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DOI: 10.1055/s-0042-1760335
Causal Associations Between Cardiovascular Risk Factors and Venous Thromboembolism
Funding This work was supported by the National Key Research and Development Program of China (2017YFC1700503), CAMS Innovation Fund for Medical Sciences (2016-I2M-1-009), and the Twelfth Five-Year Planning Project of the Scientific and Technological Department of China (2011BAI11B02).
Abstract
Objective The aim of the study is to assess the causal effects of cardiovascular risk factors on venous thromboembolism (VTE) and its subtypes including deep vein thrombosis (DVT) and pulmonary embolism (PE).
Methods A summary-level Mendelian randomization (MR) analysis was performed by extracting data from public and large-scale genome-wide association studies for cardiovascular risk factors (hypertension, systolic blood pressure [SBP], diastolic blood pressure [DBP], total cholesterol, triglycerides, high-density lipoprotein [HDL], low-density lipoprotein [LDL], type 2 diabetes, fasting glucose, body mass index [BMI], smoking, alcohol, and physical activity), VTE, DVT, and PE to identify genetic instruments.
Results BMI (per standard deviation [SD] increase; odds ratio [OR]: 1.39; 95% confidence interval [CI]: 1.25–1.54; p = 8.02 × 10−10) could increase the VTE risk, whereas SBP (per SD increase; OR: 0.99; 95% CI: 0.98–0.99; p = 0.0005) could decrease the VTE risk. For DVT, BMI (per SD increase; OR: 1.48; 95% CI: 1.28–1.72; p = 1.53 × 10−7) could increase the risk, whereas physical activity (per SD increase; OR: 0.05; 95% CI: 0.01–0.33; p = 0.0020) could decrease the risk. For PE, BMI (per SD increase; OR: 1.29; 95% CI: 1.12–1.49; p = 0.0005) could increase the risk, whereas SBP (per SD increase; OR: 0.99; 95% CI: 0.98–1.00; p = 0.0032) could decrease the risk. Suggestive evidence between smoking and higher risks of VTE and DVT was also observed.
Conclusion Our study supports that BMI is a causal risk factor for VTE, DVT, and PE. SBP is a protective factor for VTE and PE. Physical activity is a protective factor for DVT. However, the effects of other cardiovascular risk factors are not identified.
Keywords
coronary heart disease - venous thromboembolism - deep venous thrombosis - pulmonary embolism - cardiovascular risk factors - Mendelian randomizationPublikationsverlauf
Artikel online veröffentlicht:
11. Januar 2023
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References
- 1 MacDougall DA, Feliu AL, Boccuzzi SJ, Lin J. Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic syndrome. Am J Health Syst Pharm 2006; 63 (20, suppl 6): S5-S15
- 2 Beckman MG, Hooper WC, Critchley SE, Ortel TL. Venous thromboembolism: a public health concern. Am J Prev Med 2010; 38 (Suppl. 04) S495-S501
- 3 Cohen AT, Agnelli G, Anderson FA. et al; VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost 2007; 98 (04) 756-764
- 4 Heit JA. Venous thromboembolism epidemiology: implications for prevention and management. Semin Thromb Hemost 2002; 28 (Suppl. 02) 3-13
- 5 Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology. Investigation and management of heritable thrombophilia. Br J Haematol 2001; 114 (03) 512-528
- 6 Becattini C, Agnelli G, Prandoni P. et al. A prospective study on cardiovascular events after acute pulmonary embolism. Eur Heart J 2005; 26 (01) 77-83
- 7 Prandoni P, Bilora F, Marchiori A. et al. An association between atherosclerosis and venous thrombosis. N Engl J Med 2003; 348 (15) 1435-1441
- 8 Hansson PO, Eriksson H, Welin L, Svärdsudd K, Wilhelmsen L. Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: “the study of men born in 1913”. Arch Intern Med 1999; 159 (16) 1886-1890
- 9 Goldhaber SZ, Grodstein F, Stampfer MJ. et al. A prospective study of risk factors for pulmonary embolism in women. JAMA 1997; 277 (08) 642-645
- 10 Deguchi H, Pecheniuk NM, Elias DJ, Averell PM, Griffin JH. High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men. Circulation 2005; 112 (06) 893-899
- 11 Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA 2017; 318 (19) 1925-1926
- 12 Nikpay M, Goel A, Won HH. et al. A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet 2015; 47 (10) 1121-1130
- 13 Sudlow C, Gallacher J, Allen N. et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 2015; 12 (03) e1001779
- 14 Willer CJ, Schmidt EM, Sengupta S. et al; Global Lipids Genetics Consortium. Discovery and refinement of loci associated with lipid levels. Nat Genet 2013; 45 (11) 1274-1283
- 15 Chen J, Spracklen CN, Marenne G. et al; Lifelines Cohort Study, Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC). The trans-ancestral genomic architecture of glycemic traits. Nat Genet 2021; 53 (06) 840-860
- 16 Xue A, Wu Y, Zhu Z. et al; eQTLGen Consortium. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat Commun 2018; 9 (01) 2941
- 17 Liu M, Jiang Y, Wedow R. et al; 23andMe Research Team, HUNT All-In Psychiatry. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nat Genet 2019; 51 (02) 237-244
- 18 Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 2015; 44 (02) 512-525
- 19 Prandoni P. Venous thromboembolism and atherosclerosis: is there a link?. J Thromb Haemost 2007; 5 (Suppl. 01) 270-275
- 20 Gregson J, Kaptoge S, Bolton T. et al; Emerging Risk Factors Collaboration. Cardiovascular risk factors associated with venous thromboembolism. JAMA Cardiol 2019; 4 (02) 163-173
- 21 Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen PW. Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation 2008; 117 (01) 93-102
- 22 Mahmoodi BK, Cushman M, Anne Næss I. et al. Association of traditional cardiovascular risk factors with venous thromboembolism: an individual participant data meta-analysis of prospective studies. Circulation 2017; 135 (01) 7-16
- 23 Quist-Paulsen P, Naess IA, Cannegieter SC. et al. Arterial cardiovascular risk factors and venous thrombosis: results from a population-based, prospective study (the HUNT 2). Haematologica 2010; 95 (01) 119-125
- 24 Wattanakit K, Lutsey PL, Bell EJ. et al. Association between cardiovascular disease risk factors and occurrence of venous thromboembolism. A time-dependent analysis. Thromb Haemost 2012; 108 (03) 508-515
- 25 Fronek A, Criqui MH, Denenberg J, Langer RD. Common femoral vein dimensions and hemodynamics including Valsalva response as a function of sex, age, and ethnicity in a population study. J Vasc Surg 2001; 33 (05) 1050-1056
- 26 Davies HO, Popplewell M, Singhal R, Smith N, Bradbury AW. Obesity and lower limb venous disease – the epidemic of phlebesity. Phlebology 2017; 32 (04) 227-233
- 27 Lee KW, Lip GY. Effects of lifestyle on hemostasis, fibrinolysis, and platelet reactivity: a systematic review. Arch Intern Med 2003; 163 (19) 2368-2392
- 28 Pomp ER, Rosendaal FR, Doggen CJ. Smoking increases the risk of venous thrombosis and acts synergistically with oral contraceptive use. Am J Hematol 2008; 83 (02) 97-102
- 29 Tsai AW, Cushman M, Rosamond WD, Heckbert SR, Polak JF, Folsom AR. Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology. Arch Intern Med 2002; 162 (10) 1182-1189
- 30 van Stralen KJ, Le Cessie S, Rosendaal FR, Doggen CJ. Regular sports activities decrease the risk of venous thrombosis. J Thromb Haemost 2007; 5 (11) 2186-2192
- 31 Glynn RJ, Rosner B. Comparison of risk factors for the competing risks of coronary heart disease, stroke, and venous thromboembolism. Am J Epidemiol 2005; 162 (10) 975-982
- 32 Holst AG, Jensen G, Prescott E. Risk factors for venous thromboembolism: results from the Copenhagen City Heart Study. Circulation 2010; 121 (17) 1896-1903
- 33 Joyner MJ, Casey DP. Regulation of increased blood flow (hyperemia) to muscles during exercise: a hierarchy of competing physiological needs. Physiol Rev 2015; 95 (02) 549-601
- 34 Rauramaa R, Salonen JT, Seppänen K. et al. Inhibition of platelet aggregability by moderate-intensity physical exercise: a randomized clinical trial in overweight men. Circulation 1986; 74 (05) 939-944
- 35 Ray JG, Mamdani M, Tsuyuki RT, Anderson DR, Yeo EL, Laupacis A. Use of statins and the subsequent development of deep vein thrombosis. Arch Intern Med 2001; 161 (11) 1405-1410
- 36 Freeman DJ, Robertson M, Brown EA. et al. Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). BMC Geriatr 2011; 11: 8
- 37 Larsson SC, Burgess S, Mason AM, Michaëlsson K. Alcohol consumption and cardiovascular disease: a mendelian randomization study. Circ Genom Precis Med 2020; 13 (03) e002814