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AJM theme issue: Obesity and diabetes Clinical research study| Volume 118, ISSUE 9, P978-980, September 2005

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Obesity as a risk factor in venous thromboembolism

      Abstract

      Purpose

      Whether obesity is an independent risk factor for pulmonary embolism or deep venous thrombosis has not been fully determined.

      Methods

      We used the database of the National Hospital Discharge Survey to further investigate the potential risk of obesity in venous thromboembolic disease.

      Results

      The relative risk of deep venous thrombosis, comparing obese patients with non-obese patients, was 2.50 (95% confidence interval [CI] = 2.49-2.51). The relative risk of pulmonary embolism was 2.21 (95% CI = 2.20-2.23). Obese females had a greater relative risk for deep venous thrombosis than obese males, 2.75 (95% CI = 2.74-2.76) versus 2.02 (95% CI = 2.01-2.04). Obesity had the greatest impact on both men and women aged less than 40 years.

      Conclusion

      The data indicate that obesity is a risk factor for venous thromboembolic disease in men as well as women.

      Keywords

      Although obesity has been suggested to be a risk factor for fatal pulmonary embolism since 1927,
      • Snell A.M.
      The relation of obesity to fatal postoperative pulmonary embolism.
      whether obesity is an independent risk factor for pulmonary embolism or deep venous thrombosis has not been fully determined. Investigations that reported an increased risk because of obesity have been criticized because they failed to control for hospital confinement or other risk factors.
      • Heit J.A.
      • Silverstein M.D.
      • Mohr D.N.
      • et al.
      The epidemiology of venous thromboembolism in the community.
      Although high proportions of patients with venous thromboembolic disease have been found to be obese,
      • Anderson Jr, F.A.
      • Wheeler H.B.
      • Goldberg R.J.
      • et al.
      A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study.
      • Anderson Jr, F.A.
      • Wheeler H.B.
      • Goldberg R.J.
      • Hosmer D.W.
      • Forcier A.
      The prevalence of risk factors for venous thromboembolism among hospital patients.
      the importance of the association is diminished because of the high proportion of obesity in the general population.
      • Hedley A.A.
      • Ogden C.L.
      • Johnson C.L.
      • et al.
      Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002.
      Even so, investigations have shown an increased risk ratio for deep venous thrombosis or pulmonary embolism in women.
      • Goldhaber S.Z.
      • Grodstein F.
      • Stampfer M.J.
      • et al.
      A prospective study of risk factors for pulmonary embolism in women.
      • Goldhaber S.Z.
      • Savage D.D.
      • Garrison R.J.
      • et al.
      Risk factors for pulmonary embolism. The Framingham Study.
      • Abdollahi M.
      • Cushman M.
      • Rosendaal F.R.
      Obesity risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.
      • Coon W.W.
      • Coller F.A.
      Some epidemiologic considerations of thromboembolism.
      In men, the data are less compelling. One investigation showed obesity to be a risk factor in men
      • Hansson P.O.
      • Eriksson H.
      • Welin L.
      • Svardsudd K.
      • Wilhelmsen L.
      Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: “the study of men born in 1913.”.
      and 2 investigations did not.
      • Goldhaber S.Z.
      • Savage D.D.
      • Garrison R.J.
      • et al.
      Risk factors for pulmonary embolism. The Framingham Study.
      • Coon W.W.
      • Coller F.A.
      Some epidemiologic considerations of thromboembolism.
      Some found no evidence that obesity was an independent risk factor in men or women.
      • Heit J.A.
      • Silverstein M.D.
      • Mohr D.N.
      • et al.
      The epidemiology of venous thromboembolism in the community.
      Case series of morbidly obese patients (>100 lb overweight or twice the ideal weight) who underwent gastric bypass surgery showed only a small incidence of postoperative venous thromboembolism.
      • Kerstein M.D.
      • McSwain Jr, N.E.
      • O’Connell R.C.
      • Webb W.R.
      • Brennan L.A.
      Obesity is it really a risk factor in thrombophlebitis?.
      • Printen K.J.
      • Miller E.V.
      • Mason E.E.
      • Barnes R.W.
      Venous thromboembolism in the morbidly obese.
      We used the database of the National Hospital Discharge Survey (NHDS)

      US Department of Health and Human Services, Public Health Service, National Center for Health Statistics National Hospital Discharge Survey 1979-1999 Multi-year Public-Use Data File Documentation. Available at: http://www.cdc.gov/nchs/about/major/hdasd/nhds.htm. Acessed June 30, 2005.

      to further investigate the potential risk of obesity in venous thromboembolism.

      Materials and methods

      Data sources

      The number of patients discharged from hospitals with a diagnostic code of obesity between 1979 and 1999 was obtained from the NHDS.

      US Department of Health and Human Services, Public Health Service, National Center for Health Statistics National Hospital Discharge Survey 1979-1999 Multi-year Public-Use Data File Documentation. Available at: http://www.cdc.gov/nchs/about/major/hdasd/nhds.htm. Acessed June 30, 2005.

      Among these patients the number with pulmonary embolism or deep venous thrombosis was determined.
      The NHDS consists of data obtained annually from 181 000 to 307 000 sampled patient abstracts from 400 to 494 non-Federal short-stay hospitals in 50 states and the District of Columbia.

      US Department of Health and Human Services, Public Health Service, National Center for Health Statistics National Hospital Discharge Survey 1979-1999 Multi-year Public-Use Data File Documentation. Available at: http://www.cdc.gov/nchs/about/major/hdasd/nhds.htm. Acessed June 30, 2005.

      The NHDS samples approximately 8% of short-stay non-Federal hospitals and approximately 1% of discharges.

      Identification of obesity

      The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code used to identify obesity was 278.0. The basis for the diagnosis of obesity was not stated.

      Identification of pulmonary embolism

      The ICD-9-CM codes used for identification of patients with pulmonary embolism were 415.1, 634.6, 635.6, 636.6, 637.6, 638.6, and 673.2.

      Identification of deep venous thrombosis

      The codes used for deep venous thrombosis were 451.1, 451.2, 451.8, 451.9, 453.2, 453.8, 453.9, 671.3, 671.4, and 671.9. Five-digit codes, such as 451.11 (included under the code 451.1), were not listed because they were included under the corresponding 4-digit codes.

      Identification of venous thromboembolic disease

      Patients with either pulmonary embolism or deep venous thrombosis were identified as having venous thromboembolism.

      Statistical analysis and methodologic considerations

      Relative risks and 95% confidence intervals (CIs) were calculated with the “calculator for confidence intervals of relative risk.”

      Hutchon DJR. Available at: http://www.hutchon.freeserve.co.uk/ConfidRR.htm. Acessed June 28, 2005.

      Standard deviation was calculated with SPSS version 11.5 (SPSS, Inc, Chicago, Ill).

      Results

      The proportion of hospitalized patients diagnosed with obesity ranged from 1.4% to 2.4% over the 21-year period of observation. Among hospitalized patients diagnosed with obesity, 91 000 of 12 015 000 (0.76%) had pulmonary embolism. Among hospitalized patients who were not diagnosed with obesity, pulmonary embolism was diagnosed in 2 366 000 of 691 000 000 (0.34%). Deep venous thrombosis was diagnosed in 243 000 of 12 015 000 patients (2.02%) diagnosed with obesity and in 5 524 000 of 691 000 000 patients (0.80%) who were not diagnosed with obesity. The average ages of obese patients with pulmonary embolism (57 ± 17 years) (mean ± standard deviation) and deep venous thrombosis (55 ± 15 years) were lower than the average ages of non-obese patients with pulmonary embolism (64 ± 12 years) and deep venous thrombosis (61 ± 11 years).
      The relative risk of deep venous thrombosis, comparing obese patients with non-obese patients, was 2.50 (95% CI = 2.49-2.51). The relative risk of pulmonary embolism was 2.21 (95% CI = 2.20-2.23). Obese females had a greater relative risk for deep venous thrombosis than obese males, 2.75 (95% CI = 2.74-2.76) versus 2.02 (95% CI = 2.01-2.04). Data were sufficient for comparison of the relative risk of pulmonary embolism according to age and sex only among patients aged 60 to 69 years and 70 to 79 years. For those aged 60 to 69 years, the relative risk for pulmonary embolism was 1.48 (95% CI = 1.45-1.50) in women and 1.27 (95% CI = 1.24-1.30) in men. For those aged 70 to 79 years, the relative risk for pulmonary embolism was 2.12 (95% CI = 2.09-2.16) in women and 1.90 (95% CI = 1.85-1.95) in men.
      Obesity had the greatest impact on patients aged less than 40 years, in whom the relative risk for pulmonary embolism in obese patients was 5.19 (95% CI = 5.11-5.28) and the relative risk for deep venous thrombosis was 5.20 (95% CI = 5.15-5.25) (Table 1). In females aged less than 40 years, the relative risk for deep venous thrombosis comparing obese with non-obese patients was 6.10 (95% CI = 6.04-6.17). In males aged less than 40 years, the relative risk for deep venous thrombosis was 3.71 (95% CI = 3.64-3.79).
      Table 1Relative risks of pulmonary embolism and deep venous thrombosis according to age among obese and non-obese patients
      Age groupsPulmonary embolismDeep venous thrombosis
      Obese vs non-obeseObese vs non-obese
      Relative risk(95% CI)Relative risk(95% CI)
      <40 y5.19(5.11–5.28)5.20(5.15–5.25)
      40–49 y1.94(1.91–1.97)2.13(2.11–2.15)
      50–59 y1.25(1.23–1.27)1.67(1.65–1.68)
      60–69 y1.42(1.40–1.44)1.88(1.87–1.90)
      70–79 y2.07(2.04–2.10)1.89(1.87–1.91)
      >80 y3.15(3.08–3.22)2.16(2.12–2.20)
      All ages2.18(2.16–2.19)2.50(2.49–2.51)
      CI = confidence interval.

      Discussion

      These data show that obesity is a risk factor for pulmonary embolism and deep venous thrombosis in men as well as women. Obesity seems to be a stronger risk factor in women and in men and in women less than 40 years of age.
      An advantage of the NHDS database is its extensive coverage of all races, ages, and regions of the United States. A disadvantage is that the basis for the diagnosis of obesity was not defined. Even so, the proportion of hospitalized patients diagnosed with obesity was within a narrow range over the period of observation, indicating consistency in the diagnostic process. Previous investigators used several indices of obesity including a body mass index (BMI) greater than 35 kg/m2, BMI 30 to 35 kg/m2,
      • Farmer R.D.
      • Lawrenson R.A.
      • Todd J.C.
      • et al.
      A comparison of the risks of venous thromboembolic disease in association with different combined oral contraceptives.
      BMI greater than 30 kg/m2,
      • Goldhaber S.Z.
      • Savage D.D.
      • Garrison R.J.
      • et al.
      Risk factors for pulmonary embolism. The Framingham Study.
      • Printen K.J.
      • Miller E.V.
      • Mason E.E.
      • Barnes R.W.
      Venous thromboembolism in the morbidly obese.
      BMI greater than 29 kg/m2,
      • Goldhaber S.Z.
      • Grodstein F.
      • Stampfer M.J.
      • et al.
      A prospective study of risk factors for pulmonary embolism in women.
      weight more than 20% of median recommended weight for height,
      • Anderson Jr, F.A.
      • Wheeler H.B.
      • Goldberg R.J.
      • et al.
      A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study.
      and waist circumference greater than 100 cm.
      • Hansson P.O.
      • Eriksson H.
      • Welin L.
      • Svardsudd K.
      • Wilhelmsen L.
      Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: “the study of men born in 1913.”.
      The physicians’ assessment was accepted in 28% to 33% of patients reported by Anderson and associates.
      • Anderson Jr, F.A.
      • Wheeler H.B.
      • Goldberg R.J.
      • et al.
      A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study.
      • Anderson Jr, F.A.
      • Wheeler H.B.
      • Goldberg R.J.
      • Hosmer D.W.
      • Forcier A.
      The prevalence of risk factors for venous thromboembolism among hospital patients.
      It is likely that all patients with obesity diagnoses in the NHDS database were in fact obese, irrespective of the criteria used. However, some obese patients may not have had a listed discharge diagnosis of obesity, and they would have been included in the non-obese group. This would have tended to reduce the relative risk of obesity in venous thromboembolism. The somewhat younger ages of obese patients with pulmonary embolism and deep venous thrombosis, compared with non-obese patients, would have decreased the relative risk of obesity.
      The relative risks for pulmonary embolism and deep venous thrombosis were similar to relative risks reported in smaller investigations that used defined criteria for obesity. In women with a BMI greater than 30 kg/m2, the relative risk for deep venous thrombosis, compared with non-obese women, was 2.4.
      • Abdollahi M.
      • Cushman M.
      • Rosendaal F.R.
      Obesity risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.
      In women with a BMI of 29 kg/m2 or more, the relative risk for pulmonary embolism was 2.9.
      • Goldhaber S.Z.
      • Grodstein F.
      • Stampfer M.J.
      • et al.
      A prospective study of risk factors for pulmonary embolism in women.
      In the Framingham Study, obesity was a risk factor only in women.
      • Goldhaber S.Z.
      • Savage D.D.
      • Garrison R.J.
      • et al.
      Risk factors for pulmonary embolism. The Framingham Study.
      Coon and Coller
      • Coon W.W.
      • Coller F.A.
      Some epidemiologic considerations of thromboembolism.
      also showed that obesity was a risk factor only in women. Oral contraceptives in obese women increased the relative risk of deep venous thrombosis to 9.8.
      • Abdollahi M.
      • Cushman M.
      • Rosendaal F.R.
      Obesity risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.
      Men with a waist circumference of 100 cm or more had a relative risk of 3.9 for venous thromboembolism compared with men with smaller waists.
      • Hansson P.O.
      • Eriksson H.
      • Welin L.
      • Svardsudd K.
      • Wilhelmsen L.
      Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: “the study of men born in 1913.”.
      Among men and women together, the risk ratio for deep venous thrombosis, comparing obese with non-obese patients, was 2.39.
      • Samama M.M.
      An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients the Sirius study.
      Some found that obesity was not an independent risk factor for venous thromboembolism.
      • Heit J.A.
      • Silverstein M.D.
      • Mohr D.N.
      • et al.
      The epidemiology of venous thromboembolism in the community.
      In conclusion, the data indicate that obesity is a risk factor for venous thromboembolism in men as well as women.

      Acknowledgment

      Julia Sanchez, MD, and Tehmina Siddiqui, MD, assisted with this investigation.

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      1. US Department of Health and Human Services, Public Health Service, National Center for Health Statistics National Hospital Discharge Survey 1979-1999 Multi-year Public-Use Data File Documentation. Available at: http://www.cdc.gov/nchs/about/major/hdasd/nhds.htm. Acessed June 30, 2005.

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        • Farmer R.D.
        • Lawrenson R.A.
        • Todd J.C.
        • et al.
        A comparison of the risks of venous thromboembolic disease in association with different combined oral contraceptives.
        Br J Clin Pharmacol. 2000; 49: 580-590
        • Samama M.M.
        An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients.
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