Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target.

Abdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor ß signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9 loss of function prevented the development of AAA in a preclinical mouse model.

Periodontal status and the incidence of selected bacterial pathogens in periodontal pockets and vascular walls in patients with atherosclerosis and abdominal aortic aneurysms.

The aim of the study was to examine the periodontal status of patients with atherosclerosis and abdominal aortic aneurysms. The occurrence of 5 periodontopathogens was evaluated in periodontal pockets and atheromatous plaques together with specimens from pathologically changed vascular walls of aortic aneurysms. The study comprised 39 patients who qualified for vascular surgeries. Patients with periodontitis and concomitant atherosclerosis or aneurysms were enrolled in the study. Periodontal indices were evaluated, and subgingival plaque samples were examined together with atheromatous plaques or specimens from vascular walls to identify, by polymerase chain reaction (PCR), the following periodontopathogens: Porphyromonas gingivalis, Tanarella forsythia, Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Treponema denticola. The majority of patients had chronic severe generalized periodontitis in stages III and IV. Laboratory investigations showed the occurrence of one or more of the five targeted periodontopathogens in 94.6% of the periodontal pockets examined. Of the examined periodontopathogens, only Porphyromonas gingivalis was confirmed in 1 atheromatous plaque sample collected from the wall of an aortic aneurysm. Therefore, the occurrence of this bacterium in these vessels was considered to be occasional in patients with chronic periodontitis.

The Expression and Prognostic Significance of VEGF and CXCR4 in Gastric Cancer: Correlation with Angiogenesis, Lymphangiogenesis and Progression.

The cellular response to hypoxia includes the expression of hypoxia-inducible factor-1 (HIF-1) and its target genes: vascular endothelial growth factor (VEGF) and CXC chemokine receptor 4 (CXCR4). The aim of this study was to investigate the expression and prognostic significance of VEGF and CXCR4, which are responsible for angiogenesis and progression in gastric cancer. Twenty-eight gastric cancer patients were analyzed. The mRNA expression was examined in primary tumors and corresponding normal gastric mucosa by RT-PCR. The protein level was examined by immunohistochemistry staining. The high expression of VEGF and CXCR4 was found in 71.0 and 64.0% of tumors, respectively. The mean levels of VEGF and CXCR4 were upregulated in primary tumors compared to normal mucosa (p = 0.0007, p = 0.0052). A correlation between VEGF expression and tumor invasion (p = 0.0216) and stage (p = 0.0181) was found. CXCR4 expression correlated with lymph node metastases (p = 0.0237) and stage (p = 0.0054). The VEGF expression correlated with microvessel density (MVD) (p = 0.0491). The overall 3-year survival rate was 46.4% and correlated negatively with high CXCR4 mRNA expression (p = 0.0089). VEGF and CXCR4 play an important role in tumor progression. Their overexpression correlates with a bad prognosis and may improve high-risk patient selection, and these patients may obtain additional survival benefits if treated more aggressively.

Mid-Term Results of Endovascular Aneurysm Sealing in the Treatment of Abdominal Aortic Aneurysm With Unfavorable Morphology.

PURPOSE: To report mid-term results of endovascular aneurysm sealing (EVAS) of abdominal aortic aneurysms (AAA) deemed unsuitable for a standard endovascular aneurysm repair (EVAR). METHODS: A prospectively maintained database of 42 patients with EVAR-unfavorable anatomy treated by EVAS combined with chimney grafts in case of the proximal AAA neck shorter than 5 mm was analyzed. Early outcomes included final angiographic result, intra- and early post-operative deaths, and complications. Mid-term outcomes included all-cause mortality (ACM), aneurysm-related mortality (ARM), patency of the stents, occurrence of endoleaks, serious complications and graft failures defined as the AAA growth of more than 5 mm, type I endoleak, occlusion of the stent-graft or chimney graft, aorto-duodenal fistula, or aneurysm rupture. RESULTS: The procedure was completed in all patients. Twenty-eight chimney grafts were implanted in 19 patients. Patients were followed for a median of 24 months (range 12-34 months). There were 2 intraoperative ruptures and 1 patient died in an early postoperative period. The cumulative ACM was 15, 21, and 36% at 12, 24, and 36 months, respectively, and the cumulative ARM was 8, 11, and 27% at 12, 24, and 36 months, respectively. Three out of 5 aneurysm-related deaths were due to a secondary aorto-duodenal fistula. The cumulative incidence of graft failure was 20, 27, and 42% at 12, 24, and 36 months, respectively. The cumulative incidence of an endoleak was 5, 9, and 23% at 12, 24, and 36 months, respectively. The graft failure increased significantly both ACM (p = .012) and ARM (p = .00003). The implantation of chimney grafts at the initial procedure increased ARM significantly (p = .008). The presence of an endoleak did not have any significant influence on ACM and ARM. CONCLUSION: Patients treated with EVAS for AAAs with EVAR-unfavorable anatomy, especially those with chimney grafts, exhibit a high risk of graft failure and subsequent death.

Midterm Results of the Treatment of Penetrating Abdominal Aortic or Iliac Artery Ulcer with the BeGraft Balloon-Expandable Covered Stent-A Single-Center Experience.

BACKGROUND: The purpose of the study was to evaluate the feasibility and efficacy of the novel BeGraft covered stent for the treatment of abdominal penetrating aortic ulcer (PAU) or penetrating ulcers of the iliac arteries (PUIAs). METHODS: This was a single-center observational study, which included 24 consecutive patients who underwent endovascular surgery due to abdominal PAU or PUIA between June 2017 and September 2019. Demographics of patients, lesion characteristics, diameter and length of the BeGraft stents, and postoperative events were prospectively collected and retrospectively analyzed. Follow-up examinations were performed at 1, 6, 12, and 24 months with clinical and hemodynamic evaluation. Outcome measures included technical success, perioperative complications, and stent patency. RESULTS: A total of 24 patients (13 men and 11 women), with a median age of 67 years (range, 42-81 years), were analyzed. Among them, 20 patients were symptomatic, and 4 patients underwent elective surgery because of the size of PAU. A total of 54 BeGraft stents (26 aortic and 28 peripheral) were successfully delivered and deployed to cover 13 aortic and 13 common iliac artery ulcer lesions. The technical success rate was 100%. The average procedural time was 53.8 ± 12.8 min. Complications included one case of the access-site pseudoaneurysm, which was successfully treated by thrombin injection. During a median follow-up of 20.5 months (range, 6-33 months), all stents remained patent, without endoleak or ulcer recurrence. CONCLUSIONS: BeGraft stents used during endovascular treatment of abdominal PAU and PUIA lesions are associated with favorable outcomes regarding technical success and patency. The primary use of BeGraft covered stents provides a valid option for patients with abdominal PAU. Long-term follow-up is required to confirm these promising results.

The intravascular ultrasound morphometry of iliac veins in subjects without severe chronic venous insufficiency and its implications for treatment indications and stent size selection.

OBJECTIVES: The purpose of this study is to report the intravascular ultrasound morphometry of iliac veins and its relation to demographic and anthropometric factors in subjects without chronic venous insufficiency. METHODS: Thirty-three patients, without chronic venous insufficiency - qualified to great saphenous vein stripping due to unilateral, primary varicose veins - participated in the study. During the surgery, left and right external iliac veins, common iliac veins and inferior vena cava were interrogated with intravascular ultrasound. The morphometric analysis included measurement of a cross-sectional area at normal, non-stenosed vein segments (ref-CSA) and at the point of the most prominent narrowing (minimal lumen area (MLA)). Based on these measurements, a percentage of stenosis (S%) and calculated lumen diameter of interrogated veins were determined according to the following formulas, S% = (ref-CSA-MLA)/ref-CSA × 100 and CLD = 2 × âˆš(ref-CSA/π), respectively. RESULTS: Median ref-CSA, S% and calculated lumen diameter were 265.3 mm2, 45.8% and 18.4 mm for inferior vena cava; 193.9 mm2, 62.4% and 15.7 mm for left common iliac veins; 166.9 mm2, 35.7% and 14.2 mm for right common iliac veins; 136.5 mm2, 48.0% and 12.8 mm for left external iliac veins and 140.9 mm2, 46.3% and 13.5 mm for right external iliac veins. There were statistically significant differences between left and right common iliac veins ref-CSA, common iliac veins S% and common iliac veins calculated lumen diameter (p = 0.03, p < 0 and p = 0.03, respectively). The S% of left external iliac veins was greater in women 52.2 versus 37.2% in men (p = 0.04). Neither age nor anthropometric factors had any influence on the calculated lumen diameter of the analysed veins. A negative correlation between the left common iliac veins S% and the age was observed (p = 0.03). CONCLUSIONS: In adult subjects, the calculated lumen diameter of the common iliac veins is greater on the left side and is not influenced by age and body size. Common iliac vein stenosis occurs more frequently on the left side, decreases with age and tends to be more frequent in women.

The influence of the nylon balloon stiffness on the efficiency of the intra-aortic balloon occlusion.

In interventional procedures, the balloon inflation is used to occlude the artery and thus reduce bleeding. There is no practically accepted measure of the procedure efficiency. A finite element method model with state-of-the-art modelling techniques was built in order to predict the occlusion levels under the influence of different balloon inflation and its material stiffness. The geometries of a healthy human thoracic aorta and an occlusion balloon were idealized. The non-linear constitutive material of Gasser-Ogden-Holzapfel model was employed for the thoracic aorta; the balloon was model as the hyperelastic model. The realistic physiological blood pressure and the balloon inflation pressures were applied to simulate the different occlusion levels. The final outcome shows an important influence of the material stiffness on the balloon deformation and thus the occlusion efficiency.

Associations and interactions between variants in selenoprotein genes, selenoprotein levels and the development of abdominal aortic aneurysm, peripheral arterial disease, and heart failure.

BACKGROUND: Little is known on the role of selenoprotein genes in cardiovascular disease. This study examines the associations of the SEPP1, SELENOS, TXNRD1, TXNRD2, GPX4, and SOD2 polymorphisms and selenoprotein P (SeP) and thioredoxin concentrations with the development of abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AOID), as well as their influence on cardiac phenotype. METHODS: 564 patients with AAA, 400 patients with AIOD, and 543 controls were enrolled and characterized for coronary artery disease, myocardial infarction, and systolic heart failure (HF) occurrence. In AAA, the coexistence of peripheral arterial disease (PAD) was examined. Genotypes were determined using TaqMan-based assays. Selenoprotein concentration was assessed using the ELISA method. RESULTS: The SELENOS rs34713741T, SEPP1 rs3877899A, and GPX4 rs713041T alleles were related to a 30-60% increase in the AIOD/PAD risk in the recessive or dominant model (all associations at P < .05). The SEPP1 rs3877899A allele was a protective factor for the development of AAA without concomitant PAD (OR = 0.68 for the dominant model, P = .014), but not AAA with concomitant PAD. The cumulative two-locus effects of selenoprotein genes on the AAA/AIOD risk were observed, including the multiplicative interaction between the SELENOS rs34713741T and GPX4 rs713041T alleles (both in the recessive model) affecting the AIOD risk (OR = 5.27, P = .001) and its clinical phenotype. Coexistence of HF in aortic diseases was related to both the SEPP1 rs7579A allele (OR = 1.83 for carriers, P = .013) and increased SeP concentrations; SeP level ≥8.5 mg/mL caused a 3.5-fold increase in the risk of HF. In AAA, SeP levels were correlated with BMI (r = -0.575, P < .0001). CONCLUSIONS: Our results provide evidence that selenoprotein polymorphisms constitute a risk factor for HF and peripheral atherosclerosis, but prevent the development of AAA. Excessive weight might result in reduced antioxidant reserve efficiency in AAA. Validation studies are required to establish whether SeP concentration may be a marker for HF.

Superb Micro-vascular Imaging (SMI): a Doppler ultrasound technique with potential to identify, classify, and follow up endoleaks in patients after Endovascular Aneurysm Repair (EVAR).

PURPOSE: The aim of the study was to assess the effectiveness of Superb Micro-vascular Imaging (SMI) as an alternative to Contrast-Enhanced Ultrasound (CEUS) and Computed Tomography Angiography (CTA) for endoleak detection and classification in patients followed up after endovascular abdominal aortic aneurysm repair (EVAR). MATERIALS AND METHODS: From May 2015 to January 2017, 30 patients underwent post-EVAR follow-up with Color Doppler Ultrasound (CDUS), CEUS, SMI, and CTA examinations. Aneurysmal sac diameter and graft patency were evaluated; endoleaks were identified and classified. Sensitivity, specificity, and accuracy values were calculated for each of the four diagnostic methods of endoleak detection. A percentage of agreement and Cohen's Kappa coefficient were calculated for comparison of methods in terms of endoleak identification. RESULTS: CTA revealed fifteen endoleaks (50%): three type Ia, nine type II, and three type III. The sensitivity of CDUS, CEUS, and SMI relative to CTA was 27%, 100%, and 100%, respectively. Specificity was 93%, 93%, and 93%, respectively. Accuracy was 60%, 97%, and 97%, respectively. There were no differences between SMI and CEUS in terms of sensitivity, specificity, or accuracy (100%, 93%, and 97%). We do not observe statistically significant differences between CTA, CEUS, and SMI concerning endoleak identification ability. The weakest method in endoleak identification was CDUS. CONCLUSIONS: The analysis showed that SMI is effective, repeatable, and comparable with the CEUS modality in identification endoleaks after EVAR; it may be considered as a potential tool to monitor patients after EVAR implantation, especially those with renal insufficiency or with an allergy to any contrast media.

Morphology-Related Limitations of Endovascular Aneurysm Repair Applicability in the Treatment of Abdominal Aortic Aneurysm in West-Central Poland.

BACKGROUND: Morphology is one of the most important factors influencing the long-term durability of endovascular repair of an infrarenal abdominal aortic aneurysm (AAA). The knowledge of morphological characteristics of AAA that may differ in various populations seems to be important for further development of a technology of endovascular repair as well as for planning of treatment strategies. To analyze the current applicability of endovascular aneurysm repair (EVAR) in patients with an infrarenal AAA with an indication for elective treatment in west-central Poland. METHODS: Computed tomography angiograms of 100 consecutive patients with infrarenal AAA deemed to require treatment were analyzed with an OsiriX DICOM viewer in 3D-multiplanar reconstruction mode. Proximal neck diameter, length, angulation, shape, the presence of thrombus and calcification, distal neck diameter, and morphology of the iliac arteries were determined. Three sets of morphological criteria were established. The optimal criteria consisted of a nonconical proximal neck without moderate or severe calcification or thrombus, with a diameter of 18-28 mm, length of ≥15 mm, and ß angulation of <60%; a distal neck with a diameter of ≥20 mm; a landing zone in the common iliac arteries (CIAs) with a length of ≥10 mm and diameter of ≤20 mm; and external iliac arteries with diameters of ≥7 mm. The suboptimal criteria included proximal neck diameters of 18-32 mm, neck lengths ≥10 mm, infrarenal neck angulations of up to 75°, and CIA diameters of up to 25 mm. Finally, the extended suboptimal criteria included proximal neck diameters of 16-34 mm and infrarenal neck angulations ≤90°, without limits in the maximal diameter of the CIAs. RESULTS: The median maximum aneurysm diameter was 61 mm. The optimal, suboptimal, and extended suboptimal criteria were met by 23%, 32%, and 53% of patients, respectively. The most common deviations were wide, conical, and angulated proximal necks and aneurysmal iliac arteries. CONCLUSIONS: The majority of patients with AAA deemed to be candidates for elective repair do not meet the most favorable criteria for EVAR. Availability of better endovascular solutions for conical, angulated, and wide necks and aneurysmal iliac arteries would likely expand EVAR applicability. Open repair remains a valid option.

The forearm basilic vein looped transposition fistula as a tertiary option for upper limb vascular access.

INTRODUCTION:: The forearm basilic vein can serve as an option for haemodialysis access but may not be possible in cases where the wrist arteries are unsuitable. In this setting, the forearm basilic vein can be used in a looped transposition with a brachial artery anastomosis. AIMS:: The aims of this study were to assess the outcome of forearm basilic vein looped transposition as an option for vascular access. MATERIAL AND METHODS:: Data from January 2007 to December 2010 were prospectively collected and analysed. Outcome measures were operative success, complications, maturation and primary and secondary patency following 5 years of follow-up. RESULTS:: From a total of 583 patients receiving autologous vascular access for haemodialysis, 24 (4.1%) underwent a forearm basilic vein looped transposition. The median age was 60 years (range, 27-80 years), with a slight male predominance (13 male:11 female). Mean follow-up was 34 months (1-60 months). Two patients died and other three were transplanted with subsequent fistula closure. All procedures were successful (100%); however, maturation failure occurred in one case (4.2%). No serious perioperative complications were observed. In two cases, we observed late false aneurysm formation requiring intervention. Primary patency at 1, 2, 3 and 5 years was the following: 77%, 62%, 21% and 10%, whereas secondary patency was the following: 81%, 71%, 61% and 32%, respectively. CONCLUSION:: Autologous forearm basilic vein looped transposition is an effective surgical procedure for the creation of access for haemodialysis. This may be a useful option in patients with compromised peripheral arterial diameter or flow and should be considered in patients with a suitable forearm basilic vein.

Gait pattern in patients with peripheral artery disease.

BACKGROUND: The aim of the present paper is to assess the gait pattern of patients with Peripheral Artery Disease (PAD). A more specific aim is to compare the gait pattern of PAD patients before and after the appearance of intermittent claudication symptoms. METHODS: The study involved 34 PAD patients with a claudication distance ≥200 m and 20 participants without PAD, who formed the control group. The gait pattern of PAD patients was assessed twice: before the appearance of intermittent claudication symptoms (pain-free conditions) and after the appearance of intermittent claudication symptoms (pain conditions). RESULTS: Compared to the control group, PAD patients presented a statistically significant decrease in step length both during pain-free conditions (52.6 ± 12.5 vs. 72.8 ± 18.5 cm, p = 0.008) and in pain conditions (53.3 ± 13.3 vs. 72.8 ± 18.5 cm, p = 0.006). As for the remaining spatiotemporal parameters, there were no differences observed between the patient group and the controls. Intermittent claudication symptom induced by the walking test on the treadmill did not bring about any new abnormalities in the gait pattern or intensify the existing abnormalities of the gait. CONCLUSIONS: PAD patients have a tendency to shorten their step length regardless of the presence of intermittent claudication.

Peripheral vascular malformations - modern imaging.

Currently the major aim in peripheral vascular malformation diagnosis, crucial for subsequent management and treatment, is to identify its haemodynamic characteristics. Other significant features that should be specified by a radiologist are the exact location of the anomaly, its size, and its morphology. Until recently the diagnostic methods available for comprehensive evaluation of malformations have been rather limited. Moreover, they were often associated with the necessity of exposing the patient to X-ray radiation and with invasive procedures, as for example in angiography. The development of imaging techniques used in the diagnosis of vascular abnormalities in recent years, especially magnetic resonance imaging, has contributed to improved diagnostic value of the tests. In this article we review the currently available imaging modalities with particular consideration of magnetic resonance imaging and its capability to distinguish between high- and low-flow malformations.

Early Experience With Endovascular Aneurysm Sealing in Combination With Parallel Grafts for the Treatment of Complex Abdominal Aneurysms: The ASCEND Registry.

PURPOSE: To report the results of the ASCEND Registry of cases involving endovascular aneurysm sealing (EVAS) in combination with chimney grafts (chEVAS) for the treatment of para- and juxtarenal aortic aneurysms (AAA). METHODS: A retrospective, multicenter registry established in 8 vascular centers between 2013 and 2016 recorded the treatment results and follow-up of chEVAS procedures for nonruptured AAAs; data were analyzed using standardized outcome measures. In the observation period, 154 patients (mean age 72.3±7.7 years; 124 men) underwent elective treatment for de novo juxtarenal and pararenal aneurysms and formed the study group. RESULTS: Sixty-two (40.3%) of the cohort were treated using a single parallel graft, 54 (35.1%) with double chimneys, 27 (17.5%) with triple chimneys, and 11 (7.1%) with 4 chimneys. The 30-day mortality was 2.8%, and there were 4 perioperative strokes (1 fatal). At 1 year, the freedom from all-cause mortality was 89.8% and the freedom from aneurysm-related mortality was 94.3%. There were 3 endoleaks within 90 days of the procedure, one type Ia and 2 type Ib. The freedom from type Ia endoleaks was 95.7% at 1 year. There were no types II or III endoleaks in this series; the freedom from all endoleaks was 94.2% at 1 year. Freedom from reintervention at 1 year was 89.2%. Target vessel patency rates at 1 year were 97.7%, 99.3%, 100%, and 100% for the left renal, right renal, superior mesenteric artery, and celiac axis stents, respectively. CONCLUSION: The ASCEND Registry supports a proof of concept for the use of polymer technology and EVAS with parallel grafts in managing patients with complex aortic disease. The future role of chEVAS will be defined by studies that assess mid- to long-term durability.

Career in vascular surgery - the medical student's perspective.

AIM: Under the supervision of the Department of General and Vascular Surgery of Poznan University of Medical Sciences, a questionnaire was distributed online or as a paper version to medical students (MSs) in order to better understand the attitudes towards surgery as a specialty and to determine the reasons why students do and do not choose vascular surgery as their career path. MATERIALS AND METHODS: The questionnaire was distributed online or as a paper version to MSs in the 3rd, 5th, and 6th year of the PUMS 6-year M.D. PROGRAM: It provided the data on the year of study, grade point average (GPA), sex, age, respondent's specialty choice, 33 questions with responses on a 1-5 Likert scale (1 was the least important reason and 5 was the most important reason), and 2 questions with socres between 0 and 4. A total of 136 Polish MSs of PUMS completed the survey. RESULTS: For MSs who choose vascular surgery as their career path, "endovascular capabilities of vascular surgery" and "higher income possibilities than a general surgeon" were the most important reasons. The "poor availability of work in other places than the vascular surgery department of your choice, few such clinics in the region" was the most important reason not to choose vascular surgery. A role of gender was also noted - 13% of male MSs classified gender as an "important factor", in contrast to 60% of female MSs. CONCLUSIONS: The findings of this study might help to develop better strategies to attract future trainees to surgical specialties, particularly vascular surgery, and improve work environment.

Successful surgical treatment of a subtotal descending aortic occlusion.

We present the case of a 33-year-old man with middle aortic syndrome. The final diagnosis was established with magnetic resonance imaging. He underwent a successful aorto-aortic bypass. Two-year follow-up imaging showed the new graft was patent, with no abnormalities at the anastomosis sites. At the last follow-up examination he was asymptomatic with no neurological dysfunction.

Atherectomy using a solid-state laser at 355 nm wavelength.

Peripheral arterial disease (PAD), caused by atherosclerotic processes, is allied with an increased risk of ischemic events, limb loss, and death. Recently, the use of a solid-state laser at 355 nm within a hybrid catheter was suggested for that purpose. In this work, short nanosecond pulses of a solid-state laser at 355 nm delivered through a hybrid catheter, composed of optical fibers and a blunt mechanical blade, are used to conduct a pre-clinical study and two clinical cases. The pre-clinical study consisted of an atherosclerotic calcified cadaveric leg and a porcine in vivo trial within the iliac artery, respectively. The clinical cases include chronic total occlusions with a calcified lesion. The occluded cadaveric leg is recanalized successfully and no evidence of thermal necrosis is indicated in the histopathology analysis of the porcine study. No arterial wall damage is demonstrated on the animals' treated arteries and no significant impact on blood count and biochemistry analysis is noted in the animal trial. Successful recanalization of the occluded arteries followed by balloon angioplasty is obtained in both clinical cases. Our work constitutes a proof of concept for using a solid-state pulsed laser at 355 nm in atherectomy.

Is hyperhomocysteinemia a causal factor for heart failure? The impact of the functional variants of MTHFR and PON1 on ischemic and non-ischemic etiology.

BACKGROUND: Hyperhomocysteinemia was found to be uniformly associated with the development of heart failure (HF) and HF mortality; however, it is uncertain whether this relation is causative or not. We used Mendelian randomization to examine the associations of the methylene tetrahydrofolate gene (MTHFR) and paraoxonase 1 gene (PON1) variants as a proxy for lifelong exposure to high Hcy and Hcy-thiolactone concentrations with the development of HF in men aged ≤60years and the occurrence of adverse effects at one-year follow-up. METHODS: The study enrolled 172 men with HF: 117 with ischemic etiology (iHF) related to coronary artery disease (CAD) and 55 with non-ischemic etiology (niHF) related to dilated cardiomyopathy (DCM). The reference group of 329 CAD patients without HF and the control group of 384 men were also analyzed. RESULTS: Hyperhomocysteinemia (OR=2.0, P<0.05) and the MTHFR 677TT/1298AA, 677CC/1298CC genotypes (OR=1.6, P=0.03) were associated with HF regardless of its etiology, especially among normotensives (OR=4.6, P=0.001 and OR=2.3, P=0.003, respectively). In niHF, the PON1 162AA (OR=2.3, P=0.03) and 575AG+GG (OR=0.46, P=0.01) genotypes also influenced the risk. The interaction between HDLC<1mmol/L and the PON1 575GG genotype was found to influence the risk of iHF (OR=7.2, P=0.009). Hyperhomocysteinemia improved the classification of niHF patients as 'high-risk' by 10.1%. Ejection fraction <30% and DCM increased the probability of HF death or re-hospitalization within one year. CONCLUSION: Our results provide evidence that hyperhomocysteinemia is a causal factor for niHF in DCM, while dysfunctional HDL could contribute to the pathogenesis of iHF.

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.

RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies. METHODS AND RESULTS: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. CONCLUSIONS: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.

The Impact of Walking Exercises and Resistance Training upon the Walking Distance in Patients with Chronic Lower Limb Ischaemia.

Objective. The objective of this paper is to compare the impact of supervised walking and resistance training upon the walking distance in PAD patients. Materials and Methods. The examination involved 50 PAD patients at the 2nd stage of the disease according to Fontaine's scale. The participants were randomly allocated to two groups: one exercising on the treadmill (n = 24) and one performing resistance exercises of lower limbs (n = 26). Results. The 12-week program of supervised rehabilitation led to a significant increase in the intermittent claudication distance measured both on the treadmill and during the 6-minute walking test. The group training on the treadmill showed a statistically significant increase of the initial claudication distance (ICD) and the absolute claudication distance (ACD) measured on the treadmill, as well as of ICD and the total walking distance (TWD) measured during the 6-minute walking test. Within the group performing resistance exercises, a statistically significant improvement was observed in the case of parameters measured on the treadmill: ICD and ACD. Conclusions. The supervised rehabilitation program, in the form of both walking and resistance exercises, contributes to the increase in the intermittent claudication distance. The results obtained in both groups were similar.