One's grandparents as the determinant of effective antihypertensive therapy

We have known for 70 years that familial factors influence blood pressure level. Modern genetics suggest that 30-40% of blood pressure variation reflects genetic factors. We have known for more than 40 years that patients differ in their response to specific antihypertensive agents, with little insight beyond demographics into the responsible mechanism for the variation in that response. Only recently has interest been evident in attempts to bring these two questions together. Specifically, do familial factors influence the response to specific antihypertensive therapy? One example involves the attempt to use the response to angiotensin- converting enzyme (ACE) inhibitors as an intermediate phenotype. An analogous attempt involves recognition of the fact that ACE inhibition reverses many of the features of non-modulation- which is an expression of an angiotensinogen (AGT) gene polymorphism. The ESPRIT Study was the first to enroll hyper-tensive sibling pairs into a therapeutic trial, designed to assess responses to ACE inhibitor treatment with lisinopril. This pathway of investigation is likely to be very fruitful over the next several decades, to the point that 'pharmacogenetics' will be an element in selecting antihypertensive therapy.