Cardiovascular disease is the leading cause of death in industrialized countries. Advancing age is an important risk factor for cardiovascular disease. With the rising number of elderly people in our society cardiovascular disease has a major impact on healthcare. The prevention of cardiovascular disease is critically dependent on lipid lowering therapy including the 3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). Statins are the most prescribed class of drugs worldwide and therapy is generally associated with a reduction of cardiovascular events by 20-30%. However, clinical response is highly variable and adverse effects occur in a minority of patients. Recent research provides evidence that genetic variation contributes importantly to this variable drug response. Pharmacogenomics focuses on unraveling the genetic determinants of such variable drug responses, both in intended, beneficial effects and unintended, adverse effects .
Here we present the PHASE study that for the first time will establish which genetic variation is responsible for the variation in response to statins.
We make use of the PROspective Study of Pravastatin in the Elderly at risk (PROSPER), a large prospective European multi-national placebo-controlled randomized clinical trial with 5804 participants. In all participants we perform a 660K genome-wide scan to assess the genetic variation responsible for variation in lowering low-density lipoprotein levels, variation in clinical outcome and for the occurrence of adverse effects. For all participants extensive data on lipoproteins, inflammatory markers and other biochemical analyses are also available for validation. Moreover, the PROSPER study has an excellent Biobank to perform additional serum measurements depending on the outcome of the genome wide scan. Positive associations will be confirmed in two large independent clinical trials, the WOSCOPS and the CARE study.