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A statistical analysis of follow-up data on untreated hypertensives Besler, Murray Jack Andrew


Hypertension (commonly known as "high blood pressure") is a disorder whose effects - either direct or indirect - are now widely recognized as capable of creating serious health problems in the segment of the population so affected. Estimates of the size of this segment depend on such factors as the criteria employed in the diagnosis of hypertension, but an overall figure of around 10% of the adult population is commonly quoted - along with the observation that the prevalence is greater among blacks, the elderly, and males in general. The major targets of hypertensive damage are the heart, the brain, the kidneys, and the retinae; consequently, heart attack and heart failure, stroke, and kidney failure are common causes of death among these patients. Unfortunately, the cause of the elevated arterial pressure can be "positively" identified in only some eight to twelve percent of all cases seen; the remaining patients are classified as "primary" or "essential" hypertensives. Research involving essential hypertension has been hampered by the complexity of the (as yet) poorly understood hemodynamic mechanisms of the body, and any sort of consensus here seems to be very slow in developing. Meanwhile, the disease is now being treated - upon discovery - with any one or a combination of three basic anti-hypertensive agents, all of which involve inconvenience, expense, and some rather unpleasant side effects. The wide-spread acceptance of these drugs has also had an unhappy effect on the evolution of our understanding of the clinical course of untreated hypertension, since now only the "mildest" cases may be studied in their natural form. Thus, many questions concerning hypertensive disease remain without satisfactory answers; an appreciation of the degree of uncertainty surrounding many of the issues may be had by examining the work of as few as three or four authors on the subject. Some of the unresolved (or only partially settled) issues include: the relative prognostic significance of the various signs and symptoms that are often associated with high blood pressure; the inter-relations that exist among these signs and symptoms; the pattern of change of the various symptoms over time and the relationship of such changes to the patient's outlook; and, finally, the nature and extent of the part played by hypertension within the broader problem of cardiovascular disease in general - and atherosclerosis in particular. Data on 48 male and 50 female primary hypertensives who received essentially no anti-hypertensive drug therapy, and who were followed until death (or for a maximum of ten years) are analyzed in this thesis, with the aim of illuminating the issues raised above - and others as well. Factors such as age, sex, blood pressure (average as well as extreme values), heart, brain, kidney, and retinal symptoms are examined, both in terms of their association with survival time as well as their inter-relations; sex differences and time trends are also explored. The bulk of the exploratory work is done with ordinary multiple regression and linear discriminant models. Considerable effort is devoted to attempts to reduce the instability that results from the presence of highly correlated variables within the prediction equation. Finally, the relatively new hazard function methodology proposed by Cox is used to obtain an objective and comprehensive formula for use in creating (or identifying) groups of patients who share a similar prognosis. Such a criterion would, for example, be helpful in designing a study to compare different forms of treatment of hypertension.

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