The Role of Opioid Receptor Antagonists in Regulation of Blood Pressure and T-Cell Activation in Mice Selected for High Analgesia Induced by Swim Stress.

Opioid peptides and their G protein-coupled receptors are important regulators within the cardiovascular system, implicated in the modulation of both heart and vascular functions. It is known that naloxone-an opioid antagonist-may exert a hypertensive effect. Recent experimental and clinical evidence supports the important role of inflammatory mechanisms in hypertension. Since opioids may play a role in the regulation of both blood pressure and immune response, we studied these two processes in our model. We aimed to evaluate the effect of selective and non-selective opioid receptor antagonists on blood pressure and T-cell activation in a mouse model of high swim stress-induced analgesia. Blood pressure was measured before and during the infusion of opioid receptor antagonists using a non-invasive tail-cuff measurement system. To assess the activation of T-cells, flow cytometry was used. We discovered that the non-selective antagonism of the opioid system by naloxone caused a significant elevation of blood pressure. The selective antagonism of µ and κ but not δ opioid receptors significantly increased systolic blood pressure. Subsequently, a brief characterization of T-cell subsets was performed. We found that the blockade of µ and δ receptors is associated with the increased expression of CD69 on CD4 T-cells. Moreover, we observed an increase in the central memory CD4 and central memory CD8 T-cell populations after the δ opioid receptor blockade. The antagonism of the µ opioid receptor increased the CD8 effector and central memory T-cell populations.

Efficacy and safety of bisoprolol 5 mg plus amlodipine 5 mg in patients with hypertension uncontrolled on monotherapy with 5 mg of amlodipine, a phase III multicenter, randomized, double-blind, placebo-controlled clinical trial - the AMCOR study.

OBJECTIVE: To evaluate the antihypertensive effect and safety of bisoprolol 5 mg (BISO5mg) and amlodipine 5 mg (AMLO5mg) combination in comparison to AMLO5mg in hypertensive subjects uncontrolled with AMLO5mg. METHODS: Phase III, prospective, randomized, double-blind, placebo-controlled, 8-week trial with parallel design (EudraCT Number: 2019-000751-13). RESULTS: 367 patients aged 57.58 ± 14.62 years were randomized to BISO5mg once daily on top of AMLO5mg (n = 181) or placebo on top of AMLO5mg (n = 186). Systolic/diastolic blood pressure (SBP/DBP) in the bisoprolol-treated group was reduced by 7.2 ± 12.74/3.95 ± 8.85 mmHg at 4 weeks (both p < .0001) and by 5.5 ± 12.44/3.84 ± 9.46 mmHg at 8 weeks (p < .0001/p < .0002) compared to placebo control. Bisoprolol-treated group had lower heart rate than placebo control (difference -7.23 ± 9.84/-6.25 ± 9.26 beats per minute at 4 and 8 weeks, respectively, both p < .0001). Both target SBP and DBP was achieved at 4 weeks by 62 vs. 41% (p = .0002) and at 8 weeks by 65 vs. 46% (p = .0004) of bisoprolol-treated patients and placebo group patients, respectively. SBP <140 mmHg was achieved at 4 and 8 weeks in 68 and 69% of bisoprolol-treated patients and 45 and 50% of placebo group patients, respectively. No deaths and serious adverse events were reported. Adverse events occurred in 34 bisoprolol-treated patients vs. 22 patients in the placebo group (p = .064). Bisoprolol was withdrawn due to adverse events in 7 patients, mostly (n = 4) due to asymptomatic bradycardia. CONCLUSIONS: Addition of bisoprolol to patients uncontrolled with amlodipine monotherapy significantly improves blood pressure control. We can expect additional 7.2/3.95 mmHg SBP/DBP lowering effect by adding bisoprolol 5 mg to amlodipine 5 mg.

Mouse CCL9 Chemokine Acts as Tumor Suppressor in a Murine Model of Colon Cancer.

Colorectal cancer is the third most frequently diagnosed cancer in the world. Despite extensive studies and apparent progress in modern strategies for disease control, the treatment options are still not sufficient and effective, mostly due to frequently encountered resistance to immunotherapy of colon cancer patients in common clinical practice. In our study, we aimed to uncover the CCL9 chemokine action employing the murine model of colon cancer to seek new, potential molecular targets that could be promising in the development of colon cancer therapy. Mouse CT26.CL25 colon cancer cell line was used for introducing lentivirus-mediated CCL9 overexpression. The blank control cell line contained an empty vector, while the cell line marked as CCL9+ carried the CCL9-overexpressing vector. Next, cancer cells with empty vector (control) or CCL9-overexpressing cells were injected subcutaneously, and the growing tumors were measured within 2 weeks. Surprisingly, CCL9 contributed to a decline in tumor growth in vivo but had no effect on CT26.CL25 cell proliferation or migration in vitro. Microarray analysis of the collected tumor tissues revealed upregulation of the immune system-related genes in the CCL9 group. Obtained results suggest that CCL9 reveals its anti-proliferative functions by interplay with host immune cells and mediators that were absent in the isolated, in vitro system. Under specific study conditions, we determined unknown features of the murine CCL9 that have so far bee reported to be predominantly pro-oncogenic.

Association Between Achieved Low-Density Lipoprotein Cholesterol Levels and Long-Term Cardiovascular and Safety Outcomes: An Analysis of FOURIER-OLE.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for atherosclerotic cardiovascular disease. However, the optimal achieved LDL-C level with regard to efficacy and safety in the long term remains unknown. METHODS: In FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), 27 564 patients with stable atherosclerotic cardiovascular disease were randomized to evolocumab versus placebo, with a median follow-up of 2.2 years. In the open-label extension (FOURIER-OLE), 6635 of these patients were transitioned to open-label evolocumab regardless of initial treatment allocation in the parent trial and were followed for an additional median of 5 years. In this prespecified analysis, we examined the relationship between achieved LDL-C levels (an average of the first 2 LDL-C levels measured) in FOURIER-OLE (available in 6559 patients) and the incidence of subsequent cardiovascular and safety outcomes. We also performed sensitivity analyses evaluating cardiovascular and safety outcomes in the entire FOURIER and FOURIER-OLE patient population. Multivariable modeling was used to adjust for baseline factors associated with achieved LDL-C levels. RESULTS: In FOURIER-OLE, 1604 (24%), 2627 (40%), 1031 (16%), 486 (7%), and 811 (12%) patients achieved LDL-C levels of <20, 20 to <40, 40 to <55, 55 to <70, and ≥70 mg/dL, respectively. There was a monotonic relationship between lower achieved LDL-C levels-down to very low levels <20 mg/dL-and a lower risk of the primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina or coronary revascularization) and the key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) that persisted after multivariable adjustment (adjusted Ptrend<0.0001 for each end points). No statistically significant associations existed in the primary analyses between lower achieved LDL-C levels and increased risk of the safety outcomes (serious adverse events, new or recurrent cancer, cataract-related adverse events, hemorrhagic stroke, new-onset diabetes, neurocognitive adverse events, muscle-related events, or noncardiovascular death). Similar findings were noted in the entire FOURIER and FOURIER-OLE cohort up to a maximum follow-up of 8.6 years. CONCLUSIONS: In patients with atherosclerotic cardiovascular disease, long-term achievement of lower LDL-C levels, down to <20 mg/dL (<0.5 mmol/L), was associated with a lower risk of cardiovascular outcomes with no significant safety concerns. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01764633.

A new threshold for kidney asymmetry improves association with abnormal renal-aortic ratio for diagnosis of renal artery stenosis.

BACKGROUND: Renal artery stenosis (RAS) reflects more widespread atherosclerosis deposition and is associated with high morbidity and mortality. According to the guidelines, a discrepancy in the size of the kidneys of over 15 mm found in an ultrasound should initiate the RAS diagnostic algorithm. This study aims to find the optimal threshold for renal asymmetry that better reflects the frequency of a significantly abnormal renal-aortic ratio (RAR), justifying further RAS diagnostic workup, than the currently used cut-off of 15 mm difference in renal diameters. METHODS: The analysis included 1175 patients (mean age: 52 years, IQR: 38-66, men/women: 597/578) who underwent Doppler ultrasonography screening of renal arteries with recorded kidney size and RAR calculation. Ultrasound features of RAS were defined as a RAR greater than 3.5 or signs of renal artery occlusion. Receiver operating characteristic (ROC) curves were created and analyzed for absolute differences in kidney size and abnormal RAR. We calculated the area under the curve (AUC) and optimal cut-off values for sensitivity and specificity analysis. RESULTS: The final analysis included 169 patients with a significant difference in renal dimension. RAS features were met in 61 patients. According to ROC curve analysis, the optimal index of renal asymmetry was 12 mm. The sensitivity and specificity for this method were 82.0% and 83.3%, respectively, and AUC was 86.3%. CONCLUSION: Changing the definition of a significant difference in kidney size from 15 mm to 12 mm increases sensitivity and specificity for abnormal RAR and this finding may accelerate the diagnosis of RAS.

Red blood cell distribution width is associated with increased interactions of blood cells with vascular wall.

The mechanism underlying the association between elevated red cell distribution width (RDW) and poor prognosis in variety of diseases is unknown although many researchers consider RDW a marker of inflammation. We hypothesized that RDW directly affects intravascular hemodynamics, interactions between circulating cells and vessel wall, inducing local changes predisposing to atherothrombosis. We applied different human and animal models to verify our hypothesis. Carotid plaques harvested from patients with high RDW had increased expression of genes and proteins associated with accelerated atherosclerosis as compared to subjects with low RDW. In microfluidic channels samples of blood from high RDW subjects showed flow pattern facilitating direct interaction with vessel wall. Flow pattern was also dependent on RDW value in mouse carotid arteries analyzed with Magnetic Resonance Imaging. In different mouse models of elevated RDW accelerated development of atherosclerotic lesions in aortas was observed. Therefore, comprehensive biological, fluid physics and optics studies showed that variation of red blood cells size measured by RDW results in increased interactions between vascular wall and circulating morphotic elements which contribute to vascular pathology.

The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience.

Introduction: Recently published case reports suggest the benefit of empagliflozin use in subjects with glycogen storage disease Ib (GSD Ib). Methods: We present the clinical and laboratory data of 2 adult brothers with GSD Ib treated with empagliflozin for 12 months. Results: There was no severe infection during administration of empagliflozin. The improvement of clinical symptoms of inflammatory bowel disease and arthritis along with reduction in serum CRP levels and urinary albumin excretion was noted. Neutrophil count increased, allowing for reduction or temporary withdrawal of G-CSF treatment. Conclusions: Empagliflozin may be a new safe treatment in GSD Ib patients with an advanced stage of the disease.

A growing evidence base for the fixed-dose combination of bisoprolol and amlodipine to manage hypertension.

OBJECTIVES: Hypertension is a major cause of morbidity and mortality worldwide. Although current drug therapies can be effective, management of hypertension is closely linked to patient adherence to therapy. A fixed-dose combination (FDC) of bisoprolol and amlodipine has shown to be effective and convenient, and to significantly improve patient adherence. METHODS: This narrative review evaluates recent evidence from four studies which explore the efficacy, safety, and adherence of FDC bisoprolol and amlodipine in patients with hypertension: one observational study; two randomized clinical trials (RCTs); and one indirect comparison analysis. RESULTS: All four studies support the efficacy of FDC bisoprolol and amlodipine in the management of hypertension, highlighting clinically meaningful reductions in systolic and diastolic blood pressure (BP), and high adherence. In a large cohort study exploring FDC bisoprolol and amlodipine in daily practice, high adherence improved BP and heart rate control versus baseline. In a Phase 3 RCT, FDC bisoprolol and amlodipine demonstrated superiority over monotherapies in BP control and a positive tolerability profile, further supporting its use to manage hypertension in second line following monotherapy. In another Phase 3 RCT, the combination of bisoprolol and amlodipine led to significant BP reductions versus monotherapy with amlodipine with a comparable safety profile. Finally, in the indirect treatment comparison, a low dose combination of bisoprolol and amlodipine showed a similar decrease in systolic BP compared with a maximum dose of amlodipine. CONCLUSIONS: This review adds to growing evidence supporting the efficacy, safety, and tolerability of FDC bisoprolol and amlodipine in managing hypertension.

Prevalence of self­reported heart failure in the adult Polish population: results of the NATPOL 2011 study.

INTRODUCTION: Chronic heart failure (CHF) is a growing medical and economic problem, especially in Central and Eastern Europe. However, only a few studies analyzed the prevalence of CHF in this region. OBJECTIVES: The aim of the study was to assess the prevalence of CHF in a representative sample of adult Poles. PATIENTS AND METHODS: The NATPOL 2011 project was a cross­sectional study of a representative sample of the adult Polish population that included 2413 individuals (1245 women, 1168 men) aged 18 to 79 years (mean [SD] age, 45.8 [16.7] years). All participants completed a detailed questionnaire and underwent laboratory tests. We evaluated the prevalence of CHF based on self­reported symptoms, Pol-ish National Health Fund database, and the N-terminal pro-B-type natriuretic peptide (NT­proBNP) level. RESULTS: The proportion of patients that reported the diagnosis of CHF was 4.3% (95% CI, 3.6%-5.2%). Only 0.2% of people aged under 40 years reported CHF, compared with 3.2% of those aged 40 to 59 years and 13.2% of those aged 60 to 79 years. The distribution of NT­proBNP levels in the patients with CHF was markedly skewed to the right, with the median value of 181 pg/ml (interquartile range, 90.8-531). Among the 104 individuals who declared having CHF, almost 56% had a record of at least 1 outpatient visit or hospitalization related to the ICD­10 I50 code in the National Health Fund database, which translates to 2.4% of confirmed diagnoses of CHF in all Polish adults. CONCLUSIONS: The results of our study indicated that the proportion of inhabitants of Poland aged 18 to 79 years with heart failure was somewhere between 2.4% and 4.3%. This corresponds to 720 000 to 1 200 000 of diagnosed CHF cases in Poland.

Preference and Adherence to a Fixed-Dose Combination of Bisoprolol-Aspirin and Blood Pressure Control: Results of an Open-Label, Multicentre Study.

This study assessed blood pressure (BP) control and adherence in patients given a fixed-dose combination (FDC) of bisoprolol (BIS) + aspirin (ASA) compared to those given these two drugs as separate tablets. Patients with hypertension and/or coronary heart disease treated with two-pill BIS (5−10 mg) and ASA (75−100 mg) were switched to FDC BIS + ASA (either 5/75 mg or 10/75 mg) ≥4 weeks prior to study initiation. Adherence was estimated from pill counts and patients' diaries (1−2 months and 3 months after inclusion) and using Morisky's Medication Adherence Scale (MMAS) at 3 months. BP control with the two treatments was compared. A total of 356 patients were enrolled (mean (SD) age: 64.3 ± 11.9 years, 56.5% male). Mean (SD) duration of prior treatment with two-pill BIS and ASA was 17.8 ± 26.6 months. FDC adherence was excellent or good (≥76%) in 98.3% and 98.0% of patients based on pill counts and patients' diaries, respectively. Overall MMAS score was 3.1 ± 1.0. A significant decrease was observed in mean systolic BP, mean diastolic BP and heart rate over the 3-month period (all p < 0.001). FDC BIS + ASA was associated with excellent adherence and improved BP control. The majority (78.7%) of patients preferred the FDC.

Familial SDHB gene mutation in disseminated non-hypoxia-related malignant paraganglioma treated with [90Y]Y/[177Lu]Lu- DOTATATE.

Familial paraganglioma may be related to mutations in succinate dehydrogenase (SDH) enzyme complex genes. Among patients with hereditary paraganglioma, SDH subunit B (SDHB) gene mutations are associated with the highest morbidity and mortality related to a higher malignancy rate. We report a family with the c.689G>A (p.Arg230His) mutation in the SDHB gene identified in two family members, a father and his daughter. While the 14-year-old daughter had no evidence of clinical disease, recurrent and later disseminated [131I]metaiodobenzylguanidine uptake-negative head and neck paraganglioma with multiple bone metastases developed in the father who underwent peptide receptor radionuclide therapy with [90Y]Y/[177Lu]Lu-dodecane tetraacetic acid octreotate (DOTATATE) at the time of the genetic diagnosis. This treatment was repeated 6 years later due to disease progression and the patient, who is currently 49 years old, remains alive and in good overall clinical condition at 8 years of follow-up after the original presentation at our unit. The growing armamentarium of imaging methods available for such patients may inform decision making regarding choice of the optimal treatment approach, potentially contributing to improved outcomes.

Cardiovascular Effects Mediated by HMMR and CD44.

Cardiovascular disease (CVD) is the leading cause of death worldwide. The most dangerous life-threatening symptoms of CVD are myocardial infarction and stroke. The causes of CVD are not entirely clear, and new therapeutic targets are still being sought. One of the factors involved in CVD development among vascular damage and oxidative stress is chronic inflammation. It is known that hyaluronic acid plays an important role in inflammation and is regulated by numerous stimuli, including proinflammatory cytokines. The main receptors for hyaluronic acid are CD44 and RHAMM. These receptors are membrane proteins that differ in structure, but it seems that they can perform similar or synergistic functions in many diseases. Both RHAMM and CD44 are involved in cell migration and wound healing. However, their close association with CVD is not fully understood. In this review, we describe the role of both receptors in CVD.

The Effect of Antihypertensive Medications on Testing for Primary Aldosteronism.

Primary aldosteronism (PA) is a potentially curable form of secondary hypertension caused by excessive renin-independent aldosterone secretion, leading to increased target organ damage and cardiovascular morbidity and mortality. The diagnosis of PA requires measuring renin and aldosterone to calculate the aldosterone-to-renin ratio, followed by confirmatory tests to demonstrate renin-independent aldosterone secretion and/or PA subtype differentiation. Various antihypertensive drug classes interfere with the renin-angiotensin-aldosterone axis and hence evaluation for PA should ideally be performed off-drugs. This is, however, often precluded by the risks related to suboptimal control of blood pressure and serum potassium level in the evaluation period. In the present review, we summarized the evidence regarding the effect of various antihypertensive drug classes on biochemical testing for PA, and critically appraised the issue whether and which antihypertensive medications should be withdrawn or, conversely, might be continued in patients evaluated for PA. The least interfering drugs are calcium antagonists, alpha-blockers, hydralazine, and possibly moxonidine. If necessary, the testing may also be attempted during treatment with beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers but renin and aldosterone measurements must be interpreted in the context of known effects of these drugs on these parameters. Views are evolving on the feasibility of testing during treatment with mineralocorticoid receptor antagonists, as these drugs are now increasingly considered acceptable in specific patient subsets, particularly in those with severe hypokalemia and/or poor blood pressure control on alternative treatment.

Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System.

The opioid system is well-known for its role in modulating nociception and addiction development. However, there are premises that the endogenous opioid system may also affect blood pressure. The main goal of the present study was to determine the impact of different endogenous opioid system activity and its pharmacological blockade on blood pressure. Moreover, we examined the vascular function in hyper- and hypoactive states of the opioid system and its pharmacological modification. In our study, we used two mouse lines which are divergently bred for high (HA) and low (LA) swim stress-induced analgesia. The obtained results indicated that individuals with low endogenous opioid system activity have higher basal blood pressure compared to those with a hyperactive opioid system. Additionally, naloxone administration only resulted in the elevation of blood pressure in HA mice. We also showed that the hypoactive opioid system contributes to impaired vascular relaxation independent of endothelium, which corresponded with decreased guanylyl cyclase levels in the aorta. Together, these data suggest that higher basal blood pressure in LA mice is a result of disturbed mechanisms in vascular relaxation in smooth muscle cells. We believe that a novel mechanism which involves endogenous opioid system activity in the regulation of blood pressure will be a promising target for further studies in hypertension development.

Socioeconomic correlates and biochemical profiles of smokers in Poland: a cross-sectional study.

INTRODUCTION: Epidemiological studies have shown a fairly constant association between the socioeconomic status and smoking. However, associations between smoking and the biological indicators of health status have not been well described yet. OBJECTIVES: This study aimed to determine the relationship among smoking, biochemical risk factors, and sociodemographic characteristics in the Polish population. PATIENTS AND METHODS: A survey was carried out in a representative sample of Polish residents aged 18 to 79 years. A total of 2413 randomly selected subjects participated in the survey. Logistic regression analysis as well as parametrical and nonparametrical tests were performed. RESULTS: Significantly higher cholesterol, apolipoprotein B, and potassium levels were observed in smoking women and men compared with the nonsmoking population. Significantly lower bilirubin levels were noted in smoking individuals. Higher C­reactive protein and lower creatinine levels were reported only in the smoking male population compared with nonsmokers. There was a significant inverse gradient in the relationship between income and smoking. Single women and men were at greater risk of being smokers (odds ratio [OR], 1.9 and 2.39, respectively). Individuals from small towns (less than 50 000 inhabitants) were at significantly greater risk of smoking compared with those living in rural areas (OR, 1.45 and 1.64 in women and men, respectively). CONCLUSIONS: We found differences regarding socioeconomic characteristics and major biochemical parameters between smokers and nonsmokers in Poland. However, it is difficult to establish which associations are causal for cardiovascular risk owing to the cross­sectional design of this study.

Diagnostic role of chest computed tomography in coronavirus disease 2019.

Coronavirus disease 2019 (COVID­19) is an infectious disease caused by a novel strain of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2), that appeared in China in December 2019 and spread globally, evolving into the currently observed pandemic. The laboratory diagnosis of SARS­CoV­2 infection is currently based on real­time reverse transcriptase-polymerase chain reaction (RT­PCR) testing, and imaging cannot replace genetic testing in patients with suspected COVID­19. However, with predominant respiratory manifestations of COVID­19, particularly in more severe cases, chest imaging using computed tomography (CT) plays a major role in detecting viral lung infection, evaluating the nature and extent of pulmonary lesions, and monitoring the disease activity. The role of chest CT as a diagnostic tool may be increased when the laboratory testing capacities using RT­PCR prove inaccurate or insufficient during a major outbreak of the disease. In these settings, a rapid presumptive diagnosis of COVID­19 potentially offered by CT might be an advantage, in addition to obvious benefits of delineating the nature and extent of pulmonary lesions. In the present paper, we reviewed the diagnostic role of chest CT in patients with COVID­19.

An Exploratory Analysis of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition and Aortic Stenosis in the FOURIER Trial.

Importance: Despite recent advances in treatment of severe aortic valve stenosis (AS), AS remains a life-threatening condition with no proven disease-modifying therapy. Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) have been implicated in the pathobiology of AS. The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab reduces circulating LDL-C concentrations by 50% to 60% and Lp(a) by 20% to 30%. Objective: To determine whether evolocumab reduces the risk of AS events in patients with atherosclerotic cardiovascular disease. Interventions: Patients were randomized 1:1 to evolocumab or placebo. Design, Setting, and Participants: Exploratory analysis of the FOURIER trial, which enrolled 27 564 patients with stable atherosclerotic cardiovascular disease who were taking statin therapy at 1242 sites in 49 countries from February 2013 to November 2016. Patients were randomized to evolocumab or placebo and followed up for a median (interquartile range) of 2.2 (1.8-2.5) years. This post hoc analysis was performed from September 2019 to February 2020. Main Outcomes and Measures: Site-reported adverse events of new or worsening AS or aortic valve replacement (termed AS events). The adjusted risk of AS events was calculated with a multivariable model including concentrations of Lp(a) and LDL-C corrected for Lp(a) content, plus age, sex, diabetes, hypertension, current smoking, and estimated glomerular filtration rate. Evolocumab efficacy was tested using a Cox proportional hazards model. Results: Aortic stenosis events occurred in 63 patients (48 men [76%]; mean [SD] age, 69 [9] years) over a median of 2.2 years. Elevated Lp(a) concentration was associated with higher rates of AS events (adjusted hazard ratio [aHR], 1.55 [95% CI, 1.17-2.05] per SD; P = .002), including aortic valve replacement (aHR, 2.22 [95% CI, 1.38-3.58] per SD; P = .001), after multivariable adjustment. The corrected LDL-C concentration was not significantly associated with AS events (aHR, 1.23 [95% CI, 0.93-1.61] per SD; P = .14). The overall HR for AS events with evolocumab was 0.66 (95% CI, 0.40-1.09), with no apparent association in the first year (HR, 1.09 [95% CI, 0.48-2.47]) but an HR of 0.48 (95% CI, 0.25-0.93) after the first year of treatment. Conclusions and Relevance: In this exploratory analysis of the FOURIER trial, higher Lp(a) levels, but not Lp(a)-corrected LDL-C levels, were associated with a higher risk of subsequent AS events, including aortic valve replacement. Long-term therapy with evolocumab may reduce AS events, and this raises the possibility that specific pharmacologic lipid-lowering therapy could offer a means to prevent or slow the progression of AS. These exploratory findings merit further investigation with a dedicated randomized clinical trial. Trial Registration: ClinicalTrials.gov Identifier: NCT01764633.

Geographic disparities in the application of endovascular repair of unruptured abdominal aortic aneurysm - Polish population analysis.

PURPOSE: Differences between the regions of the same country regarding the management of abdominal aortic aneurysm (AAA) have rarely been published. The aim of the study was to analyze the absolute and relative number of unruptured AAA repairs, utilizing endovascular aneurysm repair (EVAR) vs. open aneurysm repairs (OAR) and compare the AAA patients population from all 16 administrative districts in Poland. MATERIAL AND METHODS: We used the Polish National Health Fund data of all patients who underwent elective treatment of AAA between 1st January 2011 and 22nd March 2016 and analyzed the absolute/relative number of all AAA repairs, OAR, EVAR and incidence of concomitant diseases in distinctive regions. Relationships between the utilization of EVAR and the number of procedures, age, gender and concomitant diseases were studied. RESULTS: A total of 7805 patients (mean age 70.9 ± 8.1 yrs) underwent OAR (n = 2336) or EVAR (n = 5469). The age and the incidence of concomitant diseases differed significantly between districts. The highest absolute number of all repairs was performed in the Masovian district (n = 1442), while the highest relative number of all repairs in the Lublin district (36.3/100,000 65+/year). The utilization of EVAR ranged from 34.5% to 93.9% and correlated positively with the number of EVAR, age and chronic obstructive pulmonary disease occurrence and negatively with OAR number. CONCLUSIONS: Striking differences in the relative numbers of unruptured AAA repairs and in the population characteristics in various districts of the country point to the possibility of different health needs in the regions and variations in standards of care.

Red-cell distribution width is associated with higher risk of vascular complications after carotid thromboendartherectomy.

Red Cell Distribution Width (RDW) is associated with increased morbidity and mortality in subjects with clinically manifested vascular diseases as well as predicts cardiovascular incidents and different types of cancer in a healthy population. AIM: The aim of the study was to evaluate relationship between clinical outcomes in patients after carotid thromboendarterectomy and initial RDW values. MATERIALS AND METHODS: Data from 115 subsequent patients who underwent carotid thromboendartherectomy (TEA) were retrospectively analyzed. All patients had complete blood count measured including RDW and were observed for 18 months post-operatively. On each visit doppler ultrasound of carotid arteries was performed to evaluate the development of restenosis and progression of atherosclerosis. RESULTS: Primary endpoint defined as cardiovascular death, new cerebrovascular incidents (stroke or TIA), any new revascularization procedure (carotid, coronary or peripheral) and restenosis of the operated artery occurred in 28 patients. They differed from subjects with uneventful course with increased prevalence of previous cerebrovascular incidents (75.0% and 42.5%, respectively; p=0.0028) and higher RDW values (14,37±1.55% and 13.77±0.96%, p=0.0155). CONCLUSIONS: In patients with high risk for cerebrovascular incidents, RDW identifies population at increasingly high probability of vascular complications which should be subjected to intensive therapeutic regimen.