Ambulatory systolic blood pressure patterns in elderly hypertensives.

In a recent study we found that patients with isolated systolic hypertension (ISH) had two patterns of systolic blood pressure (SBP) elevations by ambulatory BP monitoring (ABPM), sustained (S) and intermittent (I), the prognostic significance of which seems to be different. In the present study we tried to determine whether such patterns of SBP elevations may be detected among other hypertensives as well. Twenty-eight elderly patients (mean age 65.5+/-5.1 years), nine with ISH, 10 with systolodiastolic hypertension (SDH), and nine with white coat hypertension (WCH), underwent ABPM. Average clinic BP in the ISH group was 184/83 mm Hg, in the SDH group 172/101 mm Hg, and in the WCH group 166/91 mm Hg, where as the ABPM averages were 169/80, 167/95 and 132/73 mm Hg, respectively, and differences held true for both daytime and night-time. Five ISH and four SDH patients had S patterns on ABPM, while the other four ISH and six SDH patients exhibited I patterns; none of the nine WCH subjects had either S or I patterns. ECG revealed left ventricular hypertropy (LVH) and/or ischaemic changes in eight patients with S patterns (ISH and SDH groups combined), as opposed to two patients with I patterns and only one patient of the WCH group. This seems to further suggest that an S pattern of SBP elevation on ABPM may have worse prognostic implications than either an I pattern or no SBP elevation.

[Cerebral blood flow in elderly hypertensives after enalapril of calcium channel blockers].

25 elderly hypertensive patients (mean age 66.5 +/- 5.0 years) were given enalapril (E) 20-40 mg daily, or calcium channel blockers (CCB): either slow-release nifedipine (40 mg) or long-acting verapamil (120-360 mg) daily, 6 weeks each, in a single-blind crossover study. At the end of each treatment period cerebral blood flow (CBF) was assessed by single proton emission, computed tomography, using 99m-Tc-exametazime. In the 20 patients who completed the study, supine BP was lowered from 194/106 to 167/90 mmHg (p less than 0.001/0.001) by E and from 185/104 to 172/91 (p less than 0.01/0.001) by CCB. Standing BP was lowered from 184/106 to 160/93 (p less than 0.001/0.001) by E and from 175/102 to 162/93 (p less than 0.01/0.01) by CCB. Although there were great interpatient differences in CBF, the individual pattern remained unaltered by either E or CCB and mean quantitative changes were not significant. We conclude that in elderly hypertensives both E and CCB effectively lower BP, while cerebral perfusion is not adversely affected by either.

[Effect of captopril on pulmonary function].

During the past few years, dry cough has been described as a possible adverse effect of treatment with angiotensin converting enzyme (ACE) inhibitors. There have been several studies of the effect of long-term administration of ACE inhibitors on pulmonary function. We examined spirometrically the effect of a single oral dose of captopril (25 mg) on bronchial tonus in those who had not received the drug previously, in 4 patients who had previously had dry cough during ACE inhibitor therapy, in 20 patients with obstructive pulmonary disease and in 20 control subjects without pulmonary disease. 1 hour after ingestion of captopril there were no significant changes in the spirometric tests of any group. These findings supplement the results of similar tests done during longterm administration of ACE inhibitors, indicating that the pathogenesis of cough elicited by ACE inhibitor therapy does not seem to have an asthmatic basis.

Massive hepatic infarction in systemic lupus erythematosus.

Liver disease in systemic lupus erythematosus, as demonstrated by abnormal histopathology, is rare and usually mild; typically, this hepatic disease is of chronic nature and not related to a hypercoagulable state. A patient is described in whom life-threatening hypercoagulability in association with systemic lupus erythematosus resulted in extensive liver infarction. Follow-up radionuclide liver scintigraphy suggested that regenerative recovery in the infarcted areas of the liver may be delayed or absent, but there was no evident functional hepatic impairment.

Comparison of the acute effects of captopril and of nifedipine on left ventricular diastolic function in elderly hypertensive patients.

The acute effects of single doses of captopril (C) 12.5 mg, of nifedipine (N) 10 mg, or of their combination (C + N) on parameters of left ventricular (LV) function were assessed in 18 elderly hypertensive subjects using radionuclide ventriculography. Blood pressure (BP) was lowered by C from 177/100 to 164/92 mmHg, by N from 177/100 to 161/91 mmHg (p less than 0.02/less than 0.05 for both C and N) and by C + N from 176/100 to 151/83 mmHg (p less than 0.01/less than 0.01). Nifedipine accelerated heart rate from 74 to 85 and C + N from 74 to 82 beats/min (p less than 0.01 in both cases), whereas C left it unchanged. Left ventricular ejection fraction (EF) was not significantly affected by either drug alone or by both drugs combined. Peak ejection rate (PER) and peak filling rate (PFR) were slightly, but not significantly, enhanced by all treatments. Captopril shortened the time to peak filling rate (TPFR) by 21 msec (p less than 0.05), N by 26 msec (p less than 0.01) and their combination by 22 msec (p less than 0.05); however, when corrected for RR interval or length of diastole, TPFR was shortened only by C (p less than 0.05). Tachycardia induced by acute administration of N may have an unwanted effect on LV diastolic function, which can be partially blunted by the concomitant administration of a converting enzyme inhibitor.

Comparison of oxprenolol vs methyldopa as second-line antihypertensive agents in the elderly.

Direct within-patient comparisons of the effects of centrally acting sympathetic inhibitors and beta-blockers on blood pressure (BP) of the elderly have not been done. In the present study, 32 elderly hypertensive patients were treated with a diuretic. Methyldopa (500 mg/d) (16 patients, subgroup A) or slow-release oxprenolol (80 mg/d) (subgroup B) was added as a second-step antihypertensive agent for a period of eight weeks, after which the second-step agents were switched, respectively, for another period of eight weeks. In subgroup A the supine BP dropped from 193/99 to 169/93 mm Hg and the standing BP from 183/100 to 163/92 mm Hg, whereas in subgroup B the supine BP fell from 190/103 to 182/97 mm Hg and the standing BP from 187/101 to 172/95 mm Hg. After switching the drugs, the respective BP values were 177/91 and 170/95 mm Hg and 170/90 and 156/89 mm Hg. In the doses given, methyldopa therapy is more effective than oxprenolol therapy in lowering the BP of elderly hypertensive patients.

Patient characteristics and their influence on therapy and its outcome in hypertension of the elderly.

A retrospective study was undertaken to analyze the effects of various patient factors on therapy and its outcome in elderly hypertensive subjects. Two hundred and three male hypertensives with a mean age of 63.1 years at entry, were followed in a special hypertension clinic by nurse practitioners under physician supervision, for 2 years or more (mean 3.7 years). Good patient compliance (84%) and blood pressure (BP) reduction were achieved and these were enhanced by advancing age. Neither excessive weight, nor widespread atherosclerosis seemed to interfere with BP control. However, while diastolic BP was well controlled with antihypertensive therapy, systolic BP tended to remain higher than 160 mm Hg in many of the older and more atherosclerotic subjects. Pharmacological treatment did not prevent a gradual although modest deterioration of renal function, which was related to both age and hypertension, and represents a greater problem in black patients. Because of the limitations of such a retrospective study, its conclusions may not be extrapolated for treatment of hypertension in all the elderly.

Once-a-day triple therapy with low-dose minoxidil for moderate hypertension.

Minoxidil was given to 16 men with hypertension of various degrees of severity, in conjunction with a diuretic and atenolol. Mean supine and standing blood pressures (BP) on diuretic + atenolol were 172/106 and 162/104 mm Hg, respectively. Minoxidil was added and the dose titrated to lower the diastolic pressure to less than 90 mm Hg. All drugs were taken together once daily. At the end of a maintenance period of 6 months on an average dose of minoxidil of 12 mg (range 2.5 to 20.0 mg), supine BP was 147/87 and standing BP 139/88 mm Hg. Similar BP had been measured throughout the maintenance period, and monitoring of the BP showed that the once daily regimen provided good control for 24 h. A strong correlation was found between the dose of minoxidil necessary to normalize the BP and the mean arterial pressure prior to minoxidil (r = 0.73, P less than 0.005). Serious adverse effects of the drug were observed only in patients receiving doses greater than 10 mg or those with widespread atherosclerosis, or both. We conclude that, when added to a diuretic and a beta-blocker in a once-a-day regimen, minoxidil in a daily dose of less than or equal to 10 mg is effective and well tolerated in mild to moderate hypertension, especially in patients who are free of atherosclerotic complications.

Comparison of low-dose captopril and propranolol as second-line drugs in mild and moderate hypertension.

Captopril in low doses has been used recently with success in the treatment of mild to moderate hypertension. In the present study we compared the effects of captopril, 50 mg/day, to propranolol, 80 mg/day, as second-line antihypertensive agents. By administering each of these drugs together with hydrochlorothiazide, the mean blood pressure was lowered from 156/99 to 140/84 and from 15/98 to 140/85 mm Hg, respectively. Although serious adverse effects were infrequent in both groups of patients, bradycardia and fatigue were common among the subjects receiving propranolol, whereas captopril left the quality of life largely unaltered. Captopril appears to be a safe and effective antihypertensive agent in mild and moderate hypertension when used in low doses in addition to a thiazide diuretic.

Hypertension and renal failure (scleroderma renal crisis) in progressive systemic sclerosis. Review of a 25-year experience with 68 cases.

This paper reports the experiences of our group with 68 patients with progressive systemic sclerosis (PSS) admitted to hospitals of the University of Pittsburgh Health Center between 1955 and 1981 with scleroderma renal crisis (SRC). The onset of SRC was characterized by four features, namely, onset or aggravation, usually abrupt, of arterial hypertension; appearance of Grade III or IV retinopathy; elevations of peripheral renin activity to at least twice the upper limit of normal; and rapid deterioration of renal function within a period of less than one month. Over 90% of our patients in whom these criteria could be determined had at least three of them present with the onset of SRC. Management of these patients during the first 15 years of this period was uniformly ineffective. Before 1971, no patients lived longer than a year; usual survival ranged from 1 to 3 months. With the advent of renal dialysis and the more effective treatment of severe hypertension, along with the utilization of bilateral nephrectomy in selected anuric patients, some improvement in longevity was achieved. However, only in the past few years have we accumulated a group of 11 patients who have survived for longer than one year. The clinical characteristics of the onset and progression of SRC suggest the sudden imposition of severe stress such as cold or an autoimmune insult affecting vulnerable arteries and arterioles. The renal damage becomes self-perpetuating with extremely high renin activity causing further rise in blood pressure and additional renal and systemic vascular damage. Progress in the last few years seems to have been achieved primarily by the advent of pharmacologic agents that specifically block the effect of angiotensin II by inhibiting the angiotensin I converting enzyme. When diagnosis is prompt and the condition is treated as an emergency with these compounds, we and others have found that normal renal function can be restored in a number of patients. The result is a considerably brighter outlook for patients with this previously rapidly fatal complication of progressive systemic sclerosis.

Combined treatment with minoxidil and captopril in refractory hypertension.

The BP of four patients with severe hypertension could not be controlled by treatment with a variety of drugs including minoxidil and captopril. Satisfactory responses were obtained only when minoxidil and captopril were given in combination (along with diuretic and beta-adrenergic blocking agents). The doses of minoxidil could be reduced by the addition of captopril and adverse effects were thus minimized. The state of the renin-angiotensin system prior to therapy was not a reliable predictor of the hypotensive response of the combination.

Cerebral blood flow changes with diuretic therapy in elderly subjects with systolic hypertension.

It has been feared that lowering the blood pressure (BP) of elderly patients with systolic hypertension (SH) may compromise cerebral perfusion. To test this hypothesis, BP, cerebral blood flow (CBF), plasma renin activity (PRA), blood counts, urinary and serum electrolytes and other blood chemistries were measured in fifteen elderly patients (ages 61-76 years) with SH (systolic BP greater than 170 and diastolic BP less than 100 mmHg). Gray matter flow (Fg) was calculated from clearance curves of inhaled 133-Xenon. All subjects were studied while untreated, as well as during long-term treatment (average 15 weeks) with hydrochlorothiazide. BP fell during treatment from 186/90 to 160/86 while average Fg and cerebrovascular resistance (CVR) were not significantly changed. There was some suggestion, however, that in patients who became normotensive the CVR decreased (p less than 0.05) while in those who did not Fg fell (p less than 0.05). Cerebrovascular response to 5% CO2 inhalation was impaired during both the treated and untreated states. Individual changes in Fg and CVR did not correlate with changes in BP or with changes in PRA, electrolytes or other chemistries. In general, cautious, gradual reduction of BP with a thiazide diuretic in SH of the elderly seems not to impair cerebral perfusion, but individual differences exist and further studies are needed to characterize them.

Complications of antihypertensive therapy.

Effective use of modern antihypertensive agents requires an intimate understanding of the various side effects associated with each of the drugs. Some of the undesirable side effects are unavoidable because they are inherent in the action of the drug. For example, hypokalemia and hyperuricemia are inherent side effects of diuretic therapy. Other adverse reactions are idiosyncratic and difficult to predict. With careful monitoring and individual therapeutic planning, these side effects need not inhibit efforts to control hypertension.