Systolic Hypertension in the Elderly Program (SHEP). Part 8: Electrocardiographic characteristics.
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Aged↗
Biomedical subjects
W Frishman
Publications and source records attributed to W Frishman.
Lipids, vascular disease, and dementia with advancing age. Epidemiologic considerations.
Elevated plasma lipid and lipoprotein levels are associated with an increased risk of cardiovascular disease in middle-aged men and women. It is still not clear, however, whether lipid and lipoprotein abnormalities continue to be risk factors for cardiovascular disease in the elderly population. It is not even clear what normal lipid values are in the elderly, and whether diet or drug therapy should be advised on the basis of lipid values established in middle-aged populations. Ischemic heart disease does remain the leading cause of death in the elderly, and there is now preliminary evidence from epidemiologic studies that relative elevations of levels of lipid and lipoprotein fractions in an elderly population might be associated with an independent and increased risk of coronary heart disease, stroke, and possibly dementia. Intervention studies are about to begin that will assess various lipid-and lipoprotein-modifying therapies and their ability to reduce vascular disease risk in the elderly.
Aged↗
Probucol: pharmacology and clinical application.
Increased levels of cholesterol, LDL-cholesterol, and VLDL-cholesterol are known risk factors for the development of atherosclerotic vascular disease. Probucol is an orally active agent that can reduce total cholesterol and LDL-cholesterol. The drug also reduces HDL-cholesterol. However, it may modify the lipoprotein in such a way that removal of cholesterol from peripheral tissues is still enhanced. Probucol also has antioxidant activity, which may inhibit the oxidative modification of LDL that contributes to lipid deposition in blood vessel walls. Probucol is a well tolerated agent. However, its ability to prolong life in human subjects still needs to be determined.
Animals↗
Development of dementing illnesses in an 80-year-old volunteer cohort.
We have prospectively followed over a 5-year period 434 volunteers who were at intake ambulatory, functional, presumably nondemented, and between 75 and 85 years of age. Fifty-six (an incidence of 3.53 per 100 person-years at risk) developed a progressive dementia: 32 met diagnostic criteria for Alzheimer's disease (AD) (an incidence of 2.0 per 100 person-years at risk), 15 had vascular or mixed dementia, and 9 had other disorders or remain undiagnosed. New cases of dementia were as common as myocardial infarction and twice as common as stroke. Risk factors for both dementia and AD were age (over 80) and gender (female); other reported risk factors such as family history, prior head injury, thyroid disease, maternal age, and smoking were not risk factors for AD in this elderly cohort. Prior stroke was the major risk factor for vascular or mixed dementia; diabetes and left ventricular hypertrophy but not a history of hypertension per se were also risk factors for vascular dementia. The major predictor of the development of AD was the mental status score on entry. The 58.5% of the cohort who made zero to two errors on a 33-item mental status test had a less than 0.6% per year chance of developing AD, whereas the 16% of the cohort with five to eight errors on this test developed AD at a rate of over 12% per year. Thus, it is possible to identify a large cohort of 80-year-olds who are at low risk for AD and a smaller cohort at very high risk.
Aged↗
Electromechanical dissociation: diagnosis, pathophysiology, and management.
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Death, Sudden↗
Diltiazem, nifedipine, and their combination in patients with stable angina pectoris: effects on angina, exercise tolerance, and the ambulatory electrocardiographic ST segment.
The efficacy and safety of oral nifedipine and diltiazem were compared in 20 patients with stable angina pectoris with use of a placebo run-in, randomized, double-blind titration to maximal effect crossover protocol. The effects of treatment withdrawal were also analyzed. All patients received placebo for 2 weeks and were then randomly assigned to receive either diltiazem or nifedipine. A 2 week drug titration phase in which patients received either diltiazem (180 to 360 mg/day) or nifedipine (30 to 120 mg/day) in three divided doses was followed by a 1 week maintenance phase. Patients then received placebo for 1 to 2 weeks, followed by crossover to the other treatment regimen and a second placebo washout period of 1 week. Patients (n = 13) who remained symptomatic on both diltiazem and nifedipine during the monotherapy periods entered a 3 week combination treatment phase, followed by a final 1 week placebo washout period. Frequency of angina, nitroglycerin consumption, exercise tolerance (Naughton protocol), and frequency of daily episodes of ST segment deviations on the electrocardiogram (1 mm of ST segment depression persisting for at least 1 min with and without chest pain) on an ambulatory electrocardiographic monitor were assessed during the baseline placebo, active monotherapy, placebo withdrawal, and combination treatment phases. Plasma drug levels were also measured. Compared with initial placebo values, the frequency of angina and the amount of nitroglycerin treatment were reduced by both diltiazem (p less than .001) and nifedipine (p less than .02). Diltiazem was more effective than nifedipine in reducing angina (p less than .02). Exercise duration increased with both drugs (p less than .0001). Diltiazem was significantly better than nifedipine in reducing the episodes of ST segment depression on the ambulatory monitor (p less than .01). Diltiazem reduced the resting heart rate (p less than .01); both drugs reduced the resting blood pressure and rate-pressure product. Overall, combination therapy was more effective in patients who did not maximally respond to diltiazem or nifedipine alone with respect to anginal and exercise variables and in reducing blood pressure at rest and during exercise. Plasma drug levels could not predict an individual patient's treatment response. Diltiazem may increase nifedipine drug levels when the drugs are combined. Fewer side effects were observed with diltiazem than nifedipine; the most side effects were seen with combination treatment. There were no apparent withdrawal effects observed with either treatment regimen.(ABSTRACT TRUNCATED AT 400 WORDS)
Angina Pectoris↗
Enalapril: a long-acting angiotensin-converting enzyme inhibitor.
The development of angiotensin-converting enzyme (ACE) inhibitors is of landmark importance in the understanding and treatment of cardiovascular disorders, particularly hypertension and congestive heart failure. Enalapril has recently joined captopril as an approved, orally active ACE inhibitor. Like captopril, it has been effective in the treatment of hypertension and congestive heart failure, with minimal adverse reactions noted. Differences in pharmacology exist between enalapril and captopril which may prove to be of clinical significance.
Angiotensin-Converting Enzyme Inhibitors↗
Malignant pericardial diseases: diagnosis and treatment.
Pericardial involvement in malignant disease is fairly common. Usually the various clinical presentations--effusion, tamponade, constriction--occur in patients with known malignancy. Primary malignancy of the pericardium is rare, whereas secondary tumor involvement of the pericardium is more frequently observed. The common secondary solid tumors involving the pericardium are from lung and breast carcinomas; of the nonhematologic malignancies, lymphomas and leukemias are most frequent. A high index of suspicion in patients with malignancy, along with a history, physical examination, x-ray films, ECG, and echocardiography, will often make the diagnosis in a hemodynamically compromised patient. Occasionally, cardiac catheterization and pericardial biopsy are necessary to differentiate malignant pericardial disease from radiation pericarditis and restrictive heart disease. Therapy is dependent on the underlying condition and includes pericardiectomy, chemotherapy to obliterate the pericardial space, and external beam radiotherapy. These therapies are all palliative, but provide months of hemodynamic relief. The underlying prognosis of malignant pericardial disease remains grave.
Heart Neoplasms↗
The safety and efficacy of once-daily dilevalol in patients with mild hypertension: a placebo-controlled study.
Dilevalol is a stereoisomer of labetalol, with a unique combination of beta-adrenergic blocking effects and selective beta 2-agonist activity. The safety and efficacy of dilevalol in patients with systemic hypertension were evaluated in a placebo-controlled, double-blind, randomized study. After a 4-week placebo run-in period, patients with mild hypertension (supine diastolic blood pressure of 95-105 mmHg) were randomized to receive either placebo (n = 14) or increasing doses of dilevalol (n = 15), 100-800 mg, once daily, to achieve normalization of pressure and/or a reduction of supine diastolic pressure of greater than or equal to 10 mmHg. This was followed by a 4-week maintenance phase. Compared with placebo, dilevalol, 200-800 mg/day, lowered supine and standing systolic and diastolic blood pressures significantly, while causing a modest reduction in heart rate. The drug was well tolerated without evidence of orthostasis. Dilevalol, in doses of 200-800 mg/day, is a safe and effective drug for the treatment of patients with mild hypertension.
Clinical Trials as Topic↗
Twice-daily administration of oral verapamil in the treatment of essential hypertension.
The antihypertensive effect of twice-daily administration of verapamil hydrochloride was evaluated in 21 adult patients with mild to moderate essential hypertension. Following four weeks of placebo therapy, verapamil was given for four weeks with a treatment goal of sitting diastolic blood pressure (BP) of less than 90 mm Hg, or to a maximum dose of 160 mg twice daily. Sitting and standing BPs, heart rate, and verapamil plasma levels were determined weekly, ten to 12 hours post dose. At the maximal dose (mean, 154 +/- 19.2 mg), heart rate was not affected, side effects were minimal, and sitting diastolic BP was significantly reduced from placebo baseline, with 12 of 21 patients having a fall in sitting diastolic BP of 10 mm Hg or more or less than 90 mm Hg. A trough verapamil plasma level of greater than 80 ng/mL was associated with a good hypotensive response. These data indicate the safety and utility of twice-daily verapamil administration for the treatment of essential hypertension and suggest the value of obtaining verapamil plasma levels as a guide to dosage determination.
Administration, Oral↗
Rest and exercise hemodynamic and adrenergic responses to enalapril, hydrochlorothiazide, and combination treatment in patients with systemic hypertension.
The effects of enalapril (10-20 mg twice daily), hydrochlorothiazide (25-50 mg twice daily), and combination enalapril-hydrochlorothiazide therapy (10-20 mg enalapril/25-50 mg hydrochlorothiazide in combination tablet twice daily) were evaluated and compared to no therapy (control) in eight patients with mild to moderate hypertension at rest and during treadmill exercise. All active treatments reduced standing blood pressure in patients at rest compared to the control group (p less than 0.05); however, none produced significant reductions of standing blood pressure in patients at peak exercise. Standing heart rates of patients at rest and at peak exercise were not changed with active therapy. However, standing heart rate in patients at rest was lower with enalapril than with hydrochlorothiazide and combination therapy (p less than 0.05). Heart rate of patients on hydrochlorothiazide was higher than with control and other therapies at Stage I of exercise (p less than 0.01). Supine norepinephrine levels in patients at rest were elevated with both hydrochlorothiazide and combination therapy when compared to that in patients with enalapril and control (p less than 0.05). Treatment with enalapril alone produced no changes in plasma catecholamine levels compared to control. There were no differences between control and all treatment regimens in peak exercise levels of catecholamines. Thus, enalapril, hydrochlorothiazide, and combination therapy, although effective in lowering resting blood pressure, may not be effective in blunting the blood-pressure response to exercise. The drugs do not appear to have any significant effects on catecholamine levels in patients at peak exercise.
Adult↗
Improvement in exercise capacity despite cardiac deteriora tion: nonivasive assessment of long-term therapy with amrinone in severe heart failure.
Seven patients with severe congestive heart failure (CHF) were treated with oral amrinone for a mean duration of 39 weeks (range 16 to 72). During the first week of therapy, exercise capacity as assessed on a treadmill using the Naughton protocol, increased substantially from 7.6 +/- 4.2 to 12.1 +/- 4.4 minutes (p less than 0.01). At an early period of follow-up (8 to 12 weeks), a further significant increase in exercise capacity to 14.7 +/- 5.0 minutes (p less than 0.05) was demonstrated, while at a later follow-up exercise capacity had decreased to 11.4 +/- 6.8 minutes (p less than 0.05). This was still significantly greater than prior to amrinone therapy (p less than 0.01). Left ventricular ejection fraction was increased from 14 +/- 4 to 19 +/- 4% (p less than 0.05) during the first week of therapy, but was not significantly different from control at the early and late periods of follow-up. Left ventricular end-diastolic dimension index increased from control value of 43 +/- 5 to 47 +/- 7 mm/m2 (p less than 0.01) at the late period of follow-up. Thus long-term amrinone therapy resulted in a substantial improvement in exercise capacity despite a slow, but progressive decline in cardiac performance.
Adult↗
Beta-adrenergic blockade and the gastrointestinal system.
As beta-adrenergic blockers grow increasingly popular for the therapy of a wide variety of disorders, it becomes increasingly important to appreciate the spectrum of physiologic effects on the gastrointestinal system and the potential hazards associated with use of these agents. This review details the effects of the beta-adrenergic blocking agents on the gastrointestinal tract.
Adrenergic beta-Antagonists↗
Antiarrhythmic drug therapy during pregnancy.
Pregnancy increases the work demands on the heart by increasing blood volume and thereby cardiac output. Therefore, in pregnant patients with organic heart disease, arrhythmias may have significant hemodynamic consequences to the mother with harm to the fetus. As a result of improved medical therapy, an increasing number of women with cardiac diseases or rhythm disorders reach their reproductive years and require medication. Information on the effect of antiarrhythmic agents on the human fetus as well as the possible changes in therapeutic response during the altered state of pregnancy is limited. In principle, the approach to the treatment of arrhythmias in pregnant patients is similar to that in nonpregnant patients. Special consideration, however, must be given with regard to drug selection and dosage in order to avoid adverse effects on the mother and fetus.
Adrenergic beta-Antagonists↗
Variable clinical response to long-term angiotensin inhibition in severe heart failure: demonstration of additive benefits of alpha-receptor blockade.
The effects of long-term therapy with captopril (CPT) were studied in 11 patients with severe chronic congestive heart failure (CHF). At initiation of therapy, cardiac index increased from 1.88 +/- 0.56 to 2.12 +/- L/min/m2 (p less than 0.05), while pulmonary capillary wedge pressure decreased from 27.9 +/- 7.2 to 17.8 +/- 7.6 mm Hg (p less than 0.01). This improvement in resting cardiac performance was maintained during maximal exercise; however, maximal oxygen uptake was not acutely increased by CPT. During chronic therapy, 6 of 11 patients showed symptomatic improvements; however, only three of these six patients demonstrated an increase in maximal oxygen uptake, which was measured at an average of 13.2 weeks following initiation of therapy. Five patients did not improve clinically during chronic therapy. In these patients, hemodynamic measurements that had improved initially after CPT returned to baseline values during chronic therapy. The addition of prazosin to chronic CPT therapy elicited a beneficial hemodynamic response in all five patients. Thus, the results of long-term therapy with CPT are variable in patients with severe CHF, and symptomatic improvement does not always correlate with objective measurement of exercise capacity. Combined alpha-adrenergic blockade and angiotensin-converting enzyme inhibition appears safe in patients who failed to exhibit a sustained improvement on CPT alone.
Adrenergic beta-Antagonists↗
Treatment of angina pectoris with pindolol: the significance of intrinsic sympathomimetic activity of beta blockers.
Although all beta blockers have been found to be effective in the symptomatic relief of angina pectoris, the importance of intrinsic sympathomimetic activity (ISA) has not been studied extensively. In a randomized, double-blind study, we administered equipotent doses of propranolol (10, 20, and 40 mg four times a day) and pindolol (2.5, 5, and 10 mg four times a day), a beta blocker with significant ISA, to 52 patients with angina. Both agents were found to be effective in the treatment of angina. At peak dose, propranolol reduced the number of angina attacks per 2 weeks from 29.29 +/- 4.79 to 18.0 +/- 4.4 (p = 0.021) (a 39% reduction) and increased the exercise tolerance on the treadmill from 7.55 +/- 0.67 METS to 9.36 +/- 0.58 (p = 0.002). Pindolol decreased the number of anginal attacks per 2 weeks from 16.48 +/- 2.63 to 8.65 +/- 2.46 (p = 0.0027) (a 48% reduction) and increased exercise tolerance from 7.95 +/- 0.56 METS to 9.40 +/- 0.57 (p = 0.0245). At the end of the maximum tolerated exercise, propranolol decreased the heart rate from 110.00 +/- 3.41 to 99.71 +/- 3.74 (p = 0.0015). Pindolol also decreased the heart rate at the maximum tolerated exercise from 113.59 +/- 3.24 to 108.12 +/- 3.16 (p = 0.0102). At rest, however, propranolol induced a more pronounced (p = 0.0066) decrease in heart rate (from 69.00 +/- 1.85 to 61.50 +/- 1.99; p = 0.0018), whereas pindolol did not significantly affect the resting heart rate (65.37 +/- 1.47 to 65.5 +/- 1.44; p = 0.9392). In addition propranolol decreased echocardiographically determined ejection fraction from 0.57 +/- 0.02 to 0.15 +/- 0.01 (p = 0.04) and increased the left ventricular end-diastolic volume from 71.8 +/- 3.2 to 92.2 +/- 1.9 ml (p = 0.003), whereas pindolol did not affect the ejection fraction and caused a less pronounced (p = 0.03) increase in end-diastolic volume (from 70.8 +/- 1.8 to 80.2 +/- 2.8; p = 0.02). The data indicate that both propranolol and pindolol are effective in the treatment of angina pectoris and that pindolol decreases the resting heart rate and ejection fraction and increases the left ventricular end-diastolic volume to a lesser extent than propranolol.
Adult↗
Clinical relevance of verapamil plasma levels in stable angina pectoris.
Plasma levels of verapamil and norverapamil were evaluated in 77 patients who received oral verapamiL for treatment of angina pectoris. There was a sixfold interpatient variation in verapamil plasma concentrations, but plasma concentrations were linearly related to doses of the drug (240 to 480 mg/day) in the same patient (r = 0.81). Plasma concentrations of norverapamil, the major active metabolite of verapamil, were similar to those of verapamil. Although verapamil produced a significant improvement in exercise tolerance in most patients, the increase in exercise time was not related to plasma levels of the drug; however, most patients with improvement had plasma levels exceeding 100 ng/ml. An increase in the dose of verapamil from 320 to 480 mg daily produced a substantial (71%) increase in plasma levels of the drug but no significant increase in exercise tolerance (4%). The average increase in the P-R interval with 480 mg of verapamil in these 77 patients was small (8%) (161 +/- 18 to 174 +/- 22 ms); on.y six patients had first-degree heart block. These minor effects on atrioventricular conduction were noted despite plasma verapamil concentrations in 76 patients that exceeded 100 ng/ml, a level that successfully converts supraventricular tachycardias after intravenous drug administration. We differences between the effects of oral and intravenous verapamil on atrioventricular conduction may be the result of stereoselective hepatic inactivation of verapamil's I-isomer. Determination of plasma levels of verapamil is of limited value in the management of patients with angina pectoris, but may be useful in the identification of nonresponders with plasma levels less than 100 ng/ml who may benefit from a further increment in drug dose.
Administration, Oral↗
Nifedipine in hypertension. Expanding applications of a new drug.
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Antihypertensive Agents↗