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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Metabolic syndrome is associated to high-sensitivity cardiac troponin T elevation.

INTRODUCTION: Metabolic syndrome (MetS) and high-sensitivity cardiac troponin T (hs-TnT) are associated with higher risk for cardiovascular diseases (CVD). Our aim was to assess the relation between hs-TnT elevation and MetS in a general population sample. MATERIALS AND METHODS: Individuals participating in an annual health survey program between 2010 and 2016 were included in the study. Blood samples including hs-TnT levels were collected. The study population was divided into three groups based on hs-TnT levels - undetectable (<5 ng/L), intermediate (5-14 ng/L) and elevated (>14 ng/L). RESULTS: A total of 5994 subjects were included in the study, the mean age was 48.5 and 4336 (72%) were males. Compared with subjects with undetectable hs-TnT the prevalence of MetS was higher in those with detectable and elevated levels - 392 (10%) vs. 270 (15%) and 51 (33%), respectively (p < 0.001). In a multivariate model adjusted for age, gender and multiple co-morbidities, the number of MetS components and presence of MetS were significantly associated with an increased risk for detectable hs-TnT levels (OR = 1.02 {for each component}; 95% CI [1.00-1.05], p = 0.04) and (OR = 1.13; 95% CI [1.07-1.2], p < 0.001) respectively. Only the waist, glucose and hypertension components of the MetS were significantly associated with elevated troponin. CONCLUSIONS: The MetS and its distinct components have a cumulative impact on hs-TnT levels in apparently healthy subjects.

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

BACKGROUND: Resting 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. METHODS: In 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. RESULTS: RHR 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). CONCLUSIONS: Our results highlight the need for examining individual patients' ∆RHR. Reinforcing that a positive ∆RHR is an indicator of poor adherence to a healthy lifestyle.

Elevated high-sensitive troponin T in negative stress test individuals.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: Among subjects referred for EST as part of an annual health survey, we found no significant association between EST results to hs-cTnT detection.

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

BACKGROUND: Albuminuria 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. METHODS: A 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. RESULTS: Exercise 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). CONCLUSION: Exercise 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.

Eosinophil levels predict lung function deterioration in apparently healthy individuals.

BACKGROUND: While chronic respiratory diseases are among the leading causes of mortality and morbidity worldwide, little is known about the effect of blood eosinophil levels on lung function trajectories among healthy individuals. METHODS: We analyzed data of apparently healthy individuals (n=18,089) recruited for the Tel Aviv Medical Center Inflammation Survey. Blood eosinophil levels were compared between participants with normal and those with abnormal lung function. Multivariate regression was used to assess the OR of forced expiratory volume in 1 second (FEV1) deterioration according to baseline eosinophils in subjects with normal lung function (n=4,141) during a follow-up period of 4 years. RESULTS: Participants with an abnormal, as opposed to a normal, pulmonary function test (PFT) (n=1,832, 10.1%) had significantly higher eosinophil levels, expressed as a percentage or count (2.99%±2.00% compared to 2.67%±1.88% and 0.2210e3/µL±0.163/µL compared to 0.1810e3/µL±0.183/µL, respectively; P<0.001 for both). Among participants with a normal PFT at baseline, those with an eosinophil percentage higher than 4% showed a higher risk for FEV1 decline above 60 mL/year (OR=1.199, 95% CI=1.005-1.431, P=0.044). CONCLUSION: Our study suggests that higher blood eosinophil levels can predict PFT deterioration even in apparently healthy subjects, implying that these individuals could benefit from frequent lung function evaluation.

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

BACKGROUND: Family 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. HYPOTHESIS: FH-HD is associated with elevated hs-cTnT in apparently healthy individuals. METHODS: In 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. RESULTS: Elevated 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). CONCLUSIONS: FH-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.

Hypertension is associated with increased post-exercise albuminuria, which may be attenuated by an active lifestyle.

Albuminuria is a known marker for endothelial dysfunction and cardiovascular events, even below the threshold of moderately increased albuminuria (MIA). Post-exercise increased albuminuria may precede the appearance of rest MIA, enabling detection of early injury. Modifying lifestyle for a population at risk for MIA is therefore of interest. Our aim was to evaluate post-exercise albuminuria in hypertensive compared with normotensive individuals and to analyze the effect of an active lifestyle on rest and post-exercise albumin excretion. The study cohort consisted of 3931 adults who participated in a health-screening program. Albuminuria was measured as urine albumin-to-creatinine ratio (ACR). Lifestyle was divided into three groups: non-active, less-active, and active according to regular sport activity, categorized as follows: none, <2.5 and ≥2.5 hours per week. Mean age was 47.7 years, and 31.2% (n = 1228) were diagnosed with hypertension. Both rest and post-exercise ACR were higher in hypertensive compared to normotensive participants. Rest ACR was higher in non-active compared to less-active and active hypertensive participants. Hypertensive participants with an active lifestyle had significantly lower post-exercise and delta ACR compared to less-active and non-active hypertensive participants. Parameters related to delta ACR in hypertensive participants were increased age, BMI, and diabetes, while active lifestyle and fitness (measured as METS achieved by a stress test) were protective. In conclusion, there is an association between hypertension and increased albumin excretion post-exercise, which can be attenuated with an active lifestyle.

The ability of the wide range CRP assay to classify individuals with low grade inflammation into cardiovascular risk groups.

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.