Blood pressure and coronary heart disease.
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Benzothiadiazines↗
Biomedical subjects
S MacMahon
Publications and source records attributed to S MacMahon.
Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context.
There are 14 unconfounded randomised trials of antihypertensive drugs (chiefly diuretics or beta-blockers): total 37,000 individuals, mean treatment duration 5 years, mean diastolic blood pressure (DBP) difference 5-6 mm Hg. In prospective observational studies, a long-term difference of 5-6 mm Hg in usual DBP is associated with about 35-40% less stroke and 20-25% less coronary heart disease (CHD). For those dying in the trials, the DBP difference had persisted only 2-3 years, yet an overview showed that vascular mortality was significantly reduced (2p less than 0.0002); non-vascular mortality appeared unchanged. Stroke was reduced by 42% SD 6 (95% confidence interval 35-50%; 289 vs 484 events, 2p less than 0.0001), suggesting that virtually all the epidemiologically expected stroke reduction appears rapidly. CHD was reduced by 14% SD 5 (95% CI 4-22%; 671 vs 771 events, 2p less than 0.01), suggesting that just over half the epidemiologically expected CHD reduction appears rapidly. Although this significant CHD reduction could well be worthwhile, its size remains indefinite for most circumstances (though beta-blockers after myocardial infarction are of substantial benefit). At present, therefore, a sufficiently high risk of stroke (perhaps because of age, blood pressure, or, in particular, history of cerebrovascular disease) may be the clearest indication for antihypertensive treatment.
Antihypertensive Agents↗
Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias.
The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420,000 individuals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. Previous analyses have described the uncorrected associations of DBP measured just at "baseline" with subsequent disease rates. But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an individual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of individuals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.
Adult↗
Future directions for randomized trials of cardiovascular disease prevention in hypertensive patients.
Coronary artery disease (CAD) is the major cause of death in hypertensive patients in Western populations and further efforts are required to determine how best to reduce its incidence. Large-scale placebo-controlled trials of blood pressure reduction could resolve the uncertainty about the effects of antihypertensive treatment on CAD incidence, but at present, such trials could probably only be conducted in patients with mild hypertension (or normotension). If such patients were selected on the basis of clinically manifest vascular disease, the sample size necessary to detect plausible treatment effects may be practicable (i.e., several thousand patients). In moderately or severely hypertensive patients, "active-controlled" trials could be conducted to determine the relative effects of different anti-hypertensive drugs on CAD morbidity and mortality. However, because any difference between such regimens is likely to be modest in magnitude (and smaller than the difference between treatment and no treatment), the sample size required to detect such differences would be very large (i.e., tens of thousands). With somewhat smaller numbers of patients, it would be possible to conduct placebo-controlled trials to study the effects on CAD of other potentially cardioprotective interventions, such as cholesterol reduction and aspirin, both of which may offer effective means for CAD prevention in hypertensive patients.
Cardiovascular Diseases↗
Antihypertensive drug treatment: the potential, expected and observed effects on vascular disease.
Re-analysis of the results of several prospective observational studies indicates that modest long-term differences in usual diastolic blood pressure are associated with larger differences in the primary incidence of stroke and of coronary heart disease than was previously believed. A prolonged difference of 5-6 mmHg in usual diastolic blood pressure was associated with at least one-third fewer strokes and at least one-fifth fewer coronary heart disease events. The results of randomly allocated trials of antihypertensive drug therapy (mostly diuretics) indicate that a similar difference in diastolic blood pressure maintained for just a few years appears to produce much or all of the potential long-term benefits for stroke. The incidence of coronary heart disease was also significantly reduced by treatment (2P less than 0.01). However, for coronary disease, the trial results, even in combination, are inadequate to allow a reliable determination of the size of the treatment effects and the proportion of the long-term potential benefit achieved by a few years of diuretic-based treatment.
Antihypertensive Agents↗
Electrocardiographic left ventricular hypertrophy and effects of antihypertensive drug therapy in hypertensive participants in the Multiple Risk Factor Intervention Trial.
Data are reported on electrocardiographic left ventricular hypertrophy (ECG LVH) among 8,012 men classified as hypertensive at baseline in the Multiple Risk Factor Intervention Trial. Compared with those allocated to the usual care (UC) control group, men allocated to the special intervention (SI) group experienced a mean reduction of 4 mm Hg in diastolic blood pressure and 7 mm Hg in systolic blood pressure, over 6 years of follow-up. There were 378 new cases of ECG LVH during follow-up; the incidence in the SI group was about 23% less than that in the UC group (4.2 vs 5.4% 2P less than 0.01). Among the 189 men with ECG LVH at baseline, those in the SI group experienced about 24% more annual follow-up visits at which they were free of ECG LVH (4.6 vs 3.7 visits; 2P less than 0.01). This reduced incidence and increased reversal of ECG LVH in the SI group compared with that in the UC group was consistent with significant overall reductions (2P less than 0.001) among SI men in mean wave amplitude in those leads in which voltage is correlated with left ventricular mass (T wave in V1, R wave in aVL and S wave in V3). In SI and UC groups combined, the presence of ECG LVH either at baseline or at follow-up was associated with several-fold increases in death from cardiovascular diseases in general, and death from coronary artery disease in particular.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Antihypertensive drug treatment. Potential, expected, and observed effects on stroke and on coronary heart disease.
The effects of prolonged differences in diastolic blood pressure (DBP) on the risks of stroke and of coronary heart disease (CHD) were estimated from nine major prospective observational studies involving about 420,000 men and women who were followed up for intervals of 6-25 years. The results indicate that a prolonged difference of about 6 mm Hg in DBP was associated with approximately 37% fewer strokes and 23% fewer CHD deaths and nonfatal myocardial infarctions. The effects of equivalent reductions in DBP produced by antihypertensive drug treatment but maintained for only a few years have been estimated in several overviews of randomized trials involving a total of 30,000-40,000 patients. The results of the overviews indicate that treatment reduced the risk of stroke by about 40%, suggesting that most or all the long-term potential benefits for stroke due to lower DBP were achieved within about 3 years of beginning treatment. The risks of nonfatal myocardial infarction and CHD death may have been reduced by about 10% among patients allocated to active treatment; the 95% confidence limits for the difference ranged from about zero to about 20%. Whatever the true effect of treatment on CHD, it would appear somewhat less than the difference in risk estimated from the observational studies for a prolonged difference in DBP of the same size. This apparent shortfall in benefit may reflect a long time-course for changes in DBP to have their full effects on CHD, possible adverse side effects of the principal trial treatments, or both.
Antihypertensive Agents↗
The effects of antihypertensive drug treatment on the incidence of stroke and of coronary heart disease.
The effects of differences in usual diastolic blood pressure (DBP) on the risks of stroke and of coronary heart disease (CHD) were estimated from nine major prospective observational studies involving about 420,000 men and women, followed up over intervals of 6 to 25 years. The results indicated that a prolonged difference in usual DBP of approximately 6 mmHg was associated with about 36% (+/- 2) fewer strokes and 22% (+/- 1) fewer CHD deaths and non-fatal myocardial infarctions. The effects of equivalent reductions in DBP produced by antihypertensive drug treatment but maintained for just a few years, have been estimated in several overviews of randomised controlled trials, involving totals of between 30,000 and 40,000 hypertensive patients. The results of the overviews indicated that antihypertensive treatment reduced the risk of stroke by about 40%, suggesting that all of the long-term potential benefit for stroke of lower DBP was achieved within about 3 years of beginning treatment. The risk of CHD may have been reduced by about 10% among patients allocated active treatment, but the 95% confidence limits for the difference ranged from about zero to about 20%. Whatever the true effect of treatment on CHD, it would appear to be somewhat less than the difference in risk estimated from the prospective observational studies for a prolonged difference in DBP of the same size. This apparent shortfall may reflect chronic pathophysiological processes in the relationship between DBP and CHD, and/or possible cardiotoxic side-effects of the principal trial treatments.
Antihypertensive Agents↗
Prevention of cardiovascular morbidity and mortality in hypertension: benefits of blood pressure reduction and cholesterol lowering.
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Antihypertensive Agents↗
Effects of prophylactic lidocaine in suspected acute myocardial infarction. An overview of results from the randomized, controlled trials.
The effects of prophylactic lidocaine hydrochloride on early ventricular fibrillation and death in patients with suspected acute myocardial infarction were investigated in an overview of 14 randomized trials. During follow-up intervals of one to four hours in the trials of intramuscular lidocaine infusion (6961 patients) and 24 to 48 hours in the trials of intravenous lidocaine injection (2194 patients), a total of 103 cases of ventricular fibrillation and 137 deaths were recorded. Overall, allocation to lidocaine was associated with a reduction in the odds of ventricular fibrillation of about one third, with a 95% confidence interval that ranged from a 3% to a 56% reduction. There was no evidence of any beneficial effect on early mortality; indeed, the odds of early death were about one third greater among patients allocated lidocaine, though this difference was not statistically significant (95% confidence interval, 2% reduction to 95% increase). Because of the small numbers of reported events, the short follow-up periods, and the unavailability of data for some specific causes of death, even an overview of all the trial results does not provide good evidence as to whether prophylactic lidocaine is likely to be helpful or harmful. To answer this question reliably, future trials will need to involve large numbers of patients and prolonged follow-up.
Clinical Trials as Topic↗
Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomised trials.
About 2000 patients have been randomised in ten trials of intravenous nitroglycerin or nitroprusside in acute myocardial infarction. Taken separately, the individual trials have all been too small to provide a reliable estimate of the effects of treatment on mortality, but collectively they provide strong evidence of benefit. In total there have been 136 nitrate and 193 control deaths, and an appropriate overview of the separate trial results indicated a "typical" reduction of 35% (SD 10) in the odds of death (2p less than 0.001, with 95% confidence limits of about one-sixth to one-half). Both nitroglycerin and nitroprusside reduced mortality, the reduction being non-significantly greater with nitroglycerin than with nitroprusside. The greatest reduction in mortality occurred during the first week or so of follow-up, with a non-significant further reduction after this early period. This suggests that the early benefit is not rapidly lost.
Clinical Trials as Topic↗
Alcohol consumption and the risk of alcohol related cirrhosis in women.
The risks in women of cirrhosis with a likely primary alcohol aetiology were estimated for various levels of alcohol consumption in a case-control study. Data were obtained from 41 women with a first diagnosis of cirrhosis who had no evidence of non-alcohol-related cirrhosis; three matched controls were interviewed for each case. Significant increases in the risk of cirrhosis were detected at levels of consumption between 41 and 60 g daily; above this level a dose-response relation was observed. The risk of cirrhosis did not appear to be influenced by other nutritional factors or history of liver disease or use of hepatotoxic drugs. One per cent of Australian women consume more than 40 g alcohol daily, yet more than 90% of women identified with cirrhosis consumed alcohol at this level. Preventive interventions to reduce alcohol consumption in the small group of women who consume more than 40 g daily have the potential to reduce substantially the incidence of alcohol related cirrhosis.
Adult↗
Obesity and hypertension: epidemiological and clinical issues.
The relationship between obesity and hypertension has been investigated in a large number of cross-sectional population studies and a smaller number of prospective, observational studies. The results indicate that in most populations, blood pressure increases linearly with increasing body weight or body mass index. The relationship is present across all subgroups, although the magnitude of the association appears greater in whites than blacks and greater in younger than older persons. It is estimated that as much as one-third of all hypertension may be attributable to obesity in populations where hypertension and obesity are widely prevalent. Evidence from prospective studies and clinical trials suggests that hypertension in obese patients increases the risk of cardiovascular disease and that drug treatment of hypertension reduces the risk. However, it is uncertain whether the risks associated with hypertension and the benefits of treatment are as great in obese hypertensives as they are in lean hypertensives. The effects of weight reduction on blood pressure have been investigated in a small number of randomized, controlled trials involving a total of about 600 participants. Overall, the results of the trials indicate that weight reduction lowers blood pressure over intervals of up to one year. The magnitude of the blood pressure response appears to be directly proportional to the amount of weight loss achieved. However, the latter is inversely related to the length of follow-up. Adequate maintenance of weight loss remains a major problem for the much-needed, long-term trials of the effects of weight reduction on blood pressure and the cardiovascular complications of hypertension.
Adult↗
Treatment of high blood pressure in overweight patients.
Weight reduction was compared with metoprolol (200 mg daily) in a randomized placebo-controlled trial of first-line treatment of mild hypertension (diastolic blood pressure 90-109 mm Hg) in 56 overweight patients aged under 55 years. After 21 weeks of follow-up the weight-reduction group had lost an average of 7.4 kg. The fall in their systolic pressure of 13 mm Hg was significantly greater than that in the placebo group (7 mm Hg) but not different from that in the metoprolol group (10 mm Hg). Their fall in diastolic pressure (10 mm Hg) was greater than that in both the metoprolol (6 mm Hg) and placebo (3 mm Hg) groups. At the end of the follow-up period, 50% of patients in the weight-reduction group had a diastolic pressure of less than 90 mm Hg. In the weight-reduction group, left ventricular mass decreased by 18% in comparison with placebo; in the metoprolol group left ventricular mass was unchanged. In the weight-reduction group there was a decrease both in total cholesterol and in the ratio of total to HDL-cholesterol; in the metoprolol group there was a decrease in high density lipoprotein(HDL)-cholesterol and an increase in the ratio of total to HDL-cholesterol. In this study, weight reduction produced significant falls in both blood pressure and left ventricular mass but not the adverse effects on plasma lipids commonly associated with antihypertensive drug therapy.
Adult↗
Alcohol consumption and hypertension.
An increased prevalence of hypertension in groups with high alcohol consumption has been recognized for a number of years. More recently, several studies have suggested an independent association between alcohol consumption and blood pressure levels in samples from general populations. Of 30 cross-sectional population studies reviewed, the majority reported small but significant elevations in blood pressure in those consuming three drinks or more per day in comparison with nondrinkers. In 25% of studies, elevations in blood pressure were also reported at lower levels of consumption; in about 40%, the blood pressure of nondrinkers was greater than that of those consuming one to two drinks per day. In two studies, one from the United States and one from Australia, the maximum contribution to the prevalence of hypertension of alcohol consumption greater than two drinks per day was estimated to be 5 to 7%; the contribution in men (11%) was greater than that in women because of their greater alcohol consumption. A prospective association of alcohol consumption with change in blood pressure was observed in five studies. In a small number of experimental studies, short-term falls in blood pressure accompanied alcohol restriction in both normotensive and hypertensive subjects. Uncontrolled observations in heavy drinking populations suggest that the effect on blood pressure of alcohol withdrawal may be lasting. However, firm conclusions about the long-term effects of alcohol restriction, particularly in moderate consumers who represent a large proportion in many populations, must await long-term controlled trials.
Alcohol Drinking↗
Hypertension--time to move on.
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Cardiovascular Diseases↗
Patient preference for ketamine: a case report of multiple anesthesias.
A 17-year-old underwent 17 anesthetic procedures during a period of 40 days with several different general anesthetics and declared the ketamine technic to be the most satisfactory. The authors consider subjective experiences very important in selecting anesthetic agents for patients undergoing multiple anesthesias.
Adolescent↗
Primary and secondary prevention of stroke.
Data from prospective observational studies indicate that usual levels of blood pressure are directly and continuously related to the risk of stroke. a prolonged difference in usual diastolic blood pressure levels of just 5 mmHg would eventually confer about a one-third difference in stroke risk, with similar proportional effects in hypertensives and non-hypertensives. The results of randomised trials of blood pressure lowering drugs in hypertensive patients suggest that much or all of this long-term potential stroke avoidance can be achieved within just a few years of beginning treatment. Overall in 17 randomised trials of antihypertensive treatment, a net blood pressure reduction of 10-12 mmHg systolic and 5-6 mmHg diastolic, conferred a reduction in stroke incidence of 38% SD 4, with similar reductions in fatal and non-fatal stroke. Additionally, the sizes of the reductions were similar in trials in mild, moderate or more severe hypertension, in trials in older or younger patients and in trials in patients with or without a history of cerebrovascular disease. Because the proportional effects of treatment were similar in all these groups, the absolute effects of treatment on stroke varied in direct proportion to the background risk of stroke. The greatest benefits were, therefore, observed among those with a history of cerebrovascular disease, those above the age of 60 years, and those with more severe hypertension.
Adult↗