Correspondence
An Association between Atherosclerosis and Venous Thrombosis
N Engl J Med 2003; 349:401-402July 24, 2003
- Article
To the Editor:
Prandoni et al. (April 10 issue)1 report the results of a case–control study suggesting an association between atherosclerosis and deep venous thrombosis. In fact, the 95 percent confidence interval for the prevalence of plaque in the patients with spontaneous thrombosis (39.1 to 55.0) overlapped slightly with that in the control subjects (24.5 to 39.5), and the lower limit of the 95 percent confidence interval of the crude odds ratio for carotid plaque in the patients with spontaneous thrombosis as compared with the controls barely exceeded 1 (1.1). To appraise the meaning of these results, it is critical to include all the variables that may reasonably affect the outcome in the multivariate analysis. Because the use of statins reduces the development of carotid plaque2 and lowers the risk of the development of deep venous thrombosis,3,4 it is important to include this variable in the model. Similarly, data regarding the levels of high-density lipoprotein cholesterol would have been helpful, given the inverse relation between high-density lipoprotein cholesterol levels and carotid atherosclerosis.5 In addition, the authors' definitions of hypertension (a systolic blood pressure >160 mm Hg or a diastolic blood pressure >90 mm Hg) and smoking (habitual use of ≥10 cigarettes daily) can misclassify the presence of risk factors in the study groups.
5 ReferencesMurali K. Duggirala, M.D.
David A. Cook, M.D.
Karen F. Mauck, M.D.
Mayo Clinic, Rochester, MN 55905
duggirala.murali@mayo. edu 1
Prandoni P ,Bilora F ,Marchiori A , et al. An association between atherosclerosis and venous thrombosis. N Engl J Med 2003;348:1435-1441
Full Text | Web of Science | Medline2
MacMahon S ,Sharpe N ,Gamble G , et al. Effects of lowering average of below-average cholesterol levels on the progression of carotid atherosclerosis: results of the LIPID Atherosclerosis Substudy. Circulation 1998;97:1784-1790[Erratum, Circulation 1998;97:2479.]
Web of Science | Medline3
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;161:1405-1410
CrossRef | Web of Science | Medline4
Grady D ,Wenger NK ,Herrington D , et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease: the Heart and Estrogen/progestin Replacement Study. Ann Intern Med 2000;132:689-696
Web of Science | Medline5
Heiss G ,Sharrett AR ,Barnes R ,Chambless LE ,Szklo M ,Alzola C . Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study. Am J Epidemiol 1991;134:250-256
Web of Science | Medline
To the Editor:
Prandoni et al. found a significant association between spontaneous thrombosis and atherosclerosis even after adjustment for risk factors for these two conditions. It is unclear, however, why less than 50 percent of the subjects with spontaneous or secondary thrombosis were screened for thrombophilia. This is an important point because among those who tested positive for thrombophilia, a substantial proportion had hyperhomocysteinemia, factor V Leiden, or a lupus-like anticoagulant, with the greater number of thrombophilic abnormalities overall detected in the group with spontaneous thrombosis. These thrombophilic conditions are known to be risk factors for both atherosclerosis and venous thrombosis. Therefore, the thrombophilic status of the remaining, untested subjects could have significantly confounded the outcome of the study, especially because these conditions seem to have been more prevalent in the group with spontaneous thrombosis.
Yen F. Tai, M.B., B.S.
Imperial College London, London W12 0NN, United Kingdom
yen.tai@ic. ac. uk Author/Editor Response
Dr. Tai expresses the concern that testing for thrombophilic conditions in less than 50 percent of the subjects could have confounded the outcome of our study, since thrombophilia is more frequent in patients with spontaneous thrombosis and since some thrombophilic factors are known to be associated with atherosclerosis. However, among the patients with venous thrombosis, similar proportions of patients with spontaneous thrombosis and secondary thrombosis were tested. Therefore, confounding is unlikely since, after adjustment in the multivariate analysis, which included the variables “tested for thrombophilia” and “thrombophilia present,” the odds ratio for carotid lesions in those with spontaneous thrombosis as compared with those with secondary thrombosis (2.4) remained essentially the same as it had been in the univariate analysis (2.3).
Dr. Duggirala and colleagues stress the importance of including all variables that may reasonably affect the outcome in the multivariate analysis, since the lower limit of the 95 percent confidence interval of the crude odds ratio for carotid plaque in the patients with spontaneous thrombosis as compared with the controls barely exceeded 1. Unfortunately, high-density lipoprotein cholesterol levels were not measured. The use of statins was included in the definition of hyperlipidemia. However, statins were used by only a few patients in each group, since patients and controls with symptomatic atherosclerosis were excluded. Hence, statin use could not be included separately in the multivariate analysis. Although differential misclassification can indeed bias case–control studies, it is unlikely to have occurred with regard to hypertension and smoking status in our study, since none of the subjects were hospitalized or known to have an atherosclerotic condition. Therefore, if misclassification occurred, it would have resulted in a nondirectional bias.
Paolo Prandoni, M.D., Ph.D.
University of Padua Medical School, 35128 Padua, Italy
paoloprandoni@tin.it Anthonie W.A. Lensing, M.D., Ph.D.
University of Amsterdam, 1105 AZ Amsterdam, the NetherlandsMartin H. Prins, M.D., Ph.D.
Maastricht University, 6229 HX Maastricht, the Netherlands- Citing Articles (1)
Citing Articles
1
Michael G. Oefelein. (2008) Androgen suppression therapy and prostate cancer. Cancer 113:12, 3275-3278
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