Elevated leptin and decreased adiponectin independently predict the post-thrombotic syndrome in obese and non-obese patients

Abstract

Post-thrombotic syndrome (PTS) is a common complication of deep vein thrombosis (DVT). Little is known about the involvement of adipokines in the pathogenesis of DVT. We evaluated whether adipokines can predict PTS. In a prospective cohort study, 320 DVT patients aged 70 years or less were enrolled. Serum adiponectin, leptin and resistin levels were measured three months since the index first-ever DVT. After 2 years’ follow-up PTS was diagnosed in 83 of 309 available patients (26.9%) who had 13.9% lower adiponectin and 16% higher leptin levels compared with the remainder (both p < 0.0001). No PTS-associated differences in C-reactive protein, fibrinogen, D-dimer, plasminogen activator inhibitor-1 and resistin were observed. The multivariable logistic regression adjusted for age, sex, obesity and tissue plasminogen activator (tPa) showed that lower adiponectin (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.31–0.56) and higher leptin levels (OR, 1.49; 95% CI, 1.31–1.69) are independent predictors for PTS. Obesity-stratified logistic regression analysis confirmed that lower adiponectin (OR, 0.49; 95% CI, 0.38–0.64) and higher leptin (OR, 1.41; 95% Cl, 1.25–1.58) levels predicted PTS. Our findings showed that lower adiponectin and higher leptin measured 3 months after DVT, regardless of obesity, can independently predict PTS, which suggests novel links between adipokines and thrombosis.

Leukocyte gene expression in post-thrombotic syndrome

“…However, RNA sequencing data is often considered to be reliable in itself, since DESeq2 normalization corrects for all gene expression. In respect to the difference in BMI, it is promising that the predictive value of adiponectin was shown to be independent of BMI [7]. Nevertheless, additional research is needed to confirm our findings.…”

“…In a recent cohort study, low adiponectin levels at three months after DVT were shown to predict the onset of PTS. [7] Finally, there was a decreased expression of the gene PPIA, which codes for cyclophilin A. Besides an intracellular role in protein trafficking, this protein is also secreted by leukocytes in response to inflammatory stimuli.…”

Plasma Levels of Leptin and Risk of Future Incident Venous Thromboembolism

“…In a prospective cohort study comprising 320 patients with a first DVT, higher leptin levels, independent of obesity, predicted the occurrence of post thrombotic syndrome. 23…”

“…In a prospective cohort study comprising 320 patients with a first DVT, higher leptin levels, independent of obesity, predicted the occurrence of post thrombotic syndrome. 23 In contrast to the scarce clinical data on the relationship between leptin and VTE risk, several in vitro studies have investigated the effect of leptin on platelet activation parameters 36 and on the expression of key hemostatic factors for blood coagulation and fibrinolysis. [17][18][19]37,38 In human peripheral mononuclear cells, leptin was shown to induce TF activity, antigen and messenger ribonucleic acid (mRNA) expression, 17,18 as well as the release of TF-bearing microparticles.…”

“…Data on the role of leptin in VTE are scarce, with previous studies reporting an association of increased leptin levels with DVT after total knee arthroplasty, 21 peripheral chronic venous disease, 22 and postthrombotic syndrome. 23 The clarification of the association between leptin and VTE may shed more light on the molecular pathways in the pathogenesis of VTE in obese, which could thereby serve as potential targets for VTE prevention. However, the assessment of the relationship between leptin and VTE may be challenging because leptin, as a satiety hormone, can influence body weight and BMI.…”