Edward S. Cooper

The Effect of Treatment on Mortality in Mild Hypertension: Results of the Hypertension Detection and Follow-up Program

In the Hypertension Detection and Follow-up Program, 7825 (71.5 per cent) of the 10,940 participants had diastolic blood pressures averaging between 90 and 104 mm Hg on entry into the study and were designated Stratum 1. Half were referred to their usual source of care in the community (the referred-care group), and half were treated intensively in special clinics (the stepped-care group). Five-year mortality in the Stratum 1 patients given stepped care was 20.3 per cent lower than in those given referred care (P less than 0.01). Particularly noteworthy was the beneficial effect of stepped-care treatment on persons with diastolic pressures of 90 to 104 mm Hg who had no evidence of end-organ damage and were not receiving antihypertensive medication when they entered the study. This subgroup had 28.6 per cent fewer deaths at five years among those treated with stepped care than among those treated with referred care (P less than 0.01). These findings support a recommendation that in patients with mild hypertension, treatment should be considered early, before damage to end organs occurs.

Cerebral autoregulation in man.

Autoregulation was tested by regional blood flow (rCBF) and cardiohemodynamic measurements before and after induced systemic arterial hypertension in 16 patients with varying neurological disorders. Hypertension was induced by increasing the arterial blood pressure by an intravenous infusion of Aramine. Seven (Group 1) of the patients had a mean increase in mean arterial pressure (MAP) of 32 mm Hg and had preserved autoregulation while nine (Group 2) with a 56 mm Hg increase in MAP showed complete or mixed loss of autoregulation. Group 1 had a higher baseline mean CBF than did the group with loss of autoregulation. The group with loss of autoregulation also generally had more severe involvement on the cerebral angiogram than did the other. Baseline cardiac index and cardiac work were lower in the group with loss of autoregulation. During Aramine infusion the MAP was increased by 38% in Group 1 and 59% in Group 2. The mean CBF was essentially unchanged in Group 1 but increased 24% in Group 2. When autoregulation is lost, rCBF may increase homogeneously or heterogeneously with some areas increasing while others remained unchanged or even decreased. In four instances there was an intracerebral steal during induced hypertension with a fall in rCBF. Whether or not autoregulation is preserved could be related to: (1) the greater induced increase in MAP in Group 2 than Group 1, (2) greater angiographical involvement with a lower baseline in CBF in Group 2 than in Group 1 or (3) a direct or indirect influence of various cardiovascular factors.

Transient responses of cerebral blood flow and ventilation to changes in PaCO2 in normal subjects and patients with cerebrovascular disease.

In the present study, the dynamics of the cerebral blood flow (CBF) and ventilatory response to hypercapnia was investigated in a group of patients with cerebrovascular disease and compared to responses measured in a group of normal volunteers. There was a significant correlation between the rapidity of the transient CBF and ventilatory responses and the severity of the cerebrovascular disease. While the steady state CBF response showed no such correlation, the steady state ventilatory response was reduced in patients with severe cerebrovascular disease. Various explanations for the differences in the dynamic responses of CBF and ventilation in patients with mild or severe cerebrovascular disease compared to normal sbjects are considered. Measurement of these circulatory and ventilatory responses may be sensitive means for assessing the changing status of patients with cerebrovascular disease.

Regional cerebral blood flow and cardiovascular effects of hexobendine in stroke patients

WHETHER OR NOT cerebral vasodilator therapy in occlusive cerebrovascular disease will alter the clinical course of the disorder remains speculative. The fact, however, that regional cerebral circulation can be improved, even in ischemic areas, following the administration of basodilating agents has been dem0nstrated.l-3 Until recently, no agents other than papaverine or carbon dioxide have been shown to cause specific regional cerebral vasodilatation in man. Now, hexobendine, a new vasodilator, has been found to increase cerebral blood flow by approximately 15% in monkeys4 and up to 40% in dogs.5 A 15% increase in cerebral blood flow has also been demonstrated in man.6 Earlier investigation7 showed hexobendine to be a potent coronary vasodilator. The purpose of this study was to evaluate the effects of intravenous hexobendine on regional cerebral blood flow (rCBF), metabolism, and cardiac function in patients with cerebrovascular disease.

The Relation Between Cardiac Function and Cerebral Blood Flow in Stroke Patients. 1. Effect of CO2 Inhalation

The effects of CO2 inhalation were determined on 23 stroke patients with and without hypertension who underwent clinical, cardiohemodynamic, cerebral blood flow (hemispheric mean and regional), cerebral metabolic rate and cerebral angiographical studies. Cardiac output, heart rate, systemic and pulmonary arterial blood pressures and cardiac work rose in essentially all patients during CO2 inhalation, and fell to below baseline levels in approximately half of the patients studied after CO2, inhalation was discontinued. Baseline cardiac output was normal in normotensive stroke patients without cardiac dysfunction, but was low in hypertensive stroke patients. A statistically significant increase in cerebral blood flow occurred during CO2 inhalation, with an observed decrease in cerebrovascular resistance. The percentage increase in cerebral blood flow exceeded the increase in cardiac output. Since hypercarbia causes a rise in systemic and pulmonary arterial blood pressure, CO2 inhalation should be used cautiously in patients with systemic or pulmonary hypertension. The rise in cardiac work during CO2 inhalation could jeopardize patients with coronary heart disease and those with heart failure. Following cessation of CO2 inhalation, blood pressure and cardiac output may fall below baseline levels, with a risk of posthypercapnic fall in cerebral blood flow. Occasionally, cardiac arrhythmia occurs during or following CO2 inhalation.

Atrial fibrillation with ventricular slowing in a patient with spontaneous subarachnoid hemorrhage

Abstract A patient with atrial fibrillation, ventricular slowing and rising blood pressure in association with spontaneous subarachnoid hemorrhage is described. The possible mechanisms underlying these phenomena in this patient are discussed. Vagal stimulation secondary to an intracranial lesion should be considered in stuporous patients who have atrial fibrillation and unexplained slow ventricular rate.

Effective Control of Hypertension

Hypertension, the subject of two articles written by Phillips and associates in this issue of the Proceedings (pages 691 to 699 and 700 to 706), is the most pervasive, chronic, remediable disease in the United States today. It is estimated to affect more than 60 million persons who either have been found to have elevated blood pressure (140/90 mm Hg or greater) or have reported being told by a physician that they have high blood pressure. 1 Hypertension is the major risk factor for stroke and a critical one for myocardial in- farction, congestive heart failure, renal disease, retinopathy, aortic dissection, and peripheral vas- cular disease. Both diastolic and systolic hyper- tension have deleterious effects on the circulatory system, and adequate control of high blood pres- sure prevents these adverse effects. Programs for control of hypertension are mainly responsible for the 50% decline in death rates attributable to stroke in the United States during the past 15 years and partially account for the somewhat less dramatic decrease in death rates due to myocardial infarction and other cardio- vascular diseases. Death rates from stroke actu- ally began to decline in the 1920s before effective antihypertensive drugs became available, but the accelerated decrease in stroke-related deaths dur- ing the past few decades is almost certainly due to improved control of hypertension. Except for a small percentage of cases of hypertension with secondary causes, high blood pressure is seldom cured but usually simply controlled. Thus, metic- ulous follow-up of patients is crucial to maintain control. Moreover, well-designed public or profes- sional educational and motivational programs along with easy access and use of health services for patients with hypertension are necessary to curb this silent killer. Hypertension seldom causes symptoms in its early stages; thus, the disease is often overlooked or given low priority by patients, especially be- cause appropriate medications can be expensive or inconvenient to take and frequently cause multiple side effects. The ideal situation would be prevention of the initial onset of hyperten- sion—that is, the primary prevention of hyper- tension itself rather than concentrating on the sec- ondary prevention of complications. In my opinion, such primary prevention programs are not likely to be available on a large scale in the immediate future and will first necessitate the support of much more research and study, including the type of investigation reported herein by Phillips and colleagues. National Studies.—Many national studies have demonstrated the relationship between hyper- tension and complicating diseases of the circu- latory system and have proved the effectiveness of control of high blood pressure in preventing these cardiovascular complications. The Fram- ingham Study, 2 which is not a treatment project

Edward S. Cooper, MD

A professorship chair established at the University of Pennsylvania School of Medicine for Edward S. Cooper, MD, was endowed with

Special Report From the National Institute of Neurological Disorders and Stroke

2 million. This new professorship is in honor of the wonderful physician who has dedicated his life to the field of cardiovascular disease and stroke, while epitomizing excellence in research, teaching, and patient care.