Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: results from phase 1 of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group.

Phase 1 of the Trials of Hypertension Prevention was conducted in 2182 adults, aged 35-54 y, with diastolic blood pressure of 80-89 mm Hg to test the feasibility and blood pressure-lowering effects of seven nonpharmacologic interventions (weight loss, sodium reduction, stress management, and supplementation with calcium, magnesium, potassium, and fish oil). At 6 and 18 mo, weight loss and sodium reduction were well-tolerated and produced significant declines in systolic and diastolic blood pressures (-2.9/-2.4 and -2.1/-1.2 mm Hg for weight loss and sodium reduction, respectively, at 18 mo). None of the other interventions lowered blood pressure significantly at either the 6- or 18-mo follow-up visits. These results suggest that both weight loss and sodium reduction provide an effective means to prevent hypertension. The long-term effects of both of these interventions are being tested in phase 2 of the trial.

Combinations of potassium, calcium, and magnesium supplements in hypertension.

Dietary intakes of potassium, calcium, and magnesium have each been reported to lower blood pressure, but the extent of blood pressure reduction in epidemiological studies and clinical trials has tended to be small and inconsistent. We hypothesized that combinations of these mineral supplements would lower blood pressure and that the reductions would be greater than that usually reported in studies of each cation alone. One hundred twenty-five patients 82 men and 43 women) with untreated mild or borderline hypertension were randomly assigned to daily treatment with one of the following four regimens: 60 mmol potassium and 25 mmol (1000 mg) calcium, 60 mmol potassium and 15 mmol (360 mg) magnesium, calcium and magnesium, or placebo. Standardized clinic blood pressure measurements were obtained on 3 days at baseline and after 3 and 6 months of treatment. At baseline, systolic and diastolic blood pressures (mean +/- SD) were 139 +/- 12 and 90 +/- 4 mm Hg, respectively, and dietary intakes of potassium, calcium, and magnesium were 77 +/- 32, 19 +/- 13, and 12 +/- 52 mmol/d, respectively. The mean differences (with 95% confidence intervals) of the changes in systolic and diastolic blood pressures between the treatment and placebo groups were not significant: -0.7 (-4.3 to +2.9) and -0.4 (-2.9 to +2.1) for potassium and calcium, -1.3 (-4.4 to +1.8) and 0.4 (-2.5 to +3.3) for potassium and magnesium, and +2.1 (-1.8 to +6.0) and +2.2 (-1.0 to +5.4) for calcium and magnesium. In conclusion, this trial provides little evidence of an important role of combinations of cation supplements in the treatment of mild or borderline hypertension.

The effect of potassium supplementation in persons with a high-normal blood pressure. Results from phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

We conducted a randomized, double-blind, placebo-controlled trial of oral potassium chloride supplementation (60 mmol/d) in 353 men and women with an initial average diastolic blood pressure between 80 and 89 mm Hg. In the active (n = 178) compared to the placebo (n = 175) treatment group, the urinary potassium level was significantly (p < 0.001) increased by an average of 44.0 and 42.3 mmol/24 h following 3 and 6 months of therapy, respectively. Compared to placebo, active treatment was associated with a small (mean = 1.8 mm Hg) but significant (p = 0.04) reduction in diastolic blood pressure following 3 months of therapy. Following 6 months, however, this apparent treatment effect had virtually disappeared (mean reduction in diastolic blood pressure = 0.3 mm Hg). There was no significant effect of potassium supplementation on systolic blood pressure at either follow-up visit. There was a significant, independent, dose-response relationship between change in both 24-hour urinary potassium excretion and urinary sodium-potassium ratio and the corresponding change in diastolic blood pressure (-1.49 mm Hg for the highest versus the lowest quartile of change in urinary potassium excretion.

Lack of blood pressure effect with calcium and magnesium supplementation in adults with high-normal blood pressure. Results from Phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase I of the Trials of Hypertension Prevention (TOHP) was a randomized, multicenter investigation that included double-blind, placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults (10.5% blacks and 31% women) aged 30 to 54 years with high-normal diastolic blood pressure (DBP) (80 to 89 mm Hg). Very high compliance (94 to 96% by pill counts) with daily doses of 1 g of calcium (carbonate), 360 mg of magnesium (diglycine), or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women. Overall, neither calcium nor magnesium produced significant changes in blood pressure at 3 and 6 months. Analyses stratified by baseline intakes of calcium, magnesium, sodium, or initial blood pressures also showed no effect of supplementation. These analyses suggested that calcium supplementation may have resulted in a DBP decrease in white women and that response modifiers in this subgroup might have included lower initial urinary calcium levels, urinary sodium levels, or lower body mass index. However, overall analyses indicated that calcium and magnesium supplements are unlikely to lower blood pressure in adults with high-normal DBP. The subgroup analyses, useful to formulate hypotheses, raise the possibility of a benefit to white women, which requires testing in future trials.

Short report: the effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the Trials of Hypertension Prevention.

OBJECTIVE: To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol. METHODS: The participants were 350 normotensive men and women aged 30-54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention. They were randomly assigned to receive placebo or 6 g purified fish oil once a day, which supplied 3 g n-3 polyunsaturated fatty acids for 6 months. RESULTS: Baseline blood pressure was (mean +/- SD) 123 +/- 9/81 +/- 5 mmHg. The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant. There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressure in the upper versus the lower quartile (132/87 versus 114/75 mmHg), low habitual fish consumption (0.4 versus 2.9 times a week) or low baseline plasma levels of n-3 fatty acids. Fish oil increased HDL2-cholesterol significantly compared with the placebo group. Subgroup analysis showed this effect to be significant in the women but not in the men. Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure. CONCLUSION: Moderate amounts of fish oil (6 g/day) are unlikely to lower blood pressure in normotensive persons, but may increase HDL2-cholesterol, particularly in women.

The effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group.

OBJECTIVE: To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol. METHODS: The participants were 350 normotensive men and women aged 30-54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention. They were randomly assigned to receive placebo or 6 g purified fish oil once a day, which supplied 3 g n-3 polyunsaturated fatty acids for 6 months. RESULTS: Baseline blood pressure was (mean +/- SD) 123 +/- 9/81 +/- 5 mmHg. The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant. There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressures in the upper versus the lower quartile (132/87 versus 114/75 mmHg), low habitual fish consumption (0.4 versus 2.9 times a week) or low baseline plasma levels of n-3 fatty acids. Fish oil increased HDL2-cholesterol significantly compared with the placebo group. Subgroup analysis showed this effect to be significant in the women but not in the men. Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure. CONCLUSION: Moderate amounts of fish oil (6 g/day) are unlikely to lower blood pressure in normotensive persons, but may increase HDL2-cholesterol, particularly in women.

Baseline characteristics of participants in phase I of the Trials of Hypertension Prevention.

Phase I of the Trials of Hypertension Prevention was designed to test the effectiveness and safety of three life-style (weight loss, sodium restriction, and stress management) and four nutrition supplement (calcium, magnesium, potassium, and fish oil) interventions in reducing diastolic blood pressure (DBP) in persons with a high-normal blood pressure. A total of 2182 persons with a DBP between 80 and 89 mm Hg met the eligibility criteria for participation in phase I and were randomized to one of the active intervention or control treatment groups. Most were white (82%), male (70%), married (76%), nonsmoking (88%), college graduate (53%), full-time employees (91%). The average blood pressure prior to entry into the trial was 124.9 mm Hg systolic and 83.8 mm Hg diastolic. A variety of baseline observations, including sociodemographic characteristics, personal and family medical history, health habits, diet, and biologic measurements, were documented before randomization and compared among the seven active intervention and control groups. As might be expected in a randomized trial of this sample size, the distribution of measured baseline characteristics was virtually identical in the treated and control groups. Based on this finding and the knowledge that randomization procedures were implemented without deviation from the phase I protocol, it is probable that unknown potential confounders were also equally distributed at entry into the study. Given the achievement of high rates of follow-up, subsequent differences in blood pressure are unlikely to have been due to baseline differences between the active treatment and control groups, and can probably be attributed to effects of the active interventions.

Trials of hypertension prevention. Phase I design.

Phase I of the Trials of Hypertension Prevention (TOHP) was a National Heart, Lung, and Blood Institute-sponsored, 3-year, national, multicenter, randomized, controlled trial designed to test the feasibility and efficacy of three life-style (weight loss, sodium restriction, and stress management) and four nutrition supplement (calcium, magnesium, fish oil, and potassium) interventions aimed at lowering diastolic blood pressure in those whose blood pressure was initially in the high normal range (80 to 89 mm Hg). A total of 2182 volunteers were recruited and allocated to the various treatment arms, such that each hypothesis was tested with a power of 85% or higher to detect a diastolic blood pressure treatment effect of 2 mm Hg. The four nutrition supplement interventions were delivered in a double-blinded fashion and the three life-style interventions, single (observed) -blinded. Phase I was designed to provide a rigorous test of short-term lowering of blood pressure for each of the seven treatments chosen and provides the basis for planning of a subsequent long-term trial of hypertension prevention.

Coffee consumption and serum cholesterol in the hypertension detection and follow-up program.

The relation between coffee consumption and serum cholesterol level was investigated in a group of 9,043 hypertensive adults who were in the Hypertension Detection and Follow-up Program. In this study, men and women aged 30-69 years at baseline (1973-1974) had their serum cholesterol level measured at the two-year examination (1975-1976). Information about coffee, tea, and cola consumption was also obtained at that time from a food frequency questionnaire. The relation of coffee consumption and serum cholesterol level with potentially confounding variables including age, race, sex, diuretic status, diastolic blood pressure, cigarette smoking, relative weight, physical activity, stress, and education level was examined. When these variables were entered into a multiple regression equation, a positive association with coffee consumption and serum cholesterol level (p less than 0.05) was present. There was no significant relation between serum cholesterol level and consumption of tea, cola, or decaffeinated coffee--the other major contributors of caffeine to the diet--or total caffeine intake. This study indicates a significant positive relation between coffee consumption and serum cholesterol level.

Relationship of diuretic therapy and serum magnesium levels among participants in the Multiple Risk Factor Intervention Trial.

Thiazide-like diuretics cause an increased excretion of magnesium in the urine. Low serum and selected tissue magnesium levels have been reported among diuretic users. Low magnesium levels have been associated with cardiac arrhythmias, neuromuscular changes, and increases in lipoprotein levels. The dietary intake of magnesium is borderline compared with the recommended dietary allowances. Water sources may therefore play an important role. Hard water contains more magnesium than soft water. The authors studied serum magnesium levels among special intervention Multiple Risk Factor Intervention Trial participants in two centers: Pittsburgh, Pennsylvania and Davis, California. These participants were men aged 35-57 years at entry to the trial in 1972-1974; the blood samples were obtained primarily in 1980-1981. Diuretic users primarily of chlorthalidone had an average 1 ppm lower serum magnesium level than nondiuretic users. About 15% of diuretic users had persistently lower magnesium levels on two samples approximately four months apart. The serum magnesium level was not correlated with the serum potassium level. This study is the first long-term follow-up of a well-defined group of hypertensives taking thiazide-like diuretics versus suitable controls. The results suggest that within similar populations, low serum magnesium levels are relatively rare even in the absence of supplementation with magnesium. Specific high-risk populations may exist in which a combination of diuretic therapy and low intake may contribute to magnesium deficiency. Further epidemiologic studies should include monitoring both serum and intracellular levels of magnesium among these potential high-risk groups on diuretic therapy. This approach may offer the best method of testing the relationship between water hardness, minerals, and cardiovascular disease.