Cardiovascular remodeling in active and controlled acromegaly: association with sleep-disordered breathing

Abstract

Purpose: We hypothesized that an unfavorable cardiovascular profile in acromegaly is associated with sleep-disordered breathing (SDB), while acromegaly control improves both respiratory sleep characteristics and the cardiovascular profile.

Methods: The patients underwent the assessment of breathing during sleep and cardiovascular profile assessment at the start of the study including arterial stiffness, blood pressure, echocardiography, nocturnal heart rate variability (HRV). The assessment was repeated in patients with acromegaly at 1 year after transsphenoidal adenectomy (TSA).

Results: A total of 47 patients with acromegaly and 55 control subjects were enrolled. At one year after TSA, 22 patients with acromegaly were reassessed. Multiple linear regression analysis with adjustment for age, sex and body mass index (BMI) showed the associations of insulin growth-like factor 1 (IGF-1) with obstructive apnea index (OAI: β=0.035/h, p<0.001), but not with cardiovascular parameters, in patients with acromegaly. The analysis of combined acromegaly and control dataset with adjustment for age, sex and BMI showed the association the presence of acromegaly with diastolic blood pressure (DBP; β=17.99 mmHg, p<0.001), ejection fraction (EF; β=6.23%, p=0.009), left heart remodeling (left ventricle posterior wall: β=0.81 mm, p=0.045) and the association of the presence of SDB (apnea-hypopnea index≥15/h) with left ventricular function (EF: -4.12%, p=0.040; end systolic volume: 10.12 ml, p=0.004). Control of acromegaly was accompanied by the decrease in OAI (5.9 [0.8, 14.5]/h and 1.7 [0.2, 5.1]/h, p=0.004) and nocturnal heart rate (66.1 [59.2, 69.8] bpm and 61.7 [54.0, 67.2] bpm, p=0.025) and by the increase in blood pressure (DBP: 78.0 [70.3, 86.0] mm Hg and 80.0 [80.0, 90.0] mm Hg, p=0.012).

Conclusion: The comorbidities of acromegaly, including sleep-disordered breathing, appear to have a long-term effect on cardiovascular remodeling in active acromegaly. Future studies should investigate the applicability of the treatment of SDB for the reduction of cardiovascular risk in acromegaly.

Keywords: acromegaly; arterial stiffness; cardiovascular remodeling; echocardiography; nocturnal heart rate variability; obstructive sleep apnea; sleep-disordered breathing.