Henrik Scharling

Very Low Levels of Microalbuminuria Are Associated With Increased Risk of Coronary Heart Disease and Death Independently of Renal Function, Hypertension, and Diabetes

Background—The aim of this study was to assess the level of urinary albumin excretion (microalbuminuria), which is associated with increased risk of coronary heart disease and death, in the population. Microalbuminuria has been suggested as an atherosclerotic risk factor. However, the lower cutoff level of urinary albumin excretion is unknown. It is also unknown whether impaired renal function confounds the association. Methods and Results—In the Third Copenhagen City Heart Study in 1992 to 1994, 2762 men and women 30 to 70 years of age underwent a detailed cardiovascular investigation program, including a timed overnight urine sample. The participants were then followed up prospectively by registers until 1999 with respect to coronary heart disease and until 2001 with respect to death. During follow-up, 109 incident cases of coronary heart disease and 276 deaths were traced. A urinary albumin excretion above the upper quartile, ie, 4.8 μg/min, was associated with increased risk of coronary heart disease (RR, 2.0; 95% CI, 1.4 to 3.0; P <0.001) and death (RR, 1.9; 95% CI, 1.5 to 2.4; P <0.001) independently of age, sex, renal creatinine clearance, diabetes mellitus, hypertension, and plasma lipids. Lower levels of urinary albumin excretion were not associated with increased risk. Conclusions—Microalbuminuria, defined as urinary albumin excretion >4.8 μg/min (corresponding to ≈6.4 μg/min during daytime), is a strong and independent determinant of coronary heart disease and death. Our suggestion is to redefine microalbuminuria accordingly and perform intervention studies.

Developing COPD: a 25 year follow up study of the general population

Background: Smokers are more prone to develop chronic obstructive pulmonary disease (COPD) than non-smokers, but this finding comes from studies spanning 10 years or less. The aim of this study was to determine the 25 year absolute risk of developing COPD in men and women from the general population. Methods: As part of the Copenhagen City Heart Study, 8045 men and women aged 30–60 years with normal lung function at baseline were followed for 25 years. Lung function measurements were collected and mortality from COPD during the 25 year observation period was analysed. Results: The percentage of men with normal lung function ranged from 96% of never smokers to 59% of continuous smokers; for women the proportions were 91% and 69%, respectively. The 25 year incidence of moderate and severe COPD was 20.7% and 3.6%, respectively, with no apparent difference between men and women. Smoking cessation, especially early in the follow up period, decreased the risk of developing COPD substantially compared with continuous smoking. During the follow up period there were 2912 deaths, 109 of which were from COPD. 92% of the COPD deaths occurred in subjects who were current smokers at the beginning of the follow up period. Conclusion: The absolute risk of developing COPD among continuous smokers is at least 25%, which is larger than was previously estimated.

Rising rates of hospital admissions for atrial fibrillation.

Background: Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality. We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospective population-based cohort study spanning 2 decades (the Copenhagen City Heart Study). Methods: The study included baseline data collected in 1981 through 1983 on 10,955 persons age 40 to 79 years and baseline data collected in 1991 through 1994 on 7212 persons age 40 to 79 years. We used hospital diagnosis data from the Danish National Hospital Discharge Register to determine the rate of first hospital admission for atrial fibrillation during 7 years following each of the 2 baseline data collecting periods. Changes in admission rates were analyzed using Cox proportional hazard models. Results: During the 2 7-year periods, 379 subjects were admitted with a hospital diagnosis of atrial fibrillation. The rate of hospital admissions for atrial fibrillation increased among both men and women from the first to the second period (relative risk = 1.6; 95% confidence interval = 1.3–1.9 [adjusted for age, sex, prior myocardial infarction, arterial hypertension, diabetes mellitus, electrocardiographic left ventricular hypertrophy, decreased lung function, smoking, height, and weight]). Conclusion: During the latest 10 to 20 years, there has been a 60% increase in hospital admissions for atrial fibrillation independent of changes in known risk factors. This increase could result from changes in admission threshold or coding practices, or it could reflect a genuine increase in the population incidence of atrial fibrillation.

Reduced lung function and risk of atrial fibrillation in The Copenhagen City Heart Study

Chronic obstructive pulmonary disease has been associated with a high frequency of arrhythmias. Few studies have analysed the role of reduced lung function in predicting atrial fibrillation (AF). The aim of the present study was to investigate the relationship between forced expiratory volume in one second (FEV1) and risk of first episode of AF in a prospective study. Data from 13,430 males and females without previous myocardial infarction, who participated in the Copenhagen City Heart Study, were analysed. New AF was assessed at re-examination after 5 yrs and by hospital admission for AF during a period of 13 yrs. Multivariate analyses were used with adjustment for cardiopulmonary risk factors. There were 62 new cases of AF at 5-yr follow-up (0.58%) and 290 cases (2.20%) diagnosed at hospitalisations. Risk of new AF at re-examination was 1.8-times higher for FEV1 between 60–80% of predicted compared with FEV1 ≥80% after adjustment for sex, age, smoking, blood pressure, diabetes and body mass index. The risk of AF hospitalisation was 1.3-times higher for FEV1 between 60–80% and 1.8-times higher for FEV1 <60% compared with FEV1 ≥80%, when additional adjustment was made for education, treatment with diuretics and chest pain at activity. The authors conclude that reduced lung function is an independent predictor for incident atrial fibrillation.

Long-term physical activity in leisure time and mortality from coronary heart disease, stroke, respiratory diseases, and cancer. The Copenhagen City Heart Study

Background The purpose of this study was to describe the associations between different levels of long-term physical activity in leisure time and subsequent causes of deaths. Design The Copenhagen City Heart Study is a prospective cardiovascular population study of 19 329 men and women aged 20–93 in 1976. Physical activity in leisure time was estimated at the examinations in 1976–78 and 1981–83. This analysis consists of 2136 healthy men and 2758 women aged 20–79 years, with unchanged physical activity at the two examinations, and with all covariates included in the multivariate analyses: smoking, total-cholesterol, high-density lipoprotein-cholesterol, systolic blood pressure, diabetes mellitus, alcohol consumption, body mass index, education, income, and forced expiratory volume in 10.78 (% predicted). Results Adjusted relative risks (95% confidence interval) for coronary heart disease were, for moderate physical activity 0.71 (0.51, 0.99) and for high 0.56 (0.38, 0.82). For cancer, moderate activity 0.77 (0.61, 0.97) and high activity 0.73 (0.56, 0.95) and for all-cause mortality, moderate 0.78 (0.68, 0.89) and high 0.75 (0.64, 0.87) for both sexes combined. Using Kaplan—Meier plots we calculated gained years of expected lifetime from age 50. Men with high physical activity survived 6.8 years longer, and men with moderate physical activity 4.9 years longer than sedentary men. For women the figures were 6.4 and 5.5 years, respectively. Conclusion Long-term moderate or high physical activity was in both sexes associated with significantly lower mortality from coronary heart disease, cancer and all-causes. The same tendency was found for stroke and respiratory diseases, but the associations did not reach statistical significance. Eur J Cardiovasc Prev Rehabil 13:173–179

New Definition of Microalbuminuria in Hypertensive Subjects: Association With Incident Coronary Heart Disease and Death

Microalbuminuria has so far been defined as urinary albumin excretion between 20 and 200 &mgr;g/min (or 15 to 150 &mgr;g/min overnight). In a recent report, an overnight urinary albumin excretion >5 &mgr;g/min was strongly predictive of coronary heart disease and death in the general population. The aim of the present study was to confirm this observation in a population of hypertensive individuals. In The Third Copenhagen City Heart Study in 1992 to 1994, 1734 men and women aged 30 to 70 years with hypertension, but no history of coronary heat disease, delivered a timed overnight urine sample. They were followed-up prospectively by registers until 2000 with respect to coronary heart disease, and until 2004 with respect to death. During follow-up, 123 incident cases of coronary heart disease and 308 deaths were traced. Incident coronary heart disease occurred in 11% of subjects with urinary albumin excretion ≥5 &mgr;g/min compared with 5% in subjects with urinary albumin excretion <5 &mgr;g/min (P<0.001). Similarly, the cumulative mortality was 28% versus 13% (P<0.001). The relative risks of coronary heart disease and death associated with urinary albumin excretion ≥5 &mgr;g/min were 2.0 (1.4 to 2.9; P<0.001) and 1.9 (1.5 to 2.3; P<0.001), respectively, after adjustment for age, sex, blood pressure level, antihypertensive drugs, diabetes, creatinine clearance, smoking, lipoproteins, and body mass index. In conclusion, our study supports the new definition of microalbuminuria as urinary albumin excretion >5 &mgr;g/min. In future risk assessment in hypertensive individuals, measurement of microalbuminuria has to be included.

Inhaled corticosteroids and decline of lung function in community residents with asthma

Background: Inhaled corticosteroids (ICS) constitute the cornerstone of treatment for asthma. Many studies have reported beneficial short term effects of these drugs, but there are few data on the long term effects of ICS on the decline in forced expiratory volume in 1 second (FEV1). This study was undertaken to determine whether adults with asthma treated with ICS have a less pronounced decline in FEV1 than those not treated with ICS. Methods: Two hundred and thirty four asthmatic individuals from a longitudinal epidemiological study of the general population of Copenhagen, Denmark were divided into two groups; 44 were treated with ICS and 190 were not treated with ICS. The annual decline in FEV1 was measured over a 10 year follow up period. Results: The decline in FEV1 in the 44 patients receiving ICS was 25 ml/year compared with 51 ml/year in the 190 patients not receiving this treatment (p<0.001). The linear regression model with ICS as the variable of interest and sex, smoking, and wheezing as covariates showed that treatment with ICS was associated with a less steep decline in FEV1 of 18 ml/year (p = 0.01). Adjustment for additional variables including age, socioeconomic status, body mass index, mucus hypersecretion, and use of other asthma medications did not change these results. Conclusions: Treatment with ICS is associated with a significantly reduced decline in ventilatory function.

Intensity versus duration of walking, impact on mortality: the Copenhagen City Heart Study.

Background Current recommendations prescribe that every adult should accumulate 30 min or more of moderate-intensity physical activity in leisure time, preferably all days of the week. To further support these recommendations we examined the impact of walking intensity and walking duration on all-cause mortality. Design Relative intensity and duration of walking were recorded in 7308 healthy women and men aged 20-93 at the third examination (1991-1994) of the Copenhagen City Heart Study. During an average of 12 years of follow-up 1391 deaths were recorded. Results For both sexes we found a significant inverse association between walking intensity and risk of death, but only a weak inverse association to walking duration. For women walking with average intensity, the adjusted hazard ratio (HR) of death was 0.75 [95% confidence interval (CI) 0.61–0.92; P < 0.01] and walking with fast intensity 0.48 (95% CI 0.35–0.66; P > 0.001) compared to women walking with slow intensity. For men the relative risks were 0.54 (95% CI 0.45–0.67; P < 0.001) and 0.43 (95% CI 0.32–0.59; P < 0.001), respectively. Conclusion Our findings indicate that the relative intensity and not the duration of walking is of most importance in relation to all-cause mortality. Thus our general recommendation to all adults would be that brisk walking is preferable to slow. Eur J Cardiovasc Prev Rehabil 14: 72-78

Microalbuminuria and obesity: impact on cardiovascular disease and mortality

Objective  Microalbuminuria and obesity are both associated with cardiovascular disease (CVD). The aim of this study was to determine the association between obesity (measured by body mass index, waist‐to‐hip ratio, waist circumference) and different levels of microalbuminuria. We also aimed to determine the risk of death and CVD at different levels of microalbuminuria and obesity.

Hypercholesterolaemia and risk of coronary heart disease in the elderly: Impact of age: The Copenhagen City Heart Study

BACKGROUND Population and interventional studies have shown that high plasma-cholesterol is a risk factor of coronary heart disease (CHD). However, in most of the studies elderly people were excluded. AIM This paper assesses whether the effect of total plasma-cholesterol on the risk of incident CHD decreases with age in a healthy population. METHODS Within the Copenhagen City Heart Study in 1981-1983, 4647 men and 5829 women, aged 40-93 years, underwent a cardiovascular health examination including measurement of plasma-cholesterol. The cohort was followed with respect to incident CHD until 1994, i.e. before statins were introduced in Denmark. RESULTS In people below 60 years of age plasma-cholesterol levels on 5-6; 6-8; and >8 mmol/L were associated with relative risks of CHD on 2.0 (95% confidence interval (CI) 1.2-3.2, P=0.004); 3.1 (CI 2.0-5.0, P<0.001); and 5.1 (CI 2.8-9.3, P<0.001), respectively (reference group: plasma-cholesterol <5 mmol/L). In people aged 60-70 years a plasma-cholesterol level on 5-6 mmol/L was not associated with increased risk, whereas plasma-cholesterol on 6-8 mmol/L and >8 mmol/L was associated with relative risks on 1.3 (CI 1.0-1.8, P=0.03), and 2.3 (CI 1.6-3.4, P<0.001), respectively. In people aged 70-80 years only plasma-cholesterol >8 mmol/L conferred increased relative risk on 1.6 (CI 1.2-2.4, P=0.007). In people above 80 years of age increased plasma-cholesterol was not associated with increased risk of incident CHD. CONCLUSION The risk of incident CHD associated with high plasma-cholesterol declines with age. This finding should be considered in future recommendations of plasma-cholesterol levels in elderly people without atherosclerotic cardiovascular disease.