Synergistc effects of calcium antagonists and statins on endothelial function: a new lesson from the ASCOT trial.

Essential hypertension is a major cardiovascular risk factor. Although pharmacological treatment is highly effective in reducing cardiovascular risk, it is worth noting that it is not sufficient to reduce the relative risk of hypertensive patients to the level of normotensive individuals. On the other hand, although all antihypertensive drug classes are able, by reducing blood pressure, to proportionally improve the patients’ prognosis, clinical and experimental data suggest that some classes of antihypertensive drugs, such as calcium antagonists and lipid-lowering drugs, namely statins, are able to provide beneficial effects that go beyond their effect on the specific clinical target. Another aspect that will be addressed in the present article is the interaction between different therapeutic strategies. In particular, the positive synergy between calcium antagonists and statins will be analysed. Sub-analysis of the ASCOT trial demonstrates that the combination of an atorvastatin and amlodipine-based regimen produces a greater beneficial effect, mainly on coronary events, as compared with the combination of the statin with the atenolol-based regimen. A likely explanation for this positive interaction is a synergistic effect of these compounds on endothelial function. Impaired endothelium-dependent vasodilatation is a characteristic of essential hypertensive patients with high cardiovascular risk and it is a mechanism promoting atherosclerosis and cardiovascular events. Both amlodipine and atorvastatin are molecules effective in reversing endothelial dysfunction, as demonstrated in experimental models and in patients. Since the therapeutic improvement of endothelial dysfunction can lead to a better prognosis, the synergistic beneficial effect of calcium antagonists and statins, in terms of cardiovascular events, can be the consequence of their endothelium protecting effect. Therefore, the possible mechanisms of interaction between statins and calcium antagonists on endothelial function will also be discusse