Lifelong benefits on myocardial infarction mortality: 40-year follow-up of the randomized Oslo diet and antismoking study.

BACKGROUND: The effects of saturated fat on atherosclerotic vascular disease are currently debated. OBJECTIVES: In the Oslo cardiovascular study initiated in 1972/1973, a 5-year randomized intervention was conducted in healthy middle-aged men at high risk of coronary heart disease to compare the effects on coronary heart disease incidence of diet and antismoking advice versus control (no intervention). A significant reduction (47%) in first myocardial infarction incidence was observed. We have followed mortality up to 40 years to establish whether a lifelong benefit on mortality risk of myocardial infarction could be observed. METHODS: In the present study, a total of 16 203 men (63% of those invited), aged 40-49 years, participated in a screening examination. Overall, 1232 men with total serum cholesterol levels of 6.9-8.9 mmol L(-1) (80% smokers) were included in the study. The dietary intervention consisted of mainly decreasing the intake of saturated fats and increasing fish and vegetable products, as well as weight reduction in overweight subjects. Smokers were advised to stop smoking. Cox regression analysis was used for statistical analyses. RESULTS: The intervention group showed a sustained reduced risk of death at first myocardial infarction (hazard ratio 0.71, 95% confidence interval 0.51-1.00; P = 0.049), compared to control subjects up to 40 years. During follow-up, the beneficial effect developed gradually but proportionally up to about 15 years after randomization. Later, the curves were parallel. All-cause mortality decreased in the period 8-20 years after randomization, but not thereafter. CONCLUSIONS: Receiving advice about a healthy lifestyle led to a long-term reduced risk of coronary mortality during the following 40 years. Our results suggest that systematically providing effective counselling for a healthy lifestyle for 5 years can lead to lifelong benefits.

Follow-up of diet and cardiovascular risk factors 20 years after cessation of intervention in the Oslo Diet and Antismoking Study.

OBJECTIVE: The Oslo Diet and Antismoking study was a 5-year randomised trial initiated in 1972-1973, which studied the effect of dietary change and smoking cessation for the prevention of coronary heart disease among high-risk middle-aged men. To test the long-term maintenance of lifestyle change, we examined diet and cardiovascular risk factors in subjects initially randomised to the control and intervention groups 20 years after cessation of the intervention. SUBJECTS AND DESIGN: Of the original cohort that included 1232 participants, 910 survivors were identified in 1997 and cardiovascular risk factors were measured in 563 (62%) in 1997-1999. Of these, 558 (99%) also completed questionnaires about their food intake and attitudes to health and diet. RESULTS: Cigarette smoking was nearly halved between baseline and 20-year follow-up in each of the intervention and control groups (P<0.001 within groups), but did not differ between the intervention group (39%) versus the control group (34%); P=0.07. Body mass index increased by 1.4+/-2.6 and 1.6+/-2.6 kg/m(2) between baseline and 20-year follow-up in the intervention and control groups, respectively (P<0.001 within groups; NS between groups). Serum total cholesterol and triglyceride concentrations decreased substantially in subjects treated or untreated with statins (P<0.001 within the intervention and control groups) but did not differ between the groups (total cholesterol change of -1.4+/-1.3 and -1.3+/-1.2 mmol/l, respectively, and triglyceride change of -0.5+/-1.0 mmol/l in both groups). Men in the intervention group reported a less atherogenic fat quality score and lower intakes of fat, saturated fat and cholesterol, higher intakes of long chain polyunsaturated fatty acids, protein and beta-carotene and greater attention to lifestyle and change of diet than the control group (all P<0.05). The fatty acid concentrations did not differ, however, between the intervention and control groups (P>0.05). CONCLUSIONS: No long-term differences in smoking rates or lipid concentrations between the intervention and control groups were observed in the surviving attendees two decades after the end of the trial. Lifestyle intervention still influenced the dietary intake, though modestly.

Lifestyle changes may reverse development of the insulin resistance syndrome. The Oslo Diet and Exercise Study: a randomized trial.

OBJECTIVE: To compare and assess the single and joint effect of diet and exercise intervention for 1 year on insulin resistance and the development leading toward the insulin resistance syndrome. RESEARCH DESIGN AND METHODS: An unmasked, randomized 2 x 2 factorial intervention trial was applied with a duration of 1 year for each participant. The trial comprised 219 men and women with diastolic blood pressure of 86-99 mmHg, HDL cholesterol < 1.20 mmol/l, triglycerides > 1.4 mmol/l, total cholesterol of 5.20-7.74 mmol/l, and BMI > 24 kg/m2. Participants were randomly allocated to diet group (n = 35), diet and exercise group (n = 67), exercise group (n = 54), and control group (n = 43). The diet included increased intake of fish and reduced total fat intake. The exercise program entailed supervised endurance exercise three times a week. Baseline cross-sectional changes and 1-year changes in insulin resistance, fasting serum levels of insulin, C-peptide, proinsulin, glucose, and lipids as well as weight, mean blood pressure, and plasminogen activator inhibitor 1 (PAI-1) values were recorded. RESULTS: The cross-sectional results at baseline showed significant correlations between the calculated insulin resistance and BMI (r = 0.54) and correlations between the mean blood pressure (mBP) (r = 0.26) and PAI-1 (r = 0.40). The 1-year diet intervention gave a significant decrease in the calculated insulin resistance from 4.6 to 4.2 and a positive correlation between the changes in insulin resistance and changes in BMI (r = 0.40). The diet and exercise intervention also led to significantly decreased insulin resistance (from 5.0 to 4.0). The exercise intervention did not significantly change insulin resistance. CONCLUSIONS: The cross-sectional and 1-year intervention results supported each other and underscored the important connection between increased BMI and the development leading toward the insulin resistance syndrome.

Increased plasma vasopressin in low renin essential hypertension.

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acyl pattern of adipose tissue triglycerides, plasma free fatty acids, and diet of a group of men participating in a primary coronary prevention program (the Oslo Study).

The acyl pattern of adipose tissue triglycerides and of plasma free fatty acids were determined after 7 yr of diet intervention on elevated plasma cholesterol in 42 men taking part in the smoking-lipid trial of the Oslo Study. Twenty-two of the men were advised to change dietary habits (mainly reduce saturated fat) whereas the remaining 20 were controls. The adipose tissue from men in the intervention group contained relatively more linoleic and linolenic acids and relatively less saturated and monounsaturated fatty acids compared to men in the control group. There were strong correlations between the relative content of several fatty acids in adipose tissue triglycerides and plasma free fatty acid. Furthermore, there was a close correlation between the intake of polyunsaturated fatty acids found in a dietary survey done 2 to 3 yr before this study and the relative content of polyunsaturated fatty acids in adipose tissue.

Effect of long-term changes in diet and exercise on plasma leptin concentrations.

BACKGROUND: Although it is known that plasma leptin concentrations correlate with the amount of adipose tissue in the body, little information is available on the long-term effects on leptin concentrations of changes in diet and exercise. OBJECTIVE: We wanted to examine whether changes in dietary energy sources and exercise-mediated energy expenditure, alone or in combination, affect plasma leptin concentrations. DESIGN: In a randomized, 2 x 2 factorial trial, 186 men with metabolic syndrome were divided into 4 groups: diet, exercise, a combination of diet and exercise, and control. Data on dietary intake, physical fitness, and demographics were collected and plasma leptin concentrations were measured before and after a 1-y intervention period. RESULTS: Plasma leptin concentrations, body mass index, and fat mass decreased in association with long-term reductions in food intake as well as increased physical activity. By adjusting for either body mass index or fat mass, we observed a highly significant reduction in plasma leptin concentration after both the diet and the exercise interventions. There was no interaction between the interventions, suggesting a direct and additive effect of changes in diet and physical activity on plasma leptin concentrations. CONCLUSION: Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass.

Exercise-induced increase in lipoprotein (a).

In the Oslo Diet and Exercise Study (ODES) 219 healthy middle-aged physically inactive persons with moderately deranged risk factor levels (increased bodyweight, diastolic blood pressure, serum cholesterol, triglycerides, decreased HDL-cholesterol) were randomized to 4 intervention groups: dietary intervention, exercise, diet + exercise and control. The purpose of the study was to test if these interventions maintained for a year, isolated or in combination, would change coronary risk factor levels as compared to control. One of the risk factors included was lipoprotein (a) (Lp(a)). The hypothesis to be tested was if physical exercise would be associated with increased levels of Lp(a) as a result of intervention. Those who exercised increased their Lp(a) levels with 15.4 (S.E. = 8.0) mg/l as compared to no exercise (P < 0.05). Also, dietary intervention tended to increase Lp(a), but the increase did not reach statistical significance. There was no detectable interaction on the effect on Lp(a) of the two intervention modalities. A dose-response relationship was found between change in the exercise-specific variables heart rate and peak oxygen uptake, and Lp(a)-change and this dose-response was most pronounced in the exercise group. Change in Lp(a) was associated to change in several lifestyle related variables such as alcohol intake and waist circumference, pointing to the possibility that Lp(a), at least in some subpopulations, is more amenable to change through lifestyle alterations than reported so far.

Effects of lovastatin alone and in combination with cholestyramine on serum lipids and apolipoproteins in heterozygotes for familial hypercholesterolemia.

We have studied the effect of lovastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase), alone and in combination with the bile acid sequestrant cholestyramine on lipid parameters in 30 heterozygous patients with familial hypercholesterolemia (FH) during a 20-week open trial. Lovastatin 40 mg bid (twice daily) decreased significantly total serum cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides and apolipoprotein B by 36%, 45%, 29% and 11%, respectively, while high density lipoprotein (HDL)-cholesterol and apolipoprotein A-I were increased significantly by 16% and 37%, respectively. These data are consistent with a reduction in both the number of LDL particles and in their cholesterol content. Addition of cholestyramine 4 g bid caused a significant further decrease in total serum cholesterol and LDL-cholesterol to a total of 43% and 61%, respectively. The addition of 4 g bid or 8 g bid of cholestyramine caused only minor changes in the other lipid parameters. No effect was found by these drugs on Lp(a) lipoprotein level. We conclude that lovastatin alone or in combination with a small dose of cholestyramine normalizes the lipid profile in most FH heterozygotes.

Oslo Study Diet and Antismoking Trial. Results after 102 months.

The five year (60-month) results from the Oslo Study Diet and Antismoking Trial were published in the Lancet in December 1981. The trial involved 1,232 healthy men, aged 40 to 49 years, at high risk for coronary heart disease, with serum cholesterol values in the range of 7.5 to 9.8 mmol/liter (enzymatic method: 6.9 to 9.0, mean value 7.8 mmol/liter). Eighty percent of the men were daily cigarette smokers at the start of the study, and all participants were normotensive, i.e., systolic blood pressure was less than 150 mm Hg. Subjects were randomly assigned to either a control or intervention group. Follow-up visits were scheduled every six months for the intervention group and yearly for the control group. Once the trial was completed, the regular six-month follow-up visits were discontinued, but eight to nine years (96 to 108 months) after the start of the trial, participants were called for a new follow-up. Risk factors were recorded, and clinical events were diagnosed according to the same procedure as during the trial. The mean serum cholesterol levels in the intervention group remained unchanged three years after the end of the trial, but the cholesterol levels in the control group declined. Daily cigarette smoking increased in the intervention group but remained stable in the control group. At the new follow-up, the difference in incidence of fatal and nonfatal myocardial infarction and sudden coronary death was the same as at the end of the trial three years earlier, yielding significant differences between the two groups for sudden death, total coronary death, and total coronary events. Although the study was not designed to show differences in total mortality, this difference became marginally significant, with 19 deaths in the intervention group and 31 in the control group. It is concluded that although net differences in risk factors between the two groups had been reduced during the three years after the regular intervention period, the significant difference in coronary events and sudden death was maintained.

Serum triglycerides and serum uric acid in untreated and thiazide-treated patients with mild hypertension. The Oslo study.

Levels of serum lipids, uric acid and body weight are reported from a controlled trial of drug treatment of middle-aged men with uncomplicated mild hypertension. The results come from 300 men after three years of follow up; 150 men in the treatment group and 150 men in the control group. The treatment has been standardized starting with hydrochlorothiazide alone and adding alpha methyldopa when necessary. In case of side effects, alpha methyldopa was replaced with propranolol. Pretreatment results demonstrated a strong covariation among body weight, uric acid and triglycerides. In the entire treatment group, there was no significant change in triglycerides after three years (increase from 1.85 to 2.02 mM/liter, P greater than 0.05). Cholesterol was also unchanged. Further analysis showed that certain patients reacted with an increase in triglycerides during treatment: those prone to a distinct increase in uric acid and those gaining weight. Those who needed combination therapy (having the highest pretreatment blood pressure) showed most of the increase in triglyceride and uric acid. In the group treated with hydrochlorothiazide alone, the triglycerides were unchanged. However, those selected from this group with a distinct increase in uric acid also showed an increase in triglycerides. The treatment increased the pretreatment positive correlation between uric acid and triglycerides.

Serum glucose levels during long-term observation of treated and untreated men with mild hypertension. The Oslo study.

Serum glucose levels, triglyceride levels, and body weight are reported from a controlled drug trial in men, aged 40 to 49, with uncomplicated mild hypertension. The drug treatment started with hydrochlorothiazide alone, and methyldopa was added when necessary. If side effects occurred, methyldopa was replaced by propranolol. No detailed advice about diet, smoking, or weight reduction was given to any group. The untreated control subjects had a small increase in serum glucose levels during five years, from 6.08 to 6.21 mmol/liter. Those treated with hydrochlorothiazide alone and those treated with hydrochlorothiazide plus methyldopa had a small increase in serum glucose levels of the same order as that in the control subjects. However, those receiving the thiazide/propranolol combination experienced a sizeable increase in glucose levels, from 5.96 to 6.53 mmol/liter (p less than 0.001). This increase was significantly greater than the increase in the other groups (p less than 0.001). The thiazide/propranolol group also showed a significant increase in serum triglyceride levels (p less than 0.05). There was no difference in serum potassium levels in the different drug groups. The results indicate that moderate thiazide doses do not have significant effects on serum glucose levels in this age group. Propranolol in combination with thiazide seems to increase the level of serum glucose.

Risk of fatal stroke according to blood pressure level: an 18-year follow-up of the Oslo Study.

OBJECTIVE: To determine how blood pressure level predicts the incidence of fatal stroke. DESIGN: The Oslo Study is a prospective cohort study of preventive and epidemiological aspects of cardiovascular disorders in middle-aged men. Of 25,915 men invited, 16,209 aged 40-49 years attended the screening. A 7% random sample of men aged 20-39 years were also invited to attend. METHODS: The screening started in May 1972 and the analysis presented is an 18-year follow-up for fatal strokes. Men with a history of stroke were excluded from the analyses. RESULTS: Of 16,173 men with no history of stroke 85 died from stroke. Results from Cox proportional hazards regression analysis confirm diastolic (DBP) and systolic blood pressure (SBP) as strong independent risk factors of fatal stroke, with DBP being the stronger predictor. Analyses of risk of fatal stroke by quintile values show SBP to give significantly increased risk from the third quintile (136 mmHg), and DBP from the fifth quintile (95 mmHg) relative to the first quintile. No levelling off at highest levels can be seen when analysing decile values. No J-shape of the curve was evident. Men on drug treatment for hypertension with no stroke history (n = 440) had 4.7-fold (crude) and 2.8-fold (adjusted for age and DBP) the rate of stroke mortality of men not on drug treatment for hypertension. CONCLUSION: DBP was a stronger predictor than SBP, with increasing risk from the fifth quintile of DBP and the third quintile of SBP. Men on drug treatment for hypertension at screening were at increased risk during the follow-up period, indicating that their treatment did not sufficiently reduce their risk of stroke.

Increased platelet and vascular smooth muscle reactivity to low-dose adrenaline infusion in mild essential hypertension.

During low-dose adrenaline infusion, platelet count, platelet size, plasma beta-thromboglobulin (BTG) and forearm vascular resistance (FVR) were measured in twelve 40-year-old men with mild, untreated hypertension. The average platelet count increased from 195 to 226 X 10(9)/l (P less than 0.001), platelet size from 7.31 to 7.53 X 10(-15)/l (P less than 0.01), BTG from 0.61 to 1.08 nmol/l (P less than 0.02) and FVR decreased from 97 to 58 (arbitrary units; P less than 0.001) during the infusion. The change in platelet count reflects splenic release of platelets, the change in plasma BTG reflects platelet release reaction, while the reduced FVR reflects vascular smooth muscle cell relaxation. In 11 normotensive men aged 40 years, platelet count increased from 187 to 201 X 10 g/l (P less than 0.01) during an equal low-dose adrenaline infusion. This increase in platelet count is significantly less than in the hypertensive group (P less than 0.01). There was statistically no significant change in platelet size, BTG or FVR in the normotensive group. Arterial adrenaline rose from 0.5 to 2.5 nmol/l in the hypertensive and from 0.5 to 2.4 nmol/l in the normotensive group. A third group of 12 normotensive men received saline infusion: neither platelet parameters nor FVR changed in this group. Thus, a small and equal dose of adrenaline elicited a greater increase in platelet count, an enhanced platelet release reaction and a more pronounced forearm vasodilation in hypertensive than in normotensive subjects.

Increased platelet size and release reaction in essential hypertension.

Basal platelet function was measured in 35 40-year-old men with untreated mild essential hypertension and compared with 44 age-matched normotensive men. The groups differed significantly with respect to platelet size in venous blood (hypertensive, 7.46 +/- 0.10 X 10(-15) l versus normotensive, 7.11 +/- 0.09 X 10(-15) l; P = 0.01) and arterial concentration of the platelet-specific protein beta-thromboglobulin (hypertensive, 1.11 +/- 0.23 nmol/l versus normotensive, 0.59 +/- 0.04 nmol/l; P = 0.02). The normotensive subjects had significantly higher beta-thromboglobulin (BTG) in venous than in arterial blood (P less than 0.01). The hypertensive men showed no such difference. In contrast to the normotensive subjects, the hypertensive group had reduced arterial compared with venous platelet count (P less than 0.01). This may reflect an increased liability in the hypertensive subjects to lose platelets through adherence to the cannula during arterial blood sampling. The above findings point to increased platelet activity in essential hypertension, particularly in arterial blood.

Decreased central dopaminergic activity in essential hypertension.

Baseline serum prolactin (PRL) was found to be similar in 35 men with untreated essential hypertension (149 +/- 2/98 +/- 1 mmHg; means +/- s.e.) and 44 healthy normotensive men (126 +/- 1/80 +/- 1 mmHg), all 40 years old. A correlation between baseline PRL and aldosterone was found in the normotensive (r = 0.534, P less than 0.001), but not in the hypertensive group (r = -0.011, NS). Ten subjects from each group received intravenous metoclopramide, a competitive dopamine antagonist, while another 12 normotensive subjects were given saline only, and the effect on PRL, vasopressin (AVP) and catecholamines was followed. An exaggerated PRL response to metoclopramide was observed in the hypertensive group compared with the normotensive (P less than 0.05), and the mean normotensive peak value never exceeded the hypertensive. Plasma noradrenaline increased significantly compared with baseline (P less than 0.05) and the control group (P less than 0.001), concomitant with increased heart rate (P less than 0.05), after the administration of metoclopramide both in the hypertensive and normotensive group. After intravenous injection of metoclopramide, forearm blood flow increased significantly by 50% in the hypertensive (P less than 0.001), and 80% in the normotensive group (P less than 0.001) compared with the control group. Mean blood pressure remained unchanged as did plasma AVP, dopamine and adrenaline. The present study indicates an altered central dopaminergic activity in essential hypertension. Even at rest, endogenous dopamine exerts a modulating effect on noradrenaline release in both hypertensive and normotensive men.

Coronary risk factors and their pathway of action through coronary raised lesions, coronary stenoses and coronary death. Multivariate statistical analysis of an autopsy series: the Oslo Study.

From 1972 to 1973, 16,202 Oslo men, aged 40 to 49 years, were examined for cardiovascular disease and coronary heart disease (CHD) risk factors. This report describes the results of autopsy examinations from 204 of 471 men who died in this cohort with regard to associations between selected risk factors and (1) raised coronary atherosclerotic lesions (RL), (2) coronary artery stenosis, and (3) CHD death. Total serum cholesterol and blood pressure levels were positively associated with all 3 measures of coronary atherosclerosis and its complications, both in univariate and multivariate analyses, whereas high-density lipoprotein (HDL) cholesterol was highly and inversely related. Triglyceride levels, cigarette smoking, social class and physical activity at work and at leisure were not significantly associated with either of the 3 measures. When RL was added to the model with stenosis as the dependent variable, the risk factors no longer appeared as independent; this is consistent with the hypothesis that these factors, when significant, work through the development of RL to produce stenosis. HDL cholesterol was the only risk factor independently and significantly associated with CHD death when RL or stenosis or both were put into the model for CHD. This points to the possibility of HDL cholesterol also working through mechanisms other than the prevention of RL and stenosis toward CHD death.

Strategies for dietary and anti-smoking advice. Practical experiences from the Oslo Study.

One of the 2 controlled preventive trials within the Oslo Study was a non-drug trial on the effect of diet and smoking intervention on coronary heart disease in 1232 middleaged, normotensive, healthy men. All had elevated serum cholesterol and 4 out of 5 smoked every day. The participants in the intervention group met every 6 months during the 5-year study for clinical examination and for dietary and smoking counselling. The effect on serum cholesterol was a 13% lowering (i.e. 10% net reduction compared with control group), and about a 50% reduction in cigarette consumption. The effect on coronary heart disease (fatal and non-fatal myocardial infarction or sudden death) was a 47% lowering of the 5-year incidence in the intervention group compared with the control group (p = 0.02, 2-sided). The main intervention strategies were: information about the risk factor concept to participant and spouse (in groups) individual diet and anti-smoking counselling after finishing an extensive clinical and electrocardiographic examination, including exercise-ECG basis and background for the counselling strategy: the total situation of the participant. Some of the most important items: personality, motivation, diet history, bodyweight, blood lipids and blood sugar anti-smoking advice given individually to all smokers in the intervention group advice that smoking cessation was expected to be of special importance for those with elevated blood lipids.

The influence of dietary change on hemostatic risk variables.

In the 1970s in the Diet-Antismoking Trial, of the Oslo Study, colleagues and I found that the majority of high-risk men with elevated serum cholesterol and elevated triglyceride concentrations had impaired fibrinolytic capacity. Later on, both our group and others found a similar negative correlation between serum triglyceride levels and fibrinolytic capacity. Furthermore, in a prospective study of dietary intervention in individuals with both elevated cholesterol and triglyceride levels, we found that dietary lowering of serum triglyceride levels was significantly and positively correlated with an improvement in fibrinolytic capacity. In another study, we made the same observation for the coagulation factor VII-phospholipid complex: the more the triglycerides were reduced by diet, the greater was the change in factor VII complex. This correlation was highly significant and independent of changes in serum cholesterol. Platelet function is also influenced by dietary habits, but except for the effects of a fish oil-enriched diet, few data are available about the dietary effects on platelet function. It seems, however, that in individuals with elevated lipid levels and elevated blood pressure, increased platelet reactivity is a highly prevalent finding. Many of the hemostatic risk variables are associated with the so-called "metabolic risk syndrome" characterized by an increase in serum insulin level, together with increased relative body weight, mild hypertension, hyperlipidemia, and physical inactivity. This syndrome can often be influenced favorably by life-style changes. A controlled study with interventions in diet and activity level has just been started by our group.

Quality-adjusted meta-analysis of the hypertension/coronary dilemma.

Primary investigators of randomized drug trials in hypertension were invited to rate quality of such trials. The intention of the survey was to ask if antihypertensive drug therapy reduces incidence of coronary heart disease (CHD) in hypertensive patients. Response was obtained for 7 of the 11 invited investigators, covering 69% of patients and 75% of CHD cases. Principal component analysis was used to construct a quality score based on answers to 12 questions along visual analog scales. The score correlated well with the answer to a global question of overall quality given by the raters. No systematic tendency toward favoring one's own trial could be demonstrated, therefore, all raters have contributed to the rating. The trials with the highest rated quality to answer the research question were Systolic Hypertension in the Elderly Program (SHEP), Australian National Blood Pressure Study, Medical Research Council, Veterans Administration, and European Working Party of Hypertension in the Elderly. The large Heart Detection and Follow-up Program (HDFP) trial was rated at 11th place among the trials with a score of < 40% of the SHEP. The small trials performed in the 1960s were placed at the bottom of the ranking list. Because SHEP is the only trial without diastolic hypertension, results were given with and without SHEP results. When incorporating the quality score into a meta-analysis of CHD outcome, results were dependent on whether SHEP was included or not. For diastolic hypertension only, the effect of therapy was estimated to be about 8% for all higher quality studies, whereas inclusion of the lower quality HDFP changed it to 14%. When isolated systolic hypertension trial was pooled with the others, no major relation to quality rating was observed. A 14% CHD preventive efficacy was established when pooling the three top quality studies. This stayed unchanged until HDFP at rank 11 was included raising this estimate to 16%. Inclusion of the two latest published trials in the elderly, the Medical Research Council trial of treatment of hypertension in older adults and the Swedish Trial in Old Patients with hypertension, did not change this overall estimate of 16% (standard error = 3.8%). It is concluded that if all randomized drug trials in hypertension had the same treatment efficacy, the estimated CHD prevention would be in the range of 15%. Subgroup analyses revealed no relationship to age, but a difference in efficacy was shown depending on whether the trials were performed in the United States or elsewhere. Also, patients at higher risk levels showed better benefit than lower risk patients.

Effect of dietary counselling on blood pressure and arterial plasma catecholamines in primary hypertension.

There is still a need of support for nonpharmacologic treatment of uncomplicated, mild-to-moderate essential hypertension. We investigated whether a low sodium-based diet implemented by a nutritionist could lower blood pressure and affect sympathetic activity. Middle-aged, otherwise healthy men with never-treated essential hypertension (n = 95) were randomized to an intervention group, a blood pressure control group, and a time control group. The intervention group was advised to use less sodium chloride in their diet, and if necessary, less saturated fat and decrease body weight. They attended regular clinic visits as did the blood pressure control group. After 1 year, the intervention group had achieved on average 72 mmol/24 h lower urinary sodium excretion (P < .001) and a decrease in body weight of 2.7 +/- 0.5 kg (P < .001). Both supine and standing mean blood pressure were on average 8 to 10 mm Hg lower after intervention compared with the two control groups (P < .001). Arterial plasma epinephrine, measured in all 40-year-old subjects (n = 30), decreased in parallel in all three groups (P < .05), indicating some habituation to the invasive procedure and clinic visits. However, the decrease in norepinephrine was significant (P < .001) only in the intervention group; it correlated with the weight loss (r = 0.76, P < .05) and was significantly higher (P < .05) than in both control groups. These results suggest that broad dietary advice (ie, low intake of sodium chloride, saturated fat and energy), implemented by a nutritionist, may have a significant blood pressure lowering effect and a favorable sympathicolytic effect in uncomplicated, mild-to-moderate essential hypertension.