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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

THE AUTHORS OF THIS PAPER SUMMARIZED the major themes that emerged from a 2-day workshop entitled Epidemiology of Hypertension in Hispanic Americans, Native Americans, and Asian/Pacific Islander Americans, sponsored by the National Heart, Lung, and Blood Institute (NHLBI) in Washington, DC. Data from the papers were synthesized using seven points: similarities, variability within and between groups, lost prevention opportunities, emergence of explanatory variables, differences in types of data collected, missing or inconsistently reported data, and socioeconomic characteristics. Virtually all of the population groups demonstrated rises in blood pressure with age. These rises appear to be largely attributable to potentially modifiable risk factors, for example, high body mass index (BMI). Despite high levels of awareness, the levels of control of high blood pressure were poor in each population studied. Based on the themes that emerged from the data, we presented several recommendations to the workshop. One was that data be collected on these population groups repeatedly and in a standardized fashion. Another called for increased efforts aimed at control of high blood pressure in these groups. A third recommended major nationwide programmatic efforts aimed at the prevention and control of high blood pressure.
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PMID:Putting it all together: summary of the NHLBI Workshop on the Epidemiology of Hypertension in Hispanic American, Native American, and Asian/Pacific Islander American Populations. 889 84

NEUROHUMORAL SYSTEMS AS SUPERCONTROLLERS: The brain and closely linked hormone systems play a crucial part in short- and long-term cardiovascular control and have many features of adaptive control systems. The cardiovascular control system is a multivariate system, while changes in environmental conditions often result in alterations in system parameters and other non-linearities, in contrast to the fixed parameters of linear control systems. In blood pressure control these features are exemplified by diurnal circadian fluctuations, alterations in lifestyle and psychosocial stress. Because the neurohumoral controllers are involved in virtually all aspects of homeostasis, they can be regarded as supercontrollers. THE CIRCULATORY SYSTEM AND THE BRAIN: Analysis in conscious animals of the effects of circulatory disturbances suggests that the central nervous system integrates information from multiple sources of afferents. Integration of the information associated with most reflex and behavioural disturbances is mediated by many neuron groups at different levels of the neuraxis, including suprapontine brain regions. The disturbances considered include baroreflexes in intact animals, some central actions of alpha-methyldopa and reflex responses to hypoxia and haemorrhage. The operations involve the brain in comparisons of the relative magnitude of different inputs, while the occurrences of non-linear changes in baroreflex properties signify alterations in the parameters of the controller. NEUROHUMORAL MECHANISMS AND CARDIOVASCULAR DEVELOPMENT: Neurohumoral mechanisms also play a key role in cardiovascular development. Increased sympathetic activity early in life causes hypertension in spontaneously hypertensive rats (SHR) and accounts for the differences in blood pressure and structural variables from corresponding values in Wistar-Kyoto (WKY) rats. In contrast, the renin-angiotensin system affects early cardiovascular development in the same way in each strain, so that it is unlikely to be a cause of hypertension in SHR. However, after drug withdrawal following treatment of young rats with the angiotensin converting enzyme inhibitor enalapril, there were between-strain differences in late cardiovascular development. Late development is relatively small in SHR compared to WKY rats, which contributes to the long-term attenuation of hypertension in SHR and to the normalization of blood pressure in WKY rats.
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PMID:Circulatory control and the supercontrollers. 890 3

Aldosterone, the most important mineralocorticoid, regulates electrolyte excretion and intravascular volume mainly through its effects on renal distal tubules and cortical collecting ducts, where it acts to increase sodium resorption from and potassium excretion into the urine. Excess secretion of aldosterone or other mineralocorticoids, or abnormal sensitivity to mineralocorticoids, may results in hypokalemia, suppressed plasma renin activity, and hypertension. The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension in which 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is defective. This enzyme converts cortisol to its inactive metabolite, cortisone. Because mineralocorticoid receptors themselves have similar affinities for cortisol and aldosterone, it is hypothesized that the deficiency allows these receptors to be occupied by cortisol, which normally circulates at levels far higher than those of aldosterone. We cloned cDNA and genes encoding two isozymes of 11 beta-HSD. The liver (L) or type 1 isozyme has relatively low affinity for steroids, is expressed at high levels in the liver but poorly in the kidney, and is not defective in AME. The kidney (K) or type 2 isozyme has high steroid affinity and is expressed at high levels in the kidney and placenta. Mutations in the gene for the latter isozyme have been detected in all kindreds with AME. Moreover, the in vitro enzymatic activity conferred by each mutation is strongly correlated with the ratio of cortisol to cortisone metabolites in the urine [tetrahydrocortisone (THF) +allo-THF]/THE. This suggests that the biochemical phenotype of AME is largely determined by genotype.
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PMID:11 beta-Hydroxysteroid dehydrogenase and its role in the syndrome of apparent mineralocorticoid excess. 897 85

BLOOD PRESSURE REDUCTION AND CARDIOVASCULAR MORBIDITY AND MORTALITY: Several hypertension trials have shown that antihypertensive treatment can reduce the cardiovascular morbidity and mortality accompanying this condition. They have also shown, however, that the reduction does not entirely normalize the risk of hypertensive patients. STRATEGIES TO IMPROVE THE BENEFIT OF ANTIHYPERTENSIVE TREATMENT: Although some of the risk of the hypertensive patient may prove to be irreversible, pathophysiological and clinical evidence obtained in recent years suggests that some modifications to antihypertensive treatment strategies might increase the benefit. For example, greater use of drugs such as calcium antagonists and angiotensin converting enzyme (ACE) inhibitors as first-line agents might bring greater benefits, because some properties of these drugs which are additive to their blood pressure lowering effects, such as regression of cardiovascular structural changes, nephroprotection and delay of atherogenesis, may provide a degree of protection against target-organ damage. ONGOING CLINICAL TRIALS AND THE INTERNATIONAL NIFEDIPINE (GITS) GASTROINTESTINAL SYSTEM STUDY OF INTERVENTION AS A GOAL IN HYPERTENSIVE TREATMENT (INSIGHT): Several ongoing clinical trials are aimed at comparing the effects of calcium antagonists and ACE inhibitors versus beta-blockers and diuretics on cardiovascular morbidity and mortality. INSIGHT is particularly interesting because the effects of nifedipine GITS and a combined thiazide and potassium-sparing diuretic on cardiovascular morbidity and fatal events are being compared in patients with hypertension plus one or more additional risk factors, such as hypercholesterolemia, smoking, diabetes, left ventricular hypertrophy, etc. INSIGHT is therefore the first trial to address, in a prospective fashion, the prognostic influence of antihypertensive treatment in hypertensives with concomitant risk factors.
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PMID:Benefit versus risk of calcium antagonists in hypertensive patients with concomitant risk factors. 898 41

The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension in which 11 beta-hydroxysteroid dehydrogenase (11-HSD) is defective. This enzyme converts cortisol to its inactive metabolite, cortisone. The deficiency allows mineralocorticoid receptors to be occupied by cortisol, because these receptors themselves have similar affinities for cortisol and aldosterone. There are two isozymes of 11-HSD, a liver (L) or type 1 isozyme with a relatively low affinity for steroids, and a kidney (K) or type 2 isozyme with high steroid affinity. Mutations in the gene for the kidney isozyme of 11-HSD have been detected in all kindreds with AME. We expressed enzymes carrying all known missense mutations in cultured cells and determined their activity. For each patient with AME, we compared the enzymatic activity predicted by the genotype with the ratio of cortisol to cortisone metabolites in the urine, (THF + aTHF)/THE. These were strongly correlated, suggesting that the biochemical phenotype of AME is largely determined by genotype. The K isozyme of 11-HSD is also expressed in high levels in the placenta, where its function is unclear. AME patients often have low birth weight. By analogy with AME, low placental 11-HSD K activity in humans might be a risk factor for low birth weight and subsequent hypertension. However, we found that there was no significant correlation between 11-HSD activity, mRNA levels, and either fetal or placental weight.
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PMID:Molecular analysis of 11 beta-hydroxysteroid dehydrogenase and its role in the syndrome of apparent mineralocorticoid excess. 902 20

TREATMENT OF ELDERLY HYPERTENSIVES: Treatment of hypertension in the elderly is nowadays an accepted and highly effective medical intervention following the positive reports on the benefits of lowering elevated arterial pressure in elderly patients. Most of the intervention studies an antihypertensive treatment in elderly patients have used diuretics or beta-blockers or the two in combination as the therapy by which blood pressure was lowered. However, from a theoretical point of view, novel therapies such as calcium antagonists could offer advantages that would translate into an even greater reduction in cardiovascular morbidity and mortality than has been obtained with the traditional antihypertensive therapies used so far. DATA ON CALCIUM ANTAGONISTS IN THE ELDERLY: Some of the studies in elderly hypertensives that are currently in progress are using calcium antagonists as one of the main therapies, e.g. the Swedish Trial in Old patients with hypertension (STOP-Hypertension)-2 study and the Systolic hypertension in Europe (Syst-Eur) study. Another source of information is a large database on nicardipine, a dihydropyridine-derived calcium antagonist, used in the treatment of elderly hypertensives.
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PMID:Hypertension in the elderly. 912 Jun 61

AGE-RELATED CARDIOVASCULAR CHANGES: Age-related changes in vascular structure and function may contribute to isolated systolic hypertension and target-organ damage. These include cardiac hypertrophy, systolic as well as diastolic dysfunction, congestive heart failure, coronary artery disease, cardiac arrhythmias, cerebrovascular diseases, peripheral vascular diseases and renal insufficiency. POTENTIAL ADVANTAGES OF CALCIUM ANTAGONISTS IN THE ELDERLY: Dihydropyridine calcium anatagonists have been advocated as first choice agents for the treatment of hypertension in the elderly on the grounds that (1) they may be more active in lowering blood pressure because of the predominantly low renin status in elderly hypertensives, (2) they may be better tolerated because side effects related to the activation of the sympathetic system may be less frequent because of attenuation of baroflexes during ageing and (3) they may have beneficial effects on a variety of concomitant cardiovascular diseases which are frequently present in the elderly. These assumptions, however are not always proven in clinical practice. ADVANTAGES OF NICARDIPINE: Additional to its potent vasodilatator action, nicardipine has anti-ischemic effects in both the coronary and the cerebral circulation, including antiplatelet and hemorrheological effects, and protection at ther cellular level against calcium overload and ischemia. The results of a large number of studies in cerebrovascular insufficiency suggest that nicardipine, may favourably affect the cerebral circulation and may improve the patient's cognitive function. Nicardipine may decrease left ventricular mass by about 4-12% and may reduce both the frequency and the severity of arrhythmias. The anti-anginal effects of nicardipine are well established. The drug is also able to decrease the progression of new atherosclerotic lesions in coronary arteries and is consequently potentially beneficial in elderly hypertensives with coronary artery disease. Nicardipine has no clinically significant negative inotropic effect. Nevertheless, in congestive heart failure, the use of calcium antagonists is usually not recommended because of the lack of clinical benefit and of possible harmful effects, including sympathetic and renin-angiotensin system stimulation. Although kidney protection may be provided by a strict and long-term control of blood pressure, the effects of nicardipine on long-term protection of renal function are not clear at present. RECENT CONTROVERSY CONCERNING SHORT-ACTING CALCIUM ANTAGONISTS: Much-debated recent case-control studies suggest that hypertensive patients treated with short-acting calcium antagonists may have an increased incidence of myocardial infarction and possibly of cardiovascular and total mortality. However, only well designed prospective comparative trials can answer this question.
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PMID:Concomitant diseases in elderly hypertensives: the position of nicardipine. 912 Jun 65

ADVANTAGES OF AMBULATORY BLOOD PRESSURE MONITORING: Ambulatory blood pressure monitoring is now used widely to assess the efficacy of antihypertensive drugs in daily life conditions. These 24-h measurements have a number of advantages compared to conventional sphygmomanometric readings. Although a small placebo effect is observed in the first few hours after placebo administration, 24-h average blood pressure is substantially devoid of any placebo effect. Moreover, ambulatory blood pressure is not affected by the alerting reaction usually observed during the doctor's visit. When the 24-h average value is considered, ambulatory blood pressure is more reproducible than clinic blood pressure. Finally, ambulatory blood pressure is prognostically more important than clinic blood pressure, since the end-organ damage associated with hypertension is more closely related to 24-h than to clinic blood pressure. Ambulatory blood pressure monitoring is therefore particularly useful when testing the efficacy of new antihypertensive agents on 24-h blood pressure. TESTING THE COMBINATION OF VERAPAMIL AND TRANDOLAPRIL: In a recent study we evaluated the efficacy of a fixed combination of verapamil and trandolapril using both clinic and ambulatory blood pressure measurements. Ambulatory blood pressure monitoring showed that the effect of the combination of verapamil and trandolapril was greater than the effect of either of the two drugs administered alone. However, the clinic blood pressure measurements failed to show any systemically greater effect with the combination versus monotherapy. This further indicates that ambulatory blood pressure is superior to conventional blood pressure in the assessment of antihypertensive drugs.
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PMID:Assessment of antihypertensive treatment by ambulatory blood pressure. 921 98

MIBEFRADIL IN THE TREATMENT OF HYPERTENSION: The antihypertensive efficacy of mibefradil, a new selective transient (T)-channel calcium antagonist, was studied in eight randomized, double-blind, parallel-design trials: four placebo-controlled and four active drug-controlled versus other calcium antagonists. These studies established that at doses of 50 and 100 mg, mibefradil is an effective, well tolerated and safe treatment for high blood pressure. The antihypertensive effect of mibefradil was achieved gradually, with the full activity reached within 1-2 weeks. The decrease in arterial pressure was smooth and sustained over the entire 24-h dosing interval. The antihypertensive action was associated with a dose-related reduction in the heart rate. The efficacy results were similar across all demographic subpopulations studied, including high-risk groups: individuals with chronic renal failure; the elderly; and hydrochlorothiazide-treated patients. In studies comparing mibefradil with other calcium antagonists at their recommended doses, 100 mg mibefradil demonstrated significantly better antihypertensive efficacy than controlled-dose (CD) diltiazem at 360 mg or slow release (SR) nifedipine at 40 mg twice a day, and similar efficacy to that of 10 mg amlodipine or 60 mg nifedipine gastrointestinal therapeutic system (GITS). MIBEFRADIL IN THE TREATMENT OF ANGINA PECTORIS: The efficacy, safety, and tolerability of 50 and 100 mg mibefradil in the treatment of chronic stable angina pectoris was tested in six randomized parallel-design studies. Significant increases in exercise duration and a significant delay in the onset of ischemia during exercise were found in most studies with the 50-mg dose and in all studies with the 100-mg dose. Weekly anginal attacks and nitroglycerine consumption decreased significantly in a dose-related manner and, similarly, a significant dose-related decrease in the number and duration of silent ischemic episodes was observed on 48-h Holter monitoring. In the two studies with active drug controls, 100 mg mibefradil was significantly better than 10 mg amlodipine and equivalent to 120 mg diltiazem SR twice a day in improving anti-anginal and anti-ischemic parameters. In all studies, mibefradil treatment produced a dose-related reduction in the heart rate and the rate-pressure product at rest and at the end of exercise, and the magnitude of these decreases was larger than that observed with the other two calcium antagonists. SAFETY AND TOLERABILITY: An integrated analysis of combined data on the safety and tolerability of mibefradil from studies on hypertension and angina pectoris confirmed that mibefradil and diltiazem were equally well tolerated, but the incidence of leg edema was clearly higher in patients treated with the dihydropyridine calcium antagonists amlodipine and nifedipine.
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PMID:Differential properties of mibefradil in hypertension and angina. 948 14

ACTIONS OF THE SYMPATHETIC NERVOUS SYSTEM: The sympathetic nervous system is an important cardiovascular regulator, particularly during stress and exercise; its sympathetic nervous activity is regulated in centers in the brain stem and transmitted to organs and blood vessels that are innervated by sympathetic nerve endings. In the heart, the sympathetic nervous system increases heart rate and contractility. The effect of the sympathetic nervous system in different vascular beds depends on the degree of innervation, the distribution of postjunctional receptors and the effect of local mediators. Overactivation of the sympathetic nervous system may lead to hypertension and is involved in heart failure. The degree of sympathetic activation determines prognosis in heart failure. Hence, vasodilators ideally should also blunt sympathetic activity, or at least avoid activating it. DIFFERENCES AMONG CALCIUM ANTAGONISTS: Calcium antagonists are widely used for the treatment of hypertension and coronary artery disease. Their main mechanism of action is inhibition of L-type Ca2+ channels. Short-acting nifedipine leads to a marked increase in heart rate, sympathetic nerve activity and plasma catecholamines, similar to those induced by a cold pressor test. With long-acting nifedipine heart rate does not increase, but sympathetic nerve activity does increase. Other calcium antagonists have been less thoroughly investigated, but indirect evidence suggests differences between the different classes. Verapamil and diltiazem lower heart rate. Plasma noradrenalin measurements suggest that verapamil does not stimulate the sympathetic nervous system, but tends to suppress it. Second-generation dihydropyridines with longer duration of action do not increase heart rate; their effects on peripheral sympathetic nerve activity are not clear. Thus, in summary, the different classes of calcium antagonists differ with regard to their effects on sympathetic nerve activation. A decrease in heart rate and nerve activity might be beneficial for long-term prognosis, particularly in hypertension and heart failure.
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PMID:Calcium antagonists and sympathetic nerve activation: are there differences between classes? 953 92


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