Metabolic syndrome increases risk of venous thromboembolism recurrence after acute deep vein thrombosis.

An improved understanding of which patients are at higher risk of recurrent venous thromboembolism (VTE) is important to designing interventions to reduce degraded quality of life after VTE. Although metabolic syndrome (MetS), the clustering of hypertension, hyperlipidemia, diabetes mellitus, and obesity has been associated with a hypofibrinolytic state, data linking VTE recurrence with MetS remain limited. The purpose of this study was to measure the prevalence of MetS in patients with deep vein thrombosis (DVT) across a large population and determine its effect on VTE recurrence. This was a retrospective analysis of a large statewide database from 2004 to 2017. We measured the frequency with which patients with DVT carried a comorbid International Coding of Diseases diagnosis of MetS components. Association of MetS with VTE recurrence was tested with a multiple logistic regression model and VTE recurrence as the dependent variable. Risk of VTE recurrence conferred by each MetS component was assessed by Kaplan-Meier curves with the log-rank statistic. A total of 151 054 patients with DVT were included in this analysis. Recurrence of VTE occurred in 17% overall and increased stepwise with each criterion for MetS. All 4 components of MetS had significant adjusted odds ratios (OR) for VTE recurrence, with hyperlipidemia having the largest (OR, 1.8), representing the 4 largest ORs of all possible explanatory variables. All 4 MetS variables were significant on Kaplan-Meier analysis for recurrence of VTE. These data imply a role for appropriate therapies to reduce the effects of MetS as a way to reduce risk of VTE recurrence.

[1]  D. Lloyd‐Jones,et al.  Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity , 2018, JAMA cardiology.

[2]  J. Pell,et al.  The impact of confounding on the associations of different adiposity measures with the incidence of cardiovascular disease: a cohort study of 296 535 adults of white European descent , 2018, European heart journal.

[3]  D. Tousoulis,et al.  The molecular mechanisms of obesity paradox. , 2017, Cardiovascular research.

[4]  F. Rosendaal,et al.  Recurrent venous thrombosis related to overweight and obesity: results from the MEGA follow‐up study , 2017, Journal of thrombosis and haemostasis : JTH.

[5]  K. Khunti,et al.  Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies , 2017, European heart journal.

[6]  M. Abdel-Daim,et al.  Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity , 2017, Journal of diabetes research.

[7]  B. Kissela,et al.  Hyperlipidemia is associated with lower risk of poststroke mortality independent of statin use: A population-based study , 2017, International journal of stroke : official journal of the International Stroke Society.

[8]  G. Pierce,et al.  Anxiety Independently Contributes to Elevated Inflammation in Humans with Obesity , 2016, Obesity.

[9]  J. Hansen,et al.  Ischemic Stroke and Risk of Venous Thromboembolism in the General Population: The Tromsø Study , 2016, Journal of the American Heart Association.

[10]  F. Rosendaal,et al.  The association of statin therapy with the risk of recurrent venous thrombosis , 2016, Journal of thrombosis and haemostasis : JTH.

[11]  J. Kline,et al.  Variable Resistance to Plasminogen Activator Initiated Fibrinolysis for Intermediate-Risk Pulmonary Embolism , 2016, PloS one.

[12]  S. Shariff,et al.  Identifying venous thromboembolism and major bleeding in emergency room discharges using administrative data. , 2015, Thrombosis research.

[13]  M. Cushman,et al.  The safety and efficacy of early‐initiation exercise training after acute venous thromboembolism: a randomized clinical trial , 2015, Journal of thrombosis and haemostasis : JTH.

[14]  E. Mathiesen,et al.  Atrial fibrillation and future risk of venous thromboembolism:the Tromsø study , 2015, Journal of thrombosis and haemostasis : JTH.

[15]  S. Steffens,et al.  Adipokines at the crossroad between obesity and cardiovascular disease , 2014, Thrombosis and Haemostasis.

[16]  John A. Heit,et al.  The epidemiology of venous thromboembolism , 2003, Journal of Thrombosis and Thrombolysis.

[17]  P. Prandoni,et al.  Aspirin for the Prevention of Recurrent Venous Thromboembolism: The INSPIRE Collaboration , 2014, Circulation.

[18]  O. Dekkers,et al.  Statin use and venous thromboembolism recurrence: a combined nationwide cohort and nested case–control study , 2014, Journal of thrombosis and haemostasis : JTH.

[19]  J. Hansen,et al.  Venous Thromboembolism Increases the Risk of Atrial Fibrillation: The Tromsø Study , 2014, Journal of the American Heart Association.

[20]  I. Markaki,et al.  High cholesterol levels are associated with improved long-term survival after acute ischemic stroke. , 2014, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[21]  S. Samson,et al.  The Metabolic Syndrome: A Common Hyperinsulinemic Disorder With Severe Health Effects , 2006 .

[22]  Hiram Beltrán-Sánchez,et al.  Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999-2010. , 2013, Journal of the American College of Cardiology.

[23]  V. Hainer,et al.  Obesity Paradox Does Exist , 2013, Diabetes Care.

[24]  A. Folsom,et al.  Statin therapy and levels of hemostatic factors in a healthy population: the Multi‐Ethnic Study of Atherosclerosis , 2013, Journal of thrombosis and haemostasis : JTH.

[25]  I. Lazareth [Aspirin for preventing the recurrence of venous thromboembolism]. , 2013, Journal des maladies vasculaires.

[26]  S. Goldhaber Venous thromboembolism: epidemiology and magnitude of the problem. , 2012, Best practice & research. Clinical haematology.

[27]  W. Ageno,et al.  Aspirin for preventing the recurrence of venous thromboembolism. , 2012, The New England journal of medicine.

[28]  T. Wakefield,et al.  Statins, inflammation and deep vein thrombosis: a systematic review , 2012, Journal of Thrombosis and Thrombolysis.

[29]  S. Salim,et al.  Inflammation in anxiety. , 2012, Advances in protein chemistry and structural biology.

[30]  B. Medoff,et al.  Obesity and pulmonary arterial hypertension: Is adiponectin the molecular link between these conditions? , 2011, Pulmonary circulation.

[31]  D. Corella,et al.  The metabolic syndrome and its individual components: its association with venous thromboembolism in a Mediterranean population. , 2011, Metabolic syndrome and related disorders.

[32]  J. Kline,et al.  Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension: A Scientific Statement From the American Heart Association , 2011, Circulation.

[33]  S. Kahn The post-thrombotic syndrome. , 2010, Hematology. American Society of Hematology. Education Program.

[34]  P. Wells,et al.  Systematic Review: Case-Fatality Rates of Recurrent Venous Thromboembolism and Major Bleeding Events Among Patients Treated for Venous Thromboembolism , 2010, Annals of Internal Medicine.

[35]  G. Moneta Recent Trends in Clinical Outcomes and Resource Utilization for Pulmonary Embolism in the United States: Findings From the Nationwide Inpatient Sample , 2010 .

[36]  F. Anderson,et al.  Recent trends in clinical outcomes and resource utilization for pulmonary embolism in the United States: findings from the nationwide inpatient sample. , 2009, Chest.

[37]  A. Folsom,et al.  Metabolic syndrome and risk of venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology , 2009, Journal of thrombosis and haemostasis : JTH.

[38]  W. Ageno,et al.  New evidence on the potential role of the metabolic syndrome as a risk factor for venous thromboembolism , 2009, Journal of thrombosis and haemostasis : JTH.

[39]  E. Mathiesen,et al.  Abdominal obesity is essential for the risk of venous thromboembolism in the metabolic syndrome: the Tromsø study , 2009, Journal of thrombosis and haemostasis : JTH.

[40]  W. Ageno,et al.  Venous Thromboembolism: Mechanisms, Treatment, and Public Awareness Metabolic Syndrome Is Associated With Venous Thromboembolism in the Korean Population , 2009 .

[41]  S. Kahn,et al.  Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy , 2008, Canadian Medical Association Journal.

[42]  Oswald Wagner,et al.  Overweight, obesity, and the risk of recurrent venous thromboembolism. , 2008, Archives of internal medicine.

[43]  G. Raskob,et al.  Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[44]  M. Schindewolf,et al.  Impact of sex and traditional cardiovascular risk factors on the risk of recurrent venous thromboembolism: results from the German MAISTHRO Registry , 2008, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[45]  T. Olsen,et al.  Higher Total Serum Cholesterol Levels Are Associated With Less Severe Strokes and Lower All-Cause Mortality: Ten-Year Follow-Up of Ischemic Strokes in the Copenhagen Stroke Study , 2007, Stroke.

[46]  W. Dorda,et al.  Venous thromboembolism--a manifestation of the metabolic syndrome. , 2007, Haematologica.

[47]  W. Ageno,et al.  The metabolic syndrome and the risk of venous thrombosis: a case–control study , 2006, Journal of thrombosis and haemostasis : JTH.

[48]  Anindita Das,et al.  Hypercholesterolemia Enhances Tolerance to Lethal Systemic Hypoxia in Middle-Aged Mice: Possible Role of VEGF Downregulation in Brain , 2006, Molecular and Cellular Biochemistry.

[49]  Paul Enright,et al.  Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. , 2004, The American journal of medicine.

[50]  K. Asplund,et al.  Regular leisure time physical activity predicts high activity of tissue plasminogen activator: The Northern Sweden MONICA Study. , 1996, International journal of epidemiology.

[51]  M. El-sayed,et al.  Effects of Exercise on Blood Coagulation, Fibrinolysis and Platelet Aggregation , 1996, Sports medicine.

[52]  J. Lai,et al.  In vitro oxidation of vitamin E, vitamin C, thiols and cholesterol in rat brain mitochondria incubated with free radicals , 1995, Neurochemistry International.

[53]  M. Cerqueira,et al.  Effects of Physical Conditioning on Fibrinolytic Variables and Fibrinogen in Young and Old Healthy Adults , 1991, Circulation.