PURPOSE: People with resistance to thyroid hormone due to defective thyroid receptor β (RTHβ) exhibit adverse cardiovascular outcomes and premature mortality. Whether this reflects increased global cardiovascular disease (CVD) risk or hyperthyroxinemia-associated effects on cardiac rhythm and contractility is unknown. We determined CVD risk and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations as a marker of reduced cardiac function in 99 individuals (mean age 41 years, 37% males) with RTHβ. RESULTS: The mean (SD range) QRISK3 score for 82 participants was 2.0% (0.5-8.8%) vs 1.3% (0.3-5.0%) for age, sex, and ethnicity-matched healthy controls ( CONCLUSION: Elevated NT-proBNP concentrations, seen even in young people with RTHβ, suggest that myocardial dysfunction contributes to early adverse cardiovascular outcomes in this disorder, with increased atherosclerotic disease risk likely manifesting later in life. Measurement of NT-proBNP and assessment of cardiovascular risk should be considered at first presentation and periodically during follow-up of RTHβ.