Yaron Arbel

Neutrophil/lymphocyte ratio is related to the severity of coronary artery disease and clinical outcome in patients undergoing angiography

BACKGROUND White blood cell count is an independent predictor of cardiovascular events and mortality. Neutrophil/lymphocyte ratio (NLR) is a biomarker that can single out individuals at risk for vascular events. OBJECTIVE To evaluate whether NLR adds additional information beyond that provided by conventional risk factors and biomarkers for coronary artery disease (CAD) severity and adverse outcome, in a large cohort of consecutive patients referred for coronary angiography. MATERIALS AND METHODS NLR was computed from the absolute values of neutrophils and lymphocytes from the complete blood count of 3005 consecutive patients undergoing coronary angiography for various indications. CAD severity was determined by an interventional cardiologist unaware of the study aims. The association between NLR and CAD severity was assessed by logistic regression and the association between NLR and 3-years outcome were analyzed using Cox regression models, adjusting for potential clinical, metabolic, and inflammatory confounders. RESULTS The cohort was divided into 3 groups according to the NLR value (<2, 2-3, and >3). NLR was independently associated with CAD severity and it contributed significantly to the regression models. Patients with NLR >3 had more advanced obstructive CAD (OR = 2.45, CI 95% 1.76-3.42, p < 0.001) and worse prognosis, with a higher rate of major CVD events during up to 3 years of follow-up (HR = 1.55, CI 95% 1.09-2.2, p = 0.01). CONCLUSION Neutrophil/lymphocyte ratio is independently associated with CAD severity and 3-years outcome. NLR value appears additive to conventional risk factors and commonly used biomarkers.

Prevalence and Predictors of Concomitant Carotid and Coronary Artery Atherosclerotic Disease

OBJECTIVES The purpose of this research was to evaluate the relationship between coronary and carotid atherosclerotic disease using current guidelines for the definition of carotid artery stenosis (CAS). BACKGROUND The reported prevalence of concomitant coronary and carotid atherosclerotic disease has varied among studies due to differences in study populations and methodologies used. METHODS We performed a retrospective analysis of prospectively collected data obtained between January 2007 and May 2009 from consecutive patients undergoing same-day coronary angiography and carotid Doppler studies. Spearman correlations and multinomial logistic regression models were used to identify independent correlates of CAS. RESULTS The study included 1,405 patients (age 65 ± 11 years, 77.2% male), of whom 12.8% had significant CAS (peak systolic velocity [PSV] >125 cm/s) and 4.6% had severe CAS (PSV >230 cm/s). Mild CAS (PSV <125 cm/s and the presence of a sonographic atherosclerotic lesion) was present in 58%. The severity of CAS and the extent of coronary artery disease (CAD) were significantly correlated (r = 0.255, p < 0.001). Independent predictors of severe CAS defined by PSV were the presence of left-main or 3-vessel CAD, increasing age, a history of stroke, smoking status, and diabetes mellitus. CONCLUSIONS The degree of internal carotid artery (ICA) stenosis is related to the extent of CAD, though the prevalence of clinically significant ICA stenosis is lower in specific CAD subsets than previously reported.

Inflammatory Bowel Disease Is Not Associated With Increased Intimal Media Thickening

OBJECTIVES:Several studies have suggested that chronic inflammatory diseases might be associated with an acceleration of the atherosclerotic process. There is little information on the effect of chronic inflammation in patients with inflammatory bowel disease (IBD) on the presence of increased intimal media thickening (IMT), a surrogate marker for atherosclerotic diseases. In this work our aim was to determine whether IBD is a risk factor for increased IMT.METHODS:IMT was measured by ultrasound of the carotid arteries; a computer software program was used to analyze 80–100 independent IMT samples from each carotid artery segment in 61 patients with IBD (45 with Crohns disease and 16 with ulcerative colitis) and in 61 controls matched for age (±2 yr), sex, body mass index (BMI, ±2 kg/m2), and smoking status.RESULTS:Inflammatory markers (erythrocyte sedimentation rate, fibrinogen, high−sensitive C-reactive protein) were significantly (P < 0.001) elevated in IBD patients compared with controls. Even though there was a disease duration of 8.7 ± 8.5 yr, the mean IMT of IBD patients was similar to that of the control group (0.66 ± 0.09 vs 0.64 ± 0.07 mm; P > 0.05).CONCLUSIONS:Despite chronic inflammation, IBD patients had IMT values similar to those of the controls. Thus, unlike other inflammatory diseases, IBD appears not to be a risk factor for accelerated atherosclerosis.

Red blood cell distribution width and the risk of cardiovascular morbidity and all-cause mortality. A population-based study.

Red blood cell distribution width (RDW) has been shown to predict cardiovascular mortality in various populations, but studies were less conclusive regarding cardiovascular morbidity. We aimed at evaluating the prognostic effect of RDW on cardiovascular morbidity and all-cause mortality in the largest community cohort to date.We utilised the computerised database of a large community based healthcare maintenance organization (HMO) in Israel to identify a cohort of 225,006 eligible patients aged 40 or above who performed a blood count during 2006. We evaluated the relationship between 1% increments of RDW values and major cardiovascular events and all-cause mortality over a period of five years. A total of 21,939 incident cases of a major cardiovascular event and 4,287 deaths were documented during a total of six years of follow up, respectively. In comparison with patients with RDW level <13%, the hazard ratio for total mortality gradually increased to 4.57 (95% confidence interval [CI]: 3.35-6.24, p<0.001) among male patients and to 3.26 (95% CI: 2.49-4.28, p<0.001) among female patients with a RDW of 17% or above. Similar results were evident in anaemic and non-anaemic populations. RDW above 17% was also associated with a modest increased risk of major cardiovascular events in females 1.26 (95% CI: 1.03-1.52, p=0.021), while in men it was not significant, 1.08 (95% CI: 0.82-1.41, p=NS). In conclusion, increasing RDW levels significantly increased risk of cardiovascular morbidity and all-cause mortality. Our observation is evident in both anaemic and non-anaemic patients.

Comparison of early and late outcomes of TAVI alone compared to TAVI plus PCI in aortic stenosis patients with and without coronary artery disease

To assess the safety and effectiveness of performing percutaneous coronary intervention (PCI) before transcatheter aortic valve implantation (TAVI).

Correlated Expression of High-Sensitivity C-Reactive Protein in Relation to Disease Activity in Inflammatory Bowel Disease: Lack of Differences between Crohn’s Disease and Ulcerative Colitis

Background/Aims: As opposed to regular C-reactive protein (CRP) assays, the introduction of high-sensitivity ones has enabled us to detect low grade inflammation in patients with inflammatory bowel disease (IBD). We addressed the subject of the degree of correlation between the concentration of high-sensitivity CRP (hs-CRP) and the inflammatory IBD activity score. Methods: Included were 90 patients with Crohn’s disease (CD), 70 with ulcerative colitis (UC) and 160 controls. Disease activity was determined using CD activity index (CDAI) for CD and Mayo score for UC. The Dade Boering BNII Nephelometer was used to determine the hs-CRP concentrations. Results: The coefficient of correlation between hs-CRP and the disease activity score was similar for both UC (0.26) and CD (0.36). Conclusions: These findings are relevant for therapeutic intervention in which a greater absolute reduction in the hs-CRP concentration in CD patients (who generally present higher CRP concentrations than those found in UC) might be interpreted as a better response compared to the same absolute reduction in UC patients. This information is needed for clinicians using the hs-CRP assay to estimate IBD disease activity in daily practice.

Decline in serum cholinesterase activities predicts 2-year major adverse cardiac events.

Parasympathetic activity influences long-term outcome in patients with cardiovascular disease, but the underlying mechanism(s) linking parasympathetic activity and the occurrence of major adverse cardiovascular events (MACEs) are incompletely understood. The aim of this pilot study was to evaluate the association between serum cholinesterase activities as parasympathetic biomarkers and the risk for the occurrence of MACEs. Cholinergic status was determined by measuring the cumulative capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to hydrolyze the AChE substrate acetylthiocholine. Cholinergic status was evaluated in randomly selected patients undergoing cardiac catheterization. The patients were divided into two groups of 100 patients in each group, with or without occurrence of MACEs during a follow-up period of 40 months. Cox regression models adjusted for potential clinical, metabolic and inflammatory confounders served to evaluate association with clinical outcome. We found that patients with MACE presented lower cholinergic status and AChE values at catheterization (1,127 ± 422 and 359 ± 153 nmol substrate hydrolyzed per minute per milliliter, respectively) than no-MACE patients (1,760 ± 546 and 508 ± 183 nmol substrate hydrolyzed per minute per milliliter, p < 0.001 and p < 0.001, respectively), whose levels were comparable to those of matched healthy controls (1,622 ± 303 and 504 ± 126 nmol substrate hydrolyzed per minute per milliliter, respectively). In a multivariate analysis, patients with AChE or total cholinergic status values below median showed conspicuously elevated risk for MACE (hazard ratio 1.85 (95% confidence interval (CI) 1.09–3.15, p = 0.02) and 2.21 (95% CI 1.22–4.00, p = 0.009)) compared with those above median, even after adjusting for potential confounders. We conclude that parasympathetic dysfunction expressed as reduced serum AChE and AChE activities in patients compared to healthy controls can together reflect impaired parasympathetic activity. This impairment predicts the risk of MACE up to 40 months in such patients. Monitoring these parasympathetic parameters might help in the risk stratification of patients with cardiovascular disease.

The Obesity Paradox in Patients Undergoing Transcatheter Aortic Valve Implantation

Obesity is a major risk factor for cardiovascular morbidity and mortality. A considerable number of studies, however, showed better outcomes for overweight patients undergoing cardiovascular interventions—the so called obesity paradox.

Platelet Inhibitory Effect of Clopidogrel in Patients Treated With Omeprazole, Pantoprazole, and Famotidine: A Prospective, Randomized, Crossover Study

Concerns about an inhibitory effect of proton pump inhibitors (PPIs) on clopidogrel metabolism have been raised. Because the pharmacological effect of clopidogrel is dependent on genetically determined activity of the hepatic cytochrome P450 isoenzymes system, it is important to examine the interaction between different PPIs and high on‐treatment platelet reactivity (HPR) after controlling for genetic variability. The aim of the study was to assess the effect of 2 PPIs and a histamine‐2 (H2) receptor‐blocker on platelet reactivity in a crossover trial where each patient was alternately treated with each drug.

Erythrocyte aggregation as a cause of slow flow in patients of acute coronary syndromes

BACKGROUND There are multiple lines of evidence to suggest the role of erythrocyte aggregation (EA) in microcirculatory dysfunction during conditions of very slow flow. Such conditions might develop in the myocardium of patients with acute coronary syndromes (ACS). METHODS EA as a function of shear stress was evaluated by using a cell flow properties analyzer (CFA) in a cohort of 91 ACS patients and in 36 patients with non specific chest pain or heart failure at the time of cardiac catheterization. RESULTS The ACS group included 34 patients with acute myocardial infarction and 57 patients with unstable angina. In addition, we examined 36 patients who underwent angiography for non specific chest pain or heart failure. A significant (r=0.44, p<0.0005) correlation was found between the concentration of fibrinogen and the average aggregate size (AAS) only when using conditions of very slow flow and applying relatively low (0.15 dyn/cm(2)) shear stress in the ACS group. This correlation decreased and became insignificant when applying shear stress forces of 1 dyn/cm(2) and more. This correlation was nonsignificant for all the 5 shear stress forces (between 0.15 and 4 dyn/cm(2)) in the samples obtained from the non-ACS group. CONCLUSION Erythrocytes that are suspended in autologous plasma obtained from patients with ACS tend to aggregate in conditions of very slow flow. These findings might be detrimental in terms of microcirculatory flow in ACS patients and might open new therapeutic options such as the use of low dose thrombolysis following PCI.