Central retinal artery occlusion (CRAO) is a common cause of blindness and visual morbidity. In the majority of cases, it is related to thrombotic embolism. Nevertheless, the role of inherited or ...acquired thrombophilic risk factors in CRAO pathogenesis has not been comprehensively studied.
In 126 CRAO patients (66 52.4% men, median age 55 range: 18-80 years) and 107 matched controls (56 52.3% men, median age 53 range: 34-78 years) we evaluated classical atherosclerotic risk factors, including serum lipid profile and glucose level, analyzed intima-media complex thickness (IMT) of external carotid arteries, and performed transthoracic echocardiography. Furthermore, we established the prevalence of inherited and acquired thrombophilic risk factors, such as factor V Leiden (FVL) and prothrombin 20210 G/A genetic variants, plasma activity of factor (F) VIII, protein C and antithrombin activity, and free protein S levels. We also assessed the presence of antiphospholipid antibodies (APLA) and evaluated blood homocysteine in all enrolled subjects. Additionally, we estimated the occurrence of Val34Leu polymorphism of the A subunit of coagulation factor XIII (FXIII-A) in both groups as a potential thrombosis-protecting factor.
Among traditional atherosclerotic risk components, obesity/overweight and hypercholesterolemia were the most common in the CRAO group and occurred in 103 (81.7%) and 85 (67.5%) patients, respectively. CRAO patients also had elevated IMT and altered echocardiographic parameters, indicating diastolic cardiac dysfunction. In thrombophilia investigations, at least one laboratory risk factor occurred in 72.2% (n = 91) of CRAO patients, with APLA as the most frequent, detected in 38.1% (n = 48) of them (almost seven times more frequent than in controls, p < 0.001). Deficiencies in protein C activity and free protein S levels were also common in the CRAO group, reported in 17.5% (n = 22) and 19.8% (n = 25) of patients, respectively. Interestingly, among two analyzed prothrombotic genetic variants, only the FVL was related to CRAO, with the allelic frequency 2.4 times more prevalent than in controls (p = 0.044). Finally, the CRAO group was characterized by hyperhomocysteinemia, almost twice as common as in controls (p = 0.026). Antithrombin deficiency, elevated FVIII, and FXIII-A Val34Leu polymorphism were not associated with CRAO.
Our findings suggest that thrombophilia plays a vital role in the pathogenesis of CRAO. Thus, proper laboratory screening should be considered in the primary and secondary prevention of those episodes, with implementing appropriate therapy as needed.
Patients with systemic sclerosis experience endothelial dysfunction and damage even in the absence of clinical manifestations.
To evaluate various methods for assessing the endothelial function for ...their applicability to clinical practice.
Forty-two patients (7 men and 35 women) with systemic sclerosis and 36 controls (11 men and 25 women) matched for age, sex, body mass index, smoking habit, and comorbidities were enrolled in the study. We assessed each participant for typical risk factors for cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1) and thrombomodulin together with flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography.
Patients with systemic sclerosis did not differ from controls in serum levels of VCAM-1 and thrombomodulin, however, the statistical analysis with adjustment for potential confounders revealed increased levels of thrombomodulin in the patients (
= 0.03). They also had a 45% lower relative increase of FMD (FMD%), and 13% higher IMT (
< 0.01, both, also after adjustment for potential confounders). In a simple regression model, lower FMD% was determined by age (β = -0.57, 95% confidence interval (CI): -0.72 to -0.43) and C-reactive protein levels (β = -0.38, 95% CI: -0.55 to -0.22). Thicker IMT was related to age (β = 0.64, 95% CI: 0.52-0.67), glomerular filtration rate (β = -0.34, 95% CI: -0.5 to -0.18), and blood thrombomodulin levels (β = 0.45, 95% CI: 0.13-0.76).
Patients with systemic sclerosis present with endothelial dysfunction which may be detected using ultrasonographic methods. The exact mechanism of observed abnormalities is unknown, but it is possibly related to the chronic inflammation and ischemia-reperfusion injury.
Central retinal artery occlusion (CRAO) is an emergency state characterized by sudden, painless vision impairment. Patients with CRAO have an increased risk of cardiovascular events, including ...stroke, likely related to vascular endothelial damage. Therefore, we investigated flow-mediated dilatation (FMD) of the brachial artery as a marker of endothelial dysfunction, intima-media complex thickness (IMT) of the common carotid artery, pointing to the arterial wall atherosclerotic alteration, and transthoracic echocardiographic parameters in 126 consecutive CRAO patients (66 men 52.4%, median age 55 years) and 107 control participants (56 men 52.3%, matched by age, sex, and body mass index). Most CRAO patients (n = 104, 82.5%) had at least one internal medicine comorbidity, mainly hypercholesterolemia and hypertension, which coexisted in one-fourth of them. Furthermore, they had a 38.2% lower relative increase of FMD (FMD%) and a 23.1% thicker IMT compared to the controls (p < 0.001, both, also after adjustment for potential confounders). On echocardiography, the CRAO group was characterized by increased dimensions of the left atrium and thicker left ventricular walls, together with impaired left ventricular diastolic function. CRAO is related to vascular endothelial damage, atherosclerosis, and left ventricular diastolic cardiac dysfunction. Thus, non-invasive ultrasound assessments, such as FMD%, IMT, and echocardiography, may be helpful in screening patients with increased CRAO risk, particularly those with other comorbidities.
Tumor necrosis factor (TNF)-α is a proinflammatory cytokine that plays an important role in the pathogenesis of autoimmune diseases. The aim of the study was to establish an association between TNF-α ...promoter variability and systemic sclerosis (SSc). The study included 43 SSc patients and 74 controls. Four single nucleotide polymorphisms (rs361525, rs1800629, rs1799724, and rs1799964) located at the promoter of the TNFA gene were genotyped using commercially available TaqMan allelic discrimination assays with real-time PCR. The rs1799724 allele was associated with an increased SSc susceptibility (
= 0.028). In turn, none of the polymorphisms studied were related to the clinical and laboratory parameters of SSc patients, except for a higher prevalence of anti-Ro52 antibodies in the AG rs1800629 genotype in comparison to GG carriers (
= 0.04). Three of four cancer patients had both CT rs1799964 and AG rs361525 genotypes; thus, both of them were related to the increased risk of cancer, as compared to the TT (
= 0.03) and GG carriers (
= 0.0003), respectively. The TNFA C rs1799724 variant is associated with an increased risk of SSc, while the CT rs1799964 and AG rs361525 genotypes might enhance cancer susceptibility in SSc patients, although large observational and experimental studies are needed to verify the above hypothesis.
Atrial fibrillation (AF) is a frequent comorbidity in malignant patients. Anticancer therapies complicate anticoagulant strategy. We evaluated the safety and efficacy of long-term use of direct oral ...anticoagulants (DOACs) in breast cancer women.
In a prospective cohort study we enrolled 48 consecutive radically treated breast cancer women with AF (median age 63 interquartile range 56–69 years, CHA2DS2–VASc 2 2,3) score) and adjuvant hormonal therapy. Thromboembolic complications (stroke, transient ischemic attack TIA, venous thromboembolism VTE) and bleeding events (major and clinically relevant non-major bleeding CRNMB) were recorded in follow-up.
During a median follow-up of 40 (interquartile range 28–50.5) months 13 (27%) patients received apixaban, 22 (46%) rivaroxaban, and 13 (27%) dabigatran. One stroke (2.3%/year) and two CRNMBs (4.6%/year) were observed on apixaban. One TIA (1.3%/year), three major bleedings and two CRNMBs (6.7%/year, combined) were reported on rivaroxaban. Three VTE were documented in dabigatran treated individuals (7.8%/year), without any bleeding or cerebrovascular events. Women with thromboembolic events had higher body mass index (32 29–33) vs. 26 24–29) kg/m2, p = 0.02) and CHA2DS2–VASc score (3 3) vs. 2 1–3), p = 0.02). Most thromboembolic complications (n = 4, 80%) and all three major bleedings were observed in tamoxifen users, while three of four CRNMBs occurred on aromatase inhibitors. Mortality rates were low (apixaban, n = 1 2.3%/year, rivaroxaban, n = 3 5.22%/ year, and dabigatran, n = 2 4%/ year). No death was related to bleeding.
This study suggests that DOACs are an effective and safe therapeutic option in breast cancer patients with AF during adjuvant hormonal therapy.
A•There have been no published studies on the use of direct oral anticoagulants in breast cancer patients receiving hormonal therapy.•In our study the frequency of unfavorable clinical events was similar to those reported in large clinical trials.•Direct oral anticoagulants are safe and effective in long-term therapy of breast cancer women with atrial fibrillation during adjuvant hormonal therapy.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis associated with asthma and eosinophilia. Endothelial dysfunction has been well documented in other types of ...vasculitis but not in EGPA. Thirty patients (10 men and 20 women) diagnosed with EGPA and remaining in a remission, and 58 controls (24 men and 34 women) matched for age, sex, and body mass index, were enrolled in the study. We assessed each participants for typical risk factors of cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also measured flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Patients with EGPA had 20% higher serum level of VCAM-1 (
p
< 0.001) and 41.9% of thrombomodulin (
p
< 0.001). They also had 38.8% lower relative increase of FMD (FMD%) (
p
< 0.001), indicating endothelial dysfunction. These differences remained significant also after adjustment for potential confounders. Laboratory and ultrasonographic parameters of endothelial injury were correlated to the markers of inflammation and impaired kidney function. Determinants of lower FMD% in a simple regression model were pack-years of smoking (
β
= − 0.3 95% confidence interval (CI) − 0.5 to − 0.1), serum level of IL-6 (
β
= − 0.36 95% CI − 0.62 to − 0.1), and thrombomodulin (
β
= − 0.34 95% CI − 0.6 to − 0.08). EGPA patients are characterized by inflammatory endothelial injury that is likely related to the pathogenesis of the disease. Proper immunosuppressive treatment is the best method to prevent atherosclerosis and future cardiovascular events, the patients may also benefit from additional preventive interventions.
Background
Granulomatosis with polyangiitis (GPA) is a rare granulomatous vasculitis affecting small- and medium-sized blood vessels. In optimally treated patients with long-standing disease, the ...common cause of death is atherosclerosis even in the absence of typical risk factors.
Objective
To evaluate endothelial dysfunction in GPA patients.
Methods
44 patients (21 men and 23 women) diagnosed with GPA and 53 controls matched for age, sex, BMI and typical risk factors for cardiovascular diseases (22 men and 31 women) were enrolled in the study. We measured each participant’s serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also studied flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness (IMT) of the common carotid artery and aortic stiffness using echocardiography.
Results
Patients with GPA showed a 15.9% increase in serum levels of VCAM-1 (
p
= 0.01), 66% of IL-6 (
p
< 0.001) and 50.9% of thrombomodulin (
p
< 0.001) compared to controls. FMD% was 48.9% lower in patients with GPA in comparison to controls (
p
< 0.001), after adjustment for potential confounders, with no differences regarding IMT or aortic stiffness. FMD% was negatively associated with duration of the disease (
β
= − 0.18 95% CI: − 0.32 to − 0.04), C-reactive protein (
β
= − 0.17 95% CI: − 0.27 to − 0.07), IL-6 (
β
= − 0.29 95% CI: − 0.39 to − 0.19), blood creatinine level (
β
= − 0.2 95% CI: − 0.3 to − 0.1), and IMT (
β
= − 0.14 (− 0.24 to − 0.04). In a multiple linear regression model, kidney function, IMT, pack-years of smoking, diabetes and level of VCAM-1 were independent predictors of lower FMD%.
Conclusion
GPA is characterized by endothelial dysfunction. FMD is a useful tool for the detection of endothelial injury.
Higher levels of stress impact the prevalence of metabolic syndrome (MetS) and coronary heart disease. The association between MetS, impaired pulmonary function and low level of physical activity is ...still pending assessment in the subjects exposed to stress. The study aimed to examine whether higher levels of stress might be related to MetS and the plaque presence, as well as whether MetS might affect pulmonary function.
The study embraced 235 police officers (mean age 40.97 years) from the south of Poland. The anthropometrics and biochemical variables were measured; MetS was diagnosed using the International Diabetes Federation criteria. Computed tomography coronary angiography of coronary arteries, exercise ECG, measurements of brachial flow-mediated dilation, and carotid artery intima-media thickness were completed. In order to measure the self-perception of stress, 10-item Perceived Stress Scale (PSS-10) was applied. Pulmonary function and physical activity levels were also addressed. Multivariate logistic regression analyses were applied to determine the relationships between: 1/ incidence of coronary plaque and MetS per se, MetS components and the number of classical cardiovascular risk factors, 2/ perceived stress and MetS, 3/ MetS and pulmonary function parameters.
Coronary artery atherosclerosis was less associated with MetS (OR = 2.62, 95%CI 1.24-5.52; p = 0.011) than with a co-existence of classical cardiovascular risk factors (OR = 5.67, 95% CI 1.07-29.85, p = 0.03; for 3 risk factors and OR = 9.05; 95% CI 1.24-66.23, p = 0.02; for 6 risk factors, respectively). Perceived stress increased MetS prevalence (OR = 1.07, 95% CI 1.03-1.13; p = 0.03), and impacted coronary plaque prevalence (OR = 1.05, 95% CI 1.001-1.10; p = 0.04). Leisure-time physical activity reduced the chances of developing MetS (OR = 0.98 95% CI 0.96-0.99; p = 0.02). MetS subjects had significantly lower values of certain pulmonary function parameters.
Exposure to job-specific stress among police officers increased the prevalence of MetS and impacted coronary plaque presence. MetS subjects had worse pulmonary function parameters. Early-stage, comprehensive therapeutic intervention may reduce overall risk of cardiovascular events and prevent pulmonary function impairment in this specific occupational population.
Certain mediators, such as soluble growth factors and cytokines, among others, are implicated in the immunopathogenesis of systemic sclerosis (SSc).
This study aimed to examine the association ...between serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), interferon alpha (IFN-α), and basic fibroblast growth factor (bFGF) and the clinical presentation and course of SSc.
This longitudinal, observational study included 43 patients with SSc and 24 healthy subjects. Serum concentrations of VEGF, IL-8, IFN-α, and bFGF were measured at baseline in patients previously treated for SSc. Medical history of patients was analyzed retrospectively at the time of cytokine measurement to infer clinical correlations, and during follow-up for a median of 5 years, assessing the incidence of death or cancer.
The bFGF and IFN-α concentrations differed between SSc patients and controls (p < 0.01). In turn, organ involvement and SSc phenotypes did not impact studied cytokine concentrations, similar to systemic steroid and/or immunosuppressant use at enrollment. However, we have documented a positive correlation between the current oral steroid dose and serum levels of IL-8 and bFGF. Furthermore, patients with a VEGF level ≥95.7 pg/mL and IFN-α level ≥3.6 pg/mL required cyclophosphamide therapy more often, currently or in the past (approx. 3-fold and 4-fold, respectively). Substantially elevated VEGF and IFN-α concentrations at baseline were associated with higher cancer occurrence (n = 4) during follow-up, while elevated circulating IL-8 level was associated with an increased risk of death (n = 9).
The SSc group was characterized by higher serum concentrations of bFGF and IFN-α compared to healthy controls. Patients treated with cyclophosphamide or receiving higher systemic steroid doses, thus suffering from a more severe disease type, had increased cytokine levels. Elevated circulating IFN-α and VEGF levels might be correlated with cancer, whereas raised IL-8 levels may be associated with an increased risk of death. However, further research is needed to verify our findings.
Sarcoidosis is a multisystem inflammatory granulomatous disease of unknown cause that most commonly affects lungs and lymph nodes, with frequent yet asymptomatic cardiac involvement. The ...epidemiologically associated cardiovascular risk suggests an underlying prothrombotic state and endothelial dysfunction, currently understudied in the available literature. Therefore, we aimed to investigate prothrombotic plasma properties together with selected echocardiographic and laboratory biomarkers of cardiovascular injury in that disease. N = 53 patients with pulmonary sarcoidosis in clinical remission and N = 66 matched controls were assessed for inflammatory and endothelial injury biomarkers, plasma thrombin generation profile, and echocardiographic and lung function parameters. Sarcoidosis cases had impaired systolic and diastolic left ventricular function, higher concentrations of inflammatory markers, D-dimer and factor VIII activity compared to the controls. The coexistence of extrapulmonary disease was associated with elevated circulating vascular cell adhesion molecule 1, while cases with hypercalcemia had higher thrombomodulin concentration. Sarcoidosis was characterized by the unfavorably altered thrombin generation profile, reflected by the 16% higher endogenous thrombin potential (ETP), 24% increased peak thrombin concentration, and 12% shorter time to thrombin peak in comparison to the control group. ETP was higher in cases with proxies of pulmonary restriction, extrapulmonary-extracutaneous manifestation, and need for corticosteroids use. Despite the clinical remission, sarcoidosis is related to prothrombotic plasma properties and signs of endothelial injury, likely contributing to the higher risk of cardiovascular events. In addition, subclinical cardiac involvement may play an additional role, although further clinical and experimental studies are needed to verify these findings.
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