GFR estimation is complicated by a high incidence of non-steady-state serum creatinine concentrations at the emergency department.

BACKGROUND: Acquiring a reliable estimate of glomerular filtration rate (eGFR) at the emergency department (ED) is important for clinical management and for dosing renally excreted drugs. However, renal function formulas such as CKD-EPI can give biased results when serum creatinine (SCr) is not in steady-state because the assumption that urinary creatinine excretion is constant is then invalid. We assessed the extent of this by analysing variability in SCr in patients who visited the ED of a tertiary care centre. METHODS: Data from ED visits at the University Medical Centre Utrecht, the Netherlands between 2012 and 2019 were extracted from the Utrecht Patient Oriented Database. Three measurement time points were defined for each visit: last SCr measurement before visit as baseline (SCr-BL), first measurement during visit (SCr-ED) and a subsequent measurement between 6 and 24 hours during admission (SCr-H1). Non-steady-state SCr was defined as exceeding the Reference Change Value (RCV), with 15% decrease or 18% increase between successive SCr measurements. Exceeding the RCV was deemed as a significant change. RESULTS: Of visits where SCr-BL and SCr-ED were measured (N = 47,540), 28.0% showed significant change in SCr. Of 17,928 visits admitted to the hospital with a SCr-H1 after SCr-ED, 27,7% showed significant change. More than half (55%) of the patients with SCr values available at all three timepoints (11,054) showed at least one significant change in SCr over time. CONCLUSION: One third of ED visits preceded and/or followed by creatinine measurement show non-stable serum creatinine concentration. At the ED automatically calculated eGFR should therefore be interpreted with great caution when assessing kidney function.

The Impact of a Standardized Pre-visit Laboratory Testing Panel in the Internal Medicine Outpatient Clinic: a Controlled "On-Off" Trial.

BACKGROUND: In several settings, a shorter time to diagnosis has been shown to lead to improved clinical outcomes. The implementation of a rapid laboratory testing allows for a pre-visit testing in the outpatient clinic, meaning that test results are available during the first outpatient visit. OBJECTIVE: To determine whether the pre-visit laboratory testing leads to a shorter time to diagnosis in the general internal medicine outpatient clinic. DESIGN: An "on-off" trial, allocating subjects to one of two treatment arms in consecutive alternating blocks. PARTICIPANTS: All new referrals to the internal medicine outpatient clinic of a university hospital were included, excluding second opinions. A total of 595 patients were eligible; one person declined to participate, leaving data from 594 patients for analysis. INTERVENTION: In the intervention group, patients had a standardized pre-visit laboratory testing before the first visit. MAIN MEASURES: The primary outcome was the time to diagnosis. Secondary outcomes were the correctness of the preliminary diagnosis on the first day, health care utilization, and patient and physician satisfaction. KEY RESULTS: There was no difference in time to diagnosis between the two groups (median 35 days vs 35 days; hazard ratio 1.03 [0.87-1.22]; p = .71). The pre-visit testing group had higher proportions of both correct preliminary diagnoses on day 1 (24% vs 14%; p = .003) and diagnostic workups being completed on day 1 (10% vs 3%; p < .001). The intervention group had more laboratory tests done (50.0 [interquartile range (IQR) 39.0-69.0] vs 43.0 [IQR 31.0-68.5]; p < .001). Otherwise, there were no differences between the groups. CONCLUSIONS: Pre-visit testing did not lead to a shorter overall time to diagnosis. However, a greater proportion of patients had a correct diagnosis on the first day. Further studies should focus on customizing pre-visit laboratory panels, to improve their efficacy. TRIAL REGISTRATION: NL5009.

Publisher Correction: Optimization of large animal MI models; a systematic analysis of control groups from preclinical studies.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Exploring the value of routinely measured hematology parameters for identification of elderly patients at high risk of death at the Emergency Department.

Of the warning scores in use for recognition of high-risk patients at the Emergency Department (ED), few incorporate laboratory results. Although hematological characteristics have shown prognostic value in small studies, large studies in elderly ED populations are lacking. We studied the association between blood cell and platelet counts and characteristics as well as C-reactive protein (CRP) at ED presentation with mortality in non-multitrauma patients ≥ 65 years. Comparison between survivors and non-survivors showed small, significant differences with AUROCs ranging between 56.6% and 65.2% for 30-day mortality. Combining parameters yielded an evident improvement (AUROC of 70.4%). Efforts should be pursued to study the added value of hematological parameters on top of clinical data when assessing patient risk.

Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults.

Childhood obesity coincides with increased numbers of circulating classical CD14++CD16- and intermediate CD14++CD16+ monocytes. Monocytes are key players in the development and exacerbation of atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes to atherogenesis over the years. Here, we dissected the monocyte gene expression profile in childhood obesity using an Illumina microarray platform on sorted monocytes of 35 obese children and 16 lean controls. Obese children displayed a distinctive monocyte gene expression profile compared to lean controls. Upon validation with quantitative PCR, we studied the association of the top 5 differentially regulated monocyte genes in childhood obesity with obesity and complexity of coronary atherosclerosis (SYNTAX score) in a cohort of 351 adults at risk for ischemic cardiovascular disease. The downregulation of monocyte IMPDH2 and TMEM134 in childhood obesity was also observed in obese adults. Moreover, downregulation of monocyte TMEM134 was associated with a higher SYNTAX atherosclerosis score in adults. In conclusion, childhood obesity entails monocyte gene expression alterations associated with obesity and enhanced complexity of coronary atherosclerosis in adults.

Optimization of large animal MI models; a systematic analysis of control groups from preclinical studies.

Large animal models are essential for the development of novel therapeutics for myocardial infarction. To optimize translation, we need to assess the effect of experimental design on disease outcome and model experimental design to resemble the clinical course of MI. The aim of this study is therefore to systematically investigate how experimental decisions affect outcome measurements in large animal MI models. We used control animal-data from two independent meta-analyses of large animal MI models. All variables of interest were pre-defined. We performed univariable and multivariable meta-regression to analyze whether these variables influenced infarct size and ejection fraction. Our analyses incorporated 246 relevant studies. Multivariable meta-regression revealed that infarct size and cardiac function were influenced independently by choice of species, sex, co-medication, occlusion type, occluded vessel, quantification method, ischemia duration and follow-up duration. We provide strong systematic evidence that commonly used endpoints significantly depend on study design and biological variation. This makes direct comparison of different study-results difficult and calls for standardized models. Researchers should take this into account when designing large animal studies to most closely mimic the clinical course of MI and enable translational success.

Classical determinants of coronary artery disease as predictors of complexity of coronary lesions, assessed with the SYNTAX score.

BACKGROUND: We need new biomarkers that can predict cardiovascular disease to improve both diagnosis and therapeutic strategies. The CIRCULATING CELLS study was designed to study the role of several cellular mediators of atherosclerosis as biomarkers of coronary artery disease (CAD). An objective and reproducible method for the quantification of CAD extension is required to establish relationships with these potential biomarkers. We sought to analyse the correlation of the SYNTAX score with known CAD risk factors to test it as a valid marker of CAD extension. METHODS AND RESULTS: A subgroup of 279 patients (67.4% males) were included in our analysis. Main exclusion criteria were a history of previous percutaneous coronary intervention or surgical revascularisation that prevent an accurate assessment of the SS. Diabetes mellitus, smoking, renal insufficiency, body mass index and a history of CAD and myocardial infarction were all positively and strongly associated with a higher SYNTAX score after adjustment for the non-modifiable biological factors (age and sex). In the multivariate model, age and male sex, along with smoking and renal insufficiency, remain statistical significantly associated with the SYNTAX score. CONCLUSION: In a selected cohort of revascularisation-naive patients with CAD undergoing coronary angiography, non-modifiable cardiovascular risk factors such as advanced age, male sex, as well as smoking and renal failure were independently associated with CAD complexity assessed by the SYNTAX score. The SYNTAX score may be a valid marker of CAD extension to establish relationships with potential novel biomarkers of coronary atherosclerosis.

Time-dependent trends in cardiovascular adverse events during follow-up after carotid or iliofemoral endarterectomy.

BACKGROUND: Recent observations have suggested a decline in vulnerable carotid artery and iliofemoral atherosclerotic plaque characteristics over the past decade. The aim of this study was to determine whether, in the presence of clinically manifest carotid or peripheral artery disease, secondary adverse cardiovascular events decreased over this period. METHODS: Patients included in the Athero-Express biobank between 2003 and 2012 were analysed. During 3-year follow-up, composite cardiovascular endpoints were documented yearly, including: myocardial infarction, coronary interventions, stroke, peripheral interventions and cardiovascular death. The major cardiovascular endpoint consisted of myocardial infarction, stroke and cardiovascular death. RESULTS: Some 1684 patients who underwent carotid endarterectomy (CEA) and another 530 who had iliofemoral endarterectomy (IFE) were analysed. In total, 405 (25·2 per cent) and 236 (45·9 per cent) patients had a composite cardiovascular endpoint within 3 years after CEA and IFE respectively. Corrected for possible confounders, the percentage of patients with a secondary cardiovascular event after CEA did not change over time (hazard ratio (HR) 0·91, 95 per cent c.i. 0·65 to 1·28; P = 0·590, for 2011-2012 versus 2003-2004). In patients who had IFE, the incidence of secondary cardiovascular events significantly decreased only in the last 2 years (HR 0·62, 0·41 to 0·94; P = 0·024), owing to a decrease in peripheral (re)interventions in 2011-2012 (HR 0·59, 0·37 to 0·94; P = 0·028). No decrease in major cardiovascular events was observed in either group. CONCLUSION: In patients who had undergone either CEA or IFE there was no evidence of a decrease in all secondary cardiovascular events. There were no differences in major cardiovascular events.

The ethnicity-specific association of biomarkers with the angiographic severity of coronary artery disease.

BACKGROUND: Risk factor burden and clinical characteristics of patients with coronary artery disease (CAD) differ among ethnic groups. We related biomarkers to CAD severity in Caucasians, Chinese, Indians and Malays. METHODS: In the Dutch-Singaporean UNICORN coronary angiography cohort (n = 2033) we compared levels of five cardiovascular biomarkers: N-terminal pro-brain natriuretic peptide (NTproBNP), high-sensitivity C-reactive protein (hsCRP), cystatin C (CysC), myeloperoxidase (MPO) and high-sensitivity troponin I (hsTnI). We assessed ethnicity-specific associations of biomarkers with CAD severity, quantified by the SYNTAX score. RESULTS: Adjusted for baseline differences, NTproBNP levels were significantly higher in Malays than in Chinese and Caucasians (72.1 vs. 34.4 and 41.1 pmol/l, p < 0.001 and p = 0.005, respectively). MPO levels were higher in Caucasians than in Indians (32.8 vs. 27.2 ng/ml, p = 0.026), hsTnI levels were higher in Malays than in Caucasians and Indians (33.3 vs. 16.4 and 17.8 ng/l, p < 0.001 and p = 0.029) and hsTnI levels were higher in Chinese than in Caucasians (23.3 vs. 16.4, p = 0.031). We found modifying effects of ethnicity on the association of biomarkers with SYNTAX score. NTproBNP associated more strongly with the SYNTAX score in Malays than Caucasians (ß 0.132 vs. ß 0.020 per 100 pmol/l increase in NTproBNP, p = 0.032). For MPO levels the association was stronger in Malays than Caucasians (ß 1.146 vs. ß 0.016 per 10 ng/ml increase, p = 0.017). Differing biomarker cut-off levels were found for the ethnic groups. CONCLUSION: When corrected for possible confounders we observe ethnicity-specific differences in biomarker levels. Moreover, biomarkers associated differently with CAD severity, suggesting that ethnicity-specific cut-off values should be considered.

Treatment variation in stent choice in patients with stable or unstable coronary artery disease.

AIM: Variations in treatment are the result of differences in demographic and clinical factors (e.g. anatomy), but physician and hospital factors may also contribute to treatment variation. The choice of treatment is considered important since it could lead to differences in long-term outcomes. This study explores the associations with stent choice: i.e. drug-eluting stent (DES) versus bare-metal stents (BMS) for Dutch patients diagnosed with stable or unstable coronary artery disease (CAD). METHODS & RESULTS: Associations with treatment decisions were based on a prospective cohort of 692 patients with stable or unstable CAD. Of those patients, 442 patients were treated with BMS or DES. Multiple logistic regression analyses were performed to identify variables associated with stent choice. Bivariate analyses showed that NYHA class, number of diseased vessels, previous percutaneous coronary intervention, smoking, diabetes, and the treating hospital were associated with stent type. After correcting for other associations the treating hospital remained significantly associated with stent type in the stable CAD population. CONCLUSIONS: This study showed that several factors were associated with stent choice. While patients generally appear to receive the most optimal stent given their clinical characteristics, stent choice seems partially determined by the treating hospital, which may lead to differences in long-term outcomes.

Influence of segmented vessel size due to limited imaging resolution on coronary hyperemic flow prediction from arterial crown volume.

Computational predictions of the functional stenosis severity from coronary imaging data use an allometric scaling law to derive hyperemic blood flow (Q) from coronary arterial volume (V), Q = αV(ß) Reliable estimates of α and ß are essential for meaningful flow estimations. We hypothesize that the relation between Q and V depends on imaging resolution. In five canine hearts, fluorescent microspheres were injected into the left anterior descending coronary artery during maximal hyperemia. The coronary arteries of the excised heart were filled with fluorescent cast material, frozen, and processed with an imaging cryomicrotome to yield a three-dimensional representation of the coronary arterial network. The effect of limited image resolution was simulated by assessing scaling law parameters from the virtual arterial network at 11 truncation levels ranging from 50 to 1,000 µm segment radius. Mapped microsphere locations were used to derive the corresponding relative Q using a reference truncation level of 200 µm. The scaling law factor α did not change with truncation level, despite considerable intersubject variability. In contrast, the scaling law exponent ß decreased from 0.79 to 0.55 with increasing truncation radius and was significantly lower for truncation radii above 500 µm vs. 50 µm (P< 0.05). Hyperemic Q was underestimated for vessel truncation above the reference level. In conclusion, flow-crown volume relations confirmed overall power law behavior; however, this relation depends on the terminal vessel radius that can be visualized. The scaling law exponent ß should therefore be adapted to the resolution of the imaging modality.

Elevated mean neutrophil volume represents altered neutrophil composition and reflects damage after myocardial infarction.

Myocardial infarction (MI) induces an inflammatory response in which neutrophils fulfill a prominent role. Mean neutrophil volume (MNV) represents the average size of the circulating neutrophil population. Our goal was to determine the effect of MI on MNV and investigate the mechanisms behind MNV elevation. MNV of 84 MI patients was compared with the MNV of 209 stable angina patients and correlated to simultaneously measured CK levels. Fourteen pigs were subjected to temporary coronary balloon occlusion and blood was sampled at multiple time points to measure MNV. Echocardiography was performed followed by ex vivo infarct size assessment after 72 h. MNV was higher in MI patients compared to stable angina patients (602 SD26 AU vs. 580 SD20 AU, p < 0.0001) and correlated with simultaneously measured CK levels (R = 0.357, p < 0.0001). In pigs, MNV was elevated post-MI (451 SD11 AU vs. 469 SD12 AU), p < 0.0001). MNV correlated with infarct size (R = 0.705, p = 0.007) and inversely correlated with left ventricular ejection fraction (R = -0.718, p = 0.009). Cell sorting revealed an increased presence of banded neutrophils after MI, which have a higher MNV compared to mature neutrophils post-MI (495 SD14 AU vs. 478 SD11 AU, p = 0.012). MNV from coronary sinus blood was higher than MNV of neutrophils from simultaneously sampled arterial blood (463 SD7.6 AU vs. 461 SD8.6 AU, p = 0.013) post-MI. The current study shows MNV is elevated and reflects cardiac damage post-MI. MNV increases due to altered neutrophil composition and systemic neutrophil activation. MNV may be an interesting parameter for prognostic assessment in MI and provide new insights into pathological innate immune responses evoked by ischemia-reperfusion.

Autologous Mesenchymal Stem Cells Show More Benefit on Systolic Function Compared to Bone Marrow Mononuclear Cells in a Porcine Model of Chronic Myocardial Infarction.

Cardiac cell therapy is a strategy to treat patients with chronic myocardial infarction (MI). No consensus exists regarding the optimal cell type. First, a comparison between autologous bone marrow-derived mononuclear cells (BMMNC) and mesenchymal stem cells (MSC) on therapeutic efficacy after MI was performed. Next, the effect of repetitive, NOGA-guided transendocardial injection was determined via a crossover design. Nineteen pigs were allocated in three groups: (1) placebo (at 4 and 8 weeks), (2) MSC (followed by placebo at 8 weeks), or (3) BMMNC (followed by MSC at 8 weeks) delivery including a priming strategy to enhance MSC effect. At 4 weeks, ejection fraction (EF) was significantly improved after MSC injection and not by BMMNC injection. After 8 weeks, no difference was observed in EF between cell-treated groups demonstrating the positive systolic effect of MSC. This study showed that MSC rather than BMMNC injection improves systolic function in chronic MI.

Perfusion territories subtended by penetrating coronary arteries increase in size and decrease in number toward the subendocardium.

Blood flow distribution within the myocardium and the location and extent of areas at risk in case of coronary artery disease are dependent on the distribution and morphology of intramural vascular crowns. Knowledge of the intramural vasculature is essential in novel multiscale and multiphysics modeling of the heart. For this study, eight canine hearts were analyzed with an imaging cryomicrotome, developed to acquire high-resolution spatial data on three-dimensional vascular structures. The obtained vasculature was skeletonized, and for each penetrating artery starting from the epicardium, the dependent vascular crown was defined. Three-dimensional Voronoi tessellation was applied with the end points of the terminal segments as center points. The centroid of end points in each branch allowed classification of the corresponding perfusion territories in subendocardial, midmyocardial, and subepicardial. Subendocardial regions have relatively few territories of about 0.5 ml in volume having their own penetrating artery at the epicardium, whereas the subepicardium is perfused by a multitude of small perfusion territories, in the order of 0.01 ml. Vascular volume density of small arteries up till 400 µm was 3.2% at the subendocardium territories but only 0.8% in the subepicardium territories. Their higher volume density corresponds to compensation for flow impeding forces by cardiac contraction. These density differences result in different scaling law properties of vascular volume and tissue mass per territory type. This novel three-dimensional quantitative analysis may form the basis for patient-specific computational models on coronary perfusion and aid the interpretation of image-based clinical methods for assessing the transmural perfusion distribution.

Increased cytokine response after toll-like receptor stimulation in patients with stable coronary artery disease.

OBJECTIVE: Atherosclerosis is associated with increased levels of plasma cytokines and expression of Toll-like receptors (TLRs). Yet, little is known about the potential use of TLR ligand induced cytokine release as a biomarker of coronary artery disease (CAD). In this study, we investigated whether TLR ligand induced cytokine release is associated with atherosclerotic disease severity and its predictive value for future cardiovascular events. METHODS: Blood samples were obtained from 260 patients with stable angina and 15 healthy controls. Cytokine levels of TNFα, IL-8 and IL-6 were measured after 2 h of whole blood stimulation with 10 ng/ml lipopolysaccharide (LPS, TLR4 ligand) and P3C 500 ng/ml (TLR2 ligand). In a subgroup, dose-response curves were created using additional LPS concentrations. RESULTS: LPS induced whole blood release of TNFα and IL-6, but not IL-8, was significantly higher in patients compared to healthy controls. Among CAD patients, TLR responses did hardly differ when associated with the presence of traditional risk factors and atherosclerotic disease severity (number of diseased vessels and coronary stenosis degree). Patients with secondary events during follow-up showed a trend towards an increased TLR response. Furthermore, positive associations were found between CRP levels and TLR-induced TNFα (CRP<2: 2055 pg/ml; CRP>2: 2364 pg/ml) and IL-6 production (CRP<2: 1742 pg/ml; CRP>2: 2250 pg/ml). CONCLUSION: In conclusion, TLR-induced whole blood cytokine release in patients with stable angina indicates the presence of coronary atherosclerosis but does not reflect its severity.

Admittance-based pressure-volume loop measurements in a porcine model of chronic myocardial infarction.

The aim of this study was to validate admittance-based pressure-volume (PV) loop measurements for the assessment of cardiac function in a porcine model of chronic myocardial infarction. The traditional PV loop measurement technique requires hypertonic saline injections for parallel conductance correction prior to signal conversion into volume. Furthermore, it assumes a linear relationship between conductance and volume. More recently, an admittance-based technique has been developed, which continuously measures parallel conductance and uses a non-linear equation for volume calculation. This technique has not yet been evaluated in a large-animal model of myocardial ischaemia. Eleven pigs underwent invasive PV measurements with the admittance system (AS) and the traditional conductance system followed by three-dimensional echocardiography (3DE). After baseline measurements, pigs were subjected to 90 min left anterior descending coronary artery occlusion, followed by the same measurements at 8 weeks follow-up. In the healthy heart, the AS showed good agreement with 3DE for left ventricular volumes and a reasonable correlation for ejection fraction (r = 0.756, P = 0.007). At follow-up, an increase in end-systolic volume was observed with 3DE (+15.4 ± 14.4 ml, P = 0.005) and the AS (+34.6 ± 36.1 ml, P = 0.010). The ejection fraction measured with 3DE (-13.2 ± 5.2%, P < 0.001) and the AS (-20.3 ± 11.2%, P < 0.001) significantly decreased. We conclude that the AS can be used for quantitative monitoring of changes in cardiac function induced by myocardial infarction and provides comparable results to 3DE, rendering it a useful tool for functional testing in large-animal cardiac models.

Systemic inflammation in childhood obesity: circulating inflammatory mediators and activated CD14++ monocytes.

AIMS/HYPOTHESIS: In adults, circulating inflammatory mediators and activated CD14(++) monocytes link obesity to its metabolic and cardiovascular complications. However, it is largely unknown whether these inflammatory changes already occur in childhood obesity. To survey inflammatory changes during the early stages of obesity, we performed a comprehensive analysis of circulating inflammatory mediators, monocyte populations and their function in childhood obesity. METHODS: In lean and obese children aged 6 to 16 years (n = 96), 35 circulating inflammatory mediators including adipokines were measured. Hierarchical cluster analysis of the inflammatory mediator profiles was performed to investigate associations between inflammatory mediator clusters and clinical variables. Whole-blood monocyte phenotyping and functional testing with the toll-like receptor 4 ligand, lipopolysaccharide, were also executed. RESULTS: First, next to leptin, the circulating mediators chemerin, tissue inhibitor of metalloproteinase 1, EGF and TNF receptor 2 were identified as novel inflammatory mediators that are increased in childhood obesity. Second, cluster analysis of the circulating mediators distinguished two obesity clusters, two leanness clusters and one mixed cluster. All clusters showed distinct inflammatory mediator profiles, together with differences in insulin sensitivity and other clinical variables. Third, childhood obesity was associated with increased CD14(++) monocyte numbers and an activated phenotype of the CD14(++) monocyte subsets. CONCLUSIONS/INTERPRETATION: Inflammatory mediator clusters were associated with insulin resistance in obese and lean children. The activation of CD14(++) monocyte subsets, which is associated with increased development of atherosclerosis in obese adults, was also readily detected in obese children. Our results indicate that inflammatory mechanisms linking obesity to its metabolic and cardiovascular complications are already activated in childhood obesity.

Aneurysm-express: human abdominal aortic aneurysm wall expression in relation to heterogeneity and vascular events - rationale and design.

OBJECTIVE: Elective repair of abdominal aortic aneurysms (AAA) is associated with significant morbidity and mortality. Large amounts of AAA tissue are necessary to assess heterogeneity among AAA and to correct for potential confounders such as known risk factors. The Aneurysm-express study aims to identify different types of AAA using inflammatory markers in the aneurysm wall that predict postoperative cardiovascular adverse events and mortality, therefore allowing individual risk assessment. METHODS: The Aneurysm-express is an ongoing prospective cohort study including AAA patients undergoing open repair. At baseline, blood is drawn, relevant clinical data are collected and the standard diagnostic modalities are performed. During surgery a specimen of the ventral AAA wall is collected and processed to study protein expressions and histology. INTERIM RESULTS: The study commenced in 2003 in 2 medical centers and currently holds information and material of >300 AAA patients, making it the largest reported aneurysm biobank. Patients are followed for 3 years after surgery for occurring cardiovascular events. The current mean follow-up is 2.1 ± 1.3 years with an event rate of 27%. CONCLUSION: The large amount of structurally stored tissue and blood combined with clinical characteristics and follow-up provide an excellent soil for indepth pathophysiological analyses, with assessment of AAA heterogeneity in combination with postoperative clinical outcome.

Different effects of commonly prescribed statins on abdominal aortic aneurysm wall biology.

BACKGROUND: Pharmaceutical stabilisation of the abdominal aortic aneurysm (AAA) wall can delay surgery and improve outcome. Observational studies indicate statins can be used to reduce AAA growth but mechanistic data are scarce. In this study, our aim was to determine the pleiotropic effects of different statins on AAA wall composition. METHODS: We included 216 patients undergoing open AAA repair, of which 60 used simvastatin, 52 atorvastatin and 23 pravastatin. The AAA wall histology and protein expression (IL 1beta,2,4,5,6,8,10,12, interferon-gamma (IFNgamma), tumour necrosis factor (TNF)alpha,beta, matrix metalloproteinase (MMP)2 and 9 activities, total MMP8,9 and cathepsin A and B levels) between statin users and non-users were compared as also among the use of different statins. RESULTS: As far as histological inflammation goes, the AAA walls of statin users did not differ from those not using them. After multivariate adjustment for risk factors, pravastatin use was associated with tendencies of increased MMP8 (p = 0.022), active MMP9 (p = 0.040) and higher cathepsin B (p = 0.056) levels. The AAA walls of simvastatin and atorvastatin users showed no differences in proteases or cytokines in multivariate analyses. CONCLUSIONS: The use of statins was not associated with a decrease in protease levels or inflammation. The trends of elevated protease levels associated with pravastatin use suggest pleiotropic differences among the various statins, supporting the need for further research to target pharmaceutical AAA treatment.

Cryoplasty of the venous anastomosis for prevention of intimal hyperplasia in a validated porcine arteriovenous graft model.

OBJECTIVES: Cryoplasty combines conventional angioplasty - percutaneous transluminal angioplasty (PTA) - with cold thermal energy. In this animal study, we investigated if preventive cryoplasty could reduce intimal hyperplasia (IH) at the venous anastomosis. DESIGN: We investigated cryoplasty versus PTA of the venous anastomosis in a validated porcine, bilateral, arteriovenous graft model. ANIMALS AND METHODS: In 12 pigs, 24 expanded polytetrafluoroethylene (ePTFE) grafts were bilaterally inserted between the common carotid artery and internal jugular vein. Directly after surgery, one venous anastomosis was treated with cryoplasty at -10 degrees C, the contralateral anastomosis with conventional PTA. At 4 weeks, graft flow was measured, quantitative angiography was performed and grafts with adjacent vessels were excised for histological analysis. RESULTS: Due to a number of thromboses, data for paired analysis were available from eight pigs. Angiographic outflow vein diameter and graft blood flow were not different between treatment groups. Compared with the control group, IH at the venous anastomosis was reduced by 47% (P=0.21) and intima/media ratio was reduced by 45% (P=0.07) by cryoplasty. Effects were most profound in those animals that tended to develop most IH. CONCLUSION: Our results suggest that preventive cryoplasty of the venous anastomosis might help to reduce IH in those cases that develop most profound IH.