Irene Grundvold

High prevalence of atrial fibrillation in long-term endurance cross-country skiers: echocardiographic findings and possible predictors — a 28-30 years follow-up study

Background Lone atrial fibrillation (LAF) seems to be more common in endurance-trained male athletes than in men in the general population. The reason for this has not been found. Aim To determine the prevalence of LAF in long-term endurance cross-country skiers and to examine possible predictors. Methods Of 149 healthy, long-term trained cross-country skiers from three different age groups who were invited, 122 and 117 participated in the studies in 1976 and 1981, respectively. At follow-up in 2004-2006, 78 men participated, with 33 in age group I (54-62 years), 37 in group II (72-80 years) and eight in group III (87-92 years), whereas 37 individuals had died and seven could not be tracked. The examination programme applied in 1976, 1981 and 2004-2006 consisted of an electrocardiographic monitoring during rest and exercise and a maximal exercise test. Echocardiography was performed in 2004-2006. Results A high prevalence (12.8%) of LAF was found. The only predictor from both 1976 and 1981 associated with LAF was a long PQ time (r = 0.38, P = 0.001 and r = 0.27, P = 0.02, respectively), whereas bradycardia was another predictor from 1981 (r = 0.29, P = 0.012). At follow-up, left atrial enlargement was a marker associated with LAF (P < 0.001). Conclusion Long PQ time, bradycardia and left atrial enlargement seem to be important risk factors for LAF among long-term endurance cross-country skiers.

Upper Normal Blood Pressures Predict Incident Atrial Fibrillation in Healthy Middle-Aged Men: A 35-Year Follow-Up Study

Hypertension is the most prevalent risk factor for incident atrial fibrillation (AF). Recently, even high normal blood pressures (BPs) have been established as predictive of AF in women. We aimed to study the long-term impact of upper normal BP on incident AF in a population-based study of middle-aged men. From 1972 to 1975, 2014 healthy Norwegian men were included in a prospective cardiovascular survey and underwent a comprehensive clinical examination including standardized BP measurements. During up to 35 years of follow-up, 270 men were documented with AF by scrutinizing all hospital discharges. Risk estimations for incident AF were analyzed in quartiles of BP using multivariate adjusted Cox proportional hazards. Men with baseline systolic BP ≥140 mm Hg and upper normal BP 128 to 138 mm Hg had 1.60-fold (95% CI 1.15–2.21) and 1.50-fold (1.10–2.03) risk of AF, respectively, compared with men with BP <128 mm Hg. Baseline diastolic BP ≥80 mm Hg increased the risk of incident AF 1.79-fold (95% CI 1.28–2.59) compared with diastolic BP <80 mm Hg. When adjusting for the occurrence of diabetes mellitus or cardiovascular diseases before an AF event, the results still maintained significance. Additional analyses, on average 7 years after baseline, including men still healthy, showed that sustained upper normal systolic BP remained a significant predictor of subsequent AF. In conclusion, upper normal blood pressures are long-term predictors of incident AF in initially healthy middle-aged men.

Low Heart Rates Predict Incident Atrial Fibrillation in Healthy Middle-Aged Men

Background—Low resting heart rate (HR) has been associated with atrial fibrillation (AF) in athletes. We aimed to study whether low HR at rest or during exercise testing was a predictor of AF in initially healthy middle-aged men. Methods and Results—A total of 2014 healthy Norwegian men participated in a prospective cardiovascular survey, including a standardized bicycle exercise test in 1972 to 1975. During ⩽35 years of follow-up (53 000 person-years of observation), 270 men developed incident AF, documented by scrutiny of health charts in all Norwegian hospitals. Risk estimation was analyzed with Cox proportional hazard models. Low exercise HR after 6 minutes exercise on the moderate workload of 100 W (HR100W) was a predictor of incident AF. Men with HR100W <100 beats per minute (n=260) were characterized by high physical fitness, low resting and low maximum HR, and they had 1.60-fold AF risk (95% confidence interval, 1.11–2.26) compared with men with HR100W ≥100 beats per minute when adjusted for age, systolic blood pressure, and physical fitness. Additional adjustment for relative heart volume slightly reduced the association. The subgroup of men (n=860) with hypertensive blood pressure measurements at baseline had the highest risk difference between low and high HR100W with hazard ratio 2.08 (1.19–3.45). Conclusions—Our data indicate that low exercise HR on a moderate workload is a long-term predictor of incident AF in healthy middle-aged men. Elevated baseline blood pressure substantially amplifies this risk. The present results suggest a relationship between increased vagal tone, high stroke volumes and incident AF, and particularly so in physically fit men.

Importance of Physical Fitness on Predictive Effect of Body Mass Index and Weight Gain on Incident Atrial Fibrillation in Healthy Middle-Age Men

The incidence of both atrial fibrillation (AF) and obesity is increasing in the community, and lifestyle intervention is recommended. We aimed to test whether the predictive effect of body mass index (BMI) and weight change from age 25 years to midlife on incident AF were influenced by physical fitness. In 1972 to 1975, 2,014 healthy middle-age men conducted a bicycle exercise electrocardiographic test as a part of a cardiovascular survey program, defining physical fitness as work performed divided by body weight. During 35 years of follow-up, 270 men developed AF, documented by scrutiny of the health files in all Norwegian hospitals. Risk estimation was analyzed using Cox proportional hazard models and tested for age-adjusted physical fitness above and below the median. The mean BMI of 24.6 kg/m(2) defined a lean baseline cohort. The men with a baseline BMI of ≥28 kg/m(2) (11%) compared to a BMI <28 kg/m(2) had a 1.68-fold risk of AF (95% confidence interval 1.14 to 2.40) and men reporting weight gain of ≥10 kg (24%) compared to weight loss (11%) of 1.66-fold (95% confidence interval 1.00 to 2.89), respectively. The dichotomy into men with age-adjusted physical fitness above and below the median, demonstrated statistically significant risk associations only for men with low fitness. The overall risk of AF was reduced by 23% in the fit men. In conclusion, within our lean baseline cohort of healthy middle-age men, a BMI of ≥28 kg/m(2) and weight gain of ≥10 kg from age 25 to midlife were long-term predictors of incident AF in men with physical fitness below the population median. The fit men had an overall slightly reduced risk of AF.

The role of beta-blockers in the treatment of chronic heart failure

The introduction of beta-blockers in the treatment of cardiovascular diseases was a milestone and one of the most important contributions to clinical medicine in the 20th century. For many years, beta-blockers were considered contraindicated in patients with chronic heart failure owing to the negative inotropic action of these substances. With increasing evidence of neurohormonal activation in heart failure patients, there was a focus on the potential role of beta-blockers in the treatment of chronic heart failure. Several large randomized placebo- controlled clinical trials have shown favorable effects of beta-blockers on mortality and morbidity in heart failure patients with impaired systolic function. Beneficial effects in patients with preserved left ventricular systolic function are less clear. A reduction in heart rate is one of several mechanisms by which beta-blockers exert beneficial effects in chronic heart failure. In this article we present results from major clinical trials examining beta-blocker treatment in chronic heart failure patients and discuss heart rate as a therapeutic target in these patients.

Candesartan, NT-proBNP and recurrence of atrial fibrillation after electrical cardioversion.

BACKGROUND Some small studies have suggested that low levels of brain natriuretic peptide (BNP) measured before electrical cardioversion for atrial fibrillation (AF) may be associated with maintenance of sinus rhythm after the procedure. We hypothesized that 1) plasma levels of N-terminal fragment of proBNP (NT-proBNP) measured before cardioversion were predictive of AF recurrence, 2) treatment with candesartan would influence the levels of NT-proBNP, and 3) restoration of sinus rhythm would reduce the levels of NT-proBNP. METHODS We investigated 171 patients with persistent AF who underwent electrical cardioversion in a prospective, blinded, placebo-controlled clinical trial (Candesartan in the Prevention of Relapsing Atrial Fibrillation, CAPRAF). Plasma levels of NT-proBNP were measured at baseline and at the end of the study. Patients with congestive heart failure were excluded from the study. RESULTS Baseline NT-proBNP levels were similar in patients with unsuccessful cardioversion (n=22), patients with successful cardioversion remaining in sinus rhythm (n=40) and patients with successful cardioversion who had a relapse of AF (n=89): median (interquartile range) 73.9 pmol/L (43.2, 145.6); 88.2 pmol/L (59.2, 147.5) and 90.0 pmol/L (55.3, 138.4), respectively. Maintenance of sinus rhythm was associated with a significant reduction in NT-proBNP levels, whereas NT-proBNP levels were not affected by treatment with candesartan. CONCLUSIONS Plasma NT-proBNP concentration measured before electrical cardioversion did neither predict cardioversion success nor relapse of AF in patients without heart failure. Treatment with candesartan did not affect the levels of NT-proBNP. Maintained sinus rhythm during follow-up was associated with a significant reduction in NT-proBNP levels.

Heart rate reserve predicts cardiovascular death among physically unfit but otherwise healthy middle-aged men: a 35-year follow-up study

Background Heart rate reserve (HRR) has been reported to be inversely associated with cardiovascular (CV) disease and death. The impact of physical fitness (PF) on this relationship has not, however, been described in detail. We investigated how different levels of PF influenced the association between HRR and CV death during a 35-year follow-up. Methods and results HRR and PF were measured in 2014 apparently healthy, middle-aged men during a symptom-limited bicycle exercise test in 1972–75. The men were divided into tertiles (T1-T3) by age-adjusted HRR. Morbidity and mortality data were registered from hospital charts through 2007 and the Norwegian Cause of Death Registry. Adjusted Cox proportional hazard regression models were used to calculate risks. Incidence of CV death was 528 (26%) during median 30 years of follow-up. Men with the lowest HRR had 41% (HR 1.41 [1.14–1.75]) increased risk of CV death compared with the men with the highest. We found a significant interaction between age-adjusted PF and HRR. After stratifying the men by PF, results were statistically significant only among men with the lowest PF, where the men with lowest HRR had a 70% (HR 1.70 [1.12–2.67]) increased risk of CV death compared with the men with the highest. Conclusions Low HRR was independently associated with increased risk of CV death in apparently healthy, middle-aged men. The predictive impact of HRR on CV death risk was, however, confined to unfit men.

Seven-Year Increase in Exercise Systolic Blood Pressure at Moderate Workload Predicts Long-Term Risk of Coronary Heart Disease and Mortality in Healthy Middle-Aged Men

Exercise systolic blood pressure (SBP) predicts coronary heart disease (CHD) in the general population. We tested whether changes in exercise SBP during 7 years predict CHD (including angina pectoris, nonfatal myocardial infarction, and fatal CHD) and mortality over the following 28 years. Peak SBP at 100 W workload (=5.5 METS [metabolic equivalents]; completed by all participants) was measured among 1392 apparently healthy men in 1972–75 and repeated in 1979–82. The men were divided into quartiles (Q1–Q4) of exercise SBP change. Relative risks were calculated using Cox proportional hazard regression adjusting for family history of CHD, age, smoking status, resting SBP, peak SBP at 100 W, total cholesterol at first examination (model 1), and further for physical fitness and change in physical fitness (model 2). The highest quartile, Q4, was associated with a 1.55-fold (95% confidence interval, 1.17–2.03) adjusted (model 1) risk of CHD and a 1.93-fold (1.24–3.02) risk of coronary heart death compared with the lowest, Q1. Q4 had a 1.40-fold (1.06–1.85) risk of CHD and a 1.70-fold (1.08–2.68) risk of coronary heart death using model 2. Q4 was associated with increased risk of cardiovascular death and all-cause death compared with Q1 in model 1, but not in model 2. Our results indicate that an increase in exercise SBP at 100 W over 7 years is independently associated with increased long-term risk of CHD and substantiate our previous finding that high exercise SBP is an important risk factor for CHD in healthy men.

Triglycerides-diabetes association in healthy middle-aged men: modified by physical fitness? A long term follow-up of 1962 Norwegian men in the Oslo Ischemia Study.

AIMS To examine the impact of physical fitness (PF) on the association between fasting serum triglycerides (FTG) and diabetes risk and whether temporal changes in FTG predict diabetes risk in healthy middle-aged men. METHODS FTG and PF (bicycle exercise test) were measured in 1962 men aged 40-59 years in 1972-1975 (Survey 1) and repeated in 1387 still healthy men on average 7.3 years later (Survey 2). Diabetes was diagnosed according to WHO 1985-criteria. RESULTS During 35 years follow-up 202/1962 (10.3%) men developed diabetes. Compared with the lowest, the upper FTG tertile had a 2.58-fold (95% CI: 1.81-3.74) diabetes risk adjusted for age, fasting blood glucose and maternal diabetes, and a 2.29-fold (95%CI: 1.60-3.33) when also adjusting for PF. Compared with unchanged (±25%) FTG levels (n=664), FTG reduction of more than 25% (n=261) was associated with 56% lower (0.44; 95% CI: 0.24-0.75) diabetes risk, while FTG increase of more than 25% (n=462) was associated with similar risk. These associations were unchanged when adjusted for PF and PF change. CONCLUSIONS High FTG-levels predicted long-term diabetes risk in healthy middle-aged men, and the association was only modestly weakened when adjusted for PF. A reduction in FTG was associated with decreased diabetes risk.

HDL-cholesterol and prediction of coronary heart disease: Modified by physical fitness? A 28-year follow-up of apparently healthy men

OBJECTIVE High-density lipoprotein cholesterol (HDL) and physical fitness (PF) have both been shown to predict cardiovascular disease (CVD), particularly coronary heart disease (CHD). Increased PF is associated with increased HDL and may partly explain the benefit of HDL. We tested the hypothesis that PF influences the prognostic impact of HDL for CHD and also for CHD-, CVD- and all-cause death. METHODS HDL was measured 1979-1982 in 1357 healthy men aged 44-69 years followed up to 28 years. PF was measured using bicycle exercise test. Hazard ratios (HRs) adjusted for age, smoking, systolic blood pressure, and total cholesterol and further for PF between HDL quartiles were calculated using Cox proportional survival model. RESULTS The highest HDL quartile was associated with lower risk of CHD (HR: 0.57, 95% confidence interval [CI]: 0.43-0.74), fatal CHD (HR: 0.56, CI: 0.36-0.86), fatal CVD (HR: 0.64, CI: 0.46-0.88) and all-cause death (HR: 0.80, CI: 0.65-0.99) compared to the lowest quartile. Adjustments for PF or changes in PF over 8.6 years did not change the results except for all-cause death, which was not significantly different between HDL quartiles. We found no interaction between HDL and PF. CONCLUSIONS HDL is a strong predictor of long term risk of CHD, fatal CHD and fatal CVD in healthy middle-aged men. Physical fitness or its changes had no impact on the ability of HDL to predict CHD.