Velipekka Suominen

Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

Background Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. Methodology/Principal Findings We characterized the genes generally involved in human advanced atherosclerotic (AHA type V–VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25). Conclusions This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds.

Fenestrated and Chimney Endografts for Juxtarenal Aneurysms: Early and Midterm Results

Aim: To assess the early and short-term outcome of fenestrated and chimney grafting for juxtarenal aortic aneurysms. Material and Methods: A prospective vascular registry of 28 patients who had undergone elective primary endovascular repair for abdominal aortic aneurysm between December 2007 and August 2011 with infrarenal neck anatomy unacceptable for conventional endovascular repair. Fenestrated endografts were designed based on reconstructed computed tomography (CT) data by the authors. Off-the-shelf grafts and stents were used for chimney cases. Patients were followed up until 31 May 2012. Results: A total of 21 (75%) patients were treated with fenestrated endografts, while 7 (25%) received chimney grafts. The mean aneurysm diameter was 65 mm (standard deviation = 7 mm) and the median neck length 2.5 mm (range: 0–10 mm). Altogether, 63 (mean = 2.3/patient) visceral arteries were incorporated (42 renal, 21 superior mesenteric arteries). The overall primary technical success rate was 93% (one type I and one type III endoleak). The mean follow-up was 22 months (standard deviation: 14 months). The primary type III endoleak resolved spontaneously with thrombosis of the target vessel, while the patient with primary type I endoleak died of acute myocardial infarction 3 weeks after the procedure. Two late endoleaks developed: one type II endoleak without aneurysm sac growth remains under surveillance, while in another patient, multiple attempts to treat type I endoleak proved unsuccessful and the patient later died of gastrointestinal bleeding. A total of 4 (14%) patients so far required additional procedures. Two patients died within 30 days of the device implantation and another six during the follow-up. No rupture occurred. The cumulative survival for patients with fenestrated endografts was 85% at 1 year and for those treated with chimney technique 57%. Conclusions: The treatment of juxtarenal aortic aneurysms seems to be feasible by exploiting various endovascular techniques. Even with a low volume of cases, good immediate and short-term results can be achieved, especially with fenestrated endografts.

The Fate of AAA Patients Referred Electively to Vascular Surgical Unit

Background: The ideal treatment of abdominal aortic aneurysms (AAA) is to operate aneurysms likely to rupture, without exposing other cases to major surgery. The purpose here was to analyse retrospectively the management of AAA in a well-defined geographical region in the 1990s. Methods: 194 new vascular surgical outpatient consultations due to AAA were done to the regional vascular centre during the years 1990, 1992, 1994, 1996 and 1998. Data were collected from case records. Statistics Finland provided causes and dates of death. Results: The mean observed annual AAA incidence was 9.0 per 100 000 inhabitants and it rose significantly (33.3 %) during the study period. The duration of follow-up varied between 0 and 129 months. The 5/8-year cumulative mortality was 37.3/50.7 %. The most common causes of death were AAA-related (31.7 %), cardiac (29.1 %) or malignancy (19.0 %). Twenty-five patients with small AAA were referred to primary health care sector for further follow-up. There were no RAAA (ruptured AAA) deaths in this group. The cumulative 5/8-year mortality was 43.2/49.9 %. One hundred patients underwent an elective aneurysm repair with in-hospital mortality of 7.0 %. The cumulative 5/8-year mortality was 23.7/35.4 %. Twelve patients refused elective treatment. The cumulative 5/8-year mortality was 45.1/63.4 % and 5/7 deaths were due to RAAA. Twenty-three patients were unfit for elective repair. The cumulative 5/8-year mortality was 87.0 %/100 % and 5/20 deaths were caused by RAAA. The cumulative 5/8-year RAAA-rate in the patients with AAA more than 5.0 cm in diameter and outside elective aneurysm-repair (n = 23) was 51.9 %/100.0 %. Conclusion: The observed incidence of AAA increased during the 1990s. Half of the patients underwent an elective procedure. Patients unfit for surgery died mainly for other reasons than RAAA. Most patients with AAA over 5.5 cm not subjected to elective procedure, died of rupture.

Peripheral arterial disease, diabetes and postural balance among elderly Finns: a population-based study

Background and aims: Little is known about the role of peripheral arterial disease (PAD)in the development of balance impairment. The aim of this study was to assess postural balance among people having PAD or PAD combined with diabetes. Methods: As part of the comprehensive health examination of the Health 2000 survey (two-stage stratified cluster sampling), 1323 people aged 65 years or older took part in balance assessments using a force platform system. The presence of PAD was confirmed with data from the National Hospital Discharge Registry. Individuals with hospitalization due to PAD were regarded as having severe disease, whereas those with solely self-reported diagnosis were considered possible cases. Diabetes was ascertained on the basis of self-reported physicians’ diagnoses subsequently confirmed in a clinical examination. Results: Forty-five (3.4%) individuals had previously been hospitalized due to PAD, and 32 (2.4%) reported that they had been diagnosed with the disease. 413 (31%) participants had diabetes. Compared with people without PAD, those with confirmed diagnoses exhibited significantly increased movement of the center of pressure while standing, indicating deteriorated balance. Those with possible PAD formed an intermediate group. Diabetes exacerbated the deterioration in balance, but the interaction term between PAD and diabetes did not reach statistical significance. The risk of failing tandem stance tests was over three-fold (OR 3.20, 95% CI 1.09–9.37) among those with confirmed PAD and almost one and a half-fold (OR 1.44, 95% CI 1.07–1.93) among those with diabetes, in comparison to those without these diseases. Conclusions: Individuals over 65 years of age with severe PAD showed increased balance impairment, a known risk factor for falls and disability in aged people. Diabetes affected balance somewhat less than PAD, but there was no formal evidence of the synergetic effect of the two diseases. Additional studies are indicated to reveal the possible effect of proper treatment of PAD and diabetes, combined with suitabletraining interventions on slowing down the progression of balance impairment.

Ten-Year Outcomes after Endovascular Aneurysm Repair (Evar) and Magnitude of Additional Procedures

Background and Aims: With any new technology complications are possible, and problems with first-generation aortic stentgrafts have been extensively reported. The long-term outcome of this patient population and the magnitude of additional secondary procedures are, however, less well covered. Materials and Methods: Between February 1997 and November 1999, 48 patients (44 men and 4 women; mean age 70 years; range 54–85) with AAA (average 57mm, range 40–90mm) were treated with a Vanguard® endoprosthesis. Stentgrafts were sized by CT and angiography-based measurements. Results were continuously assessed using contrast-enhanced CT before discharge, 1, 3, 6 and 12 months after the procedure and thereafter annually. Since 2001 plain abdominal X-rays have been performed annually. Results: The technical implant success rate was 100%. Median follow-up was 91 months (range 7.6–120 months). None of the patients was lost during this period. Hospital mortality was 0%. There were 25 subsequent deaths (52%), the most common cause being coronary artery disease. There were ten late conversions to open surgical repair, including three emergency operations: two due to rupture and one to thrombosis. EVAR-related complications were encountered in 43 patients (90%): 12 primary endoleaks (all type II), 36 late endoleaks (16 type I, 2 type II and 18 type III), 22 migrations, 25 row separations, 20 thromboses, one endotension and 3 ruptures of the AAA. Secondary procedures were required in 39 patients (81%): 1 re-endografting by aortoiliac bifurcated graft and 3 with a uni-iliac graft; 33 limb graft repairs were performed and 19 infrarenal cuffs were placed. There were 4 late embolizations and 4 attempts, and 6 thrombolyses, four of which were successful. Further, 9 femoro-femoral crossover by-pass and 2 axillo-femoral by-pass operations and 2 amputations were carried out during the follow-up. Only one patient was alive without complications. Conclusions: The impact of long-term follow-up of patients treated with the new technology was emphasized in this patient population. A careful surveillance protocol and active endovascular treatment of complications can yield acceptable results and low AAA rupture and aneurysm mortality rates, also with the first-generation endovascular graft. A new technology, however, may involve unpredictable problems which can magnify the workload and incur high costs over several years after the initial procedure.

Vascular comorbidities and demographics of patients with ruptured abdominal aortic aneurysms

BACKGROUND The results of previous studies reporting the epidemiology of ruptured abdominal aortic aneurysm (RAAA) are highly heterogeneous. Furthermore, although RAAA and the preceding abnormal dilation of the abdominal aorta (AAA) are associated with other cardiovascular comorbidities, the demographic profile of all patients with RAAA has not been thoroughly investigated. OBJECTIVE To document accurately the epidemiology, survival, and demographic data (including vascular comorbidities and previous use of health care services) in RAAA-patients. MATERIAL AND METHODS We conducted a comprehensive retrospective register study of all RAAA patients (operatively treated RAAA patients as well as in- and out-of-hospital nonsurvivors) in a well-defined geographic area during an 11-year period. RESULTS We found 488 RAAA cases in a catchment area of 689,000. The annual incidence of RAAA was 6.5/100,000. Of these patients 43.2% were underwent surgery. Overall mortality was 79.5%, and 27.5% of the population died out-of-hospital. Age was the only independent risk factor affecting survival (P < .0001). The mean age at the time of RAAA was 73.6 years for men and 82.3 years for women. Off all unexpected RAAA patients, 40% had a previous history of cardiovascular disease (most often coronary artery disease: 32%), and 38% had visited a physician within the previous year. CONCLUSION RAAA remains a highly lethal condition with age as the only significant risk factor for mortality. The proportion of women increases strongly with age. A large proportion of patients with unexpected RAAA have history of cardiovascular disease.

Peripheral arterial disease and its clinical significance in nonagenarians

Background and aims: The purpose of this study was to characterize the prevalence and clinical features of peripheral arterial disease (PAD) among 90-year-old individuals and to assess its relationship to lower extremity functional status and survival over one year. Methods: A prospective, population-based study of all 90-year-old residents of Jyväskylä, Finland. Fifty-eight out of the 79 registered residents were examined for ankle-brachial index (ABI). Lower extremity functional status was assessed as self-reported difficulty in performing specific physical activities of daily living (PADL). In a subgroup of 36 individuals, lower extremity functioning was further assessed by measuring walking endurance and walking velocity. Death dates were collected for one year after the examination from the hospital register. Results: Thirteen persons (22%) had an ABI<0.9. PAD was asymptomatic in 11 of them and the diagnosis of PAD new to 12 of them. Thirty (52%) subjects had a normal ABI (0.9–1.4) and in 15 (26%) cases the ABI was pathologically high (>1.4). A significant accumulation of cardiovascular risk factors was observed among those with an ABI<0.9 compared with those with normal or high ABI (2.0±0.8 vs 1.3±0.8 vs 1.5±0.5, p=0.03). Those with low or high ABI reported more difficulties in the PADL tasks than those with normal ABI, but the results did not reach statistical significance. No difference in maximal walking velocity was observed according to ABI in the subgroup with data available. After one year, nine people had died, of whom only two (7%) with normal ABI and seven with low or high ABI (25%) (p=0.05). Conclusions: PAD was found to be mainly asymptomatic among 90-year-old people. An abnormal ABI was also associated with increased mortality risk over a one-year follow-up. Although our study was small-scale, it does provide novel information about the prevalence of PAD and clinical significance of ABI in very old people.

Long-Term Experience of Endovascular Repair for Thoracic Aortic Aneurysms and Dissections

Purpose: To report the long-term results of thoracic endovascular aortic repair (TEVAR) in both elective and emergency cases of thoracic aortic aneurysm (TAA) and type B dissection. Material and Methods: A prospective single-center study of 78 TEVAR patients treated between February 1998 and February 2013. Stent-graft implantation was performed in 51 (65%) patients for TAA (43 elective and 8 emergency cases) and in 27 (35%) patients for type B dissection (11 elective and 16 emergency cases). Short- and long-term results were evaluated, and a subgroup of patients with left subclavian artery (LSA) coverage was also analyzed. Results: The patients were followed for a mean of 55 months (1-160 months). The technical success rate was 81% and 30-day mortality 6.4% (n = 5). The stroke rate was 7.7% (n = 6) and permanent paraparesis 2.6% (n = 2). In follow-up, there were 28 (36%) primary (15 type I and 13 type II) and 10 secondary endoleaks (8 type I and 2 type II). Multivariate analysis showed no significant predictive factors for developing a type I endoleak. Secondary interventions were required in 24% of the patients. There was 1 late thoracic aortic rupture and 1 late conversion (1.3%). Patients with LSA coverage had a higher incidence of stroke (12.5% vs 4.3%, P = .18) and paraparesis (3.1% vs 2.2%, P = .79) compared to those without LSA coverage, although this difference was not statistically significant. Stroke rates were significantly higher in patients treated in an emergency setting (P = .048). Conclusion: Thoracic endovascular aortic repair is a relatively safe and effective therapy for different aortic pathologies with good long-term success. The risk of stroke and paraparesis is notable whether the LSA is covered, and strokes clearly accumulate in the emergency setting. A type I endoleak is the most common complication, but there are no predictive factors for its development.

Hybrid Repair of Thoracoabdominal Aortic Aneurysms Is a Durable Option for High-Risk Patients in the Endovascular Era:

Objective: To report our long-term experience in using the hybrid technique in complex thoracoabdominal aortic aneurysms (TAAAs). Methods: Between March 2005 and September 2013, 10 patients with TAAA underwent hybrid procedures with open renovisceral revascularization and thoracoabdominal aortic endografting. Patients were analyzed retrospectively. Results: Six men and 4 women with a mean age of 66 years (range 54-81 years) were treated electively during the study period. All 4 visceral vessels were revascularized in 8 patients, whereas 1 patient underwent 3-vessel revascularization and another 2-vessel revascularization. The primary technical success rate was 100%. Eight of the procedures were single staged, and the 2 most recent cases were performed in 2 stages. Perioperative and 30-day mortality was 0%. The mean follow-up was 55 months (4-133 months). None of the patients died due to aortic complications. Major complications included paraplegia (10%, n = 1) and bowel ischemia (n = 1). Postoperative cerebrospinal fluid (CSF) pressure and mean arterial pressure measurements were systematically monitored and corrected. The CSF drainage solved another 4 cases of paraparesis. Three patients required postoperative dialysis, but none of them required permanently. Postoperative spinal cord ischemia and renal complications accumulated in extensive TAAA cases. One renal graft was occluded 45 days after the initial procedure but was successfully treated with thrombolysis. One type I and 1 type III endoleak were noted and successfully treated with an additional stent graft. Two cases of type II endoleak were detected—one with a growing aneurysm sac was treated successfully and another showed no growth and further procedures were abandoned after 2 embolization attempts. In long-term follow-up, 90% of the aneurysms showed shrinkage by a mean of 23 mm (range 7-45 mm). Conclusion: The results of hybrid repair on high-risk patients with complex TAAAs are encouraging, and this approach is a valuable alternative when branched and fenestrated endovascular techniques are not considered an option.

Muraglitazar-eluting bioabsorbable vascular stent inhibits neointimal hyperplasia in porcine iliac arteries.

PURPOSE To evaluate the biocompatibility of a new muraglitazar-eluting polylactide copolymer stent and investigate its ability to prevent the formation of intimal hyperplasia. MATERIALS AND METHODS Ten self-expandable muraglitazar-eluting poly-96 L/4D-lactic acid (PLA96) stents and 10 self-expandable control PLA96 stents were implanted into porcine common iliac arteries. After 28 days follow-up, all stent-implanted iliac arteries were harvested and prepared for quantitative histomorphometric analysis. RESULTS Angiographic analysis revealed that one control PLA96 stent had occluded and one had migrated. Histomorphometric analysis demonstrated that, with the control PLA96 stent, the luminal diameter and area were decreased versus the muraglitazar-eluting PLA96 stents (means ± standard error of the mean, 3.58 mm ± 0.34 vs 4.16 mm ± 0.14 and 9.83 mm(2) ± 2.41 vs 13.75 mm(2) ± 0.93, respectively). The control PLA96 stent induced more intimal hyperplasia than the bioactive muraglitazar-eluting PLA96 stent (557 µm ± 122 vs 361 µm ± 32). Vascular injury scores demonstrated only mild vascular trauma for both stents (muraglitazar-eluting, 0.68 ± 0.07; control, 0.75 ± 0.08). Inflammation scores also showed mild inflammation for both stents (muraglitazar-eluting, 1.05 ± 0.17; control, 1.23 ± 0.19). CONCLUSIONS This new muraglitazar-eluting PLA96 stent was shown to be biocompatible with a tendency for better patency and less intimal hyperplasia compared with the control PLA96 stents.