Risk for cardiovascular disease development in rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis have significant cardiovascular mortality and morbidity. OBJECTIVE: To investigate the effects of chronic inflammation in rheumatoid arthritis on cardiovascular morbidity association with cardiovascular risk factors risk factors. Mortality report is secondary just to show trends without sufficient statistical power as it is accidental endpoint. METHODS: A total of 201 individuals without previous cardiovascular disease, 124 with rheumatoid arthritis (investigation group) and 77 with osteoarthritis (control group), were included in the study and followed up for an average of 8 years to assess the development of fatal or non-fatal cardiovascular diseases. The incidence and prevalence of cardiovascular risk factors were also investigated. RESULTS: The total incidence of one or more fatal or nonfatal cardiovascular events was 43.9% in the investigation group and 37.5% in the control group. Of these patients, 31.7% and 30.9% survived cardiovascular events in the investigation and control groups, respectively. The most common cardiovascular disease among participants who completed the study and those who died during the study was chronic heart failure. The results of the subgroup analysis showed that strict inflammation control plays a central role in lowering cardiovascular risk. CONCLUSION: A multidisciplinary approach to these patients is of paramount importance, especially with the cooperation of immunologists and cardiologists for early detection, prevention, and management of cardiovascular risks and diseases.

The Influence of Rheumatoid Arthritis and Osteoarthritis on the Occurrence of Arterial Hypertension: An 8-Year Prospective Clinical Observational Cohort Study.

Rheumatoid arthritis (RA) increases the risk of cardiovascular mortality and morbidity, including a 50-60% increased risk of cardiovascular disease (CVD). Arterial hypertension (HT) is considered the major contributing risk factor for CVD development in RA patients. In this investigation, we compared the incidence and prevalence of HT between RA and osteoarthritis (OA) and the influence of HT on CVD development in CVD-naive patients in both groups. This was a prospective clinical cohort investigation with an 8-year follow-up period. A total of 201 participants, 124 with RA (investigation group) and 77 with OA (control group), without diagnosed CVD or symptomatic heart failure were included. After selection according to inclusion and exclusion criteria, both groups underwent initial and final visits, and the investigation group underwent annual visits to assess disease activity. Case report forms were completed for each visit. The obtained data were analyzed by a statistician. No difference in the incidence or prevalence of HT was found between the investigation and control groups. No difference in the prevalence of HT was reported between the study groups and age-standardized data from the general population. The investigation group had a higher incidence of CVD than the control group. RA participants with long-term remission had a marginally lower HT prevalence. Although previous studies reported a higher HT prevalence in RA than in OA and the general population, our findings did not support this. The RA group had a higher incidence of CVD, but it is possible that optimal disease control with long-term remission could reduce HT incidence and prevalence while also having beneficial effects on other cardiovascular risk factors (CV) and, consequently, CVD occurrence.

Immunomodulatory Effects of SGLT2 Inhibitors-Targeting Inflammation and Oxidative Stress in Aging.

Given that the increase in the aging population has grown into one of the largest public health issues, inflammation and oxidative stress, which are closely associated with the aging process, became a focus of recent research. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, a group of drugs initially developed as oral antidiabetics, have shown many beneficial effects over time, including improvement in renal function and cardioprotective effects. It has been shown that SGLT2 inhibitors, as a drug class, have an immunomodulatory and antioxidative effect, affecting endothelial function as well as metabolic parameters. Therefore, it is not surprising that various studies have investigated the potential mechanisms of action of SGLT2 inhibitors in age-related diseases. The proposed mechanisms by which SGLT2 inhibitors can achieve their anti-inflammatory effects include influence on AMPK/SIRT1/PGC-1α signaling, various cytokines, and the NLRP3 inflammasome. The antioxidative effect is related to their action on mitochondria and their influence on the signaling pathways of transforming growth factor ß and nuclear erythroid 2-related factor 2/antioxidant response element. Also, SGLT2 inhibitors achieve their anti-inflammatory and antioxidative effects by affecting metabolic parameters, such as uric acid reduction, stimulation of ketogenesis, reduction of body weight, lipolysis, and epicardial fat tissue. Finally, SGLT2 inhibitors display anti-atherosclerotic effects that modulate inflammatory reactions, potentially resulting in improvement in endothelial function. This narrative review offers a complete and comprehensive overview of the possible pathophysiologic mechanisms of the SGLT2 inhibitors involved in the aging process and development of age-related disease. However, in order to use SGLT2 inhibitor drugs as an anti-aging therapy, further basic and clinical research is needed to elucidate the potential effects and complex mechanisms they have on inflammation processes.

Role of Inflammatory Cytokines in Rheumatoid Arthritis and Development of Atherosclerosis: A Review.

Uncontrolled chronic inflammation results in cardiovascular disease and early death. In this review, we studied the impact of rheumatoid arthritis on the cardiovascular system, including the early and accelerated development of atherosclerosis and its clinical manifestations, focusing on the inflammatory mechanisms leading to arterial wall damage, rapid atherosclerotic plaque formation, and thrombosis. Furthermore, the effect of medications used to treat rheumatoid arthritis on the cardiovascular system was studied. The effect of chronic inflammation and medication on traditional cardiovascular risk factors is not the main subject of this review. We observed that uncontrolled chronic inflammation and some medications directly impact all the stages of atherosclerosis. In conclusion, reducing inflammation and maintaining long-term remission in rheumatoid arthritis may prevent early atherosclerosis. We believe that this review will encourage a better interdisciplinary approach to the management of these patients and further research in this field.

The Association of Severe Coronary Tortuosity and Non-Obstructive Coronary Artery Disease.

Background and Objectives: There is an increasing interest in the coronary tortuosity as a novel pathophysiological mechanism of ischemia in coronary artery disease without significant obstruction, but there are a lack of studies to confirm this relationship in the clinical setting. The aim of our study was to evaluate the association of severe coronary tortuosity and the potential role of coronary blood supply dominance in the appearance of myocardial ischemia in patients with non-obstructive coronary artery disease (non-CAD), compared to patients with obstructive coronary artery disease (CAD). Materials and Methods: The study enrolled 131 participants (71 male and 60 female), recruited among patients referred to cardiologists due to angina symptoms with ischemic alterations established by cardiac stress tests, as well as those admitted to the hospital for acute coronary syndrome. Results: Mean age of recruited patients was 61.6 (±10.1) years. According to the coronary angiography, they were divided into two groups: non-obstructive and obstructive CAD (77 and 54, respectively). There were significantly more women (61% vs. 24%, p < 0.001) in the non-CAD group. Both tortuous coronary arteries (50.6% vs. 14.8%, p < 0.001) and left coronary dominance (37.7% vs. 16.7%, p = 0.006) were more frequent in the non-CAD group compared to the CAD group. Female sex (OR = 17.516, p = 0.001), tortuous coronary arteries (OR = 7.962, p = 0.006) and left dominance of blood supply were significant predictors for non-CAD. Conclusions: Non-obstructive CAD is common among patients, especially women, who are referred for coronary angiography. Severe coronary artery tortuosity is the strongest independent predictor of non-obstructive CAD, followed by female gender and left coronary dominance.

Coronary Tortuosity Index vs. Angle Measurement Method for the Quantification of the Tortuosity of Coronary Arteries in Non-Obstructive Coronary Disease.

Coronary tortuosity has been recognized as a potential pathophysiological mechanism in the development of non-obstructive coronary artery disease (CAD). The aim of this study was to examine the role of two coronary tortuosity measurement methods in the detection of clinically significant coronary tortuosity. The study included 160 patients with angina symptoms and myocardial ischemia detected by cardiac stress tests in chronic settings and those diagnosed with acute coronary syndrome. After coronary angiography, tortuosity of coronary arteries was assessed by two methods, including measurement of tortuosity angles and calculating of tortuosity index. Significantly more tortuous coronary arteries were detected in the group with non-obstructive CAD (p < 0.01 for all three arteries), with significantly higher tortuosity index (TI) for all three coronary arteries in this group of patients, compared to patients with obstructive CAD. The highest TI for LCX was found in patients with lateral ischemia (p < 0.001) and for LAD in patients with anterior ischemia (p < 0.001). When measured by the angle method, the only association was found between LCX tortuosity and lateral ischemia (OR 4.9, p = 0.046). In conclusion, coronary tortuosity represents a pathophysiological mechanism for myocardial ischemia in non-obstructive CAD. The coronary tortuosity index could be a reliable and widely applicable tool for the quantification of coronary tortuosity.

Plasma advanced oxidation products as an additional tool in assessment of post-infarction heart failure.

OBJECTIVE: To define which oxidative stress markers could be used as diagnostic tools in the assessment of post-infarction heart failure (HF). METHODS: This observational study enrolled patients with HF that were divided into three subgroups (ejection fraction [EF] ≥ 50%; EF 40-49%; EF < 40%) and age- and sex-matched healthy control subjects. The plasma concentrations of advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances, catalase activity and free thiols were determined in all participants. RESULTS: The study enrolled 81 patients with HF and 68 healthy control subjects. There were significant differences in the values ​​of oxidative stress markers between patients and controls. Oxidative stress parameters did not differ between the subgroups of patients, except for AOPP, which was significantly higher in the EF < 40% group. Univariate and multivariate logistic regression analyses showed an association between AOPP and HF in the EF ≥ 50% group, while receiver operating characteristic (ROC) curve analysis identified a cut-off value of 60.89 µmol/l for AOPP. CONCLUSIONS: Based on the ROC curve analysis of AOPP and the higher significance in the multivariate analyses for patients with EF ≥ 50%, these current results suggest that AOPP could be a useful additional tool in the assessment of post-infarction HF.

The hepatoprotective effect of aminoguanidine in acute liver injury caused by CCl4 in rats.

In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl4 at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl4, at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H2O2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl4. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1ß, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl4 alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl4 group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl4. The hepatoprotective mechanisms in CCl4 induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis.

The influence of type 2 diabetes mellitus on the frequency and complexity of ventricular arrhythmias and heart rate variability in patients after myocardial infarction.

Background/Aim: After myocardial infarction arrhythmic cardiac deaths are significantly more frequent compared to non-arrhythmic ones. The aim of the study was to investigate the influence of type 2 diabetes mellitus (T2DM) on the frequency and complexity of ventricular arrhythmias after myocardial infarction. Methods: The study included 293 patients, mean age 59.5 ± 9.21 years, who were at least six months after acute myocardial infarction with the sinus rhythm, without atrioventricular blocks and branch blocks. In the clinical group 95 (32.42%) patients were with T2DM, while 198 (67.57%) patients were without diabetes. All of the patients were subjected to the following procedures: standard ECG according to which the corrected QT dispersion (QTdc) was calculated, exercise stress test, and 24-hour holter monitoring according to which, the four parameters of time domain of heart rate variability (HRV) were analyzed: standard deviation of all normal RR intervals during 24 hours (SDNN), standard deviation of the averages of normal RR intervals in all five-minute segments during 24 hours (SDANN), the square root of the mean of the sum of the squares of differences between adjacent normal (RMS-SD), and percentage of consequtive RR intervals which differed for more than 50 ms during 24 hours (NN > 50 ms). Results: In patients after myocardial infarction, patients with T2DM had significantly higher percentage of frequent and complex ventricular arrhythmias compared to the patients without diabetes (p < 0.001). The patients with T2DM had significantly higher percentage of residual ischemia (p < 0.001), and arterial hypertension (p < 0.001), compared to patients without diabetes. The patients with T2DM had significantly lower values of HRV parameters: SDNN (p < 0.001); SDANN (p < 0.001); RMS-SD (p < 0.001), and NN > 50 ms (p < 0.001), and significantly higher values of QTdc (p < 0.001) compared to the patients without diabetes. Conclusion: The study showed that type 2 diabetes mellitus has significant influence on ventricular arrhythmias, HRV parameters and QT dispersion in patients after myocardial infarction.

Relation between major and minor depression and heart rate, heart-rate variability, and clinical characteristics of patients with acute coronary syndrome.

This study examined the prevalence of major and minor depression in patients with acute coronary syndrome and their relation with heart rate and heart-rate variability, and clinical characteristics. The study group included 297 patients, 200 men and 97 women, between ages of 21 and 70 years (M age = 57.5 +/- 9.6), who were admitted to a coronary care unit with acute coronary syndrome and survived to discharge from the hospital. Major and minor depression were diagnosed using DSM-IV. There were 44.1% patients with acute coronary syndrome without depression, 29.3% with minor depression, and 26.6% with major depression. The prevalence of minor and major depression was more elevated in patients with non-ST-segment elevation myocardial infarction and unstable angina than in patients with ST-segment elevation myocardial infarction. Ventricular fibrillation and atrial fibrillation were more common in patients with major and minor depression than in patients without depression. The 24-hr. duration of heart-beat intervals and heart-rate variability were significantly lower in patients with major and minor depression than in patients without depression. This study implies that clinical depression was significantly comorbid with the acute coronary syndrome and was related to hypertension, diabetes mellitus, age, sex, type of acute coronary syndrome, left ventricular failure, higher heart rate, and lower heart-rate variability.