Effects Of Long-term Therapy Research Articles

Comparative Effects of Long-Term Therapy with Captopril and Ibopamine in Chronic Congestive Heart Failure in Old Patients

Little is known concerning the long-term drug management of chronic heart failure (CHF) in old patients (greater than or equal to 75 years). Accordingly, this double-blind, placebo-controlled trial compared the long-term (over 6 months) effect of captopril (37.5-75 mg/day) and of ibopamine (150-300 mg/day) on exercise testing, symptoms and subjective feeling of well-being, in 150 CHF elderly patients (mean age 75 years) under treatment with digitalis and/or diuretics. During an additional open follow-up of approximately 1.5 years, morbid events and deaths were also recorded. Captopril and ibopamine performed better (p less than 0.01) than placebo, improving the 6-min walking distance (captopril from 300 to 404 m, ibopamine from 282 to 385 m; placebo from 283 to 299 m). NYHA status, symptom score and patients' global assessment. The difference between the active study drugs was not statistically significant (p greater than 0.05). Complicating events, including diuretic use, frequency of hospitalization, worsening of CHF and deaths, were grouped by patient-years. These events were significantly (p less than 0.01) lower (captopril: 28/75 patient-years; ibopamine 33/74 patient-years) in the active treatment groups with respect to placebo (58/96 patient-years). Captopril and ibopamine showed a different safety profile. Creatinine increase (2 patients), symptomatic hypotension (4 patients), hyperkalemia (2 patients) and upper respiratory symptoms were mostly associated with captopril treatment. Gastrointestinal adverse events were observed in 11 patients under ibopamine treatment. The study provides evidence of the clinical usefulness of both captopril or ibopamine in the long-term treatment of CHF in old patients. The safety profile of each drug will suggest the preferred therapeutic application.

Antiproteinuric Effect of Angiotensin-Converting-Enzyme Inhibitors in Patients with Primary Glomerular Disease and Normal Renal Function

The antiproteinuric efficacy of angiotensin-converting-enzyme inhibitors (ACEI) has been extensively investigated in patients with several types of nephropathy, but there are few data on the use of ACEI in patients with primary glomerular disease without renal function impairment. We evaluate the effect of long-term therapy with captopril on arterial pressure and proteinuria in 13 patients with primary glomerular disease, selected on the following criteria: persistent proteinuria greater than 600 mg/day, serum creatinine less than or equal to 1.5 mg/dl, no dietary restriction or antihypertensive or immunosuppressive therapy for at least 9 months prior to enrolment. Ten of 13 patients were normotensive. The treatment with captopril induced an early and persistent decrease in proteinuria (41%), and a significant increase in serum albumin. We did not find a significant correlation between changes in MAP and changes in protein loss or between variations in serum creatinine and in proteinuria. Our results demonstrate that captopril is effective in reducing proteinuria in patients with primary glomerular disease with normal renal function. Since the antiproteinuric effect is not associated to a concomitant decrease in arterial pressure, we presume that it might be due to a specific intrarenal action of captopril.

Rapid onset of uricosuria after oral administration of irtemazole, an uricosuric substance.

A single 50 mg dose of irtemazole was given orally to ten healthy male volunteers. The onset of effects was tested. Plasma uric acid began to decrease 15 to 25 min after irtemazole was administrated. Renal uric acid excretion and uric acid clearance increased 10 to 20 min after drug administration. Maximal renal uric acid excretion (mean 197.4 mg/h) and maximal uric acid clearance (mean 78.4 ml/min) were reached after 15 to 55 min. No side effects were observed. The effects of irtemazole occur earlier than those of benzbromarone. The therapeutic effects of long-term therapy remain to be investigated.

Long-term follow-up of aggressively treated idiopathic rapidly progressive glomerulonephritis.

We wanted to examine the long-term effects of aggressively treating idiopathic rapidly progressive glomerulonephritis (RPGN), with a particular focus on clinically characterizing the patient population, assessing the short- and long-term effects of therapy on renal function, and determining complications of the therapy. Twenty-three consecutive patients with RPGN were treated and followed from one to 11 years. On renal biopsy, 13 had immune complexes, eight had no immune complexes, and two had antiglomerular basement membrane deposits. All had greater than 25 percent crescents and 19 of 23 had greater than 50 percent crescents. Every patient responded on a short-term basis to either large-dose pulse methylprednisolone or plasma exchange, with reduction of the mean plasma creatinine level from 6.5 +/- 2.0 mg/dl to 2.9 +/- 1.0 mg/dl (p less than 0.001). Each patient received oral prednisone and all but one received cyclophosphamide. Three died of non-renal causes. Fifty percent of the remaining 20 patients maintained stable renal function for at least two years. Four of nine patients followed-up for longer than two years had a relapse, but all responded again to therapy. No characteristic clinical symptoms predicting relapse were found, although nearly all had hematuria and proteinuria. Complications of therapy were frequent and may have contributed to death in two patients. Thus, long remissions are seen in most patients with RPGN treated aggressively.

Long-Term Immunoregulatory Effects of Therapy with Corticosteroids and Anti-Thymocyte Globulin

Corticosteroids and anti-thymocyte globulin (ATG) have been extensively used in the treatment of autoimmune diseases, aplastic anemia and organ graft rejection; nonetheless, the precise mechanisms of action of these agents are unknown. Studies of their long term immunoregulatory effects, particularly in humans, have been limited. We examined the long term effects of therapy with ATG given for 2-4 weeks and prednisone for 2 months in 4 patients with newly diagnosed insulin dependent diabetes (IDD). Three matched newly-diagnosed untreated IDD patients and 17 healthy volunteers served as controls. No differences in total lymphocyte count, percentage of B cells, percentage of total T cells (CD3), helper-inducer T cells (CD4) or cytotoxic-suppressor cells (CD8), lymphocyte blastogenesis assays, or pokeweed mitogen-induced IgG secretion in T & B cell co-cultures were detected before therapy. A transient lymphopenia following ATG administration was the only immunological defect found in the first month of therapy. At 2 months, however, patients treated with ATG and prednisone had diminished immunoregulatory T cell function demonstrated by production of only 28 +/- 3% IgG expected in T & B co-culture, compared to 205 +/- 35% for untreated IDD patients and 107 +/- 13% for normals (p less than 0.01). This diminished IgG production resulted from excessive suppressor function, since co-cultures of T cells from treated patients with T and B cells from normal volunteers suppressed the latter's IgG production by 76 +/- 9%. This enhanced suppressor activity persisted for 3-6 months following therapy. Other immunological functions were not statistically different from those present at the inception of the study. Thus, treatment with corticosteroids and ATG produces long-term enhanced suppressor activity, a finding which suggests that treatment with combination ATG and Prednisone is a rational form of immunomodulation in conditions associated with decreased suppressor function.

Clozapine in the treatment of 121 out-patients.

Retrospectively, effects of long-term therapy with clozapine were evaluated in 121 out-patients. They were treated for 32 +/- 43 months in a daily dosage of 131 +/- 99 mg. Sixty nine patients were schizophrenic and had previously received one or more neuroleptics but with insufficient response or severe side effects. Nine patients suffered from tardive dyskinesia (TD), 44 patients had other diagnoses. Twenty two per cent of the schizophrenic patients improved slightly, 65% markedly and in 13% the symptoms nearly totally disappeared. Fourty per cent of chronic schizophrenics showed improvement of anergia. Eleven per cent of the patients with TD did not improve, 22% showed slight and 67% marked improvement. Clinically relevant side-effects occurred in 64% of patients: Generally sedation/hypotension, EG and ECG alterations, changes of white blood cell count, increase of liver enzymes and weight gain. EEG alteration correlated significantly with dosage of clozapine (P less than 0.01). In 6% of patients, severe side-effects led to discontinuation of clozapine treatment. No case of agranulocytosis occurred. Most patients tolerated the drug well and were compliant. Under careful control of hematological and other variables, the benefit/risk ratio of clozapine long-term treatment appears to be high and acceptable.

158 INTEGRATED CONCENTRATION OF PLASMA CORTISOL LEVEL IN ASTHMATIC CHILDREN TREATED WITH LONG TERM INHALED STEROIDS

To assess the effect of long term therapy with inhaled beclomethasone dipropionate (BDP) on the pituitary-adrenal axis we measured the integrate concentration of plasma Cortisol level (ICPCL) in 8 asthmatic children (aged 6-16 yrs) who received BDP doses of 200-600 μg/d for 6-48 mos. Controls were 4 children (aged 6-16 yrs) whose ICPCL measured for other reasons were normal. All patients did not receive any oral steroids during the 3 months prior to the study. The ICPCL was determined using a portable withdrawal pump to enable continuous blood specimen collection (every 1/2h) for 24 h. mean ICPCL. Mean ICPCL of the asthmatic children on long term BDP therapy was significantly low (4.9 ± 3-3 μg%, mean±S.D.) as compared to the healthy controls (8.7±2 μg%)(p<0.05, Mann-Whitney U-test). In 5/8 asthmatics the ICPCL was lower than the mean -2SD of the controls: 1.6;2.8;3.1; 3.6;3.8 μg%. Response of Cortisol secretion to IV administration of 0.25 mg ACTH was abnormal in two of the five asthmatic children with low ICPCL. No correlation was found between ICPCL and severity of the asthma, height percentile and the tunner stage. We conclude that long term therapy with inhaled BDP may cause reduction in the normal physiological secretion of Cortisol even with relatively low doses. This effect is probably due to partial depression of the pituitary-adrenal axis.

12 LHRH analogues in the management of uterine fibroids, premenstrual syndrome and breast malignancies

Agonist analogues of LHRH are of potential value in the management of oestrogen-dependent conditions in women. However, their clinical effectiveness is a direct consequence of ovarian suppression which is in itself associated with adverse effects, in particular loss of bone mass. They are thus unsuitable for long-term use in premenopausal women with benign conditions but in future may have a wider role in combination with other agents. In women with uterine fibroids, therapy leads to reduction of uterine volume and alleviation of symptoms although the benefit is rapidly reversed when therapy ceases. Although there is a theoretical potential for combined therapy, successful combinations have yet to be identified. Thus, at the present time, agonists of LHRH do not offer a true alternative to surgery for the majority of women. They will be of value where there is a contra-indication to surgery and for women approaching the age of the natural menopause. They may also be of use prior to surgery, both in controlling symptoms and in reducing surgical morbidity and blood loss. LHRH agonists appear to be beneficial in the management of some women with severe premenstrual tension but intensify symptoms in others. Particular care is required in selection of women for such therapy because of the uncertain nature of the condition and its high rate of response to placebo therapy. Response is dependent on the degree of ovarian suppression and long-term use of LHRH agonists alone is clearly undesirable. However LHRH agonists alone or in combination with ovarian steroids are of potential value as a research tool. In premenopausal women with advanced breast cancer, concerns about the long-term effects of therapy with LHRH agonists are less important and these drugs offer a medical alternative to oophorectomy as first-line treatment in women with oestrogen receptor-positive tumours. Future developments are likely to include evaluation of combined therapy and comparative studies in women with early disease. As such studies involve long-term treatment, they will generate very useful information about the effects of therapy. This will be of great value to clinicians evaluating the role of LHRH agonists in the management of benign conditions.

Effect of mouth rinsing with two polyvinylpyrrolidone-iodine mixtures on iodine absorption and thyroid function.

A prospective study was conducted to investigate the effect of long term therapy with two iodine-containing mouth rinses on thyroid function. Two groups of subjects were treated daily for 6 months with either a 5% polyvinylpyrrolidone (PVPI)-1.5% H2O2 mixture (Perimed) or a 5% PVPI-water mixture. Thyroid function studies, serum iodine concentrations, and urinary iodine excretion were measured before treatment, at 6-week intervals during the 6-month treatment period, and 3 weeks after the last treatment. There was evidence of significant iodine absorption (elevated serum total iodine and inorganic iodide concentrations and urinary iodine excretion) from daily use of both Perimed and the PVPI-water mixture. Serum T3 and T4 concentrations and the free T4 index did not change. There was a small significant rise in serum TSH concentrations during mouth rinse therapy, but all values remained within the normal range. This small increase in serum TSH is a normal adaptive response to the antithyroid effect of increased iodine intake and accounts for the maintenance of normal serum T4 and T3 concentrations. While daily use of these iodine-containing mouth rinses does result in significant iodine absorption, there is no evidence for the development of thyroid dysfunction during a 6-month course of therapy.

Effects of Long-Term Therapy with Oral Piroximone on Resting Hemodynamics, Peak Aerobic Capacity, and the Anaerobic Threshold in Patients with Heart Failure

Piroximone (MDL 19205), a new imidazole derivative with positive inotropic and vasodilating properties, was administered to 10 patients with congestive heart failure. After acute intravenous (0.90 +/- 0.12 mg/kg, mean +/- SEM) and oral (1.41 +/- 0.18 mg/kg) administration, cardiac index and stroke volume index increased and were accompanied by a decline in systemic vascular resistance, pulmonary capillary wedge pressure, and right atrial pressure. Mean arterial pressure was unchanged, but heart rate increased modestly after intravenous piroximone. An increase in premature ventricular contractions was documented in four patients after drug administration. Seven of the 10 patients completed 12 weeks of therapy with piroximone; one patient withdrew after 8 weeks because of deterioration in clinical status; one developed severe ventricular arrhythmias and died after 5 days of treatment; and a drug-induced hepatitis was documented in one subject at 4 weeks. No significant improvement in oxygen uptake at peak exercise and the anaerobic threshold was observed after long-term treatment (assessed at 6 and 12 weeks). Hemodynamic responsiveness to piroximone was sustained in five patients who underwent repeat evaluation at 12 weeks. Thus, long-term treatment with piroximone was not associated with an improvement in maximal and submaximal exercise capacity in patients with congestive heart failure. Serious adverse effects were observed with the administration of this drug.

Breathing difficulty: Changes in respiratory function

HE INDIVIDUAL with cancer is at risk of experiencing difficulty in breathing or changes in respiratory function related directly to the disease itself, secondary effects of the disease, or problems related to immediate or long-term effects of therapy. Three major functions are necessary for normal respiratory function: normal and unobstructed anatomical respiratory structure; normal tissue elasticity and expansibility of lung, rib muscles, and diaphragm; and normal vascular supply of adequate gaseous components in blood to both sides of the blood-gas barrier. PREEXISTING ALTERATIONS IN OXYGENATION AND/OR VENTILATION Preexisting respiratory conditions resulting in alterations in oxygenation and/or ventilation, ie, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and anemia, impact on clinical status, proposed therapies, prognosis, and nursing management of the patient with cancer. 2-~2 Other commonly occurring conditions affecting respiratory function are chronic bronchitis, pulmonary emphysema, and a variety of pulmonary infections. 2.s-7,~ Pulmonary infection with mycobacterium tuberctdosis is a common infection in overcrowded areas. ~3 Mycobacteria other than M. tuberctdosis (atypical mycobacteria) also produce disease in man and presently are being discovered more frequently in association with individuals who exhibit Acquired Immune Deficiency Syndrome (AIDS). Some pulmonary organisms previously uncommon are more prevalent in the compromised cancer patient. One example is pneumocystis carinii, a protozoan, that was primarily associated with ill or premature infants. P. carhfii now infects an estimated 65% to 85% of all persons with AIDS. ~4 Pneumonia, superimposed on a cancer diagnosis, is a major cause of death in individuals with cancer. At least 50% of all cancer occurs in individuals over the age of 6515; therefore, many of the affected individuals may have already experienced alterations in pulmonary anatomy and/or physiology prior to malignant changes. In addition, normal structural and functional changes that are associated with the aging process compromise air intake in the elderly. Environmental, occupational, and social factors may have carcinogenic qualities, as well as an impact on the outcomes of the superimposed malignant process by initiating inflammatory processes and fibrotic changes in lung tissue that result in decreased lung compliance and diffusion defects. ~6 For example, asbestos is known to induce mesothelioma, lung cancer, and possibly colon cancer. Exposure to asbestos is known to enhance carcinogenic processes in persons who smoke. 17 Excess alcohol consumption is related to many cancers involving the upper respiratory airways. Nasal airway cancers are related to exposure to isopropyl alcohol and wood dusts. Lung cancers are associated with exposure to arsenic (ie, pesticides), nickel (nickel refiners), and polycyclic hydrocarbons associated with mineral oil and tar workers.IS Cigarette smoking, the major single unnecessary and preventable cause of illness and early death in the United States, is associated with cardiovascular disease, cerebral vascular accidents, emphysema, chronic bronchitis, and other chronic health problems, w Smoking is related to cancers of the larynx, oral cavity, and esophagus, all significant in the ventilatory processes, and also to cancers of the urinary bladder, kidney, pancreas, and cervix, w Approximately 90% of all lung cancer, 30% of all cancer deathsfl 6 and 25% of deaths from cardiovascular disease ~9 can be attributed to smoking. Needless to say, a smoking history is pertinent to both concurrent health care issues or problems of the person with cancer as well as to etiology of the cancer. 2°

Carcinoma of the prostate. Hormonal therapy.

A selective review of the literature regarding hormonal therapy for patients with carcinoma of the prostate is presented to assess the current status of the following: therapeutic advantages, disadvantages and risks of alternate approaches to hormonal therapy; observations to predict the magnitude and duration of response to therapy; indications for initiating hormone therapy; the short-term and long-term effects of therapy; and role of hormone therapy in patients with recurrent tumor activity after initial hormonal measures.

Treatment of Sleep-maintenance Insomnia: A Case Study Using Time-series Analysis

A behaviour-therapeutic approach in a case of chronic insomnia is illustrated. Based on research reported in the literature the treatment programme consists of sleep-related interventions as well as of training in coping with conditions which influence sleep negatively. Data on the short- and long-term effects of therapy, especially during the follow-up period of two years, are discussed.

Effects of long-term therapy with oral ibopamine on resting hemodynamics and exercise capacity in patients with heart failure: relationship to the generation of N-methyldopamine and to plasma norepinephrine levels.

N-Methyldopamine (epinine), one of the few modifications of the dopamine (DA) molecule that retains agonist activity at the DA1 receptor, was administered orally as the diisobutyric ester, ibopamine (100, 200, and 300 mg), to 15 patients with congestive heart failure. An increase in cardiac index and decline in systemic vascular resistance was observed with each dose, and these hemodynamic effects persisted for 3 to 6 hr. Small transient increments in right atrial and pulmonary capillary wedge pressures occurred 0.5 hr after ingestion of 200 and 300 mg of ibopamine, but these pressures returned to baseline or lower levels within 30 min. Heart rate and mean arterial pressure were unchanged. Plasma concentrations of epinine peaked 0.5 hr after administration of drug and then declined to minimal levels at 3 hr. Ten patients enrolled in a trial to evaluate the efficacy of long-term therapy with ibopamine; after 8 weeks of treatment, the initial hemodynamic responses to the drug were attenuated and no significant improvement in oxygen uptake at peak exercise was observed. A decline in plasma norepinephrine concentrations, which could be attributed to activation of alpha 2-adrenoceptors and/or DA2 receptors on sympathetic nerves, was observed after initial administration of ibopamine and persisted after long-term drug ingestion; no long-term hemodynamic benefit could be ascribed to the reduction in sympathetic activity.

Long-term Effects of Nitrendipine on Hemodynamics and Oxygen Transport in Patients with Cor Pulmonale

Recent studies have suggested that vasodilators may acutely improve pulmonary hemodynamics in patients with chronic obstructive pulmonary disease and cor pulmonale, but the effects of long-term therapy have not been assessed. We evaluated the hemodynamic and gas exchange effects of nitrendipine, a calcium channel blocker with a cardiovascular profile similar to nifedipine, acutely and after five days and six weeks of therapy in eight patients with stable COPD and cor pulmonale. After six weeks, nitrendipine significantly decreased both mean pulmonary artery pressure (40.4 +/- 10.3 to 31.2 +/- 6.6 mm Hg, p less than 0.01) and pulmonary vascular resistance (6.8 +/- 3.9 to 3.0 +/- 1.1 units, p less than 0.01), while cardiac index increased (2.4 +/- 0.8 to 3.6 +/- 1.0 L/min/m2, p less than 0.001). Despite a fall in arterial PO2 (53.1 +/- 18.7 to 45.5 +/- 11.3 mm Hg, p = NS), systemic oxygen transport increased by over 30 percent (843 +/- 284 to 1,111 +/- 373 ml/min, p less than 0.05). Systemic arterial pressure, pulmonary capillary wedge pressure, and heart rate were unchanged. Despite these hemodynamic changes, three patients died from complications of their underlying disease while receiving long-term therapy after eight, nine, and ten months. These preliminary findings suggest that long-term vasodilator therapy can result in persistent hemodynamic improvement in some patients with cor pulmonale secondary to COPD, although the impact of this form of therapy on survival remains to be clarified.

The long-term effects of cranial irradiation on the central nervous system.

Cranial irradiation and chemotherapy may have significant long-term deleterious effects on children with brain tumors. Intellectual deterioration, endocrinopathies, leukoencephalopathy, extraneural metastases, and oncogenesis may all complicate the treatment of central nervous system neoplasia. These long-term effects of therapy have important implications, as some are amenable to treatment and others may be prevented by the careful monitoring of drug and radiation administration. Until recently, the survivals of children with brain tumors were limited, so that concerns over long-term effects of therapy were unnecessary. As children with certain types of brain tumors now have a better prognosis, these long-term and possibly remediable effects have important implications. This article emphasizes radiation effects on intellect, endocrine function, and oncogenesis. Recommendations for baseline and longitudinal evaluations of children with brain tumors are suggested.

高血圧症に対するacebutolol使用の血中脂質濃度に対する影響

Recent studies suggest that the therapy of hypertension with β-blocking agents may result in changes of the serum levels of lipids: increase of total cholesterol (TC) and triglyceride (TG), and decrease of HDL-cholesterol. The present paper describes the effects of long term therapy of hypertension with a β-1 selective blocking agent, acebutolol (400mg/day for 6 to 18 months) on the serum levels of TC, HDL-cholesterol, TG, LDL (low density lipoprotein), VLDL (very low density lipoprotein) and LCAT (lecithine cholesterol acyltransferase). None of the serum lipid fraction showed a significant change during the therapy with acebutolol. Four case reports were also presented. These results suggest that the therapy of hypertension with acebutolol has more advantage than the other β-blocking agents in respect of lipid metabolism.

A component analysis of behavioral marital therapy: 1-year follow-up

The present study provides 1-yr follow-up data for a comparison between a complete behavioral marital therapy package (CO) and two of its major components, behavior exchange (BE) and communication/problem-solving training (CPT), each presented in isolation. Data are reported for 60 married couples who were randomly assigned to one of these three treatments or to a waiting-list control (WLC) group. Four doctoral candidates and one masters-level counselor served as therapists. All treatments involved 12–16 therapy sessions. The long-term effects of therapy were evaluated with measures of global marital satisfaction and presenting problem checklists. While BE couples tended to reverse their progress relative to those in the CO condition during the first 6 months following termination, statistically significant differences between groups were no longer in evidence by the 1-yr follow-up. However, couples treated with CO were most likely to be happily married and least likely to be separated or divorced.

Antihypertensive and metabolic effects of long-term therapy with nifedipine slow-release tablets.

Sixteen nonhospitalized men, average age 41.3 years with essential hypertension (WHO I-II) were given nifedipine slow-release tablets of 20 mg twice daily for 48 weeks. Both supine and standing blood pressure values were significantly reduced, but heart rate was not significantly changed by the drug. A significant decrease in serum sodium and potassium was found. A slight increase in serum magnesium throughout the study became statistically significant at 48 weeks (p less than 0.05). It is suggested that a possible diuretic activity, and the increase in magnesium, may add to the direct nifedipine-induced blood pressure reduction. Serum creatinine increased significantly after 24 and 48 weeks of nifedipine administration; serum urea, cholesterol, triglycerides, uric acid, and blood glucose remained essentially unchanged. Most of the patients had low plasma renin activity (PRA) in the control period, and nifedipine significantly increased PRA. Body weight was kept constant. Side effects were few and of no clinical significance. The slow-release preparation of nifedipine seems to be a potent and effective drug in treating essential hypertension of a mild to moderate degree.

Effects of antihypertensive therapy on plasma lipids and lipoproteins in the multiple risk factor intervention trial

The Multiple Risk Factor Intervention Trial was a randomized clinical trial that studied the efficacy of multiple risk factor reduction in lowering coronary heart disease mortality in high-risk men. Nutrition counseling based on a fat-modified eating pattern resulted in a significant reduction of total cholesterol and low-density lipoprotein cholesterol. However, based on further analysis not involving comparisons of randomized groups, the reduction in total cholesterol appeared to be blunted by the effects of the antihypertensive medication utilized in the stepped-care therapy in this study. The use of diuretics was associated with an increase in triglycerides and a lesser decrease in total plasma cholesterol when compared with non-diuretic users. The use of diuretic therapy was also associated with a slight decrease in high-density lipoprotein cholesterol, when compared with changes in those not receiving diuretic therapy. The combination of diuretics plus propranolol was related to a substantial decrease in high-density lipoprotein cholesterol in both the Special Intervention and Usual Care participants. The changes in lipoproteins for men receiving diuretic therapy are probably influenced substantially by nutritional factors, especially weight change. Concomitant nutritional changes must be considered when analyzing the short- and long-term effects of therapy with diuretics or other antihypertensive drugs on lipoprotein metabolism.