Takayasu Arteritis in Terms of Disease Duration and Sex Differences

Systemic vasculitis is a multisystemic vasculopathy, classified primarily by the size of the affected vessels (Chapel Hill classification).¹ The term “large vessel” is used for conditions involving the aorta and its major branches, and the most common etiologies of large-vessel vasculitis (LVV) are Takayasu arteritis (TAK) and giant cell arteritis.² Identification of vasculitis in the early stage is important because it reduces the risk of death. Delayed diagnosis or disease left unchecked with incorrect management³ can lead to progression that could otherwise have been avoided or mitigated, directly leading to a greater number and severity of complications and even worse life expectancy. Therefore, recognition of the incidence and prevalence rates, and clinical characteristics of patients with vasculitis, as well as sex, ethnic, and regional differences, is of great importance.

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TAK is a LVV affecting a relatively younger population. The prevalence and incidence of TAK are reported to be higher in Asia than in other parts of the world. For instance, the prevalence is reported to be 40 per million in Japan and ≈5 per million in the UK.⁴ On the other hand, the incidence rate in South Korea is reported to be 2.5 per million per year.⁴

TAK causes stenosis, occlusion or dilation of the aorta, and/or its first branches, and/or pulmonary arteries, resulting in cerebral ischemic attack, aortic regurgitation, aortic aneurysm, heart failure, blindness, renal failure, pulmonary hypertension, and pulmonary aneurysm, etc.⁵ Although the precise etiology of TAK is unknown, the possible involvement of genetic factors has been suggested. For instance, HLA-B*52 is reported to be associated with TAK.⁶ In addition, 2 independent susceptibility loci in the HLA region (HLA-B/MICA and HLA-DQB1/HLA-DRB1) were identified in a study of Turkish, North American, and European patients.⁷

In their epidemiological study, Comarmond et al analyzed 318 TAK patients from referral centers in the French Takayasu network, which included multiple ethnicities, and reported that the median age at TAK diagnosis was 36 (25–47) years, and 86.8% (276 patients) were female.⁵ They also reported that male sex was associated with relapse-free survival, but there was no sex difference in the prevalence of complications.⁵ In a cross-country study in Japan, Watanabe et al⁸ analyzed the clinical characteristics of a larger population of 1,372 TAK patients who were newly registered. Their study revealed a median age at onset of 35 years (quartiles 1–3, 22–56.8 years), with women (median age 34 years) having a younger age of onset than men (median age 43.5 years). The mean duration of disease was also reported to be longer in women, but interestingly, both the presence and frequency of complications were more common in men. For example, ischemic heart disease (14.4% vs. 9.9%; men vs. women), ocular complications (18.9% vs. 13.9%), aortic aneurysm (24.3% vs. 13.2%), aortic dissection (4.5% vs. 1.4%) and renal dysfunction (15.3% vs. 10.4%) were all more prominent in male than female patients. The number of complications per patient was reported to be ≈2 for men and 1 for women. In addition, when classified by interval from onset to registration of <1 year or >1 year, female patients who have had these complications for <1 year have a lower frequency of these complications. However, it is unclear whether these complications and their severity actually affect patients’ quality of life, and whether there is a sex difference.

In this issue of the Journal, the study by Yoshifuji and co-workers⁹ is a valuable report of the data from the Japanese Ministry of Health, Labor and Welfare (MHLW) registry for TAK, which analyzed 2,013 cases out of a total of 2,795 cases in the 2013 fiscal year. Because most Japanese patients with confirmed diagnoses of TAK would have been enrolled in this program on the assumption that they would receive financial assistance, this big data set is considered to be a reliable reflection of the current status of TAK in Japan.

It has been difficult to analyze patients stratified by disease duration or sex due to the small number of cases in many previous reports, whereas the big data set used by Yoshifuji et al⁹ made it possible. First, they stratified patients into 4 groups based on disease duration (new-onset, early-onset, late-onset, and very late-onset), and analyzed the prevalence of symptoms, organ damage, and inflammatory markers by disease duration. The prevalence of organ damage such as aortic regurgitation, aortic aneurysm, ischemic heart disease, renal dysfunction, brain ischemia, visual impairment, and blindness increased with increasing disease duration, while the proportion of patients who did not require nursing care decreased. The second point worth mentioning is the comparison of clinical characteristics by sex. In the present study’s patient population, as in previous reports, the male-to-female ratio of prevalence was 1 : 9 (i.e., the proportion of male patients in the analysis was low), but analysis of data from a large population made it possible to compare male and female patients. They reported that female patients had a lower age of onset and a longer disease duration than male patients, similar to previous results.⁸ In terms of organ damage, women showed a higher prevalence of aortic regurgitation and renal dysfunction. Interestingly, quality of life was also examined using indices of nursing care and employment and school attendance, and the results revealed that female patients had a higher risk of needing nursing care and lower employment or school attendance rate.

As a limitation, this study analyzed only patients with TAK in Japan, which can be considered as almost one race. Previous reports have suggested that racial differences may cause differences in event-free survival. Future studies are needed to determine whether the present results are directly applicable to other regions or other ethnic groups.⁵ Nevertheless, the current study is the first to present epidemiological evidence regarding the effect of disease duration or sex differences on organ damage and the social activity level of patients with TAK. Based on these findings, early diagnosis of TAK is expected to reduce the number and severity of complications and improve quality of life.

Acknowledgment

Supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 22K08201) to Y.S.

Disclosures

T.M. is a member of Circulation Journal’s Editorial Team.

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