Therapeutic Targeting of Cellular Stress to Prevent Cardiovascular Disease: A Review of the Evidence.

The availability of effective drugs targeting the major risk factors of cardiovascular disease (CVD) has reduced morbidity and mortality. Cumulative relative risk of CVD events can be reduced by 75 % with a combination of aspirin, a β-adrenoceptor antagonist (β-blocker), an HMG-CoA reductase inhibitor (statin), and an angiotensin-converting enzyme inhibitor. The principal pharmacodynamics of these drugs cannot explain the entirety of their cardioprotective action, as other drugs with similar pharmacologic targets have not been associated with favorable clinical effects. This raises the possibility that the cardioprotective drugs have a unique pleiotropic activity that contributes to their clinical efficacy. Recent data suggest that reducing cellular stress such as oxidative, inflammatory, and endoplasmic reticulum stress, might be a common denominator of the drugs with proven efficacy in reducing CVD risk. In this communication, the evidence in favor of this hypothesis is discussed, and ongoing trials with therapeutic agents targeting cellular stresses are reviewed.