Tel-Aviv Medical Center Inflammation Survey Research Articles

The effect of body mass index reduction on intraocular pressure in a large prospective cohort of apparently healthy individuals in Israel.

To investigate the effect of change in body mass index (BMI) on intraocular pressure (IOP) in a large cohort of apparently healthy volunteers who underwent an annual comprehensive screening examinations. This study included individuals who were enrolled in the Tel Aviv Medical Center Inflammation Survey (TAMCIS) and had IOP and BMI measurements at their baseline and follow up visits. Relationships between BMI and IOP and the effect of change in BMI on IOP were investigated. A total of 7,782 individuals had at least one IOP measurement at their baseline visit, and 2,985 individuals had ≥2 visits recorded. The mean (SD) IOP (right eye) was 14.6 (2.5) mm Hg and mean (SD) BMI was 26.4 (4.1) kg/m2. IOP positively correlated with BMI levels (r = 0.16, p<0.0001). For individuals with morbid obesity (BMI≥35 kg/m2) and ≥2 visits, a change in BMI between the baseline and first follow-up visits correlated positively with a change in the IOP (r = 0.23, p = 0.029). Subgroup analysis of subjects who had a reduction of at least 2 BMI units showed a stronger positive correlation between change in BMI and change in IOP (r = 0.29, p<0.0001). For this subgroup, a reduction of 2.86 kg/m2 of BMI was associated with a reduction of 1 mm Hg in IOP. BMI loss correlated with reduction in IOP, and this correlation was more pronounced among morbidly obese individuals.

Non-alcoholic Fatty Liver and Liver Fibrosis Predictive Analytics: Risk Prediction and Machine Learning Techniques for Improved Preventive Medicine.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with a prevalence of 20%-30% in the general population. NAFLD is associated with increased risk of cardiovascular disease and may progress to cirrhosis with time. The purpose of this study was to predict the risks associated with NAFLD and advanced fibrosis on the Fatty Liver Index (FLI) and the 'NAFLD fibrosis 4' calculator (FIB-4), to enable physicians to make more optimal preventive medical decisions. A prospective cohort of apparently healthy volunteers from the Tel Aviv Medical Center Inflammation Survey (TAMCIS), admitted for their routine annual health check-up. Data from the TAMCIS database were subjected to machine learning classification models to predict individual risk after extensive data preparation that included the computation of independent variables over several time points. After incorporating the time covariates and other key variables, this technique outperformed the predictive power of current popular methods (an improvement in AUC above 0.82). New powerful factors were identified during the predictive process. The findings can be used for risk stratification and in planning future preventive strategies based on lifestyle modifications and medical treatment to reduce the disease burden. Interventions to prevent chronic disease can substantially reduce medical complications and the costs of the disease. The findings highlight the value of predictive analytic tools in health care environments. NAFLD constitutes a growing burden on the health system; thus, identification of the factors related to its incidence can make a strong contribution to preventive medicine.

Exercise capacity and body mass index - important predictors of change in resting heart rate

BackgroundResting heart rate (RHR) is an obtainable, inexpensive, non-invasive test, readily available on any medical document. RHR has been established as a risk factor for cardiovascular morbidity, is related to other cardiovascular risk factors, and may possibly predict them. Change in RHR over time (∆RHR) has been found to be a potential predictor of mortality.MethodsIn this prospective study, RHR and ∆RHR were evaluated at baseline and over a period of 2.9 years during routine check-ups in 6683 subjects without known cardiovascular disease from the TAMCIS: Tel-Aviv Medical Center Inflammation Survey. Multiple linear regression analysis with three models was used to examine ∆RHR. The first model accounted for possible confounders by adjusting for age, sex and body mass index (BMI). The 2nd model included smoking status, baseline RHR, diastolic blood pressure (BP), dyslipidemia, high-density lipoprotein (HDL) and metabolic equivalents of task (MET), and in the last model the change in MET and change in BMI were added.ResultsRHR decreased with age, even after adjustment for sex, BMI and MET. The mean change in RHR was − 1.1 beats/min between two consecutive visits, in both men and women. This ∆RHR was strongly correlated with baseline RHR, age, initial MET, and change occurring in MET and BMI (P < 0.001).ConclusionsOur results highlight the need for examining individual patients’ ∆RHR. Reinforcing that a positive ∆RHR is an indicator of poor adherence to a healthy lifestyle.

Familial history of heart disease and increased risk for elevated troponin in apparently healthy individuals

BackgroundFamily history of heart disease (FH‐HD) is associated with an increase drisk of subsequent HD. High sensitive cardiac troponin T (hs‐cTnT) is arecognized biomarker of myocyte injury even in HD free patients. We examined the association between FH‐HD and hs‐cTnT in apparently healthy individuals.HypothesisFH‐HD is associated with elevated hs‐cTnT in apparently healthy individuals.MethodsIn a cross sectional study we analyzed data of apparently healthy individuals (n=3,821) recruited for the Tel‐Aviv Medical Center Inflammation Survey (TAMCIS). Blood samples were obtained for hs‐cTnT and high sensitive CRP (hs‐CRP) among other tests. FH‐HD was defined as first degree family member with HD diagnosis and classified as premature if the diagnosis was done before the age of 55 for men or 65 for women.ResultsElevated hs‐cTnT (>14 ng/L) was more common in FH‐HD of any age, and in premature FH‐HD (FH‐P‐HD) participants than in participants without FH‐HD (4.4% vs 2.0%, p<0.001 and 4.3% vs 2.0%, p=0.001, respectively). Adjustmentfor potential risk factors with association to elevated hs‐cTnT (age, sex, BMI, hypertension, diabetes, hs‐CRP, smoking and physical activity), showed that FH‐HD and FH‐P‐HD remained significantly associated with elevated hs‐cTnT (OR=1.62, p=0.025 and OR=1.70, p=0.039, respectively). Furthermore, we found that a significant interaction between FH‐HD or FH‐P‐HD and high levels ofhs‐CRP (>3 mg/L) increased the risk for elevated hs‐cTnT (OR=3.07, p=0.036 for FH‐HD and OR=3.25, p=0.053 for FH‐P‐HD).ConclusionsFH‐HD and its interaction with elevated hs‐CRP levels were significantly associated with elevated hs‐cTnT in apparently healthy individuals suggesting that an inflammatory process may be involved in this association.

Increase of body mass index and waist circumference predicts development of metabolic syndrome criteria in apparently healthy individuals with 2 and 5 years follow-up.

The metabolic syndrome (MetS) is associated with overweight and abdominal obesity. Our aim was to use longitudinal measurements to provide clinically relevant information on the relative influence of changes in body mass index (BMI), waist circumference (WC), and weekly physical exercise duration on the development of each of the MetS components. We analyzed data collected at the Tel-Aviv Medical Center Inflammation Survey (TAMCIS). Apparently healthy individuals with two consecutive visits that were not treated for any metabolic criteria were included in this study. We analyzed the influence of changes in BMI, WC, and time engaged in physical exercise on the change in each of the components of the metabolic syndrome using linear regressions. Included were 7532 individuals (5431 men, 2101 women) with 2 years follow-up. Participants who gained two BMI points, had the mean number of criteria increase from 1.07 to 1.52, while participants who lost two BMI points, decreased from 1.64 to 1.16. A long-term analysis over 5 years showed similar results. Furthermore, an increase in WC was independently associated with increased severity of each of the other components, when controlling for increase in BMI. Increase in weekly exercise duration had a small but statistically significant favorable effect on blood triglycerides and HDL levels, but not on blood pressure or HbA1C. Changes in BMI and WC are highly associative with the likelihood and severity of the MetS independently of the baseline levels, suggesting that obese individuals can substantially improve their MetS prognosis by losing both body weight and abdominal fat.

Total serum cholinesterase activity predicts hemodynamic changes during exercise and associates with cardiac troponin detection in a sex-dependent manner

BackgroundImbalanced autonomic nervous system (ANS) activity is associated with poor cardiovascular outcome. However, clinically validated biomarkers to assess parasympathetic function are not yet available. We sought to evaluate parasympathetic dysfunction by measuring serum cholinesterase activity and to determine its relationship to high sensitive cardiac troponin T (hs-cTnT) as well as traditional non-invasive parameters of ANS function during exercise in apparently healthy individuals.MethodsWe enrolled 1526 individuals (mean age 49 ± 11 yr., 75% men) from the Tel Aviv Medical Center Inflammation Survey (TAMCIS). We used the acetylcholine (ACh) analog acetylthiocholine (ATCh) as a substrate that is hydrolyzed by both ACh degrading enzymes and reflects the total serum capacity for acetylcholine hydrolysis, referred to as cholinergic status (CS). All subjects performed a cardiac stress test reviewed on the spot by a cardiologist and multiple physiological and metabolic parameters including hs-cTnT were measured.ResultsCS values at rest predicted multiple exercise-hemodynamic changes. Heart rate recovery after exercise was inversely correlated to CS values (p < 0.01 and p = 0.03 for women and men respectively), and a hypertensive reaction during exercise was associated with elevated CS levels in women. Most importantly, women with detectable hs-cTnT (> 5 ng/L) presented with elevated CS levels compared to women with undetectable levels; 1423 ± 272.5 vs 1347 ± 297.9 (p = 0.02). An opposite trend was observed in men. Metabolic dysfunction parameters were also associated with CS elevation in both men and women.ConclusionsParasympathetic dysfunction assessed by total serum cholinesterase activity predicts hemodynamic changes during exercise. CS is also associated with hs-cTnT detection in women and inversely so in men. Future studies to assess the potential clinical use of this new sex-specific biomarker in cardiovascular disease risk stratification are warranted.Graphical

Elevated high‐sensitive troponin T in negative stress test individuals

The exercise ECG stress test (EST) is still the first step of work-up in intermediate risk patients in many clinical scenarios. High-sensitive cardiac troponin T (hs-cTnT) elevation is related to future cardiovascular events in the general population and in patients with ischaemic heart disease. The relation between these 2 tests is not well described. A total of 2780 participants from the Tel-Aviv Medical Center Inflammation Survey cohort (mean age 49 years, 79% men) were analysed. Multiple physiologic and metabolic parameters including hs-cTnT were collected. All participants completed an EST manually reviewed by a cardiologist. A positive EST was documented in 224 subjects (8%). The majority (91%) of participants with hs-cTnT levels of 5-14 ng/L had a negative EST as well as 89.3% of subjects with levels >14 ng/L. The proportion of subjects with a positive EST and detectable hs-cTnT levels (>5 ng/L) was not significantly greater compared to those with a negative EST (53.1% vs 46.2%, respectively, P = .09). Among subjects referred for EST as part of an annual health survey, we found no significant association between EST results to hs-cTnT detection.

Obesity-related acetylcholinesterase elevation is reversed following laparoscopic sleeve gastrectomy

Impaired sympathetic/parasympathetic response, expressed by elevated Acetylcholinesterase (AChE) is associated with obesity, metabolic syndrome and inflammation. However, the association between morbid obesity and AChE and the changes in cholinergic tone following bariatric laparoscopic sleeve gastrectomy (LSG) surgery-induced weight reduction were never analyzed. Two studies are presented; the first (the "apparently healthy cohort") was a cross-sectional study and the second (the "LSG cohort") was a prospective-cohort study with 12 months of follow-up. The "apparently healthy cohort" included 1450 apparently healthy participants who volunteered to the Tel-Aviv Medical Center Inflammation Survey (TAMCIS) during a routine annual checkup visit. The "LSG cohort" included 77 morbid obese patients before and at 3, 6, and 12 months following LSG surgery. Main outcomes included anthropometric measurements, Hemoglobin A1c (HbA1C), serum AChE, insulin test and Homeostasis Model Assessment (HOMA). Among the TAMCIS participants, serum AChE activity increased with BMI in a dose-dependent manner until it reached a peak level at BMI of 30-35 kg/m², followed by a plateau. Following LSG, a significant decrease in AChE activity between baseline and 12 months post-surgery was found for men, but not for women (-122.2 ± 135.3, P < 0.001 vs. -21.8 ± 120.5, P = 0.258 nmol substrate hydrolyzed/min per ml, respectively). The reduction in AChE activity was negatively correlated with %excess weight loss (EWL) and positively correlated with %body fat reduction at 12 months post-surgery among women (r = -0.329, P = 0.034 and r = 0.350, P = 0.023, respectively). In men, AChE activity reduction was positively correlated with the HOMA reduction (r = 0.358, P = 0.048). Obesity-related AChE resistance phenotype may be reversed following LSG and correlates with metabolic outcomes. Further long-term studies will be needed to validate and evaluate the beneficial effect of AChE reduction post bariatric surgery.

Sex difference in the risk for exercise-induced albuminuria correlates with hemoglobin A1C and abnormal exercise ECG test findings

BackgroundAlbuminuria is an established marker for endothelial dysfunction and cardiovascular risk in diabetes and prediabetes. Exercise induced albuminuria (EiA) appears earlier and may be a more sensitive biomarker for renal endothelial damage. We sought to examine the association between EiA, parameters of the metabolic syndrome, A1C levels, exercise ECG test results and sex related differences in a large cohort of healthy, pre-diabetic and diabetic subjects.MethodsA total of 3029 participants from the Tel-Aviv Medical Center Inflammation Survey cohort (mean age 46 years, 73% men) were analyzed. Multiple physiologic and metabolic parameters including A1C were collected and albuminuria was measured in all subjects before and immediately after completing an exercise ECG test.ResultsExercise increased urinary albumin to creatinine ratio (ΔEiA) by 2.8 (0–13.6) mg/g for median (IQR) compared to rest albuminuria (p < 0.001). An increase in ΔEiA was observed with accumulating parameters of the metabolic syndrome. ΔEiA showed significant interaction with sex and A1C levels; i.e. women with A1C > 6.5% had an increased risk of higher ΔEiA (p < 0.001). Using a cutoff of ΔEiA > 13 mg/g (top quartile) we found that women with ΔEiA > 13 mg/g were at greater risk for abnormal exercise ECG findings, (OR = 2.7, p = 0.001).ConclusionExercise promotes excessive urinary albumin excretion in dysmetabolic patients. In women, a significant correlation exists between ΔEiA and A1C levels. A cutoff of ΔEiA > 13 mg/g in women may be used to identify populations at risk for abnormal exercise ECG test findings and perhaps increased cardiovascular risk. Future studies will be needed to further validate the usefulness of ΔEiA as a biomarker for cardiovascular risk in women with and without diabetes.

Multiplicity of Dysmetabolic Components in Males is Associated with Elevated Cardiac Troponin T Concentrations

Background: There are multiple lines of evidence to suggest that chronic myocardial stress and increased cardiovascular risk is associated with the enhanced release of cardiac troponin in patients with ischemic heart disease. However, there is a paucity of data regarding the relation of cardiac troponin to the metabolic syndrome (MetS), a leading risk factor for cardiovascular morbidity. Methods: We determined the prevalence of measurable high sensitivity cardiac Troponin T (hs-cTnT) with a fifth generation assay and evaluated its association to the presence of the male metabolic syndrome (MetS) components in a cohort of patients undergoing a health survey in the Tel Aviv Medical Center Inflammation Survey (TAMCIS). Results: A total of 1,641 men with no known cardiovascular disease were recruited and MetS was diagnosed in 330 (20.1%) of them. Hs-cTnT concentrations were higher in patients with MetS (p<0.001). The number of MetS components was associated with the concentration ofhs-cTnT (p<0.001 for trend). The 99th percentile concentration was 27.6 ng/l and 16.03 ng/l for those with and without the MetS, respectively. Five percent of patients with MetS had hs-cTnT concentrations higher than the 99th percentile predetermined by the manufacturer. Conclusions: The MetS in males is associated with higher levels of hs-cTnT than the general population, with each component increasing hs-cTnT value.

T-Wave Amplitude Is Related to Physical Fitness Status

Abnormalities in repolarization may reflect underlying myocardial pathology and play a prominent role in arrhythmogenesis The T-wave amplitude has been associated with cardiovascular outcome in patients with acute myocardial infarction (MI) Additionally, T-wave amplitude is considered a predictor of arrhythmias, as well as being related to an individual's inflammatory status. The combined influence of different variables, such as inflammation, cardiovascular risk factors and physical fitness status, on the T-wave amplitude has not been evaluated to date. The aim of this study was to identify factors that affect the T-wave amplitude. Data from 255 consecutive apparently healthy individuals included in the Tel Aviv Medical Center Inflammation Survey (TAMCIS) were reviewed. All patients had undergone a physical examination and an exercise stress test, and different inflammatory and metabolic biomarkers (fibrinogen, potassium, and high-sensitivity C-reactive protein) were measured. Multivariate stepwise analysis revealed that the body mass index and the resting heart rate were significantly associated with the T-wave amplitude (β=-0.34, P < 0.001; β=-0.19, P = 0.03, respectively) in males, while the recovery rate and the usage of statins significantly affected the T-wave amplitude in females (β= 0.36, P = 0.002; β= 0.35, P = 0.002, respectively). Inflammatory variables had no significant affect on the T-wave amplitude of either gender. In conclusion, the T-wave amplitude is linked to an individual's physical fitness and not to his/her inflammatory status.

Comparison of Different Anthropometric Measurements and Inflammatory Biomarkers

Introduction. Different anthropometric variables have been shown to be related to cardiovascular morbidity and mortality. Our aim was to compare the association between different anthropometric measurements and inflammatory status. Methods and results. A cross-sectional study design in which we analyzed the data collected during a five-year period in the Tel Aviv Medical Center Inflammation Survey (TAMCIS). Included in the study were 13,033 apparently healthy individuals at a mean (SD) age of 43. Of these, 8,292 were male and 4,741 female. A significant age-adjusted and multiple-adjusted partial correlation was noted between all anthropometric measurements and all inflammatory biomarkers. There was no significant difference in the correlation coefficients between different biomarkers and anthropometric variables. Conclusion. Most of the common used anthropometric variables are similarly correlated with inflammatory variables. The clinician can choose the variable that he/she finds easiest to use.

The association of higher levels of within-normal-limits liver enzymes and the prevalence of the metabolic syndrome

BackgroundMetabolic syndrome (MetS) is frequently characterized by elevated liver enzymes, including gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT). Our objective was to evaluate the range of prevalence of MetS in apparently healthy individuals whose liver enzyme concentrations were all within-normal-range.MethodsWe have performed a cross sectional analysis on participants of the Tel-Aviv medical center inflammation survey (TAMCIS) recruited between the years 2003-2009. Analyzed were a cohort of 6,561 men and 3,389 women.ResultsThe prevalence of MetS increased significantly from the first quintile to the fifth for both GGT and ALT, all the five quintiles being in the normal range. Logistic regression analysis for the presence of MetS showed crude odds ratios of 2.7 and 2.4 between the first and fourth quintiles and 3.6 and 3.2 for the fifth quintile in men and women respectively for ALT. For GGT the respective odds being 3.6 and 3.2 for the fourth quintile and 3.9 and 3.4 for the fifth quintile in men and women, respectively.ConclusionsA relatively high prevalence of MetS was noted in a cohort of apparently healthy individuals with liver enzyme concentrations within-normal-limits. Practical consequences include the need to follow up these enzyme concentrations as continuous variables and to take into consideration that even relatively small elevations within the normal range might reflect the presence of dysmetabolism.

Waist circumference as the predominant contributor to the micro-inflammatory response in the metabolic syndrome: a cross sectional study

BackgroundThe metabolic syndrome (MetS) is associated with the presence of low grade inflammation. Our aim was to analyze the inter-relations between each of the components of the metabolic syndrome (MetS) and four inflammatory markers, namely high sensitivity C-reactive protein (hs-CRP), the erythrocyte sedimentation rate, the concentration of fibrinogen and the white blood cell count.MethodsWe have analyzed data collected between September 2002 and June 2009 in the Tel-Aviv medical center inflammation survey (TAMCIS). We recruited both apparently healthy individuals and individuals presenting with atherothrombotic risk factors. All participants were enrolled during their routine annual health check-up and gave their written informed consent. This is a cross sectional study in which we have fitted linear regression models using inflammatory markers as the dependant variables and adjust them according to the different components of the MetS and multiple other confounders.ResultsIncluded were 12,072 individuals of whom there were 7,760 men at a mean (S.D.) age of 44 (11) years, and 4,312 women aged 44 (11) years. A significant correlation was noted between most components of the MetS and all inflammatory markers, the most significant one being with hs-CRP. In the multi-adjusted regression analysis, waist was the factor that best explained the variability of hs-CRP, in both women and men. It also remained a significant variable for the other inflammatory markers.ConclusionsFrom amongst the various components of the MetS, waist circumference appears to exert the most influence upon the presence and intensity of the micro-inflammatory response.