Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene ( LPA ) on vascular diseases with different atherosclerotic and thrombotic components. ...Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST Trial of Org 10172 in Acute Stroke Treatment subtypes) (effective sample size ne = 9,396); peripheral arterial disease ( ne = 5,215); abdominal aortic aneurysm ( ne = 4,572); venous thromboembolism ( ne = 4,607); intracranial aneurysm ( ne = 1,328); CAD ( ne = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio OR: 1.27; p = 6.7 × 10–4 ), peripheral artery disease (OR: 1.47; p = 2.9 × 10–14 ), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 × 10–5 ), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 × 10–12 ). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (–1.58 years/allele; p = 8.2 × 10–8 ) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes.
Objective To evaluate compliance with screening and prevalence of abdominal aortic aneurysm (AAA) in relation to background data regarding area-based socioeconomic status. Methods Our department ...annually invites 4300 65-year-old men from the city of Malmö and 15 neighboring municipalities to ultrasound AAA screening. In a cross-sectional cohort study, compliance and AAA prevalence among 8269 men were related to background socioeconomic data such as mean income, proportion of immigrants, percentage of subjects on welfare, smoking habits, and unemployment rate in the different municipalities. The 10 different administrative areas in Malmö were evaluated separately. Results Compliance with screening in the entire area was 6630/8269 (80.2%) but varied between 64.4% and 89.3% in different municipalities ( P < .001). In univariate analysis, compliance increased with increasing mean income ( r = 0.873; P < .001) but decreased with increasing proportion of immigrants ( r = −0.685; P =.005) and subjects on welfare ( r = −0.698; P = .004). Compliance in 10 different administrative parts of Malmö ( P = .002) also increased with increasing mean income ( r = 0.948; P < .001), and decreased with increasing proportion of immigrants ( r = −0.650; P = .042) and increasing unemployment rate ( r = −0.796; P = .006). Altogether, 117 (1.8%) AAAs were found, the prevalence differing between both different municipalities ( P =.003) and the 10 different administrative parts of Malmö ( P =.02). The prevalence of AAA in the 10 administrative parts of Malmö increased with increasing percentage of smokers ( r = 0.784; P = .007), percentage of immigrants ( r = 0.644; P = .044), and unemployment rate ( r = 0.783; P =.007) but decreased with increasing mean income ( r = −0.754; P = .012). Conclusions Compliance with ultrasound screening for AAA differed between different geographical areas. In areas with low socioeconomic status, compliance rates were lower, whereas AAA prevalence was higher. The identification of contextual factors associated with low compliance is important to be able to allow targeted actions to increase efficacy of ultrasound screening for AAA. Targeted actions to increase compliance in those areas are being scientifically investigated and implemented.
Objective Endovascular abdominal aortic repair requires an adequate sealing zone. The chimney graft (CG) technique may be the only option for urgent high-risk patients who are unfit for open repair ...and have no adequate sealing zone. This single-center experience provides long-term results of CGs with endovascular repair for urgent and complex aortic lesions. Methods Between July 2006 and October 2012, 51 patients (16 women) with a median age of 77 years (interquartile range, 72-81 years), were treated urgently (within 24 hours 61%) or semiurgently (within 3 days 39%) with endovascular aortic repair and visceral CGs (n = 73). Median follow-up was 2.3 years (interquartile range, 0.8-5.0 years) for the whole cohort, 3 years for 30-day survivors, and 4.8 years for patients who are still alive. Results Five patients (10%) died within 30 days. All of them had a sacrificed kidney. All-cause mortality was 57% (n = 29), but the chimney- and procedure-related mortality was 6% (n = 3) and 16% (n = 8), respectively. Chimney-related death was due to bleeding, infection, renal failure, and multiple organ failure. There were two postoperative ruptures; both were fatal although not related to the treated disease. The primary and secondary long-term CG patencies were 89% (65 of 73) and 93% (68 of 73), respectively. Primary type I endoleak (EL-I) occurred in 10% (5 of 51) of the patients, and only one patient had recurrent EL-I (2%; 1 of 51). No secondary endoleak was observed. Chimney-related reintervention was required in 16% (8 of 51) of the patients because of EL-I (n = 3), visceral ischemia (n = 4), and bleeding (n = 2). The reinterventions included stenting (n = 5), embolization (n = 3), and laparotomy (n = 2). Thirty-one visceral branches were sacrificed (9 celiac trunks, 9 right, and 13 left renal arteries). Among the 30-day survivors, 8 of 17 patients (47%) with a sacrificed kidney required permanent dialysis; of these, seven underwent an urgent index operation. The aneurysm sac shrank in 63% (29 of 46) of cases. Conclusions The 6% chimney-related mortality and 93% long-term patency seem promising in urgent, complex aortic lesions of a high-risk population and may justify a continued yet restrictive applicability of this technique. Most endoleaks could be sealed endovascularly. However, sacrifice of a kidney in this elderly cohort was associated with permanent dialysis in 47% of patients.
Objective This study reports the early and midterm to long-term experience of chimney grafts (CGs) in urgent endovascular repair of complex lesions in the thoracic aorta. Methods Twenty-nine ...high-risk patients (20 men) who were unfit for open repair were treated using CG technique for ruptured (n = 14) or symptomatic (n = 15) aortic lesions engaging the aortic arch itself (n = 9), the descending aorta (n = 10), or the thoracoabdominal aorta (n = 10). Twenty-two patients (76%) were treated urgently (≤24 hours) and seven were semiurgent (≤3 days). Of 41 chimneys used, 24 were placed in supra-aortic branches and 17 in visceral branches. Median follow-up (interquartile range) for the entire cohort was 2 years (0.6-3.8 years), 2.5 years (1-4 years) for 30-day survivors, and 3.5 years (1.9-6.4 years) for those who were still alive. Results Four patients (14%) died ≤30 days of cerebral infarction (n = 1), visceral ischemia secondary to the initial rupture (n = 1), multiple organ failure (n = 1), or heart failure (n = 1). There were 11 late deaths (38%); however, only two deaths were related to the CG technique. The primary and secondary technical success rates were 86% (25 of 29) and 97% (28 of 29), respectively. The secondary patency rate of CGs was 98%. Seventeen (68%) of the aortic lesions shrank significantly. Three patients (10%) had primary type I endoleak and another three (10%) had secondary type I endoleak. The endoleaks were managed with Onyx (ev3 Endovascular, Inc, Plymouth, Minn) or coil embolization (n = 2), restenting (n = 1), and conversion to open repair (n = 2). One secondary endoleak is still under observation after >20 months. All primary endoleaks and one secondary endoleak originated from CGs in the brachiocephalic trunk (4 of 6 67%). Conclusions The midterm to long-term results of the CG technique for urgent and complex lesions of the thoracic aorta in high-risk patients are promising, with low early mortality and long durability of the CGs. More patients with longer follow-up are still needed.
Objective Chimney grafts have proven useful for urgent endovascular repair of juxtarenal aortic aneurysms. Stenting of juxtarenal aortic occlusive disease is not routinely advocated due to the risk ...of visceral artery obstruction. We report on the potential applicability of chimney grafts in 10 patients with juxtarenal aortic stenosis or occlusion. To our best knowledge, chimney grafts have not been applied previously in this challenging setting. Methods Ten high-risk female patients (mean age, 68 years) with severe stenosis or occlusion of the aorta at the level of the visceral arteries were offered stenting. “Chimney” stents or stent grafts (20-40 mm long) were implanted from a brachial approach into visceral arteries that needed to be covered by the aortic stent. The chimney stents were then temporarily obstructed by balloon catheters to prevent visceral embolization until the aortic stent or stent graft was deployed. Results All procedures were technically successful, and patency was obtained in all visceral arteries and the aorta without distal embolization. One patient died after 9 days of acute heart failure. The nine surviving patients presented no complications, and all stented vessels remained patent at up to 6 years. Another patient died after 5.5 years due to lung cancer. All three patients with renal impairment have improved renal function, and a reduction in antihypertensive medication has been possible. Conclusions Chimney grafts may allow stenting of juxtarenal aortic occlusive disease by protecting the patency of visceral arteries. Further evaluation with more patients and longer follow-up is required.
Objective This study assessed prognostic factors regarding long-term outcome for amputation and death among patients who underwent intra-arterial thrombolysis due to lower limb ischemia. Methods ...Consecutive patients with intra-arterial thrombolysis due to lower limb ischemia treated at the Department of Vascular Diseases, University Hospital of Malmö, between January 1, 2001, and December 31, 2005, were retrospectively reviewed. A multivariate Cox regression analysis was performed to determine independent predictors for amputation and death. Results A total of 220 intra-arterial thrombolysis procedures were performed in 195 patients (46% women). Median age was 73 years. Complete and partial thrombolysis was obtained in 41% and 38%, respectively. Hemorrhagic complications were documented in 33%, but only 6% (13 of 220) were interrupted. The amputation rate was 26% and mortality was 35% during a median follow-up of 32 months. Degree of lysis (hazard ratio HR, 4.8; 95% confidence interval CI, 2.4-9.7; P < .001), motor deficit at admission (HR, 4.0; 95% CI, 1.8-8.7; P = .001), foot ulcers (HR, 7.2; 95% CI, 2.2-23.4; P = .001), and ischemic heart disease (HR, 2.3; 95% CI, 1.1-4.8; P = .024) remained as independent factors associated with amputation. Renal insufficiency (HR, 2.4; 95% CI, 1.4-4.2; P = .003), ischemic heart disease (HR, 2.1; 95% CI, 1.2-3.7; P = .007), cerebrovascular disease (HR, 2.2; 95% CI, 1.2-4.0; P = .009), foot ulcers (HR, 3.2; 95% CI, 1.2-8.6; P = .019), and acute lower limb ischemia (HR, 3.4; 95% CI, 1.1-10.1; P = .028) remained as independent factors associated with mortality. Conclusions Thrombolysis is successful, with few major complications in most patients with lower limb ischemia. Patients with ischemic heart disease and foot ulcers are at higher long-term risk for both amputation and death. A lesser degree of lysis and motor deficit were associated with higher amputation rates. The presence of such negative prognostic factors may help clinicians to deny further invasive vascular treatment. Renal insufficiency, cerebrovascular disease, and acute lower limb ischemia were associated with increased mortality.
Objective Critical limb ischemia (CLI) is a peripheral arterial disease manifested by drastically diminished blood flow to the legs, pain at rest, nonhealing wounds, and gangrene caused by ...atherosclerosis. Significant tissue necrosis is associated with late stage CLI and the patients have a poor prognosis. Necrotic and apoptotic cells activate complement and bind complement inhibitor C4b-binding protein (C4BP). The major isoform of C4BP is composed of seven identical α-chains and one β-chain, here termed C4BPβ , whereas upon inflammation a normally less abundant isoform is upregulated that is exclusively composed of α-chains. Measuring the α-chains of C4BP includes both isoforms and is termed total C4BP (C4BPtot ). The hypothesis of this study was that levels of complement activation and C4BP are predictive for the severity of the disease and that their measurement might be of clinical advantage. Methods This was a prospective, single-center study of 259 consecutive patients with CLI admitted to a secondary referral center for vascular diseases. Interventions included evaluation of soluble terminal complement complexes (C5b-9), C4BPtot and C4BPβ , lipid levels, the inflammatory mediators tumor necrosis factor-α, interleukin-6, 8-iso-prostaglandin F2α , high-sensitivity C-reactive protein, neopterin, plasma homocysteine, and plasma endothelin-1 in plasma as well as resistance to activated protein C and ankle blood pressure. All data were compared with an age-matched population based control group of 219 currently healthy individuals. Results The data are presented as mean ± SEM/median. CLI patients showed systemic complement activation (1.17 ± 0.06/1.13 AU/mL vs 0.69 ± 0.07/0.59 AU/mL in healthy controls, P < .0001), which was even higher in patients with gangrene (1.33 ± 0.11/1.28 AU/mL vs 1.1 ± 0.08/1.0 AU/mL, P = .0264), who also showed increased C4BP levels (421 ± 28.6/386 μg/mL vs 341 ± 10.8/318 μg/mL for C4BPtot , P = .0248; 374 ± 25.4/332 μg/mL vs 305 ± 9.5/285 μg/mL for C4BPβ , P = .0581). C4BP plasma levels were significantly elevated in CLI patients in comparison to healthy controls (351 ± 8.1/322 μg/mL vs 297 ± 8.0/288 μg/mL for C4BPtot , P = .0001; 314 ± 7.0/287 μg/mL vs 265 ± 7.0/263 μg/mL for C4BPβ , P = .0004) and correlated to levels of interleukin-6 ( Ptot/β = .0048/.0019), high-sensitivity C-reactive protein ( P < .0001), leukocyte ( Ptot/β = .0086/.0043) and platelet count ( P = .0001), LDL/HDL ratio ( Ptot = .0151) and HDL ( Ptot/β = .0047/.0177), but not to tumor necrosis factor-α. Conclusions Increased complement activation and C4BP plasma levels are related to the degree of tissue necrosis and disease severity of critical limb ischemia. This knowledge in combination with the found correlations to other biomarkers is useful for understanding the pathophysiology of the disease.
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