Physiologic rationale for calcium antagonist therapy in essential hypertension.

Two basic concepts that are relevant to hypertensive cardiovascular disease are often ignored despite being central to a proper understanding and clinical approach to our patients. First, high blood pressure is an abnormal physical sign; a 'vital' sign, as are temperature, pulse, and respiration. Although people often consider hypertension as a disease, it is itself not a disease, but rather one sign of a disease: a warning manifestation of a disease. Approximately 90% of the time, the underlying cause(s) of this sign are unknown and, thus, the condition itself is named according to its sign, as essential hypertension. Commonly, physicians are told that by eliminating the messenger bearing the bad news--i.e., by merely suppressing the blood pressure, the excess morbidity and mortality associated with the underlying disease process will be reversed. Unfortunately, the cumulative experience of over two decades of world-wide clinical trials indicates that getting rid of only one aspect of hypertensive disease, the elevated blood pressure, gets rid of only part of the excess cardiovascular risk associated with hypertension. By contrast, we now appreciate that what we call hypertension carries with it other peripheral manifestations present in other body systems, such as left ventricular hypertrophy, that may exist prior to and progress independently of the hypertension itself; and insulin resistance, reflecting the same underlying pathophysiology in skeletal muscle, fat, and other tissues. Thus, the disease we call hypertension is not just a 'numbers' game. As such, a reasonable goal not yet attained would be to identify common factors underlying not only the elevations of blood pressure, but the other multisystemic aspects of hypertensive cardiovascular disease as well. Focusing on such underlying factors would allow treatment of the disease process itself, rather than just the level of blood pressure. A second concept, also often overlooked but quite obvious, is the pathophysiologic and clinical heterogeneity of hypertension. People are different. By analogy with an elevated temperature, the same elevation of blood pressure that leads to the diagnosis of 'essential' hypertension may result from many different "primary" causes, which just happen to have hypertension as one shared clinical manifestation. This immediately implies that when we ask, "Is this drug good, or preferred for hypertension?" the answer should be, "It depends." As an obvious example, to be discussed in more detail below, the salt-sensitive hypertensive responds to dietary salt recommendations and to different drug classes differently from an individual who is not salt-sensitive.