Management of Acute Lower Limb Ischemia Without Surgical Revascularization - A Population-Based Study.

OBJECTIVES: To evaluate outcomes of management without surgical revascularization in patients with acute lower limb ischemia (ALI) in a population-based setting. DESIGN: Retrospective observational population-based study. MATERIALS: Patients from Malmö, Sweden, hospitalized for ALI between 2015 and 2018. METHODS: In-hospital, surgical, radiological, and autopsy registries were scrutinized for descriptive data on ALI patients managed by endovascular and open vascular surgery, conservative vascular therapy, primary major amputation, and palliative care. RESULTS: Among 161 patients, 73 (45.3%) did not undergo any operative revascularization. Conservative vascular therapy, primary amputation, and palliative care were conducted in 25 (15.5%), 26 (16.1%), and 22 (13.7%) patients, respectively. Conservatively treated patients had Rutherford class ≥ IIb ischemia and embolic occlusion in 33% and 68% of cases, respectively. Their median C-reactive protein level at admission was 7 mg/L (interquartile range 2 - 31 mg/L). Among conservatively treated patients, anticoagulation therapy in half to full dose was given to 22 (88%) patients for six weeks or longer, and analgesics in low or moderate doses were given to twelve (48%) patients at discharge. The major amputation rate at 1 year was 8% among conservatively treated patients, and four patients with foot embolization had not undergone amputation at 1 year. CONCLUSION: Patients selected for initial conservative therapy of ALI with anticoagulation alone may have a good outcome, even when admitted with Rutherford class IIb ischemia. A low C-reactive protein level at admission seems to be a favorable marker when choosing conservative therapy. A prospective, preferably multicenter, study with a predefined protocol in these conservatively treated patients is warranted to better define the dose and length of anticoagulation therapy.

A population-based study on hyperinsulinaemia and arterial stiffness in men with and without abdominal aortic aneurysm.

Objectives: Patients with type 2 diabetes mellitus (DM) run lower risk for abdominal aortic aneurysm (AAA, aortic diameter ≥ 30 mm) and its complications. We aimed to evaluate associations between disturbances in glucose metabolism and arterial stiffness, AAA, and abdominal aortic diameter in 65-year-old men. Methods: Forty-eight 65-year-old men with screening-detected AAA and 115 men with normal abdominal aortic diameter underwent examination of glucose metabolism and arterial stiffness. Results: Men with AAA had higher BMI, waist-hip ratio (WHR), frequency of DM, haemoglobin A1c, smoking exposure, and plasma insulin levels at 0, 60 and 120 min during OGTT compared to those without. The increase in p-insulin (P < 0.001) after OGTT was also higher in men with AAA, adjusted for smoking, WHR, and nadir value of p-insulin. In analyses adjusted for smoking, use of lipid-lowering agents, and WHR, the increase in p-insulin at 2-hours (P = 0.006) after OGTT and p-homocysteine were associated with abdominal aortic diameter. There were no differences between groups in aortic stiffness or skin autofluorescence Advanced Glycation End products. Conclusion: In this population-based study hyperinsulinaemia as a marker of insulin resistance, but not hyperglycaemia or aortic stiffness, was associated with AAA and abdominal aortic diameter in 65-year-old men.

Illness perception, health literacy, self-efficacy, adherence and quality of life in patients with intermittent claudication - a longitudinal cohort study.

BACKGROUND: Patients with intermittent claudication need lifelong treatment with secondary prevention to prevent cardiovascular events and progression of atherosclerotic disease. Illness perception, health literacy, self-efficacy, adherence to medication treatment, and quality of life are factors influencing patients' self-management. Knowledge of these factors could be important when planning for secondary prevention in patients with intermittent claudication. AIM: to compare illness perception, health literacy, self-efficacy, adherence to treatment, and quality of life in in patients with intermittent claudication. METHODS: A longitudinal cohort study was conducted with 128 participants recruited from vascular units in southern Sweden. Data were collected through medical records and questionnaires regarding illness perception, health literacy, self-efficacy, adherence to treatment, and quality of life. RESULTS: In the subscales in illness perception, patients with sufficient health literacy reported less consequences and lower emotional representations of the intermittent claudication. They also reported higher self-efficacy and higher quality of life than patients with insufficient health literacy. In comparison between men and women in illness perception, women reported higher illness coherence and emotional representations associated with intermittent claudication compared to men. A multiple regression showed that both consequences and adherence were negative predictors of quality of life. When examining changes over time, a significant increase in quality of life was seen between baseline and 12 months, but there were no significant differences in self-efficacy.. CONCLUSION: Illness perception differs in relation to level of health literacy and between men and women. Further, the level of health literacy seems to be of importance for patients' self-efficacy and quality of life. This illuminates the need for new strategies for improving health literacy, illness perception, and self-efficacy over time. For example, more tailored information regarding secondary prevention could be provided to strengthen self-management to further improve quality of life in patients with intermittent claudication.

Characterization of the Mitochondrial Genetic Landscape in Abdominal Aortic Aneurysm.

Background Abdominal aortic aneurysm (AAA) is a vascular disease with a mortality rate of >80% if ruptured. Mitochondrial dysfunction has been previously implicated in AAA pathogenesis. In this study, we aimed to characterize the mitochondrial genetic landscape in AAA. Methods and Results Whole mitochondrial genome sequencing and bioinformatics analysis were performed in comorbidity matched 48 cases without AAA and 48 cases with AAA, objectively diagnosed, and selected from a cohort of 65-year-old men recruited for a screening program. We identified differential mutational landscapes in men with and without AAA, with errors in mitochondrial DNA replication or repair as potential sources. Heteroplasmic insertions and overall heteroplasmy of structural rearrangements were significantly elevated in AAA cases. Three heteroplasmic variants were associated with risk factors of AAA: leukocyte concentration, plasma glucose, and cholesterol levels, respectively. Interestingly, mutations were more prevalent in regulatory part of the mitochondria, the displacement loop region, in AAA as compared with controls (P value <0.05), especially in the conserved and critical mitochondrial extended termination-associated sequence region. Moreover, we report a novel 24 bp mitochondrial DNA duplication present exclusively in cases with AAA (4%) and 75% of the unmatched AAA biopsies. Finally, the haplogroup cluster JTU was overrepresented in AAA and significantly associated with a positive family history of AAA (odds ratio, 2.9 [95% CI, 1.1-8.1]). Conclusions This is the first study investigating the mitochondrial genome in AAA, where important genetic alterations and haplogroups associated with AAA and clinical risk factors were identified. Our findings have the potential to fill in gaps in the missing genetic information on AAA.

Health literacy in patients with intermittent claudication in relation to clinical characteristics, demographics, self-efficacy and quality of life - A cross-sectional study.

BACKGROUND: Intermittent claudication requires treatment with secondary prevention to reduce disease progression and the risk of cardiovascular events and to improve quality of life. Health literacy and self-efficacy are important preconditions for the health behaviour changes necessary for adhering to secondary prevention. AIM: Evaluate health literacy in patients with intermittent claudication regarding clinical characteristics, demographics, self-efficacy and quality of life. METHODS: A cross-sectional study evaluating health literacy, self-efficacy and quality of life using questionnaires. Patients with intermittent claudication from vascular units in the south of Sweden were included. RESULTS: In total, 158 patients were included, of which, 52.5% reported "inadequate" (0-8 points) or "problematic" (9-12 points) health literacy with no differences between men and women. A significant higher proportion of patients living alone reported "inadequate" or "problematic" health literacy than "sufficient" (13-16 points) health literacy. Patients with "sufficient" health literacy reported significantly higher self-efficacy and quality of life and were more physically active than patients with "inadequate" or "problematic" health literacy. Also, patients with a university degree reported a significantly higher ability to "access" (seek, find and obtain) and "understand" (comprehend the accessed) information relevant to health. CONCLUSION: The majority of patients with intermittent claudication have "inadequate" or "problematic" health literacy. Also, an "inadequate" or "problematic" health literacy level is more common among patients living alone, and education level appears to be more important when "accessing" and "understanding" information relevant to health. This illuminates the importance of not only the patients' health literacy but also demographics when planning for secondary prevention.

Negative Pressure Wound Therapy for the Prevention of Surgical Site Infections Using Fascia Closure After EVAR-A Randomized Trial.

BACKGROUND: Surgical site infections (SSI) in the groin after vascular surgery are common. The aim of the study was to evaluate the effect of negative pressure wound therapy (NPWT) on SSI incidence when applied on closed inguinal incisions after endovascular aneurysm repair (EVAR). METHODS: A multicenter randomized controlled trial (RCT). Between November 2013 and December 2020, 377 incisions (336 bilateral and 41 unilateral) from elective EVAR procedures with the primary intent of fascia closure were randomized and included, receiving either NPWT or a standard dressing. In bilateral incisions, each incision randomly received the opposite dressing of the other side, thereby becoming each other's control. The primary endpoint was SSI incidence at 90 days postoperatively, analyzed on an intention-to-treat basis. Uni and bilaterally operated incisions were analyzed separately, and their respective p-values combined using Fisher's method for combining P-values. Study protocol (NCT01913132). RESULTS: The SSI incidence at 90 days postoperatively in bilateral incisions was 1.8% (n = 3/168) in the NPWT and 4.8% (n = 8/168) in the standard dressing group, and in unilateral incisions 13.3% (n = 2/15) and 11.5% (n = 3/26), respectively (combined p = 0.49). In all SSIs, bacteria were isolated from incisional wound cultures. No additional SSIs were diagnosed between 90 days and 1 year follow-up. CONCLUSIONS: No evidence of difference in SSI incidence was seen in these low-risk inguinal incisions when comparing NPWT with standard dressings after EVAR with the primary intent of fascia closure. CLINICAL TRIALS: NCT01913132.

Novel cardiovascular biomarkers associated with peripheral arterial disease in men screened for abdominal aortic aneurysm.

Background: Peripheral arterial disease (PAD) is a common atherosclerotic disease with severity ranging from asymptomatic to chronic limb threatening ischemia. The aim of the present cross-sectional study was to identify novel biomarkers associated with PAD. Patients and methods: Levels of 91 cardiovascular specific proteins in plasma samples were measured by the Proseek Multiplex CVD III96x96 panel from a cohort consisting of 267 65-year-old men recruited from a screening program for abdominal aortic aneurysm (AAA) Levels of protein biomarkers were compared in men with and without PAD (defined as an ankle brachial index of <0.9) and their diagnostic potential was calculated by receiver-operating characteristic analysis. Results: The prevalence of PAD was 14.2% (38/267). After adjustment for multiple comparisons, levels of the following 11 biomarkers remained significantly higher (p<0.0001) in patients with PAD: secretoglobin family 3A member 2, osteoprotegerin, urokinase-type plasminogen activator surface receptor, serum macrophage chemokine ligand 16, matrix metalloproteinase 9, p-selectin, growth differentiation factor 15, elafin, cystatin B, trefoil factor 3, and fatty acid-binding protein 4. Multivariable logistic regression analysis (adjusted for smoking, use of antihypertensive and lipid-lowering medication, and metformin) showed that 11 biomarkers were significantly associated with higher risk of PAD with odds ratios ranging from 1.6 to 2.4. Area under curve calculated by receiver operating characteristic curve analysis (diagnostic value) for each protein biomarker ranged from 0.63 to 0.74. Conclusions: We have identified multiple proteins with a potential to be diagnostic biomarkers for PAD, and further research is warranted to clarify their potential predictive and prognostic value.

Circulating Biomarkers Predict Symptomatic but Not Asymptomatic Carotid Artery Stenosis.

BACKGROUND: Subjects exposed to risk factors such as age, gender, hypertension, diabetes mellitus, and smoking are prone to atherosclerotic events. AIMS: The main aim of this longitudinal cohort study was to determine whether the role of novel plasma biomarkers for atherosclerotic carotid artery disease is different in subjects developing symptomatic carotid artery stenosis (CAS), as opposed to those with incident asymptomatic CAS. METHODS: The following biomarkers were measured in 5,550 middle-aged subjects in a population-based cohort study: C-reactive protein (CRP), lipoprotein-associated phospholipase A2 mass and activity, proneurotensin, midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT pro-BNP), copeptin, and cystatin C. After exclusion of those with prevalent CAS, subjects were thereafter followed in national patient registers for 23.4 (interquartile range 19.5-24.3) years regarding incident symptomatic and asymptomatic CAS. RESULTS: Among 110 patients with confirmed incident CAS, 56 were symptomatic and 54 were asymptomatic. When including conventional risk markers in a Cox regression analysis, NT pro-BNP (hazard ratio [HR] 1.59; 95% confidence interval [CI]: 1.20-2.11), MR-proADM (HR 1.40; CI: 1.13-1.73), cystatin C (HR 1.21; CI: 1.02-1.43), and CRP (HR 1.53; CI: 1.13-1.73) were independently associated with incident symptomatic CAS, whereas no plasma biomarker was associated with incident asymptomatic CAS. CONCLUSION: Plasma biomarkers NT pro-BNP, MR-proADM, cystatin C, and CRP were independently associated with incident symptomatic CAS, whereas no such association could be demonstrated with incident asymptomatic CAS. As these biomarkers indicate future development of clinically relevant atherosclerotic CAS, their potential utility in relation to intensified preventive measures and selection of potential candidates for carotid surgery should be further evaluated.

Diabetes mellitus was not associated with lower amputation-free survival after open revascularization for chronic limb-threatening ischemia - A nationwide propensity score adjusted analysis.

The risk of major amputation is higher after urgently planned endovascular therapy for chronic limb-threatening ischemia (CLTI) in patients with diabetes mellitus (DM). The aim of this nationwide cohort study was to compare outcomes between patients with and without DM following urgently planned open revascularization for CLTI from 2010 to 2014. Out of 1537 individuals registered in the Swedish Vascular Registry, 569 were registered in the National Diabetes Register. A propensity score adjusted Cox regression analysis was conducted to compare outcome between the groups with and without DM. Median follow-up was 4.3 years and 4.5 years for patients with and without DM, respectively. Patients with DM more often had foot ulcers (p = 0.034) and had undergone more previous amputations (p = 0.001) at baseline. No differences in mortality, cardiovascular death, major adverse cardiovascular events (MACE), or major amputation were observed between groups. The incidence rate of stroke was 70% higher (95% CI: 1.11-2.59; p = 0.0137) and the incidence rate of acute myocardial infarction (AMI) 39% higher (95% CI: 1.00-1.92; p = 0.0472) among patients with DM in comparison to those without. Open vascular surgery remains a first-line option for a substantial number of patients with CLTI, especially for limb salvage in patients with DM. The higher incidence rates of stroke and AMI among patients with DM following open vascular surgery for infrainguinal CLTI require specific consideration preoperatively with the aim of optimizing medical treatment to improve cardiovascular outcome postoperatively.

Vasoactive Biomarkers Associated With Long-Term Incidence of Symptomatic Peripheral Arterial Disease and Mortality.

We evaluated if plasma biomarkers can predict incident peripheral arterial disease (PAD) and mortality in a longitudinal cohort study. Men (n = 3618) and women (n = 1542) were included in the Malmö Preventive Project and underwent analysis of: C-terminal endothelin-1 (CT-proET-1), N-Terminal prosomatostatin (NT-proSST), midregional proatrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and copeptin. Participants were followed up for incident PAD and mortality until December 31, 2016. Median follow-up was 11.2 years (interquartile range 9.4-12.2). Cumulative incidence of PAD was 4.3% (221/5160), 4.5% in men (164/3618) and 3.7% in women (57/1542; P = .174). In an adjusted Cox proportional hazards regression model, higher CT-proET-1 (hazard ratio [HR] 1.8; 95% confidence interval [CI] 1.4-2.3), NT-proSST (HR 1.5; 95% CI 1.2-2.0), and MR-proANP (HR 1.7; 95% CI 1.3-2.3) were independently associated with incident PAD, and higher CT-proET-1 (HR 1.3; 95% CI 1.2-1.5), NT-proSST (HR 1.2; 95% CI 1.1-1.3), MR-proANP (HR 1.4; 95% CI 1.3-1.6), PCT (HR 1.1; 95% CI 1.0-1.2), and copeptin (HR 1.2; 95% CI 1.1-1.4) were independently associated with mortality. Increased levels of CT-proET-1, NT-proSST, and MR-proANP were independently associated with incident PAD, whereas all the vasoactive biomarkers were independently associated with mortality during follow-up.

Illness perceptions in patients with peripheral arterial disease: A systematic review of qualitative studies.

BACKGROUND: Patients with chronic diseases create their own subjective beliefs about their conditions based on their illness perceptions. In the common-sense model, illness perceptions constitute personal beliefs about illness with regard to five components: identity, timeline, cause, control/cure, and consequences. Patients' illness perceptions affect both their management of their disease and their adherence to treatment. Since patients with peripheral arterial disease need life-long treatment for secondary prevention, generating knowledge about illness perceptions in patients with peripheral arterial disease is essential. OBJECTIVES: To systematically review and synthesise the literature on illness perceptions in patients with peripheral arterial disease. DESIGN: A systematic review DATA SOURCES: PubMed, CINAHL, and PsycINFO. REVIEW METHODS: A systematic search strategy was conducted in December 2017, with an update in July 2019. Two team members independently screened all titles and abstracts. A relevance and quality appraisal of the studies was performed. The references from the included studies were evaluated for additional studies. The data from 14 studies were extracted and synthesised using a "best-fit" approach to framework analysis. A deductive analysis was conducted using the common-sense model. The data not suitable for the framework were analysed separately using inductive conventional content analysis, yielding an additional component representing the retrospective consequences of peripheral arterial disease. FINDINGS: The findings showed diversity in illness perceptions in each of the five components of the framework as well as in the additional component. The findings showed participants' lack of understanding of the chronic nature of the disease, i.e., about the timeline, the identity of the symptoms and the cause of the disease. The patients' beliefs about control and cures varied from having high motivation to engage in physical activity to thinking that walking could make their situations worse. There was fear about the future, as patients perceived disease progression and decreasing control to be consequences of their illness. Living with the disease, the emphasis in the additional component, was a process for regaining control and adapting to their situations. CONCLUSIONS: Patients with peripheral arterial disease shape their own understandings of their conditions. These beliefs may influence their management of their disease and adherence to treatment. Therefore, the current study suggests that illness perceptions should be addressed when planning secondary prevention for patients with peripheral arterial disease.

The impact of diabetes mellitus on major amputation among patients with chronic limb threatening ischemia undergoing elective endovascular therapy- a nationwide propensity score adjusted analysis.

AIM: To investigate the risk of major amputation after elective endovascular therapy in patients with chronic limb threatening ischemia (CLTI) comparing patients with and without diabetes mellitus (DM). METHODS: In this nationwide cohort study, all patients registered in the Swedish Vascular Register after elective endovascular therapy for CLTI caused by infra-inguinal arterial disease from 2010 to 2014 were included. Among 4578 individuals, 2251 had DM and were registered in the National Diabetes Register between 2009 and 2014. A propensity score adjusted Cox regression analysis was conducted to compare outcomes between groups. Median follow-up was 4.0 and 3.6 years for patients with DM and without DM, respectively. RESULTS: The incidence rates of major amputation and acute myocardial infarction (AMI) were 43% (95% CI 1.23-1.67) and 37% (95% CI 1.13-1.67) higher, respectively, among patients with DM compared to patients without DM. There was no difference in mortality (HR 1.04, 95% CI 0.95-1.14). CONCLUSIONS: Patients with DM had a higher risk of major amputation and AMI compared to those without DM after elective endovascular therapy for CLTI. Prevention of DM with CLTI is of utmost importance to reduce the risk of adverse limb and cardiovascular outcomes.

Cost-effectiveness analysis of negative pressure wound therapy dressings after open inguinal vascular surgery - The randomised INVIPS-Trial.

AIM: While the scientific evidence in favour of negative pressure wound therapy (NPWT) dressings on sutured incisions in the prevention of surgical site infections (SSIs) has increased, the cost-effectiveness after vascular surgery has not been evaluated. The aim of this study was to evaluate the cost-effectiveness of NPWT compared to standard dressings for the prevention of SSIs after open inguinal vascular surgery. MATERIALS AND METHODS: Patient data were retrieved from the randomised INVIPS-trial's open arm, which included patients randomised to either NPWT or standard dressings. The patients were surveyed for SSIs for 90 days postoperatively. The patients' individual cost data were included and analysed from a healthcare perspective. The patients' quality of life was measured using the Vascuqol-6 questionnaire pre- and 30 days postoperatively. Cost-effectiveness of NPWT was determined by decreased or equal total costs and a significant reduction in SSI incidence. RESULTS: The mean vascular procedure-related costs at 90 days were €16,621 for patients treated with NPWT (n = 59) and €16,285 for patients treated with standard dressings (n = 60), p = 0.85. The SSI incidence in patients treated with NPWT was 11.9% (n = 7/59) compared to 30.0% (n = 18/60) with standard dressings, p = 0.015. This corresponds to an increased mean cost of €1,853 per SSI avoided. The cost-effectiveness plane of incremental vascular procedure-related costs and difference in Vascuqol-6 score showed that 42% of estimates were in the quadrant where NPWT was dominant. CONCLUSION: NPWT is considered cost-effective over standard dressings in patients undergoing open inguinal vascular surgery due to reduced SSI incidence at no higher costs.

Higher long-term cardiovascular morbidity after open surgery for intermittent claudication caused by infrainguinal atherosclerotic disease in patients with diabetes - a nationwide observational cohort study.

Background: Diabetes mellitus (DM) is a risk factor for peripheral arterial disease (PAD). Indications for open surgery in infrainguinal intermittent claudication (IC) are limited, and reports are lacking regarding outcomes in DM patients. Study aims were to compare short and long-term effects on major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, major amputation, and mortality after infrainguinal open surgery for IC in patients with and without DM, and to evaluate relationships between glycaemic control and outcomes. Methods: Nationwide observational cohort study of all patients registered in the Swedish Vascular Registry after planned infrainguinal open surgery for IC from January 1st 2010 to December 31st 2014. Patients registered in the National Diabetes Registry were compared with patients without diabetes by propensity score adjusted comparison of MACE, AMI, stroke, major amputation, and mortality. Results: After 30 days, there were no differences in MACE, AMI, stroke, major amputation, or mortality between patients with (n = 323, mean age 70.5 [SD 7.4] years, 92 [28.5%] females) and without (n = 679, mean age 69.7 years [SD 11.2], 234 [34.5%] females) DM. At last follow-up after median 5.2 years, patients with DM showed higher rates of MACE (Hazard ratio [HR] 1.33, confidence interval [CI] 1.08-1.62; p < 0.01), and AMI (HR 2.21, CI 1.46-3.35; p < 0.01) than patients without diabetes. Among DM patients, higher glycated haemoglobin (HbA1c) was associated with higher rates of MACE (HR 1.02, CI 1.00-1.03; p = 0.02), stroke (HR 1.05, CI 1.00-1.11; p = 0.04), and total mortality (HR 1.03, CI 1.01-1.06; p < 0.01), during follow-up, whereas duration of diabetes was associated with higher rate of major amputation (HR 1.08, CI 1.02-1.15; p < 0.01). Conclusions: DM patients showed higher rates of MACE and AMI in propensity score adjusted analysis five years after planned infrainguinal open surgery for IC. Higher HbA1c was associated with MACE, stroke, and total mortality in patients with DM, whereas longer duration of DM was associated with major amputation.

Pro B-type Natriuretic Peptide and Midregional Proadrenomedullin are Associated with Incident Carotid Stenosis During Long Term Follow-up.

BACKGROUND: Plasma biomarkers may be useful to detect healthy individuals at increased risk for atherosclerotic manifestations, such as carotid artery stenosis. The aim of this longitudinal cohort study was to evaluate new biomarkers in relation to C-reactive protein and conventional risk factors for carotid artery stenosis during long term follow-up METHODS: The following markers were measured in 5550 middle-aged subjects: C-reactive protein, lipoprotein-associated phospholipase A2, proneurotensin, midregional pro-adrenomedullin, midregional pro-atrial natriuretic peptide, N-terminal pro B-type natriuretic peptide, copeptin, and cystatin C. Subjects with prevalent carotid artery stenosis were excluded. Subjects were followed in national patient registers for 23.4 (interquartile range 19.5-24.3) years regarding incident carotid artery stenosis, both operated and non-operated. RESULTS: When including conventional risk markers in Cox regression, N-terminal pro B-type natriuretic peptide (Hazard ratio 1.36; 95% confidence interval 1.12-1.65; p = 0.002) was independently associated with incident carotid artery stenosis, whereas there were trends for C-reactive protein (HR 1.20; 95% confidence interval 0.98-1.48; p = 0.071), and midregional pro-adrenomedullin (Hazard ratio 1.21; 95% confidence interval 0.99-1.47; p = 0.061). Midregional pro-adrenomedullin (Hazard ratio 1.30; 95% confidence interval 1.03-1.65; p = 0.029) was independently associated with incident surgery for carotid artery stenosis, whereas there was a trend for N-terminal pro B-type natriuretic peptide (Hazard ratio 1.31; 95% confidence interval 1.00-1.72; p = 0.052). CONCLUSIONS: N-terminal pro B-type natriuretic peptide and midregional pro-adrenomedullin can be used as predictors for clinically detected carotid artery stenosis during long-term follow-up of healthy subjects.

Worse cardiovascular prognosis after endovascular surgery for intermittent claudication caused by infrainguinal atherosclerotic disease in patients with diabetes.

BACKGROUND: Diabetes mellitus (DM) is an established risk factor for intermittent claudication (IC) and other manifestations of atherosclerotic peripheral arterial disease. Indications for surgery in infrainguinal IC are debated, and there are conflicting reports regarding its outcomes in patients with DM. Aims of this study were to compare both short- and long-term effects on total- and cardiovascular (CV) mortality, major adverse cardiovascular events (MACEs), acute myocardial infarction (AMI), stroke, and major amputation following infrainguinal endovascular surgery for IC in patients with and without DM. We also evaluated potential relationships between diabetic control and outcomes in patients with DM. METHODS: Nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Registry. Propensity score adjusted comparison of total and CV mortality, MACE, AMI, stroke, and major amputation after elective infrainguinal endovascular surgery for IC in 626 patients with and 1112 without DM at 30 postoperative days and after median 5.2 [interquartile range (IQR) 4.2-6.3] years of follow-up for patients with DM, and 5.4 (IQR 4.3-6.5) years for those without. RESULTS: In propensity score adjusted Cox regression after 30 postoperative days, there were no differences between groups in morbidity or mortality. At last follow-up, patients with DM showed higher rates of MACE [hazard ratio (HR) 1.26, confidence interval (CI) 1.07-1.48; p < 0.01], AMI (HR 1.48, CI 1.09-2.00; p = 0.01), and major amputation (HR 2.31, CI 1.24-4.32; p < 0.01). Among patients with DM, higher HbA1c was associated with higher total mortality during follow-up (HR 1.01, CI 1.00-1.03; p = 0.045). CONCLUSION: Patients with DM have higher rates of MACE, AMI, and major amputation in propensity score adjusted analysis during 5 years of follow-up after infrainguinal endovascular surgery for IC. Furthermore, HbA1c is associated with total mortality in patients with DM. Prevention and treatment of DM is important to improve cardiovascular and limb outcomes.

Associations of global DNA methylation and homocysteine levels with abdominal aortic aneurysm: A cohort study from a population-based screening program in Sweden.

Abdominal aortic aneurysm (AAA) is a life-threatening condition with a mortality rate of over 80%. Persistent smoking, which is a risk factor for AAA, has lasting effects on DNA methylation. Moreover, a plasma-amino acid, homocysteine, previously implicated in vascular diseases, including aneurysms, has well-established biological association with methylation. In the present study, we aimed to determine the global DNA methylation, homocysteine levels and their association with AAA and its growth. Enzyme-linked immunosorbent assay (ELISA) was used to quantify global DNA methylation in whole blood-DNA samples and diagnostic enzymatic assay quantified plasma homocysteine, from 65-year old men with (n = 116) and without AAA (n = 230) diagnosed at ultrasound screening. We found significantly higher global DNA methylation (p < .001) and homocysteine levels (p < .001) in men with AAA compared to those without AAA, and direct linear associations with baseline aortic diameter. On multivariable regression analysis, global DNA methylation (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.1-2.9) and homocysteine levels (OR: 1.1; 95% CI:1.0-1.1) were positively associated with AAA, independent of smoking, medication use, and major co-morbidities. However, we did not find any significant association between DNA methylation or homocysteine levels with AAA growth during follow-up. We found that global DNA methylation and homocysteine levels are higher in men with AAA but are not associated with AAA growth. This indicates that different pathways and mechanisms may be involved in initiation and progression of AAA. More studies are needed to understand the precise role of DNA methylation, homocysteine and their interplay in AAA pathophysiology.

Identification of novel diagnostic and prognostic biomarkers for abdominal aortic aneurysm.

AIMS: Abdominal aortic aneurysm is a life-threatening condition due to the risk of aneurysm growth and rupture. There are no approved diagnostic or prognostic biomarkers for abdominal aortic aneurysm. We aimed to identify diagnostic and prognostic biomarkers for abdominal aortic aneurysm and to investigate their relationship with abdominal aortic aneurysm diameter and growth. METHODS: In this case-control study, patients were included from an abdominal aortic aneurysm screening study on men aged ≥65 years. Of 24,589 examined men, 415 had abdominal aortic aneurysm, out of whom 134 consented to participate in the present study. One hundred and thirty-six screened men with aortic diameter <30 mm, matched for comorbidities and time of sampling were included as non-abdominal aortic aneurysm patients. Ninety-one cardiovascular specific proteins in plasma samples were measured by the Proseek Multiplex CVD III96x96 panel. RESULTS: After Bonferroni correction, plasma levels of 21 proteins associated with proteolysis, oxidative-stress, lipid metabolism, and inflammation were significantly increased, whereas levels of paraoxonase 3, associated with high-density lipoprotein metabolism, were decreased in abdominal aortic aneurysm patients. Combination of growth/differentiation factor 15 and cystatin B had the best ability to discriminate abdominal aortic aneurysm from non-abdominal aortic aneurysm (area under the curve, 0.76; sensitivity, 80% and specificity, 52%). Myeloperoxidase showed the best prognostic value (area under the curve, 0.71; sensitivity, 80% and specificity, 59%) and higher baseline levels of myeloperoxidase were significantly associated with faster abdominal aortic aneurysm growth compared with lower levels, independent of baseline diameter. CONCLUSIONS: We have identified multiple proteins associated with abdominal aortic aneurysm diameter and growth with a potential to become novel diagnostic and prognostic biomarkers for abdominal aortic aneurysm.

Nationwide comparison of long-term survival and cardiovascular morbidity after acute aortic aneurysm repair in patients with and without type 2 diabetes.

OBJECTIVE: Epidemiologic data indicate decreased risk for development, growth, and rupture of abdominal aortic aneurysm (AAA) among patients with type 2 diabetes mellitus (DM). We therefore evaluated mortality and cardiovascular morbidity after acute repair of AAA in diabetic and nondiabetic patients. METHODS: In this nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Register, we compared mortality and morbidity after acute open (n = 1357 [61%]) or endovascular (n = 860 [39%]) repair of ruptured (n = 1469 [66%]) or otherwise symptomatic (n = 748 [34%]) AAAs in 363 patients with and 1854 patients without DM with propensity score-adjusted analysis. RESULTS: Follow-up was 3.91 years for patients with DM and 3.18 years for those without. In propensity-adjusted analysis, diabetic patients showed lower total mortality (relative risk [RR], 0.75; 95% confidence interval [CI], 0.59-0.95; P = .016) and cardiovascular mortality (RR, 0.17; 95% CI, 0.06-0.50; P = .01) than those without DM, whereas there were no differences in rates of major adverse cardiovascular events (RR, 1.10; 95% CI, 0.87-1.42; P = .42), acute myocardial infarction (RR, 1.36; 95% CI, 0.70-2.63; P = .37), or stroke (RR, 1.31; 95% CI, 0.84-2.03; P = .23). CONCLUSIONS: Patients with type 2 DM had lower rates of both total and cardiovascular mortality after acute AAA repair than those without DM, whereas rates of cardiovascular events, acute myocardial infarction, and stroke did not differ between groups. This might be explained by putative protective effects of DM on the aortic wall.

Survival, cardiovascular morbidity, and reinterventions after elective endovascular aortic aneurysm repair in patients with and without diabetes: A nationwide propensity-adjusted analysis.

Epidemiological data indicate decreased risk for development and growth of abdominal aortic aneurysm (AAA) among patients with diabetes mellitus (DM). On the other hand, DM adds to increased cardiovascular (CV) morbidity and mortality. In a nationwide observational cohort study of patients registered in the Swedish Vascular Register and the Swedish National Diabetes Register, we evaluated potential effects of DM on total mortality, CV morbidity, and the need for reintervention after elective endovascular aneurysm repair (EVAR) for AAA. We compared 748 patients with and 2630 without DM with propensity score-adjusted analysis, during a median 4.22 years of follow-up for patients with DM, and 4.05 years for those without. In adjusted analysis, diabetic patients showed higher rates of acute myocardial infarction (AMI) during follow-up (relative risk (RR) 1.44, 95% CI 1.06-1.95; p = 0.02), but lower need for reintervention (RR 0.12, CI 0.02-0.91; p = 0.04). There were no differences in total (RR 0.88, CI 0.74-1.05; p = 0.15) or CV (RR 1.58, CI 0.87-2.86; p = 0.13) mortality, or stroke (RR 0.95, CI 0.68-1.32; p = 0.75) during follow-up. In conclusion, patients with DM had higher rates of AMI and lower need for reintervention after elective EVAR than those without DM, whereas neither total nor CV mortality differed between groups. The putative protective effects of DM towards further AAA enlargement and late sac rupture may help explain the lower need for reintervention and absence of excess mortality.