Introduction: Patients with acromegaly have increased mortality, primarily related to cardiovascular/cerebrovascular disease. The objective of this study was to evaluate whether GH/IGF-1 excess increases vascular disease by adversely affecting fibrin network characteristics.
Methods: In this casecontrol study, 40 patients with acromegaly (21 males, age 53±13 years, 45% disease remission) and 40 age and gender-matched controls were recruited. Clot structure parameters were analysed using a validated turbidimetric assay and fibrin networks were visualised by laser scanning confocal microscopy (LSCM). Parameters of metabolic profile, body composition, plasma fibrinogen and PAI-1 were also assessed.
Results: Patients had higher BMI (30±5.5 vs. 26.7±4.1 kg/m2, P=0.003), waist/hip ratio (0.91±0.08 vs. 0.87±0.08, P=0.045), total fat mass (29.8±10 vs. 23.4±10 kg, P=0.003), fibrinogen [3.1 (2.64.1) vs. 2.6 (2.52.7) mg/ml, P<0.001] and clot maximum absorbance (0.38±0.13 vs. 0.32±0.08 arbitrary units, P=0.02). There was a trend towards greater clot lysis area (measure of clot density, fibre thickness and lysis potential) in patients [634 (452905) vs. 501 (429784) arbitrary units, P=0.08], however there was no difference in lysis time or PAI-1 levels. LSCM showed increased fibrin network density in patients compared with controls, with increased number of fibrin fibres. Changes in clot density and fibrinogen were more pronounced amongst patients with active acromegaly and were eliminated when comparing patients in remission with controls. BMI, fat mass and skinfold thickness were associated with higher clot density and longer lysis time. Disease remission was associated with reduction in lysis area.
Conclusions: Patients with acromegaly have more compact clots secondary to higher fibrinogen levels, thus conferring increased thrombosis risk. The adverse metabolic profile and disease activity contribute to these abnormal clot structure properties. Prothormbotic fibrin networks may represent one mechanism for enhanced vascular risk in individuals with acromegaly, particularly during active disease.