This second issue of the Journal of the American Society of Hypertension (JASH) contains several new concepts that enhance our understanding of the interactions between organs, tissues and cytokines in the occurrence of cardiovascular events. We have succinct reviews of novel and emerging topics, observations of decreased stroke occurrence, and new fundamental observations regarding vascular and endothelial function. I hope that you will find the articles informative and stimulating and that you will consider submitting your own research observations to JASH and encourage your friends and colleagues to do so as well.
Desir reviews the evidence that the normal kidney secretes an oxidase (renalase) that is involved in the metabolism of catecholamines and that the production of this novel protein is reduced in chronic kidney disease (CKD). He speculates that this renalase deficiency could contribute to the increased cardiovascular event rate seen in CKD patients. The potential for the development of a novel therapeutic approach based on renalase in the prevention of such events is an intriguing possibility
Asmar has reviewed the evidence for pharmacological intervention influencing arterial stiffness. He points out that the site of the artery studied may account for some differences in observations as well as the fact that arterial stiffness is more difficult to alter in older individuals. A major requirement in the assessment of the effects of pharmacological intervention on vascular stiffness is for study duration of months rather than weeks in order to observe a change in vascular elasticity. In addition, it appears that higher doses of drugs than are required for blood pressure reduction, in the case of antihypertensive agents, or lipid reduction for lipid-lowering agents, are needed to observe a reduction in stiffness. The effects of the drugs on vascular elasticity appear to be independent of their blood pressure or lipid effects, adding to the list of pleotrophic effects of these agents. Finally, despite all of the limitations of the studies that have been done to evaluate the effects of antihypertensive agents on vascular stiffness, it appears that diuretics and beta adrenergic blocking agents do not consistently alter stiffness, while angiotensin converting enzyme inhibitors, angiotensin receptor blockers and calcium channel entry blockers do have beneficial vascular effects, independent of blood pressure change, after many months of treatment.
While it is acknowledged that an elevation of blood pressure increases vascular inflammation, the mediators of this response and their interactions as well as the effects of antihypertensive agents upon them is less clear. A review, focusing on C-reactive protein (CRP), is a helpful way to gain insight into the current information in this area and for the identification of future therapeutic avenues. CRP has many known interactions with other vasoactive substances and cytokines in mediating the inflammatory response. The impact of specific drugs on these factors and their possible relationship to cardiovascular events is beginning to emerge from several large trials. We have much to learn in this area. The final paper in this issue provides additional new information on this topic.
A review of the cardiometabolic syndrome provides a current synthesis of the relationships between blood pressure, obesity, dyslipidemia, insulin resistance and cardiovascular events by reviewing the evidence that adipose tissue is a metabolically active organ and that each of the components of the cardiometabolic syndrome have influences on vascular, cardiac and renal tissues, thus contributing to morbidity and mortality. The effects of antihypertensive drugs on components of the syndrome are also reviewed in the light of current evidence.
The current evidence relating blood pressure to cognitive decline with aging has revealed a “U” shaped relationship, with subjects having elevated systolic pressure, or those with hypotension having the greatest risk for a decrease in mental performance. The treatment of systolic hypertension, a prevalent problem in those in the older age group in which cognitive decline is most frequently seen, appears to have a consistent benefit in reducing the overt occurrence or progression of such impairment, when present. A growing body of data from randomized controlled trials provides further information regarding the possible differential effects of specific antihypertensive agents, but the bulk of the evidence suggests the benefit of treating hypertension as a protective approach to the prevention of dementia. With the growing age of the population, it is certain that this will become increasingly important in the future and any new information regarding the benefit of specific drug classes or agents for the treatment of hypertension in the reduction of dementia will assume major importance.
From a multi-center Veteran’s Adminstration group we have a brief report of the significant reduction in stroke among over 50,000 veterans during the period of 1991-1997. While it may seem to be only a part of a secular decline in stroke prevalence, the fact that the population studied is an aging one, with many risk factors for stroke, makes this an important new observation. Over half of those sustaining stroke were hypertensive and more than 20% were diabetic. The gratifying, almost 30%, decline in the incidence of stroke in such a short time period among this susceptible population could well be attributed to improved detection and more effective treatment of hypertension and diabetes. This report has recently been confirmed by the report from the Framingham Study1 involving a much smaller, exclusively Caucasian, population of men and women followed over a longer period of time in whom the incidence of stroke also decreased, but the lifetime risk of stroke did not decline, presumably due to a lengthened life expectancy resulting from better control of systolic pressure, cholesterol and reduced smoking despite an increase in obesity and diabetes over the same period.
The final paper in this issue is an original research paper that carefully examines the contribution of endothelin (ET) to vascular inflammation by evaluating the effects of ETA and ETB receptor antagonists and the PPARγ agonist, rosiglitazone on the action of endothelin on vascular smooth muscle cells from hypertensive and normal control rats. It is likely that investigation of these experimental agents as well as the “glitazones” in clinical trials may provide new understanding of the pathophysiology of, and new therapeutic approaches to, the prevention of cardiovascular disease in the future.
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