Caffeine, blood pressure, and serum lipids.

To study the effects of caffeine on serum lipids and blood pressure, we conducted a double-blind, randomized trial with two parallel groups in 69 young, healthy subjects. After a 3-wk run-in period, subjects were randomly assigned to one of two groups receiving either 4-6 140-mL cups filtered decaffeinated coffee per day and an equal number of pills containing 75 mg caffeine or 4-6 140-mL cups filtered decaffeinated coffee per day and an equal number of placebo pills, for 9 wk. In both groups caffeine intake from other sources was not allowed. The main finding of this study is that abstinence from caffeine for a period of 9 wk has no effect on either serum lipids or blood pressure.

Coffee, caffeine and hemostasis: results from two randomized studies.

The influence of coffee and caffeine consumption on hemostatic factors was studied in 2 randomized trials. Both studies were conducted in young, healthy adults. In the first study, 107 participants were randomly allocated to one or 3 intervention groups, drinking filtered coffee, boiled coffee or no coffee at all, respectively, for a period of 9 weeks. In the second study, 69 subjects received either 4-6 tablets containing 75 mg caffeine or the same amount of placebo tablets, while using decaffeinated coffee. In this double-blind study caffeine intake from any other source was not allowed. Blood samples for hemostatic factors were obtained at baseline and after 9 weeks of intervention. The findings indicate no effect of coffee consumption on fibrinogen, clotting factor VII activity, factor VIII antigen, protein C and protein S and also no effect of caffeine consumption on fibrinogen and factor VII activity.

The effect of hormone replacement therapy on serum homocysteine levels in perimenopausal women: a randomized controlled trial.

Serum homocysteine levels may be lowered by hormone replacement therapy, but randomized controlled trial data are scarce. We performed a single center randomized placebo-controlled trial to assess the 6 months effect of hormone replacement therapy compared with placebo on fasting serum homocysteine levels in 121 perimenopausal women free of cardiovascular disease, and recruited from the general population. The trial was double-blind with respect to a sequential combined regimen of oral 17 beta-estradiol and desogestrel (17 beta E(2)-D) and the placebo group and open with respect to a combination of conjugated equine estrogens and norgestrel (CEE-N). At baseline and after 6 months, fasting serum homocysteine levels were measured. Differences in 6 months serum homocysteine levels from baseline between treatment and placebo groups were calculated, and expressed as a percentage of the 6 months placebo level. After 6 months, the difference in serum homocysteine levels between women receiving 17 beta E(2)-D and placebo was -6.3% (95% CI, -12.4%; 0.0%, P=0.06). The difference between women receiving CEE-N and placebo was -10.1% (95% CI, -16.7%; -2.9%, P<0.01). The difference between the combined group of both types of hormone replacement therapy users and placebo was -7.8% (95% CI, -13.2%; -2.0%, P=0.01). No significant difference was observed between the two active regimens. Our results indicate that hormone replacement therapy decreases homocysteine levels in perimenopausal women.

Hormone replacement therapy and endothelial function. Results of a randomized controlled trial in healthy postmenopausal women.

OBJECTIVE: To compare the effects of 3 months treatment with tibolone (a single entity synthetic steroid hormone with estrogenic, progestanic and androgenic activities), or continuous combined conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA), with placebo, on endothelial function. DESIGN: A single center, randomized, double-blind, placebo-controlled study. SETTING: Research center as part of the University Medical Center Utrecht. SUBJECTS: One hundred and five healthy postmenopausal women, sampled from the general population. INTERVENTIONS: Three months treatment with tibolone or CEE+MPA or placebo. MAIN OUTCOME MEASURE: At baseline and after 3 months, endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. RESULTS: Results are presented as mean differences between treatment groups of endothelium dependent flow mediated dilatation (fmd) and endothelium independent nitroglycerine induced dilatation with 95% confidence intervals (95% CI). After treatment, there was a significant difference in mean fmd between the CEE+MPA group and the placebo group of 2.5% (95% CI: 0.3-4.6) while the tibolone group and the placebo group did not differ significantly (0.6%; 95% CI: 1.6-2.8). Nitroglycerine induced dilatation did not differ significantly between the groups. CONCLUSIONS: Hormone replacement therapy with CEE+MPA for 3 months increases endothelium dependent fmd of the brachial artery in healthy postmenopausal women. Tibolone did not alter fmd. The clinical significance of this improvement in fmd for cardiovascular disease risk needs to be established.

Lipoprotein (a) is associated with endothelial function in healthy postmenopausal women.

BACKGROUND: Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. The atherogenic potential of Lp(a) may be by impairment of endothelial function. Objectives. We investigated the relation of Lp(a) plasma levels to endothelium dependent and independent dilatation of the brachial artery in healthy postmenopausal women. METHODS: One hundred and five healthy postmenopausal women aged 52-67 years were included in the study. Endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. RESULTS: Flow mediated dilatation was inversely related to the plasma logLp(a) level. Mean change per unit logLp(a) increase:-2.83% (95% CI: -5.22--0.43). Elevated Lp(a) (>239 mg/l) (upper quartile) was associated with an impaired flow mediated vasodilatation (2.4%+/-1. 2) compared to Lp(a) < or =239 mg/l (5.2%+/-0.7). Adjustment for other cardiovascular risk factors did not change the magnitude of the association. Nitroglycerine-induced vasodilatation was not significantly lower in the high Lp(a) level group, compared to the group with normal levels of Lp(a) (< or =239 mg/l) (8.0+/-1.2 vs. 11.4%+/-0.8). CONCLUSION: Elevated lipoprotein (a) levels are associated with an impaired endothelial function in healthy postmenopausal women, independent of conventional risk factors for cardiovascular disease. Since Lp(a) may be pathogenetically important for early vascular damage, elevated Lp(a) levels might contribute to the increased cardiovascular risk seen in postmenopausal women.

The effect of hormone replacement therapy on arterial distensibility and compliance in perimenopausal women: a 2-year randomised trial.

A single centre randomised placebo-controlled trial was performed to assess the 2-year effects of hormone replacement therapy compared to placebo on mechanical arterial properties in 99 perimenopausal women recruited from the general population. The trial was double-blind with respect to a sequential combined regimen of oral 17beta-oestradiol and desogestrel (17betaE(2)-D) and the placebo group and open with respect to combination of conjugated equine oestrogens and norgestrel (CEE-N). At baseline, distensibility and compliance of the common carotid artery were measured non-invasively with B-mode ultrasound and a vessel wall movement detector system, and the distensibility coefficient (DC) and compliance coefficient (CC) were calculated. Measurements were repeated after 6 and 24 months. Change in DC and CC in treatment groups was compared to placebo. After 24 months, changes for 17betaE(2)-D compared to placebo were -1.4x10(-3)/kPa (95% CI -4.4; 1.7, P=0.39) for DC and 0. 26 mm(2)/kPa (95% CI -0.01; 0.53, P=0.07) for CC. Changes for CEE-N compared to placebo were 0.4x10(-3)/kPa (95% CI -1.0; 1.9, P=0.79) and 0.11 mm(2)/kPa (95% CI -0.14; 0.37, P=0.40). For systolic blood pressure (SBP), diastolic blood pressure (DBP) and arterial lumen diameter no changes were found. In this study no significant differences in changes in distensibility and compliance were found between perimenopausal women using 17betaE(2)-D or CEE-N and women using placebo after 6 and 24 months.

Effects of nitrendipine and enalapril on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension.

OBJECTIVE: To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension. DESIGN: A double-blind randomized, placebo-controlled trial. SETTING: General practitioners referred patients to the trial physician. PATIENTS: The study population comprised 121 patients with non-insulin-dependent diabetes mellitus. Inclusion criteria for blood pressure were diastolic blood pressure 90-115 mmHg and systolic blood pressure < or = 200 mmHg, while subjects were not being administered blood-pressure-lowering drugs for 3 weeks. INTERVENTION: Patients were randomly allocated to receive nitrendipine (n = 40), enalapril (n = 40) or placebo (n = 41). The treatment period was 48 weeks. MAIN OUTCOME MEASURES: The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment. The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly. Left ventricular mass was measured by M-mode echocardiography. RESULTS: Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures. During 48 weeks left ventricular mass index decreased by 5% for patients in the nitrendipine group (decrease by 12 g/m2, 95% confidence interval 1-23), remained about the same for patients in the enalapril group (decrease by 1 g/m2, 95% confidence interval decrease by 10 to increase by 9) and increased by 9% for patients in the placebo group (increase by 9 g/m2, 95% confidence interval 2-16). CONCLUSION: These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index. Enalapril appears not to induce regression, but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo.

Rationale, design, and baseline characteristics of a trial of prevention of cardiovascular and renal disease with fosinopril and pravastatin in nonhypertensive, nonhypercholesterolemic subjects with microalbuminuria (the Prevention of REnal and Vascular ENdstage Disease Intervention Trial [PREVEND IT]).

This study describes the rationale, design, and baseline characteristics of a trial to determine whether treatment with fosinopril 20 mg/day and/or pravastatin 40 mg/ day will prevent cardiovascular and renal disease in nonhypertensive (RR <160/100 mm Hg and not using antihypertensive medication) and nonhypercholesterolemic (total cholesterol <8.0 or <5.0 mmol/L in case of previous myocardial infarction and not using lipid lowering medication) men and women with persistent microalbuminuria (urinary albumin excretion >10 mg/L once in an early morning spot urine and 15 to 300 mg/24-hour at least once in two 24-hour urine collections). The Prevention of REnal and Vascular ENdstage Disease Intervention Trial is a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design. The 864 randomized subjects will be monitored for a minimum of 4 years and a maximum of 5 years. The primary efficacy parameter is defined as the combined incidence of all-cause mortality or hospital admission for documented (1) nonfatal myocardial infarction, (2) myocardial ischemia, (3) heart failure, (4) peripheral vascular disease, (5) cerebrovascular accident and/or (6) end-stage renal disease.

Efficiency optimization of the selection period in therapeutic trials.

To determine eligibility for a (randomized) clinical trial, measuring the inclusion and exclusion criteria can be extended over a period of time. During this period, known as the selection period, a patient is repeatedly examined at certain time intervals. This study describes an approach for optimizing the efficiency of the selection period. Efficiency is defined as the costs of randomizing one patient. The objective is to construct prediction models based on data obtained early in the selection period to predict subsequent exclusions. A prediction model increases the efficiency if after its application the costs per randomization are lower. The approach is illustrated using data from the selection period of the Rotterdam Cardiovascular Risk Intervention (ROCARI) trial which was composed of five consecutive patient visits. At each visit, data to determine eligibility was obtained. We found that logistic regression models based on data of the first and second visit could predict exclusions during the third visit. Application of the prediction models suggested that in this particular trial the costs per randomization would decrease by $52. As the initial costs per randomization were $1444, there would be a 3.6% (52/1444) savings in recruitment costs under the prediction models, accounting for a savings of more than $450,000. We conclude that the use of data obtained early in a selection period can predict subsequent exclusions, and therefore could increase the efficiency of such a period. The approach could be applied to data obtained in a pilot study as well as data obtained in the beginning of a prolonged intake period.

A randomized study on coffee and blood pressure.

The effects of coffee on blood pressure and heart-rate and the mediating effect of two common brewing methods, were studied in a randomized trial in 107 young, normotensive adults. After a three-week run-in period, subjects were randomly assigned to one of three groups, receiving either (1) 4-6 cups filtered coffee per day, (2) 4-6 cups boiled coffee per day, or (3) no coffee at all for a period of nine weeks. Because all participants consumed filtered coffee before the trial, the group continuing on filtered coffee was considered as the reference group. Both systolic (SBP) and diastolic blood pressure (DBP) decreased in the abstinence group. Compared to the filter group, only the fall in SBP after 9 weeks was statistically significant, -6.1 mmHg (95% confidence limits -10.8, -1.4). After adjustment for SBP at baseline and body weight change during the study, the observed reduction decreased, to -3.4 mmHg (-7.1, 0.3). The patterns for SBP and DBP were remarkably similar in the groups using either filtered coffee or boiled coffee. After 9 weeks of boiled coffee, mean changes from baseline for SBP and DBP were 0.4 mmHg (-3.7, 4.5) and -0.1 mmHg (-3.4, 3.2), compared to the filter group. The heart rate showed a slight, non-significant decrease in the abstinence group. In conclusion, these findings suggest that abstinence from coffee for a period of several weeks may slightly reduce blood pressure in young normotensive subjects.

Long-term moderate sodium restriction does not adversely affect the serum HDL/total cholesterol ratio.

We examined the effect of long-term moderate sodium restriction on the HDL/total cholesterol ratio within a randomised trial of the effect of mineral salt on blood pressure (BP). Eighty nine untreated hypertensive men and women aged 55-75 years were included in the analysis. During 24 weeks, 46 subjects used a low sodium, high potassium, high magnesium salt and 43 controls used common salt. Serum cholesterol levels were measured at baseline and at the end of the trial. After 24 weeks, 24 h urinary sodium was decreased by 41 mmol (95% Cl 23-60 mmol, P < 0.0001) in the mineral salt group compared with the controls. Serum total cholesterol was decreased in both groups, but 0.45 mmol/l (95% Cl 0.12-0.78, P = 0.01) more in the controls than in the mineral salt group after adjustment for age, sex and changes in body weight, serum total protein and potassium excretion. Serum HDL-cholesterol was decreased by 0.07 mmol/l in the controls and increased by 0.06 mmol/l in the mineral salt group, yielding a difference of 0.14 mmol/l (95% Cl 0.05-0.22 mmol/l, P = 0.003). The change in HDL/total cholesterol ratio was more favourable in the mineral salt group than in the controls (0.014 and 0.004 units, respectively, P = 0.014). We conclude that long-term moderate sodium restriction does not adversely affect the serum HDL/total cholesterol ratio and is a safe dietary measure for lowering BP.

Effect of hormone replacement therapy on lipids in perimenopausal and early postmenopausal women.

OBJECTIVE: To determine the effects of oral sequential hormone replacement therapy (HRT) on lipid-profile in perimenopausal and early postmenopausal women. METHODS: We performed a single-center, randomized, placebo-controlled trial. The trial was double blind with respect to 17beta-estradiol/desogestrel (17beta-E-D) and placebo and open with respect to conjugated estrogens/norgestrel (CEE-N). A total of 125 healthy perimenopausal and early postmenopausal women, aged 43-58 years, were recruited from the general population in Zoetermeer, the Netherlands. The intervention consisted of 6 months treatment with 1.5 mg 17beta-estradiol/0.15 mg desogestrel (n=53), 0.625 mg conjugated estrogens/0.15 mg norgestrel (n=36) or placebo (n=36). At baseline, cycle 1, 3 and 6, overnight fasting blood samples were obtained in which lipids were determined. We used linear regression analysis to calculate differences in mean change from baseline in lipids in the active treatment groups compared to placebo. RESULTS: In both treatment groups significant (P<0.05) falls in low-density-lipoprotein (LDL)-cholesterol (17beta-E-D: -7.8% and CEE-N: -8.4%) and lipoprotein(a) (17beta-E-D: -11.7% and CEE-N: -28.3%) were found compared to placebo. Apolipoprotein A1 (17beta-E-D: 6.8% and CEE-N: 7.3%) and HDL-cholesterol (17beta-E-D: 6.4% and CEE-N: 8.0%) significantly increased compared to placebo. No significant changes were found in the other lipids. Mean changes from baseline in total cholesterol, LDL-cholesterol and apolipoprotein B were significantly more pronounced in postmenopausal women compared to perimenopausal women, adjustment for age-differences did not change the results. CONCLUSION: Treatment of perimenopausal and early postmenopausal women with 17beta-E-D or CEE-N changes their lipid-profile in a potentially anti-atherogenic direction. Changes appear to be more pronounced in postmenopausal women compared to perimenopausal women.

Hormone replacement therapy in perimenopausal women and 2-year change of carotid intima-media thickness.

OBJECTIVES: To assess the 2-year effects of a combined regimen of oral 17beta-estradiol and desogestrel (17betaE-D) and a sequential combination of conjugated equine estrogens and norgestrel (CEE-N) on common carotid intima-media thickness and end-diastolic lumen diameter in comparison to placebo in perimenopausal women. METHODS: The study was a single center, randomized, group-comparative, double-blind study with respect to the 17betaE-D and placebo groups and open with respect to CEE-N. After cycle 6, the blind was broken and the trial was continued as an open trial for another 18 months for the active study arms. The study included 121 perimenopausal women recruited from the general population. Common carotid intima-media thickness and end-diastolic lumen diameter were measured at baseline and cycle 24 with B-mode ultrasonography. RESULTS: At cycle 24 small changes in intima-media thickness and lumen diameter were observed. Relative to placebo, changes in intima-media thickness were -0.009 mm [95% CI -0.045; 0.027] for 17betaE-D and -0.016 mm [95% CI -0.055; 0.024] for CEE-N. For end-diastolic lumen diameter the changes were -0.091 mm [95% CI -0.236; 0.055] and -0.125 mm [95% CI -0.820; 0.032] for 17betaE-D and CEE-N, respectively. CONCLUSIONS: In this study among perimenopausal women a significant effect of 17betaE-D and CEE-N on common carotid intima-media thickness and lumen diameter could not be demonstrated. Although the sample size of the present trial is too limited to provide definite conclusions, the direction of the effect is in agreement with evidence from earlier studies on the effects of hormone replacement therapy in postmenopausal women.

Coffee, caffeine and hemostasis: a review.

The effects of coffee and caffeine on haemostatic variables are reviewed. The potential relationship between coffee and cardiovascular disease warrants the study of possible links between coffee and haemostasis. The presently available evidence in favour or against such an association, however, is not very convincing and sometimes even conflicting. The findings on fibrinogen level and platelet in vivo activation as measured by plasma beta-thromboglobulin, seem to be the most reliable. If anything, these reports indicate an unfavourable effect of coffee, i.e. coffee may enhance thrombotic tendencies. Before more definite conclusions on the interference of coffee use with the haemostatic system can be made, more data are needed. In particular, randomized studies of coffee and caffeine intake in humans are indicated to assess the impact and the potential significance of coffee in such quantities as are commonly used by millions of people.

Reduction in blood pressure with a low sodium, high potassium, high magnesium salt in older subjects with mild to moderate hypertension.

OBJECTIVE: To examine the effect of a reduced sodium and increased potassium and magnesium intake on blood pressure. DESIGN: Randomised double blind placebo controlled trial. SETTING: General population of a suburb of Rotterdam. SUBJECTS: 100 men and women between 55 and 75 years of age with untreated mild to moderate hypertension. INTERVENTIONS: During 24 weeks the intervention group received a mineral salt (sodium: potassium: magnesium 8:6:1) and foods prepared with the mineral salt. Controls received common salt and foods. MAIN OUTCOME MEASURE: Change in blood pressure. RESULTS: Complete follow up was achieved for 97 of the 100 randomised subjects. Systolic blood pressure (mean of measurements at weeks 8, 16, and 24) fell by 7.6 mm Hg (95% confidence interval 4.0 to 11.2) and diastolic blood pressure by 3.3 mm Hg (0.8 to 5.8) in the mineral salt group compared with the controls, with a 28% decrease in urinary sodium excretion and a 22% increase in urinary potassium excretion. Twenty five weeks after the study the difference in blood pressure between the groups was no longer detectable. CONCLUSION: Replacing common sodium salt by a low sodium, high potassium, high magnesium mineral salt could offer a valuable non-pharmacological approach to lowering blood pressure in older people with mild to moderate hypertension.

[Antithrombotic treatment following acute ischemic heart disease: acetylsalicylic acid and (or) oral anticoagulants?; ASPECT-II, a new study]. / Antitrombotische behandeling na een acute ischemische hartziekte: acetylsalicylzuur en (of) orale anticoagulantia?; ASPECT-II, een nieuw onderzoek.

In order to compare the efficacy and safety of three regimens of long-term antithrombotic treatment in patients with acute ischaemic syndromes, a prospective, randomized, open-label, multicentre study is being conducted in which 60-70 Dutch hospitals will participate. Eligible patients discharged following hospitalization for acute myocardial infarction or unstable angina pectoris are randomly assigned to receive either (a) adjusted full intensity oral anticoagulation (target range: 3.0-4.0 International Normalised Ratio (INR), (b) low dose aspirin or (c) combined therapy of low dose aspirin and adjusted low intensity oral anticoagulation (target range INR: 2.0-2.5). It is planned to enroll 8,700 patients within three years. During an estimated mean follow-up of 2.5 years the evolutions of total mortality, non-fatal myocardial infarction, non-fatal stroke and major bleeding complication will be assessed.

Abstinence from coffee leads to a fall in blood pressure.

The long-term effects of coffee use on blood pressure and the effects of two common brewing methods were studied for 12 weeks in 107 young normotensives. The subjects were randomly assigned to one of three groups, receiving either (1) 4-6 cups of filtered coffee per day, (2) 4-6 cups of boiled coffee per day, or (3) no coffee for a period of 9 weeks. During the 9 weeks of abstinence, systolic and diastolic blood pressure decreased. The fall in systolic blood pressure amounted to 4.9 mmHg, compared with the filter group (P = 0.02). There was no difference with either brewing method. Our findings suggest that abstinence from coffee may reduce blood pressure in young normotensive subjects.

The effect on serum cholesterol levels of coffee brewed by filtering or boiling.

Previous reports have indicated that coffee consumption may increase serum cholesterol levels. We studied the effects of coffee prepared by two common brewing methods (filtering and boiling) on serum lipid levels in a 12-week randomized trial involving 107 young adult subjects with normal serum cholesterol levels. After a three-week run-in period during which they all consumed filtered coffee, the participants were randomly assigned to one of three groups receiving four to six cups of boiled coffee a day, four to six cups of filtered coffee a day, or no coffee, for a period of nine weeks. As compared with the change from base line in the filtered-coffee group, the serum total cholesterol level increased after the consumption of boiled coffee by 0.48 mmol per liter (95 percent confidence limits, 0.13 and 0.83), and the low-density lipoprotein cholesterol level increased by 0.39 mmol per liter (95 percent confidence limits, -0.04 and 0.82). There was no significant difference in the change in serum total or low-density lipoprotein cholesterol levels between the filtered-coffee group and the group that drank no coffee. The levels of high-density lipoprotein cholesterol and apolipoproteins were not affected by boiled or filtered coffee. We conclude that drinking filtered coffee does not affect serum lipid levels. The consumption of boiled coffee, however, has an effect on serum cholesterol levels amounting to a mean net increase of 10 percent of the base-line level after nine weeks.

Diet and pravastatin in moderate hypercholesterolaemia: a randomized trial in 215 middle-aged men free from cardiovascular disease.

OBJECTIVE: To evaluate the effect of diet and drug intervention separately and combined in the treatment of primary hypercholesterolemia. DESIGN: The study was conducted as a randomized, placebo-controlled factorial trial, double-blinded for drug intervention. SETTING: Subjects were recruited from a population-based cholesterol screening programme. SUBJECTS: 215 middle-aged men with primary hypercholesterolemia, free from cardiovascular disease. INTERVENTIONS: Subjects were randomized to one of four intervention groups: (1) placebo and US National Cholesterol Education Program step 1 diet; (2) placebo and step 2 diet; (3) pravastatin 20 mg day-1 and step 1 diet; or (4) pravastatin 20 mg day-1 and step 2 diet. The intervention period was 6 months. MAIN OUTCOME MEASUREMENTS: Efficacy measurements included: serum total cholesterol, HDL cholesterol, triglycerides, apolipoproteins A1 and B. LDL cholesterol was calculated. For safety, values of ALAT, ASAT and CK were measured. RESULTS: In the group receiving the step 1 diet only, lipid values were stable during the study period. In the placebo group on the step 2 diet, total cholesterol decreased by 6.3% (0.47 mmol L-1 (95% CI: 0.28, 0.67)) during 6 months. In the group receiving both pravastatin and the step 1 diet, there was a mean reduction in serum total cholesterol of 19.4% (1.46 mmol L-1 (95% CI: 1.20, 1.72)). In the group treated with pravastatin and the step 2 diet, the 6 months of data show a reduction of 20.7% (1.55 mmol L-1 (95% CI: 1.30, 1.80)). CONCLUSIONS: If drug therapy with a HMG-CoA reductase inhibitor is considered necessary, a step 2 diet has no additional lipid-lowering effect compared with a step 1 diet in men with primary hypercholesterolaemia. However, favourable 'side-effects' of a lipid-lowering diet, such as weight loss and lowering of blood pressure, may still warrant a low-fat diet in these cases.