Discussion

Our data show that patients with AS are at a higher risk for comorbidities involving multiple systems than the general population. We found the comorbidity profiles were largely similar between Chinese and Western populations with AS. The use of a nationwide database in our study provides sufficient statistical power to detect subtle differences. Nevertheless, it is unrealistic to assume all significant differences reflecting the direct pathological mechanism of AS and comorbidities. Several circumstances could explain the association between AS and the comorbidities we observed including: (1) direct casualty in the pathological mechanism; (2) shared common pathway or biological background; and (3) occult irrelevant variables beside the ‘true’ pathological mechanism. Our study provides fundamental data exploring a wide spectrum of comorbidities among the patients with AS. Careful interpretation and further clarification of our findings are suggested.

In addition, the differences between statistical significance and impact in interpreting study results should be noted for more detailed consideration of our findings. Specifically, even if the relative risk is minor, the association between AS and some comorbidities such as hypertension could still have a great impact due to its relatively high prevalence among a large affected population. On the other hand, despite the higher relative risk, ischaemic heart disease might not possess much clinical significance because the prevalence is relatively low (0.3%). Both prevalence and relative risk should thus be considered in investigating the impacts of comorbidities among patients with AS. Gender difference in comorbidity risk profiles was also notable in our study. Gender differences in clinical course and disease presentation of AS have been previously recognised.2 11 We propose that gender may be also an important factor in comorbidities associated with AS.

Inflammatory processes in autoimmune diseases are considered a factor in the initiation and progression of atherosclerosis.12 13 Studies have shown that atherosclerosis and cardiovascular risks are also increased in populations with AS.8 14 15 Our data show that cardiovascular comorbidities are also increased in a Chinese population with AS. However, we found no increased risk for stroke among patients with AS. Data for exploring the association between stroke and AS remain lacking. Establishing the risk of stroke for a Western population with AS should be considered for further research. Recently, the European League Against Rheumatism has published recommendations for cardiovascular risk management in patients with inflammatory arthritis. Adequate control of disease activity, regular cardiovascular risk assessment, controlling risk factors and pharmacological considerations are all recommended to reduce cardiovascular risk for these patients.16 Cardiovascular diseases can be associated with increased mortality and morbidity in patients with inflammatory arthritis. Adequate cardiovascular risk management can improve care for these patients.

In patients with AS who had received radiotherapy previously, a higher risk for malignancies has been reported, particularly leukaemia.17 However, radiotherapy is no longer applied AS treatment. We did not find that the risk of malignancy increased in patients with AS, consistent with a study performed in patients with AS who did not receive radiotherapy.18 We should note that our findings may be confounded by the relatively young age of our subjects. A considerable proportion of patients with AS in our study had headache. Cervical spondylitis, psychological stress or chronic use of non-steroidal anti-inflammatory drugs may be contributing factors to headache in patients with AS. Interestingly, we also found the risk of migraine was increased in patients with AS. To our knowledge, this is the first report to demonstrate an increased prevalence of migraine in the population with AS. An association between headache and migraine and other autoimmune diseases has been noted previously.19 20 Further study is suggested to confirm our findings and explore possible the pathological mechanisms.

Our study has several limitations. First, the validity of diagnoses cannot be confirmed in our study. However, we analysed the stability of AS diagnoses by our selection criteria and found the result to be acceptable. Second, because our goal is to determine the overall risk for various comorbidities in the population with AS, we did not review the subjects' medications as a confounding factor. Third, cause–effect relationships cannot be determined in our study. A longitudinal study may be needed. Finally, the design of this current study cannot preclude possible investigation bias—that is, if a patient is receiving medical care for a particular disease that increases the likelihood of finding another subclinical disease, or that the patient seeks attention for an otherwise unrelated condition. The prevalence of medical comorbidities among patients in the comparison group may therefore be underestimated.