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

The Medical Research Council's treatment trial for mild hypertension was designed to determine the effects of blood pressure reduction on cardiovascular morbidity and mortality rather than to compare the separate effects of thiazides and beta-adrenergic blocking agents. However, the simultaneous use of both active treatments was discouraged and comparisons in terms of blood pressure control, adverse drug reactions, and drug-related changes in the serum biochemistry are possible. The net differences in systolic and diastolic pressure between treated and control subjects were greater in older than in younger people; this net difference was more pronounced in the older people assigned at random to receive bendrofluazide as opposed to propranolol; this effect increased with time during the trial. The need for a supplementary drug (methyldopa) to control blood pressure at target level, was greater in the thiazide-treated group for all ages. Withdrawal from randomized treatment due to adverse reactions was greater in men receiving bendrofluazide than in those receiving propranolol, and greater for women receiving propranolol than in those receiving bendrofluazide. Thiazide treatment was shown, in a sub-study, to be associated with a significant increase in ventricular ectopic activity in long-term participants.
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PMID:Effects of diuretic and beta-blocker therapy in the Medical Research Council Trial. 670 63

Thiazide diuretics and loop-diuretics, often used for treatment of hypertension, interfere with various metabolic reactions: An increase of uric acid in plasma is a regular finding, but gout will not be caused, an elevation of plasma lipoproteins has been observed but did not proceed to pathological values, in a number of patients blood glucose has been raised but without producing diabetes mellitus. In general, these metabolic interference are of minor pathological significance. Special treatment for these side-effects are needed in a few cases only. The indicated use of thiazide diuretics should not be disregarded because of their effects on regulatory mechanisms of metabolism.
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PMID:[Metabolic effects of diuretics (author's transl)]. 679 54

Approximately 600 people with mild to moderate hypertension were treated with a regimen that started with monotherapy. Reduction in sodium intake achieved adequate blood pressure control in 38 percent, higher than that achieved without therapy (17 percent). Chlorothiazide and propranolol gave satisfactory blood pressure control in 43 and 56 percent of patients, respectively, as sole therapy. When initial blood pressure was greater than 110 mm Hg, satisfactory control was achieved in fewer patients (sodium restriction, 13 percent; chlorothiazide, 30 percent, propranolol 38 percent); in this group, therapy with reduction of sodium intake alone is rarely effective. All measures were about equally successful in treating isolated systolic hypertension. The group given thiazide diuretics alone had an increased number of deaths from myocardial infarcts compared with other groups. This was not seen if a beta-blocking drug or a centrally-acting drug was used in conjunction with the thiazide diuretic. Monotherapy can successfully reduce blood pressure in most patients with mild hypertension. No regimen can be stated to be unequivocally superior to another.
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PMID:Monotherapy in the treatment of hypertension. 682 42

The thiazide diuretics are known to cause calcium retention. In order to study the effect of thiazides on bone mineralization, we have measured the mineral content of bone at five sites (the distal radius, the distal ulna, the proximal radius, the proximal ulna, and the os calcis) in 1368 men with a mean age of 68 years, including 323 who were taking thiazides for hypertension. The results were adjusted for age and body-mass index. Thiazide users had significantly more bone mineral content at all five sites than did non-users. Untreated hypertensive patients and persons without hypertension had comparable bone mineral content, indicating that the higher mineral content found among thiazide users is related to the drug and not to the underlying hypertension. These findings suggest the possibility of a preventive or therapeutic role for thiazides in osteoporosis.
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PMID:Thiazide effect on the mineral content of bone. 686 70

Despite the beneficial therapeutic effects of antihypertensive drugs, some agents--particularly diuretics--seem to go in the "wrong direction" chemically. In fact, these changes could counteract some of the benefits resulting from lowering a patient's blood pressure. In the absence of hard evidence of the efficacy of long-term diuretic treatment of mild hypertension, we must be maximally sure that such therapy causes no harm. Thiazide and related diuretics have been associated with four distinct wrong-way chemical changes: increases in plasma concentrations of cholesterol, glucose, and uric acid, and a decrease in plasma potassium levels. The potential ramifications of such changes are well understood. The increase in circulating cholesterol, an established risk factor of myocardial infarction and stroke, is of particular concern--each year approximately one million hypertensive patients have myocardial infarctions. As a result, the search for safer and more effective diuretics must continue. Indapamide, a new antihypertensive drug, appears to meet these criteria. It is an effective diuretic with a considerable peripheral vasodilatory effect. Additionally, it does not appear to induce any significant change in circulating cholesterol, whereas chlorthalidone has been found to increase total cholesterol by 5%. Hydralazine is the only antihypertensive agent that seems to lower total cholesterol levels significantly. Neither indapamide nor hydralazine appears to affect plasma glucose levels; benzothiadiazines, however, have been found to induce an increase in circulating glucose.
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PMID:Some wrong-way chemical changes during antihypertensive treatment: comparison of indapamide and related agents. 686 7

The possible role of obesity in the development of hypertension was investigated in two study groups. In a population study of 961 subjects, 739 were found to be normotensive and 222 hypertensive. The prevalence of hypertension was 18.7 percent in the nonobese, and 33.2 percent in the obese subjects. Systolic and diastolic blood pressures increased progressively with the increase of relative body weight in both normotensive and hypertensive subjects. In addition, an endocrinologic study was made of 97 patients with essential hypertension; in 82, plasma renin activity (PRA) was inversely correlated with the increase of relative body weight but not with urinary Na excretion. Despite this decrease of PRA, the level of serum aldosterone was not influenced by relative body weight. Thus, the aldosterone/PRA ratio ratio increased progressively with the increase of relative body weight. Thiazide therapy normalized this inappropriately high ratio, and reduced body weight and blood pressure. Restriction of dietary calories and salt intake had a similar effect. With a high-salt intake in an obese subject, the aldosterone/PRA ratio is unduly increased. Apparently aldosterone contributes to the additional retention of sodium and water and thereby promotes hypertension in the presence of an expanded fluid volume.
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PMID:Changes in endocrine activities relative to obesity in patients with essential hypertension. 700 95

The renal kallikrein-kinin system, distinct from the plasma system, is an enzyme sequence producing kinins, principally lysyl bradykinin. While the functions of the system have not been conclusively established, it has been implicated in renal vasodilation and natriuresis, although the evidence is often conflicting. Measurement of urinary kallikrein excretion is the most common way to assess the system, although kallikrein excretion and kinin excretion are often dissociated. Kallikrein excretion is influenced by several hormonal systems, as well as dietary alterations, disease states (including hypertension), and numerous drugs. Kallikrein excretion is diminished in hypertension (especially hypertension with reduced renal function), suggesting involvement in the pathogenesis of the disease. Dietary sodium restriction increases kallikrein excretion while lowering blood pressure, but the blood pressure reduction correlates with plasma volume contraction rather than the increase in kallikrein. Thiazide diuretics lower blood pressure and renal vascular resistance while increasing kallikrein excretion, and blood pressure "responders" to thiazides have a greater kallikrein increment than the "nonresponders," suggesting a role for renal kallikrein in the hypotensive response to thiazides.
Hypertension
PMID:Response of the renal kallikrein-kinin system, intravascular volume, and renal hemodynamics to sodium restriction and diuretic treatment in essential hypertension. 704 33

Antihypertensive therapy has been used for almost 40 years to reduce blood pressure and to prevent morbidity and mortality related to the hypertensive state. Cardiovascular events are related to the initial elevation of blood pressure; the benefits of treating malignant, severe or moderate hypertension are well established. Although large scale clinical trials have demonstrated a decrease in morbid events when mildly elevated blood pressures is treated, the benefits are neither universal or dramatic and treatment is certainly less cost effective than no treatment. Recently it has been emphasised that the absolute risk of cardiovascular events is determined only in part by blood pressure, and that it is also influenced by age, gender, race and the presence of other cardiovascular risk factors. For example, in older individuals where the absolute risk of vascular complications is greater than in younger individuals for any given level of blood pressure, the benefits of therapy will be greater. It has been suggested that in younger individuals with mild hypertension and a low absolute risk of developing cardiovascular morbid events it may be more appropriate to monitor the effects of drug therapy on measures of cardiac and vascular damage that are associated with the hypertensive state. Drug therapy has been shown to be extremely effective in reducing the incidence of stroke, congestive cardiac failure and renal failure associated with elevated blood pressure. Meta-analysis of randomised large scale clinical trials indicates that drug therapy may not reduce coronary events to the extent expected in patients with hypertension. One plausible explanation is that the trials have been of insufficient duration to detect the benefit of blood pressure lowering on coronary heart disease. It has also been suggested that certain adverse metabolic effects associated with the use of thiazide diuretics and beta-blockers employed in these trials may have partially offset the benefits of blood pressure reduction. However, the clinical significance of these drug-induced metabolic disturbances remains unclear. Experimental data suggesting differences in the ability of antihypertensive drugs to inhibit atherosclerosis in animal models are also of interest, but again the relation of the findings to the clinical situation is unknown. Thiazide diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and alpha-blockers can produce regression of left ventricular hypertrophy (LVH). While LVH is clearly a strong and independent predictor for coronary disease, it remains to be shown that a lower risk for coronary morbid events exists in patients whose LVH has undergone regression over and above that attributable to blood pressure reduction.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Goals of antihypertensive therapy. 772 25

Thiazide diuretics are widely used in the drug treatment of hypertension but their dose-response curves for the antihypertensive and adverse metabolic effects differ. To characterize the lower end of the dose-response curve a double-blind, parallel group trial was performed as multicentre study in Scandinavia. One hundred and eleven patients with newly diagnosed or previously treated mild to moderate hypertension (untreated diastolic blood pressure of 95-115 mmHg after 4 weeks placebo) were randomly allocated to various doses of hydrochlorothiazide (3, 6, 12.5 or 25 mg) or placebo for 6 weeks. Blood pressure and biochemical variables (plasma renin activity, serum potassium, magnesium, urate, fasting glucose, total cholesterol, HDL-cholesterol, triglycerides and apolipoproteins A1 and B were measured. 12.5 mg hydrochlorothiazide had a borderline effect on blood pressure whilst 25 mg had a definite antihypertensive effect. Biochemical changes were seen in plasma renin activity, serum potassium and urate after the 12.5 and 25 mg dose. Three and 6 mg had no effect on blood pressure or metabolic parameters.
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PMID:Relation between low dose of hydrochlorothiazide, antihypertensive effect and adverse effects. 799 47

Renal cell carcinoma has been linked to hypertension and antihypertensive medications. We investigated the association between renal cell carcinoma and the use of thiazide in a case-control study of 167 men and 90 women. Subjects were members of the Kaiser Permanente Medical Care Program in northern California (United States) who had taken a multiphasic health check-up from 1964 through 1988 and who were evaluated for cancer until the end of 1989. Control subjects received the same check-up, were matched by gender, year of check-up, and age at check-up, and had to be in the health plan until the date on which renal cell carcinoma was diagnosed. Data on known and potential risk factors, including hypertension, body mass index (BMI), and smoking status, were collected from the record of the check-up. Thiazide use was abstracted from the medical chart, which was reviewed from the date of the first entry until the date on which the cancer was diagnosed or the equivalent date for control subjects. The mean follow-back to check-up was 11.3 years. Among women, we found a significantly elevated risk of 4.0 (95 percent confidence interval [CI] 1.5-10.8) associated with ever having used thiazide after we adjusted for smoking, BMI, hypertension, and history of kidney infection at check-up. We did not find a statistically significantly elevated risk in men. Smoking was related to renal cell carcinoma in men (odds ratio [OR] 2.5, CI = 1.1-5.4) for those who smoked at least one pack per day compared with those who had never smoked, but was not related in women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal cell carcinoma and thiazide use: a historical, case-control study (California, USA). 808 Sep 43


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