Initial antihypertensive drug therapy--a comparison of alpha-blocker (prazosin) and diuretic (hydrochlorothiazide). Brief summary of a randomized, controlled trial.
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Blood Pressure↗
Biomedical subjects
R Stamler
Publications and source records attributed to R Stamler.
Is Italy losing the "Mediterranean advantage?" Report on the Gubbio population study: cardiovascular risk factors at baseline. Gubbio Collaborative Study Group.
The coronary heart disease mortality rate in Italy--lower than in many other industrialized countries--has changed little in the last 20 years, whereas in the United States, a major decline in deaths resulting from coronary heart disease has occurred. These differing trends have reduced considerably the gap between the two countries in coronary mortality rates. Several recent population studies in Italy have found a change in the previously more favorable risk factor profile. In the northern hill town of Gubbio, studied in 1983-1985, median serum cholesterol level of men ages 40-59 was 223 mg/dl, considerably higher than was found in the 1960 Italian population samples of the Seven Countries Study (197-206 mg/dl). In the earlier study, the cholesterol levels in the Italian men who were still mainly consuming the traditional Mediterranean diet were 30-40 mg/dl lower than in the U.S. sample. The 1980 Gubbio levels, however, were at least as high as those of their U.S. contemporaries. Cigarette smoking was much higher among the middle-aged men of Gubbio than among a similar U.S. population sample (56% vs 36%). Hypertension prevalence was high, and several risk factors for hypertension--obesity, high salt intake, and alcohol--were common in the Gubbio as well as in other recent Italian population studies. The changing coronary risk profile in Italy, which now includes higher population levels of serum cholesterol as well as the other major coronary heart disease risk factors of cigarette smoking and hypertension, threatens to reduce markedly the "Mediterranean advantage" enjoyed by Italy in the past.
Adult↗
The effect of withdrawing antihypertensive therapy: a review.
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Antihypertensive Agents↗
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↗
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↗
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↗
The INTERSALT study: results for 24 hour sodium and potassium, by age and sex. INTERSALT Co-operative Research Group.
The relations by age and sex of urinary sodium, potassium and sodium/potassium ratio to blood pressure were examined in the 5,045 men and 5,034 women of the INTERSALT Study. With adjustment for age, and combining (pooling) regression coefficients over the 52 centres of the study, sodium excretion was positively and significantly related to the blood pressure of individuals in both men and women. These positive and significant relationships were also found in seven of eight age-sex specific analyses. In most analyses, z-scores suggested stronger associations in women than in men: the size of regression coefficients in women was as much as twice that of the corresponding coefficients in men. In age-specific analyses for men and women combined, sodium excretion was positively related to blood pressure, significantly so for systolic pressure at all ages and for diastolic pressure at ages 50-59; regression coefficients tended to be larger at older compared to younger ages. Results for sodium/potassium ratio in individuals were similar to those for sodium, being stronger in women than in men, and (at least for systolic pressure) at older compared to younger ages. With adjustment for confounding variables, potassium excretion was negatively and significantly related to the blood pressure of individuals; again these relationships tended to be more marked at older ages. Across the centres, median sodium excretion was positively and significantly related to the slope of systolic and diastolic blood pressure with age in men, in both the 52 and 48 centre analyses, and with and without adjustment for confounding variables.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Initial antihypertensive drug therapy. Final report of a randomized, controlled trial comparing alpha-blocker and diuretic.
We compared the effect on serum lipids of an alpha-blocker (prazosin) and a diuretic (hydrochlorothiazide) used as initial antihypertensive drug treatment for 102 men and women with less severe hypertension (average entry blood pressure, 148/97 mm Hg, with no major organ system damage). A two-center trial randomized patients to treatment with either prazosin or hydrochlorothiazide; the alternate drug was added if adequate blood pressure control was not achieved with the originally assigned drug, and patients were removed from any drug they were not able to tolerate. After an average of 40 weeks on the assigned drug regimen, a decline was observed in prazosin-treated patients in both serum total cholesterol (-9.3 mg/dl) and serum triglycerides (-33.9 mg/dl). In contrast, an increase in both these lipids was seen in hydrochlorothiazide-treated patients (+5.0 mg/dl for serum total cholesterol and +18.6 mg/dl for serum triglycerides). The net trial differences between the groups were 14.3 mg/dl for total cholesterol and 52.5 mg/dl for triglycerides, in favor of prazosin (p less than 0.001 for both comparisons). These differences in lipids between the two groups persisted into the second year of the trial (p less than 0.05). There were no significant differences between the drug groups in regard to the level of high density lipoprotein cholesterol or its subfractions or low density lipoprotein cholesterol. In patients who required a combination of the two drugs to achieve blood pressure control, the alpha-blocker diminished or eliminated the lipid-raising effects of the diuretic. Both drugs were similar in their ability to control the elevation of diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Sodium, lithium-countertransport and blood pressure control by nutritional intervention in 'mild' hypertension.
Erythrocyte membrane cation transport was measured in 167 adults completing the fourth year of a randomized controlled trial testing the efficacy of nutrition intervention for treatment of 'mild' hypertension. Intervention objectives consisted of weight loss, moderate sodium restriction, and reduction of alcohol intake. The mean sodium-stimulated lithium-countertransport (LCT) for 35 participants able to maintain normotensive blood pressures for 4 years by nutritional means alone was 0.29 mmol/l cells per h compared with 0.38 for the 48 subjects requiring represcription of drugs (P less than 0.01). Weight loss from baseline to year 4 was inversely related to LCT among those who were overweight at baseline (P less than 0.05); reported alcohol intakes were positively related to LCT (P less than 0.05). These findings suggest that blood pressure control by nutrition intervention in 'mild' hypertensives is associated with levels of LCT characteristic of normotension. Higher mean LCT in those requiring represcription of drugs was related to lower serum potassium and higher serum triglyceride levels in this subgroup.
Alcohol Drinking↗
Manual of operations for "INTERSALT", an international cooperative study on the relation of sodium and potassium to blood pressure.
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Adult↗
Nutritional therapy for high blood pressure. Final report of a four-year randomized controlled trial--the Hypertension Control Program.
A four-year trial assessed whether less severe hypertensives could discontinue antihypertensive drug therapy, using nutritional means to control blood pressure. Randomization was to three groups: group 1--discontinue drug therapy and reduce overweight, excess salt, and alcohol; group 2--discontinue drug therapy, with no nutritional program; or group 3--continue drug therapy, with no nutritional program. In groups 1 and 2 patients resumed drug therapy if pressure rose to hypertensive levels. Loss of at least 4.5 kg (10 + lb) was maintained by 30% of group 1, with a group mean loss of 1.8 kg (4 lb); sodium intake fell 36% and modest alcohol intake reduction was reported. At four years, 39% in group 1 remained normotensive without drug therapy, compared with 5% in group 2. Study findings demonstrated that nutritional therapy may substitute for drugs in a sizable proportion of hypertensives or, if drugs are still needed, can lessen some unwanted biochemical effects of drug treatment.
Adult↗
The role of relative weight in the positive association between age and serum cholesterol in men and women.
With advancing age from youth on, there is an increase in mean serum cholesterol level of populations in "western" industrialized countries. Since serum cholesterol is one of the established major risk factors for premature coronary heart disease, it is important to explore the degree to which this age trend is physiologic or due to modern life styles. This study used cross-sectional data for 19,730 white men and 13,872 white women from the Chicago Heart Association Detection Project in Industry to investigate one aspect of this question: does weight explain the association between age and serum cholesterol, in particular whether older age is associated with higher serum cholesterol in the absence of overweight. The relationships among age, relative weight, and serum cholesterol were examined through assessment of mean serum cholesterol levels in 25 subgroups stratified by age (18-24, 25-34, 35-44, 45-54, 55-64) and by relative weight (less than 100, 100-109, 110-119, 120-134, greater than or equal to 135). Age and serum cholesterol were positively associated with each other. In women, it was a simple, linear relationship. In men, the degree of this positive association was less in people over age 35-44 than people in younger ages. These age-cholesterol patterns were present in men and women at desirable weight. However, in men aged 18-54, the positive association between age and prevalence of marked hypercholesterolemia (serum cholesterol greater than or equal to 250) was lower in people at desirable relative weight in comparison to those at higher relative weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Cardiovascular responses to exercise of participants in a trial on the primary prevention of hypertension.
The Chicago study on the Primary Prevention of Hypertension (PPH) is a long-term, randomized controlled trial to test the ability of nutritional-hygienic non-pharmacological methods to prevent high blood pressure in hypertension-prone persons aged 30-44 years at entry. In order to assess the effects of this programme on cardiovascular responses to exercise, graded submaximal treadmill exercise tests were done serially at baseline and during the trial. Eighty-five participants (48 intervention, 37 control) successfully finished baseline and 2- or 3-year follow-up tests. The exercise maximal double product (DP) [systolic blood pressure (SBP) X heart rate/100] was significantly lower for both groups at 2-3 years compared with baseline, and this reduction was greater for the intervention than for the control group (-27.1 versus -15.5; P = 0.055). Similarly, improvement in maximal increase in DP (maximal DP minus standing DP) was greater for the intervention than the control group (-22.1 versus -9.9, respectively; P = 0.068). The lowest DP during the 6-min recovery period and the debt DP (lowest recovery DP minus standing DP) fell significantly at 2-3 years compared with baseline in the intervention but not in the control group (-12.7 versus -4.8; P = 0.017 for the first index, and -7.7 versus +0.9; P = 0.029 for the second). These interim data from this trial indicate that its intervention procedures favourably influenced cardiovascular responses to graded submaximal exercise.
Adult↗
Do hypertensive patients have a different diurnal pattern of electrolyte excretion?
Studies generally indicate that excretion of sodium, potassium, and water is greater during the day than during the night. To determine whether hypertensive patients exhibit this same pattern of excretion, diurnal variations in excretion of sodium, potassium, creatinine, and water were examined in 107 hypertensive men and women from a clinical trial on control of hypertension by nonpharmacological means--the Hypertension Control Program. Each participant provided two carefully timed 24-hour urine collections divided into daytime and overnight specimens. The median ratios of 24-hour to 8-hour overnight excretion were 2.84, 3.95, 2.99, and 2.77 for sodium, potassium, creatinine, and water, respectively. Thus, more than half of this hypertensive group exhibited a greater rate of sodium and water excretion during sleep than during daytime hours, a reversal of the usual pattern. When the group was subdivided based on age, sex, race, trial randomization group, use of diuretics, and hypertension severity, women had significantly lower ratios of 24-hour to overnight excretion for sodium and water than men and blacks had significantly lower 24-hour to overnight ratios for water and potassium than whites. When the 24-hour to overnight ratios for these hypertensive patients were compared with those for a group of 30 men and women with high-normal blood pressure, those with high-normal blood pressure had significantly larger ratios for sodium and water excretion than the hypertensive group. The results of this study suggest that hypertensive patients may have a different diurnal pattern of sodium and water excretion than normotensive subjects and that further research is needed to clarify this issue.
Adult↗
Epidemiological studies of sodium transport and hypertension.
Red blood cell membrane cation transport was measured in five population-based surveys and two randomized, controlled, dietary intervention studies to examine its associations with demographic, biological, and dietary variables in free-living individuals. A total of 508 individuals, 255 with high blood pressure, were studied. Both sexes, blacks and whites, and several age groups were represented. The intervention studies included short-term dietary sodium restriction in normotensive adolescents, and a 4-year multifactorial trial on weight, sodium, and alcohol in hypertensive adults. The findings from these surveys and intervention studies are summarized in this report. Sodium-stimulated lithium countertransport was significantly related to diastolic blood pressure in white adults (r = 0.28, p less than 0.001), and to systolic blood pressure in black children (r = 0.50, p less than 0.005) and white adolescents (r = 0.31, p less than 0.05). Lithium countertransport was related to sex and race, but not age. Body mass index had an independent relationship with lithium countertransport in some age groups. Lithium countertransport was lower in normotensive adults than in both younger and older hypertensive adults. Lithium countertransport did not differ significantly between subjects with hypertension treated with antihypertensive medications and those with untreated hypertension. Short-term dietary sodium restriction did not influence lithium countertransport in normotensive adolescents. Long-term dietary intervention was associated with low lithium countertransport in hypertensive adults able to maintain blood pressure control without medication. These findings indicate that lithium countertransport is related to blood pressure and hypertension among free-living individuals.
Adolescent↗
Initial antihypertensive drug therapy: alpha blocker or diuretic. Interim report of a randomized, controlled trial.
A two-center, randomized, controlled trial designed to evaluate and compare an alpha blocker and a diuretic as initial antihypertensive drug treatment is currently in progress. Approximately 100 men and women, aged 30 to 69 years, are being randomly assigned to treatment with either of these two agents. If diastolic blood pressure is not reduced to its target level and is 85 mm Hg or higher, the alternate agent is added. The alternate agent is substituted if a patient does not tolerate the assigned agent. This preliminary report presents data concerning 62 patients who completed at least three of the planned 12 months of drug treatment. At that point, the alpha blocker prazosin and the diuretic hydrochlorothiazide were similar in their ability to lower the average diastolic blood pressure to normal levels. Serum total cholesterol and triglyceride levels declined in prazosin-treated patients but increased in hydrochlorothiazide-treated patients, a difference that was statistically significant. No significant weight change, a possible confounding variable, occurred in either group. More patients were unable to tolerate prazosin than were unable to tolerate hydrochlorothiazide (10 of 30 receiving prazosin, compared with three of 32 receiving hydrochlorothiazide). For those able to continue with prazosin, the favorable lipid response appears to be an asset in regard to reducing possible atherogenic effects of treatment.
Adrenergic alpha-Antagonists↗
Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease mortality in men and women.
This epidemiologic study explored the sex differential in risk of death from coronary heart disease in persons with or without clinically diagnosed diabetes or asymptomatic hyperglycemia. Use was made of 9-year follow-up data from the Chicago Heart Association Detection Project in Industry for 11,220 white men and 8,030 white women aged 35-64 years at entry to the Project (November 1967-January 1973). Both clinically diagnosed diabetes and asymptomatic hyperglycemia were associated with an increased risk of death from coronary heart disease. The extent of this association was greater in women than in men in regard to relative risk. However, absolute excess risk for both diabetics and those with asymptomatic hyperglycemia was larger for men than for women. Clinical diabetes appeared to be an independent risk factor for coronary heart disease in both men and women based on multivariate Cox regression analyses. On the other hand, for men, no significant independent effect of asymptomatic hyperglycemia was apparent. Women with asymptomatic hyperglycemia had significantly higher coronary heart disease death rates than normoglycemic women, with adjustment for major coronary heart disease risk factors; in multivariate analyses, the relationship of asymptomatic hyperglycemia to risk of coronary heart disease was of borderline significance (p = 0.054). This study indicates the independent associations of diabetes and possibly asymptomatic hyperglycemia with coronary heart disease mortality, with greater relative significance in women than in men.
Adult↗
The role of weight in the positive association between age and blood pressure.
This study used cross-sectional data for 19,704 white men and 13,895 white women from the Chicago Heart Association Detection Project in Industry (November 1967 to January 1973) to investigate whether weight explains the association between age and blood pressure, and in particular, whether age is associated with blood pressure and hypertension in the absence of overweight. The relations among age, relative weight, and blood pressure were examined through assessment of mean blood pressure levels and prevalence of hypertension in 25 subgroups stratified by age (18-24, 25-34, 35-44, 45-54, and 55-64 years) and by relative weight (less than 100%, 100-109%, 110-119%, 120-134%, and greater than or equal to 135%). For all five relative weight groups, for both men and women, mean diastolic blood pressure was higher at successive ages. This phenomenon was also seen for systolic blood pressure after ages 35-44 years for men, and after ages 25-34 years for women. On the other hand, the higher the relative weight was, the higher the blood pressure was. Regression analysis demonstrated that the observed relation between age and blood pressure was consistent for all five relative weight groups, including those at desirable weight. These data indicate that for US subjects, age and blood pressure are generally associated in the absence of overweight.
Adolescent↗