Endothelial dysfunction is an early step in the atherosclerotic process and can be quantified by flow-mediated vasodilation (FMD). Our aim was to investigate the effect of long-term rosuvastatin therapy on endothelial function in patients with inflammatory joint diseases (IJD) with established atherosclerosis. Furthermore, to evaluate correlations between change in FMD (ΔFMD) and change in carotid plaque (CP) height, arterial stiffness [aortic pulse wave velocity (aPWV) and augmentation index (AIx)], lipids, disease activity and inflammation. Eighty-five statin-naïve patients with IJD and ultrasound-verified CP (rheumatoid arthritis: n = 53, ankylosing spondylitis: n = 24, psoriatic arthritis: n = 8) received rosuvastatin treatment for 18 months. Paired-samples t tests were used to assess ΔFMD from baseline to study end. Linear regression models were applied to evaluate correlations between ∆FMD and cardiovascular risk factors, rheumatic disease variables and medication. The mean ± SD FMD was significantly improved from 7.10 ± 3.14 % at baseline to 8.70 ± 2.98 % at study end (p < 0.001). Improvement in AIx (p < 0.05) and CP height reduction (p = 0.001) were significantly associated with ΔFMD (dependent variable). Long-term lipid lowering with rosuvastatin improved endothelial function in IJD patients with established atherosclerotic disease. Reduced arterial stiffness and CP regression were longitudinally correlated with the improvement in endothelial function measured by FMD. ClinicalTrials.gov NCT01389388 . Registered 16 April 2010.

Objectives: To assess the effect of high-intensity interval training (HIIT) delivered in physiotherapy primary care on the primary outcome of cardiorespiratory fitness (CRF) in patients with inflammatory arthritis (IA). Additionally, to explore the effects of HIIT on secondary outcomes, including cardiovascular disease (CVD) risk factors and disease activity. Methods: Single-blinded randomised controlled trial with 60 patients randomly assigned to either a control group receiving usual care or an exercise group receiving usual care and 12 weeks of individualised HIIT at 90%–95% peak heart rate. Outcomes were assessed at baseline, 3 months and 6 months post baseline and included CRF measured as peak oxygen uptake (VO_2peak), classic CVD risk factors, disease activity, anthropometry and patient-reported physical activity, pain, fatigue, disease impact and exercise beliefs and self-efficacy. Results: Intention-to-treat analysis demonstrated a significant between-group difference in VO_2peak at 3 months (2.5 mL/kg/min, 95% CI 0.9 to 4.0) and 6 months (2.6 mL/kg/min, 95% CI 0.8 to 4.3) in favour of the exercise group. A beneficial change in self-reported physical activity in favour of the exercise group was observed at 3 and 6 months. The HIIT intervention was well-tolerated with minimal adverse events and no apparent impact on disease activity. Differences in secondary outcomes related to CVD risk factors, disease impact, pain, fatigue and exercise beliefs and self-efficacy were generally small and non-significant. Conclusion: After 12 weeks of supervised HIIT delivered in physiotherapy primary care, patients with IA demonstrated a favourable improvement in CRF, with sustained effects at 6-month follow-up. Trial registration number: NCT04922840.

Peripheral circulation is severely compromised in the advanced stages of peripheral arterial disease. Recently, it was shown that the application of −40 mmHg intermittent negative pressure (INP) to the lower leg and foot enhances macro‐ and microcirculation in healthy volunteers. In this case report, we describe the effects of INP treatment on four patients with lower limb ischemia and hard‐to‐heal leg and foot ulcers. We hypothesized that INP therapy may have beneficial hemodynamic and clinical effects in the patients. Four patients (age range: 61–79 years) with hard‐to‐heal leg and foot ulcers (6–24 months) and ankle‐brachial pressure indices of ≤0.60 on the affected side were included. They were treated with an 8‐week intervention period of −40 mmHg INP (10 sec negative pressure and 7 sec atmospheric pressure) on the lower limbs. A custom‐made vacuum chamber was used to apply INP to the affected lower leg and foot for 2 h per day. After 8 weeks of INP therapy, one ulcer healed completely, while the other three ulcers were almost completely healed. These cases suggest that INP may facilitate wound healing. The theoretical foundation is that INP assists wound healing by improving blood flow to the small blood vessels in the affected limb, increasing the flow of oxygen and nutrients to the cells.

The aim of this study was to explore the effects during 12 months follow-up of 12 weeks of supervised exercise therapy (SET) after percutaneous transluminal angioplasty (PTA) compared to PTA alone on physical function, limb hemodynamics and health-related quality of life (HRQoL) in patients with intermittent claudication. Fifty patients were randomised to an intervention or a control group. Both groups received usual post-operative care and follow-up measurements at three, six and 12 months after PTA. The intervention group performed 12 weeks of SET after PTA. The control group did not receive any additional follow-up regarding exercise. During the 12 months’ follow-up, the members of the intervention group had significantly better walking distance than the control group. The intervention group had a significantly higher HRQoL score in the physical component score of the SF-36, and the domains of physical function, bodily pain and vitality. For limb hemodynamics, there was a non-significant trend towards better results in the intervention group compared to the control group. Conclusion: SET after PTA yielded statistically significantly better results for walking distance and HRQoL in the intervention group than the control group during the 12 months of follow-up.

Vascular disease is a major cause of death worldwide, and the growing need for replacement vessels is not fully met by autologous grafts or completely synthetic alternatives. Tissue engineering has emerged as a compelling strategy for the creation of blood vessels for reconstructive surgeries. One promising method to obtain a suitable vessel scaffold is decellularization of donor vascular tissue followed by recellularization with autologous cells. To prevent thrombosis of vascular grafts, a confluent and functional autologous endothelium is required, and researchers are still looking for the optimal cell source and recellularization procedure. Recellularization of a decellularized scaffold with only a small volume of whole blood was recently put forward as a feasible option. Here we show that, in contrast to the published results, this method fails to re-endothelialize decellularized veins. Only occasional nucleated cells were seen on the luminal surface of the scaffolds. Instead, we saw fibrin threads, platelets and scattered erythrocytes. Molecular remnants of the endothelial cells were still attached to the scaffold, which explains in part why earlier results were misinterpreted. Decellularized vascular tissues may still be the best scaffolds available for vascular tissue engineering. However, for the establishment of an adequate autologous endothelial lining, methods other than exposure to autologous whole blood need to be developed.

Intermittent negative pressure (INP) applied to the lower leg and foot increases foot perfusion in healthy volunteers. The aim of the present study was to describe the effects of INP to the lower leg and foot on foot macro- and microcirculation in patients with lower extremity peripheral arterial disease (PAD). In this experimental study, we analyzed foot circulation during INP in 20 patients [median (range): 75 (63-84yrs)] with PAD. One leg was placed inside an air-tight vacuum chamber connected to an INP-generator. During application of INP (alternating 10s of -40mmHg/7s of atmospheric pressure), we continuously recorded blood flow velocity in a distal foot artery (ultrasound Doppler), skin blood flow on the pulp of the first toes (laser Doppler), heart rate (ECG), and systemic blood pressure (Finometer). After a 5-min baseline sequence (no pressure), a 10-min INP sequence was applied, followed by 5-min post-INP (no pressure). To compare and quantify blood flow fluctuations between sequences, we calculated cumulative up-and-down fluctuations in arterial blood flow velocity per minute. Onset of INP induced an increase in arterial flow velocity and skin blood flow. Peak blood flow velocity was reached 3s after the onset of negative pressure, and increased 46% [(95% CI 36–57), P<0.001] above baseline. Peak skin blood flow was reached 2s after the onset of negative pressure, and increased 89% (95% CI 48–130), P<0.001) above baseline. Cumulative fluctuations per minute were significantly higher during INP-sequences compared to baseline [21 (95% CI 12–30)cm/s/min to 41 (95% CI 32–51)cm/s/min, P<0.001]. Mean INP blood flow velocity increased significantly ~12% above mean baseline blood flow velocity [(6.7 (95% CI 5.2–8.3)cm/s to 7.5 (95% CI 5.9–9.1)cm/s, P = 0.03)]. INP increases foot macro- and microcirculatory flow pulsatility in patients with PAD. Additionally, application of INP resulted in increased mean arterial blood flow velocity.