The effect of withdrawing antihypertensive therapy: a review.
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Antihypertensive Agents↗
Biomedical subjects
J Stamler
Publications and source records attributed to J Stamler.
Blood pressure (systolic and diastolic) and risk of fatal coronary heart disease.
Among the 356,222 men screened for the Multiple Risk Factor Intervention Trial who had no history of hospitalization for heart attack at entry, more than 2,000 coronary deaths occurred during 6 years of follow-up. With this large data set, detailed cross-tabulations clearly and simply showed the strong graded relation between blood pressure and coronary heart disease death. This risk gradient was evident in each of five age groups ranging from 35 to 57 years and for levels of diastolic blood pressure ranging from less than 75 mm Hg to greater than 115 mm Hg. Systolic blood pressure was more strongly associated with coronary heart disease death than was diastolic blood pressure, and isolated systolic blood pressure elevation was found to be an important risk factor in these middle-aged men. The risk of coronary death was increased among hypertensive men who had elevated serum cholesterol levels or who smoked cigarettes. Because less than 10% of hypertensive men had cholesterol levels in the lowest quintile (below 182 mg/dl) and were nonsmokers, a multi-intervention approach for the large majority of hypertensive persons is clearly indicated. Risks of death were also substantially increased among those hypertensive men who already had end-organ damage, emphasizing the importance of early treatment to prevent such damage. These findings have implications for the design of prevention trials and clinical practice, as it is clear that systolic as well as diastolic blood pressure should be considered in treating hypertensive patients. Additionally, treatment goals should be directed at preventing not only death but many other morbid events, clinical and subclinical, that are associated with elevated blood pressure and that are preventable with appropriate treatment.
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↗
Controlling hypertensive disease and its complications among black Americans. Current challenges.
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Age Factors↗
INTERSALT study findings. Public health and medical care implications.
INTERSALT found a significant association between 24-hour urine sodium excretion and systolic blood pressure in individuals. There was also a significant association between sodium and slope (increase) of blood pressure with age across population samples. The weight of evidence from animal-experimental, clinical, intervention, and epidemiological data favors a causal relation. INTERSALT data from 52 centers in 32 countries permit an estimate of effect on average population blood pressure of lower sodium intake. Based on the sodium-blood pressure association in individuals, it was estimated that a habitual population sodium intake that was lower by 100 mmol/day (e.g., 70 vs. 170 mmol/day) would correspond to an average population systolic pressure that was lower by at least 2.2 mm Hg. This size difference in systolic blood pressure in major US and UK population studies is associated with 4% lower risk of coronary death and 6% lower risk of stroke death in middle age. If habitual diet is both lower in sodium and higher in potassium with lower alcohol intake and less obesity, INTERSALT data estimate average population systolic pressure would be lower by 5 mm Hg. This was calculated to correspond to a 9% lower risk of coronary death and a 14% lower risk of stroke death. INTERSALT cross-population data also suggest that, with a 100 mmol/day lower sodium intake over the life span, the average increase in population systolic pressure from age 25 to 55 years would be less by 9 mm Hg, corresponding at age 55 to a 16% lower risk of subsequent coronary death and 23% lower risk of stroke death.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor.
Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets. Bovine aortic endothelial cells were grown on microcarrier beads and pretreated with aspirin before use. Endothelial cells stimulated with bradykinin or exposed to stirred medium expressed a dose-dependent inhibition of platelet aggregation that was potentiated by the reduced thiol, N-acetylcysteine. Endothelial cell-mediated platelet inhibition was attenuated by methylene blue. Inhibition of platelet aggregation by endothelial cells was associated with a rise in platelet intracellular cyclic GMP, an effect that was enhanced by N-acetylcysteine. These data show that 1) the reduced thiol N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor and 2) this effect is associated with increasing intracellular platelet cyclic GMP levels.
Acetylcysteine↗
Towards cardiovascular health.
This paper - in tribute to Martti Karvonen not only as researcher, teacher, organizer, friend, but also as statesman and strategist - focusses on several major contemporary strategic issues central for advancing cardiovascular health. These include: 1. the importance of the North Karelia Project emphasis on mass prevention in the community, for combatting the cardiovascular disease epidemic; 2. the extensive data base for the population-wide strategy for CVD prevention; 3. the important independent contribution of dietary lipid, particularly dietary cholesterol to cardiovascular disease risk; 4. the important role of diet - especially high dietary Na and high dietary Na/K, caloric imbalance with consequent obesity, and heavy alcohol intake - in the causation of the mass occurrence in the population of blood pressure levels above optimal and of frank hypertension; 5. the ability to improve population life styles and patterns of life-style-related risk factors; 6. the relation of improvements in life style and life-style-related risk factors, achieved to date in countries like Finland and the U.S.A., to the declines in cardiovascular disease mortality in these countries.
Blood Pressure↗
The INTERSALT study: main results, conclusions and some implications.
INTERSALT is an epidemiological study of electrolyte excretion and blood pressure in 10,079 men and women from 52 centres and 32 countries. The data were collected according to strict protocol with extensive quality control, and were analysed both in individuals and across centres. In the individual analysis, with adjustment for confounding variables, significant positive associations were observed between blood pressure and twenty-four hour sodium excretion, body mass index and alcohol intake, and significant negative associations between blood pressure and potassium excretion. For a number of reasons, it is likely that the size of these relationships was underestimated. Across centres, linear slope of blood pressure with age was positively related to median sodium excretion. These observations imply that a policy combining changes in sodium and potassium intake with reductions in obesity and alcohol consumption could bring important public health benefits.
Adult↗
Peripartum cardiomyopathy. A role for cardiac stress determinants other than pregnancy?
Peripartum cardiomyopathy is a syndrome of undetermined etiology whose most common initial symptoms are those of congestive heart failure. The syndrome carries a five-year mortality estimated at 40%. Single noxious factors, such as viral infection, have been proposed as direct precipitants of this syndrome, but none have been conclusively linked to it. The cases of two patients with identifiable cardiac stress factors who developed peripartum cardiomyopathy are presented here: one with sepsis complicated by disseminated intravascular coagulopathy and severe anemia, and a second with an otherwise normal pregnancy who engaged in strenuous aerobic exercise throughout the last trimester. A review of previously published cases reveals the frequent association of multiple nonspecific cardiac stress factors that may predispose women to peripartum cardiomyopathy. Various cardiac stress factors may act synergistically with the stress of pregnancy to precipitate peripartum cardiomyopathy in susceptible women.
Adolescent↗
Cardiac status after four years in a trial on nutritional therapy for high blood pressure.
A randomized controlled trial demonstrated the ability of nutritional intervention in place of antihypertensive drugs to maintain blood pressure at normal levels for four years in 39% of less severely hypertensive patients whose blood pressure was previously well controlled by pharmacologic treatment. However, average blood pressures during the trial for patients in the intervention group were higher than those for a comparison group that continued to receive drug therapy throughout the study. Holter monitoring, echocardiography, roentgenography, and electrocardiography done at four years to determine whether blood pressure differences between groups were associated with differences in cardiac status did not indicate any differences in cardiac status favorable to one group compared with the other. Further investigation in larger samples is needed to assess any long-term differences in cardiac status based on such alternate therapies.
Adult↗
Opportunities and pitfalls in international comparisons related to patterns, trends and determinants of CHD mortality.
The experience of recent decades demonstrates the varied and rich opportunities for research in international comparisons of patterns, trends and determinants of CHD mortality. Limitations and pitfalls there are too, of course, as with every scientific method, but these can be anticipated and taken into consideration in a reasonable fashion. Particularly when considered along with the totality of the data from epidemiology and the other investigative methodologies, these data from international comparisons are very valuable in throwing light on the aetiological factors influencing CHD mortality trends in different countries, and therefore in illuminating needs for preventive efforts, both national and international.
Autopsy↗
Factors related to blood pressure in a sample of Italian children age 5 to 14: the Gubbio Population Study.
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Adolescent↗
The INTERSALT study: background, methods and main results. INTERSALT Co-operative Research Group.
The INTERSALT study used standardised methods to assess the relations of electrolyte intake and blood pressure, taking account of confounding variables, in samples of men and women aged 20-59 drawn from defined populations in 52 centres and 32 countries (10,079 individuals). Sodium excretion was significantly related to blood pressure in individuals. Corrected estimates (probably still too low) indicated, on multiple regression, that a difference of 100 mmol/day in average population sodium intake corresponded to 2.2 mmHg lower systolic pressure. Sodium excretion across centres, with median levels ranging from 0.2 to 242 mmol/24 hour, was related to slope of blood pressure with age, less consistently to median centre pressure. Estimates indicated that a 100 mmol/day lower sodium intake was associated with a 9 mmHg lower rise of systolic pressure between ages 25 and 55. Hypertension was virtually absent in four populations with very low sodium intake, and blood pressure in these samples was not higher at older ages. Potassium intake of individuals was negatively and significantly associated with blood pressure independently of other variables; body mass index and high alcohol intake were strongly positively and independently associated with blood pressure in individuals.
Adult↗
Reduced thiols and the effect of intravenous nitroglycerin on platelet aggregation.
Nitroglycerin inhibits platelet aggregation in vitro and this effect may be important in its overall mechanism of action. In addition, its use has been associated with prolonged bleeding times and hemorrhagic complications. Despite these experimental and clinical observations, no significant antiplatelet effect of nitroglycerin has been observed ex vivo during intravenous nitroglycerin administration to patients. Because the in vitro antiplatelet effects of nitroglycerin have been shown by one of the investigators participating in this study to depend on the presence of sufficient stores of reduced intracellular thiol--which are readily depleted ex vivo by nitroglycerin in the formation of S-nitrosothiols--an attempt was made to unmask nitroglycerin-mediated inhibition of platelet aggregation by exposing platelets taken from patients treated with nitroglycerin to the reduced thiol N-acetylcysteine ex vivo. The obtained data demonstrate that platelets taken from patients treated with intravenous nitroglycerin manifest attenuated aggregation responses ex vivo when thiol stores are repleted. It is therefore proposed that the mechanism of action of nitroglycerin is mediated in part by its antiplatelet effect and that this effect depends on the adequacy of reduced intracellular thiol stores.
Acetylcysteine↗
Serum lipid response to a fat-modified, oatmeal-enhanced diet.
The purpose of this study was to confirm and extend previous findings that serum cholesterol response to a fat-modified diet is enhanced by oat fiber. Participants (n = 236) were recruited from the Continental Illinois National Bank in Chicago. Data including weight, serum lipid level, lipoproteins, and 3-day food records were collected at baseline and every 4 weeks for 12 weeks. All participants were instructed to follow the fat-modified (Phase II) diet recommended by the American Heart Association (AHA). After 4 weeks, participants were randomly assigned to one of two groups. While both groups continued to follow the AHA diet, Group 1 was instructed to include 2 oz (56 g, dry wt) of oatmeal, isocalorically substituted for other carbohydrate foods. Group 2 served as the control and consumed no oat products throughout the study. Serum cholesterol values at baseline and after 4 weeks of the AHA diet were similar for both groups (203.9 and 193.0 mg/dl for Group 1 and 205.3 and 194.5 mg/dl for Group 2). After 4 weeks of oatmeal intervention, mean group differences were -6.8 and -2.1 mg/dl (P = 0.008 one-tailed t test) for Groups 1 and 2, respectively. Following an additional 4 weeks of oatmeal intervention, the Group 1 mean cholesterol increased slightly (0.9 mg/dl), while the Group 2 level decreased slightly (-0.7 mg/dl). Overall serum cholesterol responses for the two groups from Visit 2 to Visit 4 were -6.0 and -2.8 mg/dl for Groups 1 and 2, respectively (P = 0.074, one tail). Changes in weight were small and nonsignificant. Subgroup analyses revealed greater reductions in serum cholesterol among participants with the highest baseline serum cholesterol (-8.0 mg/dl vs -1.7 mg/dl for Subgroups 1 and 2, respectively). These data support previous findings that inclusion of oatmeal in a fat-modified diet is helpful in lowering serum cholesterol, particularly for individuals with elevated serum cholesterol levels.
Adult↗
Major and minor electrocardiographic abnormalities and risk of death from coronary heart disease, cardiovascular diseases and all causes in men and women.
The independent contributions of baseline major and minor electrocardiographic (ECG) abnormalities to subsequent 11.5 year risk of death from coronary heart disease, all cardiovascular diseases and all causes were explored among 9,643 white men and 7,990 white women aged 40 to 64 years without definite prior coronary heart disease in the Chicago Heart Association Detection Project in Industry. At baseline, prevalence rates of major ECG abnormalities were higher in women than in men, with age-adjusted rates of 12.9 and 9.6% (p less than 0.01), respectively. Minor ECG abnormalities were more common in men than in women (7.3 versus 4.5%, p less than 0.01). Both major and minor ECG abnormalities were associated with an increased risk of death from coronary heart disease, all cardiovascular diseases and all causes. The strength of these associations was greater in men than in women. When baseline age, diastolic pressure, serum cholesterol, cigarettes smoked per day, diabetes and use of antihypertensive medication were taken into account, major abnormalities continued to be significantly related to each cause of death in both genders with much larger adjusted absolute excess risk and relative risk for men than for women. In multivariate analyses, minor ECG abnormalities contributed independently to risk of death in men, but not clearly so in women. The results indicate the independent association between ECG abnormalities and mortality from coronary heart disease, all cardiovascular diseases and all causes, with greater relative significance in middle-aged United States men than women.
Adult↗
Risk factor modification trials: implications for the elderly.
The scientific foundations for risk factor modification in the elderly are three-fold: (1) data from long-term prospective population studies demonstrating significant independent relationships between established major risk factors--particularly blood pressure (systolic and diastolic), serum cholesterol, cigarette use, clinical diabetes--and risk of cardiovascular (CV) morbidity and mortality; (2) data from population studies on time trends of mass changes in major risk factors and parallel changes in CV mortality rates, including large sustained declines; (3) data from randomized controlled trials (RCTs). RCTs, the focus of this presentation, have been both unifactorial and multifactorial. The former include several trials of antihypertensive drug treatment, and of diet or drugs to lower serum cholesterol. When each of these two sets of unifactorial trials is considered in its totality, the positive nature of the findings is apparent. Among the antihypertensive drug trials, two--the Hypertension Detection and Follow-up Program in the U.S.A. and the study by the European Working Party on High Blood Pressure in the Elderly--involved older men and women, both with significantly favourable outcomes for their intensive treatment groups. Among the several trials on serum cholesterol reduction, the Los Angeles Veterans Administration domiciliary study involved elderly men, and showed significant reductions in incidence and mortality from atherosclerotic events in its fat-modified diet group. Multifactorial trials have involved middle-aged men. Their findings are generally positive, particularly in regard to efficacy of life-style interventions to modify diet and smoking habits. Degree of efficacy is apparently related to degree of net change in risk factors in the intervention group compared to the control group. All these findings lend strong support to the judgment that risk factor modification, in the elderly as well as at younger ages, is useful for the prevention of the major adult CV diseases and for increasing longevity with health.
Adult↗
Education, smoking and non-cardiovascular mortality: findings in three Chicago epidemiological studies.
The interrelationships among education, smoking, and non-cardiovascular (non-CVD) mortality were examined in middle-aged white males from the Chicago Peoples Gas Company Study (PG), the Chicago Western Electric Company Study (WE), and the Chicago Heart Association Detection Project in Industry (CHA). In each study, college graduates had the lowest prevalence of current smokers and the highest prevalence of former smokers. The associations between education and smoking were strongest in CHA, a study with baseline measurements 10-14 years after those of PG and WE and 3-8 years after the US Surgeon General's report on smoking and health in 1964. In PG and WE, the relative risks of non-CVD death for those who did not attend college compared to those who did were 1.50 and 1.38 (95% limits, 1.04 to 2.18 and 0.95 to 2.02). In CHA, the relative risk for those who did not graduate from college compared to those who did was 1.55 (1.17, 2.05). Differences in baseline cigarette smoking could account for only 23-29% of these increased risks. Because the associations between education and non-CVD mortality may have been confounded by changes in smoking status over the course of follow-up in these studies, non-CVD deaths were subdivided into those from causes related to smoking and causes not related to smoking. For smoking-related causes, the relative risk of death for those who did not attend/graduate from college was 1.95 (0.96, 3.95) in WE, 2.13 (1.18, 3.87) in PG, and 2.34 (1.47, 3.84) in CHA, while the relative risks for causes not related to smoking were 1.17, 1.12 and 1.16, respectively. These findings suggest that education is related inversely to non-CVD mortality primarily through smoking and smoking-related causes of death. With smoking becoming increasingly a habit of the less well-educated, these findings underscore the need for smoking prevention and cessation programmes targeted at the lower end of the socioeconomic scale.
Adult↗