NLRP3 and downstream cytokine expression elevated in the monocytes of patients with coronary artery disease

Introduction

Pattern recognition receptor (PRR)-mediated signaling pathways have recently been elucidated to bridge the innate immune system and atherosclerosis. NLRP3 is among the family members of NOD-like receptors (NLRs), a type of PRRs. At present, most studies about the NLRP3 inflammasome focus on animal models and immune cells. Limited information is available regarding the role of NLRP3 in patients with coronary artery disease (CAD).

Material and methods

In this study, we observed the expression of NLRP3 and downstream cytokines in patients with CAD by ELISA, real-time qPCR and Western blot.

Results

We found that NLRP3 and downstream cytokines were coupled with increasing severity of CAD and a dynamic variation exists in patients with acute myocardial infarction. We also found that NLRP3 was correlated with Gensini score, indicating that NLRP3 might be relevant not only for the severity of CAD but also for the severity of coronary atherosclerosis.

Conclusions

This study provides a new theoretical basis for innate immune participation in atherosclerosis development and highlights the potential of the NLRP3 inflammasome as a target for prevention and treatment of CAD.     

Comparing mortality and myocardial infarction between coronary artery bypass grafting and drug-eluting stenting in patients with diabetes mellitus and multivessel coronary artery disease: a meta-analysis

Introduction

We aim to compare the midterm outcomes between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in diabetic patients who had multivessel coronary artery diseases (CAD).

Material and methods

A comprehensive literature search was conducted to identify the related clinical studies with a follow-up for 1 year at least. The endpoints were death, myocardial infarction, and major adverse cardiac and cerebrovascular events (MACCE).

Results

Finally, the analysis of ten studies involving 5,264 patients showed that patients with CABG had worse baseline characteristics, a higher rate of stable angina pectoris, a higher percentage of triple-vessel disease, higher incidence of chronic total occlusion and a higher SYNTAX score. However, there was no significant difference in mortality between the two groups. Additionally, the rates of myocardial infarction and MACCE were markedly decreased in the CABG group.

Conclusions

The strategy of CABG is better than PCI for diabetic patients with multivessel CAD. The CABG can significantly reduce the rates of myocardial infarction and MACCE and is comparable in mortality despite the worse baseline characteristics.     

Aortic valve calcification in 499 consecutive patients referred for computed tomography

Introduction

Aortic valve calcification (AVC) is the most common cause of aortic stenosis. The aim of the study was to assess the prevalence of aortic valve, coronary artery and aortic calcifications and to evaluate the correlation between calcification of the aortic valve, coronary arteries and aorta.

Material and methods

The study included 499 patients aged 60 years and over who underwent coronary computed tomography because of chest pain. Beside coronary artery calcium score (CAC), we evaluated AVC and ascending aorta calcifications (AAC).

Results

Aortic valve calcification was found in 144 subjects (28.9% of the whole study population). Prevalence of CAC and AAC was higher than AVC and amounted to 73.8% and 54.0%. Prevalence of AVC, CAC and AAC was significantly lower in the group of patients ≤ 70 years than in the group of patients > 70 years of age (p = 0.0002, p < 0.0001, p < 0.0001). Aortic valve calcification was more often observed in men than women (34.7% vs. 25.4%, p = 0.02). Degree of aortic valve calcification was also significantly higher among men than women (median score 4 vs. 0, p = 0.01). Similar observations were true for CAC and AAC, where both prevalence and degree of calcification was higher among men than women. In the whole study population no correlation was noted between AVC and CAC or AAC (p = 0.34, p = 0.85). There was a significant correlation between AAC and CAC (p < 0.0001).

Conclusions

Despite some similarities in pathological mechanism and risk factors, a degenerative defect of the aortic valve could be independent of atheromatous lesions in the coronary arteries and aorta.     

Comparison of Common Carotid Artery Intima-Media Thickness Between Brazilian Euro-Descendants and Afro-Descendants with Atherosclerosis Risk Factors

OBJECTIVE:

To compare common carotid intima-media thickness (IMT) between the two major Brazilian ethnic groups (those of African descent and those of European descent) among individuals with one or more risk factors for atherosclerotic disease.

METHOD:

Two hundred and six patients with one or more risk factors for atherosclerotic disease were evaluated in a cross-sectional study in which their clinical, ethnic and Demographic characteristics were collected. All patients underwent duplex ultrasound examination of their carotid vessels to obtain IMT measurements.

RESULTS:

One hundred and fifty-three patients (74.3%) had a carotid IMT greater than 1.0 mm at one or more point of measurement in at least one common carotid artery. There was a significant correlation between older age and mean carotid wall thickness (R=0.479 / P<0.01). Multivariate analysis identified male sex, arterial hypertension and older age as variables associated with increased IMT (P<0.05 for all variables). When IMT was compared between the two ethnic groups in this study, no significant differences were noted. Euro-descendants and Afro-descendants had similar IMT values, even when the groups were stratified by degree of IMT (normal vs. increased) and presence of stroke and/or transient ischemic attack (yes vs. no).

CONCLUSIONS:

The risk factors associated with increased common carotid artery IMT in Brazilian individuals are similar to those in previously described populations. No differences were observed between the two main Brazilian ethnic groups. Longitudinal studies are required for a better evaluation of the incidence, etiologic factors and evolution of carotid intimomedial thickening in this population.     

The relationship between coronary artery calcification and renal function in nondialyzed patients

Purpose

Coronary artery calcification (CAC) has been described in individuals with chronic kidney disease (CKD), and its presence is associated with an increased risk of cardiovascular death. However, it is unclear whether there is an independent relationship between renal function and CAC. Therefore, we evaluated the association between renal function and CAC.

Materials and Methods

We retrospectively reviewed 870 Korean patients who had undergone computed tomographic coronary angiography. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease study formula with an ethnic factor for the Korean population. The CKD stages were classified using estimated GFR (eGFR) and proteinuria.

Results

The mean age of the participants was 56.8±11.8 years, and the mean eGFR was 89.4±16.5 mL/min/1.73 m². Hypertension and diabetes were noted in 41.5 and 17.0% of patients, respectively. There were 584 and 286 patients with no CAC and with CAC, respectively. After adjusting for confounding variables, late stage CKD was associated with CAC [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.05-7.46]. However, early stage CKD was not associated with CAC (OR 1.61, 95% CI 0.92-2.82). Diabetes was an independent risk factor of CAC (OR 2.06, 95% CI 1.36-3.13). There was no significant association between proteinuria and CAC (OR 1.65, 95% CI 0.96-2.85).

Conclusion

CAC is related to late stage CKD in nondialyzed patients. These findings emphasize that individuals with CAC should be considered a high-risk population for decreased renal function.     

Association between serum inhibin-B levels and coronary artery disease in aging males

Introduction

Atherosclerosis is a systemic disorder. It is a frequent leading cause of coronary artery disease (CAD). Similarly, atherosclerotic vascular alterations could lead to testicular arterial blood flow reduction and impairment of testicular function with age. Inhibin-B has been validated as a valuable serum marker of testicular functions and its correlation with testicular volume was shown in some studies done before. The purpose of this study is to investigate the association between serum inhibin-B levels and CAD in elderly men.

Material and methods

Between March 2009 and March 2010, fifty-two 50-80-year-old consecutive patients with Gensini score over 20 and ejection fraction (EF) > 50% were included in the study as the CAD group. Fifty healthy men without any cardiac disease history were recruited as the control group. All patients in the CAD group who had indications for coronary artery angiography underwent selective coronary artery angiography.

Results

Inhibin-B, total testosterone and testicular volume levels were found to be significantly lower in the CAD group in comparison with the control group (p = 0.004, p < 0.0001, and p = 0.001 respectively).

Conclusions

In this study, although no correlation was found in CAD patients between Gensini score and inhibin-B or testicular volume, inhibin-B levels and testicular volume were significantly lower in patients with CAD than in healthy men. In order to fully assess the relationship between serum inhibin-B levels and CAD, multi-centered prospective and longitudinal studies must be done in elderly male patients.     

Epicardial adipose tissue and pericoronary fat thickness measured with 64-multidetector computed tomography: potential predictors of the severity of coronary artery disease

OBJECTIVE:

The aim of the present study was to investigate the relationship between pericoronary fat and the severity and extent of atherosclerosis, quantified using 64-multidetector computed tomography, in patients with suspected coronary artery disease.

METHODS:

The study population consisted of 131 patients who were clinically referred for noninvasive multislice computed tomography coronary angiography for the evaluation of coronary artery disease. Patients were classified as follows: no atherosclerosis, Group 1; nonobstructive atherosclerosis (luminal narrowing <50% in diameter), Group 2; and obstructive atherosclerosis (luminal narrowing ≥50%) in a single vessel or obstructive atherosclerosis in the left main coronary artery and/or multiple vessels, Group 3. Epicardial adipose tissue was defined as the adipose tissue between the surface of the heart and the visceral layer of the pericardium (visceral epicardium). Epicardial adipose tissue thickness (mm) was determined in the right ventricular anterior free wall. The mean thickness of the pericoronary fat surrounding the three coronary arteries was used for the analyses.

RESULTS:

The average thickness over all three regions was 13.2 ± 2.1 mm. The pericoronary fat thickness was significantly increased in Group 3 compared with Groups 2 and 1. The epicardial adipose tissue thickness was significantly increased in Group 3 compared with Groups 2 and 1. A receiver operating characteristic curve for obstructive coronary artery disease was assessed to verify the optimum cut-off point for pericoronary fat thickness, which was 13.8 mm. A receiver operating characteristic curve for obstructive coronary artery disease was also assessed to verify the optimum cut-off point for epicardial adipose tissue, which was 6.8 cm.

CONCLUSION:

We showed that the epicardial adipose tissue and pericoronary fat thickness scores were higher in patients with obstructive coronary artery diseases.     

Risk factor reduction in progression of angiographic coronary artery disease

Introduction

To investigate differences between outpatients with progressive and nonprogressive coronary artery disease (CAD) measured by coronary angiography.

Material and methods

Chart reviews were performed in patients in an outpatient cardiology practice having ≥ 2 coronary angiographies ≥ 1 year apart. Progressive CAD was defined as 1) new non-obstructive or obstructive CAD in a previously disease-free vessel; or 2) new obstruction in a previously non-obstructive vessel. Coronary risk factors, comorbidities, cardiovascular events, medication use, serum low-density lipoprotein cholesterol (LDL-C), and blood pressure were used for analysis.

Results

The study included 183 patients, mean age 71 years. Mean follow-up duration was 11 years. Mean follow-up between coronary angiographies was 58 months. Of 183 patients, 108 (59%) had progressive CAD, and 75 (41%) had nonprogressive CAD. The use of statins, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and aspirin was not significantly different in patient with progressive CAD or nonprogressive CAD Mean arterial pressure was higher in patients with progressive CAD than in patients with nonprogressive CAD (97±13 mm Hg vs. 92±12 mm Hg) (p<0.05). Serum LDL-C was insignificantly higher in patients with progressive CAD (94±40 mg/dl) than in patients with nonprogressive CAD (81±34 mg/dl) (p=0.09).

Conclusions

Our data suggest that in addition to using appropriate medical therapy, control of blood pressure and serum LDL-C level may reduce progression of CAD.     

Transthoracic measurement of left coronary artery flow reserve improves the diagnostic value of routine dipyridamole-atropine stress echocardiogram

Introduction

We hypothesized that coronary flow reserve (CFR) in the left anterior descending artery (LAD) can be effectively measured during an accelerated dipyridamole-atropine stress echocardiography (DASE) protocol to improve the diagnostic performance of the test.

Material and methods

In 64 patients with suspected or known coronary artery disease scheduled for coronary angiography DASE with concomitant CFR measurement in LAD was performed.

Results

Coronary flow reserve measurement and calculation were feasible in 83% of patients. The positive predictive value of undetectable LAD flow was 81% for severe LAD disease. Measured values of CFR were in the range 1.3–4.1 (mean: 2.2 ±0.7). Significantly lower CFR was found in patients with LAD disease (1.97 ±0.62 vs. 2.55 ±0.57, p = 0.0015). The optimal cutoff for detecting ≥ 50% stenosis was CFR ≤ 2.1 (ROC AUC 0.776), corresponding with 68% sensitivity and 84% specificity. In patients with negative DASE results 67% of patients with LAD disease had abnormal CFR, whereas in patients with a positive DASE result 92% of patients with normal LAD had normal CFR. The DASE diagnostic accuracy for the detection of coronary artery disease (CAD) increased from 75% to 85% when CFR measurement was added to wall motion abnormality (WMA) analysis. No test with both abnormalities was false positive for the detection of coronary disease.

Conclusions

Incorporation of CFR measurement into WMA-based stress echocardiography is feasible even in an accelerated DASE protocol and can be translated into an approximate gain of 10% in overall test accuracy.     

Using ultrasound radio frequency technology to assess regression of the structure and function of the carotid artery by radioiodine therapy in hyperthyroidism patients

Introduction

The aim of the study was to investigate the structure and function of the carotid artery in patients with hyperthyroidism by ultrasound radio frequency data technology (RF data) and the effect of ¹³¹I on them.

Material and methods

Seventy patients with primary hyperthyroidism and 74 healthy volunteers were enrolled in this study. Structural and functional parameters of the common carotid artery were measured in every patient before and after ¹³¹I treatment through the RF data, such as intima media thickness (IMT), functional compliance coefficient (CC), stiffness index (β), and pulse wave velocity (PWV). We also analyzed the correlation between these parameters and patients’ age, body mass index, hemodynamic parameters (blood pressure, heart rate), thyroid hormone levels and other risk factors.

Results

There was a significant difference in IMT between hyperthyroid patients and the control group at baseline (483.6 vs. 443.3 µm, p < 0.01); after treatment, the IMT decreased significantly (428.7 vs. 483.6 µm, p < 0.001). Furthermore, the IMT was correlated with patients’ age and systolic blood pressure (r = 0.525, p < 0.01 and r = 0.289, p < 0.05, respectively). The β and PWV were also higher than the control group (7.26 vs.5.87, 6.27 vs. 5.57 m/s, respectively; all p < 0.001); CC was lower than the control group (0.98 vs. 1.19 mm²/KPa, p < 0.01); after treatment, PWV and β were lower than baseline (5.66 vs. 6.27, 5.81 vs. 7.26 m/s, respectively; all p < 0.01), and CC was higher than baseline. In addition, they were significantly correlated with age (r = 0.525, p < 0.01 and r = 0.289, p < 0.05, respectively). However, these parameters were not correlated with the level of thyroid hormones.

Conclusions

Six-month ¹³¹I treatment for patients with hyperthyroidism reverses the structural and functional damage in the carotid artery, which is sensitively evaluated by the RF data technique.     

Association between soluble lectin-like oxidized low-density lipoprotein receptor 1 levels and coronary slow flow phenomenon

Introduction

The coronary slow flow phenomenon (CSFP) has been associated with myocardial ischemia, myocardial infarction, life-threatening arrhythmias, sudden cardiac death and increased cardiovascular mortality similar to coronary artery disease (CAD). Possible underlying mechanisms of CSFP are endothelial dysfunction, chronic inflammation, microvascular dysfunction and diffuse atherosclerosis. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) seems to play an important role in the pathogenesis of atherosclerosis. We hypothesized that sLOX-1 might be associated with CSFP, and aimed to research the relationship between sLOX-1 and CSFP.

Material and methods

Forty patients with angiographically proven CSFP and 43 patients with a normal coronary flow pattern (NCFP) were included in this study. Coronary blood flow was measured according to the Thrombolysis In Myocardial Infarction (TIMI) frame count method. sLOX-1 levels were measured in all study subjects.

Results

Serum levels of sLOX-1 were significantly higher in the CSFP group than the NCFP group (1061.80 ±422.20 ng/ml vs. 500.043 ±282.97 ng/ml, p < 0.001, respectively). Multivariate logistic regression analysis including sLOX-1, MPV, GGT and uric acid levels revealed a significant association between sLOX-1 levels and CSFP (Exp (B)/OR: 1.006, 95% CI: 1.002–1.010, p = 0.001).

Conclusions

The present study demonstrated that serum sLOX-1 levels were significantly higher in patients with CSFP and there was a strong association between high sLOX-1 levels and CSFP. High serum sLOX-1 levels may have an important role in the pathogenesis of CSFP. Future studies are needed to confirm these results.     

Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease

Introduction

CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy.

Material and methods

The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic parameters in Caucasian patients with early onset coronary artery disease. The study group comprised 100 patients. Electrocardiography and echocardiography were performed in all patients. Amplicons of exons 4 to 6 including fragments of introns were studied using the denaturing high-performance liquid chromatography technique.

Results

IVS3-6TC (rs3173798) heterozygotes had impaired left ventricle diastolic function. 573GA heterozygotes (rs5956) had higher frequency of pseudonormal left ventricular diastolic function and it was confirmed by the increase in wave A’ in the tissue Doppler. 591AT genotype was associated with borderline higher posterior wall end-diastolic thickness and lower E/A ratio. These results are consistent with electrocardiography parameters which could reflect left ventricular hypertrophy (higher R_V5(6) and R_V5(6) + S_V1(2) parameters, depressed ST segments and tendency to longer Qtc II interval) in 591AT heterozygotes.

Conclusions

Detected variant alleles of CD36 may be associated with features of left ventricular hypertrophy and impaired diastolic function.     

Induction of anesthesia in coronary artery bypass graft surgery: the hemodynamic and analgesic effects of ketamine

OBJECTIVE

The aim of this prospective, randomized study was to evaluate the hemodynamic and analgesic effects of ketamine by comparing it with propofol starting at the induction of anesthesia until the end of sternotomy in patients undergoing coronary artery bypass grafting surgery.

INTRODUCTION

Anesthetic induction and maintenance may induce myocardial ischemia in patients with coronary artery disease. A primary goal in the anesthesia of patients undergoing coronary artery bypass grafting surgery is both the attenuation of sympathetic responses to noxious stimuli and the prevention of hypotension.

METHODS

Thirty patients undergoing coronary artery bypass grafting surgery were randomized to receive either ketamine 2 mg.kg⁻¹ (Group K) or propofol 0.5 mg.kg⁻¹ (Group P) during induction of anesthesia. Patients also received standardized doses of midazolam, fentanyl, and rocuronium in the induction sequence. The duration of anesthesia from induction to skin incision and sternotomy, as well as the supplemental doses of fentanyl and sevoflurane, were recorded. Heart rate, mean arterial pressure, central venous pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index, systemic and pulmonary vascular resistance indices, stroke work index, and left and right ventricular stroke work indices were obtained before induction of anesthesia; one minute after induction; one, three, five, and ten minutes after intubation; one minute after skin incision; and at one minute after sternotomy.

RESULTS

There were significant changes in the measured and calculated hemodynamic variables when compared to their values before induction. One minute after induction, mean arterial pressure and the systemic vascular resistance index decreased significantly in group P (p<0.01).

CONCLUSION

There were no differences between groups in the consumption of sevoflurane or in the use of additional fentanyl. The combination of ketamine, midazolam, and fentanyl for the induction of anesthesia provided better hemodynamic stability during induction and until the end of sternotomy in patients undergoing coronary artery bypass grafting surgery.     

The effect of postoperative positive end-expiratory pressure on postoperative bleeding after off-pump coronary artery bypass grafting

Introduction

To compare postoperative prophylactic use of two positive end-expiratory pressure (PEEP) levels in order to prevent postoperative bleeding in patients undergoing off-pump coronary artery bypass grafting (CABG) surgery.

Material and methods

Sixty patients undergoing an elective off-pump CABG operation were included in this prospective, nonrandomized clinical trial. Patients were divided into two groups as receiving either 5 cm H₂O (group 1) or 8 cm H₂O PEEP (group 2) after the operation until being extubated. Chest tube outputs, use of blood products and other fluids, postoperative hemoglobin levels, accumulation of pleural and pericardial fluid after the removal of chest tubes, and duration of hospital stay were recorded and compared.

Results

Low- and high-pressure PEEP groups did not differ with regard to postoperative chest tube outputs, amounts of transfusions and crystalloid/colloid infusion requirements, or postoperative hemoglobin levels. However, low-pressure PEEP application was associated with significantly higher pleural (92 ±37 ml vs. 69 ±29 ml, p = 0.03) and pericardial fluid (17 ±5 ml vs. 14 ±6 ml, p = 0.04) accumulation. On the other hand, high-pressure PEEP application was associated with significantly longer duration of hospitalization (6.25 ±1.21 days vs. 5.25 ±0.91 days, p = 0.03).

Conclusions

Prophylactic administration of postoperative PEEP levels of 8 cm H₂O, although safe, does not seem to reduce chest-tube output or transfusion requirements in off-pump CABG when compared to the lower level of PEEP. Further studies with larger sample sizes are warranted to confirm the benefits and identify ideal levels of PEEP administration in this group of patients.     

Comparison of coronary artery bypass grafting with percutaneous coronary intervention for unprotected left main coronary artery disease

Purpose

Coronary artery bypass grafting (CABG) is the optimal treatment option for left main coronary artery disease (LMCAD). However, LMCAD remains a constant topic of discussion between cardiac surgeons and interventional cardiologists. The aim of this study was to assess the efficacy of LMCAD treatments by comparing the mid-term outcomes of CABG and percutaneous coronary intervention (PCI) using bare metal stents or drug-eluting stents (DESs).

Materials and Methods

The study population was comprised of 199 consecutive patients admitted with unprotected LMCAD. All of the patients were assigned to PCI (88 patients) or CABG (111 patients). The primary clinical end point indicated death, stroke of acute coronary syndrome (ACS).

Results

Patients assigned to PCI were at higher operative risk than patients scheduled for CABG (6.49±4.09 vs. 4.81±2.67, p=0.0032). Comparison of the group that received DESs with the CABG group did not reveal any differences in major adverse cardio-cerebral events (MACCE) occurrence (21% vs. 16%, p=NS). Patients in the CABG and PCI groups died with similar frequency (11% vs. 16%, p=NS). The mortality rate in the CABG group was higher than among those treated with DES (11% vs. 3%, p=0.049). The rate of ACS was higher in the PCI group than in the CABG group (13% vs. 4%, p=0.016).

Conclusion

Despite the fact that patients treated with PCI were at higher operative risk, PCI with DES was shown to be comparable to CABG in terms of mortality, stroke and ACS. However, the frequency of repeat revascularizations remains a constant concern with PCI.     

Serum protein profiles predict coronary artery disease in symptomatic patients referred for coronary angiography

Background

More than a million diagnostic cardiac catheterizations are performed annually in the US for evaluation of coronary artery anatomy and the presence of atherosclerosis. Nearly half of these patients have no significant coronary lesions or do not require mechanical or surgical revascularization. Consequently, the ability to rule out clinically significant coronary artery disease (CAD) using low cost, low risk tests of serum biomarkers in even a small percentage of patients with normal coronary arteries could be highly beneficial.

Methods

Serum from 359 symptomatic subjects referred for catheterization was interrogated for proteins involved in atherogenesis, atherosclerosis, and plaque vulnerability. Coronary angiography classified 150 patients without flow-limiting CAD who did not require percutaneous intervention (PCI) while 209 required coronary revascularization (stents, angioplasty, or coronary artery bypass graft surgery). Continuous variables were compared across the two patient groups for each analyte including calculation of false discovery rate (FDR ≤ 1%) and Q value (P value for statistical significance adjusted to ≤ 0.01).

Results

Significant differences were detected in circulating proteins from patients requiring revascularization including increased apolipoprotein B100 (APO-B100), C-reactive protein (CRP), fibrinogen, vascular cell adhesion molecule 1 (VCAM-1), myeloperoxidase (MPO), resistin, osteopontin, interleukin (IL)-1β, IL-6, IL-10 and N-terminal fragment protein precursor brain natriuretic peptide (NT-pBNP) and decreased apolipoprotein A1 (APO-A1). Biomarker classification signatures comprising up to 5 analytes were identified using a tunable scoring function trained against 239 samples and validated with 120 additional samples. A total of 14 overlapping signatures classified patients without significant coronary disease (38% to 59% specificity) while maintaining 95% sensitivity for patients requiring revascularization. Osteopontin (14 times) and resistin (10 times) were most frequently represented among these diagnostic signatures. The most efficacious protein signature in validation studies comprised osteopontin (OPN), resistin, matrix metalloproteinase 7 (MMP7) and interferon γ (IFNγ) as a four-marker panel while the addition of either CRP or adiponectin (ACRP-30) yielded comparable results in five protein signatures.

Conclusions

Proteins in the serum of CAD patients predominantly reflected (1) a positive acute phase, inflammatory response and (2) alterations in lipid metabolism, transport, peroxidation and accumulation. There were surprisingly few indicators of growth factor activation or extracellular matrix remodeling in the serum of CAD patients except for elevated OPN. These data suggest that many symptomatic patients without significant CAD could be identified by a targeted multiplex serum protein test without cardiac catheterization thereby eliminating exposure to ionizing radiation and decreasing the economic burden of angiographic testing for these patients.

     

Point of care serum lactate levels as a prognostic marker of outcome in complex pediatric cardiac surgery patients: Can we utilize it?

Background:

Post-operative course after complex pediatric cardiac surgery is unpredictable. Although, change in arterial lactate levels has been used as a surrogate marker for many years, scientific evidence correlating the early perioperative lactate levels with outcome is still lacking.

Objective:

To evaluate the trends in lactate levels from intraoperative period to an extended post-operative period in pediatric intensive care unit (PICU) and to assess its usefulness as a prognostic marker.

Design:

Prospective observational study.

Setting:

Tertiary pediatric cardiac surgical unit.

Patients:

Thirty-five non-consecutive children aged 1-140 months who underwent surgery for congenital heart diseases (CHD) on cardiopulmonary bypass (CPB).

Intervention:

None.

Materials and Methods:

Arterial blood lactate levels were obtained at the following time points: After induction of anesthesia, 15 and 45 min after institution of CPB, at the start of rewarming, after sternotomy closure, then at 1, 6, 24, and 48 h in PICU. Other hemodynamic and clinical variables, CPB variables, blood gas values, and laboratory variables were also recorded.

Results:

Four patients died out of 35 patients (11.4%). Non-survivors showed significant persistent elevation in lactates (>4.0 mmol/l). Peak lactates correlate significantly with longer aortic cross clamp time, CPB duration, ventilation hours and PICU stay.

Conclusion:

Early point of care lactate can be a useful prognostic marker in post-cardiac surgery patients in adjunct with other parameters measured in PICU. This reiterates the importance of measuring lactates and timely recognition of at-risk patients, which on early intervention can help in reducing post-operative morbidity and mortality.     

Simultaneous transfer of cholesterol, triglycerides, and phospholipids to high-density lipoprotein in aging subjects with or without coronary artery disease

OBJECTIVE:

To verify whether the capacity of high-density lipoprotein (HDL) to simultaneously receive non-esterified cholesterol, triglycerides, cholesteryl esters, and phospholipids changes with aging and the presence of coronary artery disease.

DESIGN:

Cross-sectional study with biochemical analyses.

SUBJECTS:

Eleven elderly patients with coronary artery disease (74±5 years) were compared with the following groups of non-coronary artery disease subjects (referred to as “healthy”): 25 young (25±5 years), 25 middle-aged (42±6 years), and 25 elderly subjects (75±8 years).

METHODS:

Plasma samples were incubated with a nanoemulsion labeled with radioactive lipids; the transfer of the lipids from the nanoemulsion to the HDL was measured in chemically precipitated HDL. HDL size and paraoxonase-1 activity were also determined.

RESULTS:

The transfer of cholesteryl esters and phospholipids to high-density lipoprotein was significantly greater (p<0.001) in healthy elderly subjects than in the middle-aged and younger subjects. Non-esterified cholesterol and triglyceride transfer was not different among these three groups. The HDL size was significantly greater (p<0.001) in healthy elderly subjects than in the middle-aged and younger subjects. The paraoxonase-1 activity was similar among the groups. Compared with healthy elderly subjects, coronary artery disease elderly subjects had significantly less (p<0.05) transfer of non-esterified cholesterol, triglycerides, and cholesteryl esters to the HDL and a significantly smaller (p<0.05) HDL size.

CONCLUSION:

Because lipid transfer is enhanced in healthy elderly subjects but not in those with coronary artery disease, increasing lipid transfer to HDL may be a protective mechanism against the disease.     

Vascular Calcifications Seen on Mammography: An Independent Factor Indicating Coronary Artery Disease

PURPOSE

Establish a relationship between vascular calcifications seen via mammography and coronary artery disease, estimate the risk ratios, and investigate the interrelationships between vascular calcification and other risk factors for coronary artery disease.

MATERIALS AND METHODS

This was a case-control study consisting of 40 women with coronary artery disease in the case group and 40 women without any history of coronary artery disease in the control group who were matched according to age. The study was approved by the Institution’s Research Ethics Committee (consent statement was obtained). Odds ratios and confidence intervals were calculated using univariate analysis. Interrelationships among other risk factors, such as arterial hypertension, dyslipidemia, smoking and diabetes mellitus, were calculated using multivariate analysis. A p <0.05 was considered to be significant for statistical analysis.

RESULTS

The mean ages for the case and control groups were 64.65 years and 63.88 years, respectively. In multivariate analysis, the only variables related to coronary artery disease were Vascular calcification [OR 4.71 (CI 1.36–16.33) p=0.014], family history [OR 5.76 (CI 1.58–21.03) p=0.008] and arterial hypertension [OR 15.92 (CI 3.12–81.14) p=0.001]. Although smoking and diabetes are important variables in the pathogenesis of coronary artery disease, these factors did not show statistically significant associations in this sample.

CONCLUSION

The presence of vascular calcifications seen via mammography was an independent risk factor for coronary artery disease, as were hypertension and a family history of coronary artery disease.     

Vasoconstrictive effects of levobupivacaine on the basilar artery in the rabbit

Introduction

Spinal anesthesia is a widely used technique of the modern practice of anesthesia. Spinal cord ischemia is a rare but catastrophic complication of spinal anesthesia which may be caused by a direct vasoconstrictive effect of the local anesthetic. Although the vasoconstrictive effects of levobupivacaine have been widely studied, the vasoconstrictive effects of this drug on the intradural arteries have never been studied. The aim of this study is to evaluate whether levobupivacaine has vasoconstrictive effects on the basilar artery in rabbits.

Material and methods

Thirty male New Zealand white rabbits were divided randomly into three groups of ten rabbits each: group 1 (control); group 2 (0.125% levobupivacaine); group 3 (0.25% levobupivacaine). The cisterna magna was punctured as described below, then 1 ml of saline or 0.125% or 0.25% levobupivacaine was injected into the cisterna magna in 10 min by an infusion pump in groups 1, 2 and 3 respectively. All animals were euthanized by perfusion-fixation 30 min after the procedure. The luminal area and the size of the cross-sectional area for each basilar artery were measured.

Results

Both 0.125% and 0.25% levobupivacaine infusion caused significant vasoconstriction. Vasoconstriction was more significant for the 0.125% concentration.

Conclusions

The results of this study indicated that both 0.125% and 0.25% concentrations of levobupivacaine caused significant vasoconstriction of the basilar artery when administered into the subarachnoid space. This may constitute proof that subarachnoid administration of levobupivacaine may diminish the spinal cord blood flow, causing ischemia.