Coronary artery disease risk reclassification by a new acoustic-based score.

To determine the potential of a non-invasive acoustic device (CADScor®System) to reclassify patients with intermediate pre-test probability (PTP) and clinically suspected stable coronary artery disease (CAD) into a low probability group thereby ruling out significant CAD. Audio recordings and clinical data from three studies were collected in a single database. In all studies, patients with a coronary CT angiography indicating CAD were referred to coronary angiography. Audio recordings of heart sounds were processed to construct a CAD-score. PTP was calculated using the updated Diamond-Forrester score and patients were classified according to the current ESC guidelines for stable CAD: low < 15%, intermediate 15-85% and high > 85% PTP. Intermediate PTP patients were re-classified to low probability if the CAD-score was ≤ 20. Of 2245 patients, 212 (9.4%) had significant CAD confirmed by coronary angiography ( ≥ 50% diameter stenosis). The average CAD-score was higher in patients with significant CAD (38.4 ± 13.9) compared to the remaining patients (25.1 ± 13.8; p < 0.001). The reclassification increased the proportion of low PTP patients from 13.6% to 41.8%, reducing the proportion of intermediate PTP patients from 83.4% to 55.2%. Before reclassification 7 (3.1%) low PTP patients had CAD, whereas post-reclassification this number increased to 28 (4.0%) (p = 0.52). The net reclassification index was 0.209. Utilization of a low-cost acoustic device in patients with intermediate PTP could potentially reduce the number of patients referred for further testing, without a significant increase in the false negative rate, and thus improve the cost-effectiveness for patients with suspected stable CAD.

Baseline findings of the population-based, randomized, multifaceted Danish cardiovascular screening trial (DANCAVAS) of men aged 65-74 years.

BACKGROUND: The challenge of managing age-related diseases is increasing; routine checks by the general practitioner do not reduce cardiovascular mortality. The aim here was to reduce cardiovascular mortality by advanced population-based cardiovascular screening. The present article reports the organization of the study, the acceptability of the screening offer, and the relevance of multifaceted screening for prevention and management of cardiovascular disease. METHODS: Danish men aged 65-74 years were invited randomly (1 : 2) to a cardiovascular screening examination using low-dose non-contrast CT, ankle and brachial BP measurements, and blood tests. RESULTS: In all, 16 768 of 47 322 men aged 65-74 years were invited and 10 471 attended (uptake 62·4 per cent). Of these, 3481 (33·2 per cent) had a coronary artery calcium score above 400 units. Thoracic aortic aneurysm was diagnosed in the ascending aorta (diameter 45 mm or greater) in 468 men (4·5 per cent), in the arch (at least 40 mm) in 48 (0·5 per cent) and in the descending aorta (35 mm or more) in 233 (2·2 per cent). Abdominal aortic aneurysm (at least 30 mm) and iliac aneurysm (20 mm or greater) were diagnosed in 533 (5·1 per cent) and 239 (2·3 per cent) men respectively. Peripheral artery disease was diagnosed in 1147 men (11·0 per cent), potentially uncontrolled hypertension (at least 160/100 mmHg) in 835 (8·0 per cent), previously unknown atrial fibrillation confirmed by ECG in 50 (0·5 per cent), previously unknown diabetes mellitus in 180 (1·7 per cent) and isolated severe hyperlipidaemia in 48 men (0·5 per cent). In all, 4387 men (41·9 per cent), excluding those with potentially uncontrolled hypertension, were referred for additional cardiovascular prevention. Of these, 3712 (35·5 per cent of all screened men, but 84·6 per cent of those referred) consented and were started on medication. CONCLUSION: Multifaceted cardiovascular screening is feasible and may optimize cardiovascular disease prevention in men aged 65-74 years. Uptake is lower than in aortic aneurysm screening.

First experiences with model based iterative reconstructions influence on quantitative plaque volume and intensity measurements in coronary computed tomography angiography.

PURPOSE: Investigate the influence of adaptive statistical iterative reconstruction (ASIR) and the model-based IR (Veo) reconstruction algorithm in coronary computed tomography angiography (CCTA) images on quantitative measurements in coronary arteries for plaque volumes and intensities. METHODS: Three patients had three independent dose reduced CCTA performed and reconstructed with 30% ASIR (CTDIvol at 6.7 mGy), 60% ASIR (CTDIvol 4.3 mGy) and Veo (CTDIvol at 1.9 mGy). Coronary plaque analysis was performed for each measured CCTA volumes, plaque burden and intensities. RESULTS: Plaque volume and plaque burden show a decreasing tendency from ASIR to Veo as median volume for ASIR is 314 mm3 and 337 mm3-252 mm3 for Veo and plaque burden is 42% and 44% for ASIR to 39% for Veo. The lumen and vessel volume decrease slightly from 30% ASIR to 60% ASIR with 498 mm3-391 mm3 for lumen volume and vessel volume from 939 mm3 to 830 mm3. The intensities did not change overall between the different reconstructions for either lumen or plaque. CONCLUSION: We found a tendency of decreasing plaque volumes and plaque burden but no change in intensities with the use of low dose Veo CCTA (1.9 mGy) compared to dose reduced ASIR CCTA (6.7 mGy & 4.3 mGy), although more studies are warranted.

The DanCavas Pilot Study of Multifaceted Screening for Subclinical Cardiovascular Disease in Men and Women Aged 65-74 Years.

OBJECTIVE/BACKGROUND: This pilot study of a large population based randomised screening trial investigated feasibility, acceptability, and relevance (prevalence of clinical and subclinical cardiovascular disease [CVD] and proportion receiving insufficient prevention) of a multifaceted screening for CVD. METHODS: In total, 2060 randomly selected Danish men and women aged 65-74 years were offered (i) low dose non-contrast computed tomography to detect coronary artery calcification (CAC) and aortic/iliac aneurysms; (ii) detection of atrial fibrillation (AF); (iii) brachial and ankle blood pressure measurements; and (iv) blood levels of cholesterol and hemoglobin A1c. Web based self booking and data management was used to reduce the administrative burden. RESULTS: Attendance rates were 64.9% (n = 678) and 63.0% (n = 640) for men and women, respectively. In total, 39.7% received a recommendation for medical preventive actions. Prevalence of aneurysms was 12.4% (95% confidence interval [CI] 9.9-14.9) in men and 1.1% (95% CI 0.3-1.9) in women, respectively (p < .001). A CAC score > 400 was found in 37.8% of men and 11.3% of women (p < .001), along with a significant increase in median CAC score with age (p = .03). Peripheral arterial disease was more prevalent in men (18.8%, 95% CI 15.8-21.8) than in women (11.2%, 95% CI 8.7-13.6). No significant differences between the sexes were found with regard to newly discovered AF (men 1.3%, women 0.5%), potential hypertension (men 9.7%, women 11.5%), hypercholesterolemia (men 0.9%, women 1.1%) or diabetes mellitus (men 2.1%, women 1.3%). CONCLUSION: Owing to the higher prevalence of severe conditions, such as aneurysms and CAC ≥ 400, screening for CVD seemed more prudent in men than women. The attendance rates were acceptable compared with other screening programs and the logistical structure of the screening program proved successful.

Pre-treatment with a sinus node blockade, ivabradine, before coronary CT angiography: a retrospective audit.

AIM: To evaluate whether a simple pre-treatment regimen of sinus node inhibition by ivabradine taken at home for only 1 day resulted in a lower pre-scanning heart rate (HR) and reduced the need for intravenous beta-blockers (BB) prior to coronary computed tomography angiography (CTA). MATERIALS AND METHODS: The pre-treatment regimen for coronary CTA changed from using no medication at home (group 1 patients) to the use of 5 mg ivabradine twice a day (group 2 patients), to using 7.5 mg ivabradine twice a day (group 3 patients). The target HR was the same for groups 1 and 2, but lower for group 3. HRs and the use of intravenous BB before coronary CTA was performed were compared between the study groups. RESULTS: The mean HR immediately before the planned CTA procedure was significantly lower throughout groups 1-3 with values of 70 ± 12.9, 64.9 ± 9.8, and 63.2 ± 10.6 beats/min in groups 1, 2, and 3, respectively (p < 0.001). This resulted in a significantly diminished use of intravenous BB in group 2 (mean 5.1 ± 5.8 mg) compared to group 1 (mean 9 ± 7.6 mg; p = 0.002). The target HR of 65 beats/min was achieved in 37%, 47%, and 61% of groups 1, 2, and 3, respectively (p < 0.0001). CONCLUSION: In conclusion, the administration of ivabradine tablets at home for only 1 day to patients scheduled for coronary CTA resulted in a significantly lower in-clinic HR and a significantly lower mean use of intravenous BB.

The relation between coronary artery calcification in asymptomatic subjects and both traditional risk factors and living in the city centre: a DanRisk substudy.

OBJECTIVE: To evaluate the association between the risk factor for living in the city centre as a surrogate for air pollution and the presence of coronary artery calcification (CAC) in a population of asymptomatic Danish subjects. DESIGN AND SUBJECTS: A random sample of 1825 men and women of either 50 or 60 years of age were invited to take part in a screening project designed to assess risk factors for cardiovascular disease (CVD). Noncontrast cardiac computed tomography was performed on all subjects, and their Agatston scores were calculated to evaluate the presence of subclinical coronary atherosclerosis. The relationship between CAC and several demographic and clinical parameters was evaluated using multivariate logistic regression. RESULTS: A total of 1225 individuals participated in the study, of whom 250 (20%) were living in the centres of major Danish cities. Gender and age showed the greatest association with the presence of CAC: the odds ratio (OR) for men compared with women was 3.2 [95% confidence interval (CI) 2.5-4.2; P < 0.0001], and the OR for subjects aged 60 versus those aged 50 years was 2.2 (95% CI 1.7-2.8; P < 0.0001). Other variables independently associated with the presence of CAC were diabetes and smoking with ORs of 2.0 (95% CI 1.1-3.5; P = 0.03) and 1.9 (95% CI 1.4-2.5, P < 0.0001), respectively. The adjusted OR for subjects living in city centres compared to those living outside was 1.8 (95% CI 1.3-2.4; P = 0.0003). CONCLUSION: Both conventional risk factors for CVD and living in a city centre are independently associated with the presence of CAC in asymptomatic middle-aged subjects.

Impact of calibration on estimates of central blood pressures.

Using the Sphygmocor device it is recommended that the radial pressure wave is calibrated for brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP). However it has been suggested that brachial-to-radial pressure amplification causes underestimation of central blood pressures (BPs) using this calibration. In the present study we examined if different calibrations had an impact on estimates of central BPs and on the clinical interpretation of our results. On the basis of ambulatory BP measurements, patients were categorized into patients with controlled, uncontrolled or resistant hypertension. We first calibrated the radial pressure wave as recommended and afterwards recalibrated the same pressure wave using brachial DBP and calculated mean arterial pressure. Recalibration of the pressure wave generated significantly higher estimates of central SBP (P=0.0003 and P<0.0001 at baseline and P=0.0001 and P=0.0002 after 6 months). Using recommended calibration we found a significant change in central SBP in both treatment groups (P=0.05 and P=0.01), however, after recalibrating significance was lost in patients with resistant hypertension (P=0.15). We conclude that calibration with DBP and mean arterial pressure produces higher estimates of central BPs than recommended calibration. The present study also shows that this difference between the two calibration methods can produce more than a systematic error and has an impact on interpretation of clinical results.

High-sensitive C-reactive protein is associated with reduced lung function in young adults.

Systemic inflammation has been associated with reduced lung function. However, data on the interrelationships between lung function and inflammation are sparse, and it is not clear if low-grade inflammation leads to reduced lung function. Associations between high-sensitive C-reactive protein (CRP) and spirometric lung function were assessed in a population-based cohort of approximately 1,000 Danes aged 20 yrs. In males, the average decline in forced expiratory volume in one second (FEV(1)) in the highest CRP quintile was 23 mL.yr(-1) versus 1.6 mL.yr(-1) in the lowest quintile. In females, the average decline was 6.2 mL.yr(-1) in the highest CRP quintile versus an increase of 1.8 mL.yr(-1) in the lowest CRP quintile. In a multiple regression analysis adjusted for sex, body mass index, cardiorespiratory fitness, smoking, asthma, airway hyperresponsiveness and serum eosinophil cationic protein, higher levels of CRP at age 20 yrs were associated with a greater reduction in both FEV(1) and forced vital capacity between ages 20 and 29 yrs. The findings show that higher levels of C-reactive protein in young adults are associated with subsequent decline in lung function, suggesting that low-grade systemic inflammation in young adulthood may lead to impaired lung function independently of the effects of smoking, obesity, cardiorespiratory fitness, asthma and eosinophilic inflammation.

Impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic teenagers.

AIM: To investigate the impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic subjects. METHODS: In this prospective, community-based study, 271 asymptomatic adolescents with an average age at inclusion of 13.9 years were followed for 6.4 years. Airway lability was assessed at baseline by three tests, including exercise challenge, airway provocation with methacholine, and monitoring of peak expiratory flow. Atopy was defined by one or more positive reactions (> or = 3-mm weal) to 10 common aeroallergens by skin prick testing. The influence of airway lability, atopy, and smoking on the development of asthma-like symptoms was assessed by logistic regression. RESULTS: During the 6-year study period, 68 of the previously asymptomatic teenagers (25%) developed asthma-like symptoms. Among those, 50% reported cough only, 29% reported wheezing only, and 21% reported both wheezing and coughing. Hyperresponsiveness to methacholine (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.1 to 11.6), smoking (OR, 2.1; 95% CI, 1. 2 to 3.8), and atopy (OR, 3.5; 95% CI, 1.8 to 6.8) each contributed independently to explain symptom development (wheezing and cough together). Girls, but not boys, with airway lability were less likely to take up smoking, compared with subjects of that set with no airway lability (32% vs 51%; p < 0.05). No effect of airway lability on the likelihood of giving up smoking could be demonstrated, nor did the presence of atopy have any significant impact on smoking behavior. CONCLUSION: Hyperresponsiveness to methacholine, atopy, and smoking were independent risk factors for the development of asthma-like symptoms during adolescence. The presence of airway lability may prevent girls from taking up smoking.

Increased eosinophil cation protein level in sensitized nonasthmatics is linked to subsequent hyperresponsiveness to methacholine. The Odense Schoolchild Study.

BACKGROUND: Increased levels of eosinophil cation protein (ECP) in sensitized subjects may reflect early stages of an ongoing inflammatory process and therefore precede asthma and bronchial hyperreactivity. AIM: To study whether nonasthmatic subjects with sensitization to allergens and increased ECP levels are at a higher risk for subsequent increased bronchial reactivity compared with sensitized nonasthmatics with normal ECP levels. METHODS: A prospective study of 240 schoolchildren with a mean age of 13.9 years (range: 12.6-15.9) who were followed up after 6.3 years. Bronchial reactivity was assessed by methacholine provocation testing. Sensitization was defined by one or more positive reactions (>3 mm wheal) to 10 common aeroallergens by skin prick testing. Increased ECP was defined as values above 20 microg/l. This separated the subjects into four categories: group 1: healthy controls without sensitization (n = 147); group 2: sensitized subjects with a serum ECP below 20 microg/l (n = 55); group 3: sensitized subjects with an ECP level at or above 20 microg/l (n = 16), and group 4: all asthmatics (n = 22). RESULTS: Bronchial reactivity was similar in subjects of groups 2 and 3 at baseline (p = 0.8). Six years later, subjects from group 3 were more responsive to methacholine compared with subjects from group 2 (median: 12.7 versus 20.5 micromol; p < 0.05). In a logistic regression with hyperresponsiveness to methacholine at follow-up as dependent variable, the odds ratios (OR) for the groups were, with group 1 as reference: group 2: OR = 2.2 (0.8-6.6: p = 0.2), group 3: 5.9 (1. 6-21.7: p < 0.01). CONCLUSION: Subjects with sensitization and increased ECP levels are subsequently more airway-responsive to methacholine compared with sensitized subjects with normal ECP levels. This supports the hypothesis that sensitization is linked to increased bronchial reactivity through a process in which markers of inflammation are involved.

Low physical fitness in childhood is associated with the development of asthma in young adulthood: the Odense schoolchild study.

Intense physical activity in children may either improve fitness and protect against asthma, or may trigger symptoms. The aim of this study was to determine whether physical fitness in childhood has an impact on the development of asthma. In this prospective, community-based study, 757 (84%) asymptomatic children with an average age at inclusion of 9.7 yrs were followed for 10.5 yrs. In both surveys a maximal progressive exercise test on a bicycle ergometer was used to measure physical fitness (maximal workload) and to induce airway narrowing. A methacholine provocation test was performed in the subjects at follow-up. During the 10-yr study period, 51 (6.7%) of the previously asymptomatic children developed asthma. These subjects had a lower mean physical fitness in 1985 than their peers: (3.63 versus 3.89 W x kg(-1); p=0.02) in boys and (3.17 versus 3.33 W x kg(-1); p=0.02) in girls. A weak correlation was found between physical fitness in childhood and airway responsiveness to methacholine at follow-up when adjusted for body mass index, age and sex (r=0.11; p<0.01). In a multiple regression analysis, physical fitness was inversely related to the development of physician diagnosed asthma, odds ratio=0.93 (0.87-0.99). Thus, the risk for the development of asthma during adolescence is reduced 7% by increasing the maximal workload 1 W x kg(-1). In conclusion, this study showed that physical fitness in childhood is weakly correlated with the development of asthma during adolescence and that high physical fitness seems to be associated with a reduced risk for the development of asthma.

Tracking and factors predicting rising in 'tracking quartile' in blood pressure from childhood to adulthood: Odense Schoolchild Study.

This prospective study determines the degree of tracking and investigates factors predicting a rise in blood pressure (BP) quartile in a cohort of 1369 subjects who were followed for 11 years from childhood into young adulthood. In 900 of these subjects BP, height, weight, physical fitness and BP responses to a maximal exercise testing were measured both at baseline and at follow-up. BP, weight, height and body mass index (BMI) were divided into sex-specific quartiles at both examinations. Tracking was evaluated by examining the tendency of remaining in the same quartile from baseline to follow-up and by measuring product-moment correlation coefficients. Tracking in the upper and lower quartile for BP, weight, height and BMI were significant. Odds ratios for staying in the upper or lower quartile through the follow-up period ranged from 1.6 to 2.4 for diastolic BP and from 2.1 to 3.1 for systolic BP. The range of correlation coefficients for the anthropometric measurements were 0.57-0.75, for diastolic BP 0.12-0.22 and for systolic BP 0.34-0.36 respectively. Changes in weight or relative weight as well as BP response to an exercise test were the factors which predicted a rise in quartile through the 11 years of follow-up. The existence of the inevitable regression to the mean problem in large longitudinal studies of BP was demonstrated by the finding of baseline BP being a significant factor in the prediction of rising in systolic, diastolic or both systolic and diastolic BP quartiles.

Asymptomatic bronchial hyperresponsiveness to exercise in childhood and the development of asthma related symptoms in young adulthood: the Odense Schoolchild Study.

BACKGROUND: Exercise testing may be of value in identifying a group of children at high risk of subsequently developing respiratory symptoms. As few longitudinal studies have investigated this issue, the bronchial hyperresponsiveness to exercise in asymptomatic children was evaluated as a risk factor for developing asthma related symptoms in young adulthood. METHODS: A community based sample of 1369 schoolchildren, first investigated in 1985 at a mean age of 9.7 years, was followed up after a mean of 10.5 years. Nine hundred and twenty children (67%) were asymptomatic in childhood and 777 (84.9%) of these were re-investigated at follow up. At the first examination a maximum progressive exercise test on a bicycle ergometer was used to induce airway narrowing. The forced expiratory volume in one second (FEV1) after exercise was considered abnormal if the percentage fall in FEV1 was more than 5% of the highest fall in the reference subjects characterised by having no previous history of asthma or asthma related symptoms. The threshold for a positive test was 8.6% of pre-exercise FEV1. RESULTS: One hundred and three subjects (13%) had wheeze within the last year at follow up and, of these, nine (9%) had been hyperresponsive to exercise in 1985. One hundred and seventy subjects (22%) had non-infectious cough within the previous year, 11 of whom (6%) had been hyperresponsive to exercise in 1985. Multiple regression analysis showed that subjects with hyperresponsiveness to exercise had an increased risk of developing wheeze compared with subjects with a normal response to exercise when the fall in FEV1 after exercise was included as a variable (threshold odds ratio (OR) 2.3 (95% CI 1.1 to 5.5)). The trend was not significant when exercise induced bronchospasm was included as a continuous variable (OR 1.02 (95% CI 0.97 to 1.06)). CONCLUSIONS: Asymptomatic children who are hyperresponsive to exercise are at increased risk of developing new symptoms related to wheezing but the predictive value of exercise testing for individuals is low.

Ambulatory blood pressure in 570 Danes aged 19-21 years: the Odense Schoolchild Study.

Ambulatory blood pressure (ABP) measurements were performed in a Danish population of 295 males and 275 females aged 19-21 years. Individualised day and night periods were defined from the subjects own recording of bedtime and rising on the day of their ABP measurements. During these individualised periods the ABP values for daytime, night-time and for the whole 24-h period were measured. The mean +/- s.d. values for systolic/diastolic ABP for the whole population were (124+/-11)/(70+/-7) mm Hg in the daytime, (106+/-12)/(60+/-9) mm Hg in the night-time, and (120+/-11)/(68+/-7) mm Hg in the whole 24-h period. Males had a mean systolic ABP of 9 mm Hg and mean diastolic ABP of 5 mm Hg higher than females. In males mean +/- s.d. systolic/diastolic ABP values in the daytime were (129+/-10)/(73+/-7) mm Hg, in the night-time (111+/-12)/(63+/-8) mm Hg, and in the whole 24-h period (125+/-10)/(71+/-7) mm Hg. The corresponding values in females were (119+/-10)/(68+/-6) mm Hg, (103+/-11)/(57+/-8) mmHg, and (115+/-10)/(66+/-6) mm Hg, respectively. In conclusion this study provides sex-specific normal values for ABP in a 19 to 21-year-old age group based on individualised daytime and night-time periods.

[Use of thermotherapy, ultrasound and laser by practising physiotherapists. Physiotherapists' choice of treatment]. / Praktiserende fysioterapeuters anvendelse af termisk terapi, ultralyd og laser. Fysioterapeuters behandlingsvalg.

The purpose of this examination was to examine the practising physiotherapist's way of treating patients with nine selected diagnoses (fibrosites, osteoarthritis, rheumatoid arthritis, cervical slipped disc, lumbar slipped disc, generalized lumbar/back pain, generalized bursitis, generalized tendinitis, and sprains). In addition, nine different forms of therapy were examined (hot packs, infra-red light, ice packs, short waves, microwaves, diadynamic current, ultrasound, transcutaneous electric nerve stimulation and laser). All in all, 41 clinics with 2,018 treatment confrontations in the examination period, the last week of March 1990, took part in the survey. The majority of therapists were in possession of short wave, hot packs, ultrasound and laser which are also the four forms of therapy most frequently used for treatment. Compared to a Swedish examination from 1979, there is a doubling in ultrasound treatments from 24% to 48%, while the amount of short wave and microwave treatment remained unchanged. There was a remarkable variation in the physiotherapist's choice of therapy in each different diagnosed case. This can be due to the lack of specification of the diagnosis, so that different symptoms, course and stage of illness changed the treatment pattern elected.

Efficiency of the countercurrent transfer of heat and 133Xenon between the pampiniform plexus and testicular artery of the bull under in-vitro conditions.

The efficiency of countercurrent transfer of heat and 133Xenon (133Xn) in spermatic cords of the bull was measured under in-vitro conditions. Plasma was pumped through the artery and veins via two separate systems under controlled temperature conditions. Cold plasma or 133Xn-saline was introduced into the afferent veins and the transfer of heat or gas from the venous to the arterial side was measured. The mean efficiency of heat transfer was found to be 91% in five experiments. In four experiments a mean of 12% of the radioactive gas introduced into the venous system was recovered from the arterial side. It is concluded that the countercurrent transfer system in the spermatic cord is very effective with respect to the transfer of heat and probably moderately effective in the transfer of inert gases. The transfer is probably due to diffusion as eventual transfer through arterio-venous shunts was minimal.