Ingvar Hjermann

Effect of Diet and Smoking Intervention on the Incidence of Coronary Heart Disease

Improved hospital care has lowered hospital mortality from acute coronary heart disease (CHD). However, the goal of a sizeable reduction in the prevalence of CHD in young and middle age can only be achieved by postponing or preventing the disease. Intervention trials have been carried out in order to be able to demonstrate that such prevention is possible. These trials have not shown unequivocal results, except for the beneficial effect of antihypertensive treatment on prevention of stroke.

EFFECT OF PROPRANOLOL AND PRAZOSIN ON BLOOD LIPIDS: The Oslo Study

In 23 hypertensive men, aged 47-55, propranolol reduced serum high-density-lipoprotein (HDL) cholesterol by 13% reduced the ratio of HDL to low-density-lipoprotein (LDL)+very-low-density-lipoprotein (VLDL) cholesterol by 15%, increased total triglycerides by 24%, and increased serum uric acid by 10%. Prazosin reduced total serum cholesterol by 9%, LDL+VLDL cholesterol by 10%, and total triglycerides by 16%. These changes are statistically highly significant. On combined treatment with propranolol and prazosin HDL cholesterol was still significantly reduced but changes in other blood lipids were small and insignificant. Uric acid remained elevated. When decisions about long-term therapy are made, such metabolic effects might be of special importance.

Lung cancer and air pollution: a 27 year follow up of 16 209 Norwegian men

Background: The well documented urban/rural difference in lung cancer incidence and the detection of known carcinogens in the atmosphere have produced the hypothesis that long term air pollution may have an effect on lung cancer. The association between incidence of lung cancer and long term air pollution exposure was investigated in a cohort of Oslo men followed from 1972/73 to 1998. Methods: Data from a follow up study on cardiovascular risk factors among 16 209 40 to 49 year old Oslo men in 1972/73 were linked to data from the Norwegian cancer register, the Norwegian death register, and estimates of average yearly air pollution levels at the participants’ home address in 1974 to 1998. Survival analyses, including Cox proportional hazards regression, were used to estimate associations between exposure and the incidence of lung cancer. Results: During the follow up period, 418 men developed lung cancer. Controlling for age, smoking habits, and length of education, the adjusted risk ratio for developing lung cancer was 1.08 (95% confidence interval, 1.02 to 1.15) for a 10 µg/m3 increase in average home address nitrogen oxide (NOx) exposure between 1974 and 1978. Corresponding figures for a 10 µg/m3 increase in sulphur dioxide (SO2) were 1.01 (0.94 to 1.08). Conclusions: Urban air pollution may increase the risk of developing lung cancer.

Reduced expression of endothelial cell markers after 1 year treatment with simvastatin and atorvastatin in patients with coronary heart disease.

The study was aimed at investigating the effects, after treatment for 1 year, of two different statins on the levels of circulating biochemical markers of endothelial function in patients with established coronary heart disease, with the hypothesis that statins might reduce these levels. Twenty-eight patients were randomized to treatment with atorvastatin and 30 to simvastatin for 1 year. The starting dose in both groups was 20 mg/day. Soluble forms of P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined to assess inflammatory activity of the endothelium, and tissue plasminogen activator antigen (tPAag), von Willebrand factor and thrombomodulin for evaluation of the haemostatic function. In the total study population there were significantly reduced levels after 1 year treatment in ICAM-1 (P<0.001), E-selectin (P=0.022) and P-selectin (P<0.001), whereas a significant increase was observed in VCAM-1 (P=0.003). Almost the same pattern was seen within both groups although the increase in VCAM-1 was only seen in the simvastatin group (P=0.017). An overall reduction in tPAag was further observed (P=0.048). The reduction in proinflammatory and to some extent haemostatic markers of endothelial function after 1 year treatment with either simvastatin or atorvastatin may be indicative of a less activated state of the endothelium which possibly may contribute to modulation of the progression of atherosclerosis.

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.

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.

Diet and Exercise Intervention have Favourable Effects on Blood Pressure in Mild Hypertensives: The Oslo Diet and Exercise Study (ODES)

The purpose of this study was to investigate the effect of 1-year diet intervention, exercise intervention and both combined on blood pressure (BP) in normotensives and mild hypertensives. Two hundred and nineteen sedentary middle aged men and women with slightly deranged coronary heart disease (CHD) risk factors were randomised to a control, a diet, an exercise and a diet + exercise group. Based on baseline diastolic BP, participants were divided into tertiles, giving baseline average BP of 141.4/96.7 in tertile 1, 130.7/87.6 in tertile 2 and 121.9/79.0 in tertile 3. The 1-year net-difference in BP between the intervention groups and the control group decreased across the tertiles; in tertile 1 being -11.2/-6.7 (p < 0.05), -11.3/-6.7 (p < 0.05 for systolic BP only) and -7.0/-5.1 (NS) in the combined, diet and exercise group respectively. Triglycerides, HDL cholesterol, and insulin variables were significantly and favourably changed, the changes being most marked in the combined group. The results show that diet and diet + exercise are about equally effective in reducing BP, and the effects may be dependent on the baseline level. Within the upper tertile of baseline BP, the decline in BP in the combined intervention and the diet group are almost comparable to those obtained with drug treatment. In addition, other important CHD risk factors were all changed in a beneficial direction.

Effect of diet or very long chain ω-3 fatty acids on progression of atherosclerosis, evaluated by carotid plaques, intima-media thickness and by pulse wave propagation in elderly men with hypercholesterolaemia:

Background This randomized study targeted a comparison of the effect of 3-year diet counselling or ω-3 polyunsaturated fatty acid (PUFA) supplementation (2.4g/day) on the progression of atherosclerosis in carotid arteries and on finger pulse wave propagation. Methods Measurements were assessed by high-resolution B-mode ultrasound and a photopletysmographic finger pulse-sensor, respectively. Altogether, 563 elderly men with long-standing hyperlipidaemia were randomized into four groups: controls (no dietary counselling and placebo); dietary counselling (and placebo); ω-3 PUFA supplementation (no dietary counselling); dietary counselling and ω-3 PUFA supplementation. Results In the diet only group, the carotid intima-media thickness increase (0.929 to 0.967 mm) was significantly less than in the control group (0.909 to 0.977 mm), (P=0.018). Significant increase in carotid plaques score and plaques area were observed in all four groups, but without between group differences. Changes in carotid intima-media thickness and in high-density lipoprotein-cholesterol were negatively correlated (adjusted P>0.001). Pulse wave propagation time decreased significantly in the control group (206 to 198 ms; P=0.002), reflecting reduced arterial elasticity. In the group receiving ω-3 PUFA only, pulse wave propagation time increased significantly when compared with the control group (P=0.013). Conclusion Reduced progression in carotid intima-media thickness was observed after dietary counselling, whereas ω-3 PUFA supplementation imposed a favourable effect on arterial elasticity. Eur J Cardiovasc Prev Rehabil 13:325-333

The Oslo study: Diet and antismoking advice. Additional results from a 5-year primary preventive trial in middle-aged men

In this randomized, primary prevention trial of 1,232 high-risk, middle-aged Oslo men, advice during 5 years about diet and smoking brought about a significant reduction (47%) in incidence of first major coronary heart disease (CHD) events in the intervention group compared with controls. Data are presented indicating that the net difference of 10% in serum cholesterol between groups was the main cause for this achievement and that the antismoking factor, due to a rather small net difference in quit rates (17 and 24% in control and intervention groups, respectively), contributed to a lesser degree. Analysis of social class reveals that the favorable results in the intervention group were present in all social strata, despite the unexpected finding that lower class men experienced a lower CHD incidence than men of higher socioeconomic status. Antismoking advice was especially effective in lower class intervention group men. Among cigarette quitters, lower social class men reduced their serum cholesterol more than higher social class men. However, for the total intervention group, higher status men had at least as great a reduction in serum cholesterol as did lower status men. With endpoint follow-up extended to 8.5-10 years, additional cases of CHD (nonfatal and fatal myocardial infarction and sudden death) numbered 7 and 10 in the intervention and control groups, respectively; CHD cases throughout the trial totaled 25 and 45 (P approximately equal to 0.02). Total deaths numbered 19 and 31, respectively (P approximately equal to 0.05).

Improved carbohydrate metabolism after physical training and dietary intervention in individuals with the ‘atherothrombogenic syndrome’. Oslo Diet and Exercise Study (ODES). A randomized trial

Objectives. To compare the single and joint effect of 1‐year diet and exercise intervention on carbohydrate metabolism and associated coronary risk variables.