Pharmacogenetics and cardiovascular disease: impact on drug response and applications to disease management.

The genetic polymorphisms that may affect individual responses to cardiovascular agents are reviewed, and the application of pharmacogenetics to cardiovascular disease management is discussed. Pharmacogenetics is the search for genetic polymorphisms that affect responses to drug therapy. Investigators have found many associations between genetic polymorphisms and responses to cardiovascular drugs. Some of these relationships have been demonstrated in large patient populations, such as patients with ischemic heart disease receiving statins. Study data consistently show a greater response to statins in ischemic heart disease patients with genotypes associated with worse prognoses. Studies of other polymorphisms, such as those in the genes encoding anglotensin-converting enzyme and beta 1-adrenergic receptors, have less consistently found relationships between these variations and cardiovascular drug responses. For gene-drug response associations for which the data are inconsistent, the interaction of multiple polymorphisms in multiple genes coding for proteins affected by drug therapy or influencing drug metabolism may prove to have a greater influence on drug responses than any one polymorphism. Once the polymorphisms that best determine the response to a particular drug are known and tests to rapidly identify these variations are available, individual patients may be screened for genetic polymorphisms before drug therapy is begun and the information used to choose agents with the greatest potential for efficacy and least potential for toxicity. Pharmacogenetics has many possible applications in the drug therapy of cardiovascular diseases. Much more must be learned, however, before pharmacogenetic factors can be routinely incorporated into therapeutic decisions.