User-defined outcomes of the Danish cardiovascular screening (DANCAVAS) trial: A post hoc analyses of a population-based, randomised controlled trial.

BACKGROUND: The Danish cardiovascular screening (DANCAVAS) trial, a nationwide trial designed to investigate the impact of cardiovascular screening in men, did not decrease all-cause mortality, an outcome decided by the investigators. However, the target group may have varied preferences. In this study, we aimed to evaluate whether men aged 65 to 74 years requested a CT-based cardiovascular screening examination and to assess its impact on outcomes determined by their preferences. METHODS AND FINDINGS: This is a post hoc study of the randomised DANCAVAS trial. All men 65 to 74 years of age residing in specific areas of Denmark were randomised (1:2) to invitation-to-screening (16,736 men, of which 10,471 underwent screening) or usual-care (29,790 men). The examination included among others a non-contrast CT scan (to assess the coronary artery calcium score and aortic aneurysms). Positive findings prompted preventive treatment with atorvastatin, aspirin, and surveillance/surgical evaluation. The usual-care group remained unaware of the trial and the assignments. The user-defined outcome was based on patient preferences and determined through a survey sent in January 2023 to a random sample of 9,095 men from the target group, with a 68.0% response rate (6,182 respondents). Safety outcomes included severe bleeding and mortality within 30 days after cardiovascular surgery. Analyses were performed on an intention-to-screen basis. Prevention of stroke and myocardial infarction was the primary motivation for participating in the screening examination. After a median follow-up of 6.4 years, 1,800 of 16,736 men (10.8%) in the invited-to-screening group and 3,420 of 29,790 (11.5%) in the usual-care group experienced an event (hazard ratio (HR), 0.93 (95% confidence interval (CI), 0.88 to 0.98; p = 0.010); number needed to invite at 6 years, 148 (95% CI, 80 to 986)). A total of 324 men (1.9%) in the invited-to-screening group and 491 (1.7%) in the usual-care group had an intracranial bleeding (HR, 1.17; 95% CI, 1.02 to 1.35; p = 0.029). Additionally, 994 (5.9%) in the invited-to-screening group and 1,722 (5.8%) in the usual-care group experienced severe gastrointestinal bleeding (HR, 1.02; 95% CI, 0.95 to 1.11; p = 0.583). No differences were found in mortality after cardiovascular surgery. The primary limitation of the study is that exclusive enrolment of men aged 65 to 74 renders the findings non-generalisable to women or men of other age groups. CONCLUSION: In this comprehensive population-based cardiovascular screening and intervention program, we observed a reduction in the user-defined outcome, stroke and myocardial infarction, but entail a small increased risk of intracranial bleeding. TRIAL REGISTRATION: ISRCTN Registry number, ISRCTN12157806 https://www.isrctn.com/ISRCTN12157806.

Statistical Analysis Plan for the AIRCARD Study: Individual Long-term Air and Noise Pollution Exposure and Cardiovascular Disease Incidence and Mortality (AIRCARD): A Prospective Cohort Study Utilizing DANCAVAS and VIVA Screening Trials.

INTRODUCTION: The AIRCARD study is designed to investigate the relationship between long-term exposure to air and noise pollution and cardiovascular disease incidence and mortality. We aim to conduct a robust prospective cohort analysis assessing the cumulative and differential impacts of air and noise pollution exposure on cardiovascular disease and mortality. This study will adjust for relevant confounders, including traditional cardiovascular risk factors, socioeconomic indicators, and lipid-lowering agents. METHODS: This prospective cohort study will include 27,022 male participants aged 65-74, recruited from the two large Danish DANCAVAS and VIVA trials, both population-based randomized, multicentered, clinically controlled studies. We will assess long-term exposure to air pollutants using the state-of-the-art DEHM/UBM/AirGIS modelling system and noise pollution through the Nord2000 and SoundPLAN models, covering data from 1979 to 2019. This statistical analysis plan is strictly formulated to predefine the analytical approach for all outcomes and key study variables before data access. The primary analysis will utilize Cox proportional hazards models, adjusted for confounders identified in our cohort (age, body mass index, hypertension, diabetes, smoking status, family history of heart disease, socioeconomic factors, and lipid-lowering agents). This statistical analysis plan further includes Spearman rank correlation to explore inter-pollutant associations. CONCLUSION: The AIRCARD study addresses global concerns about the impact of air and noise pollution on cardiovascular disease. This research is important for understanding how the pollutants contribute to cardiovascular disease. We aim to provide insights into this area, emphasizing the need for public health measures to mitigate pollution exposure. Our goal is to provide policymakers and healthcare professionals with information on the role of environmental factors in cardiovascular health that could influence global strategies to reduce the cardiovascular disease burden associated with pollution. The design of this SAP ensures transparency and.

The association between diabetes and abdominal aortic aneurysms in men: results of two Danish screening studies, a systematic review, and a meta-analysis of population-based screening studies.

BACKGROUND: A paradoxical protective effect of diabetes on the development and progression of abdominal aortic aneurysms (AAA) has been known for years. This study aimed to investigate whether the protective role of diabetes on AAAs has evolved over the years. METHODS: A cross-sectional study, a systematic review and meta-analysis. This study was based on two large, population-based, randomised screening trials of men aged 65-74; VIVA (2008-2011) and DANCAVAS (2014-2018), including measurement of the abdominal aorta by ultrasound or CT, respectively. Analyses were performed using multiple logistic regressions to estimate the odds ratios (ORs) for AAAs in men with diabetes compared to those not having diabetes. Moreover, a systematic review and meta-analysis of population-based screening studies of AAAs to visualise a potential change of the association between diabetes and AAAs. Studies reporting only on women or Asian populations were excluded. RESULTS: In VIVA, the prevalence of AAA was 3.3%, crude OR for AAA in men with diabetes 1.04 (95% confidence interval, CI, 0.80-1.34), and adjusted OR 0.64 (CI 0.48-0.84). In DANCAVAS, the prevalence of AAA was 4.2%, crude OR 1.44 (CI 1.11-1.87), and adjusted OR 0.78 (CI 0.59-1.04). Twenty-three studies were identified for the meta-analysis (N = 224 766). The overall crude OR was 0.90 (CI 0.77-1.05) before 2000 and 1.16 (CI 1.03-1.30) after 1999. The overall adjusted OR was 0.63 (CI 0.59-0.69) before 2000 and 0.69 (CI 0.57-0.84) after 1999. CONCLUSION: Both the crude and adjusted OR showed a statistically non-significant trend towards an increased risk of AAA by the presence of diabetes. If this represents an actual trend, it could be due to a change in the diabetes population. TRIAL REGISTRATION: DANCAVAS: Current Controlled Trials: ISRCTN12157806. VIVA: ClinicalTrials.gov NCT00662480.

Basement membrane proteins in various arterial beds from individuals with and without type 2 diabetes mellitus: a proteome study.

BACKGROUND: Basement membrane (BM) accumulation is a hallmark of micro-vessel disease in diabetes mellitus (DM). We previously reported marked upregulation of BM components in internal thoracic arteries (ITAs) from type 2 DM (T2DM) patients by mass spectrometry. Here, we first sought to determine if BM accumulation is a common feature of different arteries in T2DM, and second, to identify other effects of T2DM on the arterial proteome. METHODS: Human arterial samples collected during heart and vascular surgery from well-characterized patients and stored in the Odense Artery Biobank were analysed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We included ascending thoracic aortas (ATA) (n = 10 (type 2 DM, T2DM) and n = 10 (non-DM)); laser capture micro-dissected plaque- and media compartments from carotid plaques (n = 10 (T2DM) and n = 9 (non-DM)); and media- and adventitia compartments from ITAs (n = 9 (T2DM) and n = 7 (non-DM)). RESULTS: We first extended our previous finding of BM accumulation in arteries from T2DM patients, as 7 of 12 pre-defined BM proteins were significantly upregulated in bulk ATAs consisting of > 90% media. Although less pronounced, BM components tended to be upregulated in the media of ITAs from T2DM patients, but not in the neighbouring adventitia. Overall, we did not detect effects on BM proteins in carotid plaques or in the plaque-associated media. Instead, complement factors, an RNA-binding protein and fibrinogens appeared to be regulated in these tissues from T2DM patients. CONCLUSION: Our results suggest that accumulation of BM proteins is a general phenomenon in the medial layer of non-atherosclerotic arteries in patients with T2DM. Moreover, we identify additional T2DM-associated effects on the arterial proteome, which requires validation in future studies.

Relation between Accumulated Air Pollution Exposure and Sub-Clinical Cardiovascular Disease in 33,723 Danish 60-74-Year-Old Males from the Background Population (AIR-CARD): A Method Article.

Cardiovascular disease is one of the main causes of death and disability in the Western world, and there is increasing evidence that air pollution is a risk factor for developing sub-clinical cardiovascular diseases. Previous studies have shown a correlation between cardiovascular disease and short-term exposure to elevated air pollution levels. However, the literature on the impact of long-term effect of air pollution is limited. We have a unique opportunity to evaluate this correlation. The DEHM/UBM/AirGIS model system calculates air pollution in a high temporal and spatial resolution and traces air pollution retrospectively to year 1979. The model calculates accumulated exposure using annual exposure from PM2.5 in relation to home and work addresses and takes into account working hours and holidays. We link the results from this model system to a population-based cardiovascular screening cohort of 33,723 individuals in the age of 60-74 to assess the contribution of the specific accumulated air pollution to the presence of sub-clinical arteriosclerosis in the coronary vessels, abdominal aortic aneurysms, and peripheral arterial disease. This correlation will be further analyzed in relation to specific air pollutants. This study will introduce more precise data for a longer period of time and incorporate participant's home and work addresses.

High plasma microfibrillar-associated protein 4 is associated with reduced surgical repair in abdominal aortic aneurysms.

OBJECTIVE: Identifying biomarkers for abdominal aortic aneurysms (AAA) could prove beneficial in prognosis of AAA and thus the selection for treatment. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein that is highly expressed in aorta. MFAP4 is involved in several tissue remodeling-related diseases. We aimed to investigate the potential role of plasma MFAP4 (pMFAP4) as a biomarker of AAA. METHODS: Plasma samples and data were obtained for 504 male AAA patients and 188 controls in the Viborg Vascular (VIVA) screening trial. The pMFAP4 levels were measured by Alphalisa. The Mann-Whitney U test assessed differences in pMFAP4 levels between the presence and absence of different exposures of interest. The correlation between pMFAP4 and aorta growth rate were investigated through spearman's correlation analysis. Immunohistochemistry and multiple logistic regression adjusted for potential confounders assessed the association between pMFAP4 and AAA. Multiple linear regression assessed the correlation between pMFAP4 and aorta growth rate. Cox regression and competing risk regression were used to investigate the correlation between AAA patients with upper tertile pMFAP4 and the risk of undergoing later surgical repair. RESULTS: A significant negative correlation between pMFAP4 and aorta growth rate was observed using spearman's correlation analysis (ρ = -0.14; P = .0074). However, this finding did not reach significance when applying multiple linear regression. A tendency of decreased pMFAP4 was observed in AAA using immunohistochemistry. Competing risk regression adjusted for potential confounders indicated that patients with upper tertile pMFAP4 had a hazard ratio of 0.51 (P = .001) for risk of undergoing later surgical repair. CONCLUSIONS: High levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort.

Plasma CCN2 is independently related to subsequent need for abdominal aorta aneurysm repair.

The objective of this study was to determine if plasma CCN2 is associated with abdominal aorta aneurysm (AAA), and future need for AAA repair, and further to assess the potential clinical value of CCN2 in predicting disease outcome. CCN2 was quantified in plasma samples obtained from a cohort of 679 men aged 65-74 at initial ultrasound screening for AAA in the Viborg Vascular (VIVA) screening trial. Plasma CCN2 was correlated with need for future surgical repair in the whole study population (HR = 1.457 (1.081-1.962), p = .013) and in the AAA group alone (HR = 1.431 (1.064-1.926), p = .018), yet the predictive value (CCN2 > 0 and <0 of 0.52 and 0.55, respectively) disqualified its use in clinically relevant AAA repair prediction. In conclusion, CCN2 is independently related to subsequent need for AAA repair, but has negligible predictive power for clinical use.

Microfibrillar-associated protein 4 variation in symptomatic peripheral artery disease.

BACKGROUND: Symptomatic peripheral artery disease (PAD) is an atherosclerotic occlusive disease affecting the lower extremities. The cause of symptomatic PAD is atherosclerosis, vascular dysfunctions, impaired angiogenesis and neointima formation. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein, which is highly expressed in the heart and arteries and recently introduced as a potential mediator of pathological vascular remodeling and neointima formation. We aimed to investigate the relationship between serum MFAP4 (sMFAP4) and symptomatic PAD outcomes. METHODS: A total of 286 PAD patients were analyzed if they had either intermittent claudication or critical lower-extremity ischemia (CLI) and followed for 7 years. The level of serum MFAP4 (sMFAP4) was measured by alphaLISA. Kaplan-Meier, Cox proportional hazard and logistic regression analysis were used to analyze the associations between upper tertile sMFAP4 and symptomatic PAD outcomes. RESULTS: Patients with upper tertile sMFAP4 had an odds ratio (OR) of 2.65 (p < 0.001) for having CLI diagnosis. Further analysis indicated that patients with upper tertile sMFAP4 had a hazard ratio (HR) of 1.97 (p = 0.04) for cardiovascular death during the 7-years follow-up. However, analysis of 2-year primary patency showed that patients with upper tertile sMFAP4 had decreased risk of vascular occlusion after reconstructive surgery with HR of 0.15 (p = 0.02). CONCLUSIONS: sMFAP4 has potential as a prognostic marker for cardiovascular death, primary patency of reconstructed vessels and CLI diagnosis in symptomatic PAD patients. Confirmation of observations in larger cohorts is warranted.

Glycated Hemoglobin Is Associated With the Growth Rate of Abdominal Aortic Aneurysms: A Substudy From the VIVA (Viborg Vascular) Randomized Screening Trial.

OBJECTIVE: An inverse association between abdominal aortic aneurysms (AAAs) and diabetes mellitus exists; however, the cause remains unknown. This study aimed to evaluate whether the degree of glycemia is associated with aneurysm growth. APPROACH AND RESULTS: The study was based on VIVA trial (Viborg Vascular), the randomized clinically controlled screening trial for abdominal aortic aneurysm in men aged 65 to 74 years in the Central Denmark Region. The screening included measurement of the abdominal aorta by ultrasound, analysis of glycated hemoglobin (HbA1c), and follow-up for ≤5 years for aneurysms <5 cm. Analyses were conducted using mixed-effect models. At baseline, VIVA screening identified 619 individuals (3.3%) with abdominal aortic aneurysms. A total of 103 individuals were referred for vascular evaluation, and after removal of additional individuals who were lost to follow-up or had missing blood samples, we were left with 319 individuals. Sixty-one individuals (19.1%) had diabetes mellitus. The median growth rate was 1.7 versus 2.7 mm/y in individuals with and without diabetes mellitus, respectively (P<0.001). We found a significant inverse association between aneurysmal growth rate and HbA1c in the total study population (P=0.002). Both crude and adjusted analyses identified slower growth for the group with the highest HbA1c tertile compared with the lowest HbA1c tertile. After 3 years, the mean difference was 1.8 mm (confidence interval, 0.98-2.64). Similar significant differences were observed in subgroup analysis of individuals without self-reported diabetes mellitus. CONCLUSIONS: We found an inverse association between the growth rate of abdominal aortic aneurysms and the level of HbA1c, indicating that long-lasting elevated blood sugar impairs aneurysmal progression in individuals with and without known diabetes mellitus.

Association Between Diverticular Disease and Abdominal Aortic Aneurysms: Pooled Analysis of Two Population Based Screening Cohorts.

BACKGROUND: The aetiology of abdominal aortic aneurysms (AAA) is multifactorial, and many risk factors are shared with diverticular disease. It is unknown whether an independent association exists between these conditions. METHODS: Individuals enrolled in two Danish population based randomised AAA screening trials and assigned to cross sectional screening and evaluation of cardiovascular risk factors were identified. Diagnoses of diverticular disease were interrogated from a national patient registry covering the period from 1977 to the screening date. Adjusted odds ratios (aOR) and hazard ratios (aHR) with 95% CI were calculated as risk measures. RESULTS: 24,632 individuals (median age, 69 years) were included. At screening, 687 patients had pre-existing diverticular disease. Patients with diverticular disease were more likely to have AAA at screening compared with those without diverticular disease (5.2% vs. 3.3%) (OR 1.61, 95% CI 1.14-2.27). This association persisted after adjusting for potential confounders (aOR 1.49, 95% CI 1.04-2.12) and on sensitivity analyses. The association was most pronounced for those with a diagnosis of diverticular disease for at least 10 years (aOR 2.56, 95% CI 1.49-4.38). Following screening, 6.2% of patients with diverticular disease and AAA experienced aneurysm rupture, compared with 2.2% of patients with AAA without diverticular disease (aHR 4.1, 95% CI 1.6-10.8). CONCLUSION: An association was found between diverticular disease and AAA in a large population based cohort. Biological causality remains to be established, and a potential impact of diverticular disease on the natural history of AAA needs to be explored further.

Computed tomography scan based prediction of the vulnerable carotid plaque.

BACKGROUND: Primary to validate a commercial semi-automated computed tomography angiography (CTA) -software for vulnerable plaque detection compared to histology of carotid endarterectomy (CEA) specimens and secondary validating calcifications scores by in vivo CTA with ex vivo non-contrast enhanced computed tomography (NCCT). METHODS: From January 2014 to October 2016 53 patients were included retrospectively, using a cross-sectional design. All patients underwent both CTA and CEA. Sixteen patients had their CEA specimen NCCT scanned. The semi-automated CTA software analyzed carotid stenosis using different HU values defining plaque components. The predictive values of CTA based detection of vulnerable plaques were calculated. Quantification of calcifications on CTA using region of interest (ROI)-function and mathematical equations was done manually, and validated by NCCT of the CEA specimen. RESULTS: The semi-automated CTA software had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 89.1% (95% CI, 73.6% - 96.4%), 31.3% (95% CI, 12.1% - 58.5%), 75% (95% CI, 59.3% - 86.2%) and 55.6% (95% CI, 22.6% - 84.6%). Strong correlation between in vivo CTA and ex vivo NCCT in quantification of calcification was observed, but CTA systematically underestimated calcificationsscore (CALS) with increasing calcification. CONCLUSION: The CTA-software cannot be used in risk assessment of patients, due to poor specificity and NPV. The correlation between in vivo CTA and ex vivo NCCT was strong, proposing it to be used in both scientifically and clinical settings, but studies with larger sample sizes are needed.

Impact of androgenic anabolic steroid use on cardiovascular and mental health in Danish recreational athletes: protocol for a nationwide cross-sectional cohort study as a part of the Fitness Doping in Denmark (FIDO-DK) study.

INTRODUCTION: The use of androgenic anabolic steroids (AASs) among recreational athletes is steadily increasing. However, knowledge regarding the potentially harmful effects of AAS primarily originates from case reports and small observational studies. This large-scale study aims to investigate the impact of AAS use on vascular plaque formation, preclinical coronary disease, cardiac function, circulating cardiovascular risk markers, quality of life (QoL) and mental health in a broad population of illicit AAS users. METHODS AND ANALYSES: A nationwide cross-sectional cohort study including a diverse population of men and women aged ≥18 years, with current or previous illicit AAS use for at least 3 months. Conducted at Odense University Hospital, Denmark, the study comprises two parts. In part A (the pilot study), 120 recreational athletes with an AAS history will be compared with a sex-matched and age-matched control population of 60 recreational athletes with no previous AAS use. Cardiovascular outcomes include examination of non-calcified coronary plaque volume and calcium score using coronary CT angiography, myocardial structure and function via echocardiography, and assessing carotid and femoral artery plaques using ultrasonography. Retinal microvascular status is evaluated through fundus photography. Cardiovascular risk markers are measured in blood. Mental health outcomes include health-related QoL, interpersonal difficulties, body image concerns, aggression dimensions, anxiety symptoms, depressive severity and cognitive function assessed through validated questionnaires. The findings of our comprehensive study will be used to compose a less intensive investigatory cohort study of cardiovascular and mental health (part B) involving a larger group of recreational athletes with a history of illicit AAS use. ETHICS AND DISSEMINATION: The study received approval from the Regional Committee on Health Research Ethics for Southern Denmark (S-20210078) and the Danish Data Protection Agency (21/28259). All participants will provide signed informed consent. Research outcomes will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT05178537.

Heart-to-heart with ChatGPT: the impact of patients consulting AI for cardiovascular health advice.

OBJECTIVES: The advent of conversational artificial intelligence (AI) systems employing large language models such as ChatGPT has sparked public, professional and academic debates on the capabilities of such technologies. This mixed-methods study sets out to review and systematically explore the capabilities of ChatGPT to adequately provide health advice to patients when prompted regarding four topics from the field of cardiovascular diseases. METHODS: As of 30 May 2023, 528 items on PubMed contained the term ChatGPT in their title and/or abstract, with 258 being classified as journal articles and included in our thematic state-of-the-art review. For the experimental part, we systematically developed and assessed 123 prompts across the four topics based on three classes of users and two languages. Medical and communications experts scored ChatGPT's responses according to the 4Cs of language model evaluation proposed in this article: correct, concise, comprehensive and comprehensible. RESULTS: The articles reviewed were fairly evenly distributed across discussing how ChatGPT could be used for medical publishing, in clinical practice and for education of medical personnel and/or patients. Quantitatively and qualitatively assessing the capability of ChatGPT on the 123 prompts demonstrated that, while the responses generally received above-average scores, they occupy a spectrum from the concise and correct via the absurd to what only can be described as hazardously incorrect and incomplete. Prompts formulated at higher levels of health literacy generally yielded higher-quality answers. Counterintuitively, responses in a lower-resource language were often of higher quality. CONCLUSIONS: The results emphasise the relationship between prompt and response quality and hint at potentially concerning futures in personalised medicine. The widespread use of large language models for health advice might amplify existing health inequalities and will increase the pressure on healthcare systems by providing easy access to many seemingly likely differential diagnoses and recommendations for seeing a doctor for even harmless ailments.

Protocol for a cohort study to evaluate the effectiveness and cost-effectiveness of general population screening for cardiovascular disease: the Viborg Screening Programme (VISP).

INTRODUCTION: The prevalence of cardiovascular disease (CVD) is increasing. Furthermore, asymptomatic individuals may not receive timely preventive initiatives to minimise the risk of further CVD events. Paradoxically, 80% of CVD events are preventable by early detection, followed by prophylactic initiatives. Consequently, we introduced the population-based Viborg Screening Programme (VISP) for subclinical and manifest CVD, focusing on commonly occurring, mainly asymptomatic conditions, followed by prophylactic initiatives.The aim of the VISP was to evaluate the health benefits, harms and cost-effectiveness of the VISP from a healthcare sector perspective. Furthermore, we explored the participants' perspectives. METHODS AND ANALYSIS: From August 2014 and currently ongoing, approximately 1100 men and women from the Viborg municipality, Denmark, are annually invited to screening for abdominal aortic aneurysm, peripheral arterial disease, carotid plaque, hypertension, diabetes mellitus and cardiac arrhythmia on their 67th birthday. A population from the surrounding municipalities without access to the VISP acts as a control. The VISP invitees and the controls are followed on the individual level by nationwide registries. The primary outcome is all-cause mortality, while costs, hospitalisations and deaths from CVD are the secondary endpoints.Interim evaluations of effectiveness and cost-effectiveness are planned every 5 years using propensity score matching followed by a Cox proportional hazards regression analysis by the 'intention-to-treat' principle. Furthermore, censoring-adjusted incremental costs, life-years and quality-adjusted life-years are estimated. Finally, the participants' perspectives are explored by semistructured face-to-face interviews, with participant selection representing participants with both negative and positive screening results. ETHICS AND DISSEMINATION: The VISP is not an interventional trial. Therefore, approval from a regional scientific ethical committee is not needed. Data collection from national registries was approved by the Regional Data Protection Agency (record no. 1-16-02-232-15). We ensure patient and public involvement in evaluating the acceptability of VISP by adopting an interviewing approach in the study. TRIAL REGISTRATION NUMBER: NCT03395509.

An Antibiotic-Loaded Silicone-Hydrogel Interpenetrating Polymer Network for the Prevention of Surgical Site Infections.

Surgical site infections (SSIs) are among the most frequent healthcare-associated infections, resulting in high morbidity, mortality, and cost. While correct hygiene measures and prophylactic antibiotics are effective in preventing SSIs, even in modern healthcare settings where recommended guidelines are strictly followed, SSIs persist as a considerable problem that has proven hard to solve. Surgical procedures involving the implantation of foreign bodies are particularly problematic due to the ability of microorganisms to adhere to and colonize the implanted material and form resilient biofilms. In these cases, SSIs may develop even months after implantation and can be difficult to treat once established. Locally applied antibiotics or specifically engineered implant materials with built-in antibiotic-release properties may prevent these complications and, ultimately, require fewer antibiotics compared to those that are systemically administered. In this study, we demonstrated an antimicrobial material concept with intended use in artificial vascular grafts. The material is a silicone-hydrogel interpenetrating polymer network developed earlier for drug-release catheters. In this study, we designed the material for permanent implantation and tested the drug-loading and drug-release properties of the material to prevent the growth of a typical causative pathogen of SSIs, Staphylococcus aureus. The novelty of this study is demonstrated through the antimicrobial properties of the material in vitro after loading it with an advantageous combination, minocycline and rifampicin, which subsequently showed superiority over the state-of-the-art (Propaten) artificial graft material in a large-animal study, using a novel porcine tissue-implantation model.

Insulin resistance is associated with high-risk coronary artery plaque composition in asymptomatic men between 65 and 75 years and no diabetes: A DANCAVAS cross-sectional sub-study.

BACKGROUND AND AIMS: Insulin resistance (IR) and pre-diabetes are associated with an increased risk of cardiovascular disease (CVD). We aimed to investigate vulnerable plaque composition in relation to IR and pre-diabetes in asymptomatic non-diabetic men. METHODS: All participants underwent a contrast-enhanced coronary computed tomography angiography (CCTA) to evaluate coronary artery plaque burden and plaque composition (necrotic core, dense calcium, fibrotic and fibrous-fatty volume). Homeostasis model assessment of IR (HOMA-IR) was used, and participants were stratified into tertiles. Participants underwent a standard oral glucose tolerance test (OGTT) and were categorized into 2 groups (normal glucose tolerance (NGT) or pre-diabetes). A multivariable linear regression model was used to evaluate the association between vulnerable plaque composition and IR or glycemic group. RESULTS: Four-hundred-and-fifty non-diabetic men without known CAD were included. The mean age was 70 ± 3 years. Participants in the higher HOMA-IR tertile (H-IR) had higher median necrotic plaque volume compared to the lower HOMA-IR tertile (L-IR) (18.2 vs. 11.0 mm3, p = 0.02). H-IR tertile (ß 0.37 [95% CI 0.10-0.65], p = 0.008), pack-years (ß 0.07 [95% CI 0.007-0.14], p = 0.03) and total atheroma volume (TAV) (ß 0.47 [95% CI 0.36-0.57], p < 0.001) remained associated with necrotic plaque volume in the multivariable linear regression model. CONCLUSIONS: IR was associated with necrotic plaque volume in asymptomatic men without diabetes. Thus, even in asymptomatic men without diabetes, IR seems to have an incremental effect on necrotic plaque volume and vulnerable plaque composition.

Individualized prediction of risk of ascending aortic syndromes.

OBJECTIVES: Although ascending aortic diameter changes acutely after dissection, recommendation for prophylactic surgery of thoracic aortic aneurysms rely on data from dissected aortas. In this case-control study we aim to identify risk markers for acute and chronic aortic syndromes of the ascending aorta (ACAS-AA). Furthermore, to develop a predictive model for ACAS-AA. METHODS: We collected data of 188 cases of ACAS-AA and 376 controls standardized to age- and sex of the background population. Medical history and CT-derived aortic morphology were collected. For the dependent outcome ACAS-AA, potential independent risk factors were identified by univariate logistic regression and confirmed in multivariate logistic regression. As post-dissection tubular ascending aortic diameter is prone to expand, this factor was not included in the first model. The individual calculated adjusted odds ratios were then used in ROC-curve analysis to evaluate the diagnostic accuracy of the model. To test the influence of post-ACAS-AA tubular ascending aortic diameter, this was added to the model. RESULTS: The following risk factors were identified as independent risk factors for ACAS-AA in multivariate analysis: bicuspid aortic valve (OR 20.41, p = 0.03), renal insufficiency (OR 2.9, p<0.01), infrarenal abdominal aortic diameter (OR 1.08, p<0.01), left common carotid artery diameter (OR 1.40, p<0.01) and aortic width (OR 1.07, p<0.01). Area under the curve was 0.88 (p<0.01). Adding post-ACAS-AA tubular ascending aortic diameter to the model, negated the association of bicuspid aortic valve, renal insufficiency, and left common carotid artery diameter. Area under the curve changed to 0.98 (p<0.01). CONCLUSIONS: A high performing predictive model for ACAS-AA, free of ascending aortic diameter, can be achieved. Furthermore, we have identified abdominal aortic ectasia as an independent risk factor of ACAS-AA. Integration of potential biomarkers and morphologic variables, derived from undissected aortas, would probably improve the model.

Sex Differences in Factors Associated With Progression of Aortic Valve Calcification in the General Population.

BACKGROUND: Guidelines recommend measurement of the aortic valve calcification (AVC) score to help differentiate between severe and nonsevere aortic stenosis, but a paucity exists in data about AVC in the general population. The aim of this study was to describe the natural history of AVC progression in the general population and to identify potential sex differences in factors associated with this progression rate. METHODS: Noncontrast cardiac computed tomography was performed in 1298 randomly selected women and men aged 65 to 74 years who participated in the DANCAVAS trial (Danish Cardiovascular Screening). Participants were invited to attend a reexamination after 4 years. The AVC score was measured at the computed tomography, and AVC progression (ΔAVC) was defined as the difference between AVC scores at baseline and follow-up. Multivariable regression analyses were performed to identify factors associated with ΔAVC. RESULTS: Among the 1298 invited citizens, 823 accepted to participate in the follow-up examination. The mean age at follow-up was 73 years. Men had significantly higher AVC scores at baseline (median AVC score 13 Agatston Units [AU; interquartile range, 0-94 AU] versus 1 AU [interquartile range, 0-22 AU], P<0.001) and a higher ΔAVC (median 26 AU [interquartile range, 0-101 AU] versus 4 AU [interquartile range, 0-37 AU], P<0.001) than women. In the fully adjusted model, the most important factor associated with ΔAVC was the baseline AVC score. However, hypertension was associated with ΔAVC in women (incidence rate ratios, 1.58 [95% CI, 1.06-2.34], P=0.024) but not in men, whereas dyslipidemia was associated with ΔAVC in men (incidence rate ratio: 1.66 [95% CI, 1.18-2.34], P=0.004) but not in women. CONCLUSIONS: The magnitude of the AVC score was the most important marker of AVC progression. However, sex differences were significant; hence, dyslipidemia was associated with AVC progression only among men; hypertension with AVC progression only among women. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN12157806.

Association of Left Atrial Size Measured by Non-Contrast Computed Tomography with Cardiovascular Risk Factors-The Danish Cardiovascular Screening Trial (DANCAVAS).

Left atrium (LA) size is associated with adverse cardiovascular events. The purpose of this study was to investigate the association of LA enlargement measured by non-contrast CT (NCCT) with traditional cardiovascular risk factors. Individuals aged 60-75 years from the population-based multicentre Danish Cardiovascular Screening (DANCAVAS) trial were included in this cross-sectional study. The LA was manually traced on the NCCT scans, and the largest cross-section area was indexed to body surface area. All traditional risk factors were recorded, and a subgroup received an echocardiographic examination. We enrolled 14,987 individuals. Participants with known cardiovascular disease or lacking measurements of LA size or body surface area were excluded, resulting in 10,902 men for the main analysis and 616 women for a sensitivity analysis. Adjusted multivariable analysis showed a significantly increased indexed LA size by increasing age and pulse pressure, while smoking, HbA1c, and total cholesterol were associated with decreased indexed LA size. The findings were confirmed in a supplementary analysis including left ventricle ejection fraction and mass. In this population-based cohort of elderly men, an association was found between age and pulse pressure and increasing LA size. Surprisingly, smoking, HbA1c, and total cholesterol were associated with a decrease in LA size. This indicates that the pathophysiology behind atrial cardiomyopathy is not only reflected by enlargement, but also shrinking.

Arterial blood gas analysis: as safe as we think? A multicentre historical cohort study.

PURPOSE: Arterial punctures (APs) for arterial blood gas (ABG) analyses are much-used medical procedures. To date, no large studies have been conducted on the major complication rate of APs. We aimed to describe the risk of major complications within 7 days after puncture and investigate whether using antithrombotic medication affected this. METHODS: We included all APs performed for ABG analysis at three Danish hospitals from January 1, 1993 to February 25, 2013. We excluded APs ordered by the anaesthesiology department, intensive care unit (ICU) or in patients <18 years old. Data on the patient level were extracted from the Danish National Patient Registry, Danish Civil Registration System and Odense Pharmaco-Epidemiologic Database (OPED), the latter providing us with information on antithrombotic medication. Initially, two clinicians compiled a list with all procedures and diagnoses that could possibly be a consequence of APs. The selected procedures and diagnoses were further categorised independently by three surgeons and used to indicate the complication rate. RESULTS: We analysed 473 327 APs and found 669 (0.14%, 95% CI 0.13-0.15) APs led to major complications: embolisms or thrombosis (49.0%), aneurysms (15.4%), nerve damage (1.5%), arteriovenous fistulas (0.6%) or of another kind (33.5%). The identified major complication rates in patients on antithrombotic medication were increased (OR 1.31, 95% CI 1.07-1.61). CONCLUSION: APs for ABG analyses are safe procedures. The major complication rate within 7 days was 0.14% (95% CI 0.13-0.15). Patients on antithrombotic medication carry an increased risk of developing major complications.