Johan Bodegard

Possible angina detected by the WHO angina questionnaire in apparently healthy men with a normal exercise ECG: coronary heart disease or not? A 26 year follow up study.

Objective: To determine whether men with possible angina (from their responses to the World Health Organization angina questionnaire) but a normal exercise ECG differ in long term rates of coronary heart disease events from men with no symptoms of angina. Design: During 1972–75, 2014 apparently healthy men aged 40–59 years underwent an examination programme including case history, clinical examination, exercise ECG to exhaustion, and various other tests. All men completed the WHO angina questionnaire. Subjects: Of 2014 men, 68 had possible angina, 1831 had no symptoms of angina, and 115 were excluded because they had definite angina or pathological exercise ECGs. All 68+1831 had normal exercise ECGs and none developed chest pain during the exercise test. Results: At 26 years, men with possible angina had a coronary heart disease mortality of 25.0% (17/68) v 13.8% (252/1831) among men with no symptoms of angina (p < 0.013). They also had a higher incidence of coronary artery bypass grafting (CABG) (p < 0.0004) and acute myocardial infarction (p < 0.026). The excess coronary heart disease mortality among men with possible angina only started after 15 years, whereas differences in CABG/acute myocardial infarction started early. Multivariate analysis including well recognised coronary heart disease risk factors showed that possible angina was an independent risk factor (relative risk 1.79, 95% confidence interval 1.26 to 2.10). Conclusions: Men with possible angina, even with a normal exercise test, have a greater risk of dying from coronary heart disease, having an acute myocardial infarct, or needing a CABG than age matched counterparts with no symptoms of angina.

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 (53u2009000 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.

Interaction between inflammation and blood viscosity predicts cardiovascular mortality

OBJECTIVESnInflammation and increased blood viscosity are associated with increased risk of cardiovascular mortality. Erythrocyte sedimentation rate (ESR) and hematocrit both influence blood viscosity whereas the first also is a marker of inflammation. We aimed to investigate ESR, hematocrit and the interaction between them as predictors of cardiovascular mortality during 26 years follow-up among healthy middle aged men.nnnDESIGNnFour hundred and eighty eight men aged 40-59 were extensively examined in 1972-1975 and followed over a period of 26 years. Risk estimation was made in Cox proportional hazards and adjusted for age, smoking, systolic blood pressure, total serum cholesterol, and physical fitness.nnnRESULTSnA 2.44-fold (95% CI 1.37-4.35) adjusted risk of cardiovascular mortality was found in the highest quartile of hematocrit compared to the lowest. Among the 265 men who had an ESR <6 mm/h (median), the adjusted risk of cardiovascular mortality was 3.05-fold (95% CI 1.49-6.23) in the highest quartile of hematocrit compared to the lowest. This association was not observed among the 223 men with ESR <6 mm/h.nnnCONCLUSIONnElevated hematocrit is independently associated with increased long-term risk of cardiovascular mortality in men with high ESR. Our data suggest that the combination of inflammation and blood viscosity may improve the prediction of cardiovascular risk.

Symptom-limited exercise testing, ST depressions and long-term coronary heart disease mortality in apparently healthy middle-aged men

Background Previous studies have shown that ST depressions ≤ 1.0 mm during or post-exercise increase long-term risk of dying from coronary heart disease (CHD), the need for coronary artery bypass grafting (CABG) or the development of acute myocardial infarction (AMI) in healthy men. In the present prospective cohort study we investigate whether less marked ST depressions may influence CHD mortality, incidence of AMI, the need for a CABG or having a non-fatal stroke. Methods During 1972–75, 2014 men aged 40–59 years, free from somatic diseases and not using any drugs, underwent an examination programme including case history, clinical examination, various blood tests and a symptom-limited exercise ECG-test. ECG was registered during exercise and at 30 s, 1, 2, 3 and 5 min post-exercise. The possible prognostic impact of ST-changes of 0.50–0.99 mm and ≤ 1.00 mm compared with normal ST-segments were studied separately and combined. Horizontal, down-sloping and slowly up-sloping ST-segment patterns were combined. Results After adjustment for age, smoking, blood pressure, cholesterol, maximal heart rate, left ventricular hypertrophy and physical fitness ST depressions ≤ 0.50 mm - during and/or post-exercise - were associated with a 1.47-fold [95% confidence interval (CI) 1.10–1.95], and 1.54-fold (95% CI of 1.17–2.04) increased 26 years risk of CHD-mortality, respectively. The same ST-changes also increased 22 years risk of developing non-fatal AMI or needing CABG but not developing non-fatal stroke. Conclusions Even an ST depression ≤ 0.50 mm during and/or after exercise increases the long-term risk of CHD-death, developing an AMI or needing CABG. No association was found between ST-changes and incidence of non-fatal strokes.

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.

Diabetes and CVD risk during angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment in hypertension: a study of 15 990 patients

Differences in clinical effectiveness between angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in the primary treatment of hypertension are unknown. The aim of this retrospective cohort study was to assess the prevention of type 2 diabetes and cardiovascular disease (CVD) in patients treated with ARBs or ACEis. Patients initiated on enalapril or candesartan treatment in 71 Swedish primary care centers between 1999 and 2007 were included. Medical records data were extracted and linked with nationwide hospital discharge and cause of death registers. The 11u2009725 patients initiated on enalapril and 4265 on candesartan had similar baseline characteristics. During a mean follow-up of 1.84 years, 36u2009482 patient-years, the risk of new diabetes onset was lower in the candesartan group (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69–0.96, P=0.01) compared with the enalapril group. No difference between the groups was observed in CVD risk (HR 0.99, 95% CI 0.87–1.13, P=0.86). More patients discontinued treatment in the enalapril group (38.1%) vs the candesartan group (27.2%). In a clinical setting, patients initiated on candesartan treatment had a lower risk of new-onset type 2 diabetes and lower rates of drug discontinuation compared with patients initiated on enalapril. No differences in CVD risk were observed.

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.

AIMSnTo 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.nnnMETHODSnFTG 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.nnnRESULTSnDuring 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.nnnCONCLUSIONSnHigh 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

OBJECTIVEnHigh-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.nnnMETHODSnHDL 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnHDL 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.

Rapidly upsloping ST-segment on exercise ECG: a marker of reduced coronary heart disease mortality risk

Background: The prognostic value of an isolated J-point depression, or rapidly upsloping ST-segment, on an exercise ECG has long been assumed to be a benign variant. However, little or no data supporting this assumption may be found in the literature. Our task was to examine if a rapidly upsloping ST-segment on an exercise ECG is associated with changes in risk of dying from CHD in 2014 healthy middle-aged men followed for 35 years. Methods: A group of healthy middle-aged men (nu2009=u20092014) participated in a cardiovascular survey. They underwent an examination programme including a symptom-limited ECG bicycle exercise test. Exercise induced ST-segments were categorised in three groups: normal ST-segment (nu2009=u20091383), rapidly upsloping (nu2009=u2009401), and ST-depression (nu2009=u2009230). Survival analyses were adjusted for smoking status, total cholesterol, systolic blood pressure, maximal heart rate, and physical fitness. The mean follow-up time was 35 years. Results: The rapidly upsloping group had a 30% decreased risk of CHD death (hazard ratio, HR, 0.70, 95% CI 0.51–0.95) compared to the normal ST-segment group. The risk of CVD-death was numerically lower in the rapidly upsloping group (HR 0.82, 95% CI 0.65–1.04) compared to the normal ST-segment group. The ST-depression group had a 1.45-fold (HR 1.45, 95% CI 1.09–1.90) increased risk of CHD death compared to the normal ST-segment group. Conclusions: The rapidly upsloping ST-segment was a common finding (20%) on exercise ECG among healthy middle-aged men and was associated with a 30% reduced risk of dying from CHD compared to individuals with normal ST-segment. A rapidly upsloping ST-segment on exercise ECG may represent the true healthy state.