Psoriatic arthritis (PsA) is influenced by a complex genetic predisposition. In patients with PsA, interleukin (IL)-17A plays a key role in triggering a complex autoimmune/autoinflammatory immune ...response in conjunction with other pro-inflammatory cytokines (such as tumor necrosis factor-alpha, IL-23, monocyte chemotactic protein-1, and IL-6). PsA manifests with various clinical symptoms, including musculoskeletal diseases and extra-articular manifestations. In particular, mediated by the soluble IL-17A presents a higher cardiovascular risk, suggesting connection between inflammation and cardiovascular diseases beyond the traditional risk factors. Moreover, studies have shown that patients with psoriasis are ten times at higher risk of developing dilated cardiomyopathy than those without psoriasis. Therefore, owing to the prominent role of IL-17A and psoriasis in the pathogenesis of PsA and endothelial dysfunction, we hypothesized that IL-17A is crucial in the early development of diastolic dysfunction (DD) and could serve as a tool to identify patients with asymptomatic DD and PsA. Although transthoracic echocardiography is the primary evaluation method for DD, it requires skilled personnel, routine parameters assessment, such as mitral inflow, and tissue Doppler imaging. As a result, assessing parameters such as left atrial deformity using novel techniques could be valuable for a more specific evaluation and diagnosis of DD. Clinical characteristics and laboratory parameters of PsA activity, cardiac ultrasound parameters, or cardiac functional markers like N-terminal pro-brain natriuretic peptide (NT-pro-BNP) can be correlated with the concentration of serum IL-17A. Moreover, determining the diagnostic accuracy of circulating IL-17A for early DD can also serve as a laboratory biomarker for diagnosing DD in asymptomatic patients. Thus, if the diagnostic accuracy of IL-17A for DD can be proven, the identification of biological drugs that inhibit IL-17A could be advantageous in treating patients with PsA and echocardiography-verified asymptomatic DD.
Purpose
To showcase results of arterial blood gases’ analysis in elite breath-hold divers sampled at depths where their total lung capacities are below their residual lung volume on surface.
Methods
...Three male elite breath-hold divers performed body plethysmographies to determine their lung volumes. Two dives were performed, one on normal inhalation to 60 m of depth and the second on complete exhalation to 10 m of depth. Blood samples were taken on five occasions; before the first dive, at 60 and 10 m of depth and immediately after resurfacing after both dives.
Results
Arterial blood gases’ analysis at 60 m of depth showed an increase in partial pressures of oxygen and carbon dioxide, a consequent decrease in pH and an increase in concentration of HCO
3
−
. After resurfacing, in two divers, values mostly returned to normal; hypoxemia was observed in one diver. At 10 m of depth, all values showed similar variation, and hypoxemia was observed in the same diver but at depth. Upon resurfacing, all values returned to normal.
Conclusion
This is the first study performed at depths where the total lung capacities of participants are below their residual lung volumes at the surface. Partial pressure of carbon dioxide increases at depth to higher than normal values causing pH to decrease thus exceeding the buffering potential of the blood. In addition, previous assumptions that maximum depth in breath-hold divers is where total lung capacity is reduced to their residual volume proved wrong as our group of divers had no symptoms after resurfacing.
Vitamin D deficiency is associated with cardiovascular diseases, including coronary artery diseases (CAD). As vitamin D manifests its biological function through its vitamin D receptor (VDR), VDR ...gene polymorphisms potentially affect VDR functionality and vitamin D activity. Therefore, the objective of this study was to analyze three well-studied VDR gene polymorphisms-Fok1 (rs2228570), BsmI (rs1544410) and Taq1 (rs731236)-in a cohort of CAD patients after acute myocardial infarction.
In the presented cross-sectional study, 155 participants with CAD after acute myocardial infarction and 104 participants in a control group without CAD were enrolled. The participants in both groups were Caucasians of European origin. The genotyping of VDR polymorphisms rs2228570, rs1544410 and rs731236 was assessed by RT-PCR.
The results show an association between the T/T genotype of the BsmI (rs1544410) and the G/G genotype of the Taq1 (rs731236) VDR polymorphism and CAD patients after acute myocardial infarction. There was no association between the Fok1 (rs2228570) VDR polymorphism and CAD patients after acute myocardial infarction.
The presented results suggest a potential association of the BsmI (rs1544410) and Taq1 (rs731236) VDR polymorphisms with CAD patients after myocardial infarction.
A higher prevalence of coronary heart disease, cardiac and overall mortality is associated with obesity. The development of obesity appears in different adaptations in the morphology of cardiac ...structure and function. Obesity causes eccentric hypertrophy and changes in diastolic function of left ventricle. A systolic on diastolic heart dysfunction results from the breakdown of compensatory pace to raised wall stress and dilatation of chambers. Obesity does not possess primary cause and effect relationship with cardiovascular disease, such as LDL cholesterol. It is regarded as a means of facilitating factors such as hypertension, diabetes or cigarette smoking. Adipose tissue in this manner works as the hormone generating tissue, secreting various peptides and secondary messengers and inflammatory cytokines. Pharmacotherapy can be a useful component in the global fight against obesity. Besides repeating re-evaluations of weight loosing drug treatment with respect to efficiency or safety for continuous use, one must not underappreciate the pretreatment risk-assessments and expected benefits of treatment, along with impact on the patient's quality of life and motivation. Pharmacotherapy of obesity is reserved for obese people with body mass index (BMI) ≥ 30 kg/m2 but also in individuals with BMI 27 .0 and 29 .9 kg/m2 and obesity related comorbidities as obstructive sleep apnea, hypertension, dyslipidemias, diabetes and metabolic syndrome. Although connections between obesity and cardiovascular diseases (CVD) are acknowledged for over dozen of years, there is still a lack of scientific research into the field and it is a challenge for future studies.
•Elite Freedivers do not display major changes in their immunological profile compared to non-diving controls under resting conditions.•Following an extreme freedive, CD8 T cells, NK cells and δ1+ γδ ...T cells downregulate expression of cytotoxic molecules.•Following an extreme freedive, CD8 T cells, NK cells and δ2+ γδ T cells have an increased potential to produce IFNγ and TNF.•Changes in the immunological profile of cytotoxic immune cells following a freedive are associated with psychological stress, hypoxia and changes in glucose levels.•Following extreme anaerobic exercise, the cytotoxic arm of the immune system undergoes changes that reduces its possibility to cause tissue damage, but increase its ability to signal threats, possibly as an acute adaptation mechanism.
Exercise has many beneficial effects for our body, but can become detrimental at high intensity, especially for our immune system. Little is known about the underlying mechanism of impaired immune functionality under conditions of intense physical strain. Freedivers, people who dive to high depths on a single breath, perform extreme exercise under anaerobic conditions. In this study, we investigated the impact of freediving on the cytotoxic arm of the immune system. At rest, elite freedivers did not display changes in their immunological profile compared to non-diving controls. In contrast, after a freedive, granzyme B and IL-2 production were reduced, whereas IFNγ and TNF secretion were increased by cytotoxic immune cells. Using in vitro models mimicking freedive conditions, we could show that hypoxia in combination with stress hyperglycemia had a negative impact on Granzyme B secretion, whereas IL-2 production was inhibited by stress hormones. Our findings suggest that in response to extreme exercise, cytotoxic immune cells transiently change their functional profile to limit tissue damage.
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Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is a prospective registry of outcomes from patients with newly diagnosed AF at risk of ...stroke. In the propensity score (PS)-matched global population of phase 3 GLORIA-AF, at 3 years, dabigatran-treated patients experienced reduced risk for major bleeding, and similar risk for stroke and myocardial infarction, compared with vitamin K antagonist (VKA)-treated patients.
Do patients in Eastern Europe benefit from treatment with dabigatran versus VKA?
Descriptive analysis, without PS matching. To contextualize the Eastern Europe results of GLORIA-AF phase 3, we also descriptively analyzed the global population without PS matching. Consecutive patients with newly diagnosed AF and CHA2DS2-VASc-score ≥1 were enrolled until December 2016 in 38 countries (9 in Eastern Europe).
Three-year outcomes with dabigatran and VKA.
In Eastern Europe, 1341 patients were eligible (6% of patients globally), and incidence rates (per 100 patient-years) for the following outcomes were numerically lower with dabigatran (N = 498) versus VKA (N = 466): major bleeding (0.26 vs. 0.90), all-cause death (2.04 vs. 3.50), and a composite of stroke, systemic embolism, myocardial infarction, life-threatening bleeding, and vascular death (1.37 vs. 1.92); stroke was comparable (0.51 vs. 0.50). All incidence rates were numerically lower in Eastern Europe versus the global population for both treatments. Chronic concomitant use of high bleeding risk medications (eg, nonsteroidal anti-inflammatories) was lower in Eastern Europe (dabigatran 3.8%, VKA 9.3%) than globally (dabigatran 14.8%, VKA 20.6%) and persistence with dabigatran was higher in Eastern Europe (76%) than globally (64%).
Dabigatran was associated with numerically reduced major bleeding, all-cause death, and cardiovascular (CV) composite, with comparable risk of stroke versus VKA, in Eastern Europe. Limitations of this descriptive analysis include few CV events (n = 11 for stroke, in the dabigatran and VKA groups combined) and a lack of statistical analysis and PS matching, which precludes definitive conclusions; however, the CV outcomes in Eastern Europe were consistent with the beneficial impact of dabigatran versus VKA in the statistically analyzed global population with PS matching.
Amiodarone is a potent antiarrhythmic medication used to treat life-threatening ventricular arrhythmias; however, its well-established adverse effect is a thyroid disorder. Amiodarone-induced ...thyroiditis (AIT), a clinical entity involving two types with different etiopathology and treatment approaches, may occur at the beginning or even several years after amiodarone treatment discontinuation. The toxicity profile of amiodarone becomes especially important in young patients with lifelong cardiac disorders, which are often refractory to other antiarrhythmic drugs. Herein, we report the first case of non-sustained ventricular tachycardia (NSVT), an unusual presentation of type II AIT, in a young male patient who was previously diagnosed with left ventricular cardiomyopathy with excessive trabeculation.
A 36-year-old male non-athlete presented with tiredness during regular follow-up. Continuous electrocardiographic monitoring (cECG) revealed NSVT, whereas echocardiography and cardiac magnetic resonance imaging detected discrete structural and functional changes that could not fully explain the observed cECG report. Conversely, an unmeasurably low thyrotropin level on admission and previous exposure to amiodarone pointed the diagnostic pathway in the direction of the thyroid gland. Elevated free thyroxine and undetectable autoantibody titers with unremarkable sonographic findings raised clinical suspicion of type II AIT. Scintigraphic imaging with
Tc-2-methoxyisobutylisonitrile (sestamibi) revealed decreased thyroid uptake; hence, prednisone was introduced for treatment. Clear improvements in both biochemical and electrocardiographic parameters were observed after immunomodulatory treatment of type II AIT in this young patient with cardiomyopathy and excessive trabeculation.
Treatment of reversible causes of cardiac rhythm abnormalities such as type II AIT should be considered before choosing other treatment modalities, particularly in patients with structural cardiac disorders. The importance of a multidisciplinary approach in complex cases such as the one reported, thus, cannot be emphasized enough.
We aimed to evaluate the diagnostic accuracy of the proinflammatory monocyte chemotactic protein-1 (MCP-1) in the diagnosis of asymptomatic diastolic dysfunction (DD) in patients with psoriatic ...arthritis (PsA). The disease activity in psoriatic arthritis (DAPSA) was determined using clinical and laboratory parameters, and echocardiography was performed to estimate DD. Serum MCP-1 concentrations were elevated in PsA patients with DD diagnosed with ultrasound (median (25th percentile, 75th percentile): 366.6 pg/mL (283, 407.1 pg/mL) vs. 277.5 pg/mL (223.5, 319.1 pg/mL) in controls; P<0.0017). PsA patients with serum MCP-1 concentration higher than the cut-off value of 347.6 pg/mL had a 7.74-fold higher chance of developing DD than PsA patients with lower serum MCP-1 concentrations (controls), with a specificity of 86.36% and sensitivity of 55%, as verified using ultrasound. The group with MCP-1 concentrations above the cut-off value also showed a higher late peak diastolic mitral inflow velocity, A-wave value (P=0.000005), E/E′ ratio (P=0.00005), and a lower E/A ratio (P=0.000002), peak systolic left atrial reservoir strain, SA value (P=0.0066), early peak diastolic displacement of the mitral septal annulus, E′ wave value (P=0.003), than controls. Systolic blood pressure (P=0.01), LDL cholesterol concentration (P=0.012), glucose concentration (P=0.011), and DAPSA (P=0.0000) increased in the PsA group with higher MCP-1 concentrations, although there were no differences in comorbidities and therapy between the groups compared. Thus, the serum MCP-1 concentration was a significant and independent prognostic indicator for asymptomatic DD in PsA patients (area under the curve=0.730, P=0.001). The DAPSA score in PsA patients might indicate the need for echocardiography and adjustment of anti-inflammatory treatment in terms of DD prevention.
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