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

In the present study we analyzed the data collected at the Tel-Aviv Medical Center Inflammation Survey (TAMCIS), a registered data bank of the Israeli Ministry of Justice [17‐20]. This is a relatively large survey comprising of apparently healthy individuals attending a center for periodic health examinations. Subjects attending the center for a routine health examination between September 2002 and June 2009 were invited to participate in the TAMCIS. We recruited both apparently healthy individuals and individuals presenting with atherothrombotic risk factors. All the individuals who were enrolled were recruited during their routine annual health check-up and gave their written consent in accordance with the guidelines of the institutional ethics committee. A total of 15,605 subjects gave their informed consent (9,881 males, 5,724 females). Later, 2,797 subjects were excluded from the analysis due to any malignancy, immunosuppressive therapy, known inflammatory disease (arthritis, inflammatory bowel disease, psoriasis, etc.), pregnancy, steroidal or non-steroidal treatment (except for aspirin at a dose of ≤ 325 mg/day), acute infection or invasive procedures (surgery, catheterization, etc.) during the last 6 months. An additional 168 subjects were further excluded because they had no recorded hs-CRP values. The chance that diabetics harbor multiple additional inflammatory confounders such as use of statins[21] and anti-hyperglycemic medications[22‐24], hidden infections[25], and yet undetermined inflammatory mechanisms[26] is high. Therefore, we have decided to narrow the scope of our analysis by excluding diabetics, including any individual taking medications for diabetes. Thus, 568 individuals were finally excluded due to a suspected or confirmed diagnosis of diabetes mellitus. Following these exclusions the study group comprised of 12,072 individuals (7,760 males and 4,312 females). These were all people visiting for the first time.

Blood samples were drawn in the morning hours, after a 12-h overnight fast. The WBCC and differential were performed using the Coulter STKS (Beckman Coulter, Nyon, Swiss) electronic analyzer, while fibrinogen concentrations were determined by the method of Clauss[27] and a Sysmax 6000 (Sysmex Corporation, Hyaga, Japan) analyzer. High sensitivity C-Reaeactive protein concentrations were determined by using the Behring BN II Nephelometer (DADE Behring, Marburg, Germany) analyzer and a method described according to Rifai et al. [28]. Glucose, triglycerides and high density lipoprotein cholesterol were measured using a Bayer Advia 1650 chemistry analyzer and Bayer respective kits (Bayer healthcare diagnostics division, Newbury, UK).

The results of the routine health check-up were evaluated by employing certain definitions of the various atherothrombotic risk factors. Diabetes mellitus was defined as a fasting blood glucose level of ≥ 126 mg/dl (7 mmol/L) or treatment with insulin or oral hypoglycemic medications. Hypertension was defined as displaying with blood pressure of ≥ 140/90 mmHg in two separate measurements or the intake of anti-hypertensive medications. Dyslipidemia was defined as the low density lipoprotein cholesterol (LDL-C) or non- high density lipoprotein cholesterol (non-HDL-C) concentrations, for individuals displaying elevated triglyceride concentrations of ≥ 200 mg/dl (2.26 mmol/l) above the recommended levels, according to the risk profile defined by the updated adult treatment panel III (ATP III) recommendations[29], or the intake of lipid lowering medications. The Diagnosis of the Metabolic Syndrome was based on the National cholesterol education program ATP III Criteria [29]. The criteria for impaired fasting glucose is that used by the American Diabetes Association [30] as proposed by the updated American Heart Association/National Heart, Lung, and Blood Institute scientific statement [31]. In summary, elevated waist circumference was defined as ≥ 102 cm (40 inches) in men and ≥ 88 (35 inches) in women; Elevated triglycerides were defined as ≥ 150 mg/dl (1.7 mmol/l) or a person receiving drug treatment for elevated triglycerides; Reduced HDL-C was defined as ≤ 40 mg/dL (1.03 mmol/l) in men and ≤ 50 mg/dl (1.3 mmol/l) in women or a person receiving drug treatment for reduced HDL-C; Elevated blood pressure was defined as ≥ 130 mm Hg systolic blood pressure or ≥ 85 mm Hg diastolic blood pressure or a person receiving antihypertensive drug treatment; Elevated fasting glucose was defined as ≥ 100 mg/dl. Smokers were defined as individuals who smoked at least 5 cigarettes per day while past smokers had stopped smoking for at least 30 days prior to examination. Measured waist circumference was defined according to the National cholesterol education program's ATP III guidelines [29]. To measure the waist circumference, we located the top of the right iliac crest, placed a measuring tape in a horizontal plane around the abdomen immediately above the level of the iliac crest. Measurements were made at the end of a normal expiration.

All data was summarized and displayed as mean ± standard deviation (SD) for the continuous variables and as number of patients plus the percentage in each group for categorical variables. Since hs-CRP, ESR and the triglyceride concentrations display irregular distributions, we used a logarithmic transformation which converted the distributions to normal ones for all statistical procedures. Therefore, all results of hs-CRP, ESR or triglyceride concentrations are expressed as back transformed geometrical means and standard deviations. The One-Way Kolmogorov-Smirnov test was used to assess the distributions. For all categorical variables the Chi-Square statistic was used to assess the statistical significance between the two genders. Pearson partial correlations for confounding variables were used to evaluate the age adjusted association between the various components of the MetS and the inflammatory variables. In order to assess and compare the contribution of the different components of the MetS to the variability of the various inflammatory variables, we used linear regression models. The inflammatory variables were the dependent variables and the different components of the MetS, as well as other potential confounders, were the covariates. The confounders included age, history of proven atherothrombotic disease (myocardial infarction, coronary artery bypass graft surgery, cerebrovascular event or peripheral artery occlusion disease), smoking status, alcohol consumption, level of physical activity and medication with potential influence on the inflammatory markers and/or the metabolic components such as angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, statins, fibrates and aspirin, as well as hormone replacement therapy or oral contraceptives in females. In an attempt to adjust for the association between the inflammatory variables (mainly hs-CRP) and obesity, we repeated the correlations and the linear regression models with additional adjustment for BMI. All above analyses were considered significant at p < 0.05 (two tailed). The statistical package for the Social Sciences (SPSS) was used to perform all statistical evaluation (SSPS Inc., Chicago, IL, USA).