The present study aimed to summarize the disease characteristics of hypertensive TAK patients and highlight potential determinants to the EFS. We found that: i) about 33% TAK patients in our cohort suffered from hypertension, among whom, almost half were severe hypertension; ii) three specific imaging phenotypes were identified for hypertensive TAK patients, which could be distinguished from non-hypertensive cases; iii) only 50.8% patients got controlled blood pressure in the present study and the overall EFS was 67.9% by the end of a median 48 months follow-up; iv) patients with controlled hypertension showed better EFS, while imaging phenotype also showed effects on the EFS, though not statistically significant.
Previous studies have reported that hypertension occurred in 33–83% TAK patients, with younger disease onset age (mostly < 40 years) [7–10, 21]. One former study even indicated that a combination of hypertension and elevated erythrocyte sedimentation rate (ESR) was useful for diagnosing TAK in patients < 18 years of age . Our data pointed out that 33% TAK patients suffered from hypertension, which was consistent with these previous studies. Furthermore, severe hypertension was observed in almost half of the hypertensive cases in our cohort, and severe hypertensive patients were more likely to complain of renal insufficiency and failure to control the elevated blood pressure. These findings call for physicians’ awareness of the diagnosis of TAK in young individuals presenting with hypertension, especially in those with indecipherable severe hypertension.
Previous studies have revealed that renal artery stenosis-associated hypertension was observed in about 50% of TAK cases [12, 27, 28]. In the current study, we also found that the renal artery (60%) was the most commonly involved artery in hypertensive TAK patients, and the prevalence of severe and refractory hypertension was significantly higher in patients with renal artery stenosis (data not shown), which might support the important role of renal artery stenosis in the causes of hypertension in TAK. In addition, significant differences of artery involvement was demonstrated between patients with and without hypertension, wherein it was speculated that hypertensive patients might have specific imaging phenotypes. We confirmed this by identifying three specific imaging phenotype clusters in hypertensive patients, which could be distinguished from non-hypertensive cases (Fig. 5). Younger age and worse disease status, especially the prevalence of severe hypertension and renal insufficiency, was observed in patients with Cluster 1 imaging phenotype. What is more, the imaging phenotypes defined in our study also showed significant effects on the EFS. The EFS was significantly lower in Cluster 1 (59.6%) than that in Cluster 2, but similar to that in Cluster 3, which may be related to the higher prevalence of renal insufficiency and persistent refractory and/or malignant hypertension, as well as the lower prevalence of blood pressure control in Cluster 1 and Cluster 3. In addition, although renal and abdominal aorta involvement were indicated both in Cluster 1 and Cluster 3, future studies would be needed to determine whether poor prognosis is mainly attributed to this involvement.
Except for renal artery, hypertension in TAK could be caused by multifactorial conditions. In Cluster 2, hypertension might be caused by the involvement of the ascending aorta, thoracic aorta, aortic arch, and its branches instead of the renal and abdominal aorta. Hamida et al. reported that lesions of supraaortic trunks, carotid lesions, and immunosuppressive drugs might contribute to the genesis of hypertension in TAK . Former studies have also found that dysfunctional baroreceptors are possible mechanisms involved in causing hypertension . It is well recognized that a proatherogenic effect occurs in patients with TAK, which may increase arterial stiffness and decrease elasticity of arterial walls that may contribute to elevated blood pressure. In addition, severe AR was observed in 9.3% hypertensive patients in our study, which was a little lower than that reported in a previous study . Aortic regurgitation may be also associated with hypertension in TAK, and is likely caused by directed valvular lesions, aneurysms arising from the aortic annulus, or annular dilation resulting from extensive dilatational changes of the ascending aorta. Furthermore, we also found that co-existence of severe AR was negatively related to the EFS. Thus, echocardiography monitoring is very necessary for TAK population.
In the current investigation, only 50.8% cases had blood pressure controlled during the follow-up, which was relatively low. More importantly, patients with blood pressure control showed significantly better EFS. Thus, the main treatment goal for hypertensive TAK patients should be not only to achieve and maintain disease remission, but also to achieve blood pressure control. Combined with the above data, we also made a decision tree diagram using three variables: imaging phenotype, blood pressure control status and co-existence of sever AR (shown as Supplementary Fig S2). Through the diagram, 69.2% patients could be classified into the right prognosis group. However, the power and accuracy of the decision tree diagram should be validated in the future, due to the small sample size of the present research.
Our study has two major limitations. First, due to the low incidence of TAK, association analyses between severity and controlled status as well as imaging phenotypic categories of hypertension with the prognosis may be underpowered, which warrants future larger studies to validate our results. Second, the follow-up duration was relatively short, and further studies with larger sample size and longer follow-up duration are needed to validate the results.