Increased carotid intima-media thickness in patients with radiographic axial spondyloarthritis compared to controls and associations with markers of inflammation.

OBJECTIVE: There is an increased risk for cardiovascular disease (CVD) in patients with radiographic axial spondyloarthritis (r-axSpA). In this cross-sectional study, we aimed to, overall and stratified by sex, (i) compare ultrasound derived carotid intima media thickness (cIMT), between patients and controls, and (ii) investigate associations between cIMT, clinical disease activity and inflammation-related laboratory markers in patients with r-axSpA. METHOD: In total, 155 patients diagnosed with r-axSpA using the modified New York criteria and 400 controls were included. Bilateral carotid ultrasound, laboratory testing, and questionaries were acquired. Disease-specific assessments were carried out for patients. Linear regression analysis was used to assess associations. RESULTS: Linear regression analyses showed that patients with r-axSpA had increased mean cIMT compared to controls (mean ± SD, 0.8 ± 0.1 mm vs 0.7± 0.1 mm, respectively, unstandardized ß (95% CI) -0.076 (-0.10, -0.052), P < 0.001) adjusted for smoking status and age. Linear regression analyses for patients with r-axSpA showed that only males presented significant associations between cIMT and inflammation-related laboratory markers, white blood cell (WBC) count (mean ± SD, 6.8 ± 1.6 109/L) and monocytes (0.6 ± 0.2 109/L); WBC count (unstandardized ß (95% CI) 0.019 (0.0065, 0.031), P = 0.003, R2 = 0.57) and monocytes (0.13 (0.0047, 0.26), P = 0.041, R2 = 0.55), adjusted for age, smoking status, body mass index, hypertension, dyslipidemia, diabetes mellitus, ASDAS-CRP, and treatment with DMARDs and glucocorticoids. No significant association was found between cIMT and clinical disease activity assessed by ASDAS-CRP. CONCLUSION: Patients with r-axSpA had significantly increased cIMT compared to controls. In male patients, higher WBC and monocyte count were associated with an increase in cIMT suggesting the role of inflammation in the development of atherosclerosis. Key Points •Carotid intima-media thickness was increased in patients with radiographic axial spondyloarthritis compared to controls. •White blood cell and monocyte counts were associated with carotid intima-media thickness in male patients with radiographic axial spondyloarthritis.

Patients with radiographic axial spondylarthritis have an impaired dietary intake-a cross-sectional study with matched controls from northern Sweden.

BACKGROUND: Radiographic axial spondyloarthritis (r-axSpA) is one of the most common chronic inflammatory rheumatic diseases, affecting about 0.2% of the Swedish population. Adequate nutritional intake is essential for maintaining physiological functions. A poor diet increases the risk of developing conditions such as obesity, osteoporosis, and/or atherosclerosis. Diet quality is also theorized to affect systemic inflammation. Dietary habits in patients with r-axSpA are largely unknown. The aims of this study were to assess dietary nutrient intake in r-axSpA patients and examine whether it differs compared to persons without r-axSpA. METHODS: r-axSpA patients (modified NY criteria) at the rheumatology clinic in Region Västerbotten, northern Sweden, were invited to take part in the Backbone study which investigates disease severity and comorbidities. In total, 155 patients were included. Nutritional intake was assessed by the semi-quantitative food frequency questionnaire MiniMeal-Q. Controls were collected from the Swedish CArdioPulmonary bioImage Study (n = 30,154), a study that invited participants 50-64 years of age by random selection from the Swedish population register. Out of the 155 r-axSpA patients, 81 were in the same age span. Four controls were identified for each patient, matched on age (± 1 year), sex, and geographic location. Data on dietary intake was available for 319 controls. Statistical comparisons of dietary intake between patients with r-axSpA and controls were done by exact conditional logistic regression analysis, adjusted for country of birth, educational level, single household, weight, smoking status, and energy intake. RESULTS: Patients had a comparatively significantly higher energy intake from carbohydrates, a lower fiber density, and a lower intake of marine omega-3 fatty acids. Furthermore, intake of vitamins D, E, and K as well as selenium, folate, calcium, magnesium, phosphorus, potassium, vitamin A, and ß-carotene (a precursor of vitamin A and marker of vegetable and fruit intake) was significantly lower among patients compared to controls. CONCLUSIONS: Our results suggest that r-axSpA patients have an impaired dietary intake. Notably, intake was lower in several nutrients theorized to have anti-inflammatory properties (fiber density, marine-omega-3 fatty acids, vitamin D, and selenium). We further propose that nutrition screening might be incorporated into the management of r-axSpA patients.

A self-indicating and antibacterial gelatine-chitosan blended hydrogel enabling real-time quality control and sustained bioactive agent delivery.

Hydrogels are one type of materials that are widely exploited for bioactive agent delivery, partly owing to their high biocompatibility and low toxicity. When hydrogels are used as carriers, their performance in agent loading and sustained agent release are predominately determined by the gel structure, which can be largely affected by variations during gel preparation. Till now, effective and easy methods to enable monitoring of such variations in real time have been lacking, making quality control of the generated gel-based carrier technically challenging. To address this technical gap, in this study we take advantage of the clusteroluminogenic properties of gelatine and chitosan to generate a crosslinked blended hydrogel which not only shows intrinsic antibacterial properties and high tunability in delivery performance but also shows a self-indicating capacity to enable quality control during hydrogel preparation. Upon fitting the curves of agent release into different kinetic models, the release profiles of the agent-loaded gels have been found to follow the Higuchi model well, with the non-Fickian mechanism being the major mechanism of the release process. Along with their high efficiency in agent loading, our gels warrant further exploitation for use in bioactive agent delivery and related biomedical applications.

Left atrial contraction strain during a Valsalva manoeuvre: A study in healthy humans.

BACKGROUND: Cardiac mechanics are influenced by loading conditions as well as sympathetic tone. Left atrial (LA) contractile function assessed by two-dimensional (2D) strain has been described in the setting of controlled preload alterations; however, studies show conflicting findings about change or direction of change. We hypothesized that the controlled preload reduction and the sympathetic nervous system activation that occurs during a standardized Valsalva manoeuvre would bring about a change in LA contraction strain. METHODS: Healthy young adults of both sexes were recruited. Transthoracic echocardiographic ultrasound images were collected before and during a Valsalva manoeuvre. Standard imaging windows for LA strain assessment were used and the images were copied and stored for later offline analysis. These were assessed for adequate atrial wall visualization in 2D strain assessment. Paired comparisons were carried out using Student's T test. RESULT: Thirty-eight participants were included and there were 22 complete studies with paired pre- and during Valsalva manoeuvre. LA contraction strain at baseline was 10.5 ± 2.8% (standard deviation) and during the Valsalva manoeuvre 10.6 ± 4.6%, p = 0.86. CONCLUSION: The Valsalva manoeuvre, a combination of preload reduction and sympathetic nervous system activation, seems not to be associated with a change in LA contraction strain in healthy young individuals. LA contraction strain should be interpreted in the context of both atrial loading conditions and prevailing autonomic nervous system activity.

Left atrial contraction strain and controlled preload alterations, a study in healthy individuals.

BACKGROUND: In order to assess left atrial contractile function in disturbed circulatory conditions, it is necessary to have a clear understanding of how it behaves in a normal resting state with changes in loading conditions. However, currently the understanding of this relationship is incomplete. We hypothesize that in healthy individuals, left atrial contraction strain and its peak strain rate are increased or decreased by increasing or decreasing preload, respectively. METHODS: Controlled maneuvers used to change preload included continuous positive airway pressure by mask (CPAP 20 cmH2O) for preload decrease, and passive leg raise (15 degrees angle) for preload increase. Cardiac ultrasound 4-chamber views of the left atria and left ventricle were acquired at baseline and during maneuver. Acquired images were post processed and analyzed offline. Comparisons were made using paired t-test and means with 95% confidence interval. RESULTS: There were 38 participants, complete results were obtained from 23 in the CPAP maneuver and 27 in the passive leg raise maneuver. For the CPAP group, left atrial contraction strain was 11.6% (10.1 to 13.1) at baseline and 12.8% (11.0 to 14.6) during the maneuver (p = 0.16). Left atrial contraction peak strain rate was - 1.7 s- 1 (- 1.8 to - 1.5) at baseline and - 1.8 s- 1 (- 2.0 to - 1.6) during the maneuver (p = 0.29). For the passive leg raise-group, left atrial contraction strain was 10.1% (9.0 to 11.2) at baseline and 10.8% (9.4 to 12.3) during the maneuver (p = 0.28). Left atrial contraction peak strain rate was - 1.5 s- 1 (- 1.6 to - 1.4) at baseline and - 1.6 s- 1 (- 1.8 to - 1.5) during the maneuver (p = 0.29). Left atrial area, an indicator of preload, increased significantly during passive leg raise and decreased during CPAP. CONCLUSION: In healthy individuals, left atrial contraction strain and its peak strain rate seem to be preload-independent. TRIAL REGISTRATION: The study was 2018-02-19 registered at clinicaltrials.gov ( NCT03436030 ).

Aberrant autonomic pattern during the post-exercise recovery phase in long QT syndrome patients.

OBJECTIVES: It is well-established that the autonomic nervous system (ANS) plays a central role in arrhythmogenesis. During and after exercise the ANS is particularly active, and since long QT syndrome (LQTS) patients have an increased risk of lethal arrhythmias during physical activity, it is important to investigate the autonomic function in these patients. In this study we investigate the ANS response during and after exercise in LQTS patients and healthy age and sex matched controls. METHODS: Forty-four genotype-verified adult LQTS patients and forty-four healthy age- and sex-matched controls performed a submaximal bicycle exercise stress test. Heart rate recovery (HRR) and heart rate variability (HRV) were analyzed from registered electrocardiogram (ECG) and vector electrocardiogram (VCG) recordings collected throughout rest, exercise and in the post-exercise phase. RESULTS: LQTS patients had a slower HRR than controls at 1- and 4-min post-exercise (p < 0.001). During the post-exercise phase, LQTS patients had a lower total power (p < 0.001), low frequency power (p < 0.001) and high frequency power (p < 0.001) than controls. In the same phase, LQTS patients off betablocker (BB) treatment showed a lower high frequency power (p = 0.01) and different low frequency/high frequency ratio (p = 0.003) when comparing with LQTS patients on BB treatment. CONCLUSIONS: The parasympathetic effect on both HRR and HRV after exercise appears depressed in this LQTS patient cohort compared to healthy controls. This indicates an aberrant ANS response during the post-exercise phase which might be compensated by BB treatment. Our findings emphasize the importance of performing further investigations to identify the role of the ANS in LQTS arrhythmogenesis.

Near-occlusion is difficult to diagnose with common carotid ultrasound methods.

PURPOSE: To assess the sensitivity and specificity of common carotid ultrasound method for carotid near-occlusion diagnosis. METHODS: Five hundred forty-eight patients examined with both ultrasound and CTA within 30 days of each other were analyzed. CTA graded by near-occlusion experts was used as reference standard. Low flow velocity, unusual findings, and commonly used flow velocity parameters were analyzed. RESULTS: One hundred three near-occlusions, 272 conventional ≥50% stenosis, 162 <50% stenosis, and 11 occlusions were included. Carotid ultrasound was 22% (95%CI 14-30%; 23/103) sensitive and 99% (95%CI 99-100%; 442/445) specific for near-occlusion diagnosis. Near-occlusions overlooked on ultrasound were found misdiagnosed as occlusions (n = 13, 13%), conventional ≥50% stenosis (n = 65, 63%) and < 50% stenosis (n = 2, 2%). No velocity parameter or combination of parameters could identify the 65 near-occlusions mistaken for conventional ≥50% stenoses with >75% sensitivity and specificity. CONCLUSION: Near-occlusion is difficult to diagnose with commonly used carotid ultrasound methods. Improved carotid ultrasound methods are needed if ultrasound is to retain its position as sole preoperative modality.

Biomechanical Properties of Common Carotid Arteries Assessed by Circumferential 2D Strain and ß Stiffness Index in Patients With Ankylosing Spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is associated with an elevated risk of cardiovascular disease (CVD) related to atherosclerosis, preceded by arterial stiffness. We aimed to examine common carotid artery (CCA) biomechanical properties using ultrasound to calculate ß stiffness index (indicating arterial stiffness) and, a more recently developed technique, 2-dimensional (2D) speckle tracking strain (indicating arterial motion and deformation, strain) to (1) compare with age- and sex-matched controls, and (2) analyze relationships between strain and stiffness with disease characteristics and traditional risk factors for CVD in patients with AS. METHODS: In this cross-sectional study, a cohort of 149 patients with AS, mean age 55.3 ± 11.2 years, 102 (68.5%) men, and 146 (98%) HLA-B27-positive, were examined. Bilateral CCA were examined for circumferential 2D strain and ß stiffness index. A subgroup of 46 patients was compared with 46 age- and sex-matched controls, both groups without hypertensive disease, diabetes, myocardial infarction, or stroke. RESULTS: Mean bilateral circumferential 2D strain was lower in AS patients compared with controls (7.9 ± 2.6% vs 10.3 ± 1.9%, P < 0.001), whereas mean bilateral ß stiffness index was higher (13.1 ± 1.7 mmHg/mm vs 12.3 ± 1.3 mmHg/mm, P = 0.02). In multivariable linear regression analyses, strain was associated with age, erythrocyte sedimentation rate, history of anterior uveitis, and treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARD) and/or biological DMARD (R2 0.33), while stiffness was associated with age (R2 0.19). CONCLUSION: Both CCA circumferential 2D strain and ß stiffness index differed between patients with AS and controls. Strain was associated with AS-related factors and age, whereas only age was associated with stiffness, suggesting that the obtained results reflect different pathogenic vascular processes.

Exercise Induced Worsening of Mechanical Heterogeneity and Diastolic Impairment in Long QT Syndrome.

BACKGROUND: Electromechanical heterogeneities due to marked dispersion of ventricular repolarisation and mechanical function have been associated with symptoms in long QT syndrome (LQTS) patients; Aim: To examine the exercise response of longitudinal LV systolic and diastolic myocardial function and synchronicity in LQTS patients and its relationship with symptoms; Methods: Forty seven (age 45 ± 15 yrs, 25 female, 20 symptomatic) LQTS patients and 35 healthy individuals underwent an exercise test (Bruce protocol). ECG and echo parameters were recorded at rest, peak exercise (p.e.), and recovery; Results: LQTS patients had prolonged and markedly dispersed myocardial contraction, delayed early relaxation phase, and significantly decreased filling time at all exercise phases. Unlike controls, these electromechanical disturbances deteriorated further with exercise, during which additional decrease of the LV diastolic myocardial function and attenuated LV stroke volume were noted. Such abnormal responses to exercise were seen to a greater degree in symptomatic patients and in the LQT1 subgroup and improved with B-blocker therapy. Worsening myocardial contraction dispersion at p.e. was the strongest discriminator for previous clinical events, and its discriminating power excelled further by adding early relaxation delay; Conclusions: Electromechanical disturbances were shown to worsen during exercise in LQTS patients and were more pronounced in those with previous arrhythmic events.

Factors related to health-related quality of life in ankylosing spondylitis, overall and stratified by sex.

BACKGROUND: Ankylosing spondylitis (AS) begins early in life and often leads to reduced physical function, but less is known about the impacts it has on health-related quality of life (HRQoL). The aims of this study were to assess HRQoL using the Short Form-36 (SF-36) in a cohort of patients with AS compared with controls and to examine associations between SF-36 scores and spinal radiographic changes, physical function, disease activity and demographic data overall and stratified by sex. METHODS: A cohort of patients with AS from Western Sweden were assessed using the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with spinal radiographs, clinical examination and questionnaires, including the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Patient Global (BASG) and SF-36. Each patient's SF-36 results were compared with those of five age-matched and sex-matched persons (n = 1055) from the SF-36 Swedish normative population database. Associations between SF-36 physical component summary (PCS) and mental component summary (MCS) scores and disease-related and demographic factors were investigated using univariate and multivariable ogistic regression analyses with PCS and MCS below/above their respective median values as dependent variables. RESULTS: A total of 210 patients, age (median, IQR) 49.0 (21.2) years, symptom duration 24.0 (21.0) years, men 57.6% and HLAB27 87.1% were included. Patients with AS scored significantly lower (p < 0.001) compared to controls in all SF-36 domains and component summaries; PCS 42.4 (14.5) in AS versus 52.4 (11.8) in controls and MCS 47.9 (20.0) in AS versus 54.1 (10.1) in controls. Both men and women scored significantly lower in PCS compared with MCS. Multivariable logistic regression analyses revealed that living without a partner (OR 2.38, 95% CI 1.00-5.67), long symptom duration (year in decade OR 1.66, 95% CI 1.16-2.37), higher BASFI (OR 1.98, 95% CI 1.46-2.70) and ASDAS ≥ 2.1 (OR 3.32, 95% CI 1.45-7.62) were associated with worse PCS, while living without a partner (OR 3.04, 95% CI 1.34-6.91), fatigue (visual analogue scale for global fatigue greater than the median (OR 6.36, 95% CI 3.06-13.19) and ASDAS ≥ 2.1 (OR 2.97, 95% CI 1.41-6.25) with worse MCS. Some differences between sexes were observed in the results. CONCLUSIONS: The patients with AS had significantly lower HRQoL compared with controls. PCS was more affected compared to MCS in both sexes. Both disease-related and demographic factors were associated with HRQoL, partly overlapping for PCS and MCS. Factors associated with HRQoL showed some differences between sexes. By modifying factors, such as ASDAS-CRP and fatigue, HRQoL may potentially be improved. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00858819 . Registered on 9 March 2009. Last updated on 28 May 2015.