Hypertension: from basic research to clinical practice

Giuseppe Mulè, Emilio Nardi, Massimiliano Morreale, Antonella Castiglia, Giulio Geraci, Dario Altieri, Valentina Cacciatore, Margherita Schillaci, Francesco Vaccaro, Santina Cottone

Thoracic aortic aneurysms rupture and dissection are among the most devastating vascular diseases, being characterized by elevated mortality, despite improvements in diagnostic imaging and surgical techniques.An increased aortic root diameter (ARD) represents the main risk factor for thoracic aortic dissection and rupture and for aortic valve regurgitation.Even though arterial hypertension is commonly regarded as a predisposing condition for the development of thoracic aorta aneurysms, the role of blood pressure (BP) as determinant of aortic root enlargement is still controversial. The use of different methods for indexation of ARD may have in part contributed to the heterogeneous findings obtained in the investigations exploring the relationships between ARD and BP. Indeed, the best methods for ARD indexation, as well as the normal values of aortic root size, are still a matter of debate.Several non-hemodynamic factors influence ARD, including age, gender, and anthropometric variables, such as height, weight and their derivatives body surface area (BSA) and body mass index. Of these factors, anthropometric variables have the greatest impact.Several studies documented an association between ARD enlargement, assessed by echocardiography, and some indices of hypertensive target organ damage such as left ventricular hypertrophy, diastolic dysfunction, and carotid intima-media thickening. Recently, we found that ARD, expressed either as absolute values or normalized for BSA (ARD/BSA) or height (ARD/H), was significantly greater in hypertensive subjects with chronic kidney disease (CKD) when compared to their counterparts with normal renal function. Moreover, at univariate analyses estimated glomerular filtration rate (eGFR) showed significant inverse correlations with ARD not indexed and with ARD/BSA and ARD/H. Taking into account the effect of age, sex, duration of hypertension and other potentially confounding factors, in multiple regression analyses, only the association of GFR with ARD/H and that between GFR and ARD/BSA remained statistically significant. The receiver-operating characteristic curve analysis revealed that an estimated GFR of about 50 ml/min/1.73 m(2) represents the better threshold to distinguish hypertensive patients with dilated aortic root from those with a normal one.Some population-based studies showed that an enlarged ARD might predict an adverse prognosis, even in absence of aneurysmatic alterations.In the Cardiovascular Health Study, a dilated aortic root was independently associated with an increased risk for stroke, cardiovascular and total mortality in both sexes and with incident congestive heart failure only in men. The relationship between ARD and heart failure has been observed also in the Framingham Heart Study. More recently, the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study demonstrated an independent relationship of ARD/H with incident cardiovascular morbidity and mortality.Although the relationship between BP and aortic root size is still a matter of debate, increasing evidence seems to support the notion that aortic root dilatation, even in absence of aneurysmatic alterations, may be regarded as an hypertensive organ damage paralleling other preclinical markers whose unfavourable prognostic significance is firmly established. Future studies are needed to assess whether or not antihypertensive therapy is able to reduce aortic root dimension and the increased risk associated with its enlargement.