Body Mass Index (BMI) and Its Influence on the Cardiovascular and Operative Risk Profile in Coronary Artery Bypass Grafting Patients: Impact of Inflammation and Leptin

Abstract

Background: Obesity is related to coronary artery disease (CAD) and worse outcomes in coronary artery bypass graft (CABG) patients. Adipose tissue itself is an endocrine organ that secretes many humoral mediators, such as adipokines, which can induce or reduce inflammation and oxidative stress.

Objectives: We investigate the relationship between the body mass index (BMI), inflammation, and oxidative stress by measuring serum levels of leptin, interleukin-6, and 3-nitrotyrosine in CABG patients and correlate their levels to the cardiovascular and operative risk profiles.

Methods and results: 45 men (<75 years) with a median BMI of 29 (21-51) kg/m², who were diagnosed with CAD and scheduled for elective CABG, were included after applying the following exclusion criteria: prior myocardial infarction, reoperation, female gender, and smoking. Patients' blood samples were taken preoperatively. Several markers were measured. We found significant correlations between leptin and BMI (p < 0.0001) as well as between leptin and 3-nitrotyrosine (p = 0.006). Interleukin-6 was correlated with C-reactive protein (p < 0.0001) and with the incidence of insulin-dependent diabetes mellitus (p = 0.036), arterial hypertension (p = 0.044), reduced left ventricular function (p = 0.003), and severe coronary calcification (p = 0.015). It was also associated with significantly longer extracorporeal bypass time (p = 0.009). Postoperative deep sternal wound infections could be predicted by a higher BMI (p = 0.003) and leptin level (p = 0.001).

Conclusions: There seems to be a correlation between inflammatory processes and cardiovascular morbidity in our cohort. Further, the incidence of deep sternal wound infections is related to a higher BMI and leptin serum level.

Figure 1

Flow chart of the time point of determination and documentation for each parameter/data ([0/1] = [No/yes]; 3-NT = 3-nitrotyrosine (rel. IOD, % of control normalized to loading control); AHT = arterial hypertension; BMI = body mass index; CRP=C-reactive protein; d = days; DSWI = deep sternal wound infection; ECC = extracorporeal circulation; h = hours; ICU = intensive care unit; IDDM = insulin-dependent diabetes mellitus II; IL-6 = interleukin 6; LVEF = left ventricular ejection fraction).

Figure 2

All 45 individual values for the measured parameters of inflammation are illustrated.

Figure 3

Significant correlation of BMI with leptin in 45 patients.

Figure 4

Determination of the oxidative stress parameters 3-nitrotyrosine (3-NT) (a) and 8-Isoprostane (b) by commercial ELISA assays of a proof of increased reactive oxygen and nitrogen species formation in patients with leptin levels higher than the median. Data are mean ± SEM. (c, d) Significant correlation of leptin and levels of the serum oxidative stress marker 3-NT in 40 patients (p values and correlation coefficients are provided in the graphs). Measured 3-NT staining was either normalized to Ponceau S staining (c) or transferrin content (d).

Figure 5

Correlation of IL-6 and levels of the serum oxidative stress marker 3-nitrotyrosine (3-NT) in 40 patients (correlation coefficient is provided in the graph).

Figure 6

IL-6 levels in patients with (a) AHT (n = 39) and (b) IDDM (n = 7) compared to IL-6 levels in patients without arterial hypertension (no AHT/control (a), n = 6) and without IDDM (no IDDM/control (b), n = 38). IL-6 levels were significantly higher in patients with AHT (3.5 ± 0.7 vs 11.9 ± 2.6 ng/l) and with IDDM (10.3 ± 2.6 vs 13.2 ± 2.3 ng/l). Data are mean ± SEM.

Figure 7

IL-6 levels (a) and leucocytes (b) compared in patients with intraoperative status of severe coronary calcification (sclerosis, black) or normal coronary sclerosis (control, grey). Patients with severe coronary calcification had significantly higher levels of IL-6 (6.1 ± 1.1 vs 15.8 ± 4.4 ng/l), whereas leucocytes were only increased by trend (7.7 ± 0.4 vs 10.2 ± 1.1 cells/ng, p = 0.085). Data are mean ± SEM, n = 21 − 24 patients.

Figure 8

BMI (a) and leptin levels (b) in patients with deep sternal wound infection (black, DSWI, n = 5) versus the control (grey) group (n = 40). Patients with DSWI had significantly higher BMI (29.4 ± 0.9 vs 40.0 ± 3.1 kg/m²) and significantly raised levels of leptin (12.2 ± 2.2 vs 27.7 ± 5 ng/l). Data are mean ± SEM.