than the patients without hypertension and CAD. The results revealed that serum levels of TGF-ß and IL-6 were significantly increased and decreased, respectively, in the groups 1, 2 and 3 when compared to group 4. Serum levels of TGF-ß were also increased in females in comparison to males in the group 4. DISCUSSION: According to the results it seems that Atorvastatin, Losartan and Captopril have reduced inflammation in in vivo conditions via downregulation of IL-6 and upregulation of TGF-ß.

Comparing clinical outcomes for a twelve-month trial of zotarolimus- and everolimus-eluting stents in patients with coronary artery disease: data from the THCRIC registry.

OBJECTIVES: New-generation coronary stents including zotarolimus- and everolimus-eluting stents (ZES and EES) have been shown to decrease the risk of restenosis. The purpose of this study was to compare the safety and efficacy of ZES and EES over a 12-month clinical follow up, in routine clinical practice. METHODS: This is an observational study in which 1029 consecutive patients treated with ZES (n = 669) or EES (n = 360) were enrolled. The study endpoint was major adverse cardiac events (MACE), defined as cardiac death, nonfatal myocardial infarction (MI), and target lesion or vessel revascularization at 12 months. RESULTS: Follow up was completed among 94.9% of the patients. The overall MACE occurred in 4 (0.6%) and 7 (2.0%) patients in the ZES and EES group, respectively. The occurrence of other cardiac events including nonfatal MI and target vessel or lesion revascularization was 1 (0.2%) versus 1 (0.3%) and 7 (1.1%) versus 5 (1.4%), respectively, in the ZES and EES groups of patients. Despite a slightly lower rate of MACE and cardiac death in the ZES group, the difference between these two groups was not significant (n = 0.064 for overall MACE, p = 0.129 for cardiac mortality, n = 0.999 for nonfatal MI, n = 0.468 for target vessel and n = 0.999 for target lesion revascularization). CONCLUSIONS: According to our results, it could be concluded that the difference in the rate of MACE between the ZES and EES groups was not statistically significant at 12-month follow up.

Comparison of cardiovascular risk factors and biochemical profile in patients with cardiac syndrome X and obstructive coronary artery disease: A propensity score-matched study.

BACKGROUND: This study was designed to compare the frequency of conventional cardiovascular disease risk factors and clinical biochemistry profile in patients with cardiac syndrome X (CSX) and obstructive coronary artery disease (CAD). METHODS: A cross-sectional study was conducted on patients with typical angina and positive exercise tolerance test undergoing coronary angiography in our center. 342 consecutive patients with CSX were enrolled into this study and were matched regarding age and sex with 342 patients with acute coronary syndrome (ACS) and also 342 patients with chronic stable angina (SA). Cardiovascular risk factors as well as biochemistry profile of the patients were recorded. RESULTS: Mean age of the studied patients was 53.0 years and 41.5% were male. There was no significant difference between the CSX patients and CAD patients regarding body mass index (BMI). Frequency of diabetes mellitus, hyperlipidemia, smoking, family history of premature CAD and hypertension was significantly lower in patients with CSX than ACS and SA patients. Patients with CSX had significantly higher levels of high-density lipoprotein cholesterol (HDL-cholesterol) than comparators while the levels of low-density lipoprotein cholesterol (LDL-cholesterol), total cholesterol, triglyceride and fasting blood sugar (FBS) were significantly lower in patients with CSX than CAD patients. CONCLUSION: The present study demonstrated that CSX patients had substantially lower frequency of all conventional CVD risk factors than patients with obstructive CAD. This might aid in developing novel scoring systems or appropriateness criteria for angiographic evaluation of patients with typical angina and positive exercise test in order to reduce the rate of negative results.

Impact of Angiotensin-converting enzyme inhibitors and Angiotensin receptor blockers on mortality of coronary artery bypass grafting.

BACKGROUND: There is controversy over the potential benefits/harms of the usage of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) as regards the postoperative mortality of coronary artery bypass grafting (CABG). This study investigates the correlation between the in-hospital mortality of CABG and the preoperative administration of ACEI/ARB. METHODS: Out of 10055 consecutive patients with isolated CABG from 2006 to 2009, 4664 (46.38%) patients received preoperative ACEI/ARB. Data were gathered from the Cardiac Surgery Registry of Tehran Heart Center. In-hospital mortality was defined as death within the same admission for surgery. Adjusted for confounders, multivariable logistic regression models were used to evaluate the impact of preoperative ACEI/ARB therapy on in-hospital death. RESULTS: The mean age of the patients was 60.04 ± 9.51 years and 7364 (73.23%) were male. Eighty-seven (0.86%) patients expired within 30 days. Multivariate analysis revealed that the administration of ACEI/ARB significantly protected against in-hospital deaths inasmuch as there were 33 (0.70%) vs. 54 (1.0%) deaths in the ACEI/ARB positive and negative groups, respectively (OR: 0.628; p value = 0.09). Patients without ACEI/ARB were more likely to have a higher global ejection fraction. CONCLUSION: Preoperative ACEI usage in patients undergoing CABG can be associated with decreased in-hospital mortality. Large-scale randomized clinical trials are suggested.

Discharge against Medical Advice among Inpatients with Heart Disease in Iran.

BACKGROUND: Discharge against medical advice (DAMA) is a relatively common problem worldwide. We sought to determine the prevalence of and reasons for DAMA among inpatients of our cardiac center. METHODS: From a total of 20289 discharges from our cardiac teaching hospital, 992 (4.9%) patients at a minimum age of 18 years were cases of DAMA. After excluding 49 cases due to missing data, we retrospectively analyzed our prospectively collected data from 943 patients, who were DAMA cases. Patients' characteristics, including demographic details, reason for discharge, insurance status, and length of stay before discharge, were examined. RESULTS: The mean age of the study patients was 60.7 ± 13.0 (range, 18-94 years) with a male-to-female ratio of 2.1/1. Lack of consent to surgery or other invasive procedures was the reason cited for DAMA in 31% of the patients, followed by personal or family issues (17%). No reason for DAMA was reported in 26 (2.8%) of the patients. Women compared to men were more likely to cite "lack of consent to surgery or invasive procedures" as the reason for DAMA (p value = 0.005), whereas men more prevalently stated "personal or family issues" as the reason for DAMA (18.7% vs. 12.7%, p value = 0.022). CONCLUSION: The most frequent self-reported reason for DAMA in our cardiac patients was lack of consent to surgery or invasive procedures. This may be because of fear of undergoing invasive procedures such as revascularization. Explaining the stages of a given invasive procedure to patients and comparing its risks versus benefits may lessen impulsive decision-making and DAMA.

A New Method for Extubation: Comparison between Conventional and New Methods.

BACKGROUND: Extubation is associated with the risk of complications such as accumulated secretion above the endotracheal tube cuff, eventual atelectasia following a reduction in pulmonary volumes because of a lack of physiological positive end expiratory pressure, and intra-tracheal suction. In order to reduce these complications, and, based on basic physiological principles, a new practical extubation method is presented in this article. METHODS: The study was designed as a six-month prospective cross-sectional clinical trial. Two hundred fifty-seven patients undergoing coronary artery bypass grafting (CABG) were divided into two groups based on their scheduled surgery time. The first group underwent the conventional extubation method, while the other group was extubated according to a new described method. Arterial blood gas (ABG) analysis results before and after extubation were compared between the two groups to find the effect of the extubation method on the ABG parameters and the oxygenation profile. RESULTS: In all time intervals, the partial pressure of oxygen in arterial blood / fraction of inspired oxygen (PaO(2)/FiO(2)) ratio in the new method group patients was improved compared to that in the conventional method; some differences, like PaO(2)/FiO(2) four hours after extubation, were statistically significant, however (p value=0.0063). CONCLUSION: The new extubation method improved some respiratory parameters and thus attenuated oxygenation complications and amplified oxygenation after extubation.

Glomerular filtration rate is related to severity of obstructive coronary artery disease in patients undergoing coronary angiography.

PURPOSE: Chronic kidney disease is independently associated with an increased risk of cardiovascular events; however, the relationship between the glomerular filtration rate (GFR) and coronary artery disease (CAD) in patients undergoing coronary angiography has yet to be fully elucidated. METHODS: This retrospective study enrolled a total of 7968 patients who underwent diagnostic coronary artery catheterization [mean age = 54.8 ± 10.6 years, 74.4% males] and did not have any previous history of coronary revascularization, diabetes mellitus, hypertension, end-stage renal disease treated by dialysis or renal transplantation, and were not taking diuretics or drugs acting on renin angiotensin system. The severity of CAD was defined as the number of coronary arteries with a luminal stenosis ≥50% on the angiogram, and the GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). RESULTS: There were 2133 (26.8%) patients with GFR ≥ 90 ml/min/1.73 m(2), 4574 (57.4%) patients with 60 ≤ GFR < 90 ml/min/1.73 m(2), 1073 (13.5%) with 45 ≤ GFR < 60 ml/min/1.73 m(2) and 181 (2.3%) with 15 < GFR < 45 ml/min/1.73 m(2). After adjustment for traditional cardiovascular risk factors (age, sex, dyslipidemia, low to high-density lipoprotein ratio, smoking status, and family history), the GFR showed a significant association with the severity of CAD and remained a significant predictor of CAD (Odds Ratio raised from 1.1 in patients with 60 ≤ GFR < 90 ml/min/1.73 m(2) to 1.8 in patients with 15 < GFR < 45 ml/min/1.73 m(2)). CONCLUSIONS: A reduced kidney function, even mildly, is significantly associated with CAD severity, independently of other traditional CAD risk factors.