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Objectives: Examiningthe usefulness of C-reactive protein velocity (CRPv) as an early biomarker for the presence of bacteraemia in patients presenting to the Department of Emergency Medicine with acute infection/inflammation and suspected bacteraemia., Methods: A retrospective study examining a cohort of patients who presented to the E.R and in whom blood cultures were taken. CRPv was calculated as the difference in mg/hour/litter between two consecutive CRP tests performed within 12 h., Results: 256 patients were included in the cohort. Using CRPv in patients who at first presented with a relatively low (17.9 ≤ mg/L 1stquartile) CRP concentration, we found an AUC of 0.808 ± 0.038 (p < 0.001) for the presence of positive versus negative blood cultures (what is AUC?). This was better than the AUC that was obtained when the WBC for the same purpose., Conclusions: CRPv may be a useful biomarker in the identification of patients with suspected bacteremiaand a low CRP-a challenging situation for clinicians who may underestimate the severity of illness in this patient group., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population worldwide, and its prevalence is anticipated to increase globally. While most NAFLD patients are asymptomatic, NAFLD may progress to fibrosis, cirrhosis, cardiovascular disease, and diabetes. Research reports, with daunting results, show the challenge that NAFLD's burden causes to global population health. The current process for identifying fibrosis risk levels is inefficient, expensive, does not cover all potential populations, and does not identify the risk in time. Instead of invasive liver biopsies, we implemented a non-invasive fibrosis assessment process calculated from clinical data (accessed via EMRs/EHRs). We stratified patients' risks for fibrosis from 2007 to 2017 by modeling the risk in 5579 individuals. The process involved time-series machine learning models (Hidden Markov Models and Group-Based Trajectory Models) profiled fibrosis risk by modeling patients' latent medical status resulted in three groups. The high-risk group had abnormal lab test values and a higher prevalence of chronic conditions. This study can help overcome the inefficient, traditional process of detecting fibrosis via biopsies (that are also medically unfeasible due to their invasive nature, the medical resources involved, and costs) at early stages. Thus longitudinal risk assessment may be used to make population-specific medical recommendations targeting early detection of high risk patients, to avoid the development of fibrosis disease and its complications as well as decrease healthcare costs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Detection of an eventful course in the early days of sepsis treatment is clinically relevant. The white blood cell count (WBCC) and C-reactive protein (CRP) are used in daily practice to monitor the intensity of the inflammatory response associated with sepsis. It is not entirely clear which of the two might better discriminate the outcomes of patients with sepsis., Methods: 30-day mortality was assessed in a cohort of patients who were hospitalized with sepsis in the departments of Internal Medicine in a tertiary medical center. Admission and 72-hour time points were analyzed to discriminate between patients with increased versus decreased 30 days mortality risk., Results: The study included 195 patients. Higher 72 h CRP, WBCC, neutrophil counts and neutrophils to lymphocyte ratio were associated with increased mortality (p < 0.02). Baseline WBCC and CRP failed to discriminate between patients who died and those who survived (AUC = 0.551, 0.479). In multivariate analysis of the 72 h tests, higher WBCC count (OR = 1.12, 95%CI 1.05-1.20, p = 0.001), was associated with increased mortality whereas CRP was not (OR = 1.004, 95%CI 0.998-1.01, p = 0.146)., Conclusion: Patients who presented a 72-hour leukocyte descent had a better outcome and in this regard, WBCC was superior to 72-hour CRP in predicting 30 days mortality., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: Parasympathetic dysfunction is associated with increased risk for major adverse cardiovascular events (MACE). However, clinically validated biomarkers that reflect parasympathetic activity are not yet available. We sought to assess the ability of serum cholinesterase activity to predict long term survival in patients undergoing coronary angiography., Methods: We prospectively followed 1002 consecutive patients undergoing clinically indicated coronary angiography (acute coronary syndrome or stable angina). We measured blood acetylcholinesterase (AChE) activity using the acetylcholine analog acetylthiocholine. Mortality rates were determined up to 10 years of follow-up. We divided our cohort into 3 groups with low, intermediate and high AChE activity by a Chi-square automatic interaction detection method (CHAID)., Results: Patients with lower than cutoff levels of AChE (<300 nmol/min/ml) had higher mortality rates over 10 years of follow-up, after adjusting for conventional risk factors, biomarkers, clinical indication, and use of medications (HR = 1.6, 95% CI 1.1-2.5, p = 0.02). Patients with intermediate levels of AChE (300-582 nmol/min/ml) were also at increased risk for death (HR = 1.4, 95% CI 1.1-1.9, p = 0.02). AChE was inversely correlated with C-reactive protein, troponin I, fibrinogen and neutrophil/lymphocyte ratio levels., Conclusions: Patients presenting for coronary angiography with low levels of serum AChE activity are at increased risk for death during long term follow-up., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: C-reactive protein (CRP) is considered a marker of inflammation. We sought to evaluate the association between CRP level and commonly use blood tests in apparently healthy population., Methods: A cross-sectional study of all visits in a routine health examination center between 1/2002 and 7/2018. CRP, complete blood count and chemistry blood panel were evaluated in each visit. Visits of individuals who had CRP above the 99th percentile or use statins were excluded. Correlation between CRP and blood tests was evaluated in the whole cohort as well as in sub-populations., Results: Blood parameters of 33,261 visits were included. Moderate positive correlation between CRP and white blood cells count (r = 0.269), neutrophils count (r = 0.275), triglycerides (r = 0.275), alkaline phosphatase (r = 0.221) and gamma glutamyl transpeptidase (r = 0.220) was evaluated. Correlation with triglycerides was stronger in female then in males (r = 0.38 vs. 0.25). Uric acid was positively correlated in females and males. In participants under 30 years, inverse correlation with hemoglobin, creatinine and albumin levels and positive correlation with cholesterol were documented., Conclusion: Significant moderate association between CRP and several blood tests was evaluated in apparently healthy population. This information should be used for further studies of the relationship between inflammation and biological processes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The importance of the inflammatory processes and C-reactive protein (CRP) evaluation was observed. Only few studies used cut-off value <1 mg/L. We sought to evaluate the association between very low CRP (vlCRP) and health status, to describe the repetition of vlCRP and to identify predictors for repetition., Methods: A historical cohort study of all participants who underwent a routine annual check-up between January 2002 and July 2018 at the Tel Aviv Sourasky medical center. CRP test was evaluated in all participants. Individuals who use statins or with CRP >10 mg/L were excluded. CRP ≤0.12 mg/L was considered as vlCRP., Results: The final study cohort included 14,161 individuals. Of them, 5065 were females and mean age was 43.4 years (SD 10.6). vlCRP at first check-up was observed in 1299 (9.2%) of the participants. In multivariable analysis, older age, hyperlipidemia, hypertension and smoking were significantly associated with lower probability of vlCRP. At the second check-up, 50.1% vlCRP repetition was observed with no significant predictor from previous visit., Conclusion: vlCRP is associated with younger age, non-smoking, and absence of hyperlipidemia and of hypertension. However, it may also be part of the individual physiology., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Lung function is inversely associated with coronary heart disease and cardiovascular disease. High-sensitive cardiac troponin T (hs-cTnT) was recently found to represent early subclinical cardiac disease even in healthy individuals. We explored the inter-relationship between lung function and hs-cTnT and the changes over time in these two measurements., Methods: Lung function test and hs-cTnT were determined in apparently healthy individuals from the Tel Aviv Medical Center Inflammatory Survey. Participants with normal lung function were followed up for 5 years in order to evaluate the effect of lung function deterioration on hs-cTnT levels. The correlation between annual Forced vital capacity (FVC) % predicted decline and hs-cTnT levels were analyzed., Results: A 5-year follow-up of 2,618 participants with normal lung function at baseline revealed a mean annual FVC deterioration of 31.9 (±91.3) ml/year. Lung function decline >5% was associated with an increased risk of having hs-cTnT >5 ng/L (Exp. β = 1.55 1.20-1.99, p = 0.001). Delta FVC between two consecutive visits was inversely correlated with an increase of hs-cTnT (r = -0.24, p < 0.001)., Conclusions: Deterioration of lung function predicts elevated troponin levels and may be a sign of early subclinical cardiac disease., (Copyright © 2019. Published by Elsevier Ltd.)

Albuminuria is a prognostic factor for mortality and cardiovascular events, even at low levels. Changes in albumin excretion are associated with end-stage renal disease and hypertension (HTN) in cohorts including high-risk participants. We aimed to investigate the evolvement of albumin excretion in healthy individuals with normal kidney function and normoalbuminuria, and possible associations with HTN and metabolic outcomes. The study cohort consisted of 1967 healthy adults with normal kidney function (estimated glomerular filtration rate ≥ 90 mL/min/1.73 m 2 ; urine albumin to creatinine ratio [ACR] < 30 mg/g). Delta ACR slope was calculated as ACR difference between two consecutive visits divided by the time interval. During a mean follow-up period of 93.8 months, mean delta ACR slope was 0.27 ± 3.29 mg/g/year and was higher in participants with age >40 years, obesity, a high waist circumference, higher baseline ACR, HTN, prediabetes, and metabolic syndrome. Delta ACR slopes in the upper quartile predicted diabetes (OR = 1.31, P = .027) and albuminuria (4.34, P < .001). Upper quartile of ACR slopes correlated with a higher risk for new-onset HTN (1.249, P = .031). Delta systolic and diastolic blood pressures were associated with ACR slopes in addition to age, body mass index, and baseline ACR. In conclusion, accelerated change in ACR correlates with HTN and diabetes in healthy individuals with normal kidney function and normoalbuminuria., (Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.)

Background: Emergency department (ED) revisit might be partially preventable. C-reactive protein (CRP) is an inflammatory biomarker which is commonly used as screening tool in the ED. We sought to evaluate the association between CRP level in patients visiting emergency department and 7 days revisit after discharge., Methods: A historical cohort study of all patients who visited the internal division of the emergency department between June 2007 and July 2017 and had a CRP test. New ED visit was defined when neither any emergency department visit nor any hospital admission was recorded in our files during the previous 90 days. Univariate and multivariate models were used to evaluate the association between CRP and 7 days ED revisit., Results: The study included 135,476 patients with 173,443 new visits. In 101,181 (58.3%) visits the patients were released and 7077 (7%) of them were revisited in 7 days. Even mild elevated CRP (5-25 mg/L) was independently associated with significant risk for revisit (OR 1.27, 95% CI 1.20-1.35)., Conclusion: CRP is an independent predictor for 7 days ED revisit and should be considered at the time of discharge. Prediction models for ED revisit should include CRP as a potential predictor in their models., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: High sensitivity C-reactive protein (hsCRP) has become a routine assessment tool to discriminate between patients at low, intermediate or high risk for cardiovascular events using the threshold values of 1 and 3mg/L, respectively. Over the past years, several studies have proposed the wide range C-reactive protein (wrCRP) as an alternative to the hsCRP in various clinical scenarios. However, the potential use of wrCRP in assessing the cardiovascular risk has not yet been evaluated., Methods: Both wrCRP and hsCRP were evaluated in 15,780 apparently healthy individuals who underwent a routine annual checkup in the Tel Aviv Sourasky Medical Center. Individuals with CRP levels >5mg/L were excluded. Agreement between the two methods was observed using the Bland-Altman method and the concordance correlation coefficient. Deming regression was used to build a calibration equation. Reclassification of individuals' risk level was observed and Cohen's kappa was used to evaluate risk agreement., Results: A high correlation (r=0.98) along with a significant difference (p<0.001) between hsCRP and wrCRP raised the need for calibration. A simple calibration equation (Adjusted wrCRP=0.3136+0.8803×wrCRP) led to high agreement which enabled 8.4% reclassification of the risk group. A change in the intermediate risk threshold value from 1 to 0.9mg/L led to an almost perfect agreement (kappa=0.87, p<0.001) and a low reclassification rate (7.6%), with under 0.05% of the population undergoing a major reclassification (from high to low risk or vice versa)., Conclusions: In the era of limited financial resources, wrCRP assay may be used as a reasonable routine assay to evaluate the cardiovascular risk in patients undergoing a routine annual checkup., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Recent exposure to air pollution has a decremental effect on pulmonary function. This short-term effect has only been studied for up to a few days postexposure. Our objective was to analyze the effect of air pollution on spirometric parameters in varying lag times of up to 1 week from the time of exposure., Methods: Healthy subjects, never smokers, who were participants in the Tel Aviv Sourasky Medical Center Inflammation Survey held between 2002 and 2007, were included if residing within an 11-km range to the nearest air pollution monitoring station. Linear regression models were applied to each lung function variable [first second of exhalation (FEV(1)), forced vital capacity (FVC), FEV(1)/FVC] against air pollutant variables (particulate matter under 10 microns in diameter, sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone) for increasing lag periods of up to 7 days, and they were adjusted for possible confounders that affect air pollution and spirometric measurements., Results: The study population comprised 2380 individuals. We found a statistically significant negative correlation between air pollutants, mainly SO(2), and between FEV(1) and FVC. This effect was significant from days 3 to 6, with a maximal effect noted for the fifth day and for the 7-day average before pulmonary function measurement. No significant change was found for FEV(1)/FVC ratio., Conclusions: Air pollution has a decremental effect on lung function parameters for up to 6 days after exposure in healthy adults. SO(2) emerged as the most significant air pollutant affecting short-term lung function parameters.

Objective: To explore the possibility that mild inflammatory changes exist in asymptomatic adults during bouts of acute respiratory tract infections in the general population, and may mediate atherothrombotic events., Methods: An epidemiological study that enrolled 5315 males and 2795 females attending a routine screening health program between the years 2003 and 2007. We correlated the concentrations of high sensitivity C-reactive protein (hs-CRP) and quantitative fibrinogen in completely asymptomatic and non-inflamed adults to the weekly epidemiological data for the incidence of acute respiratory tract infections in the community., Results: Significant seasonal variations in the inflammatory variables were found for both genders. The population's weekly rates of acute respiratory tract infection had a significant epidemiological influence on the inflammatory biomarkers in the asymptomatic cohort. The magnitude of this influence could reach as much as 12% (3-22%) in hs-CRP concentrations in women and 0.30 micromol/L (0.20-0.41) in fibrinogen concentrations in men, for the change between the mean August and the mean January population's respiratory illness burden., Conclusion: Increase in the concentrations of two inflammation-sensitive biomarkers can occur in completely asymptomatic adults at times of increased burden of acute respiratory tract infection in the general population. The possibility exists that these inflammatory changes represent occult and asymptomatic infections that could by themselves trigger acute atherothrombotic events.

Background: Tumor necrosis factor alpha (TNF-alpha) is a key cytokine in the pathogenesis of ischemia-reperfusion injury (I/R) that also possesses negative inotropic and direct cardiotoxic effects. We investigated whether myocardial ischemia and/or reperfusion is the trigger for TNF-alpha synthesis and whether TNF-alpha release is time dependent., Methods: Isolated rat hearts undergoing 30 min of coronary perfusion with modified Krebs-Henseleit solution followed by cardioplegic arrest for 60 min of global cardioplegic normothermic ischemia (GCI) and 30 min of reperfusion using a modified Langendorff model. Myocardial TNF-mRNA expression and TNF-alpha protein levels in effluent from the coronary sinus were measured at baseline and then after 15, 30, and 60 min of GCI and after 10 and 30 min of reperfusion., Results: GCI induced myocardial TNF-alpha mRNA expression and elevation protein TNF-alpha levels in a time-dependent manner after 30 min of ischemia from 78+/-17 pg/ml to 915+/-287 pg/ml after 60 min (p<0.0015). Reperfusion did not cause time-dependent increase of TNF-alpha synthesis and release but was accompanied by progressive decrease of left ventricular (LV) function. There was a correlation between TNF-alpha protein levels and depression of LV function immediately after GCI but not with TNF-alpha protein levels at 30 min of reperfusion., Conclusion: This study demonstrated that myocardial ischemia rather than reperfusion is the main trigger for time-dependent TNF-alpha synthesis. Depression of LV function during reperfusion correlated significantly only with TNF-alpha levels at the end of GCI.

Background: Ethnic origin affects spirometric prediction values. Our aims were to investigate the effect of ethnic origin on prediction equations in an immigrant-based society, identify possible deviations from commonly used prediction equations and analyze the effect of miscalculation in a large cohort of apparently healthy individuals., Methods: Healthy never-smokers participants from a large Israeli survey underwent lung function testing and were divided into two major ethnic groups: Ashkenazi Jews (AJ) and Sephardic Jews (SJ). Data were analyzed by multiple linear regressions. Forced vital capacity (FVC), forced expiratory volume in 1s (FEV1) and the FEV1/FVC ratio were measured according to ERS-ATS guidelines., Results: The study population comprised 3150 individuals (AJ=1817; SJ=1333). AJ tended to be older and taller than SJ (all p<0.005). Ethnicity entered as a significant regression variable for FVC for both genders and for FEV1 for females only. The final regression model for both FVC and FEV1 had R2=0.71 and the standard error of the estimate (SEE) for FVC and FEV1 were 0.54 and 0.43 L, respectively. The regression model for the FEV1/FVC ratio has less statistical strength (R2=0.06, SEE=6.15%). We found statistically significant underestimates of predicted lung volumes from the commonly used prediction equation for each ethnic group., Conclusions: Ashkenazi and Sephardic Jews have different ranges of normal pulmonary function values. Lung function prediction equations in an immigrant-based society should be based on local and not previously reported regional equations and adjusted for ethnic attributed variance.

Background: C-reactive protein (CRP) has been tested in patients with systolic heart failure (HF) and mixed results have been obtained with regards to its potential predictive value. However, the role of C-reactive protein (CRP) in patients with diastolic HF is not established. We studied the predictive role of high sensitivity CRP (hsCRP) in patients with diastolic HF., Methods: HsCRP levels were measured in a cohort of CHF outpatients, 77 patients with diastolic HF and 217 patients with systolic HF. Concentrations were compared to a large cohort of healthy population (n=7701) and associated with the HF admissions and mortality of the patients., Results: Levels of hsCRP did not differ between patients with systolic and diastolic HF and were significantly elevated compared to the cohort of healthy subjects even after adjustment to various clinical parameters (p<0.0001). In patients with diastolic HF, hsCRP levels associated with New York Heart Association functional class (NYHA-FC) (r=0.31 p=0.01). On univariate Cox regression model hsCRP levels independently predicted hospitalizations in patients with systolic but not diastolic HF (p=0.047)., Conclusion: HsCRP concentrations are elevated in patients with diastolic HF and correlate with disease severity; their prognostic value in this patient population should be further investigated.

Objectives: To evaluate the effect of short-term exposure to air pollutants on inflammation-sensitive biomarkers in apparently healthy individuals., Methods: We enrolled all participants from The Tel-Aviv Sourasky Medical Center inflammation survey held between 2003 and 2006, excluding participants with an acute or chronic inflammatory disease, pregnancy, steroidal or nonsteroidal treatment, or a recent invasive procedure. Additional subjects were excluded for living more than 11km from the nearest air pollution monitoring station. Analysis was performed separately for men and women. Linear regression models were fitted for each inflammatory variable against air pollutant variables (particulate matter under 10microm, sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone) for increasing lag times of up to 7 days, and adjusted for all possible and known confounding parameters., Results: The study population comprised 3659 individuals (2203 males and 1456 females). We found a statistically significant negative correlation in the male population between air pollutants, mainly NO2, SO2, and CO, and fibrinogen in several lag days. A positive correlation was found for PM10 at day 7. No such correlation was found for CRP and WBC, or for the female population., Conclusion: Our findings do not support the potential link between short-term exposure to air pollution and enhanced inflammation as a possible explanation for increased cardiovascular morbidity. Additional large-scale population-based studies with good methodological design are needed in order to clarify this issue.

Objectives: Tumor necrosis factor (TNF)-alpha is known to be a proinflammatory cytokine that has a pronounced negative inotropic effect and plays an important role in ischemic-reperfusion injury., Methods: Twenty isolated rat hearts were randomly divided equally into two groups (heparin and non-heparin) and were perfused with a Krebs-Henseleit solution using a modified Langendorff model. The influence of heparin on the synthesis and release of TNF-alpha by isolated rat hearts after 1 h of global cardioplegic ischemia and on left ventricular (LV) performances during 30 min of postischemic reperfusion was investigated., Results: Significant mean (+/- SEM) amounts of TNF-alpha in myocardial tissue (1,149 +/- 33.7 pg/g) and effluent (951.8 +/- 27.3 pg/mL) from the coronary sinus were detected after global cardioplegic ischemia. The addition of heparin to the cardioplegic solution significantly improved the recovery of LV function in the postischemic heart (p < 0.0001 for all measurements). TNF-alpha protein production in the heparin-treated hearts was below detectable levels despite a postischemic increase of TNF-alpha messenger RNA expression in both heparin-treated hearts and nontreated hearts (0.71 +/- 0.06 and 0.8 +/- 0.12 relative optical density, respectively)., Conclusion: This study shows, for the first time, that heparin causes the inhibition of TNF-alpha protein synthesis and release from the isolated ischemic rat heart within the posttranscriptional stage, and that it prevents the depression of LV function caused by ischemic-reperfusion injury.

Background: The determination of low grade inflammation in apparently healthy individuals (microinflammation) has prognostic significance in terms of future vascular events and accelerated atherothrombotic disease., Methods: We compared the Bayer wide range (wr)-C-reactive protein (CRP) immunoturbidometric assay on the ADVIA 1650 system to the Dade Behring high sensitivity (hs)-CRP on the BNII Nephelometer in 1446 apparently healthy individuals having a relatively low (<10 mg/l) concentration. The correlation between the 2 assays was also analyzed in relation to other commonly used microinflammatory biomarkers., Results: A significant (p<0.0005) correlation was noted between the hs-CRP and the wr-CRP for the entire cohort (r=0.99) as well as for both women (r=0.99 n=483) and men (r=0.99 n=963). The mean difference between the measures (hs-CRP minus wr-CRP) was -0.039 (SD 0.317). The Deming regression results for the entire cohort showed a slope of 1.112+/-0.004 and an intercept of -0.263+/-0.01., Conclusions: The Bayer wr-CRP assay performed presents a reasonable alternative to the Behring Dade hs-CRP assay. The advantages of the wr-CRP assay are its online and real time availability as well as lower costs.

Objective: To find the relative contribution of various inflammation-sensitive proteins including fibrinogen, immunoglobulins (IgG, IgM and IgA), ceruloplasmin and high sensitivity C-reactive protein (hs-CRP) to the induction and/or maintenance of enhanced erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with atherothrombotic risk factors., Methods: The degree of erythrocyte adhesiveness/aggregation was determined by a simple slide test and image analysis. In addition, we measured various inflammation-sensitive protein levels including fibrinogen, ceruloplasmin, immunoglobulins and hs-CRP in a group of 234 individuals with atherothrombotic risk factors and healthy ones. Pearson partial correlations and multiple linear regression analysis were performed., Results: Fibrinogen was found to be the major protein contributing to the enhanced erythrocyte adhesiveness/aggregation, explaining 30% of the model. Fibrinogen and IgG together explained 32.4% of the model. Other inflammation-sensitive proteins did not reach statistical significance and were excluded from the model., Conclusions: Among inflammation-sensitive proteins measured in our cohort, fibrinogen is the dominant contributor to erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with atherothrombotic risk factors and healthy ones. These findings may pave the way for the development of therapeutic strategies directed at the attenuation of erythrocyte aggregability in individuals with atherothrombosis.

Background: Bilateral internal thoracic artery (BITA) grafting with a composite T-graft enables right coronary artery (RCA) system revascularization with the distal end of the free right internal thoracic artery (RITA). This study compares this grafting technique to left-sided BITA grafting and RCA revascularization with the right gastroepiploic artery (RGEA) and saphenous vein grafts (SVG)., Methods: From April 1996 to July 1999, 1000 consecutive patients underwent left-sided revascularization with BITA. In 231 patients RCA grafting was performed with free RITA, in 246 with RGEA, in 142 with SVG, and 381 did not receive any graft to the RCA (no-graft group)., Results: Female gender, old age (> 70), emergency, and congestive heart failure were less prevalent in the RGEA group, and prior percutaneous transluminal coronary angioplasty was more prevalent in the no-graft group. Thirty-day mortality (3.6%, 4.9%, 2%, and 3.4% in the RITA, SVG, RGEA, and no-graft groups, respectively) and occurrence of perioperative complications (sternal infection, myocardial infarction, cerebrovascular accident, and bleeding) were similar. Overall, however, the trend was toward a higher complication rate in the RITA group (10.3%, 4.9%, 5.6%, and 7.3% respectively, p = 0.06). Midterm follow-up (40 to 78 months) showed similar 6-year survival (Kaplan-Meier) (88%, 87%, 89.5%, and 85.5%, respectively) and similar return of angina (10.8%, 6.3%, 10.6%, and 9.5%, respectively) in the four groups., Conclusions: Early and midterm results in patients undergoing left-sided BITA grafting are not affected by the conduit used for RCA grafting.

Aims: To clarify whether individuals with low concentrations of highly sensitive C-reactive protein (hs-CRP) are free of atherothrombotic risk factors or low-grade inflammation., Methods and Results: This cross-sectional study included 1266 individuals with risk factors (diabetes, hypertension, hyperlipidemia, smoking, obesity). Eighty percent of women and the same percentage of men with a low concentration (0.8 +/- 0.4 mg/l) of hs-CRP had at least one atherothrombotic risk factor. About one-fourth of the females and a one-third of the males with a low concentration of hs-CRP had at least one laboratory marker of chronic inflammation (erythrocyte sedimentation rate (ESR), white blood cell count (WBCC) or fibrinogen concentration) in the upper 75th percentile., Conclusion: Individuals presenting with low concentrations of hs-CRP are not necessarily free of atherothrombotic risk factors. One-fourth of the females and a third of the males in this group presented laboratory evidence of a low-grade inflammation as detected by increased erythrocyte sedimentation rate, white blood cell count or fibrinogen concentration.

Background: This study compares the outcome of percutaneous coronary interventions (PCI) with bilateral internal thoracic grafting (BITA) in diabetic patients., Methods: From May 1996 to December 1999, 802 consecutive diabetic patients underwent myocardial revascularization: 363 by PCI and 439 by BITA. The two groups were similar; however, left main disease (28% versus 3.3%), ejection fraction less than 0.35 (14.5% versus 5.5%), and chronic obstructive lung disease (8.4% versus 3%) were more prevalent in the BITA group, and prior percutaneous transluminal coronary angioplasty, in the PCI group (16.8% versus 10.5%)., Results: The number of coronary vessels treated per patient was higher in the BITA group (3.4 versus 1.2; p < 0.001). Thirty-day mortality was similar: 3.4% in the BITA group and 2.8% in the PCI group. Late follow-up (3 to 6.5 years) showed decreased return of angina (11% versus 64%; p < 0.001), fewer reinterventions (2.7% versus 55%; p < 0.001), and increased cardiovascular event-free survival (80% versus 30%; p < 0.001) in the BITA group. Six-year survival of BITA and PCI patients was 85.5% and 81.2%, respectively (not significant). However, survival of the subgroups of patients with left main or three-vessel coronary artery disease was significantly better with BITA (86% versus 76%; p = 0.003)., Conclusions: Despite higher risk profile of diabetic patients treated surgically by BITA, their late outcome is better than that of patients treated by PCI. The results of this study support referring diabetics with single-vessel or double-vessel disease to PCI and those with three-vessel and left main coronary artery disease to surgery.

Based on an analysis of the epidemiologic and clinical attributes of individual patients, the CaDet computer program presents physicians with data patterns that may require clinical attention with regard to early cancer detection. This study evaluated the performance of the program as a possible tool to aid clinicians in the latter. Patient data were obtained by a questionnaire from 160 healthy volunteers. Scored cancer alerts generated by the computer program in response to this data were evaluated in comparison to similar alerts provided by five expert internists who reviewed the same information in blinded fashion. The alert profiles generated by the computer for each of the patients examined were highly correlated to those provided by the clinicians. The computer's alert rate increased with the number of physicians who raised corresponding alerts (20%, 32%, 54%, 73% and 91%, respectively, for 1, 2, 3, 4 and 5 physicians, p < 0.0001) and with the overall weight assigned by the physicians to these alerts (22%, 56%, 84% and 90% for cumulative scores of 1-4, 5-8, 9-12 and 13 or more points, respectively, p < 0.0001). It is concluded that the CaDet computer program may have a role in improving early detection, pending the results of further clinical research.

Study Objectives: To assess the consequences of nitrate withdrawal in angina-free and hemodynamically stable coronary patients., Design: Prospective, open, intervention study., Setting: Cardiology outpatient clinic of a university-affiliated municipal hospital., Patients: Angina-free patients who were hemodynamically stable for at least 3 months before study onset were enrolled. They were all regularly receiving nitrates for symptom control. Those with significant reasons to avoid stopping nitrates, such as heart failure (ejection fraction <35%) or high BP (> 160 mm Hg systolic and/or > 100 mm Hg diastolic), and noncompliant patients were excluded., Interventions: After providing informed consent and undergoing an exercise test (whenever possible), the participants were randomized to abruptly discontinue (study group) or continue (control group) nitrate treatment. Follow-up continued for at least 3 months after study entry., Measurements and Results: Eighty patients were randomized to the study group and 40 patients to the control group (mean age [+/- 1 SD], 65.5 +/- 11 years and 66.1 +/- 10.9 years, respectively; p = not significant). The first month, eight study patients (10%) had a recurrence of anginal symptoms, compared with one control subject (2.5%) [p = not significant]. All eight patients responded promptly and favorably to the resumption of nitrate administration., Conclusions: Nitrate administration can be safely discontinued in angina-free and hemodynamically stable coronary patients who receive this medication on a regular basis. If relapse of anginal symptoms occurs, it will be within 1 month following nitrate withdrawal, and will resolve satisfactorily with reinstatement of treatment.

Background: Coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI) is associated with increased mortality compared with CABG in non-AMI patients. Operating without cardiopulmonary bypass (CPB) might reduce this mortality., Methods: Between January 1992 and December 1998, 225 patients underwent CABG within 7 days of AMI, 119 with CPB and 106 without. The two groups were similar regarding age, gender, left ventricular dysfunction, and incidence of cardiogenic shock. Mean number of grafts per patient was 3.1 in the CPB group, and 1.7 in the no-CPB group (p < 0.0001)., Results: Operative mortality in the CPB group was 12% compared with 3.8% without CPB (p = 0.027). Independent predictors of operative mortality were preoperative use of intraaortic balloon counterpulsation (IABP), nonuse of internal thoracic artery (ITA) to the left anerior descending artery, and the use of less than three grafts. Mortality of patients operated on with CPB within 48 hours of AMI was significantly higher (16.5% vs 4.3%, respectively; p = 0.044). However, patients operated on after 48 hours had similar mortality (5.8% vs 3.4%, respectively). Follow-up ranged from 6 to 84 months. Five-year survival (Kaplan-Meier) of both groups was similar (81%). Patients operated on with CPB had similar rates of recurrent angina; however, they had lower prevalence of reinterventions (0.8% vs 6.3%; p = 0.03)., Conclusions: Our study suggests that CPB can be used safely for most patients referred for CABG within the first week of AMI. However, for emergency patients operated on within the first 48 hours of symptom onset, we advocate avoiding CPB because it is associated with lower operative mortality.

Background: Complete myocardial revascularization with internal thoracic arteries (ITAs) improves long-term survival and decreases the rate of repeat operations, compared to vein grafts. Adequate length of the graft in coronary artery bypass graft (CABG) surgery is essential for providing complete arterial revascularization. Extra length can be obtained by skeletonization of both ITAs. In cases where the right ITA (RITA) is too short to bridge the distance to the target anastomotic site, it is used as a free graft in "composite" arterial grafting, a surgical technique in which free arterial conduits are proximally anastomosed end-to-side to an intact ITA., Objectives: To describe alternative surgical procedures adapted to accommodate special anatomic requirements., Design: Retrospective study from April 1996 to April 1999., Patients: One thousand fifty patients underwent CABG surgery using bilateral skeletonized ITAs: 650 patients (482 men and 168 women; mean +/- SD age, 69 +/- 7 years) underwent composite arterial grafting. Two hundred sixteen patients (33.2%) were diabetics, 87 patients (13.4%) had severe left ventricular dysfunction (ejection fraction < 35%), and 27 patients (4.2%) underwent emergency operations., Interventions: The RITA was used as a free graft connected to the in situ left ITA (LITA) in 618 patients. A free LITA was attached to in situ RITA in 32 patients, and minicomposite grafts (free distal LITA on the LITA or free distal RITA on the RITA) were constructed in 38 patients. The average number of grafts was 3.2 per patient (range, 2 to 6 grafts per patient)., Measurements and Results: Operative mortality was 2.9% (n = 19), and there were 11 sternal wound infections (1.7%). Early recatheterization was performed in 41 symptomatic patients. The patency rate was 95%. The mean follow-up was 25 months (range, 14 to 36 months), and the 3-year survival was 92.5%, with 97% of the surviving patients being angina free., Conclusions: Planning CABG surgery using bilateral skeletonized ITAs as arterial conduits affords greater choice in grafting approaches, especially when a composite technique is feasible.

Background: The complementary graft of choice to the right coronary artery system in patients undergoing left-sided bilateral internal thoracic artery grafting has yet to be determined. Saphenous vein graft (SVG) was compared with right gastroepiploic artery (RGEA) as the supplemental conduit to the right coronary artery when left-sided bilateral internal thoracic artery grafting is implemented., Methods: From April 1996 to July 1999, 234 patients underwent bilateral internal thoracic artery grafting to the left coronary system with RGEA grafted to the posterior descending artery (RGEA group). They were compared with 127 patients with left-sided bilateral internal thoracic artery in whom SVG was used for grafting the right coronary system (SVG group)., Results: Female sex (27% versus 14.5%), diabetic patients (40% versus 27%), emergency cases (21% versus 7.3%), and left main coronary artery disease (34% versus 23%) were more prevalent in the SVG group. Number of grafts per patient was higher in the SVG group (3.8 versus 3.5, p = 0.04). Thirty-day mortality was 3.9% in the SVG and 2.6% in the RGEA group (not significant). Occurrence of postoperative complications (myocardial infarctions, strokes, bleeding, and sternal infections) was similar. Return of angina was similar (1.6% versus 3.8% in the SVG and RGEA groups, respectively). Midterm follow-up (4 to 56 months) showed comparable 1-year and 4-year survival (Kaplan-Meier) for both groups (92.8% and 91.7% in the SVG group, and 94.7% and 88% in the RGEA group, respectively)., Conclusions: In patients undergoing left-sided bilateral internal thoracic artery grafting, the use of RGEA for revascularization of the right coronary system does not confer clinical benefits over SVG after midterm follow-up.

Myocardial revascularization using bilateral internal thoracic arteries (ITA) decreases the risk of reinterventions and provides potential survival benefit. From May 1996 to April 2000, 1,057 patients underwent myocardial revascularization using skeletonized bilateral ITAs. A free right ITA as a composite graft was used for the left anterior descending artery grafting in 38 (3.6%) cases when the left ITA was not long enough to reach the left anterior descending artery. Operative mortality was 2.6% (1 patient). There was no observable reversible myocardial ischemia on the postoperative thallium single-photon emission computed tomography study. Myocardial revascularization with the use of a skeletonized free right ITA as a composite graft to the left anterior descending artery is an alternative option in cases when an in situ ITA cannot be used.

Background: Multiple acute phase proteins and atherosclerotic risk factors increase the aggregability of erythrocytes., Methods and Results: We used a simple slide test and image analysis to determine the degree of erythrocyte adhesiveness/aggregation in the peripheral blood of 222 women and 221 men with no, one, two or more atherosclerotic risk factors. The degree of erythrocyte adhesiveness/aggregation correlated significantly with the concentration of commonly used variables of the acute phase response. We also showed that individuals with low erythrocyte adhesiveness/aggregation tend to be younger and to have fewer risk factors for atherosclerosis, including diabetes mellitus, hypertension, hyperlipidemia and smoking., Conclusions: The association between increased erythrocyte adhesiveness/aggregation, higher concentrations of acute phase proteins, and increased atherosclerotic risk factors points to a possible clinical applicability of the erythrocyte adhesiveness/aggregation test (EAAT) to reveal the presence of both low-grade subclinical smoldering inflammation and morbid biology in individuals with risk factors for atherosclerosis.

Background: Two common techniques of bilateral internal thoracic artery grafting are the composite T graft and in situ crossover graft. The superiority of one method over the other has not yet been established., Methods: From April 1996 to July 1999, bilateral skeletonized internal thoracic arteries were used as T grafts (composite group, n = 649) and in situ grafts (cross group, n = 351) in 1,000 consecutive patients. In the cross group, in situ right internal thoracic artery was routed anterior to the aorta across the midline for grafting to the left anterior descending artery, and the left internal thoracic artery was used for the circumflex branches., Results: The two groups had comparable preoperative risk profiles. Bypass time and aortic cross-clamping time were longer in the composite group (80 +/- 38 and 67 +/- 29 minutes versus 66 +/- 43 and 55 +/- 34 minutes, respectively). Number of anastomoses per patient was similar (3.1 versus 3.2). However, more sequential anastomoses were performed in the composite group (62% versus 53%), and the gastroepiploic artery was used more often in the cross group (30% versus 19%). Thirty-day mortality was 3.9% in the composite and 2.3% in the cross group (not significant). Occurrence of postoperative complications (sternal infection, myocardial infarction, cerebrovascular accident, and bleeding) was similar. Late follow-up (2 to 56 months) showed increased return of angina (6% versus 3.1%; p = 0.046) and decreased 4-year survival (Kaplan-Meier; 86% +/- 2.7% versus 92.4% +/- 1.5%; p = 0.07) in composite patients., Conclusions: Early results of bilateral internal thoracic artery grafting with composite T graft are comparable with those of in situ grafts. However, increased angina return and decreased midterm survival led us to recommend in situ grafting whenever technically possible.