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Cardiovascular morbidity and mortality increase as a function of blood pressure, but antihypertensive treatment reduces the rate of both events, thereby representing a preventive means against hypertension-related complications. This prevention, however, does not entirely normalize the risk and appears to be ineffective or only slightly effective against coronary artery disease. This paper reviews the hypotheses that have been advanced to explain the inability of antihypertensive treatment to offer less than complete protection and to provide primary cardioprotection, with emphasis on (a) the lack of full blood pressure control in a large fraction of the hypertensive population, (b) the excessive blood pressure reduction in subjects with ischemic heart disease and dependence of coronary perfusion from a relatively high blood pressure value, and (c) the multifactorial risk profile of coronary artery disease that may make blood pressure reduction alone insufficient in many patients. The last hypothesis is discussed also in relation to the best possible intervention approach to hypertension and to the choice of the antihypertensive agents that may make primary cardioprotection possible.