Systematic Long-term Follow Up After Endovascular Abdominal Aortic Aneurysm Repair With the Zenith Stent Graft.

OBJECTIVE/BACKGROUND: Although endovascular aneurysm repair (EVAR) has been widely adopted, long-term data remain limited. This study analyses the long-term outcome (16 years) after EVAR with the Zenith stent graft in a single academic centre. METHODS: From 2000 to 2010, 282 patients with an abdominal aortic aneurysm (AAA) were treated electively and monitored annually. Primary outcomes were overall and AAA rupture free survival; the secondary outcomes were complication and re-intervention free survival. Kaplan-Meier analysis was used to examine survival. RESULTS: The median patient age was 76 years (range 49-92 years) and mean aneurysm diameter 61 mm (range 40-110 mm). Patients were followed for a median of 76 months (range 0-201 months). Overall survival was 93% (SE 0.02), 61% (SE 0.08), 25% (SE 0.16), and 9% (0.19) at 1, 2, 5, 10, and 16 years, respectively. Ten (3.5%) AAA ruptures occurred, and the cumulative AAA rupture free survival was 100%, 98% (SE 0.01), 96% (SE0.02), and 79% (SE 0.12) at 1, 5, 10, and 16 years, respectively. The mean annual AAA rupture rate was 0.5%. Freedom from any stent graft related complications was 68% (SE 0.03), 58% (SE 0.09), 54% (SE 0.17), and 52% (SE 0.21), respectively; freedom from graft related re-interventions was 95% (SE 0.01), 80% (SE 0.08), 73% (SE 0.11), 70% (SE 0.16), at 1, 5, 10, and 16 years, respectively. Five (1.8%) late conversions were required during follow up. The variables that significantly and independently correlated with ruptured AAA were pre-operative aneurysm size and primary type II endoleak. The latter was the only independent significant factor to increase the risk of re-intervention. CONCLUSION: The number of graft related complications is high after EVAR, and new complications keep appearing years after the initial procedure. Even though fatal AAA rupture after EVAR is rare, it cannot be totally avoided despite systematic follow up.

Survival of Patients and Treatment-Related Outcome After Intra-Arterial Thrombolysis for Acute Lower Limb Ischemia.

BACKGROUND: The aim of this study is to evaluate the long-term survival and treatment-related outcome in patients treated with intra-arterial thrombolysis for acute lower limb ischemia. METHODS: The study was based on a prospective vascular database with retrospectively obtained supplementary information from the patients' files. Additionally, data on the patients' date and cause of death were obtained from Statistics Finland. A total of 155 patients with symptoms or signs of category I-IIa acute lower limb ischemia and angiographic evidence of native artery or bypass graft thromboembolic events were treated with intra-arterial catheter-directed thrombolysis (CDT). Patients with severe ischemic stages at admission or those with contraindications for thrombolysis (n = 185) were treated with conventional surgical modalities and excluded from further analysis. RESULTS: The mean age of the patients at admission was 73 years (95% confidence interval 70.1-74.6). For descriptive purposes, age quartiles were used (≤64, 65-74, 75-82.5, ≥83). The mean follow-up time was 126.3 months. The primary patency rates of native arteries/bypass grafts were 59.8%/31.7%, 35.4%/17.1%, and 18.7%/15.2% at 1, 5, and 10 years, respectively (P = 0.01). Correspondingly, the respective secondary patency rates were 65.2%/55.6%, 46.7%/39.8%, and 22.8%/30.5% (P = 0.88). A total of 190 additional procedures on 122 patients were required to preserve the patency after hospital discharge. At 1 year the cumulative survival was 78%, at 5 years 56%, and at 10 years 29%. The most common cause of death was cardiovascular (68.5%), predominantly presented by an acute coronary syndrome, while 9.6% died of cancer, 6.8% of pulmonary diseases, 8.2% of cerebrovascular causes, and 19.2% owing to trauma and other reasons. Atrial fibrillation (hazards ratio [HR] 2.31) and age over 83 years (HR 5.23 per age category) were significantly and independently associated with poorer cumulative post-procedural survival. Bypass graft thrombosis was associated with an increase in major amputations after CDT (HR 14.77). However, the presence of synthetic bypass grafts had a protective influence on limb salvage (HR 0.086). A total of 39 (25.2%) major amputations were performed during the follow-up period. Age over 75 years was the only significant and independent factor to negatively impact on amputation-free survival (HR 2.01), which was 24% at 10 years. CONCLUSIONS: The long-term patency after CDT is unfavorable, and additional procedures are needed to preserve adequate distal perfusion. Approximately 30% of the patients are alive at 10 years after the initial CDT. Increasing age and atrial fibrillation have a negative effect on the patients' survival.

Bacterial signatures in thrombus aspirates of patients with lower limb arterial and venous thrombosis.

OBJECTIVE: Increasing data supports the role of bacterial inflammation in adverse events of cardiovascular and cerebrovascular diseases. In our previous research, DNA of bacterial species found in coronary artery thrombus aspirates and ruptured cerebral aneurysms were mostly of endodontic and periodontal origin, where Streptococcus mitis group DNA was the most common. We hypothesized that the genomes of S mitis group could be identified in thrombus aspirates of patients with lower limb arterial and deep venous thrombosis. METHODS: Thrombus aspirates and control blood samples taken from 42 patients with acute or acute-on-chronic lower limb ischemia (Rutherford I-IIb) owing to arterial or graft thrombosis (n = 31) or lower limb deep venous thrombosis (n = 11) were examined using a quantitative real-time polymerase chain reaction to detect all possible bacterial DNA and DNA of S mitis group in particular. The samples were considered positive, if the amount of bacterial DNA in the thrombus aspirates was 2-fold or greater in comparison with control blood samples. RESULTS: In the positive samples the mean difference for the total bacterial DNA was 12.1-fold (median, 7.1), whereas the differences for S mitis group DNA were a mean of 29.1 and a median of 5.2-fold. Of the arterial thrombus aspirates, 57.9% were positive for bacterial DNA, whereas bacterial genomes were found in 75% of bypass graft thrombosis with 77.8% of the prosthetic grafts being positive. Of the deep vein thrombus aspirates, 45.5% contained bacterial genomes. Most (80%) of bacterial DNA-positive cases contained DNA from the S mitis group. Previous arterial interventions were significantly associated with the occurrence of S mitis group DNA (P = .049, Fisher's exact test). CONCLUSIONS: This is the first study to report the presence of bacterial DNA, predominantly of S mitis group origin, in the thrombus aspirates of surgical patients with lower limb arterial and deep venous thrombosis, suggesting their possible role in the pathogenesis of thrombotic events. Additional studies will, however, be needed to reach a final conclusion.

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.

Independent factors predicting early lower limb intra-arterial thrombolysis failure.

BACKGROUND: Risk factors for early catheter-directed intra-arterial thrombolysis failure in acute lower limb ischemia remain unclear. METHODS: One hundred forty-nine limbs with acute artery or bypass graft thrombosis underwent catheter-directed thrombolysis (maximum of 48 hours). A retrospective data analysis was carried out to assess possible risk factors for early, 30-day treatment failure. RESULTS: Seventy-nine men (53%) and 70 women (47%) with a median age of 70 (range 32-93) years were treated. Treatment outcomes were determined as success (N = 115, 77%) or failure (N = 34, 23%). The failure criteria comprised rapid progression of ischemia (N = 4, 2.7%) and major bleeding complications (N = 2, 1.3%), both requiring thrombolysis termination and surgery. Inability to reopen native arteries/grafts (N = 10, 6.7%), run-off vessels (N = 10, 6.7%), in-hospital death (N = 4, 2.7%), the need for major amputation (N = 13, 8.7%), and reocclusions (N = 5, 3.4%) within the 30-day follow-up period were also considered as failures. Multivariate analysis of the risk factors' impact on the success of thrombolysis revealed such independent parameters as hypercholesterolemia (OR 0.16, 95% CI 0.06-0.42, P < 0.0001), previous bypass grafting of the ipsilateral limb (OR 0.18, 95% CI 0.06-0.53, P = 0.002), and duration of ischemia prior to the initiation of thrombolysis (OR 0.95, 95% CI 0.91-0.99, P = 0.009, per day). CONCLUSION: According to our results, factors independently predicting early failure include hypercholesterolemia, previous bypass grafting, and a delay in treatment initiation. Moreover, catheter-directed intra-arterial thrombolysis can be considered safe and effective in the treatment of acute lower limb ischemia.

[Should we start AAA screening in Finland?]. / Onko vatsa-aortan aneurysman seulontaan aihetta suomessa?

Abdominal aortic aneurysms (AAA) are usually asymptomatic before rupture. Through ultrasound screening AAA can be found before rupture. In Europe England and Sweden have started one-time ultrasound screening for men at age 65. Many studies around Europe have shown that screening is cost-effective. In a recent Finnish study one-time screening for men at age 65 would be a more effective option than the current practice where no screening is offered. Screening for abdominal aortic aneurysm among 65-year-old women would entail less additional costs but fewer life years gained than screening for men. Starting the screening would require additional resources in the Finnish health care system as compared to the current policy.

Challenging treatment of multiple late complications after endovascular aneurysm repair.

BACKGROUND: To report a case of multiple additional procedures after successful endovascular treatment of abdominal aortic aneurysm. METHODS: An endovascular abdominal aortic aneurysm repair with a bifurcated aortic Vanguard endograft successfully performed in 1999 resulted in multiple complications, including endoleaks and a row separation, treated endovascularly. Subsequently, tuberculosis sepsis and prosthesis infection resulted in long-term antibiotic treatment. Additional graft leaks, aneurysm sack growth, and sack ruptures were also treated endovascularly because the patient consistently denied open repair. Endovascular procedures, however, did not solve the problem, turning to be increasingly challenging. The patient finally approved open graft removal and aortobifemoral reconstruction that were successfully performed 11 years after the initial endograft implantation. RESULTS: The patient has recovered from surgery well and is asymptomatic. No evidence of bacterial colonization was found according to the specimen taken during the laparotomy. CONCLUSION: Vanguard and other first-generation aortic endografts are associated with high incidence of complications and reinterventions. Open surgery is a method of choice in similar cases.

EVAR may reduce the risk of aneurysm rupture despite persisting type Ia endoleaks.

PURPOSE: To determine the risk of aneurysm rupture in patients with persisting proximal type Ia endoleaks following endovascular aneurysm repair (EVAR) in comparison to the risk of rupture of untreated abdominal aortic aneurysms (AAA) of similar size. METHODS: Among 400 patients who where treated with EVAR from 1996 to 2003 at a single center, 21 (5.3%) patients (13 men; mean age 78.0±5.0 years, range 67-86) with large (≥5.5 cm) aneurysms had imaging evidence of type Ia endoleaks that persisted >10 months (type Ia group) despite secondary endovascular treatment. These patients were compared to 24 untreated AAA patients (17 men; mean age 73.8±5.2 years, range 64-88) with large aneurysms from a separate geographic region with a well-established aneurysm treatment program before EVAR became available (1990-1998). RESULTS: There were no significant differences between the type Ia and the untreated AAA patients with regard to age (79±8 vs. 74±5 years), gender (38% vs. 29% women), baseline aneurysm diameter (6.1±0.7 vs. 6.4±0.9 cm), or length of follow-up (32±23 vs. 29±40 months). During the follow-up period, the rate of aneurysm enlargement was significantly lower in type Ia patients (0.19 cm/y) than in untreated AAA patients (0.54 cm/y, p = 0.03). One (4.8%) patient with a persisting type Ia endoleak and 2-cm aneurysm enlargement (0.8 cm/y) had aneurysm rupture after 2.5 years, while 12 (50%) of the 24 untreated aneurysms ruptured (p = 0.001), which was the primary cause of death in this group. The rupture rate was 1.8 per 100 patient-years in the type Ia group and 20.7 per 100 patient-years in the untreated AAA group. Aneurysm-related mortality was significantly reduced in the type Ia group compared to the untreated AAA group at 36 months (11% vs. 52%, p = 0.004). In the multivariate analysis, factors associated with death were an untreated AAA (odds ratio 97, p = 0.004), female gender (odds ratio 9.7, p = 0.02), and baseline aneurysm size (odds ratio 4.7/cm, p = 0.03). CONCLUSION: This study suggests that EVAR may reduce the risk of rupture and aneurysm-related death despite the presence of a persisting type Ia endoleak. This finding is limited to patients with aortic endografts that are in good position. The mechanism of protection from rupture is unclear but may be related to reducing the rate of aneurysm enlargement.

[Subclavian steal syndrome]. / Subclavian steal -oireyhtymä.

Subclavian steal syndrome is a circulatory disorder usually caused by atherosclerosis and accompanied by ischemic symptoms of the vertebrobasilar region and the hand. In many cases, significant vascular lesions are found also in other arteries. In more than 80% of cases the blood vessel lesion is on the left, and a significant stenosis or occlusion causes an inter-arm pressure gradient of > 20 mmHg, resulting in retrograde blood flow of the ipsilateral vertebral artery. In local stenosis, conservative treatment can be combined with an intravascular procedure, and in occlusions or other arterial lesions requiring operative treatment, with bypass surgery.

[Vascular malformations associated with Marfan syndrome, Ehlers-Danlos syndrome and neurofibromatosis 1 and their surgical treatment]. / Marfanin oireyhtymään, Ehlers-Danlosin oireyhtymään ja neurofibromatoosi 1: een liittyvät verisuonimuutokset ja niiden kirurginen hoito.

The Marfan syndrome, vascular type Ehlers-Danlos syndrome and neurofibromatosis 1 are associated with vascural complications that may be fatal. Therefore, referral to treatment should be properly timed, followed by therapy taking special features of the disease into consideration. When treating a vascular malformation related to an inherited disorder, it is important to collaborate with clinical geneticists in order to obtain genetic counseling and DNA diagnostics as well as to elucidate the status of close relatives.

Urethral in situ biocompatibility of new drug-eluting biodegradable stents: an experimental study in the rabbit.

OBJECTIVE: To assess the effect of drug-eluting properties on the degradation process and the biocompatibility of biodegradable drug-eluting urethral stents. MATERIALS AND METHODS: Braided biodegradable 80 L/20D-PLGA (copolymer of polylactide and polyglycolide) stents with drug-eluting properties were used as the test material. The drugs analysed were indomethacin, dexamethasone and ciprofloxacine. 80 L/20D-PLGA stents without a drug coating served as controls. In all, 16 male rabbits were used and divided into four groups. The stents were inserted under general anaesthesia into the posterior urethra. After 1 month, the rabbits were killed and the urethra removed for histological and optic microscopy analyses. RESULTS: Control stents and the dexamethasone-eluting stents degraded totally during the follow-up period. Conversely, in both indomethacin- and ciprofloxacine-eluting stent groups, the degradation process was significantly delayed and they induced an increase in epithelial hyperplasia. Histological analysis showed that all the stents induced eosinophilia, but there were no significant differences in the intensity of acute or chronic inflammatory reactions and fibrosis. CONCLUSIONS: A drug-eluting capacity can be added to biodegradable stents. The addition of a drug influences the biodegradation time of PLGA urethral stents. Further studies are needed, to find the proper concentrations and releasing profiles of the drugs to achieve the desired bioactivity and biocompatibility properties.

[Challenging treatment of aortic aneurysm is under change]. / Aortta-aneurysman vaativa hoito muuttumassa.

Abdominal aortic aneurysm is a common and increasing health risk. Indication for therapy in men is an aneurysm over 55 mm and in women, over 50 mm in diameter. Novel endovascular treatment procedures are nowadays suitable for a large proportion of patients and will improve patient safety, shorten the duration of therapy and speed up rehabilitation. Therapeutically very challenging problems are aneurysms affecting the renal and visceral arteries, infections of aortic prostheses as well as aneurysmal ruptures during emergency services. Managing of these problems requires experience, whereby centralizing their treatment will improve treatment outcome.

[What is known about the effectiveness of vascular surgery?]. / Mitä tiedetään verisuonikirurgian vaikuttavuudesta.

According to nationally consistent guidelines for nonurgent care, the aim is to make decisions of treatment and prioritizing on systematically clear grounds both within the public and the private sector. In vascular surgery, vertical prioritizing has been carried out and attempts have been made to extensively assess the effectiveness of therapy. We aim to provide a review of the current state of vascular surgery and the resulting health benefit by using the available rough effectiveness indicators, as a register for national quality assurance is lacking.

Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death.

BACKGROUND: Disturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2) and the SREBF cleavage-activating protein (SCAP). We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314) and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD). METHODS: Whole genome expression profiling was completed in twenty vascular samples from carotid, aortic and femoral atherosclerotic plaques and six control samples from internal mammary arteries. Three hundred sudden pre-hospital deaths of middle-aged (33-69 years) Caucasian Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death Study. Coronary narrowing and areas of coronary wall covered with fatty streaks or fibrotic, calcified or complicated lesions were measured and related to the SREBF-2 and SCAP genotypes. RESULTS: Whole genome expression profiling showed a significant (p = 0.02) down-regulation of SREBF-2 in atherosclerotic carotid plaques (types IV-V), but not in the aorta or femoral arteries (p = NS for both), as compared with the histologically confirmed non-atherosclerotic tissues. In logistic regression analysis, a significant interaction between the SREBF-2 1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p = 0.046). Men with the SREBF-2 C allele and the SCAP G allele had a significantly increased risk of SCD (OR 2.68, 95% CI 1.07-6.71), compared to SCAP AA homologous subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having complicated lesions and for the occurrence of thrombosis were found, although the results were not statistically significant. CONCLUSION: The results suggest that the allelic variants (SREBF-2 1784G>C and SCAP 2386A>G) in the cholesterol homeostasis regulating SREBF-SCAP pathway may contribute to SCD in early middle-aged men.

A method for partitioned fluid-structure interaction computation of flow in arteries.

In this paper we apply the artificial compressibility method (ACM) in strongly coupled fluid-structure interaction (FSI) computation of blood flow in an elastic artery. Previously published and here referred to as the ACM/FSI method uses the idea of artificial compressibility by Chorin 1967, except the term of pressure time derivative in the continuity equation is used to mimic the response of the walls, thereby stabilizing the iterative coupling. To reach the aim, we present a new way, the test load method, to improve ACM/FSI computations. In the test load method, the compressibility parameter is computed locally and is based on the mesh deformation of the fluid domain. The functionality of the ACM/FSI coupling with the test load method is demonstrated in an arterial flow simulation, and the combination is shown to provide a robust convergence. In order to get the test cases to correspond better to human physiology, one-dimensional FSI models are combined with the higher dimensional test models.

Differentially expressed genes and canonical pathway expression in human atherosclerotic plaques - Tampere Vascular Study.

Cardiovascular diseases due to atherosclerosis are the leading cause of death globally. We aimed to investigate the potentially altered gene and pathway expression in advanced peripheral atherosclerotic plaques in comparison to healthy control arteries. Gene expression analysis was performed (Illumina HumanHT-12 version 3 Expression BeadChip) for 68 advanced atherosclerotic plaques (15 aortic, 29 carotid and 24 femoral plaques) and 28 controls (left internal thoracic artery (LITA)) from Tampere Vascular Study. Dysregulation of individual genes was compared to healthy controls and between plaques from different arterial beds and Ingenuity pathway analysis was conducted on genes with a fold change (FC) > ±1.5 and false discovery rate (FDR) < 0.05. 787 genes were significantly differentially expressed in atherosclerotic plaques. The most up-regulated genes were osteopontin and multiple MMPs, and the most down-regulated were cell death-inducing DFFA-like effector C and A (CIDEC, CIDEA) and apolipoprotein D (FC > 20). 156 pathways were differentially expressed in atherosclerotic plaques, mostly inflammation-related, especially related with leukocyte trafficking and signaling. In artery specific plaque analysis 50.4% of canonical pathways and 41.2% GO terms differentially expressed were in common for all three arterial beds. Our results confirm the inflammatory nature of advanced atherosclerosis and show novel pathway differences between different arterial beds.

Does diabetes protect the femoral artery against atherosclerosis?

AIM: To compare the extent of angiographically detected stenoses in different segments of the lower leg arteries in diabetics and nondiabetics. METHODS: The study group consisted of 60 nondiabetic and 38 diabetic patients with lower extremity disease and no previous vascular interventions. Arterial lesions were analysed by digital subtraction angiography (DSA). The patients were evaluated by walking distance and ankle-brachial index (ABI) and the reason for hospitalization was recorded. RESULTS: Statistically significantly fewer stenoses were found in the superficial femoral artery in diabetics than in nondiabetics. Although a tendency to more diffuse changes in crural arteries was found, no statistically significant difference were found in other segments of the lower leg arteries apart from the femoral arteries. CONCLUSIONS: Judging from the present results there are fewer angiographically detectable stenoses in the superficial arteries in diabetics than nondiabetics.

Preoperative white matter lesions are independent predictors of long-term survival after internal carotid endarterectomy.

BACKGROUND: Cerebral white matter lesions (WMLs) predict long-term survival of conservatively treated acute stroke patients with etiology other than carotid stenosis. In carotid endarterectomy patients, WMLs are associated with severe carotid stenosis and unstable plaques, with the risk of perioperative complications and with increased 30-day perioperative risk of death. However, no data exist on their effect on postoperative long-term survival, a factor important when considering the net benefit from carotid endarterectomy. Whether this effect is independent of classical risk factors and indications for surgery is not known either. We hypothesized that WMLs could be evaluated from preoperative routine computed tomography (CT) scans and are predictors of postoperative survival, independent of classical cardiovascular risk factors, indication category and degree of carotid stenosis. METHODS: A total of 353 of 481 (73.4%) consecutive patients subjected to carotid endarterectomy due to different indications, i.e. asymptomatic stenosis (n = 28, 7.9%), amaurosis fugax (n = 52, 14.7%), transient ischemic attack (n = 135, 38.2%) or ischemic stroke (n = 138, 39.1%), from prospective vascular registries during the years 2001-2010 with digital preoperative CT scans, were included in the study. WMLs were rated by a radiologist (Wahlund criteria) in a blinded fashion. Internal carotid artery (ICA) stenoses were angiographically graded (<50, 50-69, 70-99 and 100%). Odds ratios (ORs) and hazard ratios (HRs) are reported (ORs and HRs ≤1 indicate a beneficial effect). The median follow-up time was 67 months (interquartile range 45.5, range 0-129 months). Spearman's rho was used to estimate intraobserver agreement. Binary logistic regression was performed to analyze the association of risk factors with WMLs. Cox regression proportional hazards analysis was used to study the effect of different factors on survival. RESULTS: WML severity could be assessed with a substantial intraobserver agreement (Spearman's rho 0.843, p < 0.0001). Only age (OR 1.10, 95% CI 1.06-1.15; p < 0.0001 per year), degree of ipsilateral ICA stenosis (OR 2.22, 95% CI 1.08-4.55; p < 0.05 per stenosis grade) and indication category (OR 1.63, 95% CI 1.19-2.24; p < 0.01 per category) remained independently associated with WMLs. Age (HR 1.04, 95% CI 1.01-1.08; p < 0.05 per year), diabetes (HR 1.59, 95% CI 1.01-2.49; p < 0.05), peripheral arterial disease (HR 2.47, 95% CI 1.46-4.15; p < 0.01), degree of ipsilateral ICA stenosis (HR 2.56, 95% CI 1.12-5.87; p < 0.05 per stenosis grade) and WMLs (HR 3.83, 95% CI 1.17-12.5; p < 0.05) remained independently associated with increased long-term mortality. CONCLUSIONS: WMLs in a preoperative CT scan provide a substantially reliable estimate of postoperative long-term survival of carotid endarterectomy patients independent of currently used criteria, i.e. cardiovascular risk factors, indication category and degree of ipsilateral ICA stenosis.

Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque.

Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged 31.9 ± 4.9) with lipids and cIMT data were included. For functional study, whole genome mRNA expression profiling was performed in 91 histologically classified atherosclerotic samples. In females, serum total, LDL cholesterol and apoB levels increased gradually according to USF1 rs2516839 genotypes TT < CT < CC and rs1556259 AA < AG < GG as well as according to USF1 H3 (GCCCGG) copy number 0 < 1 < 2. Furthermore, the carriers of minor alleles of rs2516839 (C) and rs1556259 (G) of USF1 gene had decreased USF1 expression in atherosclerotic plaques (P = 0.028 and 0.08, respectively) as compared to non-carriers. The genetic variation in USF1 influence USF1 transcript expression in advanced atherosclerosis and regulates levels and metabolism of circulating apoB and apoB-containing lipoprotein particles in sex-dependent manner, but is not a major determinant of early markers of atherosclerosis.

Dexamethasone-eluting vascular stents.

Percutaneous transluminal angioplasty (PTA) with stenting is widely used in the treatment of vascular disorders, but restenosis remains a significant problem. Drug-eluting stents (DES) have been developed as an attempt to reduce the intimal response leading to restenosis. Drugs used in DES include mainly immunosuppressive and anti-proliferative compounds. Glucocorticoids are also an interesting possibility for those purposes because they have anti-proliferative effects in vascular smooth muscle cells and down-regulate the production of cytokines and growth factors driving inflammation and fibrosis. In this MiniReview, feasibility and safety of drug-eluting metal and biodegradable vascular stents are discussed with special emphasis on dexamethasone-eluting stents.