Risk of coronary heart disease in patients with cancer: A nationwide follow-up study from Sweden
Introduction
Coronary heart disease (CHD) and myocardial infarction are the major causes of morbidity and mortality worldwide.1 An association between cancer and venous thromboembolism (VTE) has been recognised since at least 1865.2 Cancer increases the risk of VTE 4- to 6-fold.2 Patients with cancer frequently have laboratory evidence of haemostatic activation.3 Tumour cells produce various cytokines and chemokines that attract leucocytes, which result in an inflammatory response.4 This may in turn have prothrombotic and atherosclerotic effects.5, 6, 7
An increased risk of CHD has been reported in patients with lung cancer,8 breast cancer,9 Hodgkin’s lymphoma10, 11 and non-Hodgkin’s12 lymphoma who were treated with radiation. However, two studies of breast cancer patients treated with radiation did not find an increased CHD risk.13, 14 Mediastinal radiation therapy is an established risk factor for CHD among cancer patients.15 However, there are many other potential prothrombotic mechanisms in cancer patients such as increased platelet activation and aggregability, damaged or dysfunctional endothelium, increased number of circulating microparticles, procoagulants changed due to chemotherapy and angiogenesis (reviewed by Blann and Dunmore).16 Moreover, cancer and CHD share a common risk factor (tobacco smoke), and an increased risk of CHD would be expected among patients with smoking-related cancers (i.e. cancers of the lung, larynx, oesophagus, mouth and tongue, pharynx, urinary bladder, pancreas and kidney).17, 18, 19, 20 Other suspected smoking-related cancers sites include lip, liver, cervix, stomach, leukaemia and salivary gland. Thus, cancer and CHD share a number of risk factors and an increased risk of CHD among cancer patients would be expected. However, the CHD risk in cancer patients has been much less thoroughly investigated than the VTE risk.1, 2
We hypothesised that haemostatic activation and inflammation associated with cancer may affect risk of CHD. In a nationwide follow-up study of data from 1987 to 2008 we estimated risk of hospitalisation for CHD in all Swedish patients diagnosed with cancer.
Section snippets
MigMed 2 Database
This study was approved by the Ethics Committee of Lund University, Sweden. Data used in this study were retrieved from the MigMed 2 Database (an updated version of the original MigMed database), maintained at the Center for Primary Health Care Research, Lund University/Region Skåne, Malmö. MigMed 2 contains data on all individuals registered as residents of Sweden. It contains individual-level information on age, sex, occupation, geographic region of residence, hospital diagnoses and dates of
Results
Table 1 shows the basic characteristics of patients with and without cancer who were hospitalised with CHD during the study period. A total of 573,494 individuals without cancer were hospitalised with a main diagnosis of CHD (Table 1), while 34,666 individuals with cancer were subsequently hospitalised for CHD (Table 1). The four most common cancers were prostate cancer (139,510 cases), breast cancer (116,358), colon cancer (61,802) and lung cancer (59,644) (Supplementary Table 1).
The risk of
Discussion
The present study is the first nationwide study that shows that cancer is associated with an increased risk of CHD. The causes behind our findings are, however, not clear and may be related to many factors such as common risk factors, treatment, cancer related inflammation and haemostatic activation. Moreover, this effect is not limited to smoking-related cancers. Several non-smoking related cancers were also associated with increased risk of CHD (Table 2). The risk of CHD during the first 6
Role of the funding source
None.
Contributors
All authors contributed to the conception and design of the study; J.S and K.S. contributed to the acquisition of data; all authors contributed to the analysis and interpretation of data; B.Z. drafted the manuscript; and all authors revised it critically and approved the final version. All authors had full access to all of the data (including statistical reports and tables) and take responsibility for the integrity of the data and the accuracy of its analysis.
Conflict of interest statement
None declared.
Acknowledgements
The authors wish to thank the CPF’s Science Editor Stephen Gilliver for his useful comments on the text. The registers used in the present study are maintained by Statistics Sweden and the National Board of Health and Welfare. This work was supported by grants to Kristina and Jan Sundquist from the Swedish Research Council (2008-3110 and 2008-2638), the Swedish Council for Working Life and Social Research (2006-0386, 2007-1754 and 2007-1962), and Formas (2006-4255-6596-99 and 2007-1352), and to
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