Insight into cardiovascular risk factors in patients with acromegaly.

In this issue of Endocrine, Dr. Ragonese and colleagues provide a well-written, extensive study on the prediction of ischemic cardiovascular events (ICE) in acromegalic patients stratified by Framingham score (FS) and Agatston score (AS) [1]. FS is based on conventional risk factors, such as gender, age, hypertension, smoking habits, diabetes mellitus, and lipid status, while AS is calculated by the measurement of calcium burden in the main coronary arteries by electron beam computed tomography. The strength of this study [1] is represented by the extensive cardiac workup in 52 acromegalic patients with controlled and uncontrolled disease followed for 5 years. Interestingly, an AS [ 400, but not a high FS at entry, was associated with an increased risk of lethal ICE, but the total number of lethal ICE was low. Rather than summarizing study-related findings, I will comment on current and somewhat limited understanding of cardiovascular risk factors in patients with acromegaly. Increased mortality rate is primarily due to cardiovascular disease [2–5]. However, what is often controversial is whether growth hormone (GH) excess has deleterious effects per se on the cardiovascular system or whether cardiovascular disease results from the frequently observed increased prevalence of associated risk factors. Although mortality seems to decrease, improvement or reversal of cardiovascular morbidity by effective GH control also remains controversial. It is also important to determine which patients are at higher risk of lethal ICE. Cardiomyopathy of acromegaly [4] includes both structural and functional abnormalities: concentric biventricular hypertrophy (20 % in young patients and in up to 90 % of patients with long-standing disease) and diastolic dysfunction [6], leading to the development of heart failure with preserved ejection fraction. However, the clinical syndrome of heart failure is relatively uncommon (1–10 %). Is acromegalic cardiomyopathy reversible? Suppression of GH and insulinlike growth factor 1 (IGF-1) could improve diastolic function [3]; however, systolic function and exercise tolerance response are variable and dependent mostly on disease duration and the presence of hypertension and diabetes. As expected, younger patients respond better to treatment than middle-aged patients. Likewise, ventricular remodeling increases risk of mitral, aortic, and tricuspid regurgitation in the late stages of acromegaly [3]. Arrhythmias (atrial fibrillation, supraventricular tachycardia, and ventricular arrhythmias), due to phenotypic changes in membrane proteins, conduction system, and uncoupling of cardiac myocytes with increased re-entry events, and autonomic dysfunction [7] are also common. The development of atherosclerotic disease seems more ‘‘complicated’’: Hypertension and diabetes are by far the main predisposing factors, and up to half of patients could be at intermediate-to-high risk for coronary artery disease (CAD). GH and IGF-1 cause direct endothelial dysfunction, which decreases vasodilation and could increase risk of future ICE. Despite this unfavorable cardiovascular risk profile, it is not clear whether acromegalic patients have indeed an increased risk of CAD per se. Mouse models, for example, suggested that the excess mortality might be due to the development of hypertrophic cardiomyopathy rather than increased rates of atherosclerotic CAD. Growth hormone excess (which could predict the increase in low-density lipoprotein cholesterol (LDL-C), M. Fleseriu (&) Northwest Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, 3181 SW Sam Jackson Park Road (BTE 472), Portland, OR 97239, USA e-mail: fleseriu@ohsu.edu