MON-438 A Novel Insight into the Pathophysiology of Acromegalic Cardiomyopathy: Integrating Serum FSTL1 Levels and FSTL1 Polymorphisms with Cardiac MRI Findings

Abstract

Background: Despite prolonged survival, the mortality rate of acromegalic patients is still higher. Cardiovascular disorders continue to be the most common cause of death. The exact pathophysiologic mechanisms of acromegalic cardiomyopathy (AC) remain to be established. In this study, we investigated the role of FSTL1 levels and FSTL1 gene polymorphisms on AC and assessed the functional and structural properties of cardiac muscle by cardiac MRI. Finally, we examined the relationship between FSTL1 levels, FSTL1 gene polymorphism and cardiac MRI findings. Materials and Methods: Forty-six acromegalic patients (28F/18M, age: 50.3±12.1 yrs) with a median disease duration of eight years and 81 age-sex matched healthy controls (48F/33M, age: 48.4±7.2 yrs) were included in the study. The rs1259293 region of the FSTL1 gene was subjected to polymorphism analysis. SNPs were identified (TT, TC and CC). A 1.5 Tesla scanner was used to obtain cardiac images. Results: The median serum IGF- 1 level and IGF-1 index were 232.5 ng/mL (50-1278) and 0.69 (0.17-3.1), respectively. Acromegalic patients had significantly lower levels of FSTL1 (median, IQR; A: 0.88, 0.44-2.13 ng/mL, C: 1.54, 0.85-3.16 ng/mL, p=0.04). FSTL1 levels were not different among polymorphism groups (TT, TC and CC). Left ventricular (LV) mass was increased in 18 patients (41%). In 20 acromegalic patients (45.4%), regional late gadolinium enhancement (LGE) was determined. Serum IGF-1 index was positively correlated with LV end-diastolic volume index, end-systolic volume index, stroke volume index, cardiac index and cardiac mass index; r: 0.36, 0.34, 0.32, 0.31 and 0.42, p: 0.02, 0.03, 0.03, 0.04 and 0.004 respectively. The IGF-1 index was defined as an independent risk factor for LV hypertrophy (95 % CI OR: 0.89-18.84); on the other hand, the CC polymorphism was shown to be an independent protective factor (95 % CI OR: 0.06-0.87). Discussion: Our study is the first study that assesses the role of serum FSTL1 levels and FSTL1 polymorphisms in AC. We found low FSTL1 levels in patients with acromegaly. FSTL-1 prevents hypertrophy in cardiomyocytes. In a previous report, homozygous deletion of FSTL1 in mice was shown to result in enlargement of heart. The relatively low abundance of FSTL1 in acromegalic patients could be an underlying mechanism for AC. Almost half of the acromegalic patients had increased LV mass and LGE. Contrary to the previous report, we show that LV hypertrophy and regional fibrosis are common findings in acromegaly. The IGF-1 index was found to be associated with hyperdynamic cardiac functions. Furthermore, we demonstrate that high IGF-1 index is an independent risk factor for increased LV mass. Finally, we revealed that the CC polymorphism is a protective factor against the LV mass increase. Conclusions: FSTL1 can have roles in the pathogenesis of AC. Specific polymorphism at the FSTL1 gene may prevent the growth of the LV.