Stagnation and the Critical Need for Hypertension Subtyping

TLDR: Clinically, the most prevalent forms of hypertension, isolated systolic and white-coat hypertension, are poorly responsive to agents that easily lower diastolic blood pressure, which leads directly to the inability of the us food and Drug administration to approve these agents as antihypertensives, which by convention must lower both syStolic and diastolics blood pressure.

Abstract: Vol. 10 no. 3 MarCH 2008 174 Many individuals in the hypertension community have historically failed to recognize the many different pathogenetic origins and phenotypic expressions of the hypertension syndrome. Why is recognition and acceptance of this heterogeneity so important now? Despite the fact that hypertension is the single most important risk factor for cardiovascular disease, in large measure, the field is stagnant. unless we agree on a scientifically accurate, clinically meaningful classification system for hypertension, the rate of basic discovery will slow even further, and improvements in clinical management will lag. Those who think that this is just melodrama should simply look at the number of new investigators coming into the field, the numbers of new drugs under development, and the diminishing rate of improvement in cardiovascular disease. Clinically, the most prevalent forms of hypertension, isolated systolic and white-coat hypertension, are poorly responsive to agents that easily lower diastolic blood pressure. Does this pattern signify that isolated diastolic, isolated systolic, and reactive forms of hypertension arise from fundamentally different mechanisms? at present, our antihypertensive drug armamentarium largely consists of arteriolar dilators. shouldn’t we also be working on approaches to reduce vasoreactivity and central arterial stiffness? agents such as collagen cross-link breakers actually lower systolic but raise diastolic blood pressure. Here, our failure to recognize systolic hypertension as distinct from diastolic hypertension leads directly to the inability of the us food and Drug administration to approve these agents as antihypertensives, which by convention must lower both systolic and diastolic blood pressure. reliable solutions to most of the important therapeutic dilemmas in hypertension would be facilitated by applying our knowledge of the diverse mechanisms that underlie the particular hypertension phenotype. Would anyone argue that the subtyping of diabetes into insulin insufficiency and insulin resistance has provided marked improvements in therapy based on improved understanding of pathophysiology? from a translational research perspective, there are many different animal models of hypertension, each with a unique natural history and phenotypic expression. no single animal model describes all aspects of human hypertension; their only common feature is the chronic elevation of mean arterial pressure. in humans, aside from some rare monogenetic forms of hypertension, there does not seem to be a strong genetic fingerprint. Does it therefore follow that hypertension is an acquired characteristic? or could the contribution of several major genetic components have been confounded by our failure to subtype the syndrome into relevant “intermediate phenotypes” or “endophenotypes”? if wide pulse pressure hypertension is related predominantly to increased aortic impedance, or if white-coat hypertension is related to altered neural control, why should either condition be closely related to a gene that controls arteriolar structure or function? in fairness, we have made some meaningful advances in shifting the paradigm in hypertension. isolated systolic hypertension, which accounts for more than half of all hypertension cases, is now recognized worldwide as a greater public health www.lejacq.com ID: 8083 E d i t o r i a l