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

Hypertension occurs in 50% of the elderly persons in industrialized societies. This disorder of the regulation of the arterial blood pressure has different manifestations in different age groups. The young hypertensive usually has an increase in cardiac output and a normal peripheral vascular resistance. The elderly patient with hypertension exhibits a decreased cardiac output and an increased peripheral vascular resistance. In the elderly hypertensive there is a progressive anteriolar narrowing and there is hardening of the largest arteries. The vascular disease that contributes to the hypertension in the elderly also causes hypoperfusion of the target organs. During the aging process there is a decrease in cardiac output, glomerular filtration rate, vital capacity, renal plasma flow and maximal cardiac rate. There are changes in the kidneys and the liver that influence the way different medications are handled by the body. The main findings of the Australian, EWPHE, Coope & Warrender, SHEP, STOP-HYP and MRC studies of hypertension in the elderly have been summarized. The intervention studies have proven that the treatment of hypertension in the elderly patient is efficacious and decreases the mortality and morbidity due to coronary and cerebrovascular events. The pharmacologic agents available for the treatment of hypertension in the elderly are the diuretics, beta blockers, vasodilators, calcium-channel blockers, adrenergic blockers and angiotensin converting enzyme inhibitors. The morbidity and mortality benefits derived from antihypertensive trials are greater for the older than for the younger patients. The pharmacologic antihypertensive agents to be used in older patients will also depend upon the presence or not of associated illnesses in which some agents might be harmful or contraindicated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hypertension in old age]. 858 23

Treatment of hypertension plays a key role in primary prevention of cerebrovascular attacks. Meta-analysis of 17 prospective studies of the treatment of hypertension proved that reduction of the systolic and diastolic blood pressure by 8-10/5-6 mmHg leads to a reduction of fatal and non-fatal cerebrovascular attacks by 40%. In the nineties a Swedish and British investigation of systolic-diastolic hypertension in elderly subjects-STOP and MRC-provided evidence of the great impact of treatment of hypertension in primary prevention of cerebrovascular attacks also in elderly hypertensive subjects (60-80 years). It is important to treat also in advanced age frequent isolated systolic hypertension as this improves markedly the prognosis of these patients and reduces the incidence of cerebrovascular and coronary complications, as was proved by the American study SHEP. The authors demonstrate that so far only the minority of hypertensive patients is treated effectively in this country and data from abroad indicate also that treatment of hypertension is lacking in the premorbid stage in more than half the patients with a cerebrovascular attack. The drugs of choice in treatment of hypertension in the elderly are small doses of thiazide diuretics and cardioselective beta-blockers or beta-blockers with ISA. By increasing the number of treated hypertensive patients, incl. elderly patients with a hypertension, and by increasing the effectiveness of treatment it is possible to achieve a decline of the cerebrovascular mortality; our objective must be a decline of the cerebrovascular mortality by more than 50%, similarly as it happened already in the USA. Conversely the importance of treatment of hypertension in secondary prevention of cerebrovascular attacks is controversial. The authors emphasize also the importance of abstinence from smoking as well as careful treatment of diabetes and hyperlipidaemia. Antiaggregation treatment has a greater impact in secondary prevention than treatment of hypertension. As regards the latter it should suffice to reduce the blood pressure to values of cca 150-160/90 -100 mmHg and not to normal values.
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PMID:[Treatment of hypertension in primary and secondary prevention of cerebrovascular stroke]. 892 16

Diuretics were used in most of the major trials that demonstrated that lowering the blood pressure reduced cardiovascular morbidity and mortality. Nevertheless in the second half of the eighties, there were misgivings about the widespread use of thiazide diuretics, driven in part by the relative failure of the large trials to reduce myocardial infarction-to the extent predicted by large scale epidemiological studies. There was much attention on metabolic side effects of thiazide diuretics including dyslipidaemia, glucose intolerance, hypokalaemia, hyperuricaemia, and then microalbuminuria particularly in diabetic subjects. These issues were current when JNC (IV) (1988) and the WHO-ISH guidelines (1989) were being written. Three major clinical trials SHEP, STOP and MRC published in the early nineties established that thiazide diuretics alone, or in combination with beta blockers, did reduce cardiovascular morbidity and mortality in elderly subjects with hypertension. All guidelines published since 1993 include diuretics among the first line drugs. Possibly the most important factor in the restoration of diuretics has been the use of progressively lower doses that minimise the metabolic side effects. Diuretics are effective as monotherapy in the treatment of mild essential hypertension and of isolated systolic hypertension in elderly subjects. They are very useful in combination with beta blockers or with ACE inhibitors. They should be avoided in patients with gout and should not be used as first line drugs in patients with diabetes. They should only be used with caution in young obese subjects with dyslipidaemia and increased risk of coronary artery disease, facing many decades of treatment for hypertension. However there is no doubt that diuretics are effective, cheap and have a central role in the control of hypertension in all communities around the world.
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PMID:[Role of diuretics in the treatment of hypertension: from large controlled trials to international guidelines]. 895 12

We recently demonstrated that, in rat aortic smooth muscle cells, alpha-thrombin stimulated Stat3/SIF-A (signal transducers and activators of transcription 3/sis-inducing factor-A) activity [G. J. Bhat et al. (1997) Hypertension 29(Pt. 2), 356-360]. In the present study, we observed that exposure of CCL39 cells (a Chinese hamster lung fibroblast cell line) to alpha-thrombin resulted in a time-dependent decrease in basal SIF-A activity. We hypothesized that the decrease in basal SIF-A was due to the initiation of an inhibitory pathway, following alpha-thrombin exposure. To test this hypothesis, we determined if alpha-thrombin would inhibit Stat3 and SIF-A activation by interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and ciliary neurotrophic factor (CNTF). In support of this hypothesis, alpha-thrombin inhibited the Stat3/SIF-A response induced by all the above cytokines. The inhibition by alpha-thrombin was concentration dependent, was sensitive to hirudin, and was mimicked by the thrombin receptor agonist peptide. The inhibition did not require the activation of phorbol 12-myristate 13-acetate-sensitive isoforms of protein kinase C and was reversed by pretreatment with the mitogen-activated protein kinase kinase 1 (MAPKK1 or MEK1) inhibitor PD98059. Inhibitory cross talk between alpha-thrombin and IL-6 was also observed in MRC-5 cells, a fibroblast cell line derived from human lung tissue. Thus, we identify a novel alpha-thrombin inhibitory pathway which, acting through a MAPKK1-dependent mechanism, blocks IL-6-, LIF-, and CNTF-induced Stat3/SIF-A activation. This inhibitory cross talk may provide an important regulatory function to modulate gene transcription by these cytokines, during immune and inflammatory responses.
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PMID:alpha-Thrombin inhibits signal transducers and activators of transcription 3 signaling by interleukin-6, leukemia inhibitory factor, and ciliary neurotrophic factor in CCL39 cells. 947 6

We ascertained nonsteroidal anti-inflammatory drug (NSAID) use in 2,651 participants in the UK MRC treatment trial of hypertension in older adults and measured change in cognitive function over the subsequent 54 months. There was a significant, although modest, association between change in the Paired Associate Learning Test score over time and NSAID use, which was modified by age. NSAID users showed less decline, with younger subjects seeming to benefit more than older. We found no relationship between NSAID use and time taken to complete the Trail Making Test and also no relationship between anti-indigestion drug use and either cognitive outcome. These analyses highlight the need for larger studies with prospective classification of NSAID use and adequate control of confounding, including exposure to other medications. A randomized controlled trial of NSAIDs, in those known to be at risk of cognitive decline or dementia, may be indicated in the future.
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PMID:Do antiarthritic drugs decrease the risk for cognitive decline? An analysis based on data from the MRC treatment trial of hypertension in older adults. 948 56

Isolated systolic hypertension is a common disorder in the elderly carrying a high risk of stroke and cardiovascular disease. Isolated systolic hypertension is usually defined as a systolic blood pressure greater than or equal to 160 mmHg and diastolic blood pressure less than 95 mmHg. The arterial stiffening is the principal cause of increasing systolic pressure in advanced age. It is due to degeneration of the arterial wall and is associated with progressive arterial dilatation. Hypertension in elderly patients is also characterized by increase of peripheral vascular resistance. Due to the wide variability of blood pressure usually seen in old persons, the isolated systolic hypertension is not easy to recognize and final diagnosis requires a long period of observation. The ambulatory blood pressure monitoring proved to be helpful in distinguishing patients with true isolated systolic hypertension from subjects with exaggerated alarm reaction to the pressure measurement. Although the increased risk of cardiovascular and cerebrovascular mortality is well established for isolated systolic hypertension, there has been much debate whether available antihypertensive treatment can prevent or delay cardiovascular and cerebrovascular complications in this condition. During the last year several large new trials have been published, the so-called STOP-Hypertension, SHEP and MRC trials. All studies have demonstrated that the treatment of isolated systolic hypertension with diuretics or/and beta blockers (frequently used in combination) resulted in a significant reduction in the incidence of stroke and major cardiovascular events. New antihypertensive agents such as calcium channel blockers and angiotensin-converting enzyme inhibitors have also been shown to effectively lower systolic blood pressure in the elderly but the effects on long-term morbidity and mortality are still unknown.
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PMID:[Isolated systolic arterial hypertension in the elderly]. 986 68

Previously we demonstrated that pulse pressure is a strong risk factor for coronary events in male hypertensive subjects in the MRC Mild Hypertension Trial, whereas stroke is best predicted by mean blood pressure. In this study, we have assessed the implications of this finding in the treatment of mild essential hypertension. We examined the relationship between diastolic blood pressure and both coronary disease risk and stroke when these events were predicted by the above blood pressure measures using an empirical linear model and multivariate logistic regression models that contained data from the MRC trial. Under these circumstances, the predicted stroke risk increased progressively with increasing values of diastolic blood pressure, but in both empirical and formal statistical models, the predicted risk of a coronary event exhibited a J-shaped relationship with diastolic blood pressure. These results suggest that if coronary event risk in mild essential hypertension is predicted by pulse pressure then it may increase at low values of diastolic blood pressure, in contrast to stroke risk, which declines continuously as diastolic blood pressure falls within the physiological range. This raises the possibility that different sequelae of hypertension are best predicted by different measures of blood pressure and that the effect of treatment on stroke and coronary events in some circumstances may be discordant.
Hypertension 2000 Nov
PMID:Implications of pulse pressure as a predictor of cardiac risk in patients with hypertension. 1108 65

The effects of antihypertensive treatment on cerebrovascular disease and coronary artery disease (CAD) end points reported in the large-scale national trials have differed. All trials have shown stroke benefit, whereas CAD benefit has not been convincingly demonstrated in any. In three trials, the effects of thiazide- and beta-blocker-based regimens can be directly compared. In the MRC Treatment Trial for Mild Hypertension in Britain, the largest of the trials and the only one to compare these two classes of drugs with each other and with untreated controls, stroke benefit was significantly greater in the thiazide than in the beta-blocker group (p = 0.002). Indeed, the 70% reduction in fatal strokes and 65% reduction in nonfatal strokes suggested an effect on cerebral infarction as well as on cerebral hemorrhage. Opposing trends were found for CAD end points with beta-blockers and thiazides when compared with controls. For coronary events, sudden deaths, and ECG changes of infarction, significant differences were found between the reduced rates for those receiving propranolol and the higher rates for those receiving bendrofluazide. Weak evidence has been put forward by four trials-MRFIT, HDFP, the Oslo trial, and the MRC trial-suggesting that thiazide treatment for those who already have evidence of coronary disease may be harmful. In no case is the evidence conclusive, and it involves only a small (but important) subgroup. In the MRC trial, a nonselective beta-blocker, propranolol, provided greater CAD benefit as measured by the incidence of myocardial infarction, sudden death, and ECG changes, but only in nonsmokers. Hypotheses generated by these trials need further investigation.
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PMID:Beta-blockers vs. thiazides in the treatment of hypertension: a review of the experience of the large national trials. 1152 38

Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.
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PMID:beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension. 1455 68

Hypertension is strongly related to cardiovascular disease and all-cause mortality. Exercise reduces blood pressure but the response varies between individuals. The mechanisms by which physical activity energy expenditure (PAEE) modifies blood pressure are not fully defined but include modulation of sympathetic tone. Novel polymorphisms in the G-protein coupled receptor (GPR10) have been linked with high blood pressure. GPR10 may mediate the relationship between PAEE and blood pressure via central nervous mechanisms. We examined whether two GPR10 polymorphisms (G-62A and C914T) modify the association between PAEE and blood pressure in the MRC Ely study (N=687). When stratified by the C914T genotype, there were between-group differences for body mass index (BMI) (P=0.05), diastolic blood pressure (DBP) (P=0.006), and systolic blood pressure (SBP) (P=0.005). No differences were found between G-62A genotypes. The previously reported inverse relationship between PAEE and blood pressure was not observed in minor allele carriers for either polymorphism (A62 carriers: DBP beta-1.11, P=0.52; SBP beta-1.66, P=0.52. T914 carriers: SBP beta=3.27; P=0.60) but was in common allele homozygotes (G62G: DBP beta-6.18 P=0.00001; SBP beta-8.54 P=0.0001. C914C: SBP beta-7.07; P=0.00001). This corresponded to a significant interaction between PAEE and GPR10 polymorphisms on DBP (G-62A: P=0.006) and SBP (G-62A: P=0.008. C914T: P=0.068). Significant interactions were observed between haplotype (derived from G-62A and C914T), PAEE, and blood pressure (DBP: P=0.08; SBP: P=0.023). The effect of physical activity on blood pressure is highly variable at population level. Knowledge of GPR10 genotype may define those who are least likely to benefit from physical activity. These findings may have relevance in the targeted treatment of hypertensive disease.
Hypertension 2004 Feb
PMID:Association between physical activity and blood pressure is modified by variants in the G-protein coupled receptor 10. 1469 Nov 96


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