The Atherosclerosis Risk in Young Adults (ARYA) study: rationale and design.

INTRODUCTION: Despite recent advances in treatment, cardiovascular disease (CVD) is still health problem number one in western societies. Aiming at specific prevention strategies for high-risk individuals and shifting the available prevention programs towards younger age groups might increase the success of primary prevention. However, before addressing age-specific prevention programs, more insight in the determinants of early vascular damage and increased cardiovascular risk is warranted as well as insight in determinants increased cardiovascular risk, including vascular damage, at an early age. The Atherosclerosis Risk in Young Adults (ARYA) study was specifically designed to address this issue. OBJECTIVES: The ARYA study started off with studies evaluating (1) whether it is possible to predict cardiovascular risk at young adulthood by routinely measured adolescent data, and (2) evaluating the role of birth characteristics and adolescent characteristics to the development of vascular damage at young adulthood. METHODS: The ARYA study comprises of two cohorts of young adults. The Utrecht cohort includes 750 young adults, aged 27-30 years. The Hague-cohort includes 261 young adults born between 1963 and 1968. Data on birth characteristics, growth in early infancy as well as adolescent anthropometry, blood pressure, lipids, body mass index were obtained from the original medical records of the Municipal Health Service. In 1999/2001, the extent of subclinical vascular damage was measured using carotid wall thickness and aortic stiffness. Also, data on adult cardiovascular risk profile, bone density and central blood pressure were assessed, fasting blood was drawn and timed overnight urine samples were collected. CONCLUSION: The ARYA study is aimed to provide data on early determinants of cardiovascular risk, including vascular damage, at an early age. This knowledge enhances the understanding of atherosclerosis development and CVD risk and is needed to improve the available primary prevention programs.

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.

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.

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.

Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity.

OBJECTIVES: To assess the prevalence of microalbuminuria in the general population, especially in nondiabetic and nonhypertensive subjects, and its association with known cardiovascular risk factors and cardiovascular morbidity. DESIGN: Cross-sectional cohort study. SETTING: Inhabitants of the city of Groningen, the Netherlands. SUBJECTS: All inhabitants, aged between 28 and 75 years, were send a postal questionnaire and a vial to collect an early morning urine sample (n = 85 421). Of these 40 856 subjects (47.8%) responded. Cardiovascular risk factors and morbidity were validated in a well defined nondiabetic and nonhypertensive group of 5241 subjects. MAIN OUTCOME MEASURES: Microalbuminuria, self-reported cardiovascular risk and cardiovascular morbidity in the total study cohort, and additionally more detailed measurements in a subset of the total population. RESULTS: Microalbuminuria (20-200 mg L-1) was present in 7.2% of the subjects and independently associated with age, gender, hypertension, diabetes, smoking, previous myocardial infarction and stroke. Some of these associations were already observed at albuminuria levels of 10-20 mg L-1. After exclusion of the diabetic and hypertensive subjects, microalbuminuria was still prevalent in 6.6% of the subjects. CONCLUSIONS: Microalbuminuria appears to be common not only in the general population but also in a nondiabetic, nonhypertensive population and is independently associated with increased cardiovascular risk factors and cardio-vascular morbidity. Importantly, some of these associations are present at urinary albumin levels currently considered to be normal. These findings suggest that urinary albumin measurements may be useful in early risk profiling and prevention of cardiovascular disease in the population at large.

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.

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.

Higher prevalence of depressive symptoms in middle-aged men with low serum cholesterol levels.

OBJECTIVE: Investigators from several studies have reported a positive relationship between low cholesterol levels and death due to violent causes (eg, suicide and accidents), possibly mediated by depressive symptoms, aggression or hostility, or impulsivity. We set out to establish whether middle-aged men with chronically low cholesterol levels (< or =4.5 mmol/liter) have a higher risk of having depressive symptoms, according to scores on the Beck Depression Inventory, compared with a reference group of men with cholesterol levels between 6 and 7 mmol/liter. A similar comparison was also made for measures of anger, hostility, and impulsivity. METHODS: Cholesterol measurements were obtained as part of a population-based cholesterol screening study in 1990-1991. These levels were remeasured in 1993-1994. Only those whose cholesterol level remained in the same range were included in the study. Depressive symptoms were assessed by using the Beck Depression Inventory; anger, by questionnaires based on the Spielberger Anger Expression Scale and State-Trait Anger Scale; hostility, by the Buss-Durkee Hostility Inventory; and impulsivity, by the Eysenck and Eysenck Impulsivity Questionnaire. RESULTS: Men with chronically low cholesterol levels showed a consistently higher risk of having depressive symptoms (Beck Depression Inventory score > or =15 or > or =17) than the reference group, even after adjusting for age, energy intake, alcohol use, and presence of chronic diseases. No differences in anger, hostility, and impulsivity were observed between the two groups. CONCLUSIONS: Men with a lower cholesterol level (< or =4.5 mmol/liter) have a higher prevalence of depressive symptoms than those with a cholesterol level between 6 and 7 mmol/liter. These data may be important in the ongoing debate on the putative association between low cholesterol levels and violent death.

Low levels of urinary albumin excretion are associated with cardiovascular risk factors in the general population.

Microalbuminuria is associated with both an increased prevalence of cardiovascular risk factors and greater renal and cardiovascular morbidity. We questioned whether in the general population such associations can be found at lower levels of urinary albumin excretion than that of classically defined microalbuminuria. To that purpose urinary albumin concentration was measured in 40619 subjects aged 28 to 75 years. The subjects filled in a questionnaire on cardiovascular risk factors and events and were divided in deciles according to their urinary albumin concentration. Smoking was associated with albuminuria in the fifth or higher decile of urinary albumin concentration, that is with an albumin concentration of 5.1 mg/l and higher. The lower cut-off point for a positive association with hypertension was 8.8 mg/l, and for diabetes 11.2 mg/l. Family history for cardiovascular disease and hyperlipidaemia were not associated with albuminuria. We conclude that urinary albumin concentrations far below the microalbuminuric range are associated with increased prevalence of established cardiovascular risk factors. Family history for cardiovascular disease and hyperlipidaemia seems to behave differently. These data emphasize the need for more studies on the impact of albuminuria on the prediction of cardiovascular and renal disease in the general population.

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.

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.

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.

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.

[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.

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.

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.

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: 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.