Aims:Intermittent claudication (IC) is the most common manifestation of peripheral artery disease (PAD), an atherosclerotic condition associated with high cardiovascular morbidity and mortality. Management targets cardiovascular risk reduction and limb function, but effective non-invasive treatments for limb symptoms remain limited. The aim of this prospective, multicentre randomized controlled trial was to evaluate whether a 12-week multimodal smartphone-based digital health programme improves walking capacity and symptoms in patients with IC. Methods and results:The IPAD trial compared standard care alone with standard care plus a 12-week digital health intervention focused on lifestyle modification and physical activity, incorporating behavioural change techniques and gamification. The primary observer-blinded endpoint was maximum walking distance (MWD) during a 6-min walk test (6MWT), contextualized against minimal clinically important difference thresholds. Secondary endpoints included pain-free 6MWT distance and health-related quality of life (HRQoL). Over 21 months, 155 patients were randomized 1:1. Mean (SD) age was 71.8 (7.6) years. Compared with controls, the intervention group showed greater improvement in MWD (+21.44 m; 95% confidence interval [CI] 6.00-36.87; P = 0.007), exceeding the predefined 12-m MCID at the group level, and in pain-free walking distance (+32.95 m; 95% CI 0.68-65.23; P = 0.045). The relative risk of achieving an individual 12-m MCID did not differ between groups (risk ratio [RR] 1.27; 95% CI 0.91-1.76; P = 0.162). Exploratory analysis using a 20.1-m MCID showed a higher proportion of patients achieving the MCID in the intervention group (RR 1.97; 95% CI 1.16-3.34; P = 0.012). HRQoL improved nominally, with a between-group benefit on the EuroQol-5 Dimensions visual analogue scale (+6.29 points; 95% CI 1.33-11.20; P = 0.013). Conclusion:The digital health programme resulted in a clinically meaningful improvement in walking capacity in PAD patients with IC.

BACKGROUND:Individuals with high pulse wave velocity (PWV) may suffer from early vascular ageing (EVA) and face increased cardiovascular risk. Nonetheless, some individuals with EVA survive until old age, some even escaping cardiovascular complications entirely. The aim of this study was to explore characteristics of such individuals in population-based cohorts. METHODS:We used data from the Metabolic syndrome and Artery REsearch (MARE) Consortium and a MARE sub-cohort; the Malmö Diet Cancer Study - Cardiovascular (MDCS-CV) arm for analyses, both covering cardiovascular risk factors, PWV, and carotid intima-media thickness (cIMT). EVA survivors (individuals 75+ years; PWV ≥ 90th percentile for age strata), were compared to age-matched and sex-matched controls (PWV 0 to 75th percentile). Additionally, in MDCS-CV, prospective EVA escapers [without major adverse cardiovascular events (MACE) or death during 10-year follow-up], were compared to EVA nonescapers. RESULTS:EVA Elderly survivors in the MARE Consortium had a higher risk factor burden, including cIMT levels, compared to controls. In MDCS-CV, similar patterns were found; however, cIMT did not differ between EVA Elderly survivors and controls, despite higher mean PWV (17 vs. 11 m/s). Finally, in MDCS-CV, EVA Elderly escapers ( n  = 34) compared to nonescapers ( n  = 56) had lower mean cIMT (0.92 vs. 1.01 mm; P  = 0.009), despite comparable PWV (17 vs. 16 m/s). No other group differences were observed. CONCLUSION:EVA elderly survivors and escapers exist even among the very elderly. The latter are characterized by lower cIMT than EVA Elderly nonescapers. This could indicate discordant (differentiated) arterial ageing to be further explored.

Aim: This study aimed to compare the safety and effectiveness of direct oral anticoagulants (DOACs) with low-molecular-weight heparin (LMWH) in patients with venous thromboembolism (VTE) and active cancer in a real-world setting in Sweden, Norway, Finland, the UK and Germany. Materials & methods: This observational cohort study used datasets from Sweden, Norway, Finland (National Patient and Prescription Registers) the UK (Clinical Practice Research Datalink and Hospital Episode Statistics) and Germany (AOK Plus and GWQ) from 2013 to 2020. We identified treatment-naive adult patients with cancer-related VTE treated with a DOAC or LMWH.We employed inverse probability of treatment weighting for each DOACLMWH comparison and assessed recurrent VTE and bleeding risk (overall and by site: gastrointestinal [GI], intracranial hemorrhage [ICH] or other) within 6 months of treatment initiation. Fine–Gray models were fitted to estimate adjusted hazard ratios and country level estimates were meta-analyzed. Results: After inverse probability of treatment weighting, 30,002 and 2892 patients were included in the LMWHapixaban comparison, and 29,976 and 4321 in the LMWH-rivaroxaban comparison, respectively. Recurrent VTE could not be assessed comparatively because of low numbers. At 6 months, apixaban was associated with a lower risk of overall and other (HR: 0.67 [95% CI: 0.53,0.86]; 0.64 [0.41,0.998]) bleeding compared with LMWH, with similar risks for GI and ICH bleeding (0.89 [0.61,1.29]; 0.67 [0.31,1.44], respectively). Rivaroxaban had a similar risk of overall, GI, and other bleeding (0.98 [0.83, 1.15]; 0.86 [0.47,1.58]; 0.89 [0.74,1.08]) compared with LMWH, but a lower risk of ICH (0.32 [0.13, 0.82]). Conclusion: These findings suggest that apixaban may offer a safer bleeding profile than LMWH for patients with cancer-associated VTE, particularly in reducing overall and other types of bleeding. Rivaroxaban also appears to be a viable alternative to LMWH, with a notably lower risk of ICH. These results provide valuable real-world insights in an area where evidence remains very limited and support the role of DOACs as a safe alternative to LMWH in patients with VTE and cancer.

Abstract Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Type 1 Diabetes (T1D), but a subset of individuals remains free from macrovascular or renal complications despite decades of hyperglycaemia and a significant risk factor burden. We used a targeted proteomic approach (Olink Cardiovascular panel III, targeting 92 proteins) to characterize the proteomic profile of cardiovascular resilience in T1D by comparing 92 patients with long-standing T1D (age 59.8 [53.2, 69.1], duration 40.0 [35.0, 45.2] years) free from macrovascular complications or nephropathy against a reference group of 57 T1D patients with accelerated vascular pathology (age 42.0 [32.0, 56.0], duration 22.0 [18.0, 27.0] years), proliferative retinopathy and/or nephropathy in relation to diabetes duration, termed Rapid Progressors (RP). Twenty proteins differed significantly between RP and Escapers (False Discovery Rate [FDR] < 0.05) after adjustment for age, sex, HbA1c, and eGFR: Caspase-3 was significantly higher in RP (Adjusted difference: + 2.12 Normalized Protein eXpression [NPX], p < 0.001). Proteins associated with platelet activation and leukocyte adhesion with increased levels in RP included Junctional Adhesion Molecule A (+ 1.40 NPX), Glycoprotein VI (GP6: + 1.29 NPX), and P-Selectin (+ 0.82 NPX) (all p < 0.001). PECAM-1 (+ 0.55 NPX) and TNFRSF14 (+ 0.43 NPX), were also elevated. RP also showed higher levels of metabolic and tissue-remodelling proteins; Transferrin Receptor (+ 0.53 NPX) and Fatty Acid Binding Protein 4 (+ 0.52 NPX), as well as higher Bleomycin Hydrolase, Trefoil Factor 3, GDF-15, U-PAR, and Cystatin B. Conversely, von Willebrand Factor (vWF) levels (− 1.35 NPX, p < 0.001) and Paraoxonase 3 (PON3) was lower in RP (− 0.34 NPX, p = 0.003). In conclusion, escaping complications in long-term T1D appears to be associated with active molecular mechanisms. Progression is marked by apoptosis (Caspase-3), fibrosis (CHI3L1) and platelet activation (GP6), whereas resilience is associated with a distinct signature involving higher vWF and PON3. These findings highlight a profound biological divergence between extreme T1D phenotypes and provide a foundation for further research into vascular resilience.

Heart failure (HF) and arterial hypertension (AH) are strongly associated with obesity, with a linear relationship to increasing body mass index (BMI). However, some individuals with obesity do not exhibit signs of HF or AH. This study aimed to compare, for the first time in a large population-based cohort, individuals with obesity who have normal left ventricular function and remodeling (LVFR) and no AH (ObNI) with those who have impaired LVFR or AH (ObI), and corresponding individuals without obesity (NObNI and NObI). A cross-sectional analysis was performed on 4 435 participants from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Participants were grouped into four categories: (1) ObNI (n = 586), (2) ObI (n = 224), (3) NObNI (n = 3 041), and (4) NObI (n = 584). Descriptive analyses compared individuals with obesity with normal LVFR and no AH (ObNI) to the other three groups. Although no significant differences between the two subgroups with obesity could be seen regarding BMI (33.1 vs. 33.5 kg/m2, p = 0.095), there was significant differences in coronary artery calcification score (CACS) levels, where ObNI participants were more prone to show no or very low CACS in comparison with ObI participants (p < 0.001). Also compared to ObI participants, ObNI individuals had lower levels of HbA1c, fasting plasma glucose, triglycerides, and troponin I (all p < 0.001). Furthermore, significant differences were observed between the two groups regarding sedentary behavior (p = 0.041), where ObNI subjects showed a more active lifestyle. Compared with ObNI, individuals with ObI exhibited a higher left ventricular mass index (LVMI; p < 0.001) and lower diastolic function parameters (p < 0.001), while left ventricular ejection fraction (EF) did not differ significantly (p = 0.27). Relative to NObNI, ObNI participants demonstrated increased LVMI (p = 0.007), lower EF (p < 0.001), and impaired diastolic function (p < 0.001). Coronary artery calcification scores (CACS) were higher in ObI than in ObNI (p < 0.001), and ObNI also showed higher CACS than NObNI (p = 0.008). ObNI participants had lower CACS levels, more favorable metabolic profiles, better cardiac function, and greater physical activity than ObI individuals. However, compared to NObNI, they showed higher CACS, increased left ventricular mass, and reduced cardiac function, highlighting distinct cardiovascular risks across obesity phenotypes.

OBJECTIVE:Screening for abdominal aortic aneurysm (AAA) defined as an infrarenal aortic diameter (IAD) of ≥30 mm reduces mortality, but managing patients with diameters of 25 to 29 mm is debated. Incorporating body surface area into the diagnostic criteria may improve the identification of those at risk of developing treatment-requiring aneurysms in this group. In a previous study, we defined a relative AAA as an IAD ≥150% larger than expected, with the normal diameter calculated using body surface area as a scaling factor. This study aimed to determine if this criterion could identify those at risk of aneurysmal development among patients with aortic diameter of 25 to 29 mm at screening. METHODS:A cohort study was conducted on men with abdominal aortic diameters of 25 to 29 mm at AAA screening in Malmö, Sweden, with a median follow-up of 9.9 years. Growth rates were compared between the relative aneurysm group and the nonrelative aneurysm group using a linear mixed-effects model to account for both fixed and random effects. Time and hazard ratio to reach 40 mm, a marker of significant aneurysmal progression, were assessed using a log-rank test and a Cox proportional hazards model, both adjusted for smoking status and diabetes. RESULTS:In a cohort of 270 men, three developed AAAs ≥55 mm. The baseline growth rate was 0.1 mm/year (95% confidence interval [CI], 0.0-0.3). Growth rates were increased by 0.4 mm/year (95% CI, 0.0-0.7) in the relative aneurysm group, and by 0.4 mm/year (95% CI, 0.2-0.7) in smokers. The median time to reach an IAD of ≥40 mm was 11.5 years for relative aneurysms and was not reached for those without, with a significant difference shown by a log-rank test stratified for smoking (P = .009). Hazards ratio to reach an IAD of ≥40 mm for relative aneurysms was 2.77 (95% CI, 1.34-5.74; P = .006) compared with those without. CONCLUSIONS:In men with diameters of 25 to 29 mm at screening for AAAs, the use of an individualized diagnostic criterion, based on height and weight, could identify those with increased aneurysm growth and a significantly shorter time to reach 40 mm compared with baseline. The relative aortic diameter, beyond the absolute diameter, seemed to be important for aneurysmal development. However, the differences were likely too small to warrant changes in clinical practice, highlighting the need for further research to establish clinical relevance.

Aim: Clinical trial data have demonstrated that direct oral anticoagulants (DOACs) are both noninferior to and safer than conventional therapy for the treatment of venous thromboembolism (VTE). This study aimed to compare the effectiveness and safety of DOACs versus warfarin using Nordic population-based registries. Materials & methods: This observational cohort study used Swedish, Norwegian and Finnish national administrative data from 2012 to 2018. We identified treatment-naive adult patients with noncancer-related VTE treated with either a DOAC (apixaban or rivaroxaban) or warfarin. We employed inverse probability of treatment weighting for each DOAC-warfarin comparison and assessed the risks of bleeding (overall and by site: gastrointestinal bleeding [GI], intracranial bleeding [ICH], or other bleeding) and recurrent VTE within 6 months after treatment initiation. Cox proportional hazards models estimated the adjusted hazard ratios of each end point. Country estimates were combined using meta-analyses. Results: After inverse probability of treatment weighting, 22,450 warfarin, 14,542 apixaban and 23,002 rivaroxaban patients were included. At 6 months, for apixaban versus warfarin, the risk of bleeding was lower overall (hazard ratio: 0.51 [95% CI: 0.43, 0.61]) and by site (GI: 0.65 [0.45, 0.93]; ICH: 0.58 [0.34, 0.97]; other: 0.45 [0.34, 0.58]). For recurrent VTE the risk was similar for apixaban versus warfarin (0.85 [0.71, 1.02]). For rivaroxaban versus warfarin the risk of bleeding was lower for overall and other bleeding (0.86 [0.75, 0.99]; 0.81 [0.69, 0.95], respectively), but similar for GI and ICH bleeding (1.06 [0.84, 1.34]; 0.68 [0.47, 1.00], respectively). For recurrent VTE the risk was lower for rivaroxaban versus warfarin (0.74 [0.63, 0.87]). Conclusion: DOACs showed improved safety and at least similar effectiveness compared with warfarin, which is in line with clinical trial estimates.

Objectives Cancer associated venous thromboembolism (VTE) poses a dual risk of thrombosis and bleeding, making its management particularly challenging. Randomized controlled trials (RCTs) comparing apixaban, edoxaban, and rivaroxaban with low molecular weight heparins (LMWHs) have demonstrated that direct oral anticoagulants (DOACs) are effective alternatives to LMWH, offering greater convenience in many cases. These findings are reflected in current clinical guidelines, which support the use of DOACs while advising caution in patients at high risk of bleeding. However, despite their growing use in clinical practice, real-world evidence comparing the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated VTE remains limited. This study aimed to address this gap by evaluating the comparative safety and effectiveness of DOACs and LMWH in VTE patients with cancer. Methods This observational study utilized datasets from national patient and prescription registers in Sweden, Finland, and Norway, the Clinical Practice Research Datalink linked to Hospital Episode Statistics in the UK, and two social health insurance datasets in Germany (AOK PLUS and GWQ) from 2013 to 2020. We identified treatment-naive adult patients with VTE and cancer (within 6 months of the index VTE diagnosis) treated with either a DOAC or LMWH. The index date was defined as the first DOAC or LMWH dispensed from a community pharmacy within 30 days of the index VTE. Follow-up continued from the day after index date until the earliest of: 6 months post-index date, patient death, occurrence of the outcome of interest, index treatment discontinuation, emigration, placement of an inferior vena cava (IVC) filter, pregnancy, or March 31, 2020. The primary effectiveness outcome was recurrent VTE (rVTE), defined as an inpatient primary position diagnosis of VTE occurring at least 7 days post-discharge. The primary safety outcome was bleeding, defined as an inpatient hospitalization with at least one overnight stay and a primary or secondary position bleeding diagnosis. Bleeding events were categorized as gastrointestinal (GI), intracranial hemorrhage (ICH), or other, based on diagnosis codes. Analyses were conducted on-treatment, with patients considered to have discontinued treatment when no new index treatment dispensation occurred within a 60-days following end of supply of the prior dispensation. Inverse probability of treatment weighting (IPTW) was used for each DOAC-LMWH comparison to account for potential confounding. Adjusted hazard ratios (HRs) were estimated in each country using Fine-Gray models to assess the risk of rVTE and bleeding (overall and by site) within 6 months of treatment initiation; these models were used to account for competing risk of mortality. Country-specific estimates were meta-analyzed. Results Before IPTW, we identified 34,687 LMWH users, 3,045 apixaban users, 4,537 rivaroxaban users, 145 dabigatran users, and 580 edoxaban users across the five countries. Due to a limited sample size, Finland was excluded from the analysis, as were the edoxaban and dabigatran groups. After IPTW, the LMWH-apixaban comparison included 30,002 LMWH and 2,892 apixaban users, while the LMWH-rivaroxaban comparison included 29,976 LMWH and 4,321 rivaroxaban users. Comparative assessment of rVTE was not possible due to low event numbers. At 6 months, apixaban was associated with a lower risk of overall bleeding and other bleeding compared with LMWH (HR: 0.67 [95% CI, 0.53-0.86]; 0.64 [0.41-0.998]), with similar risks for GI and ICH bleeding (0.89 [0.61-1.29]; 0.67 [0.31-1.44]). For rivaroxaban versus LMWH, the risk of overall, GI, and other bleeding was similar (0.98 [0.83-1.15]; 0.86 [0.47-1.58]; 0.89 [0.74-1.08]), but the risk of ICH was lower (0.32 [0.13-0.82]). Conclusions This multi-country European study, utilizing real-world data on patients with VTE and cancer, found that apixaban was associated with a lower risk of overall bleeding compared with LMWH. The risk of overall bleeding with rivaroxaban was similar to that with LMWH. Comparative assessment of rVTE was not possible due to low event numbers. These findings contribute to the limited body of real-world evidence supporting the use of DOACs over LMWH for treating patients with VTE and cancer.

AIM:Factors associated with unexpected absence or presence of coronary atherosclerosis in individuals at high/low estimated cardiovascular (CV) risk are largely unexplored. We assessed two extreme phenotypes: 1) no coronary atherosclerosis despite very high CV risk; and 2) severe-extensive coronary atherosclerosis despite low CV risk. METHODS:A multicenter, cross-sectional nationwide, population-based cohort of 30,154 randomly invited individuals (age 50-64 years; 51% women). Coronary plaque burden was assessed by coronary computed tomography angiography using coronary artery calcium score and segment involvement score. CVD risk was estimated by the Systematic Coronary Risk Evaluation (SCORE2) and SCORE2-Diabetes, as appropriate. RESULTS:In total 10,628 individuals without and 189 with diabetes were eligible. Absence of coronary plaques despite high SCORE2-risk occurred in 1.2% non-diabetic and 14.0% diabetic subjects. Severe-extreme coronary plaques despite low SCORE2-risk occurred in 0.7% non-diabetic and 0.3% diabetic subjects. In non-diabetic subjects, severe-extensive coronary plaque burden despite low SCORE2-risk was more likely in men, with increasing age, more pack-years of smoking, previous smoking, hypertension, hyperlipidemia, family history of CVD, and higher systolic blood pressure (all p<0.002). A similar but reverse pattern was observed among subjects without coronary plaques despite high SCORE2-risk. In addition, diabetic subjects without coronary plaques and high SCORE2-risk demonstrated a higher likelihood of moderate physical activity, higher education levels, and lower body mass index (p<0.05). CONCLUSION:SCORE2-risk correlated well with presence of coronary atherosclerosis, yet 1.9% non-diabetic subjects and 14.3% diabetic subjects display extreme coronary phenotypes with a mismatch between estimated cardiovascular risk and signs of coronary atherosclerosis.

Inter-arm blood pressure differences (IABPDs) can be caused by atherosclerosis. We investigated 29 921 men and women aged 50–64 years from the nationwide population-based Swedish CArdio Pulmonary bioImage Study (SCAPIS) to evaluate if IABPD is related to risk factors for atherosclerosis and can be used as a marker of atherosclerosis as evaluated by coronary artery calcium score, arterial segment involvement score on computed tomography, carotid ultrasound, and ankle-brachial index (ABI). The overall prevalence of systolic IABPD at least 10 mmHg was 2110/29 921 (7.1%). Individuals with IABPD at least 10 mmHg were significantly ( P < 0.001) older, more often women, had higher BMI, nonhigh-density lipoprotein cholesterol, triglycerides, SBP and DBPs, and were more likely to have diabetes. In unadjusted analyses, IABPD at least 10 mmHg was associated with presence of coronary atherosclerosis, with more carotid arteries with plaque, and with pathological ABI. These associations were largely attenuated after adjustment for cardiovascular risk factors (age, sex, nonhigh-density lipoprotein cholesterol, systolic BP, smoking, diabetes, and the use of BP lowering drugs). Only ABI retained significance after these adjustments. In conclusion, a systolic IABPD of at least 10 mmHg in middle aged men and women is common in the general population, and can be used as a screening tool for subclinical atherosclerotic changes in coronary, carotid, and lower extremity arteries. However, these relationships were largely explained by correlations between IABPD and traditional cardiovascular risk factors.

An abnormal blood pressure (BP) response on standing is associated with atherosclerotic cardiovascular disease (CVD). The role of physical activity (PA) on orthostatic BP-reactions and its relation to subclinical atherosclerosis is unclear. We aimed to assess the association between PA and orthostatic BP-reactions, and whether PA modifies the relationship between orthostatic BP-reactions and subclinical atherosclerosis. A total of 5,396 middle aged subjects from the population-based SCAPIS-study were included. Associations between orthostatic BP-response and accelerometer-derived PA were studied using linear regression. Interaction analyses were performed to study modifying effects of PA on the relationship between orthostatic BP-response and subclinical coronary atherosclerosis, assessed by coronary artery calcium score (CACS). Moderate to vigorous PA (MVPA) was associated with less pronounced orthostatic systolic BP (SBP) increase but more pronounced orthostatic diastolic BP increase after adjusting for age, sex, total wear time, proportion weekend days and season (Beta per 1%-increase(mmHg):0.12; p = <0.01 and −0.06; p = 0.02, respectively). Subjects with high MVPA were less likely to have orthostatic hypertension (OHTN), but more likely to have orthostatic hypotension (OH; p = 0.002 for both). Individuals with higher CACS were more likely to have OH (p = 0.041) but not OHTN (p = 0.276). There were no interactions of PA on the association between orthostatic BP-response and CACS. In conclusion, physically active middle-aged individuals are less likely to show inappropriate SBP-increase upon standing, but more likely to have excessive SBP-decrease. PA does not modify the association between orthostatic BP-response and subclinical atherosclerosis. The relationship between PA, orthostatic BP and CVD is likely to be complex.

OBJECTIVE:Drug-coated balloons (DCB) might improve the results of below the knee (BTK) angioplasty, but sufficient randomized data comparing DCB and conventional angioplasty in treating patients with chronic limb threatening ischemia (CLTI) are lacking. This study aimed to perform a randomized comparison between a paclitaxel-coated angioplasty balloon catheter and a conventional balloon angioplasty catheter in treating BTK arterial lesions. DESIGN:A single-center prospective 1:1 randomized, single-blinded, parallel group, superiority trial. CLINICAL TRIAL REGISTRATION:NCT02750605. METHODS:Patients presenting with CLTI scheduled for endovascular treatment of BTK arterial lesions were assigned to DCB or conventional angioplasty. The primary endpoint was primary patency at 12 months. Secondary endpoints were target lesion revascularization (TLR), technical success, clinical success, amputation free survival (AFS), and serious adverse events. RESULTS:A total of 64 CLTI patients, 70 limbs, and 122 lesions were enrolled, with 35 limbs in each group. Demographics, comorbidities, and Rutherford class were similar in both treatment arms. The rates of chronic total occlusions were 81% and 89% (NS) in the DCB and control group, respectively, with corresponding median lesion lengths of 150 and 100 mm (NS) in the two groups. No significant differences were detected between groups regarding primary limb patency (hazard ratio [HR]=0.64, p=0.24, confidence interval [CI]=0.30-1.35). CONCLUSIONS:This single-center prospective randomized study could not demonstrate superiority of DCB compared with conventional balloon angioplasty regarding the primary endpoint, as primary patency, when treating BTK arterial lesions in patients with CLTI.Clinical ImpactThis randomised trial aims to pragmatically investigate whether there is a clinically relevant difference between drug eluting angioplasty and standard plain old balloon angioplasty in treating below the knee arterial lesions in subjects with chronic limb threatening ischemia. Regarding the primary endpoint variable, the study was not able to reveal a significant DCB superiority in primary patency.

Introduction:Acute lower limb ischemia (ALI) is a life and limb threatening event often affecting patients with type 2 diabetes mellitus (T2DM). Little is known about how T2DM affects the risk of adverse events in patients revascularized for ALI. This study aimed to investigate if there were differences in major outcomes between ALI patients with and without T2DM. Methods:Between 2010 and 2014, 615 patients underwent revascularization for ALI, according to the Swedish Vascular Registry (SWEDVASC). Using the National Diabetes Registry (NDR), 245 (39.8%) of the patients were identified as having T2DM. Uni- and multivariable Cox or logistic regression analyses were performed to evaluate risk differences for major amputation, mortality, major adverse cardiovascular events (MACE), and fasciotomy between patients with and without T2DM. Results:The rates of major amputation and mortality at one year were 32.7% and 21.6% in the T2DM group, compared to 21.9% and 31.9% in the non-DM group, respectively, resulting in a hazard ratio (HR) of 1.52 (95% confidence interval [CI] 1.12-2.07) for major amputation and HR of 0.64 (95% CI 0.46-0.88) for mortality. At one year, the HR for major amputation was 1.45 (95% CI 0.99-2.11), HR for mortality 0.92 (95% CI 0.61-1.39), HR for combined major amputation/mortality 1.27 (95% CI 0.94-1.72), and HR for MACE 1.24 (95% CI 0.92-1.67) for those with T2DM compared to those without in the multivariable Cox-regression analyses. The multivariable logistic regression analysis showed significantly lower odds of fasciotomy, OR 0.1 (95% CI 0.01-0.51) in the T2DM-group. Conclusion:T2DM was not significantly associated with higher hazard of major amputation, mortality, combined major amputation/mortality, or MACE after revascularization for ALI, compared to patients without T2DM. Patients with T2DM had significantly lower odds of fasciotomy.

BACKGROUND:Individuals with diabetes (DM) are often treated with statins, which have a rare side effect: peripheral neuropathy. We aimed to study whether statin treatment affects the risk of carpal tunnel syndrome (CTS) and ulnar nerve entrapment (UNE) in type 2 DM (T2DM). METHODS:We combined multiple national registers in Sweden to identify individuals diagnosed with CTS or UNE in specialized care 2011-2014. Individuals diagnosed with T2DM within 5 years before CTS or UNE diagnosis were included in the diabetes group. Statin treatment was defined as a prescription within 5 years before baseline. Multinominal regression analysis assessed the Relative Risk (RR) [95% confidence interval; CI] of CTS and UNE with statin treatment, using the general population as a reference. RESULTS:In total, 4,771,118 individuals were included; 765,114 (16%) were treated with statins. There were 45,706 cases of CTS, 8,082 cases of UNE, and 244,220 individuals with T2DM. Statin treatment increased the risk of CTS (RR 1.5 [1.4-1.5]) and UNE (RR 1.4 [1.3-1.5]), adjusted for age, sex, diabetes, cardiovascular diseases, and socioeconomy. In individuals without diabetes, risks for CTS (RR 1.5 [1.4-1.5]) and UNE (RR 1.5 [1.4-1.6]) remained higher. In T2DM patients, statins increased the risk of CTS (RR 1.3 [1.2-1.4]) but not of UNE (RR 1.1 [0.9-1.3]). In all included individuals, cardiovascular diseases elevated the risk of CTS (RR 1.2 [1.1-1.2]) and UNE (RR 1.5 [1.4-1.7]). CONCLUSION:Statin treatment is associated with a higher risk of CTS and UNE in individuals without T2DM but only of CTS in individuals with T2DM. CTS and UNE may have different aetiologies.

Background:Chronic limb-threatening ischaemia (CLTI) causes high rates of amputation and mortality. Objectives:To compare incidence, management and prognosis in hospitalised patients with CLTI with and without diabetes mellitus (DM) in 2001 and 2023. A secondary objective was to compare adherence to global vascular guidelines on risk factors between patients with and without DM in 2023. Design:Retrospective study. Methods:Group differences were tested using the Mann-Whitney U test, independent sample t test or the Chi-square test, as appropriate. The effects of DM on major amputation or mortality at 1 year were evaluated in a multivariable logistic regression model according to a directed acyclic graph. Results:The incidence of hospitalisations for CLTI was reduced from 37.4 (95% confidence interval (CI), 33.3-41.6) in 2001 to 22.8 (95% CI, 19.7-25.8) per 100,000 person-years in 2023. The proportion of patients on full-dose oral anticoagulant therapy (p < 0.001) and lipid-lowering treatment (p < 0.001) increased significantly between the two time periods. In 2023, Wounds, Ischemia and foot Infection-classification in all patients with foot ulcers was documented in 6.9%. Anaemia was present at hospital admission in 67.0% and 52.5% of patients with CLTI with and without DM, respectively (p = 0.031). Endovascular therapy was performed more often in those with DM compared to those without DM (p = 0.004). Antiplatelet therapy (p = 0.008) and smoking cessation interventions (p = 0.033) were offered less often to those with DM. DM (odds ratio (OR), 1.7 (95% CI, 1.02-2.83)) was independently associated with increased mortality at 1 year, whereas period 2023 as opposed to 2001 (OR, 0.62 (95% CI, 0.38-0.99)) was associated with decreased mortality. Conclusion:The incidence of hospitalisation for CLTI appears to have been reduced, and medical care of patients with CLTI has improved prognosis. Nevertheless, there is still room for large improvements of secondary prevention care in patients with CLTI, particularly in those with DM.

OBJECTIVE:This study aimed to report changes in the annual incidence of invasive treatment, changes in invasive treatment modalities, and sex differences in patients treated for intermittent claudication (IC) due to infrainguinal lesions in Sweden between 2009 and 2022. METHODS:Data were collected from the Swedish Vascular Registry (Swedvasc), including all registrations of invasive treatment for infrainguinal IC in Sweden between 2009 and 2022. RESULTS:The annual incidence of invasive treatments showed no statistically significant change between 2009 and 2022 (p = .21). The proportion of open surgery decreased from 38.1% in 2009 to 23.4% in 2022 (p < .001). Endovascular and hybrid interventions increased from 56.9% to 69.7% (p < .001) and from 4.8% to 7.0% (p < .001), respectively, between 2009 and 2022 according to time trend analysis. The decrease in open surgery was due to a reduction in bypass surgery from 18.8% in 2009 to 4.0% in 2022 (p < .001). The proportion of common femoral artery thrombo-endarterectomy remained unchanged (p = .24). During the study period, 42.7% of invasive treatments were performed in women. Open surgery was more frequently performed in men than women (32.5% vs. 24.0%; p < .001). However, endovascular intervention was statistically significantly more frequently performed in women than men (70.7% vs. 61.6%; p < .001). CONCLUSION:The annual incidence of invasive treatment for infrainguinal IC in Sweden was unchanged between 2009 and 2022. The proportion of endovascular interventions increased and accounted for 70% of invasive treatments in 2022, whereas bypass surgery decreased by 79%. Women were more often treated with endovascular intervention than men.

OBJECTIVE:The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with diseases of the mesenteric and renal arteries and veins, in succession to the first 2017 guidelines, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS:These guidelines are based on scientific evidence and expert opinion. By summarising and evaluating the best available evidence, recommendations for the diagnosis and treatment of patients have been formulated. The recommendations are graded according to the new ESVS clinical practice guidelines class of recommendation grading system, where the strength (class) of each recommendation is graded from I to III, and the letter A to C marks the level of evidence. RESULTS:A total of 102 recommendations have been issued on the management of chronic arterial mesenteric ischaemia, median arcuate ligament syndrome, acute arterial mesenteric ischaemia, non-occlusive mesenteric ischaemia, venous mesenteric thrombosis and ischaemia, occlusive disease of the renal arteries and veins, visceral artery aneurysms, and spontaneous isolated dissection of the visceral arteries. CONCLUSION:These 2025 ESVS clinical practice guidelines provide comprehensive and up to date advice to physicians and patients on the management of diseases of the mesenteric and renal arteries and veins.

The aim of this study was to evaluate the greatest drivers for development of lower extremity peripheral artery disease (PAD) in relation to coronary, precerebral, or cerebral artery disease This prospective study (Malm & ouml; Diet and Cancer study) included 26,681 participants. The diagnosis of incident PAD, coronary artery disease (CoAD), atherothrombotic ischemic stroke (IS) free from atrial fibrillation or flutter, and carotid artery disease (CaAD) was validated. A modified Lunn-McNeil competing risk analysis was performed to compare the Hazard Ratio (HR) strength of PAD in relation to CoAD, IS, or CaAD. The estimated population attributable risk fractions (PAF) for each atherosclerotic manifestation were estimated by first fit an age and sex adjusted Cox proportional hazard regression, and then estimate the PAF using the Direct method. Male sex, age, and hypertension were risk factors for development of all atherosclerotic manifestations. Current smoking accounted for 45.6% (95% CI 41.1-47.2), 16.1%, 14.0%, and 23.3% of the risk for development of PAD, CoAD, IS, and CaAD, respectively. Hypertension was more associated with development of PAD than CoAD (p = 0.009). Smoking and diabetes mellitus were positively associated with all four manifestations, but these associations were significantly stronger for PAD than the other three manifestations. Smoking and diabetes mellitus had a larger impact on incident PAD than incident coronary, cerebral or precerebral artery manifestations. Since the lower extremity arteries are the easiest to access and examine, they may be considered as the first arterial bed to examine in patients at increased risk for atherosclerotic manifestations.