Alpha-1 Antitrypsin (AAT), a serine protease of the SERPIN superfamily inhibits various tissue proteases such as neutrophil elastase and proteinase 3. Mutations in the corresponding gene, SERPINA1, are at the origin of AAT deficiency (AATD). The most frequent manifestations of AATD are panacinar emphysema and chronic liver disease. AATD has been occasionally associated with aneurysms and dissection of large vessels. Compared to matched controls, AATD patients homozygous for the common Z variant have larger ascending aortas with abnormal elastic properties (Vizzardi et al. Heart 2012 ; 98: 1354–58). However, so far, increased arterial stiffness and isolated systolic hypertension have not been documented in AATD patients. We describe the case of a young patient with isolated systolic refractory hypertension associated with a mild, atypical form of AATD, and discuss the potential link between both entities.

A 43-year-old non-smoker man was referred at the hypertension consultation for severe, early-onset resistant hypertension with very high pulse pressure, despite intake of eight antihypertensive drugs. He reported a history of eosinophilic esophagitis and left popliteal stent for lower limb arteriopathy.

In a context of moderate increase in ALAT (<2x ULN), a low plasma level of AAT (75mcg/dl, normal range : 95–175) was detected.

Genetic testing confirmed the presence of the frequent Z variant of SERPINA1 at the heterozygous state, in the absence of AAT-related liver or pulmonary disease. Sitting office blood pressure was 160/50mmHg. Body mass index was 31.3kg/m². Clinical examination was otherwise unremarkable. Mean day – and night-time ambulatory blood pressre were 142/58 and 115/43mmHg, respectively. Blood and urine analysis, urinary metanephrines and abdominal CT-angiography were normal. Echocardiography showed mild concentric left ventricular hypertrophy (LVMI : 134g/m²). Carotid-femoral pulse wave velocity (SphygmoCor^®) was markedly increased (14.2m/s; age-adjusted reference values : 4.6–9.8m/s). By contrast, detailed assessment of retinal and sublingual capillaries showed no evidence of microvascular dysfunction.

This case report suggests that increased arterial stiffness and isolated systolic hypertension are an integral part of the spectrum of AATD-related vascular abnormalities. Conversely, AATD may be considered in the differential diagnosis of resistant hypertension, especially in the presence of increased pulse pressure in a young patient. Future perspectives include indepth blood pressure and vascular characterization of a cohort of patients with both heterozygous and homozygous AATD.