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The major antihypertensive mechanism of calcium antagonists is by decreasing the systemic vascular resistance, modified by the counter-regulatory responses of the baroreflexes and the renin-angiotensin-aldosterone system. In severe hypertension, the concept that calcium overload of the vascular myocyte could precipitate or aggravate peripheral vasoconstriction provides a logical basis for the use of these agents as first choice therapy; nifedipine, especially, has been well tested. As monotherapy for mild to moderate hypertension each of the three first-generation agents compares well with beta-blockers. Calcium antagonists may have a special role in the therapy of certain patient groups (elderly, black) or in those subjects whose life style involves intense physical or mental exertion (hemodynamics better maintained than with beta-blockade) or in patients with early end-organ damage such as left ventricular hypertrophy or renal insufficiency. However, the goal blood pressure may not be reached during monotherapy so that drug combinations may be required. Further indications for these compounds are as follows. Verapamil and diltiazem are frequently used in supraventricular tachycardias including acute and chronic atrial fibrillation. In the arrhythmias of the Wolff-Parkinson-White syndrome, there is the potential danger of provocation of anterograde conduction. Further indications for calcium antagonists, still under evaluation, include congestive heart failure (controversial), hypertrophic cardiomyopathy (verapamil), primary pulmonary hypertension (high doses required), Raynaud's phenomenon (nifedipine and diltiazem effective), peripheral vascular disease (proof not yet documented), cerebral insufficiency and subarachnoid hemorrhage (nimodipine promising), migraine, exertional bronchospasm, renal disease, atherosclerosis (experimental), and primary aldosteronism (nifedipine inhibits aldosterone release). Second-generation agents include dihydropyridines, such as nitrendipine, nicardipine, felodipine, amlodipine, nisoldipine, nimodipine, and isradipine. From these will be selected agents that are longer acting and provide higher vascular selectivity. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine. Yet caution is required when calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as alpha-adrenergic blockers, beta-adrenergic blockers, digoxin, quinidine, and disopyramide.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Calcium channel antagonists. Part III: Use and comparative efficacy in hypertension and supraventricular arrhythmias. Minor indications. 315 29

More and more people are turning to exercise as a means of achieving long-term health. The World Health Organization has endorsed this concept. The best available evidence suggests that an employee fitness programme will result in decreased health-care costs, decreased absenteeism and increased productivity for the employer. Regular physical activity is also associated with lower mortality rates. Appropriate physical activity may be a valuable tool in therapeutic regimens for the control and amelioration (rehabilitation) of cardiovascular disease, coronary artery disease, hypertension, congenital heart disease, peripheral vascular disease, obesity, chronic obstructive pulmonary disease, diabetes mellitus, musculoskeletal disorders, end-stage renal disease, stress, anxiety and depression, etc. Regular physical activity, independent of other factors, reduces the probability of coronary artery disease and early death. Patients with risk factors for coronary artery disease need more intensive preexercise evaluation than those not a risk, and those with known or suspected cardiovascular disease need the most intensive evaluation and follow-up. Participation in vigorous sports activities, such as jogging, swimming, tennis, etc., helps to protect against the development of hypertension, even when other predisposing factors are present. Several studies have been conducted on the use of exercise in the treatment of hypertension. Physical exercise also contributes to the control of body weight. Consideration of the metabolic abnormalities in patients with type II (adult onset) diabetes indicates that they would make excellent candidates for an exercise programme. Osteoporosis is an important health problem for the elderly. The best treatment available at present is prevention, and a high level of physical activity throughout life can result in a larger skeletal mass during old age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of physical activity in the prevention and treatment of noncommunicable diseases. 323 11

Pentoxifylline, a methyl xanthine derivative, improves symptoms of peripheral vascular disease probably by reducing whole blood viscosity. The authors assessed the value of this agent in treating myocardial ischemia in 11 patients with angiographically documented coronary artery disease and stable angina pectoris. Maximal, symptom limited treadmill exercise stress tests were performed before and after six weeks of therapy with 1200 mg of pentoxifylline per day. Clinical symptoms proved in 9 [82%] of patients; none developed drug side effects. After therapy, mean total exercise time [7.7 +/- 1.3 vs 10.1 +/- 1.2 minutes], time to onset of angina [5.5 +/- 0.9 vs 7.9 +/- 1.0 minutes], heart rate at onset of angina [93.4 +/- 6.7 vs 112.0 +/- 10.5 beats/min] and rate at onset of ST depression [94.0 +/- 5.8 vs 115.9 +/- 7.4 beats/min] all increased significantly [p less than 0.05]. Mean maximum ST segment depression also decreased [1.6 +/- 0.3 vs 1.2 +/- 0.4mm], but the difference was not significant. Thus, pentoxifylline increases exercise performance in patients with angina pectoris and increases exercise capacity before development of of myocardial ischemia. It may, therefore, be a useful agent for treating ischemic heart disease.
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PMID:Efficacy of pentoxifylline in patients with stable angina pectoris. 337 71

Calcium channel blockers seem to be particularly suitable for elderly hypertensive patients since these agents do not cause salt and fluid retention, postural hypotension, sedation, depression, or biochemical abnormalities. Moreover, their use is compatible with several common diseases of old age, such as diabetes, obstructive lung disease, and peripheral vascular disease. We recently conducted a study in 21 patients (average age, 79 +/- 2 years) who completed an eight-week trial with 20-mg nifedipine tablets taken twice daily. Mean blood pressure decreased from 191 +/- 2/96 +/- 2 mm Hg to 151 +/- 4/80 +/- 3 mm Hg. In 15 patients (71 percent), blood pressure decreased to less than or equal to 160/90 mm Hg; in four additional patients (19 percent), diastolic blood pressure decreased by 15 to 25 percent. Thus, there was a sustained lowering of blood pressure in 90 percent of the participants receiving nifedipine monotherapy. A review of recent studies in elderly hypertensive patients revealed similarly favorable results with calcium channel blockers given alone or in combination with other agents. The accumulating data suggest that these compounds may offer a useful new approach to the treatment of hypertension in old age. However, in these studies, the number of patients and the duration of follow-up need to be extended to confirm the favorable impression obtained thus far.
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PMID:Calcium channel blockers in the management of hypertension in the elderly. 354 97

The recent recognition of the prevalence of asymptomatic ST-segment depression in patients with coronary artery disease demonstrates the poor sensitivity of using angina as a sign of myocardial ischemia. Possibly the greatest application of ambulatory ST-segment monitoring for the detection of asymptomatic ischemia is in diabetic patients. Coronary artery disease represents the ultimate cause of death in more than half of such patients and usually manifests itself prematurely at an advanced stage. The long-held clinical belief that infarction may be silent, or less painful, in patients with diabetes is supported by several retrospective studies (32 to 42 percent of diabetic patients lack angina at infarction, compared with only 6 to 15 percent of nondiabetic patients). Explanations for this observation have been remarkably deficient in the literature. One group has shown that in diabetic patients with painless infarction, the autonomic nerve fibers of the heart display typical lesions of autonomic neuropathy that may affect afferent sensory impulse transmission compared with those in several matched control groups. Except for a recent report from Italy, there are no data on the prevalence of asymptomatic ischemia in diabetic patients. There are obvious reasons to address this issue more comprehensively: first, given the high incidence of painless myocardial infarction, the frequency of asymptomatic ischemia may be very high; second, because the ability to evaluate patients with standard treadmill testing is limited in patients with peripheral vascular disease and diabetic neuropathy, ambulatory monitoring may be used on a more widespread basis; and third, given the higher than average incidences of sudden death and left ventricular dysfunction in diabetic patients compared with nondiabetic patients, ambulatory monitoring may represent a method of assessing the role of episodic ischemia in explaining these other cardiac events.
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PMID:Asymptomatic myocardial ischemia in diabetic patients. 370 56

The prognostic utility for predicting cardiac events was determined for dipyridamole-thallium scintigraphy, exercise stress testing (when possible; n = 69) and multiple clinical variables in 100 consecutive patients admitted for elective surgical repair of peripheral vascular disease. After initial noninvasive evaluation, 11 patients were referred for coronary angiography and the remaining 89 patients had surgery without further cardiac studies. Fifteen patients (17%) had a postoperative myocardial infarction, one of which was fatal. Of these 15 patients, 14 had thallium redistribution and 3 had positive ST segment depression during stress testing. Among the many variables tested, the presence of redistribution on serial dipyridamole-thallium images was the most significant predictor of serious cardiac events. All 11 patients who had coronary angiography had both redistribution and multivessel coronary artery disease. Four of these 11 patients died during follow-up and 6 had coronary artery bypass surgery. It is concluded that dipyridamole-thallium imaging has significant prognostic utility in predicting postoperative myocardial infarction and death in patients with severe peripheral vascular disease, and is superior to exercise testing or clinical variables in determining cardiac risk. The odds for a serious cardiac event were 23 times greater in a patient with thallium redistribution than in a patient without redistribution, strongly suggesting that myocardial imaging may be used as a primary screening test before elective vascular surgery.
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PMID:Noninvasive evaluation of cardiac risk before elective vascular surgery. 380 15

We studied 20 men (ages 46 to 69, mean 45 years) with chronic obstructive pulmonary disease (FEV1 of 0.55 to 2.1 L), to determine the relative importance of pulmonary impairment vs other occult physical or psychologic factors in the genesis of sexual dysfunction. Seven subjects had ceased sexual activity concomitant with worsening of their pulmonary symptoms; six because of erectile impotence and one due to dyspnea. Frequency of intercourse for the remaining 13 was 16 percent of prelung disease levels, and libido was decreased to 25 percent of premorbid levels. Nocturnal penile tumescence monitoring disclosed that six subjects had organogenic erectile impotence (OEI). None of the subjects showed signs of peripheral vascular disease as assessed by Doppler examination of peripheral pulses (including penile). The mean bulbocavernosus reflex latency (BCRL) for the OEI group (N = 5) was 40.2 msec, while that for the group with full nocturnal erections (N = 10) was 34.5 msec (P less than 0.005). Four subjects had occult diabetes mellitus evident on oral glucose tolerance tests, and one had evidence of an androgen deficit. The correlation coefficient for rank by sexual dysfunction vs pulmonary impairment and age was 0.66 (P less than 0.005) and 0.24 P greater than 0.05), respectively. Subjects with OEI tended to have the worst pulmonary function test results and the highest T-scores on the hypochondriasis, depression, and hysteria scales of the Minnesota Multiphasic Personality Inventory. Data suggest that sexual dysfunction worsens as lung disease worsens and that chronic obstructive pulmonary disease may be associated with male impotence in the absence of other commonly known causes.
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PMID:Sexual dysfunction and erectile impotence in chronic obstructive pulmonary disease. 680 73

To examine the effects of recombinant human erythropoietin (rHuEPO) on hospital utilization, hospital costs, and Medicare reimbursements for hospital care, a longitudinal, matched cohort study was conducted using Medicare claims data of 23,806 Medicare-eligible, dialysis patients who received rHuEPO, did not have a transplant, and were alive for 18 mo or longer and 22,720 controls matched on age, sex, race, cause of ESRD, and dialysis modality. The relative odds (rHuEPO versus control) of admission for all causes and for specific causes over 9 mo, adjusted for admission in the prior 9 mo and the per patient change in total admissions, inpatient days, hospital costs, and Medicare hospital payments between the prior 9-mo period and the subsequent 9-mo period was examined. The adjusted relative odds (95% confidence interval) of admission (rHuEPO versus control) was: higher and statistically significant for all causes, 1.08 (1.03 to 1.14); seizure, 1.52 (1.28 to 1.75); vascular access revision, 1.11 (1.06 to 1.17), and heart failure, 1.17 (1.09 to 1.26); higher but not statistically significant for angina, 1.09 (0.99 to 1.20) and stroke, 1.08 (0.86 to 1.31); and lower but not statistically significant for myocardial infarction, 0.91 (0.72 to 1.10); peripheral vascular disease, 0.81 (0.60 to 1.02); anemia, 0.86 (0.56 to 1.17); and depression, 0.89 (0.37 to 1.40). The mean change per 1,000 patients in admissions was less by 38 (P = 0.03) because of fewer readmissions, and in days was 1,309 less (P < 0.001), for patients treated with rHuEPO versus controls. The mean change per patient in hospital costs was $371 less and was statistically significant (P = 0.03) and in Medicare hospital payments was $132 less but was not statistically significant (P = 0.43) for patients treated with rHuEPO versus controls. rHuEPO was associated with an increase in the probability of hospital admission (particularly admissions potentially related to adverse effects) but a decrease in readmissions, overall admissions, hospital days, and cost to hospitals in this cohort of patients surviving for 18 mo. Although not realized short term, Medicare savings from potential rHuEPO-related reductions in hospital care may be long term through future adjustments in diagnosis-related group-based hospital payment.
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PMID:Effect of recombinant erythropoietin on hospital admissions, readmissions, length of stay, and costs of dialysis patients. 816 27

Approximately 75% of major lower-extremity amputations are the result of peripheral vascular disease (PVD). Factors that predispose a patient to PVD (smoking, hyperlipidemia, diabetes mellitus) are also risk factors for the development of cerebrovascular disease, which could adversely affect rehabilitation. The purpose of this study was to test the hypothesis that cognitive deficits are present in amputee patients with PVD. Fourteen patients with lower-extremity amputations secondary to PVD (4 women, 10 men; mean age = 67.4 years) were recruited from a tertiary-care center for physical rehabilitation. Fourteen community-dwelling healthy volunteers (9 women, 5 men; mean age = 69.9 years) served as age-matched and education-matched controls. To assess a broad range of cognitive function, we administered standard neuropsychological tests of memory and learning, language, praxis, visuospatial skills, and abstract reasoning. PVD patients performed significantly more poorly on certain measures of psychomotor speed (Wechsler Adult Intelligence Scale-Revised Digit Symbol subtest) and problem solving/abstract reasoning (Modified Card Sorting Test) relative to controls (using the Bonferroni correction for multiple comparisons, p < .002). There were trends toward poorer patient performance on certain measures of oral fluency, concentration, reasoning, and visuoperceptual organization and constructional skills (p < .01). We propose that these cognitive deficits may be the result of unrecognized concomitant cerebrovascular disease in PVD patients and are part of a generalized pattern of vascular disease. Future research should control affective factors such as stress or depression surrounding amputation and attempt to identify the etiologic or demographic factors that are associated with neuropsychological deficits in patients with PVD.
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PMID:Neuropsychological function in peripheral vascular disease amputee patients. 825 98

Physicians need to weigh the efficacy, adverse effects and cost of first-line antihypertensive agents. Calcium channel blockers lower blood pressure, improve coronary blood flow and depress cardiac contractility by relaxing smooth muscle and cardiac muscle. They have beneficial or neutral effects in hypertensive patients with angina, asthma, chronic obstructive pulmonary disease, postural hypotension, peripheral vascular disease, depression, sexual dysfunction, diabetes and hyperlipidemia. The major adverse effect of some calcium channel blockers is that they may worsen congestive heart failure in some patients. Because calcium channel blockers are metabolized in the liver, the dosage must be lowered in the elderly and in patients with hepatic disease. Diltiazem, verapamil and nifedipine represent prototypes of the three classes of calcium channel blockers, each with slightly different effects.
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PMID:Calcium channel blockers in the treatment of hypertension. 836 95


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