Benefits of hybrid methods (PET/CT, PET MRI) in the diagnosis of abdominal aortic pathology.

INTRODUCTION: Ultrasound and CT angiography are common diagnostic methods of abdominal aortic pathologies. In the last decade, hybrid methods (PET/CT, PET/MRI) have become more common in this diagnostic algorithm. Originally they were indicated in malignancies or inflammatory processes. Currently, efforts are developed to visualize possible local inflammatory activity in the aortic wall and thus to assess a certain “disease activity” with the goal to anticipate further development of aortic pathology. The aim of our study was to analyze potential benefits of hybrid methods in predicting abdominal aortic pathology progression. METHODS: In this prospective, open-label, observational study we examined 75 patients referred to PET/CT (N=61) or PET/MRI (N=14) due to any aortic pathology in 2015-2017. The patients included those with abdominal aortic aneurysm (AAA) (N=48; 64%), aortitis (N=5; 6.7%), aortic dissection (N=4; 5.3%), patients undergoing EVAR (N=6; 8%), patients with excessive atherosclerosis (N=7; 9.3%), patients with concomitant AAA and retroperitoneal fibrosis (N=4; 5.3%) and patient with an intramural hematoma (N=1; 1.3%). The minimum follow-up period was 6 months (0.5-2.5 years). Clinical symptoms, aortic diameter, growth rate and CRP levels were analyzed during the follow-up and correlation with PET/CT or PET/MRI findings was evaluated. RESULTS: Increased metabolic activity in the aorta was found in 25 of the 75 examined patients (33.3%). Based on statistical analysis there were no associations between increased activity based on PET/CT or PET/MRI in the aortic wall and disease symptoms or progression. CONCLUSION: Our results provide no evidence that hybrid methods can predict further development of pathological findings in the abdominal aorta. PET/CT- or PET/MRI-based activity did not correlate with disease symptoms, AAA progression rate or dissection, either. Our results are also supported by some recent literature data.

Plasma vitamin D levels and inflammation in the aortic wall of patients with coronary artery disease with and without inflammatory rheumatic disease.

OBJECTIVES: Vitamin D modulates inflammation, and this may explain the observed associations between vitamin D status and disorders driven by systemic inflammation, such as coronary artery disease (CAD) and inflammatory rheumatic diseases (IRDs). The aims of this study were to assess vitamin D status in patients with CAD alone and in patients with CAD and IRD, and to explore potential associations between vitamin D status and the presence of mononuclear cell infiltrates (MCIs) in the aortic adventitia of these patients. METHOD: Plasma levels of 25-hydroxyvitamin D3 [(25(OH)D3] were determined by radioimmunoassay and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by enzyme immunoassay in the 121 patients from the Feiring Heart Biopsy Study (FHBS) who had available histology data on adventitial MCIs; 53 of these had CAD alone and 68 had CAD and IRD. RESULTS: In the crude analysis, vitamin D levels were similar in CAD patients with and without IRD. After adjustment for potential confounders, IRD was associated with an increase of 8.8 nmol/L [95% confidence interval (CI) 1.0-16.6; p = 0.027] in 25(OH)D3 and an increase of 18.8 pmol/L (95% CI 4.3-33.3; p = 0.012) in 1,25(OH)2D3, while MCIs in the aortic adventitia were associated with lower levels of 1,25(OH)2D3 (ß = -18.8, 95% CI -33.6 to -4.0; p = 0.014). CONCLUSIONS: IRD was associated with higher levels of both 25(OH)D3 and 1,25(OH)2D3. These findings argue against the hypothesis that patients with high systemic inflammatory burden (CAD+IRD) should have lower vitamin D levels than those with less inflammation (CAD only). Of note, when controlled for potential confounders, low 1,25(OH)2D3 levels were associated with adventitial aortic inflammation.

Serum osteoprotegrin (OPG) in subclinical atherosclerosis in systemic lupus erythematosus.

Introduction Osteoprotegerin (OPG) is a member of the tumor necrosis factor (TNF) receptor family. It has recently been demonstrated that OPG is produced by a variety of tissues, including the cardiovascular system (heart, arteries, veins), lung, kidney, immune tissues, and bone. The OPG-RANKL signaling pathway is strongly related to vascular calcification. We determined the association of this biomarker with subclinical atherosclerosis in systemic lupus erythematous (SLE). Methods We measured OPG and markers of subclinical atherosclerosis (coronary artery calcium (CAC), carotid intima-media thickness (cIMT) carotid plaque) in 166 SLE patients (91% female, 64% Caucasian, 31% African American, 5% others, mean age 45 years). Subgroups of patients with different levels of OPG level were compared with respect to average levels of CAC, cIMT, and with respect to presence of carotid plaque. Age was adjusted for using multiple regression. Results OPG was highly correlated with age ( p < 0.0001). Individuals with higher levels of OPG tended to have higher measures of CAC, cIMT, and more carotid plaque. However, after adjustment for age, these associations, while still positive, were no longer statistically significant. Conclusion In our study much of the association observed was due to confounding by age, and after adjusting for age, our findings do not rule out the possibility of a null association.

Strength training improves cycling performance, fractional utilization of VO2max and cycling economy in female cyclists.

The purpose of this study was to investigate the effect of adding heavy strength training to well-trained female cyclists' normal endurance training on cycling performance. Nineteen female cyclists were randomly assigned to 11 weeks of either normal endurance training combined with heavy strength training (E+S, n = 11) or to normal endurance training only (E, n = 8). E+S increased one repetition maximum in one-legged leg press and quadriceps muscle cross-sectional area (CSA) more than E (P < 0.05), and improved mean power output in a 40-min all-out trial, fractional utilization of VO2 max and cycling economy (P < 0.05). The proportion of type IIAX-IIX muscle fibers in m. vastus lateralis was reduced in E+S with a concomitant increase in type IIA fibers (P < 0.05). No changes occurred in E. The individual changes in performance during the 40-min all-out trial was correlated with both change in IIAX-IIX fiber proportion (r = -0.63) and change in muscle CSA (r = 0.73). In conclusion, adding heavy strength training improved cycling performance, increased fractional utilization of VO2 max , and improved cycling economy. The main mechanisms behind these improvements seemed to be increased quadriceps muscle CSA and fiber type shifts from type IIAX-IIX toward type IIA.

Prevention of cardiovascular disease in rheumatoid arthritis.

The increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) has been recognized for many years. However, although the characteristics of CVD and its burden resemble those in diabetes, the focus on cardiovascular (CV) prevention in RA has lagged behind, both in the clinical and research settings. Similar to diabetes, the clinical picture of CVD in RA may be atypical, even asymptomatic. Therefore, a proactive screening for subclinical CVD in RA is warranted. Because of the lack of clinical trials, the ideal CVD prevention (CVP) in RA has not yet been defined. In this article, we focus on challenges and controversies in the CVP in RA (such as thresholds for statin therapy), and propose recommendations based on the current evidence. Due to the significant contribution of non-traditional, RA-related CV risk factors, the CV risk calculators developed for the general population underestimate the true risk in RA. Thus, there is an enormous need to develop adequate CV risk stratification tools and to identify the optimal CVP strategies in RA. While awaiting results from randomized controlled trials in RA, clinicians are largely dependent on the use of common sense, and extrapolation of data from studies on other patient populations. The CVP in RA should be based on an individualized evaluation of a broad spectrum of risk factors, and include: 1) reduction of inflammation, preferably with drugs decreasing CV risk, 2) management of factors associated with increased CV risk (e.g., smoking, hypertension, hyperglycemia, dyslipidemia, kidney disease, depression, periodontitis, hypothyroidism, vitamin D deficiency and sleep apnea), and promotion of healthy life style (smoking cessation, healthy diet, adjusted physical activity, stress management, weight control), 3) aspirin and influenza and pneumococcus vaccines according to current guidelines, and 4) limiting use of drugs that increase CV risk. Rheumatologists should take responsibility for the education of health care providers and RA patients regarding CVP in RA. It is immensely important to incorporate CV outcomes in testing of anti-rheumatic drugs.

Strength training improves performance and pedaling characteristics in elite cyclists.

The purpose was to investigate the effect of 25 weeks heavy strength training in young elite cyclists. Nine cyclists performed endurance training and heavy strength training (ES) while seven cyclists performed endurance training only (E). ES, but not E, resulted in increases in isometric half squat performance, lean lower body mass, peak power output during Wingate test, peak aerobic power output (W(max)), power output at 4 mmol L(-1)[la(-)], mean power output during 40-min all-out trial, and earlier occurrence of peak torque during the pedal stroke (P < 0.05). ES achieved superior improvements in W(max) and mean power output during 40-min all-out trial compared with E (P < 0.05). The improvement in 40-min all-out performance was associated with the change toward achieving peak torque earlier in the pedal stroke (r = 0.66, P < 0.01). Neither of the groups displayed alterations in VO2max or cycling economy. In conclusion, heavy strength training leads to improved cycling performance in elite cyclists as evidenced by a superior effect size of ES training vs E training on relative improvements in power output at 4 mmol L(-1)[la(-)], peak power output during 30-s Wingate test, W(max), and mean power output during 40-min all-out trial.

Irisin and FNDC5: effects of 12-week strength training, and relations to muscle phenotype and body mass composition in untrained women.

PURPOSE: To investigate the effects of strength training on abundances of irisin-related biomarkers in skeletal muscle and blood of untrained young women, and their associations with body mass composition, muscle phenotype and levels of thyroid hormones. METHODS: Eighteen untrained women performed 12 weeks of progressive whole-body heavy strength training, with measurement of strength, body composition, expression of irisin-related genes (FNDC5 and PGC1α) in two different skeletal muscles, and levels of serum-irisin and -thyroid hormones, before and after the training intervention. RESULTS: The strength training intervention did not result in changes in serum-irisin or muscle FNDC5 expression, despite considerable effects on strength, lean body mass (LBM) and skeletal muscle phenotype. Our data indicate that training affects irisin biology in a LBM-dependent manner. However, no association was found between steady-state serum-irisin or training-associated changes in serum-irisin and alterations in body composition. FNDC5 expression was higher in m.Biceps brachii than in m.Vastus lateralis, with individual expression levels being closely correlated, suggesting a systemic mode of transcriptional regulation. In pre-biopsies, FNDC5 expression was correlated with proportions of aerobic muscle fibers, a relationship that disappeared in post-biopsies. No association was found between serum-thyroid hormones and FNDC5 expression or serum-irisin. CONCLUSION: No evidence was found for an effect of strength training on irisin biology in untrained women, though indications were found for a complex interrelationship between irisin, body mass composition and muscle phenotype. FNDC5 expression was closely associated with muscle fiber composition in untrained muscle.

Reliable determination of training-induced alterations in muscle fiber composition in human skeletal muscle using quantitative polymerase chain reaction.

Determination of muscle fiber composition in human skeletal muscle biopsies is often performed using immunohistochemistry, a method that tends to be both time consuming, technically challenging, and complicated by limited availability of tissue. Here, we introduce quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)-based Gene-family profiling (GeneFam) of myosin heavy chain (MyHC) mRNA expression as a high-throughput, sensitive, and reliable alternative. We show that GeneFam and immunohistochemistry result in similar disclosures of alterations in muscle fiber composition in biopsies from musculus vastus lateralis and musculus biceps brachii of previously untrained young women after 12 weeks of progressive strength training. The adaptations were evident as (a) consistent increases in MyHC2A abundance; (b) consistent decreases in MyHC2X abundance; and (c) consistently stable MyHC1 abundance, and were not found using traditional reference gene-based qRT-PCR analyses. Furthermore, muscle fiber composition found using each of the two approaches was correlated with each other (r = 0.50, 0.74, and 0.78 for MyHC1, A, and X, respectively), suggesting that GeneFam may be suitable for ranking of individual muscle phenotype, particularly for MyHC2 fibers. In summary, GeneFam of MyHC mRNA resulted in reliable assessment of alterations in muscle fiber composition in skeletal muscle of previously untrained women after 12 weeks of strength training.

Short-term treatment with a gonadotropin-releasing hormone antagonist, cetrorelix, in rheumatoid arthritis (AGRA): a randomized, double-blind, placebo-controlled study.

OBJECTIVES: Gonadotropin-releasing hormone (GnRH) stimulates immune responses; therefore, antagonizing GnRH with cetrorelix may have anti-inflammatory effects. The aim of this study was to assess short-term cetrorelix therapy in rheumatoid arthritis (RA) patients. METHOD: In this proof-of-concept, randomized, double-blind study involving 99 patients with active, long-standing RA, 48 patients received subcutaneous cetrorelix (5 mg/day on days 1 and 2; 3 mg/day on days 3-5) and 51 received placebo. The primary end-point was the change in the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) by day 5, when the greatest GnRH suppression was anticipated. Secondary end-points included the change in tumour necrosis factor (TNF)-α, and achievement of American College of Rheumatology (ACR) responses and DAS28-CRP < 2.6 by day 5. Patients were followed up on days 10 and 15. RESULTS: By day 5, DAS28-CRP was non-significantly reduced by 0.82 in the cetrorelix group compared to a 0.57 reduction in the placebo group (p = 0.091), TNF-α (log pg/mL) was significantly reduced in the cetrorelix group compared with the placebo group [0.55, 95% confidence interval (CI) 0.08-1.01, p = 0.023], and more patients on cetrorelix achieved ACR20 responses (40% vs. 18%, p = 0.015) and DAS28-CRP < 2.6 (13% vs. 0%, p = 0.009). Inflammatory markers increased towards baseline levels after withdrawal of treatment. Rates of adverse events were similar in both groups. CONCLUSIONS: Although there was no significant difference in the primary end-point between groups, antagonizing GnRH led to significant improvements in key secondary end-points. Thus, GnRH antagonists may have rapid anti-inflammatory effects in RA, already occurring within 5 days. The data suggest a novel mode of action for TNF-α inhibition in RA, and potentially in other autoimmune diseases.

Anti-CCP and RF IgM: predictors of impaired endothelial function in rheumatoid arthritis patients.

OBJECTIVE: To determine whether the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor immunoglobulin M (RF IgM) is associated with endothelial dysfunction in patients with rheumatoid arthritis (RA). METHODS: We studied the presence of anti-CCP antibodies and RF IgM and endothelial function in terms of the reactive hyperaemic index (RHI) in 53 consecutive RA patients. Endothelial function was measured by using a finger plethysmograph. RESULTS: RHI was significantly lower in anti-CCP-positive RA patients (n = 33, RHI = 1.78, SD = 0.30) than in anti-CCP-negative RA patients (n = 20, RHI = 2.19, SD = 0.59; p = 0.008). A similar result was found in RF IgM-positive patients (n = 34, RHI = 1.77, SD = 0.30) vs. RF IgM-negative patients (n = 19, RHI = 2.23, SD = 0.58; p = 0.003). There were no significant differences between the groups regarding age, gender, traditional cardiovascular risk markers, Disease Activity Score using 28 joint counts (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), extra-articular manifestations (EAMs), use of glucocorticosteroids, statins, angiotensin-converting enzyme (ACE) inhibitors, and non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSION: The presence of anti-CCP antibodies and RF IgM was related to impaired endothelial function independent of other cardiovascular risk factors in RA patients. Thus, these autoantibodies might reflect an early reversible stage of the atherosclerotic process, and may indicate increased risk of cardiovascular disease (CVD). Further studies are needed to explore whether anti-CCP antibodies and RF IgM may act directly or indirectly to cause endothelial dysfunction, or merely reflect endothelial dysfunction in RA patients.

Spondyloarthritis: a strong predictor of early coronary artery bypass grafting.

OBJECTIVES: The main aim of the study was to examine whether patients with spondyloarthritides underwent their first coronary artery bypass grafting (CABG) at a younger age than those without spondyloarthritides. METHODS: Patients who underwent their first CABG at the Feiring Heart Clinic during 2001-2005 were preoperatively screened for spondyloarthritides, and the cardiological assessment was registered. We compared the characteristics of patients with and without spondyloarthritides. RESULTS: Of the 3852 patients undergoing their first CABG, 30 (0.78%) had spondyloarthritides. No statistically significant differences in traditional cardiovascular risk factors were found. The mean ages of patients with and without spondyloarthritides were 60.1 (SD = 8.7) and 66.9 (SD = 10.1) years, respectively. Spondyloarthritis was found by multivariate analysis to be a stronger independent predictor of early CABG than traditional cardiovascular risk factors [adjusted beta -6.2, p<0.001, 95% confidence interval (CI) -9.5 to -2.8]. Sixty per cent of spondyloarthritis patients and 52% of control patients had already suffered a myocardial infarction (p = 0.4). CONCLUSION: Spondyloarthritis was a stronger predictor of early CABG than most of the registered traditional cardiovascular risk factors. The prevalence of spondyloarthritis seemed to be higher in the CABG population than in the general population. These findings may indicate accelerated coronary artery disease (CAD) in spondyloarthritides.