Leukocyte Activation in Obese Patients

Abstract

The rising prevalence of obesity is a major global health problem. In severe obesity, bariatric surgery (BS) allows to obtain a significant weight loss and comorbidities improvement, among them one of the factors is the thrombotic risk. In this observational study, we measured indices of leukocyte activation in severely obese patients as markers of increased thrombotic risk in relation with serum markers of inflammation before and after BS.Frequency of polymorphonuclear neutrophil-platelet (PLT) and monocyte (MONO)-PLT aggregates as well as of tissue factor (TF) expressing MONOs was measured in the peripheral blood of 58 consecutive obese patients and 30 healthy controls. In 31 of the 58 obese patients, data obtained at the enrollment were compared with those obtained at 3, 6, and 12 months after BS.Compared with healthy controls, obese patients showed a higher frequency of polymorphonuclear leukocyte (PMNL)-PLT aggregates (7.47 ± 2.45 [6.82–8.11]% vs 5.85 ± 1.89 [5.14–6.55]%, P = 0.001), MONO-PLT aggregates (12.31 ± 7.33 [10.38–14.24]% vs 8.14 ± 2.22 [7.31–8.97]%, P < 0.001), and TF expressing MONOs (4.01 ± 2.11 [3.45–4.56]% vs 2.64 ± 1.65 [2.02–3.25]%, P = 0.002). PMNL-PLT and MONO-PLT aggregate frequency was positively correlated with TF expressing MONOs (R2 = 0.260, P = 0.049 and R2 = 0.318, P = 0.015, respectively).BS was performed in 31 patients and induced a significant reduction of the body mass index, and waist and hip circumferences. These effects were associated with a significant decrease of PMNL-PLT aggregates at 12 months (7.58 ± 2.27 [6.75–8.42]% vs 4.47 ± 1.11 [3.93–5.01]%, P < 0.001), and a reduction of TF expressing MONOs at 6 (3.82 ± 2.04 [3.07–4.57]% vs 1.60 ± 1.69 [0.30–2.90]%, P = 0.008) and 12 months (3.82 ± 2.04 [3.07–4.57]% vs 1.71 ± 0.54 [1.45–1.97]%, P = 0.001) after BS.These data suggest that leukocyte-PLT aggregate formation and MONO activation represent an important mechanism underlying the increased thrombotic risk of obese patients. We also show that BS is effective in normalizing these inflammatory indices.

Effect of Roux-en-Y Bariatric Bypass Surgery on Subclinical Atherosclerosis and Oxidative Stress Markers in Leukocytes of Obese Patients: A One-Year Follow-Up Study

“…Indeed, hsCRP is known to rise with the degree of adiposity [8] and is directly involved in the development of atherosclerosis through complement system activation and endothelial dysfunction [29]. In the present study, we report a significant decrease in serum levels of hsCRP, C3c, and total leukocyte count after weight loss induced by RYGB, which is in accordance with previous studies [20,23,24]. Such evidence endorses the long-lasting therapeutic value of bariatric surgery against inflammatory and lipid-related cardiovascular risk [25].…”

“…Atherogenic dyslipidemia is a major contributor to the increased cardiovascular risk currently seen in the general population [22]; it results from a combination of elevated levels of TG and highly atherogenic sdLDL particles together with a decrease in circulating antiatherogenic HDL molecules. As we and other groups have shown, patients after RYGB surgery benefit, not only from quantitative reduction of clinical LDLc and TG levels and an increase in HDLc [23][24][25], but from a complementary qualitative improvement of lipoprotein particles, including a reduction in the percentage of sdLDL and an increased presence of larger HDL [26], which frequently display inverse relationships with cardiovascular risk in epidemiological studies [27]. Furthermore, elevated levels of circulating inflammatory cytokines, and particularly hsCRP, are considered independent predictors of cardiovascular events, even more so than LDLc levels [28].…”

Effects of Obesity Surgery on Blood Coagulation and Fibrinolysis: A Literature Review

“…In the TF pathway of coagulation, MV-TF, monocyte-TF, and TF:Ag were lowered 2 to 24 months after vertical gastroplasty, 64 SG, 65 RYGB, or GB. 57,66,67 This may be explained by decreased TF-synthesis from adipose tissue, endothelial cells, and monocytes (►Fig. 2).…”

Impact of change in bedtime variability on body composition and inflammation: secondary findings from the Go Red for Women Strategically Focused Research Network

“…This study also provides novel insight into biological underpinnings of the relation between sleep variability and CVD risk. Previous work shows that LPA are inversely associated with BMI 14 and adiposity 5 in addition to experimental evidence of LPA reductions following bariatric surgery 5 . Our results thus suggest a potential pathway by which reductions in sleep variability exert effects on endothelial inflammation via reductions in adiposity.…”

“…To elucidate mechanisms underlying this relation, we tested whether body composition was impacted by changes in bedtime variability. An additional aim was to assess changes in leukocyte platelet aggregates (LPA), given data linking these inflammatory markers to adiposity and cardiometabolic disorders 3 – 5 . We studied women participating in a clinical trial from the Go Red for Women Strategically Focused Research Network; the main purpose of the study was to test the effects of sleep duration, either adequate habitual sleep (HS) or reduced sleep, on cardiometabolic risk ( Clinicalstrials.gov : NCT02835261 ).…”