Current status of antihypertensive therapy for elderly patients in Japan

To assess how elderly Japanese hypertensive patients are treated by specialists, we conducted a cross-sectional survey. A total of 1,163 outpatients aged 50 years or older were studied. Hypertension was diagnosed in 939 of these patients, and 827 were receiving drug therapy. The average blood pressure during therapy was 143 +/- 16/81 +/- 10 mmHg. In patients aged 70 years or older, systolic blood pressure during antihypertensive therapy was significantly higher (p < 0.01) and diastolic blood pressure was significantly lower (p < 0.01) than the corresponding values in those aged 50 to 59 years or 60 to 69 years. The calculated mean blood pressures were similar in the different age groups. The rate of monotherapy in the patients aged 70 years or older was 58.8%, which was significantly higher (p < 0.01) than the rates of monotherapy in the other age groups. Calcium channel blockers were prescribed in about 80% of patients, irrespective of age or comorbidity. Of the patients receiving calcium channel blockers, 43.5% were treated with monotherapy. This rate significantly (p < 0.01) increased with advancing age. Diastolic blood pressures were significantly lower (p < 0.05) in patients with stroke and in those with ischemic heart disease, diabetes mellitus, or dyslipidemia, as compared with patients with no comorbidity. Among patients aged 70 years or older, the difference in systolic blood pressure between those with ischemic heart disease and those with no comorbidity was not significant. Blood pressure in elderly hypertensive patients was reduced to a level similar to that in younger patients. The target blood pressure was influenced by the presence of comorbidity. Furthermore, specialists showed a high preference for the use of calcium channel blockers in the management of hypertension.     

Optimizing antihypertensive therapy in patients with diabetic nephropathy

The number of cases of diabetic nephropathy is increasing, especially among patients with non-insulin-dependent diabetes mellitus (NIDDM). It is difficult to prevent the occurrence or progression of NIDDM, and current levels of treatment are below standard. According to one study, actuarial 5-year survival rates are only about 38% for patients with insulin-dependent diabetes mellitus and 9% for those with NIDDM receiving renal replacement therapy. Because cardiovascular diseases are responsible for more than half of these deaths, hypertension, as a major contributing factor to cardiac death, is a crucial component in the therapy for such patients. It is well established that lowering blood pressure is an important preventive measure to be taken in patients with diabetic nephropathy; blockade of the renin-angiotensin system offers benefits beyond lowering blood pressure in type I diabetic nephropathy. Two major trials are currently underway to determine the effects of angiotensin II receptor antagonists on nephropathy in patients with NIDDM. The Irbesartan Diabetic Nephropathy Trial (IDNT) has already enrolled approximately 85% of the proposed 1650 NIDDM patients to be randomly assigned to placebo, irbesartan or amlodipine. Baseline characteristics of the initial cohort are presented. In light of the well-documented case for blockade of the renin-angiotensin system in diabetes, the potentially superior blockade afforded by angiotensin II receptor antagonists, and the superior tolerability of these agents, trials such as the IDNT take on special importance for the treatment of diabetic patients. From these data may come the justification for the belief that angiotensin II receptor antagonists impart greater benefits in the treatment of diabetes than merely their well-documented role in lowering blood pressure.     

Various combinations of antihypertensive drugs: comparative assessment in elderly patients]

Our objective in this study was a comparative evaluation of efficiency of modern drug alternatives to treat peptic ulcer, based on new algorithms of diagnosis and treatment. The results obtained suggest to us that in a major proportion of cases uncomplicated duodenal ulcers might be efficiently managed in an outpatient-clinic setting even with a two-to-four week monotherapy. The best results of treatment are recordable in those groups of patients having received inhibitors of proton pump.     

The effectiveness and safety of low dose pravastatin in elderly hypertensive hypercholesterolemic subjects on antihypertensive therapy

To evaluate the efficacy and safety of low dose (10 mg) pravastatin in hypercholesterolemic, hypertensive elderly subjects undergoing antihypertensive treatment, a randomized, double-blind, placebo-controlled 6-month trial was conducted. The subjects had a total plasma cholesterol of at least 250 mg/dL and had been, for at least 3 months, consuming a standard lipid-lowering diet (American Heart Association Step 1 Diet). Sixty elderly hypertensive patients randomly received placebo (n = 30) or pravastatin (n = 30) treatment. The dosage consisted of 10 mg of pravastatin daily during the 6-month trial. Over that period, in the pravastatin group, plasma levels of total cholesterol and LDL-cholesterol significantly (P < .01) dropped (-20% and -25%, respectively) compared to the placebo group. The plasma level of HDL-cholesterol increased (+5%) while triglycerides slightly decreased (-8%) (P < .05). No serious side effects occurred, and pravastatin was generally tolerated. Fasting hyperinsulinemia (11.0 +/- 0.8 v 9.3 +/- 0.7 microU/mL; P = .06) also improved, although not significantly, after 6 months of pravastatin therapy. Results from this study confirmed that a low dose (10 mg) of pravastatin daily is a safe and effective method of reducing plasma total and LDL-cholesterol in hypercholesterolemic, hypertensive elderly patients who are on concurrent antihypertensive drug therapy.     

Blood-brain barrier mechanisms involved in brain calcium and potassium homeostasis

This study examined the potential roles of the plasma membrane Ca2+-ATPase (PMCA) at the blood-CSF and blood-brain barriers in brain Ca2+ homeostasis and blood-brain barrier Na+/K+-ATPase subunits in brain K+ homeostasis. During dietary-induced hypo- and hypercalcemia (0.59+/-0.06 and 1.58+/-0.12 mM [Ca2+]) there was no significant change in choroid plexus PMCA (Western Blots) compared to normocalcemic rats (plasma [Ca2+]: 1.06+/-0.11 mM). In contrast, PMCA in cerebral microvessels isolated from hypocalcemic rats was 150% greater than that in controls (p<0.001). Comparison of the alpha3 subunit of Na+/K+-ATPase from cerebral microvessels isolated from hypo-, normo- and hyperkalemic rats (2.3+/-0.1, 3.9+/-0.1 and 7. 2+/-0.6 mM [K+]) showed a 75% reduction in the amount of this isoform during hyperkalemia. None of the other Na+/K+-ATPase isoforms varied with plasma [K+]. These results suggest that both PMCA and the alpha3 subunit of Na+/K+-ATPase at the blood-brain barrier play a role in maintaining a constant brain microenvironment during fluctuations in plasma composition.     

Clinical characteristics of patients with hypertension resistant to antihypertensive drug therapy

Two groups of hypertensive patients: 137 responsive (on one or two drugs) and 162 resistant on antihypertensive treatment in the similar age were compared. Resistant patients (on three or more drugs) characterize by significantly higher body weight and BMI, longer history of hypertension, more frequent hypertension prevalance in family members and lower education. Level of triglycerides in resistant on antihypertensive treatment patients was significantly higher than in responsive patients. Insulin level in blood in 31 patients with essential hypertension was significantly higher than in 36 healthy persons and 20 patients with renovascular hypertension and resistant on antihypertensive therapy. In 14 patients with essential hypertension resistant to treatment insulin level one hour after oral glucose load was significantly (p < 0.01) higher than in 16 patients with essential hypertension responsive to antihypertensive treatment.     

Incidence of asystole in electroconvulsive therapy in elderly patients

We hypothesize that selective brain cooling (SBC) can occur in hyperthermic humans despite the fact that humans have no carotid rete, a vascular structure that facilitates countercurrent heat exchange and that is located at the base of the skull in some mammals. We postulate that an increase in emissary and angular ocular venous flows contributes to SBC. The efficiency of SBC is increased by evaporation of sweat on the head and by ventilation through the nose. A body position that increases the intravenous pressure gradient across the skull increases emissary flows and hence enhances the efficiency of SBC. The validity of using tympanic temperature as an index of brain temperature is also postulated.     

Sudden cardiac death in patients with arterial hypertension and left ventricular hypertrophy on antihypertensive therapy

The hypertrophy of the left ventricle in patients with arterial hypertension is an independent risk factor which increases c 9 times the probability of sudden cardiac death. Despite the fact that the incidence of sudden cardiac death in patients with arterial hypertension is low, regarding the high occurrence of hypertension it represents a significant medical problem. The therapy of arterial hypertension is able to decrease the general and cardiovascular mortalities with significant interspecies characteristics of individual antihypertensive drugs, as well as to promote the regression of hypertrophy of the left ventricle. The therapy per se can however increase the risk of cardiovascular complications: until now the complication of the therapy by diuretics rich in potassium and beta-blockers are best distinguished. Calcium antagonists are effective antihypertensive drugs but they do not decrease the total mortality. ACE inhibitors have a marked antihypertensive effect and few adverse effects, but until now there is not a sufficient number of large prospective studies which would definitely confirm the preliminary promising findings. Despite the presented problems the cured patients with arterial hypertension have a substantially better prognosis than patients that are not being cured.     

Use of antihypertensive drugs and trends in blood pressure in the elderly

BACKGROUND: During the 1980s data became available from randomized trials concerning the clear benefits of treating hypertension in the elderly. In three large communities, we examined the impact of these findings on rates of treatment, use of specific antihypertensive drugs, and rates of elevated blood pressure as well as distributions of levels. METHODS: In 1981 the National Institute on Aging initiated population-based cohort studies in the residents of three communities who were 65 years and older. East Boston, Mass; Washington and Iowa counties, Iowa; and New Haven, Conn. Participation rates ranged from 80% to 85% across sites with 10,294 community-dwelling participants in the combined cohorts. Baseline evaluation included inhome blood pressure assessment and medication inventory. Repeated in-home evaluations occurred 3 and 6 years after baseline and follow-up rates ranged from 71% to 88%. RESULTS: Use of antihypertensive drugs increased over time in all three communities: the age- and sex-adjusted rates of use were between 14% and 32% higher in 1988 and 1989 relative to 1982 and 1983. Parallel declines in the use of thiazide diuretics occurred in all three populations along with large increases in the use of angiotensin-converting enzyme inhibitors and calcium channel blockers. In East Boston and New Haven mean systolic blood pressure decreased substantially over time and the prevalence of elevated systolic pressure (> or = 160 mmHg) decreased overall as well as by age and sex. In Iowa the mean levels of systolic blood pressure were lowest at baseline and increased slightly. CONCLUSIONS: The reported evidence about the benefits of treatment for hypertension in the elderly was followed by substantial increases in treatment rates. The use of drugs with proven efficacy declined while the use of newer agents with theoretical advantages, not yet tested in clinical trials of mortality, increased. In the United States, the ongoing therapeutic efforts to lower elevated blood pressure in elderly populations may be contributing to the continuing decline in cardiovascular and stroke mortality.     

Radiofrequency catheter ablation therapy in elderly patients with supraventricular tachycardia

In the present study, long-term and short-term rat preparations were used to develop a model for investigating external anal sphincter (EAS) reflexes in intact and spinal cord-injured (SCI) rats. In this model, EAS distension with an external probe elicits reflex contractions of the EAS in intact, unanesthetized animals. At 2 h after spinal cord transection, none of the lesioned animals displayed EAS EMG activity. In fact, once distended, the EAS was incapable of maintaining closure of the anal orifice. Over a period of 4 days, spinalized animals developed a hyperreflexia of the EAS response. By 48 h, the rectified, integrated EAS EMG was significantly elevated in comparison with nonlesioned controls (EAS hyperreflexia). In addition, the duration of the EAS EMG bursts in response to sphincter distension had significantly increased. At 6 weeks after injury, the EAS was significantly hyperreflexic as measured by EMG burst duration and burst area. As with intact animals, posttransection EAS reflexes were highly anesthesia sensitive. These studies indicate that (1) brief distension of the anal orifice is sufficient to evoke a physiologically relevant reflexive activation of the EAS in the rat, (2) the 2- to 24-h postinjury areflexia observed in these experiments may be a suitable model for the study of spinal shock, and (3) the observed EAS hyperreflexia after chronic SCI may represent the permanent effects of removing descending inhibitory circuits and segmental plasticity, making this reflex an appropriate measure of defecatory dysfunction after spinal cord injury.     

Long-term evaluation of combined antihypertensive therapy with lisinopril and a thiazide diuretic in patients with essential hypertension

For the treatment of hypertension, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic is supported by multiple lines of evidence, because these drugs have synergistic action and are expected to cancel out each other's adverse side effects. However, the long-term outcome of this combination antihypertensive therapy is not entirely clear. In the present multicenter open trial, we investigated the long-term efficacy and safety of combined antihypertensive therapy with an ACE inhibitor, lisinopril, and a thiazide diuretic, trichlormethiazide. A total of 466 patients with essential hypertension were treated with lisinopril alone (monotherapy group, n = 360) or with a combination of lisinopril with trichlormethiazide (combination therapy group, n = 106) for 1 year. The average blood pressure was effectively lowered to below 150/90 mmHg in both the monotherapy and the combination therapy groups throughout the study period. The average maintenance dose of lisinopril was lower when combined with thiazide than when given alone (9.8 vs. 11.5 mg/day, p < 0.001). Dry cough was the major side effect of lisinopril; no severe adverse effects were observed. The incidence of cough was not significantly different between the monotherapy group (13.1%) and the combination therapy group (11.3%). The increase in serum potassium observed in the monotherapy group was reversed by the concurrent use of the thiazide diuretic in the combination therapy group. Fasting blood glucose was significantly reduced in the monotherapy group; the reduction observed in the combination therapy group was not significant. Thus, the present results provide useful information as to the effectiveness and safety of combined antihypertensive therapy with lisinopril and a thiazide in comparison with monotherapy with lisinopril.     

Underutilization of antithrombotic therapy in elderly rural patients with atrial fibrillation

BACKGROUND: Antithrombotic agents are underutilized in elderly patients with atrial fibrillation. In a peer-review audit of antithrombotic use in Missouri, rural patients were given antithrombotic therapy less often than rural patients for unclear reasons. METHODS AND RESULTS: The charts of 597 hospitalized Medicare patients discharged between October 1, 1993, and December 31, 1994, from urban and rural hospitals in Missouri were reviewed. In addition to antithrombotic therapy prescribed at the time of discharge, patient and physician information, relative contraindications to antithrombotic therapy, and risk factors for stroke were identified. Rural and urban patients were similar in terms of age, sex, and risk factors for stroke. At least one stroke risk factor was noted in 87% of rural patients and in 84% of urban patients. Urban patients were more likely to have a relative contraindication to antithrombotic therapy compared with rural patients (66% vs 54%, P =.04) but received antithrombotic therapy more often (58% vs 47%, P =.02). Cardiologists prescribed antithrombotic therapy significantly more often than noncardiologists (69% vs 52%, P =.003). CONCLUSIONS: Elderly rural patients with atrial fibrillation receive antithrombotic therapy less frequently than urban patients despite having a similar high-risk profile and fewer relative contraindications. Primary care physicians prescribe antithrombotic therapy less often than cardiologists, which is one of the reasons for this underutilization.     

Effects of aging on potassium homeostasis and the endocochlear potential in the gerbil cochlea

In this study we present a strategy for the identification of novel peptide conjugates which may be used to understand the molecular details of the recognition process or to potentially regulate T cell-mediated responses. The approach involves the incorporation of cysteine into a known peptide at a position of interest and subsequent chemical conjugation using thiol-specific agents. Conjugates derived from the nonapeptide QL9 that is recognized by CTL 2C had either enhanced or reduced activity compared to the original cys-peptides. Different classes of thiol-reactive agents (alkyl halides, alkylthiolsulfonates, and disulfides) were tested with increases in activity of over 100-fold. As with standard peptide analogs, the activity depended on the position of the cysteine within the peptide and the nature of the chemically linked functional group. Use of this approach in a cysteine 'scan' of all positions of the original peptide is cost effective and with the availability of many different thiol-specific functional groups will allow the screening of considerably larger libraries of chemically modified peptides than have been used to date. Additionally, these findings may provide insight into the pathogenesis of thiol agents involved in contact sensitivity reactions.