Having provided genetic and functional evidence that a cis-EPO variant alters EPO gene expression and circulating protein levels, we used this variant as a genetic predictor for long-term therapeutic modulation of EPO levels to show that genetically predicted higher endogenous EPO levels (equivalent to 5.1 IU/L) are not associated with increased cardiovascular risk or elevated values of clinical markers (SBP, DBP, or resting heart rate) predisposing to CVD risk factors (e.g., hypertension). Here, EPO is linked to hypertensive disorder.