The Many Faces of Arterial Hypertension in Hypertrophic Cardiomyopathy and Its Phenocopies: Bystander, Consequence, Modifier

Abstract

Arterial hypertension is the most prevalent cardiovascular (CV) risk factor worldwide, and a major preventable cause of CV, cerebrovascular and renal disease [1]. Arterial hypertension causes progressive myocardial remodeling, mainly characterized by left ventricular hypertrophy (LVH), which, once developed, strongly associates with adverse CV outcomes [2, 3]. At the molecular level, multiple alterations may be found in hypertensive hearts, including fibrosis, microvascular coronary circulation impairment, imbalance in the arterial-ventricular coupling and derangement of energetic mechanisms [2, 3]. As all these abnormalities may contribute to myocardial remodeling, it is now believed that LVH in arterial hypertension is not solely the result of an overload (haemodynamic) condition. Being such a prevalent comorbidity, the influence of arterial hypertension falls far beyond its impact on the CV risk profile. The case of hypertrophic cardiomyopathy (HCM) perfectly suits to describe the many effects that arterial hypertension may exert in other cardiac conditions. Bystander. HCM is the most common genetic cardiac disease, and is a relatively common entity, with an estimated prevalence of 1:500 individuals. About 5–10% of cases in HCM are attributable to the so-called phenocopies, such as cardiac amyloidosis and Anderson–Fabry Disease (AFD). Due to growing awareness, HCM and its phenocopies are increasingly recognized in recent years [4–6]. This led to a shift in the epidemiological characteristics of contemporary HCM and phenocopies cohorts. For example, HCM patients are diagnosed at progressively older ages [7], and arterial hypertension is commonly found in HCM and transthyretin-related cardiac amyloidosis patients [6, 7]. The adverse effect of arterial hypertension, as of any other major CV risk factor, in these cohorts of patients is no different from that in the general population. Arterial hypertension, diabetes, obesity—all have been shown to contribute to adverse clinical course in HCM [8]. Consequence. In some cases, arterial hypertension is not simply a bystander comorbidity, but is a part of the clinical picture of HCM phenocopies. AFD and light-chain cardiac amyloidosis are in fact systemic diseases, involving the heart and the kidney, among other organs [4]. In this Issue of the Journal, a study by Rossi and colleagues investigates the clinical correlates of arterial hypertension in a cohort of AFD patients [9]. Blood pressure values were assessed by ambulatory blood pressure monitoring, office and home measurements, and about 20% of subjects were found to be hypertensive. These had often worse renal function and greater left ventricular mass, which corresponded to a progressive form of the disease according to the Fabry Stabilization Index assessment, as compared to those AFD patients without hypertension, and in particular without uncontrolled blood pressure values. These findings likely reflect the triggering of a vicious circle of renal-cardiac damage, typical of the progressive nature of AFD [4, 10]. Nevertheless, it should be reminded that AFD is not just a storage disease, yet it is also characterized by a pro-inflammatory state, which plays a central role in its phenotypic expression and clinical course [11]. Recent findings have shown that also arterial hypertension is associated with similar immune system activation, and some inflammatory pathways are shared between the two conditions. Hence, arterial hypertension may not be exclusively a consequence of renal involvement. Indeed, it likely exerts a synergistic, deleterious effect in AFD pathophysiology [10]. Thus, a question arises. May arterial hypertension represent a modifier condition for HCM and other phenocopies? May its effect contribute not only to disease course, but also to phenotypic expression? * Giacomo Tini [email protected]