Cardiovascular Morbidity in Acromegaly during a Long-term Follow-Up – a Nationwide Cohort Study

Abstract Objective Acromegaly has been associated with increased cardiovascular morbidity, but it is unclear to what extent this holds true in contemporary acromegaly cohorts and when the cardiovascular diseases (CVDs) evolve in relation to the time of diagnosis. Design Retrospective cohort study Methods Cardiovascular morbidity was studied in the Finnish acromegaly cohort (n = 565) and 5629 controls using Kaplan-Meier analysis from 10 years before the diagnosis of acromegaly and continuing up to >30 years after the diagnosis. Hazard ratios for CVD-related hospital visits were calculated with Cox regression analyses in the post-diagnosis period. The effects of received treatments, hypopituitarism, and biochemical control of acromegaly were studied with multivariable analyses among the patients. Results Cardiovascular morbidity increased years before the diagnosis of acromegaly and remained elevated compared to controls [HR 1.59 (95% CI 1.42–1.78)] throughout the follow-up (median 17.2 years, interquartile range 8.7–26.5 years). The highest increase was observed in diseases of pulmonary arteries [HR 2.74 (1.87–4.02)], valvular diseases and cardiomyopathies [HR 2.68 (2.09–3.44)] and hypertension [HR 2.11 (1.85–2.42)]. Radiotherapy, hypopituitarism, and post-treatment IGF-1 above or below the reference range were associated with increased cardiovascular morbidity. Even patients who achieved biochemical remission and normal pituitary function after surgery suffered from increased morbidity compared to controls. Conclusions Patients with acromegaly are still characterised by increased morbidity across a wide range of CVDs. Cardiovascular morbidity is already present before diagnosis and persists despite acromegaly-specific therapy. This underlines the importance of early diagnostics and CVD prevention for these patients.