leptin and Venous-Thromboembolism

Obesity leads to adipocyte hypertrophy and adipokine dysregulation and is an independent risk factor for venous thromboembolism (VTE). However, the association between adipokines and VTE is not well established.. To examine whether adipokines are associated with increased risk of incident VTE.. We studied 1888 participants of the Multi-Ethnic Study of Atherosclerosis cohort who were initially free of VTE and had adipokine (adiponectin, leptin, and resistin) levels measured at either examination 2 or 3 (2002-2004 or 2004-2005, respectively). During follow-ups, VTE was ascertained through hospitalization records and death certificates by using ICD-9 and 10 codes. We used multivariable Cox proportional hazards regression to assess the association between 1 standard deviation (SD) log-transformed increments in adipokines and incident VTE.. The mean ± SD age was 64.7 ± 9.6 years, and 49.8% of participants were women. Medians (interquartile range) of adiponectin, leptin, and resistin were 17.3 (11.8-26.2) mcg/mL, 13.5 (5.6-28.2) ng/mL, and 15.0 (11.9-19.0) ng/mL, respectively. There were 78 incident cases of VTE after a median of 9.7 (5.0-12.4) years of follow-up. After adjusting for sociodemographics, smoking, and physical activity, the hazard ratios (95% CIs) per 1 SD increment of adiponectin, leptin, and resistin were 1.14 (0.90-1.44), 1.29 (1.00-1.66), and 1.38 (1.09-1.74), respectively. The association for resistin persisted after further adjustments for body mass index and computed tomography-derived total visceral adipose tissue area.. Higher resistin levels were independently associated with greater risk of incident VTE. Larger prospective cohort studies are warranted to confirm this association.

Topics: Adipokines; Adiponectin; Aged; Atherosclerosis; Female; Humans; Leptin; Male; Middle Aged; Prospective Studies; Resistin; Risk Factors; Venous Thromboembolism

 Circulating levels of leptin, an adipocyte-derived hormone, are frequently elevated in obesity. Leptin has been reported to upregulate prothrombotic hemostatic factors in vitro and could potentially mediate venous thromboembolism (VTE) risk in obesity. However, whether leptin is associated with VTE remains uncertain..  This article investigates the association between plasma leptin and risk of incident VTE, and the potential of leptin to mediate VTE risk in obesity..  A population-based nested case-control study with 416 VTE cases and 848 age- and sex-matched controls was derived from the Tromsø Study. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE across leptin quartiles. Analyses were performed separately in men and women using sex-specific quartile cut-offs determined in controls..  In the age-adjusted model, the VTE risk increased across leptin quartiles, particularly in men. Compared with the lowest quartile, the ORs for VTE in the highest quartile were 1.70 (95% CI 1.04-2.79) in men and 1.36 (95% CI 0.85-2.17) in women. However, with additional adjustment for body mass index (BMI), risk estimates were markedly attenuated in men (OR 1.03, 95% CI 0.55-1.93) and women (OR 0.82, 95% CI 0.45-1.48). The ORs for VTE were increased in obese men and women (BMI ≥ 30 kg/m.  Our results indicate that the apparent association between plasma leptin levels and VTE risk is confounded by BMI and that leptin is not a relevant mediator for VTE risk in obesity.

Topics: Case-Control Studies; Female; Humans; Leptin; Male; Obesity; Risk Factors; Venous Thromboembolism

It suggests that a high leptin level may increase the risk of venous thromboembolism (VTE) in animal studies. However, clinical studies in this field are still largely unexplored. Our objective was to evaluate the relationship between the preoperative serum leptin levels and postoperative VTE incidence in osteoarthritis (OA) patients who underwent total knee arthroplasty (TKA) at our institute.We conducted a prospective and cross-sectional study in these OA patients from March 2014 to March 2016. Preoperative leptin levels were analyzed by Luminex assays. VTE was assessed preoperatively and on postoperative day 5 and 7. The potential risk factors for VTE were also documented.We enrolled 203 OA patients. No PE was detected and DVT was diagnosed in 34 patients postoperatively. There were significant differences between the median leptin levels in DVT group and non-DVT group [25.13 ng/mL (interquartile range, 14.51-44.31) vs 18.71 ng/mL (8.26-28.99), P = .007]. The relative risk of DVT significantly increased with natural logarithm (ln) leptin (per SD increase) (OR 2.37, 95% confidence interval (95% CI), 1.29-4.33, P = .005). Multivariate analyses adjusted for potential confounders showed ln leptin (per SD increase) was significantly associated with the relative risk of DVT (OR 2.17, 95% CI, 1.01-4.64, P = .046). When patients were subdivided into tertiles according to their leptin values, the OR for DVT increased with increasing tertiles of serum leptin (OR 1.03, 95% CI, 1.01-1.06, P for trend = .023).In the present study, our results indicate that a high preoperative leptin level may be an independent risk factor for postoperative DVT.

Topics: Aged; Arthroplasty, Replacement, Knee; Cross-Sectional Studies; Female; Humans; Incidence; Leptin; Male; Middle Aged; Osteoarthritis, Knee; Postoperative Complications; Preoperative Period; Prospective Studies; Risk Factors; Ultrasonography, Doppler, Duplex; Venous Thromboembolism; Venous Thrombosis

Obesity increases the risk of venous thromboembolism (VTE) in pregnancy. The pathogenesis is hypothesized to be because of multiple factors including prothrombotic changes, but there has been minimal haemostatic research looking at the combined state of obesity and pregnancy. We aimed to determine whether variation in BMI in the third trimester of pregnancy was associated with prothrombotic changes. We recruited 110 women into four groups depending on their BMI at first antenatal appointment: normal, overweight, obese and morbidly obese. Women with increased risk of VTE, and/or receiving thromboprophylaxis, and/or more than 35 years and those in labour were excluded. Thromboelastography, platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, prothrombin fragment 1 + 2, free and total protein S, plasminogen activator inhibitor type 1, tissue plasminogen activator antigen, D-dimers, soluble endoglin and leptin levels were measured. There were no significant differences in haemostatic measures with changing BMI. There was a positive correlation between BMI and both platelet count (correlation coefficient r = 0.214, P = 0.036) and leptin (r = 0.435, P < 0.001), but only leptin had a significant association with BMI once adjusted for age, gestation and parity. Despite recruitment into the morbidly obese group being suboptimal, these findings suggest that in pregnancy, the increased risk of VTE seen in obese mothers is not mediated through increased prothrombotic changes, and thus the increased risk of VTE in obese pregnant women may be because of other mechanisms, for example endothelial dysfunction, inflammation and venous stasis.

Topics: Adult; Body Mass Index; Endoglin; Female; Hemostatics; Humans; Leptin; Obesity; Pregnancy; Prospective Studies; Retrospective Studies; Thrombelastography; Venous Thromboembolism

The aim of the present study was to reveal the contribution of single nucleotide polymorphisms of the interleukin‑6 (IL‑6) gene and the progression of venous thromboembolism (VTE). A case‑control study composed of 246 VTE patients, including 160 from the Han population (76 males and 84 females, mean age 57.41±13.25 years), 86 from the Uyghur population (41 males and 45 females, mean age 51.61±13.73 years) and 292 gender and ethnicity‑matched control participants, including 170 from the Han population (91 males and 79 females, mean age 55.82±11.83 years) and 122 from the Uyghur population (64 males and 58 females, mean age 53.52±13.64 years) were enrolled in the present study. The results demonstrated that the serum levels of IL‑6, C‑reactive protein (CRP), D‑dimer, fibrinogen, plasminogen activator inhibitor‑1 and leptin were significantly higher in the VTE group compared with the control group (P<0.05). The frequencies of the ‑572C/G promoter polymorphisms of the IL‑6 genotypes CC, CG and GG were identified to be 34, 48 and 18% in the Han population and 33, 47 and 20% in the Uyghur population, respectively. The allele frequency distributions of the C and G alleles were 58 and 42% in the Han population and 56 and 43% in the Uyghur population, respectively. Significant differences were identified in the ‑572C/G promoter polymorphisms between the VTE group and the control group (P<0.05). For the ‑597G/A polymorphism, all individuals carried the GG and GA genotype; AA genotypes were not detected. Logistic regression analysis was used to identify the risk factors for VTE, adjusting by confounding factors, the results of which demonstrated that the CC homozygote of the IL‑6 ‑572G/C, CRP, IL‑6 and high‑density lipoprotein‑cholesterol were independent risk factors of VTE (P<0.05). In conclusion, the ‑572G/C genotype of IL‑6 may be a genetic marker of VTE in the Han and Uyghur populations.

Topics: Adult; Aged; Alleles; C-Reactive Protein; Case-Control Studies; Ethnicity; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Genotype; Humans; Interleukin-6; Leptin; Logistic Models; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Risk Factors; Venous Thromboembolism