Late Cardiovascular Events Research Articles

Tumour necrosis factor-α and myoglobin associated with the recovery time of coronary artery lesions in Kawasaki disease patients.

To assess the relationship between clinical parameters and medium term recovery time of coronary artery lesions (CALs). In total, 344 Kawasaki disease patients were screened and 311 Kawasaki disease patients were included and followed-up for the next 2 years. Clinical records, clinical parameters and inflammatory biomarkers were collected for all subjects. Tumour necrosis factor (TNF)-α and myoglobin (MYO) levels in patients without recovery from CALs were significantly higher than those without CALs and with recovery from CALs. Kaplan-Meier survival analysis showed that in the high-TNF-α group, the estimated median time to recovery (5.0 months, 95% confidence interval (CI) 1.436-8.564) is significantly longer than the low-TNF-α group (2.00 months, 95% CI: 0.633-3.367, P = 0.044). Also, the estimated median time (5.0 months, 95% CI: 1.836-8.164) in the high-MYO group is significantly longer than the low-MYO group (2.00 months, 95% CI: 0.405-3.595, P = 0.002). Cox regression analysis showed independent factors for recovery of CALs included age, left coronary artery to aortic annulus ratio, TNF-α and MYO levels. These findings suggest that clinical parameters such as age, left coronary artery to aortic annulus ratio, TNF-α and MYO levels associate with medium term recovery time of CALs and could help in the design of a clinical strategy for the surveillance and prevention of late cardiovascular events.

Long-term outcome of patients with atrial myxoma after surgical intervention: analysis of 403 cases.

ObjectiveTo assess long-term survival and late cardiovascular events in patients with atrial myxoma after surgical intervention.MethodsRetrospective analysis of 403 patients undergoing resection of atrial myxoma from January 2002 to December 2016 was conducted with a median follow-up period of 4.5 (range: 0.5–15) years.ResultsThe cross-clamp time and cardiopulmonary bypass times were 41.1 ± 21.4 and 65.2 ± 27.3 min, respectively. A diagnosis of myxoma was histopathologically confirmed in all cases. The early in-hospital mortality rate was 0.7% (n = 3). During the follow-up period, tumor recurrence occurred in six patients and cerebral infarction in nine. There were 48 (11.9%) patients with late onset atrial fibrillation (AF). By multivariate analysis, age (HR = 1.05, 95% CI: 1.02–1.09, P < 0.001), left atrial diameter (HR = 1.23, 95% CI: 1.08–1.36, P = 0.012), and mitral valve surgery (HR = 1.17, 95% CI: 1.05–1.29, P = 0.027) were independent predictors of late onset AF. Twenty-one (5.2%) patients died during the follow-up period. Advanced age (HR = 1.07, 95% CI: 1.04–1.10, P = 0.003) and multiple surgical procedures (HR = 1.18, 95% CI: 1.06–1.29, P = 0.012) were significantly associated with overall mortality.ConclusionsAtrial myxoma can be resected with good long-term survival. Late onset AF is common after surgery in patients with atrial myxoma. Advanced age, left atrial diameter, and mitral valve surgery were independent predictors of outcomes.

Tranexamic acid in coronary artery surgery: One-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial

BackgroundTranexamic acid reduces blood loss and transfusion requirements in cardiac surgery but may increase the risk of coronary graft thrombosis. We previously reported the 30-day results of a trial evaluating tranexamic acid for coronary artery surgery. Here we report the 1-year clinical outcomes. MethodsUsing a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score of less than 8. Secondary outcomes included a composite of myocardial infarction, stroke, and death from any cause through to 1 year after surgery. ResultsThe rate of death or disability at 1 year was 3.8% in the tranexamic acid group and 4.4% in the placebo group (relative risk, 0.85; 95% confidence interval, 0.64-1.13; P = .27), and this did not significantly differ according to aspirin exposure at the time of surgery (interaction P = .073). The composite rate of myocardial infarction, stroke, and death up to 1 year after surgery was 14.3% in the tranexamic acid group and 16.4% in the placebo group (relative risk, 0.87; 95% CI, 0.76-1.00; P = .053). ConclusionsIn this trial of patients having coronary artery surgery, tranexamic acid did not affect death or severe disability through to 1 year after surgery. Further work should be done to explore possible beneficial effects on late cardiovascular events.

Contribution of obstructive sleep apnoea to arterial stiffness: a meta-analysis using individual patient data

BackgroundArterial stiffness, measured by pulse wave velocity (PWV), is a strong independent predictor of late cardiovascular events and mortality. It is recognised that obstructive sleep apnoea (OSA) is associated with...

Astragaloside IV Improves Vasodilatation Function by Regulating the PI3K/Akt/eNOS Signaling Pathway in Rat Aorta Endothelial Cells

Coronary heart disease (CHD) remains a major public health burden. Endothelial-dependent coronary artery vasoreactivity is a significant indicator of vascular function. Endothelial dysfunction is characterized by decreased nitric oxide (NO) bioavailability and predicts late cardiovascular events. Astragaloside IV (AGIV) is the main active component of the herb Astragalus membranaceus. Although it shows a significant protective effect against vascular endothelial dysfunction, the mechanisms of AGIV promoting the vascular dilation have not been elucidated. This study investigated the vasodilator effect of AGIV on rat aortic rings and the underlying effect of AGIV via the PI3K/Akt/eNOS signaling pathway. We measured the relaxation of isolated RARs after different concentrations of AGIV treatment. Rat aorta endothelial cells were cultured with different doses of AGIV, dimethylsulfoxide, and NG-nitro L-arginine methyl ester. The expression of phosphorylated (p)-Akt and -endothelial nitric oxide synthase (p-eNOS) were tested by Western blot analysis. The messenger (m)RNA expression of eNOS was quantified by real-time polymerase chain reaction. AGIV exerted a vasodilator effect on the aortic rings and increased the NO content in a concentration-dependent manner. The vasorelaxation was suppressed by an eNOS inhibitor. AGIV regulated the PI3K/Akt/eNOS signaling pathway via phosphorylation of Akt at Ser⁴⁷³ and dephosphorylation of eNOS at Thr⁴⁹⁵. The mRNA expression of eNOS was remarkably upregulated by AGIV. AGIV significantly induced the dilation of the aortic rings, leading to the vasodilator response by enhancing the eNOS release via the PI3K/Akt/eNOS signaling pathway.

Impact of Mandibular Advancement Therapy on Endothelial Function in Severe Obstructive Sleep Apnea.

Endothelial dysfunction, a major predictor of late cardiovascular events, is linked to the severity of obstructive sleep apnea (OSA). To determine whether treatment with mandibular advancement device, the main alternative to continuous positive airway pressure, improves endothelial function in patients with severe OSA. In this trial, we randomized patients with severe OSA and no overt cardiovascular disease to receive 2 months of treatment with either effective mandibular advancement device or a sham device. The primary outcome, change in reactive hyperemia index, a validated measurement of endothelial function, was assessed on an intention-to-treat basis. An embedded microsensor objectively measured treatment compliance. A total of 150 patients (86% males; mean [SD] age, 54 [10] yr; median [interquartile range] apnea-hypopnea index, 41 [35-53]; mean [SD] Epworth sleepiness scale, 9.3 [4.2]) were randomized to effective mandibular advancement device (n = 75) or sham device (n = 75). On intention-to-treat analysis, effective mandibular advancement device therapy was not associated with improvement of endothelial function compared with the sham device. Office and ambulatory blood pressure outcomes did not differ between the two groups. Effective mandibular advancement device therapy was associated with significant improvements in apnea-hypopnea index (P < 0.001); microarousal index (P = 0.008); and symptoms of snoring, fatigue, and sleepiness (P < 0.001). Mean (SD) objective compliance was 6.6 (1.4) h/night with the effective mandibular advancement device versus 5.6 (2.3) h/night with the sham device (P = 0.006). In moderately sleepy patients with severe OSA, mandibular advancement therapy reduced OSA severity and related symptoms but had no effect on endothelial function and blood pressure despite high treatment compliance. Clinical trial registered with www.clinicaltrials.gov (NCT 01426607).

Association between obstructive sleep apnea severity and endothelial dysfunction in patients with type 2 diabetes

BackgroundObstructive sleep apnea (OSA) and type 2 diabetes (T2D) are associated with endothelial dysfunction a main predictor of late cardiovascular (CV) events. Despite the high prevalence of OSA in patients with T2D, the impact of OSA severity on endothelial function has not been clearly elucidated. The aim of this cross-sectional study was to determine whether increasing OSA severity is associated with poorer endothelial function in patients with T2D.Methods140 patients with T2D and no overt CV disease underwent polysomnography, peripheral arterial tonometry, clinic blood pressure (BP) measurement, biological assessment for CV risk factors, daytime sleepiness and health related quality of life (HRQL) questionnaires. The following commonly used cut-offs for apnea-hypopnea index (AHI) were used to define 3 categories of disease severity: AHI < 15 (no OSA or mild OSA), 15 ≤ AHI < 30 (moderate OSA), and AHI ≥ 30 (severe OSA). The primary outcome was the reactive hyperemia index (RHI), a validated assessment of endothelial function.Results21.4% of patients had moderate OSA and 47.6% had severe OSA. Increasing OSA severity and nocturnal hypoxemia were not associated with a significant decrease in RHI. Endothelial dysfunction (RHI < 1.67) was found in 47.1, 44.4 and 39.2% of patients with no OSA or mild OSA, moderate OSA and severe OSA, respectively (p = 0.76). After adjustment for confounders including body mass index, increasing OSA severity was associated with higher systolic BP (p = 0.03), lower circulating levels of adiponectin (p = 0.0009), higher levels of sP-selectin (p = 0.03), lower scores in 3 domains of HRQL including energy/vitality (p = 0.02), role functioning (p = 0.01), and social functioning (p = 0.04).ConclusionsModerate to severe OSA is very common but has no impact on digital micro-vascular endothelial function in patients with T2D.

Adverse Health Events Following Intermittent and Continuous Androgen Deprivation in Patients With Metastatic Prostate Cancer.

Although intermittent androgen-deprivation therapy (ADT) has not been associated with better overall survival in prostate cancer (PC), it has the potential for lower adverse effects. To our knowledge, the incidence of long-term adverse health events has not been reported. To examine long-term late events in elderly patients randomized to intermittent or continuous ADT to determine whether late cardiovascular and endocrine events would be lower in patients treated with intermittent ADT. This was a secondary analysis of a multicenter clinical trial using linkage between patient data from S9346, a randomized SWOG trial of intermittent vs continuous ADT in men with metastatic PC, and corresponding Medicare claims. Intermittent or continuous ADT. The main outcome was to identify long-term adverse health events by treatment arm. Patients were classified as having an adverse health event if they had any hospital claim--or at least 2 physician or outpatient claims at least 30 days apart--for any of the following diagnoses: ischemic and thrombotic events, endocrine events, sexual dysfunction, dementia, and depression. To incorporate time from beginning of observation through evidence of an event, we determined the cumulative incidence of each event. Competing risks Cox regression was used, adjusting for covariates. In total, 1134 eligible US-based male patients with metastatic PC were randomized to continuous vs intermittent ADT in the S9346 trial. A total of 636 of trial participants (56%) had at least 1 year of continuous Medicare parts A and B coverage and no health maintenance organization participation. The median age was 71.3 years. The most common long-term events were hypercholesterolemia (31%) and osteoporosis (19%). The 10-year cumulative incidence of ischemic and thrombotic events differed by arm; 24% for continuous and 33%for intermittent ADT (hazard ratio, 0.69; P = .02). There were no statistically significant differences by arm in any other adverse health events. Contrary to our hypothesis that intermittent ADT would reduce long-term health-related events compared with continuous ADT, we found that older men assigned to intermittent ADT had no apparent reduction in bone, endocrine, or cognitive events and an increased incidence of ischemic and thrombotic events. clinicaltrials.gov Identifier: NCT00002651.

Minimized contrast use with intravascular ultrasound-guidance percutaneous coronary intervention. One-year follow-up of the MOZART randomized study

ABSTRACT Background Recently, the MOZART study demonstrated that using intravascular ultrasound (IVUS) for guiding percutaneous coronary intervention (PCI) reduces the volume of contrast used in the procedure. The authors assessed the incidence of late adverse cardiovascular events in these patients. Methods Patients at risk for contrast-induced nephropathy (CIN) or volume overload were randomized to angiography-guided versus IVUS-guided PCI, and followed-up for a 1-year period. Results Eighty-three patients were included in the angiography-guided (n = 42) or IVUS-guided (n = 41) groups, of whom 77.1% were diabetics and 44.6% had creatinine clearance 2 . Clinical and angiographic characteristics did not differ between the groups. Most had type B2/C lesions (89.8%) and a median of two stents were used (interquartile range: 1.0-2.0 stents). The duration of IVUS-guided PCI was 14 minutes longer than the angiography-guided PCI group ( p = 0.006). However, the groups did not differ regarding fluoroscopy time or mean image acquisitions per procedure. CIN occurred in 19.0% vs. 7.3% ( p = 0.26). During the 1-year follow-up, 12% of patients had a major cardiovascular event, with two deaths (one in each group), and no differences were found between groups. Conclusions The contrast reduction strategy with IVUS-guided PCI in patients at risk for CIN or volume overload was shown to be safe in the short and long term.

Long-Term Outcomes in Patients With Diabetes Mellitus Related to Prolonging Clopidogrel More Than 12 Months After Coronary Stenting

BackgroundRecent large clinical trials show lower rates of late cardiovascular events by extending clopidogrel >12 months after percutaneous coronary revascularization (PCI). However, concerns of increased bleeding have elicited support for limiting prolonged treatment to high-risk patients. ObjectivesThe aim of this analysis was to determine the effect of prolonging clopidogrel therapy >12 months versus ≤12 months after PCI on very late outcomes in patients with diabetes mellitus (DM). MethodsUsing the Veterans Health Administration, 28,849 patients undergoing PCI between 2002 and 2006 were categorized into 3 groups: 1) 16,332 without DM; 2) 9,905 with DM treated with oral medications or diet; and 3) 2,612 with DM treated with insulin. Clinical outcomes, stratified by stent type, ≤4 years after PCI were determined from the Veterans Health Administration and Medicare databases and risk was assessed by multivariable and propensity score analyses using a landmark analysis starting 1 year after the index PCI. The primary endpoint of the study was the risk of all-cause death or myocardial infarction (MI). ResultsIn patients with DM treated with insulin who received drug-eluting stents (DES), prolonged clopidogrel treatment was associated with a decreased risk of death (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42 to 0.82) and death or MI (HR: 0.67; 95% CI: 0.49 to 0.92). Similarly, in patients with noninsulin-treated DM receiving DES, prolonged clopidogrel treatment was associated with less death (HR: 0.61; 95% CI: 0.48 to 0.77) and death or MI (HR: 0.61; 95% CI: 0.5 to 0.75). Prolonged clopidogrel treatment was not associated with a lower risk in patients without DM or in any group receiving bare-metal stents. ConclusionsExtending the duration of clopidogrel treatment >12 months may decrease very late death or MI only in patients with DM receiving first-generation DES. Future studies should address this question in patients receiving second-generation DES.

Preoperative Cardiovascular Assessment and Late Cardiovascular Events after Elective Abdominal Aortic Aneurysm Repair

Cardiovascular evaluation is performed before elective repair of abdominal aortic aneurysm (AAA) because of the high prevalence of cardiovascular disease. We investigated the association between preoperative cardiovascular evaluation and the incidence of late cardiovascular events after AAA repair. We retrospectively analyzed 438 patients who underwent elective repair of AAA. Echocardiography, serial coronary assessment using functional myocardial scanning or coronary angiography, and carotid ultrasound scanning were performed preoperatively. Coronary revascularization after serial coronary assessment was performed preoperatively or simultaneously in 21 patients, and 54 patients had a remote history of coronary revascularization. The 5-year survival rate, incidence rate of cardiovascular events (myocardial infarction or stroke), and incidence rate of major adverse cardiovascular events (MACE; cardiovascular death or cardiovascular events) were 86.0%, 5.7%, and 11.5%, respectively. Carotid stenosis was associated with these long-term outcomes, and hypokinesis, determined by echocardiography, increased the incidence of cardiovascular events and MACE. Serial coronary assessment findings and history of previous or preoperative coronary revascularization were not associated with these long-term outcomes. Preoperative cardiovascular evaluation and treatment are beneficial for reducing not only perioperative risk but also late cardiovascular events.

“CARDIOVASCULAR and Metabolic Complications in Patients with Hematological Malignancies Undergoing Allogeneic Hematopoietic STEM CELL Transplantation (HSCT)”

▪Background: HSCT has greatly improved the prognosis of patients affected by hematological malignancies leading to more long-term survivors. However, long-term survivors are at increased risk of developing complications; cardiovascular complications are relatively rare but, on the other hand, it seems quite common to develop cardiovascular risk factors like: arterial hypertension (AH), diabetes, dyslipidemia.Aims of the study: to observe the incidence and outcome of patients developing cardiovascular risk factors (CVRF) and cardiovascular events (CVE) after allo-HSCT, eventually identifying patient and HSCT-related risk factors for CVE (CVE predictors).Materials and methods: We retrospectively analyzed 300 patients undergoing allo-HSCT from January 2006 to December 2009. Patients were considered long-term survivors and suitable for the analysis if they were alive at 2 years after HSCT. Following variables were recorded: diagnosis, sex, age at time of HSCT, comorbidities and pre-existing risk factors, BMI, previous chemotherapy with anthracyclines, donor type, disease status at time of HSCT, conditioning regimens with or without total body irradiation (TBI), onset of acute or chronic graft versus host disease (aGVHD and cGvHD), treatment with high doses corticosteroids after HSCT. We observed incidence and outcome of early (within 2 years) and late (after 2 years) CVRF and CVE in long-term survivors; CVE were divided in non-serious (grade1-2) and serious (grade 3-4) if they required or not hospitalization. Dichothomius variables were compared with Chi-Square test or Fisher’s exact test. Continuous variables were compared with Student’s T-Test. Median Follow-Up duration was estimated with Kaplan Meier reverse survival method. Multiple linear regression models were built for multivariate analysis of CVE incidence. A two-sided p value <0.05 (<0.02 for multivariate analysis) was considered statistically significant.Results: 4 of 300 patients died of acute heart failure within 2 years from HSCT. 149 patients were alive at least 2 years after HSCT, and 125 patients (83%) were alive at the time of last follow-up, with a median follow-up of 2384 days (range 722-3098) and a median age of 40 years (range 15-72). Overall crude mortality was 24/ 149 (17%), of whom 16 patients dying of disease recurrence (66%) and 8 patients (34%) dying due to non-relapse causes (Non Relapse Mortality, NRM). Non-serious CVE were observed in 42 patients (28%), whereas serious CVE were reported in 23 cases (15%; 5 acute coronary syndrome, 4 heart failure, 5 cardiac arrythmias, 5 cerebrovascular events, 2 aortic aneurism, 2 pericarditis), with 11 patients experiencing both. Regarding CVRF, post-HSCT AH was observed in 62 patients (42%), dyslipidemia in 124 pts (83%), diabetes in 29 pts (19%). In univariate analysis older age was associated with a higher risk of developing late diabetes (p 0.025), early and late AH (p<0.001), any CVE (p=0.04). cGVHD was associated with a higher risk of early AH (p 0.018), while aGVHD, advanced disease at HSCT and use of high dose of corticosteroids were associated with serious CVE (respectively p=0.039,p=0.025,p=<0.0001). In multivariate analysis, Event Free Survival (EFS) for any CVE was lower in case of older age (p=0.01), acute and chronic GvHD (p=0.010, p=0.006), pre-existing AH (p=0.001) and smoke abuse (p=0.01), reduced intensity conditioning regimens (p=0.03), and high dose corticosteroids treatment (p=0.001). Furthermore, serious CVE were associated with male sex, reduced intensity conditioning regimen, use of TBI within conditioning regimens, older age, and pre-existing AH (respectively p=0.006, p=0.026, p=0.002, p=0.009, p=0.038). Older age was also associated with the development of late AH (p=0.001) and late diabetes (p=0.025)Conclusions: Older allo-HSCT patients have an higher risk of developing any CVE and any CVRF than age-matched non-hematologic population; interestingly, prolonged treatment with high dose steroids also seems to play a role. CVE do not show nowadays a high impact on survival since they seems to be an uncommon complication of HSCT. Furthermore an increasing number of late CVRF has been observed, possibly leading to late cardiovascular events in the future and should therefore be monitored. DisclosuresNo relevant conflicts of interest to declare.

Cardiac function and cardiac events 1-year postpartum in women with congenital heart disease

Pregnancy is increasingly common in women with congenital heart disease (CHD), but little is known about long-term cardiovascular outcome after pregnancy in these patients. We studied the incidence of cardiovascular events 1-year postpartum and compared cardiac function prepregnancy and 1-year postpartum in women with CHD. From our national, prospective multicenter cohort study, 172 women were studied. Follow-up with clinical evaluation and echocardiography and NT-proBNP measurement were performed during pregnancy and 12 months postpartum. Cardiovascular events were defined as need for an urgent invasive cardiovascular procedure, heart failure, arrhythmia, thromboembolic events, myocardial infarction, cardiac arrest, cardiac death, endocarditis, and aortic dissection. Cardiovascular events were observed after 11 pregnancies (6.4%). Women with cardiovascular events postpartum had significant higher NT-proBNP values at 20-week gestation (191 [137-288] vs 102.5 [57-167]; P = .049) and 1-year postpartum compared with women without cardiovascular events postpartum (306 [129-592] vs 105 [54-187] pg/mL; P = .014). Women with cardiovascular events during pregnancy were at higher risk for late cardiovascular events (HR 7.1; 95% CI 2.0-25.3; P = .003). In women with cardiovascular events during pregnancy, subpulmonary end-diastolic diameter had significantly increased 1-year postpartum (39.0 [36.0-48.0] to 44.0 [40.0-50.0]; P = .028). No other significant differences were found in cardiac function or size 1-year postpartum compared with preconception values. Cardiovascular events are relatively rare 1 year after pregnancy in women with CHD. Women with cardiovascular events during pregnancy are prone to develop cardiovascular events 1-year postpartum and have increased subpulmonary ventricular diameter compared with preconception values.

Effects of intra-abdominal sepsis on atherosclerosis in mice.

IntroductionSepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis.MethodsWe performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE−/−) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE−/− mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation.ResultsApoE−/− mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (−6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2 and vascular cell adhesion molecule 1) and the adhesion assay, a functional measure of endothelial activation, were elevated at 72 hours and 120 hours in mice that underwent CLP versus sham-operations (all at P <0.05).ConclusionsUsing a combination of existing murine models for atherosclerosis and sepsis, we found that CLP, a model of intra-abdominal sepsis, accelerates atheroma development. Accelerated atheroma burden was associated with prolonged systemic, endothelial and intimal inflammation and was not explained by ongoing infection. These findings support observations in humans and demonstrate the feasibility of a long-term follow-up murine model of sepsis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0469-1) contains supplementary material, which is available to authorized users.

C-reactive protein and brain natriuretic peptide as predictors of adverse events after lower extremity endovascular revascularization

High-sensitivity C-reactive protein (hsCRP) and brain natriuretic peptide (BNP) have been shown to be independent predictors of adverse cardiovascular outcomes and increased risk of secondary interventions or limb loss in patients with peripheral arterial disease (PAD). To assist clinicians in decision-making about treatment approaches and predicting postprocedure mortality and morbidity, we retrospectively examined patients with preprocedure hsCRP and BNP levels who underwent elective angioplasty or stent placement for lower extremity PAD. The study period was from January 1, 2007, to December 31, 2012, and patients were included who had angioplasty or stenting for PAD. Minimal required follow-up for study inclusion was at least one postoperative ankle-brachial index, contrast angiography, or duplex imaging of the treated limb. Events of interest included major adverse limb events (MALE), defined as target vessel revascularization, amputation, or disease progression by 1 year, and major adverse cardiovascular events (MACE; stroke, myocardial infarction, or death) by 2 years. Elevated/abnormal values for our biomarkers of interest were established by the upper limits of our institution's clinical laboratory reference range (hsCRP, >0.80 mg/dL; BNP, >100 pg/mL). A total of 159 limbs in 118 patients were included in analysis (42% men; median age [range], 64 [42-87] years). All limbs were symptomatic (Rutherford classification: 1-6). Iliac artery revascularization without other adjunct lower extremity intervention was performed in 60% of the limbs. High hsCRP levels (>0.80 mg/dL) were present in 32 patients (27%) and high BNP values (>100 pg/mL) in 24 patients (20%). Kaplan-Meier analysis with log-rank comparison demonstrated that elevated hsCRP levels were associated with MALE but only in limbs receiving interventions distal to the iliac arteries (P = .005). High BNP levels did not affect MALE rates (P = .821). Conversely, both elevated BNP levels (hazard ratio, 5.6; 95% confidence interval [CI], 2.0-5.8; P = .001) and hsCRP levels (hazard ratio, 2.9; 95% CI, 1.1-7.6; P = .034) predicted MACE at 2 years in the presence of confounders in Cox proportional hazards multivariate analysis. Patients with high preintervention values of hsCRP and BNP were 10.6 times (95% CI, 2.6-42.9; P = .001) more likely to experience MACE than were patients with normal hsCRP and BNP values. After lower extremity endovascular interventions, elevated preprocedural hsCRP levels are associated with MALE (femoral-popliteal interventions), and elevated levels of hsCRP and BNP are associated with late cardiovascular events.

C-Reactive Protein and Brain Natriuretic Peptide as Predictors of Adverse Events Following Lower Extremity Endovascular Revascularization

High sensitivity-C-reactive protein (CRP) and brain natriuretic peptide (BNP) have been shown to be independent predictors of adverse cardiovascular outcomes and potentially increased risk of secondary interventions or limb loss in patients with peripheral arterial disease (PAD). To assist clinicians in predicting postprocedure mortality and morbidity and decision-making regarding treatment approaches, we retrospectively examined patients with preprocedure CRP and BNP levels who underwent elective angioplasty and/or stent placement for lower extremity PAD. The study period included patients treated between 2007 and 2012. Minimal required follow-up was at least one postoperative ankle brachial index or duplex imaging of the treated limb. Events of interest included clinical limb failure (loss of patency, target vessel revascularization, decrease in ankle brachial index >0.15 or limb amputation) by 1 year and MACE (stroke, myocardial infarction or death) by 2 years. Elevated/ abnormal values for our biomarkers of interest were established by the upper limited of our institution's clinical laboratory reference range hs-CRP (<0.80 mg/dL), BNP (<100 pg/mL). A total of 159 limbs in 118 patients were included in analysis (42% male, mean age 64 ± 11 years). All limbs were symptomatic (Rutherford classification, 2-5). Iliac artery revascularization without other adjunct lower extremity intervention was performed in 60% of the limbs. High CRP levels (>0.80 mg/dL) were present in 32 (27%) patients and high BNP values (>100 pg/mL) in 24 (20%) patients. Kaplan-Meier analysis with log-rank comparison demonstrated that elevated CRP levels associated with clinical limb failure but only in limbs receiving interventions distal to the external iliac artery (P < .01). High BNP levels did not affect limb failure (0.91). Conversely, high BNP levels associated with a statistically elevated MACE rate at 2 years of 36% vs 14% in patients with normal BNP levels (P = .01). Patients with high CRP trended toward having higher rates of MACE (33% vs 14%) but failed to meet statistical significance (P = .053). Patients with high preintervention values of CRP and BNP were 10.6 times (95% confidence interval, 2.6-42.6; P < .01) more likely to experience MACE than patients with normal CRP and BNP values. Preprocedure biochemical markers in endovascular interventions for PAD can aide in predicting future limb related complications and late cardiovascular events. Potentially, improving biochemical markers prior to intervention could improve outcomes.

EComment. Renal dysfunction may predict early and late cardiovascular events

We read with interest the article 'Impact of occult renal impairment on early and late outcomes following coronary artery bypass grafting' by Marui et al. [1]. They concluded that occult renal impairment was an independent risk factor for early and late death as well as cardiovascular events in patients undergoing CABG with normal creatinine levels. CABG is closely related to renal dysfunction. Serum creatinine level is the most common test for renal failure. The glomerular filtration rate (GFR) provides more sensitive information about renal function than the serum creatinine level. The GFR can be measured by the formula of modification of diet in renal disease (MDRD) and the Cockcroft-Gault equation. GFR was estimated using the simplified Cockcroft-Gault equation in the current study [1]. However, the Cockcroft-Gault equation may estimate lower GFR in younger age groups compared with the MDRD formula, but it can measure higher GFR in older individuals compared with the MDRD formula [2]. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently published an equation for GFR using the same variables (serum creatinine level, age, sex and race) as the MDRD formula. However, the CKD-EPI equation more precisely categorized individuals with respect to long-term clinical risk of incident end-stage renal disease, all-cause mortality, coronary heart disease and stroke compared with the MDRD formula [3]. In conclusion, renal dysfunction is an important factor in predicting early and late outcomes following CABG. Novel methods for measurement of GFR in patients having CABG will enlighten future studies. Conflict of interest: none declared

Prognostic value of 256-row coronary computed tomography angiography in symptomatic patients with a history of coronary artery bypass surgery

Purpose: Contrast-enhanced 256-row coronary computed tomography angiography (CCTA) has high diagnostic accuracy for diagnosing coronary stenosis, but its role in predicting late clinical outcome events in pts with a history of coronary artery bypass surgery (CABG) has not been well studied. Methods: We examined the predictive value of CCTA for late major adverse cardiovascular (CV) outcome events (MACE) (CV death or non-fatal MI) in 170 pts (136 (80%) men) with a history of CABG (average 2.9 grafts/pt) who presented with a chest pain syndrome. Outcome events in relation to graft patency/occlusion and extent of native vessel coronary artery disease (CAD) by CCTA were evaluated using Cox models. Results: On CCTA, 151/491 (31%) grafts were occluded (38/232 (16%) arterial, 113/259 (44%) venous). 115/170 (67%) pts had high risk native coronary anatomy (HRCA) (triple vessel and/or left main CAD). During a mean follow-up of 2.5±1.4 years MACE occurred in 33/170 (19%) pts (MACE rate 7.6%/year); CV death in 21/170 (12%) and non fatal MI in 12/170 (7%). By univariate analysis, presence of ≥2 occluded grafts on CCTA was associated with a twofold increase in MACE (30% (14/46) vs 15% (19/124), HR=2.1, p=0.04) (Figure), and remained significant (HR 2.1, p=0.03) after adjusting for other variables (age, gender, coronary risk factors, LV function, native vessel HRCA). ![Figure][1] Conclusions: In pts with a history of CABG undergoing evaluation for a chest pain syndrome; presence of ≥2 occluded grafts on CCTA was associated with increased risk of CV death or MI during 2.5 years follow-up. 256-row CCTA is useful in predicting late clinical outcome events after CABG. [1]: pending:yes

Renal Dysfunction and Atherosclerosis of the Neointima following Bare Metal Stent Implantation

Background: Recently, neoatherosclerosis within the neointima after bare metal stent (BMS) implantation, which could cause late restenosis and very late stent thrombosis, has been a cause of concern. Renal dysfunction has been related to late cardiovascular events after coronary intervention. The present study was conducted focusing on the relationship between renal dysfunction and neointimal tissue characteristics with BMS restenosis using integrated backscatter intravascular ultrasound (IB-IVUS). Methods: We prospectively performed IB-IVUS in 80 consecutive patients requiring target lesion revascularization after BMS implantation; the patients were divided into two groups according to the estimated glomerular filtration [eGFR: ≥60 (n = 49) and <60 ml/min/1.73 m² (n = 31)]. Results: Patients with eGFR <60 ml/min/1.73 m² had a significantly higher percentage of lipid tissue volume within the neointima and a lower percentage of fibrous tissue volume than those with eGFR ≥60 ml/min/1.73 m² (23.2 ± 9.4 vs. 18.0 ± 7.0%, p = 0.005, and 75.3 ± 9.3 vs. 80.4 ± 7.0%, p = 0.007, respectively). Using logistic regression analysis, eGFR <60 ml/min/1.73 m² and duration from stent implantation ≥48 months were independent predictors of increased lipid tissue volume within the neointima (odds ratio, 3.93; 95% confidence interval, 1.15-13.46, p = 0.03, and odds ratio, 7.56; 95% confidence interval, 2.02-28.30, p = 0.003, respectively). Conclusions: Lower eGFR levels were associated with greater lipid tissue volume within the neointima after BMS deployment, suggesting the development of atherosclerosis. Renal dysfunction may affect neointimal tissue characteristics and thus leading to an increased risk of late stent failure.

Prognostic significance of high sensitivity C-reactive protein in patients with angina pectoris underwent percutaneous coronary intervention

C-reactive protein is an easily measurable acute phase reactant synthesized by hepatocytes in response to pro-inflammatory cytokines. Elevated CRP has been identified as a strong predictor of prognosis in healthy individuals, in patients with stable angina, in unstable angina and in patients after acute myocardial infarction. The prognostic significance of high sensitivity CRP level in percutaneous coronary intervention is unclear. We prospectively studied 41 patients with chronic stable angina (28 patients) and unstable angina (13 patients) who underwent elective coronary stenting. All patients had normal troponin level before the procedure. Blood samples for hs_CRP were obtained before the procedure, 24 h after the procedure. Patients followed up at 1 month and after 2 years. Mean hs_CRP before the procedure in all patients underwent PCI was 2.38 ± 2.21 μg/ml. The mean hs_CRP 24 h post procedure was 7.43 ± 10.6 μg/ml. There was significant difference between pre procedural hs-CRP and 24 h post procedural ( P = 0.007) At follow up period (1 month), No major adverse cardiac events (MACE) have occurred. However, 24 patients complain of chest pain. There was no significant correlation between either pre-procedural, or 24 h post procedure hs-CRP and chest pain ( r = 0.13, 0.2, respectively). At follow up period (2 years), 7 cases missed; MACE has occurred in 13 patients. Mechanical disruption of atherosclerotic plaque during elective coronary stent implantation causes a systemic inflammatory response. Measuring of hs-CRP either pre-procedural or post procedural in low risk patients is not useful for predicting of either early or late cardiovascular events.