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We reviewed retrospectively 126 (5 male, 121 female) patients suffering from Takayasu arteritis who had been treated in our clinics from 1971 to 1990. The patients' ages ranged from 19 to 80 yrs old (1990) with a mean age of 48.7 +/- 11.8 years. HLA typing analysis in 98 patients revealed that 45 patients (47%) were confirmed as carrying the Bw52 antigen, a high result that is statistically significant as compared with that in healthy Japanese. Arteriograms (performed in 75 patients) revealed that 28 patients (37%) were affected in the aorta and its main branches by this disease (type IV by Nasu's classification) and 23 patients (31%) were affected only in the main branches (type I). The C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) improved significantly from 2.55 +/- 0.28(+) and 57.0 +/- 5.69 mm/hr to 0.53 +/- 0.12(+) and 31.2 +/- 3.45 mm/hr, respectively after treatment including steroid and antiplatelet therapy (P < 0.01). Patients with Bw52 exhibited more severe inflammatory conditions than those without Bw52. Lung scintillations performed in 81 patients showed pulmonary arterial lesions in 50 patients (62%). Echocardiograms revealed aortic regurgitation (AR) in 44 patients (35%), with a significant difference noted between the Bw52 positive group and the Bw52 negative group [29/40 (73%) versus 11/47 (23%), respectively, P < 0.001]. Patients with Bw52 were prescribed higher doses of steroids (P < 0.05) for longer periods (P < 0.01) than those without Bw52.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart disease is the main cause of death in patients with Takayasu arteritis. It has been reported that this disease is closely related to the presence of HLA Bw52 antigen. To assess the correlation between this antigen and left ventricular involvement, we studied 40 patients with Takayasu arteritis, 21 with and 19 without Bw52, using Tl-201 stress myocardial scintigraphy and echocardiography. Those with Bw52 had a significantly higher incidence of abnormal electrocardiographic findings (67% vs 26%; P < 0.05) and of aortic regurgitation (52% vs 11%; P < 0.05). The echocardiographically determined interventricular septal wall thickness plus left ventricular posterior wall thickness (25 +/- 8 vs 17 +/- 3 mm; P < 0.01) and the left ventricular mass (257 +/- 132 vs 142 +/- 51 g; P < 0.01) were significantly increased in the patients with Bw52. Scintigraphically determined perfusion abnormalities were significantly more frequent in those with Bw52 (76% vs 32%; P < 0.05). These observations indicate that patients with Takayasu arteritis and Bw52 antigen have a more severe left ventricular involvement than the patients without that antigen. The left ventricular impairment may account for the poor prognosis of Takayasu patients with Bw52.

To characterize aortic regurgitation in patients with Takayasu arteritis, we studied 48 females with arteritis (mean age 47 +/- 12 years) by means of color Doppler echocardiography. Aortic regurgitation was confirmed in 32 out of 48 patients (67%) by color-flow mapping. Twenty-four patients had mild or no aortic regurgitation (group A), 9 had moderate (group B), and 15 had severe (group C) aortic regurgitation. We compared the echocardiographic data obtained from patients with Takayasu arteritis with those of 14 normal controls and 9 patients with severe aortic regurgitation of valvular origins (group V). The aortic root diameter (AOD) in group B (23 +/- 4 mm/M2) and group C (22 +/- 3 mm/M2) revealed a statistically significant large value as compared with that in group A (18 +/- 2 mm/M2) and normal controls (17 +/- 3 mm/M2). However, the differences, between groups B and C and groups C and V, were not significant. The AOD was not obviously dilated in a considerable number of group C patients. Aortic valve involvement was seen in several group C patients and moderate concentric left ventricular hypertrophy was present in all group C patients. Group C patients therefore, have concentric left ventricular hypertrophy but may or may not have dilatation of the aortic root which can be detected on echocardiography. We conclude that aortic valve involvement may cause aortic regurgitation in some patients with Takayasu arteritis and that aortic regurgitation is more common than previously believed.

This communication reviews the clinical and pathological features of coronary artery lesions in Takayasu arteritis. The incidence of coronary artery involvement has been reported to be 9% to 10%, and is observed mainly in autopsy cases because coronary artery disease is usually not evident until the occurrence of angina pectoris or myocardial infarction, or after the onset of congestive heart failure. On the basis of pathological features, the following three types of coronary artery lesions can be distinguished: type 1, stenosis or occlusion of the coronary ostia and the proximal segments of the coronary arteries; type 2, diffuse or focal coronary arteritis, which may extend diffusely to all epicardial branches or may involve focal segments, so-called skip lesions; and type 3, coronary aneurysm. Most of the coronary artery lesions in Takayasu arteritis are of type 1. Narrowing of the coronary arteries is mainly due to the extension of the inflammatory processes of proliferation of the intima and contraction of the fibrotic media and adventitia from the ascending aorta. In some cases, coronary stenosis may be caused by coronary arteritis as skip lesions in Takayasu arteritis, but even in these cases the lesions have been reported to affect mainly the proximal segments of the coronary arteries. Diffuse lesions of the coronary artery and coronary artery aneurysm seem to be very rare in Takayasu arteritis. Other causes of coronary ostial stenosis, coronary arteritis and coronary artery aneurysm are also discussed.

To evaluate the influence of pregnancy on the morbid condition of Takayasu arteritis, we summarized the clinical data and pregnant courses of 18 patients with Takayasu arteritis and a total of 22 deliveries. We followed C-reactive protein (CRP) scores in 16 of 18 patients (20 of 22 deliveries) to ascertain the inflammatory condition inherent in Takayasu arteritis 1 year prior to, during, and 1 year after pregnancy. We also evaluated digital plethysmograms (pulse amplitude, pulse wave, crest time) to follow the hemodynamical condition of patients before, during, and after pregnancy. CRP scores improved significantly during pregnancy and 1 year after delivery. In the digital plethysmograms, pulse amplitude and wave also exhibited improvement after delivery, but crest time remained unchanged. This indicated that pregnancy is a state favorable to this disease. Some factors, such as the sex hormone progesterone, may induce this condition, but the details are still unknown. In conclusion, inflammatory activity and the hemodynamic state improve with pregnancy in patients with Takayasu arteritis. The physiologic aspects which cause this improvement should be maintained even after pregnancy.

Little attention has been paid to the pathological features of the pulmonary artery in Takayasu arteritis. Autopsy specimens of 6 cases of this disease were studied. Lesions were found in the aortic arch and its brachiocephalic branches in all cases and in both the aortic arch and thoracoabdominal aorta in 5 cases. The pathohistologic characters of the pulmonary artery were very similar to those of the systemic artery. Stenosis-recanalization, so-called blood vessels-in-blood vessels, of the pulmonary elastic arteries were found in four cases. These lesions were not observed in the systemic arteries, and most of the newly formed channels in them seemed to be branches of bronchial arteries. Luminal obstruction of pulmonary muscular arteries was observed in 4 cases, cellular arteritis of muscular arteries in 2 cases, and angiomatoid dilatation of small blood vessels in 2 cases. Thus in this study we found peculiar stenosis-recanalization lesions of the pulmonary elastic arteries, and also showed that the pulmonary elastic and muscular arteries are frequently involved in Takayasu arteritis. These findings suggest that pulmonary hypertension could influence morbidity and long-term mortality in this disease.

To investigate genetic factors involved in the pathogenesis of Takayasu arteritis, patients in the Japanese population were examined for HLA-A, -B, and -C alleles by serological typing and for HLA-DR, DQ, and DP alleles by DNA typing using polymerase chain reaction (PCR)/sequence-specific oligonucleotide probe (SSOP) analysis. The frequencies of HLA-Bw52, DRB1*1502, DRB5*0102, DQA1*0103, DQB1*0601, and DPB1*0901 alleles were significantly increased and the frequencies of HLA-Bw54, DRB1*0405, DRB4*0101, DQA1*0301, and DQB1*0401 alleles were significantly decreased. Strong linkage disequilibria among the increased alleles and among the decreased alleles were evident in the Japanese population. Therefore, the haplotype of HLA-B252-DRB1*1502-DRB5*0102-DQA1*0103-DQB1++ +*0601-DPA1*02-DPB1*0901 may confer susceptibility to Takayasu arteritis while another haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer resistance to the disease. These observations clearly indicate that HLA-linked gene(s) are involved in the development of Takayasu arteritis.

Takayasu arteritis is a chronic vasculitis characterized by a clinical pulseless condition and is predominant in young female patients. Its loci is found mainly in Asian countries, and its etiology is still unknown. Our experiences of cases of twin sisters with Takayasu arteritis led us to suppose that hereditary factors participate in the pathophysiology of this disease. Population and family-incidence studies employing HLA analysis in Japan have focused on an complotype Aw24-DW52-C4A2-C4BQ0-Dw12 which was in disequilibrium with Takayasu arteritis. Clinical features and clinical courses were found to be intimately related to this complotype. Recent studies on HLA typing in other countries have also suggested the important roles of hereditary factors in this morbid condition and international collaborative studies on these hereditary factors are now under way.

A Japan-Korea cooperative survey on Takayasu arteritis has shown some differences in the features between Japanese and Korean patients with this disease. In angiographic findings, Japanese patients more frequently had lesions at the aortic arch and/or its branches (58% of 75 cases), while, in Korean patients, the abdominal aorta is the site of relatively frequent lesions (30% of 112 cases). Higher occurrence of HLA-Bw52 was found in Japanese patients in comparison with Korean patients (46% vs 15%). The presence of HLA-Bw52, however, might have a close association with Takayasu arteritis in Korea as well as in Japan. The complications in 126 Japanese and 88 Korean patients were also compared. The complications occurring with higher frequency in Japanese patients were aortic regurgitation, ischemic heart disease, and visual disturbances, while, in Korean patients, the more frequent complications were renovascular hypertension as well as hypertension of some other etiology.