Mortality in participants and non-participants of a multifactorial prevention study of cardiovascular diseases: a 28 year follow up of the Helsinki Businessmen Study.

OBJECTIVE: To investigate pretrial risk factors and long term mortality (1964-1992) in participants and non-participants of a multifactorial primary prevention trial. DESIGN: A prospective study among 3313 initially healthy businessmen. During the 1960s (1964 onwards), 3490 healthy male business executives born between 1919 and 1934 participated in voluntary health checks at the Institute of Occupational Health in Helsinki. From that period cardiovascular disease (CVD) risk factors were available in 3313 men. In the beginning of the 1970s these men were invited to join a multifactorial primary prevention trial of CVD. Six groups were formed: (I) healthy participants in a high risk intervention group (n = 612), and (II) their randomised control group (n = 610); (III) a non-participant low risk group (n = 593); (IV) an excluded group with signs of CVD (n = 563); (V) a refused group (n = 867); and (VI) dead (n = 68). Groups I and II participated in the five year prevention trial which started in 1974. Other groups were followed up through registers, with no personal contact. MEASUREMENTS: Cardiovascular risk factors during the 1960s. Mortality follow up using national registers up to 31 December, 1992. MAIN RESULTS: Baseline risk factors were lowest in the low risk group, highest in the excluded group, intermediate and comparable in other groups. Eighteen-year (1974-1992) mortality (per 1000) was 79.3, 106.6, 155.2, 179.9, and 259.3 in the low risk, control, intervention, refused, and excluded groups, respectively (P < 0.001). In the whole population of 3313 men, the 28-year (1964-1992) total (n = 577) and coronary deaths (n = 199) were significantly predicted by smoking, blood pressure, and cholesterol; cancer deaths (n = 163) by smoking only; and violent deaths (n = 83) by none of the risk factors. One-hour postload glucose was significantly associated with total mortality in the intervention group only. When the intervention and control groups were included in the same model, the effect of group on total mortality tended to be dependent on the 1 h blood glucose value (P = 0.06 for the group by 1 h glucose interaction term). CONCLUSION: The traditional risk factors (smoking, blood pressure, and cholesterol) are significantly associated with 28-year mortality in this high social class population with previous health education. Conversely, a "clustering" of low risk factors predicted low total, coronary, and cancer mortality. The findings on 1 h blood glucose suggest that factors related to glucose tolerance explain in part the excess mortality in the intervention group compared with the control group.

Long-term mortality after 5-year multifactorial primary prevention of cardiovascular diseases in middle-aged men.

OBJECTIVE: To investigate the long-term effects of multifactorial primary prevention of cardiovascular diseases (CVD). DESIGN: The 5-year randomized, controlled trial was performed between 1974 and 1980. The subjects and their risk factors were reevaluated in 1985. Posttrial mortality follow-up was continued up to December 31, 1989. SETTING: Institute of Occupational Health, Helsinki, Finland, and Second Department of Medicine, University of Helsinki. PARTICIPANTS: In all, 3490 business executives born during 1919 through 1934 participated in health checkups in the late 1960s. In 1974, 1222 of these men who were clinically healthy, but with CVD risk factors, were entered into the primary prevention trial; 612 were randomized to an intervention and 610 to a control group. INTERVENTIONS: During the 5-year trial, the subjects of the intervention group visited the investigators every fourth month. They were treated with intensive dietetic-hygienic measures and frequently with hypolipidemic (mainly clofibrate and/or probucol) and antihypertensive (mainly beta-blockers and/or diuretics) drugs. The control group was not treated by the investigators. MAIN OUTCOME MEASURES: Total mortality, cardiac mortality, mortality due to other causes. RESULTS: Total coronary heart disease risk was reduced by 46% in the intervention group as compared with the control group at end-trial. During 5 posttrial years, the risk factor and medication differences were largely leveled off between the groups. Between 1974 and 1989 the total number of deaths was 67 in the intervention group and 46 in the control group (relative risk [RR], 1.45; 95% confidence interval [CI], 1.01 to 2.08; P = .048); there were 34 and 14 cardiac deaths (RR, 2.42; 95% CI, 1.31 to 4.46; P = .001), two and four deaths due to other CVD (not significant), 13 and 21 deaths due to cancer (RR, 0.62; 95% CI, 0.31 to 1.22; P = .15), and 13 and one deaths due to violence (RR, 13.0; 95% CI, 1.70 to 98.7; P = .002), respectively. Multiple logistic regression analysis of treatments in the intervention group did not explain the 15-year excess cardiac mortality. CONCLUSION: These unexpected results may not question multifactorial prevention as such but do support the need for research on the selection and interaction(s) of methods used in the primary prevention of cardiovascular diseases.

Mortality rates after multifactorial primary prevention of cardiovascular diseases.

Eleven-year mortality rates were studied in middle aged men who had participated in a randomised 5-year multifactorial primary prevention trial on cardiovascular diseases during 1974-1980. The men were given health education advice before the study. The 5-year trial markedly improved the risk factor status in the men in the intervention group (n = 612), but their 5-year incidence of total coronary events tended to be higher than in the randomised non-treated control group (n = 610) and significantly higher than in an non-randomised, non-treated low risk group (n = 593). During the six years following the discontinuation of the trial, 11 deaths from cardiovascular disease occurred both in the intervention and in the control groups and three in the non-randomised low risk group. Thus, the cumulative eleven-year cardiovascular mortality rates and their 95% confidence intervals (Cl95) were 2.45% (Cl95: 1.38, 3.67) in the intervention group and 1.97% (Cl95: 1.01, 3.34) in the randomised high risk control group. In the non-randomised low risk group the mortality rate was 0.51 (Cl95: 0.01, 1.46). Multiple logistic regression analysis showed that overweight and hypercholesterolaemia, and smoking in the high risk controls, were the initial risk factors associated with the 11-year cardiovascular mortality. The latter was not accumulated in any treatment measure during the prevention period. Furthermore, despite the unfavourable effect of beta-blocking agents on total cardiac events during the intervention, beta-blockers were not associated with cardiac deaths in the 11-year follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of nicardipine and propranolol in the treatment of mild and moderate hypertension.

In a double-blind controlled trial 22 patients with mild or moderate essential hypertension were treated with nicardipine 30 mg t.d.s. and 19 patients with propranolol 80 mg t.d.s. as monotherapy for 24 weeks. Blood pressure in both groups at the end of trial was equally and significantly reduced; systolic pressure 22.2 mmHg and diastolic pressure 15.5 mmHg in the supine position, and 24.4 mmHg and 18.4 mmHg, respectively, in the standing position in those on nicardipine, and by 23.7 and 16.2 mmHg and 28.0 and 19.2 mmHg, respectively, in the propranolol group. There was an initial increase in heart rate in the nicardipine group, but the rise was only moderate (3 beats/min supine p = 0.3219, and 7 beats/min standing, p = 0.0203) at the end of the 24 weeks. In the propranolol group heart rate was reduced markedly. Adverse effects occurred in 77% of patients on nicardipine and in 63% of those on propranolol, and there were no unexpected findings. The effects were mild in both groups and did not lead any patient to stop medication. One patient on propranolol was withdrawn from the trial because of poor blood pressure control and suspected angina pectoris after 5 weeks on active medication. There were no significant changes in blood chemistry, including lipoprotein classes. Overall, in comparison with propranolol, nicardipine was effective, well-tolerated and safe to use in the monotherapy of mild or moderate essential hypertension.