Erik Thaulow

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.

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.

Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease

Aim: To investigate the role of pulmonary arterial hypertension (PAH) in adult patients born with a cardiac septal defect, by assessing its prevalence and its relation with patient characteristics and outcome. Methods and results: From the database of the Euro Heart Survey on adult congenital heart disease (a retrospective cohort study with a 5-year follow-up), the relevant data on all 1877 patients with an atrial septal defect (ASD), a ventricular septal defect (VSD), or a cyanotic defect were analysed. Most patients (83%) attended a specialised centre. There were 896 patients with an ASD (377 closed, 504 open without and 15 with Eisenmenger’s syndrome), 710 with a VSD (275, 352 and 83, respectively), 133 with Eisenmenger’s syndrome owing to another defect and 138 remaining patients with cyanosis. PAH was present in 531 (28%) patients, or in 34% of patients with an open ASD and 28% of patients with an open VSD, and 12% and 13% of patients with a closed defect, respectively. Mortality was highest in patients with Eisenmenger’s syndrome (20.6%). In case of an open defect, PAH entailed an eightfold increased probability of functional limitations (New York Heart Association class >1), with a further sixfold increase when Eisenmenger’s syndrome was present. Also, in patients with persisting PAH despite defect closure, functional limitations were more common. In patients with ASD, the prevalence of right ventricular dysfunction increased with systolic pulmonary artery pressure (OR = 1.073 per mm Hg; p<0.001). Major bleeding events were more prevalent in patients with cyanosis with than without Eisenmenger’s syndrome (17% vs 3%; p<0.001). Conclusion: In this selected population of adults with congenital heart disease, PAH was common and predisposed to more symptoms and further clinical deterioration, even among patients with previous defect closure and patients who had not developed Eisenmenger’s physiology.

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)

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.

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.

Effect of physical training in children and adolescents with congenital heart disease

In order to test the effect of systematic supervised physical training, we divided a total of 129 children and adolescents with congenital heart disease into a group undergoing intervention and a control group. All patients underwent exercise tests, measurements of physical activity, and a survey of psychosocial factors. An improvement in uptake of peak level of oxygen was observed after intervention. There was also an improvement in physical activity in both groups measured by a monitor, although this was significant only in those with intervention. The psychosocial scales measured by the Child Behavior Checklist showed a decrease in internalizing scores for those subjected to intervention. This was decreased due to decreased withdrawal and somatic complaints. In conclusion, we recommend systematic supervised training, including testing of routine follow-ups, in patients with congenital heart disease.

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.

Plasma levels of natriuretic peptides and hemodynamic assessment of patent ductus arteriosus in preterm infants.

The main purpose of this study was to investigate whether circulating natriuretic peptides in premature infants reflect the hemodynamic significance of a patent ductus arteriosus (PDA). The study comprises 120 examinations in 55 premature infants with a mean gestational age of 27.2 wk and a mean birthweight of 933 g. Based on clinical and echocardiographic findings, the hemodynamic influence of ductal shunting was classified as small, moderate or large. Blood samples for N‐terminal proatrial natriuretic peptide (Nt‐proANP) and brain natriuretic peptide (BNP) were analysed after completion of the clinical part of the study. Linear regression indicated a very strong association between Nt‐proANP and BNP (adjusted R2= 0.89). The mean levels of Nt‐proANP and BNP increased with the size of the shunt through a PDA, and peptide values followed hemodynamic alterations. The size of PDA accounted for 50% and 47% of the total variation in the plasma values of Nt‐proANP and BNP, respectively. In detecting an echocardio‐graphically significant PDA, the area under a ROC curve was 0.94 for Nt‐proANP and 0.90 for BNP.