Jan Erikssen

Physical fitness as a predictor of mortality among healthy, middle-aged Norwegian men.

BACKGROUND Despite many studies suggesting that poor physical fitness is an independent risk factor for death from cardiovascular causes, the matter has remained controversial. We studied this question in a 16-year follow-up investigation of Norwegian men that began in 1972. METHODS Our study included 1960 healthy men 40 to 59 years of age (84 percent of those invited to participate). Conventional coronary risk factors and physical fitness were assessed at base line, with physical fitness measured as the total work performed on a bicycle ergometer during a symptom-limited exercise-tolerance test. RESULTS After an average follow-up time of 16 years, 271 men had died, 53 percent of them from cardiovascular disease. The relative risk of death from any cause in fitness quartile 4 (highest) as compared with quartile 1 (lowest) was 0.54 (95 percent confidence interval, 0.32 to 0.89; P = 0.015) after adjustment for age, smoking status, serum lipids, blood pressure, resting heart rate, vital capacity, body-mass index, level of physical activity, and glucose tolerance. Total mortality was similar among the subjects in fitness quartiles 1, 2, and 3 when the data were adjusted for these same variables. The adjusted relative risk of death from cardiovascular causes in fitness quartile 4 as compared with quartile 1 was 0.41 (95 percent confidence interval, 0.20 to 0.84; P = 0.013). The corresponding relative risks for quartiles 3 and 2 (as compared with quartile 1) were 0.45 (95 percent confidence interval, 0.22 to 0.92; P = 0.026) and 0.59 (95 percent confidence interval, 0.28 to 1.22; P = 0.15), respectively. CONCLUSIONS Physical fitness appears to be a graded, independent, long-term predictor of mortality from cardiovascular causes in healthy, middle-aged men. A high level of fitness was also associated with lower mortality from any cause.

Changes in physical fitness and changes in mortality

BACKGROUND Point estimates of physical fitness give important information on the risk of death in healthy people, but there is little information available on effects of sequential changes in physical fitness on mortality. We studied this latter aspect in healthy middle-aged men over a total follow-up period of 22 years. METHODS 2014 healthy men aged 40-60 years had a bicycle exercise test and clinical examination, and completed a questionnaire in 1972-75 (survey 1). This was repeated for 1756 (91%) of 1932 men still alive by Dec 31, 1982 (survey 2). The exercise scores were adjusted for age. The change in exercise scores between surveys was divided into quartiles (Q1=least fit, Q4=fittest). An adjusted Coxs proportional hazards model was used to study the association between changes in physical fitness and mortality, with the Q1 men used as controls. FINDINGS By Dec 31, 1994, 238 (17%) of the 1428 men had died, 120 from cardiovascular causes. There were 37 deaths in the Q4 group (19 cardiovascular); their relative risks of death were 0.45 (95% CI 0.29-0.69) for any cause and 0.47 (0.26-0.86) for cardiovascular causes. There was a graded, inverse relation between changes in physical fitness and mortality irrespective of physical fitness status at survey 1. INTERPRETATION Change in physical fitness in healthy middle-aged men is a strong predictor of mortality. Even small improvements in physical fitness are associated with a significantly lowered risk of death. If confirmed, these findings should be used to influence public health policy.

Blood platelet count and function are related to total and cardiovascular death in apparently healthy men.

BackgroundExperimental animal and clinical studies indicate that blood platelets have an important role in atherosclerosis and formation of thrombi. Prospective studies presenting evidence of an association between blood platelet count and cardiovascular mortality have not been performed. Methods and ResultsFrom 1973 to 1975, blood platelets were counted, and their responsiveness to aggregating agents was studied in healthy middle-aged men. The aim was to assess the possible association between these variables and coronary heart disease. At 13.5 years of follow up, a significantly higher coronary heart disease mortality was observed among the 25% of subjects with the highest platelet counts. Platelet aggregation performed in a random subsample (150 of the 487 men), moreover, revealed that the 50%1 with the most rapid aggregation response after ADP stimulation had significantly increased coronary heart disease mortality compared with the others. These associations could not be explained by differences in age, lipids, blood pressure, or smoking habits. ConclusionsThe present study is the first to present conclusive, prospective evidence of an association between platelet concentration and aggregability and long-term incidence of fatal coronary heart disease in a population of apparently healthy middle-aged men.

Exercise blood pressure predicts cardiovascular mortality in middle-aged men.

The outcome of 1999 apparently healthy men aged 40 to 59 years investigated from 1972 through 1975 was ascertained after 16 years to determine whether systolic blood pressure measured with subjects in the sitting position during a bicycle ergometer exercise test adds prognostic information on cardiovascular mortality beyond that of casual blood pressure measured after 5 minutes of supine rest. During a total follow-up of 31,984 patient years, 278 patients died, 150 from cardiovascular causes. Casual blood pressure and pulse pressure as well as peak exercise systolic blood pressure during 6 minutes on the starting workload of 600 kpm/min (approximately 100 W, 5880 J/min) were all related to cardiovascular mortality. The relative risk (RR) of dying from cardiovascular causes associated with an increment of 48.5 mmHg (= 2 SD) in systolic blood pressure at 600 kilopondmeter (kpm)/min was significant (RR = 1.5, 95% confidence interval [CI] = 1.1-2.3, P = .040) even when adjusting for a large number of variables measured in the present study, including age, exercise capacity, smoking habits, and casual blood pressures. The influence of blood pressure at 600 kpm/min was so strong that the predictive value of resting casual blood pressures became nonsignificant when these were analyzed as continuous variables also including exercise blood pressure as a covariate. However, the maximal systolic blood pressure during the exercise test was unrelated to cardiovascular mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Fatal adverse drug events: the paradox of drug treatment.

Abstract. Buajordet I, Ebbesen J, Erikssen J, Brørs O, Hilberg T (The Norwegian Medicines Agency, Oslo; Central Hospital of Akershus, Nordbyhagen; Ullevaal University Hospital and National Institute of Forensic Toxicology, Oslo, Norway). Fatal adverse drug events: the paradox of drug treatment. J Intern Med 2001; 250: 327–341.

Exercise Blood Pressure Predicts Mortality From Myocardial Infarction

Apparently healthy men (n=1999, 40 to 59 years old) were investigated from 1972 through 1975 to determine whether systolic blood pressure during bicycle ergometer exercise predicts morbidity and mortality from myocardial infarction beyond that of casual blood pressure taken after 5 minutes of supine rest. During a follow-up of 31 984 patient-years (average, 16 years), 235 subjects had myocardial infarctions, of which 143 were nonfatal and 92 were fatal. Exercise blood pressure was more strongly related than casual blood pressure to both morbidity and mortality from myocardial infarction. Among 520 men with casual systolic blood pressure = 140 mm Hg, 304 increased their systolic blood pressure to > or = 200 mm Hg during 6 minutes of exercise at an initial workload of 600 kpm/min. These 304 men had an excessive risk of myocardial infarction (18.8% versus 9.5% among the 1294 men with casual blood pressure < 140 mm Hg and exercise blood pressure < 200 mm Hg; P < .001). As many as 58% of those with myocardial infarction in this group died, compared with 33% (range, 26% to 35%) for all other groups (P=.0011), including those with casual blood pressure > or = 140 mm Hg and exercise blood pressure < 200 mm Hg. Thus, exercise blood pressure is a stronger predictor than casual blood pressure of morbidity and mortality from myocardial infarction, and an early rise in systolic blood pressure during exercise adds prognostic information about mortality from myocardial infarction among otherwise healthy middle-aged men with mildly elevated casual blood pressure. We suggest that blood pressure taken during standardized exercise testing may distinguish between severe and less severe hypertension.

Consequences of antiepileptic drug withdrawal : A randomized, double-blind study (Akershus Study)

Objective: Despite side effects associated with the use of antiepileptic drugs (AEDs), withdrawal of AEDs remains controversial, even after prolonged seizure freedom. The main objective of this study was to assess the effects of AED withdrawal on cognitive functions, seizure relapse, health‐related quality of life (HRQOL), and EEG results. Additionally, potential predictors for freedom from seizures after AED withdrawal were studied.

Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES).

OBJECTIVES Our intent was to investigate the effect of the dihydropyridine calcium channel blocker amlodipine on restenosis and clinical outcome in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND Amlodipine has sustained vasodilatory effects and relieves coronary spasm, which may reduce luminal loss and clinical complications after PTCA. METHODS In a prospective, double-blind design, 635 patients were randomized to 10 mg of amlodipine or placebo. Pretreatment with the study drug started two weeks before PTCA and continued until four months after PTCA. The primary angiographic end point was loss in minimal lumen diameter (MLD) from post-PTCA to follow-up, as assessed by quantitative coronary angiography (QCA). Clinical end points were death, myocardial infarction, coronary artery bypass graft surgery and repeat PTCA (major adverse clinical events). RESULTS Angioplasty was performed in 585 patients (92.1%); 91 patients (15.6%) had coronary stents implanted. Follow-up angiography suitable for QCA analysis was done in 236 patients in the amlodipine group and 215 patients in the placebo group (per-protocol group). The mean loss in MLD was 0.30 +/- 0.45 mm in the amlodipine group versus 0.29 +/- 0.49 mm in the placebo group (p = 0.84). The need for repeat PTCA was significantly lower in the amlodipine versus the placebo group (10 [3.1%] vs. 23 patients [7.3%], p = 0.02, relative risk ratio [RR]: 0.45, 95% confidence interval [CI]: 0.22 to 0.91), and the composite incidence of clinical events (30 [9.4%] vs. 46 patients (14.5%), p = 0.049, RR: 0.65, CI: 0.43 to 0.99) within the four months follow-up period (intention-to-treat analysis). CONCLUSIONS Amlodipine therapy starting two weeks before PTCA did not reduce luminal loss, but the incidence of repeat PTCA and the composite major adverse clinical events were significantly reduced during the four-month follow-up period after PTCA with amlodipine as compared with placebo.

Heart rate increase and maximal heart rate during exercise as predictors of cardiovascular mortality: a 16-year follow-up study of 1960 healthy men.

BackgroundResting heart rate is directly associated and maximal exercise-induced heart rate inversely associated with cardiovascular mortality, and therefore their difference might contain prognostic information from both variables. The comparative long-term prognostic values of maximal exercise-induced heart rate and of the difference between it and resting heart rate were studied in apparently healthy middle-aged men. MethodsResting heart rate and maximal exercise-induced heart rate were measured, and their difference calculated, in 1960 apparently healthy men aged 40–59 years, and mortality was recorded over a period of 16 years. Conventional coronary risk factors were assessed at baseline. ResultsBoth the difference between the two heart rates and the maximal exercise-induced heart rate were strongly, independently and inversely associated with cardiovascular mortality after adjustment for age, smoking, systolic blood pressure, lung function, glucose tolerance, serum cholesterol level, serum triglycerides level, physical fitness and exercise ECG findings. The adjusted relative risk of cardiovascular death in heart-rate difference quartiles 3 and 4 compared with that in quartile 1 (the lowest heart-rate difference quartile) was 0.54 (95% confidence interval 0.33–0.86; P= 0.009). The corresponding value for maximal exercise-induced heart rate was 0.56 (95% confidence interval 0.34–0.89; P=0.018). Within the lowest heart-rate difference quartile, but not within the lowest maximal exercise-induced heart rate quartile, a further, strong, negative gradient in cardiovascular mortality was observed. In the high working capacity range, low heart-rate difference but not low maximal exercise-induced heart rate predicted very high cardiovascular disease mortality. Heart-rate difference and maximal exercise-induced heart rate were also inversely associated with non-cardiovascular disease mortality. ConclusionsBoth heart-rate difference and maximal exercise-induced heart rate were strong, graded, long-term predictors of cardiovascular mortality among apparently healthy middle-aged men, independent of age, physical fitness and conventional coronary risk factors. However, low heart-rate difference was a better predictor than low maximal exercise-induced heart rate for recognizing individuals who were at particularly high risk of dying prematurely from cardiovascular diseases.

Lung function, smoking and mortality in a 26-year follow-up of healthy middle-aged males

Lung function has been associated with mortality after adjusting for other risk factors; however, few studies have adjusted for physical fitness and reported separate analyses according to smoking status. In 1972–1975, spirometry, clinical and physiological parameters were recorded in 1,623 apparently healthy males aged 40–59 yrs. After 26 yrs of follow-up, the current authors investigated the association between baseline lung function and mortality, adjusting for smoking, physical fitness and other potential factors. By 2000, 615 individuals (38%) had died, with 308 (50%) of these deaths from cardiovascular (CV) causes. Forced expiratory volume in one second was a predictor of all-cause mortality (risk ratio (RR) 1.10 per reduction of 10%) after adjusting for smoking, physical fitness, age, systolic blood pressure, body mass index and serum cholesterol. The corresponding multivariate RR was 1.07 for CV causes and 1.34 for respiratory death. In conclusion, in stratified analyses among current and former smokers, forced expiratory volume in one second % predicted was a strong independent predictor of all-cause mortality and respiratory death among current smokers. Forced expiratory volume in one second % predicted was not associated with mortality among never-smokers.