Dataset Information

Association of Varicose Veins With Incident Venous Thromboembolism and Peripheral Artery Disease.

ABSTRACT: Varicose veins are common but rarely associated with serious health risks. Deep venous thrombosis (DVT), pulmonary embolism (PE), and peripheral artery disease (PAD) are also vascular diseases but associated with serious systemic effects. Little is known about the association between varicose veins and the incidence of other vascular diseases including DVT, PE, and PAD.To investigate whether varicose veins are associated with an increased risk of DVT, PE, or PAD.A retrospective cohort study using claims data from Taiwan's National Health Insurance program. Patients aged 20 years and older with varicose veins were enrolled from January 1, 2001-December 31, 2013, and a control group of patients without varicose veins were matched by propensity score. Patients previously diagnosed with DVT, PE, or PAD were excluded. Follow-up ended December 31, 2014.Presence of varicose veins.Incidence rates of DVT, PE, and PAD were assessed in people with and without varicose veins. Cox proportional hazards models were used to estimate relative hazards, with the control group as reference.There were 212?984 patients in the varicose veins group (mean [SD] age, 54.5 [16.0] years; 69.3% women) and 212?984 in the control group (mean [SD] age, 54.3 [15.6] years; 70.3% women). The median follow-up duration was 7.5 years for DVT, 7.8 years for PE, and 7.3 years for PAD for patients with varicose veins, and for the control group, follow-up duration was 7.6 years for DVT, 7.7 years for PE, and 7.4 years for PAD. The varicose veins group had higher incidence rates than the control group for DVT (6.55 vs 1.23 per 1000 person-years [10?360 vs 1980 cases]; absolute risk difference [ARD], 5.32 [95% CI, 5.18-5.46]), for PE (0.48 for the varicose veins group vs 0.28 for the control group per 1000 person-years [793 vs 451 cases]; ARD, 0.20 [95% CI, 0.16-0.24]), and for PAD (10.73 for the varicose veins group vs 6.22 for the control group per 1000 person-years [16?615 vs 9709 cases]; ARD, 4.51 [95% CI, 4.31-4.71]). The hazard ratios for the varicose veins group compared with the control group were 5.30 (95% CI, 5.05-5.56) for DVT, 1.73 (95% CI, 1.54-1.94) for PE, and 1.72 (95% CI, 1.68-1.77) for PAD.Among adults diagnosed with varicose veins, there was a significantly increased risk of incident DVT; the findings for PE and PAD are less clear due to the potential for confounding. Whether the association between varicose veins and DVT is causal or represents a common set of risk factors requires further research.

SUBMITTER: Chang SL

PROVIDER: S-EPMC5838574 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Association of Varicose Veins With Incident Venous Thromboembolism and Peripheral Artery Disease.

Chang Shyue-Luen SL Huang Yau-Li YL Lee Mei-Ching MC Hu Sindy S Hsiao Yen-Chang YC Chang Su-Wei SW Chang Chee Jen CJ Chen Pei-Chun PC

JAMA 20180201 8

<h4>Importance</h4>Varicose veins are common but rarely associated with serious health risks. Deep venous thrombosis (DVT), pulmonary embolism (PE), and peripheral artery disease (PAD) are also vascular diseases but associated with serious systemic effects. Little is known about the association between varicose veins and the incidence of other vascular diseases including DVT, PE, and PAD.<h4>Objective</h4>To investigate whether varicose veins are associated with an increased risk of DVT, PE, or ...[more]

PMID: 29486040

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Project description:Three-dimensional computed tomography venography is a useful tool to identify increased saphenous vein diameter and provides a complementary road map for surgery in patients with varicose veins. In this study, we investigated the correlation between saphenous vein diameter on computed tomography venography and venous reflux detected on duplex ultraonography. We enrolled 152 patients (213 extremities) who underwent endovenous laser ablation therapy, following high ligation of the saphenofemoral junction between January 2014 and December 2019. All patients underwent preoperative computed tomography venography evaluation. The saphenous vein diameter was measured on computed tomography venography, and venous reflux was evaluated in the operating room using Doppler ultrasonography. Among the 152 patients included in the study, 61 showed varicose veins affecting the bilateral extremities. Among the 213 extremities investigated, 165 (77.5%) and 48 (22.5%) extremities showed varicosities involving the greater and lesser saphenous veins, respectively. Among all extremities, venous reflux was detected in 172 (80.8%). The mean diameter of the greater saphenous vein measured 5 cm distal to the saphenofemoral junction was 8.07±1.82 mm in patients with reflux and 5.11±1.20 mm in patients without reflux (p < .05). The small saphenous vein diameter measured 5 cm distal to the saphenopopliteal junction was 7.65±1.74 mm in patients with reflux and 5.04±1.80 mm in patients without reflux (p < .05). Based on the receiver operating characteristic curve, the greater saphenous vein threshold diameter of 5.880 mm measured 5 cm distal to the saphenofemoral junction was the optimal cut-off value to predict reflux (sensitivity 91.4%, specificity 81.8%). The lesser saphenous vein diameter of 5.285 mm measured 5 cm distal to the saphenopopliteal junction was the optimal cut-off value to predict reflux (sensitivity 94.9%, specificity 75.0%). Vein diameter cannot be used as an absolute reference for venous reflux; however, it may have predictive value in patients with varicose veins. Computed tomography venography based measurements of vein diameter may serve as a useful diagnostic tool to predict venous reflux and recommend treatment.

Project description:Background: Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP), particularly in DNMT3A, TET2, and JAK2, are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. However, whether CHIP is associated with increased risk of peripheral artery disease (PAD) remains unknown. In addition, chemotherapy frequently causes mutations in DNA Damage Repair (DDR) genes TP53 and PPM1D, and whether CHIP caused by somatic mutations in DDR genes results in increased risk of atherosclerosis is unclear. We sought to test whether CHIP, and CHIP caused by DDR genes, associates with incident peripheral artery disease (PAD) and atherosclerosis. Methods: We identified CHIP among 50,122 exome sequences in individuals from UK and Mass General Brigham Biobanks and tested CHIP status (N=2,851) with incident PAD and atherosclerosis across multiple arterial beds. To mimic the human scenario of clonal hematopoiesis and test whether the expansion of p53-deficient hematopoietic cells contributes to atherosclerosis, a competitive bone marrow transplantation (BMT) strategy was used to generate atherosclerosis-prone Ldlr-/- chimeric mice carrying 20% Trp53-/- hematopoietic cells (20% KO-BMT mice). We then evaluated aortic plaque burden and plaque macrophage accumulation 12 weeks after grafting. Results: CHIP associated with incident PAD (HR 1.7; P=2.2x10-5) and atherosclerosis in multiple beds (HR 1.3; P=9.7x10-5), with increased risk among individuals with DDR CHIP (HR 2.0; P=0.0084). Among atherosclerosis-prone Ldlr null mice, the p53 -/- 20% KO-BMT mice demonstrated increased aortic plaque size (p=0.013) and accumulation of p53-/- plaque macrophages (P<0.001), driven by an abundance of p53-deficient plaque macrophages. The expansion of p53-deficient cells did not affect the expression of the pro-inflammatory cytokines IL-6 and IL-1β in the atherosclerotic aortic wall. Conclusions: Our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system, with evidence of increased plaque among p53 -/- 20% KO-BMT mice via expansion of plaque macrophages. These observations provide new insight into the link between CHIP and cardiovascular disease, and lend human genetic support to the concept that post-cytotoxic chemotherapy patients may benefit from surveillance for atherosclerotic conditions in addition to therapy-related myeloid neoplasms.

Project description:ImportancePrior studies have observed an association between the burden of atherosclerotic vascular disease and the risk of venous thromboembolism (VTE). The association is not well described in peripheral artery disease (PAD) after lower extremity revascularization (LER).ObjectiveTo describe the risk of, factors associated with, and outcomes after VTE, as well as the association of low-dose rivaroxaban plus antiplatelet therapy with VTE after LER.Design, setting, and participantsThis global, multicenter cohort study used data from the Vascular Outcomes Study of ASA (acetylsalicylic acid) Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER PAD) randomized clinical trial, which enrolled patients from 2015 to 2018 with median follow-up of 28 months. Participants included patients with PAD undergoing LER. Patients with an indication for therapeutic anticoagulation were excluded. Data were analyzed from September 2020 to September 2021.ExposureRandomization to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily; short-term clopidogrel was used at the discretion of the treating physician.Main outcomes and measuresSymptomatic VTE was a prespecified secondary outcome and prospectively collected.ResultsAmong 6564 patients (median [IQR] age, 67 [61-73] years; 4860 [74.0%] men), 66 patients had at least 1 VTE. The 3-year rate of VTE in patients receiving placebo was 1.7%, and the pattern of risk was linear (year 1: 0.5%; year 2: 1.1%). After multivariable modeling, weight (hazard ratio [HR], 3.04; 95% CI, 1.09-8.43), hypertension (HR, 2.11; 95% CI, 0.91-4.89), prior amputation (HR, 2.07; 95% CI, 0.95-4.53), and older age (HR, 1.81; 95% CI, 1.06-3.11) were associated with increased risk of VTE. VTE was associated with risk of subsequent mortality (HR, 7.22; 95% CI, 4.66-11.19). Compared with aspirin alone, rivaroxaban plus aspirin was associated with lower VTE risk (HR, 0.61; 95% CI, 0.37-0.998; P = .047), with benefit apparent early and sustained over time. This association was not modified by use of clopidogrel at randomization (without clopidogrel: HR, 0.55; 95% CI, 0.29-1.07; with clopidogrel: HR, 0.69; 95% CI, 0.32-1.48; P for interaction = .67).Conclusions and relevanceIn this cohort study, there was continuous risk for VTE after LER in patients with PAD, with greater risk in patients who were older and had obesity and those with more severe PAD, as reflected by prior amputation. Low-dose rivaroxaban plus aspirin was associated with lower VTE risk compared with aspirin alone, with benefits apparent early and continued over time. The spectrum of venous and arterial thrombotic events and overall benefits of more potent antithrombotic strategies for prevention should be considered after LER for PAD.

Project description:BackgroundVaricose veins are found to be associated with increased risk of venous thromboembolism (VTE) in many observational studies, but whether varicose veins are causally associated with VTE remains unclear. Therefore, we used a series of Mendelian randomization (MR) methods to investigate that association.Methods23 independent single-nucleotide polymorphisms (SNPs) for varicose veins were obtained from the Pan UK Biobank analysis. The outcomes datasets for deep vein thrombosis (DVT), pulmonary embolism (PE) and venous thromboembolism (VTE) were obtained from the FinnGen study. Before analysis, body mass index (BMI) and height were included as confounders in our MR model. Basic MR [inverse-variance weighted (IVW), weight-median, penalized weighted-median and MR-Egger methods] and MR-PRESSO were performed against each outcome using the whole SNPs and SNPs after excluding those associated with confounders. If causal associations were suggested for any outcome, a basic MR validation analysis, a multivariable MR analysis with BMI and height, a Causal Analysis Using Summary Effect estimates (CAUSE), and a two-step MR analysis with BMI and height, would follow.ResultsUsing 21 qualified SNPs, the IVW method (OR: 1.173, 95% CI: 1.070-1.286, p < 0.001, FDR = 0.002), the weighted median method (OR: 1.255, 95% CI: 1.106-1.423, p < 0.001, FDR = 0.001), the penalized weighted median method (OR: 1.299, 95% CI: 1.128-1.495, p < 0.001, FDR = 0.001) and the MR-PRESSO (OR: 1.165, 95% CI: 1.067-1.273, p = 0.003, FDR = 0.009) suggested potential causal effect of varicose veins on DVT, but no cause effect was found for PE and VTE. Excluding SNPs associated with confounders yielded similar results. The causal association with DVT was validated using a self-reported DVT cohort (IVW, OR: 1.107, 95% CI: 1.041-1.178, p = 0.001). The causal association maintained after adjustment for height (OR = 1.105, 95% CI: 1.028-1.188, p = 0.007), BMI (OR = 1.148, 95% CI: 1.059-1.244, p < 0.001) and them both (OR = 1.104, 95% CI: 1.035-1.177, p = 0.003). The causal association also survived the strict CAUSE (p = 0.018). Finally, in two-step MR, height and BMI were found to have causal effects on both varicose veins and DVT.ConclusionGenetically predicted varicose veins may have a causal effect on DVT and may be one of the mediators of obesity and taller height that predispose to DVT.

Project description:BACKGROUND:Varicose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease. METHODS:We applied machine learning to agnostically search for risk factors of varicose veins in 493?519 individuals in the UK Biobank. Predictors were further studied with univariable and multivariable Cox regression analyses (2441 incident events). A genome-wide association study of varicose veins was also performed among 337?536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development. RESULTS:Machine learning confirmed several known (age, sex, obesity, pregnancy, history of deep vein thrombosis) and identified several new risk factors for varicose vein disease, including height. After adjustment for traditional risk factors in Cox regression, greater height remained independently associated with varicose veins (hazard ratio for upper versus lower quartile, 1.74; 95% CI, 1.51-2.01; P<0.0001). A genome-wide association study identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/limb biology. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins (inverse-variance weighted: odds ratio, 1.26; P=2.07×10-16). CONCLUSIONS:Using data from nearly a half-million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.

Dataset Information

Association of Varicose Veins With Incident Venous Thromboembolism and Peripheral Artery Disease.

Publications

Association of Varicose Veins With Incident Venous Thromboembolism and Peripheral Artery Disease.

Similar Datasets

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