Paul Leren

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.

The Oslo Diet-Heart Study Eleven-Year Report

The study deals with 412 men, aged 30 to 64 years, randomized 1 to 2 years after a first myocardial infarction. For the experimental group a diet low in saturated fats and cholesterol, and high in polyunsaturated fats was recommended. After 5 years, as reported previously, the incidence of fatal and nonfatal myocardial reinfarction was found to be significantly reduced. “Sudden death” was uninfluenced. Major coronary heart disease (CHD) relapses, including fatal and nonfatal events (MI), were significantly reduced (P = 0.05).After 11 years, death from all causes had occurred in 101 of the original dieters and 108 controls. A significantly reduced myocardial infarction mortality in the original diet group was found (32 versus 57, P = 0.004). The total number of coronary deaths (fatal myocardial infarction and sudden death) was 79 in the diet group and 94 in the control group (P = 0.097).The CHD mortality was correlated with age, serum cholesterol level, blood pressure, body weight, smoking habits, and a combination of these risk factors.

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.

Mortality in relation to smoking history: 13 years' follow-up of 68,000 Norwegian men and women 35–49 years

A total of 44,290 men and 24,535 women aged 35-49 have been followed with respect to different causes of death during 13.3 years on average. A detailed history of smoking, together with other important risk factors, were recorded in a standardized way. Compared with the classical American and British studies, the excess mortality for the smokers was largely the same for the majority of causes. The exceptions were cerebrovascular mortality and suicides and accidents, which were more strongly related to smoking in this study. Furthermore, men who smoked only pipe, had nearly the same coronary heart disease mortality as men who smoked only cigarettes. The same applies to lung cancer mortality. Among men who had quit cigarette smoking, the coronary heart disease mortality decreased with time since quitting to almost the level of the never cigarette smokers after 5 years or more.

Risk factors of stroke incidence and mortality. A 12-year follow-up of the Oslo Study.

Background and Purpose The objective of this study was to determine the risk factors of stroke incidence and mortality. Methods Our data are based on a prospective cohort study of men aged 40 to 49 years after 12 years of follow-up. Results In age-adjusted Cox proportional-hazards regression analysis of 14 403 healthy men, diastolic blood pressure was a stronger predictor for stroke incidence and mortality than systolic blood pressure. Smoking was a stronger predictor of mortality than of incidence. However, there was no dose-response relation among smokers by increased cigarette consumption. Total serum cholesterol was a significant (P < .05) risk factor for stroke mortality and of borderline significance (P=.08) for stroke incidence. Increased physical activity at leisure was associated with reduced stroke incidence but not mortality. The myocardial infarction risk score comprising systolic blood pressure, total serum cholesterol, and daily cigarette smoking was a strong predictor of mortality and incidence. Body mass index, triglycerides, blood glucose, and physical activity at work were not found to be risk factors for stroke. Conclusions Reduction of blood pressure, cessation of smoking, lowered cholesterol, and increased physical activity at leisure are individual measures to reduce the risk of stroke.

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.

Evidence of increased peripheral catecholamine release in patients with long-standing, untreated essential hypertension

In 20 middle-aged men with untreated sustained essential hypertension for more than 5 years, both plasma adrenaline and noradrenaline were positively and significantly correlated with blood pressure. In both hypertensives and 19 normotensive control subjects supine arterial adrenaline concentrations were more than twice the venous concentrations consistent with adrenal production of this catecholamine. Adrenaline a--v(arterial-venous)differences(mean +/- SE) were significantly higher in the hypertensive group (82 +/- 15 pg/ml) than in the controls (50 +/- 5 pg/ml) indicating increased release of adrenaline in the hypertensives (P less than 0.05). Similarly, v-a(venous-arterial) differences of noradrenaline were significantly higher in the hypertensive (44 +/- 20 pg/ml) than in the control group (-10 +/- 16 pg/ml) indicating peripheral noradrenaline release in patients with essential hypertension. The findings are compatible with increased forearm noradrenaline and adrenal adrenaline release in these patients with long-standing untreated essential hypertension.

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.

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).