Five-year survival after elective open and endovascular aortic aneurysm repair.

BACKGROUND AND OBJECTIVE: Current evidence suggests short-term survival benefit from endovascular aneurysm repair (EVAR) versus open surgical repair (OSR) in elective abdominal aortic aneurysm (AAA) procedures, but this benefit is lost during long-term follow-up. The aim of this study was to compare short- and mid-term all-cause mortality in patients with non-ruptured aneurysm treated by OSR and EVAR; and to assess the rate of complications and reinterventions, as well as to evaluate their impact on survival. METHODS: The medical records of the non-ruptured AAA patients undergoing OSR or EVAR between 1 January 2011 and 31 December 2019 at Tartu University Hospital, Estonia, were retrospectively reviewed. We gathered survival data from the national registry (mean follow-up period was 3.7 ± 2.3 years). RESULTS: A total of 225 non-ruptured AAA patients were treated operatively out of whom 95 (42.2%) were EVAR and 130 (57.8%) were OSR procedures. The difference in estimated all-cause mortality between the OSR and EVAR groups at day 30 was statistically irrelevant (2.3% vs 0%; p = 0.140), but OSR patients showed statistically significantly higher 5 year survival compared with EVAR patients (75.3% vs 50.0%, p = 0.002). Complication and reintervention rates for the EVAR and OSR groups did not differ statistically (26.3% vs 16.9%, p = 0.122; 10.5% vs 11.5%, p = 0.981, respectively). Multivariate analysis revealed that greater aneurysm diameter (p = 0.012), EVAR procedure (p = 0.016), male gender (p = 0.023), and cerebrovascular diseases (p = 0.028) were independently positively associated with 5-year mortality. CONCLUSIONS: Thirty-day mortality, and complication and reintervention rates for EVAR and OSR after elective AAA repair were similar. Although the EVAR procedure is an independent risk factor for 5-year mortality, higher age and greater proportion of comorbidities among EVAR patients may influence not only the choice of treatment modality, but also prognosis.

The Role of RIPC in Preventing Organ Damage, Inflammation, and Oxidative Stress during Lower Limb DSA: A Randomised Controlled Trial.

OBJECTIVE: Diagnostic digital subtraction angiography (DSA) and DSA with percutaneous transluminal angioplasty (DSA-PTA) are common procedures for diagnosing and treating symptomatic lower extremity arterial disease (LEAD). However, organ damage following DSA and DSA-PTA is often underrecognised and hence undiagnosed. To reduce the risk induced by invasive procedures in symptomatic LEAD patients, the method of remote ischemic preconditioning (RIPC) has been suggested. The aim of the current study was to assess the effect of RIPC intervention on the organ damage markers profile, oxidative stress, and inflammation biomarkers in LEAD patients undergoing DSA and DSA-PTA procedure. METHODS: The RIPC intervention was performed by inflating a standard blood pressure cuff on the patient's upper arm to 200 mmHg for 5 minutes four times with 5-minute perfusion between each cycle. The sham intervention was performed similarly, but the cuff was inflated to 20 mmHg. Changes in the cardiac and renal damage biomarkers' profile, oxidative stress, and inflammation biomarkers were recorded before and 24 hours after DSA or DSA-PTA. RESULTS: A total of 111 (RIPC 54, sham 57) patients with symptomatic LEAD scheduled for endovascular procedure were randomised, and 102 patients (RIPC 47, sham 55) completed the study protocol. RIPC significantly limited the increase of adiponectine levels after DSA and DSA-PTA, compared to sham intervention (p = 0.020), but CK-MB levels were markedly lower in the sham group (p = 0.047) after procedure. There was no significant difference between the RIPC and the sham group in mean changes in hs-troponin-T (p = 0.25), NT-proBNP (p = 0.24), creatinine (p = 0.76), eGFR (p = 0.61), urea (p = 0.95), beta-2-microglobuline (p = 0.34), or cystatine C (p = 0.24) levels. CONCLUSION: In this controlled clinical study, RIPC failed to improve the profile of renal and cardiac biomarkers in patients with LEAD periprocedurally. RIPC significantly limits the rise in adiponectin levels and may influence the decrease of CK-MB levels 24 hours after endovascular procedure.

Metabolomic Profile of Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is characterized by structural deterioration of the aortic wall, leading to aortic dilation and rupture. The aim was to compare 183 low molecular weight metabolites in AAA patients and aorta-healthy controls and to explore if low molecular weight metabolites are linked to AAA growth. Blood samples were collected from male AAA patients with fast (mean 3.3 mm/year; range 1.3-9.4 mm/year; n = 39) and slow growth (0.2 mm/year; range -2.6-1.1 mm/year; n = 40), and from controls with non-aneurysmal aortas (n = 79). Targeted analysis of 183 metabolites in plasma was performed with AbsoluteIDQ p180 kit. The samples were measured on a QTRAP 4500 coupled to an Agilent 1260 series HPLC. The levels of only four amino acids (histidine, asparagine, leucine, isoleucine) and four phosphatidylcholines (PC.ae.C34.3, PC.aa.C34.2, PC.ae.C38.0, lysoPC.a.C18.2) were found to be significantly lower (p < 0.05) after adjustment for confounders among the AAA patients compared with the controls. There were no differences in the metabolites distinguishing the AAA patients with slow or fast growth from the controls, or distinguishing the patients with slow growth from those with fast growth. The current study describes novel significant alterations in amino acids and phosphatidylcholines metabolism associated with AAA occurrence, but no associations were found with AAA growth rate.

The Effect of Remote Ischaemic Preconditioning on Arterial Stiffness in Patients Undergoing Vascular Surgery: A Randomised Clinical Trial.

OBJECTIVES: The main aim of this study was to evaluate the effect of remote ischaemic preconditioning (RIPC) on arterial stiffness in patients undergoing vascular surgery. METHODS: This was a randomised, sham controlled, double blind, single centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited. A RIPC or a sham procedure was performed, using a blood pressure cuff, along with preparation for anaesthesia. The RIPC protocol consisting of four cycles of 5 min of ischaemia, followed by 5 min of reperfusion was applied. Arterial stiffness and haemodynamic parameters were measured pre-operatively and 20-28 h after surgery. Two primary outcomes were selected: augmentation index and pulse wave velocity. RESULTS: Ninety-eight patients were randomised. After dropouts 44 and 46 patients were included in the RIPC and sham groups, respectively. Both groups were comparable. There were no statistically significant differences in augmentation index (p = .8), augmentation index corrected for heart rate of 75 beats per minute (p = .8), pulse wave velocity (p = .7), large artery elasticity indices (p = .8), small artery elasticity indices (p = .6), or mean arterial pressure (p = .7) changes between the RIPC and sham groups. There occurred statistically significant (p ≤ .01) improvement in augmentation index (-5.8% vs. -5.5%), augmentation index corrected for a heart rate of 75 beats per minute (-2.5% vs. -2%), small artery elasticity indices (0.7 mL/mmHg × 100 vs. 0.9 mL/mmHg × 100), and mean arterial pressure post-operatively in both the RIPC and the sham groups (change median values in RIPC and sham groups, respectively). CONCLUSIONS: RIPC had no significant effect on arterial stiffness, but there was significant improvement in arterial stiffness after surgery in both groups. Arterial stiffness and haemodynamics may be influenced by surgery or anaesthesia or oxidative stress or all factors combined. Further studies are needed to clarify these findings. CLINICALTRIALS.GOV: NCT02689414.

Structural and biochemical characteristics of arterial stiffness in patients with atherosclerosis and in healthy subjects.

Arterial stiffness is an independent predictor of vascular morbidity and mortality in patients with atherosclerosis. Angiographic score (ASc) reflects severity of atherosclerosis in patients with peripheral arterial disease (PAD). Osteopontin (OPN) and oxidized low-density lipoprotein (oxLDL) are involved in the pathogenesis of atherosclerosis. The aim of the present study was to evaluate the association between arterial stiffness, ASc, serum OPN and oxLDL in patients with symptomatic PAD, and in clinically healthy subjects. We studied 79 men with symptomatic PAD (mean age 64±7 years) and 84 healthy men (mean age 63±8 years). Calculation of the ASc was based on severity and location of atherosclerotic lesions in the arteries of the lower extremities. Aortic pulse wave velocity (aPWV) was evaluated by applanation tonometry using the Sphygmocor device. Serum OPN and oxLDL levels were determined by enzyme-linked immunosorbent assay. The aPWV (10±2.4 vs. 8.4±1.7 (m s(-1)); P<0.001), OPN (75 (62.3-85.8) vs. 54.8 (47.7-67.9) (ng ml(-1)); P<0.001) and oxLDL (67 (52.5-93.5) vs. 47.5 (37-65.5); P<0.001) were different for the patients and for the controls. In multiple regression models, aPWV was independently determined by ASc, log-OPN, log-oxLDL and estimated glomerular filtration rate in the patients (R2=0.44; P<0.001) and by log-OPN, log-oxLDL, age and heart rate in the controls (R2=0.38; P<0.001). The independent relationship of a PWV with serum levels of OPN and oxLDL in the patients with PAD and in the controls indicates that OPN and oxLDL might influence arterial stiffening in patients with atherosclerosis and in clinically healthy subjects.

Associations of NF-kappaB and bax with apoptosis in varicose veins of women of different age groups.

The study aimed at detecting apoptotic endothelial cells (ECs) and smooth muscle cells (SMCs) together with determining expression of NF-kappaB (p105/p50) and Bax in varicose vein walls. Women (n = 35) undergoing the excision of varicose veins were divided into 3 groups: younger than 35 years (I), 36-50 years (II), and older than 50 years (III). Apoptosis was determined by the TUNEL method, NF-kappaB and Bax expression by immunohistochemistry. The percentage of apoptotic ECs and SMCs in the layers of varicose vein wall increased in groups II and III. NF-kappaB expression had the lowest level in Group II with particularly low level in the media. Contrariwise, Bax expression levels in Group II were increased. The study revealed that in varicose veins ECs and SMCs apoptosis increased with advancing age. If increase in apoptosis during earlier stages of varicosities is probably regulated by intrinsic pathway, then in older patients other signaling pathways may be involved.

ß2-microglobulin, a novel biomarker of peripheral arterial disease, independently predicts aortic stiffness in these patients.

Arterial stiffness is a prominent feature of vascular ageing and strongly predicts cardiovascular and total mortality. The ß2-microglobulin, (ß2M) a newly identified biomarker of peripheral arterial disease (PAD), is related to renal insufficiency, inflammatory and neoplastic diseases, but may also play a role in vascular dysfunction. However, the relationship between arterial stiffness and ß2M has not been previously studied in patients with atherosclerosis. In the present study we examined a possible association between ß2M and arterial stiffness in patients with PAD and in healthy subjects. Plasma ß2M levels and parameters of arterial stiffness such as aortic pulse wave velocity (aPWV) and augmentation index (AIx) were measured in 66 patients with PAD and in 66 apparently healthy subjects. Plasma levels of ß2M, aPWV and AIx were significantly increased in patients with PAD compared with controls (1858.1 ± 472.8 vs 1554.5 ± 277.9 µg/L, p < 0.001; 9.9 ± 2.2 m/s vs 7.6 ± 1.6 m/s, p < 0.001; 28 ± 8 vs 14 ± 11%, p < 0.001; respectively). There existed significant correlation between aPWV and ß2M for the patient group (R = 0.47; p < 0.001), but not for the controls (R = 0.14; p = 0.26). In multivariate analysis, ß2M remained independently associated with aPWV, fetuin-A, age and glomerular filtration rate in patients (R(2) = 0.5, p < 0.001). We found no relationship between ß2M and AIx in either group. We demonstrated that among patients with PAD elevated plasma ß2M levels were associated with higher aortic stiffness irrespective of cardiovascular disease risk factors. These data suggest that ß2M may influence the pathogenesis of aortic stiffness in atherosclerosis.

Association of osteoprotegerin with aortic stiffness in patients with symptomatic peripheral artery disease and in healthy subjects.

BACKGROUND: Arterial stiffening is an independent predictor for cardiovascular mortality. Preliminary studies have shown that arterial calcification may have an impact on increased vascular stiffness. However, there are limited data about the role of calcification inhibitor osteoprotegerin (OPG) as an independent predictor for arterial stiffness in patients with peripheral arterial disease (PAD) and in healthy subjects. The aim of this study was to evaluate the association between OPG and arterial stiffness parameters in patients with PAD and in healthy subjects. METHODS: We studied 69 men with PAD (age 63 + or - 7 years) and 68 healthy subjects (age 54 + or - 8 years). Serum OPG and oxidized low-density lipoprotein (oxLDL) were measured using the enzyme-linked immunosorbent assay method. Radial and aortic pulse wave velocity (aPWV) and augmentation index (AIx) were determined by applanation tonometry. RESULTS: The OPG (5.4 + or - 1.7 vs. 4.4 + or - 1.1 pmol/l; P < 0.001) and aPWV (10.1 + or - 2.5 vs. 7.6 + or - 1.6 m/s; P < 0.001) were different for the patients and for the controls. There was a linear relationship between OPG and aPWV in patients with PAD (R = 0.37; P = 0.003) and in healthy individuals (R = 0.40; P = 0.001). In multiple regression models after adjustment for potential confounders, OPG was independently associated with aPWV in the patients (R(2) = 0.47; P < 0.0001) and in the controls (R(2) = 0.44; P < 0.0001). The AIx or radial PWV was not correlated with OPG for either group. CONCLUSION: The independent association between OPG and aPWV in patients with PAD and in controls suggests that the calcification inhibitor OPG may influence aortic stiffening in atherosclerosis and in clinically healthy subjects.