Accelerated elastin degradation by age-disease interaction: a common feature in age-related diseases.

Aging is a major driving force for many diseases but the relationship between chronological age, the aging process and age-related diseases is not fully understood. Fragmentation and loss of ultra-long-lived elastin are key features in aging and several age-related diseases leading to increased mortality. By comparing the relationship between age and elastin turnover with healthy volunteers, we show that accelerated elastin turnover by age-disease interaction is a common feature of age-related diseases.

Improving cardiovascular health in patients with an abdominal aortic aneurysm: development of the cardiovascular risk reduction in patients with aneurysms (CRISP) behaviour change intervention.

BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cardiovascular health problem. Ultrasound screening is proven to reduce AAA mortality and programmes have been implemented in some healthcare systems. Those who are identified as having a small AAA in screening enter into a surveillance programme to monitor AAA size. Individuals in AAA surveillance are at elevated risk of cardiovascular events, which is not currently addressed sufficiently. We aimed to develop a simple intervention to reduce cardiovascular risk, which could be embedded in AAA surveillance pathways. METHODS: Intervention mapping methods were used to co-develop the intervention with individuals with AAA, families/carers, and healthcare staff. We identified "targets for change" by synthesising research evidence and international guidelines and consulting with patients, caregivers and health service providers. We conducted a series of workshops to identify barriers to and facilitators of change and used taxonomies of behaviour change theories and techniques to match intervention strategies to each target. Further stakeholder involvement work helped refine the intervention. RESULTS: The developed intervention focusses on assessment and individually tailored discussion of risk factors, exchanging information, building motivation and action planning, followed by review of progress and problem-solving. Workbooks covering physical activity, diet, stress management, alcohol, smoking, blood pressure and mental health are provided to support behaviour change. The intervention is facilitated by trained healthcare professionals during the patient's AAA screening appointment for the duration that they are in surveillance. DISCUSSION: The developed intervention will now be tested to assess whether it can be integrated with the current AAA screening programme. The developed intervention is a novel approach to reducing cardiovascular disease in the AAA population, it is also the first intervention which tries to do this in this population. TRIAL REGISTRATION: International Clinical Trial Registration: ISRCTN93993995.

Editor's Choice - Infra-Renal Aortic Diameter and Cardiovascular Risk: Making Better Use of Abdominal Aortic Aneurysm Screening Outcomes.

OBJECTIVE: Aortic diameter (AD), used traditionally for abdominal aortic aneurysm (AAA) screening may have a role in assessing cardiovascular risk. Unfortunately, AD estimates for those without AAA are underutilised, whilst cardiovascular risk is sub-optimally managed in those with AAA. Our objective was to examine the association between AD measurements and future cardiovascular risk. METHODS: Retrospective analysis of three databases of male participants screened for aortic aneurysm disease. Imaging and clinical data were obtained from three independent sources: 1) the Multi-centre Aneurysm Screening Study (MASS) trial (n = 26 882 men); 2) the 2013/14 cohort of the English NHS AAA Screening Programme (NAAASP) (n = 237 441 men) linked with NHS hospital admission and death registry data; and 3) the Framingham Heart Study (FHS) offspring cohort (n = 649). Associations between maximal aortic diameter, as measured on ultrasound or computed tomography, and cardiovascular outcomes were examined. RESULTS: Cardiovascular mortality in the MASS trial, was higher in men with AAA at 13 years of follow up, compared to those without (Hazard Ratio [HR] 2.22, 95% CI 1.97-2.50, p < .001). Contemporary risk of major adverse cardiovascular events in the NAAASP was highest in those with an AAA (HR 2.91, 95% CI 2.00-4.25), whilst, extremes of aortic diameter were associated with increased risk for cardiovascular events. Aortic diameter was an independent risk factor for cardiovascular events in the FHS dataset. CONCLUSION: Irrespective of the diagnosis of AAA, men attending for AAA screening who are found to have an abnormal aortic diameter are at high risk of future cardiovascular events. This currently unutilised data from AAA screening programmes has the potential to improve preventative management of cardiovascular risk.

An Artificial Neural Network Stratifies the Risks of Reintervention and Mortality after Endovascular Aneurysm Repair; a Retrospective Observational study.

BACKGROUND: Lifelong surveillance after endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) is considered mandatory to detect potentially life-threatening endograft complications. A minority of patients require reintervention but cannot be predictively identified by existing methods. This study aimed to improve the prediction of endograft complications and mortality, through the application of machine-learning techniques. METHODS: Patients undergoing EVAR at 2 centres were studied from 2004-2010. Pre-operative aneurysm morphology was quantified and endograft complications were recorded up to 5 years following surgery. An artificial neural networks (ANN) approach was used to predict whether patients would be at low- or high-risk of endograft complications (aortic/limb) or mortality. Centre 1 data were used for training and centre 2 data for validation. ANN performance was assessed by Kaplan-Meier analysis to compare the incidence of aortic complications, limb complications, and mortality; in patients predicted to be low-risk, versus those predicted to be high-risk. RESULTS: 761 patients aged 75 +/- 7 years underwent EVAR. Mean follow-up was 36+/- 20 months. An ANN was created from morphological features including angulation/length/areas/diameters/volume/tortuosity of the aneurysm neck/sac/iliac segments. ANN models predicted endograft complications and mortality with excellent discrimination between a low-risk and high-risk group. In external validation, the 5-year rates of freedom from aortic complications, limb complications and mortality were 95.9% vs 67.9%; 99.3% vs 92.0%; and 87.9% vs 79.3% respectively (p<0.001). CONCLUSION: This study presents ANN models that stratify the 5-year risk of endograft complications or mortality using routinely available pre-operative data.

Potential role for anti-angiogenic therapy in abdominal aortic aneurysms.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a condition that mainly affects elderly men. At present, there is no effective medical therapy that can retard aneurysm growth or prevent aneurysm rupture. There is evidence that angiogenesis within the wall of an aortic aneurysm may play key roles in aneurysm progression as well as rupture. The use of anti-angiogenic therapy as potential medical therapy in AAA is a promising strategy but has never been studied in detail. DESIGN: This paper discusses the basic mechanisms of angiogenesis, the role played by angiogenesis in aortic aneurysms and the potential therapeutic role of anti-angiogenic drugs against aneurysm expansion or rupture. RESULTS: Angiogenesis is a multi-step process which is fundamental for growth and differentiation of various tissues within a multi-cellular organism. Hypoxia and inflammation are key stimuli for activation of neoangiogenesis. Investigations in both human tissues and animal models of AAA have shown that angiogenesis is a pathological hallmark of AAA and appears to play a role in the development and progression of the condition. Pre-clinical studies have shown that anti-angiogenic drugs can potentially be effective in reducing the intensity of aneurysm formation, suggesting that such drugs may potentially be useful as novel drug therapy for AAA in humans. CONCLUSION: Current evidence suggests that angiogenesis contributes to the destructive processes within aneurysmal aortic wall. As novel drug therapy for aortic aneurysms (for use in humans) is still eluding researchers, anti-angiogenic pathway appears to be an attractive approach.

The Systemic Inflammatory Response Syndrome (SIRS)--number and type of positive criteria predict interventions and outcomes in acute surgical admissions.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a syndrome that reflects the widespread activation of inflammatory pathways. The goal of this study was to find whether the presence or absence of SIRS on emergency surgical admissions is related to the subsequent clinical outcome in terms of in-hospital interventions, length of stay, and mortality. METHODS: The presence of SIRS at admission, final diagnosis of the underlying disease, treatments, and clinical outcomes were prospectively recorded for 1 month. Comparisons of interventions and outcomes were performed between SIRS+ vs. SIRS- patients. In patients with SIRS, the contribution of each positive criterion was evaluated with regards to mortality. RESULTS: A total of 179 patients were recruited. The prevalence of SIRS at admission was 35.2%. SIRS+ patients required less diagnostic procedures compared with SIRS- (28.6% vs. 34.5%) but had more therapeutic interventions (39.7% vs. 16.4%), surgical interventions (33.3% vs. 3.4%), intensive treatments (11.1% vs. 0.9%; p < 0.05), longer hospital stay (median 6 days vs. 2 days), and more frequent deaths (11.1% vs. 2.6%). SIRS+ patients with four positive criteria had more surgical interventions, intensive treatments, and fatal outcomes compared with the others. Of importance the most influent factor was the respiratory rate followed by the white cell count and the heart rate/temperature. CONCLUSIONS: Patients with SIRS at admission apparently receive more interventions, have longer length of stay, and increased mortality than those patients without SIRS. These findings require separate validation in a larger cohort study.