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Systemic Vasculitis: an Important and Underestimated Cause of Malignant Hypertension

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Systemic Vasculitis: an Important and Underestimated Cause of Malignant Hypertension Vol. 4 No. 2 (2019) 99–108 Cardiovascular Innovations and Applications ISSN 2009-8618 DOI 10.15212/CVIA.2019.0009 RESEARCH PAPER Systemic Vasculitis: An Important and Underestimated Cause of Malignant Hypertension Qing Zhu, MD1, Shasha Liu, MD1, Mulalibieke Heizhati, MD1, Xiaoguang Yao, PhD1, Menghui Wang, MD1, Qin Luo, MD1, Lei Wang, MD1, Delian Zhang, PhD1, Guijuan Chang, MD1 and Nanfang Li, PhD, MD1 1The Center for Hypertension of the People’s Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang Uygur Autonomous Region, Urumqi, China Received: 29 June 2018; Revised: 28 January 2019; Accepted: 30 January 2019 Abstract Objectives: Malignant hypertension (MHT) is defined as severe hypertension accompanied by ischemic failure of one or more organs. The aims of this study were to evaluate the current clinical and etiologic profiles of MHT. Methods: As a retrospective study, we selected all patients admitted to our center from January 2013 to December 2016. Seventy patients with MHT were included. Results: The average age of the patients was 40 years, and more than half of the patients were male (78.57%). There were 24 patients with essential hypertension, accounting for 34.29% of the patients, and 46 with secondary hypertension, accounting for 65.71% of the patients. For secondary MHT, systemic vasculitis (25.57%) was the most common cause, followed by severe obstructive sleep apnea syndrome (15.71%), primary renal parenchymal hyperten- sion (11.43%), primary aldosteronism (7.14%), and Cushing syndrome (1.43%) and nutcracker phenomenon (1.43%). Twenty patients with systemic vasculitis were characterized by severe hypertension accompanied by damage to two or more target organs of differing severity. The levels of white blood cells, hypersensitive C-reactive protein, serum creatinine, and 24-hour urinary protein were above their normal range. Conclusion: Systemic vasculitis may be one of the main causes of MHT, and has been underestimated in the past. In future clinical work, clinicians need to pay more attention to patients with systemic vasculitis. Keywords: malignant hypertension; cause; systemic vasculitis Significance Statement: Malignant hypertension (MHT) is a life-threating manifestation of hypertension, and the underlying cause of MHT needs to be identified as early as possible. However, systemic vasculitis was one of the main causes of MHT in our study, and was ignored in the past. In future clinical work, clinicians need to pay more attention to patients with systemic vasculitis and actively treat them. Correspondence: Nanfang Li, PhD, MD, The Center for Introduction Hypertension of the People’s Hospital of Xinjiang Uygur Malignant hypertension (MHT) is a condition char- Autonomous Region, Hypertension Institute of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumuqi, acterized by severe hypertension and can cause reti- 830001 Xinjiang, China, Tel.: +86-13999179937, nal, neurologic, renal, and cardiac complications. Fax: +86-09918564816, E-mail: [email protected] If MHT is not treated, mortality is very high, the © 2019 Cardiovascular Innovations and Applications. Creative Commons Attribution-NonCommercial 4.0 International License 100 Q. Zhu et al., Systemic Vasculitis and Malignant Hypertension 2-year mortality being 80% [1]. Despite the avail- Patients for etiologic screening of hypertension admitted to our ability of a vast range of antihypertensive agents, center between January 2013 and December 2016 (n = 11,792) MHT continues to be a significant clinical chal- lenge. Although its prevalence is very low, the abso- Patients with bilateral retinopathy with hemorrhages and/or cotton wool spots or exudates, with or without papilledema lute number of new cases has not changed in recent (n = 765) decades [2, 3]. Since the clinical manifestations of MHT are not specific, when patients present with Patients with DBP ≥120 mmHg (n = 137) acute renal failure the underlying causes of MHT are difficult to identify. Generally, the causes of MHT are primary or secondary hypertension. A few stud- Patients with renal insufficiency and/or proteinuria and/or hematuria (n = 70) ies showed that about 1–5% of cases of essential hypertension may develop into MHT [4] because Patients who fulfilled the criteria for MHT (n = 70) of patients not taking antihypertensive medica- tions or abruptly stopping taking antihypertensive Figure 1 Flow Chart of Patients with Malignant medications. For the secondary causes of MHT, Hypertension (MHT). some clinical case reports and studies showed that DBP, Diastolic blood pressure. such secondary hypertension can lead to MHT as in primary aldosteronism (PA), pheochromocytoma, Cushing syndrome, obstructive sleep apnea syn- found to have high blood pressure through physical drome (OSAS), renal hypertension (including renal examination, some had headache, dizziness, palpi- vascular hypertension), hypothyroidism, and preg- tation, fatigue, and other uncomfortable symptoms, nancy [5–10]. Recent studies have indicated that the and some appeared to have experienced stoke, myo- immune system may also play an important role in cardial infarction, chronic renal insufficiency, and the development of this condition [11]. There is an other complications due to long-term hypertension. increasing amount of literature on vasculitis indi- So they were admitted to our center. cating that various types of vasculitis can also cause We selected patients who fulfilled the criteria for MHT [12–14]. Therefore, our aims were to evaluate MHT, including (1) elevated diastolic blood pres- the current clinical and etiologic profiles of MHT. sure (≥120 mmHg), (2) presence of grade III or IV hypertensive retinopathy (bilateral retinopathy Participants and Methods with hemorrhages and/or cotton wool spots or exu- dates, with or without papilledema), and (3) renal complications (increased creatinine concentration Ethics Approval of the Study Protocol and/or proteinuria and/or hematuria) (Figure 1). This study was approved by the Ethics Committee of Patients younger than 18 years, pregnant women, the People’s Hospital of Xinjiang Uygur Autonomous and patients who were already undergoing dialysis Region (Urumqi, China). It was conducted according before admission were excluded. to the standards of the Declaration of Helsinki. Diagnostic Criteria Participants Essential Hypertension We reviewed all patients admitted to our center for screening for the cause of hypertension between Patients were considered to have essential hyper- January 2013 and December 2016. Our hyperten- tension if they fulfilled the criteria for the diagnosis sion center is the biggest hypertension center in of MHT and secondary hypertension was excluded. China, and has 180 inpatient beds. Thousands of patients are referred to the center from all over Primary Aldosteronism China each year, and we have successfully identi- fied the cause of secondary hypertension in more The screening of patients for and the diagnosis of than 10,000 patients. Of these patients, some were PA were conducted by a standard process based Q. Zhu et al., Systemic Vasculitis and Malignant Hypertension 101 on the current guidelines as in a previous study vasculitis (AAV), granulomatosis with polyangiitis from our center [15]. An elevated aldosterone level (GPA), eosinophilic granulomatosis with polyangiitis (>12 ng/L) and suppressed plasma renin activity (EGPA), and microscopic polyangiitis (MPA)]. For (<1.0 μg/L h) or an aldosterone-to-renin ratio (the the classification of PAN and other necrotizing vas- ratio of plasma aldosterone concentration to plasma culitides, we referred to the consensus algorithm that renin activity) greater than 20 ng/dL per nanogram was proposed by combination of ACR and CHCC per milliliter per hour was considered as PA. PA criteria, ANCA testing, and surrogate markers of was confirmed by a saline loading test (postinfusion vascular inflammation, including clinical, laboratory, plasma aldosterone concentration >5 ng/dL). neurophysiologic, and imaging tests (Figure 2) [22]. Cushing Syndrome Takayasu Arteritis The diagnosis was on the basis of symptoms, signs, A patient was considered have TA if at least three serum cortisol and ACTH levels and CT/MRI find- of these six criteria: (1) age <40 years, (2) claudica- ings. The qualitative diagnosis and localization tion of an extremity, (3) decreased brachial artery diagnosis of Cushing syndrome were according to pulse, (4) >10 mmHg difference in systolic pressure the Endocrine Society guideline [16]. between arms, (5) a bruit over subclavian arteries or aorta and (6) angiographic evidence of narrowing Primary Renal Parenchymal Hypertension or occlusion of the aorta or its primary or proximal branches were present [17]. The presence of three Hypertension was diagnosed after a history of or more of these six criteria demonstrated sensitiv- renal disease and was confirmed by kidney biopsy, ity of 91% and specificity of 98%. excluding secondary glomerular lesions. Systemic Vasculitis Polyarteritis Nodosa The diagnosis of systemic vasculitis was based on A patient was considered to have PAN if at least the patient’s clinical manifestations (such as malaise, three of these ten criteria: (1) Weight loss 24 kg; weight loss, fever, arthralgia, and myalgia), labora- (2) Livedo reticularis; (3) Testicular pain or tory test results (such as elevated erythrocyte sedi- tenderness; (4) Myalgias, weakness, or leg ten- mentation rate and levels of C-reactive protein and derness; (5) Mononeuropathy
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