Acoustic-based rule out of stable coronary artery disease: the FILTER-SCAD trial.

BACKGROUND AND AIMS: Overtesting of low-risk patients with suspect chronic coronary syndrome (CCS) is widespread. The acoustic-based coronary artery disease (CAD) score has superior rule-out capabilities when added to pre-test probability (PTP). FILTER-SCAD tested whether providing a CAD score and PTP to cardiologists was superior to PTP alone in limiting testing. METHODS: At six Danish and Swedish outpatient clinics, patients with suspected new-onset CCS were randomised to either standard diagnostic examination (SDE) with PTP, or SDE plus CAD score, and cardiologists provided with corresponding recommended diagnostic flowcharts. The primary endpoint was cumulative number of diagnostic tests at one year and key safety endpoint major adverse cardiac events (MACE). RESULTS: In total 2008 patients (46% male, median age 63 years) were randomised from October 2019 to September 2022. When randomised to CAD score (n=1002), it was successfully measured in 94.5%. Overall, 13.5% had PTP ≤5%, and 39.5% had CAD score ≤20. Testing was deferred in 22% with no differences in diagnostic tests between groups (p for superiority =0.56). In the PTP ≤5% subgroup, the proportion with deferred testing increased from 28% to 52% (p<0.001). Overall MACE was 2.4 per 100 person-years. Non-inferiority regarding safety was established, absolute risk difference 0.4% (95% CI -1.85 to 1.06) (p for non-inferiority = 0.005). No differences were seen in angina-related health status or quality of life. CONCLUSIONS: The implementation strategy of providing cardiologists with a CAD score alongside SDE did not reduce testing overall but indicated a possible role in patients with low CCS likelihood. Further strategies are warranted to address resistance to modifying diagnostic pathways in this patient population.

Prevalence and management of familial hypercholesterolaemia in patients with chest pain admitted to hospital: a retrospective observational study.

OBJECTIVES: Patients with familial hypercholesterolaemia (FH) are genetically burdened by a lifelong elevation of the low-density lipoprotein cholesterol (LDL-C) level, putting them at a very high risk of premature ischaemic heart disease (IHD). This study aims to assess the prevalence of FH among patients admitted for IHD and the preventive treatment status before admission. DESIGN: Observational, retrospective, register-based study. SETTING: Individuals discharged with a diagnosis of IHD were enrolled consecutively throughout 2012-2016 from the cardiac care units of two hospitals in Copenhagen. PARTICIPANTS: 4223 individuals were discharged during the period. Inclusion criteria for further investigation were the availability of one measurement of LDL-C at the time of admission. In total, 2797 individuals were included for further investigation. There were no exclusion criteria. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary objective has been to determine the prevalence of FH in the population. The secondary objective has been to determine the use of lipid-lowering therapy and to which extend the individuals reach their treatment goal. RESULTS: Among the 2797 consecutive patients evaluated, the prevalence of potential FH was 7.7% (1: 13) and 6.8% (1:15) had probably or definite FH. The prevalence of FH was age-dependent: Among the 680 patients (24.3%) with premature IHD (men <55 years/women <60 years), 136 patients (20.0%) had potential FH and 21 (3.1%) had probable/definite FH. None were diagnosed and almost none attained their treatment goal. CONCLUSIONS: There is still a massive lack of recognition of FH in patients admitted to a cardiac care unit with a diagnosis of IHD. Despite a measured high LDL-C, the diagnosis was not made for any patients not even in patients who were admitted at an early age or had a previous cardiovascular event.

The prognostic value of coronary flow reserve in patients with non-obstructive coronary artery disease and microvascular dysfunction: a systematic review and meta-analysis with focus on imaging modality and sex difference.

To clarify prognosis of patients with non-obstructive coronary artery disease (NOCAD) and coronary microvascular disease (CMD) assessed as low coronary flow reserve (CFR) according to imaging modalities and sex difference. Comprehensive systematic literature review and meta-analyses were conducted. Risk of death and major adverse cardiac events (MACE) were pooled and compared in patients with abnormally low versus normal CFR using cut-off limits 2.0-2.5. Random effects model used for estimation of odds ratios (OR) and hazard ratios (HR) with 95% confidence interval (CI). Nineteen eligible observational studies provided data for death and MACE, publication bias was insignificant, p = 0.62. Risk of death and MACE were significantly higher in patients with low (n = 4.612, 29%) than normal CFR (n = 11.367, 71%): using transthoracal echocardiography (TTE) (OR 4.25 (95% CI 2.94, 6.15) p < 0.001) and (OR 6.98 (95% CI 2.56, 19.01) p < 0.001), positron emission tomography (PET) (OR 2.51 (CI 95%: 1.40, 4..49) p = 0.002) and (OR 2.87 (95% CI 2.16, 3.81) p < 0.001), and invasive intracoronary assessment (OR 2.23 (95% CI 1.15, 4.34) p < 0.018), and (OR 4.61 (95% CI 2.51, 8.48) p < 0.001), respectively. Pooled adjusted HR for death and MACE were (HR 2.45(95% CI 1.37, 3.53) p < 0.001) and (HR 2.08 (95% CI 1.54, 2.63) p < 0.001) respectively. Studies comparing men and women with abnormally low CFR demonstrated similar worse prognosis in both sexes. Low CFR is associated with poorer prognosis in patients with NOCAD regardless of sex. TTE may overestimate risk of death and MACE, while PET seems to be more appropriate. Future studies are needed to consolidate the current evidence.

Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial.

INTRODUCTION: Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS. METHODS AND ANALYSIS: FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the primary endpoint of cumulative number of diagnostic tests and a safety endpoint (MACE). Angina symptoms, quality of life and risk factor modification will be assessed with questionnaires at baseline, 3 months and 12 months after randomisation. The study is powered to detect superiority in terms of a reduction of ≥15% in the primary endpoint between the two groups with a power of 80%, and non-inferiority on the secondary endpoint with a power of 90%. The significance level is 0.05. The non-inferiority margin is set to 1.5%. Randomisation began on October 2019. Follow-up is planned to be completed by December 2022. ETHICS AND DISSEMINATION: This study has been approved by the Danish Medical Agency (2019024326), Danish National Committee on Health Research Ethics (H-19012579) and Swedish Ethical Review Authority (Dnr 2019-04252). All patients participating in the study will sign an informed consent. All study results will be attempted to be published as soon as possible. TRIAL REGISTRATION NUMBER: NCT04121949; Pre-results.

Time spent cycling, walking, running, standing and sedentary: a cross-sectional analysis of accelerometer-data from 1670 adults in the Copenhagen City Heart Study : Physical behaviours among 1670 Copenhageners.

BACKGROUND: Information about how much time adults spend cycling, walking and running can be used for planning and evaluating initiatives for active, healthy societies. The objectives of this study were to describe how much time adult Copenhageners cycle, walk, run, stand and spend sedentary using accelerometers, and to describe differences between population groups. METHODS: In the fifth examination of the Copenhagen City Heart Study, 2335 individuals gave consent to wear accelerometers (skin-attached; right thigh and iliac crest; 24 h/day, 7 consecutive days) of which 1670 fulfilled our inclusion criteria (≥16 h/day for ≥5 days; median wear time: 23.8 h/day). Daily time spent cycling, walking, running, standing and sedentary was derived from accelerometer-based data using the Acti4 software, and differences between sex, age groups, level of education and BMI were investigated using Kruskal-Wallis rank sum tests. RESULTS: Among those cycling (61%), the median cycling time was 8.3 min/day. The median time walking, running, standing and sedentary was 82.6, 0.1, 182.5 and 579.1 min/day, respectively. About 88% walked fast (i.e., ≥100 steps/min) ≥30 min/day. The shortest duration and lowest prevalence of cycling, walking and running were found among older individuals, those with a low level of education, and individuals being overweight or obese. CONCLUSIONS: We found a long duration and high prevalence of cycling and walking, but also that many adult Copenhageners spent much time sedentary. Population groups with low participation in physical activities such as cycling and walking should be targeted in future initiatives towards an active, healthy society.

Vital Exhaustion and Incidence of Dementia: Results from the Copenhagen City Heart Study.

BACKGROUND: Psychological distress is potentially linked to the risk of dementia through neurologic and cardiovascular mechanisms. Vital exhaustion (VE) is a mental state of psychological distress, which could be a risk factor for dementia. OBJECTIVE: To investigate whether VE is a risk factor for dementia in later life. METHODS: We used data from 6,807 participants attending the third survey of the Copenhagen City Heart Study in 1991-1994. VE was assessed by 17 symptoms (score: 0-17) from the Maastricht Questionnaire. Information on dementia was obtained from national registers. Risk time for dementia was counted from five years after VE assessment for participants > 55 years at the time of VE assessment. For younger participants, risk time for dementia was counted from the year they turned 60 years and onwards. Participants were followed until 2016. We used Poisson regression to calculate incidence rate ratios (IRR) and their 95% confidence intervals (CI). RESULTS: During an average follow-up of 10 years, 872 participants were registered with dementia. We found a dose-response relation between the number of VE symptoms and the incidence of dementia. For every additional VE symptom, the dementia incidence increased by 2% (IRR = 1.024; 95% CI: 1.004-1.043). Adjustment for socio-demographic and health-related factors did not change the results substantially. Neither did stratification by age, sex, educational level, and marital status. CONCLUSION: We found evidence that VE is a risk factor for dementia. Our sensitivity analyses supported that this association was not only due to VE being a potential prodromal sign of dementia.

Job-exposure matrices addressing lifestyle to be applied in register-based occupational health studies.

OBJECTIVES: Information about lifestyle factors in register-based occupational health studies is often not available. The objective of this study was therefore to develop gender, age and calendar-time specific job-exposure matrices (JEMs) addressing five selected lifestyle characteristics across job groups as a tool for lifestyle adjustment in register-based studies. METHODS: We combined and harmonised questionnaire and interview data on lifestyle from several Danish surveys in the time period 1981-2013 for 264 054 employees registered with a DISCO-88 code (the Danish version of International Standard Classification of Occupations (ISCO)-88) in a nationwide register-based Danish Occupational Cohort. We modelled the probability of specified lifestyles in mixed models for each level of the four-digit DISCO code with age and sex as fixed effects and assessed variation in terms of intraclass correlation coefficients (ICCs) and exposure-level percentile ratios across jobs for six different time periods from 1981 through 2013. RESULTS: The ICCs were overall low (0.26%-7.05%) as the within-job group variation was large relative to the between job group variation, but across jobs the calendar period-specific ratios between highest and lowest predicted levels were ranging from 1.2 to 6.9, and for the 95%/1% and the 75%/5% percentile ratios ranges were 1.1-2.8 and 1.1-1.6, respectively, thus indicating substantial contrast for some lifestyle exposures and some occupations. CONCLUSIONS: The lifestyle JEMs may prove a useful tool for control of lifestyle-related confounding in register-based occupational health studies where lacking information on individual lifestyle factors may compromise internal validity.

Explaining trends in coronary heart disease mortality in different socioeconomic groups in Denmark 1991-2007 using the IMPACTSEC model.

AIM: To quantify the contribution of changes in different risk factors population levels and treatment uptake on the decline in CHD mortality in Denmark from 1991 to 2007 in different socioeconomic groups. DESIGN: We used IMPACTSEC, a previously validated policy model using data from different population registries. PARTICIPANTS: All adults aged 25-84 years living in Denmark in 1991 and 2007. MAIN OUTCOME MEASURE: Deaths prevented or postponed (DPP). RESULTS: There were approximately 11,000 fewer CHD deaths in Denmark in 2007 than would be expected if the 1991 mortality rates had persisted. Higher mortality rates were observed in the lowest socioeconomic quintile. The highest absolute reduction in CHD mortality was seen in this group but the highest relative reduction was in the most affluent socioeconomic quintile. Overall, the IMPACTSEC model explained nearly two thirds of the decline in. Improved treatments accounted for approximately 25% with the least relative mortality reduction in the most deprived quintile. Risk factor improvements accounted for approximately 40% of the mortality decrease with similar gains across all socio-economic groups. The 36% gap in explaining all DPPs may reflect inaccurate data or risk factors not quantified in the current model. CONCLUSIONS: According to the IMPACTSEC model, the largest contribution to the CHD mortality decline in Denmark from 1991 to 2007 was from improvements in risk factors, with similar gains across all socio-economic groups. However, we found a clear socioeconomic trend for the treatment contribution favouring the most affluent groups.

The Effect of Occupational Lifting on Hypertension Risk: Protocol for a Project Using Data From the Copenhagen City Heart Study.

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease and is responsible for 14% of all annual deaths globally. The prevalence of hypertension varies across occupational groups, possibly affected by differences in the working environment. One work-related factor that might impose a risk for hypertension is lifting due to the acute large increases in blood pressure (BP) during lifting. OBJECTIVE: The aim of this study is to explore associations between heavy occupational lifting and hypertension in the Copenhagen City Heart Study. METHODS: This study will use data from the third, fourth, and fifth examination of the Copenhagen City Heart Study. The dataset contains person-based information on health as well as a large variety of biological, environmental, and lifestyle-related factors. Using a cross-sectional design, we will investigate the association between heavy occupational lifting and hypertension, defined as using antihypertensive drugs or having a measured systolic BP (SBP) ≥140 mm Hg or diastolic BP (DBP) ≥90 mm Hg. Furthermore, in a prospective design, we will investigate the association between heavy occupational lifting and risk of becoming an SBP case, defined as the shift from not using antihypertensive drugs in examination n to use of antihypertensive drugs in examination n+1 or an above median delta value of SBP (SBP in examination n+1−SBP in examination n). RESULTS: In the third examination in 1991-1994, 10,135 out of 16,560 participants attended (61.20%), in the fourth examination in 2001-2003, 6237 out of 12,599 participants attended (49.50%), and in the fifth examination in 2011-2015, 4550 out of 9765 participants attended (46.59%). On the basis of the inclusion criteria of answering to the level of occupational physical activity, 5031 observations were excluded from examination 3, 2600 from examination 4, and 1621 from examination 5. Hence, the final populations for the cross-sectional and prospective analysis are assumed to include less than 7166 participants in the cross-sectional analysis and less than 1850 participants in the prospective analysis due to the additional inclusion criteria of measured BP and use of antihypertensive drugs. CONCLUSIONS: One-third of the workforce in Europe reports to carry or move heavy loads regularly during working hours (6th survey in Eurofound). Thus, if this study shows occupational lifting to increase the risk for hypertension, the prevention for hypertension can be improved.

Design and rationale of the HITTS randomized controlled trial: Effect of High-intensity Interval Training in de novo Heart Transplant Recipients in Scandinavia.

There is no consensus on how, when, and at what intensity exercise should be performed and organized after heart transplantation (HTx). Most rehabilitation programs are conducted in HTx centers, which might be impractical and costly. We have recently shown that high-intensity interval training (HIT) is safe, well tolerated, and efficacious in maintenance HTx recipients, but there are no studies among de novo patients, and whether HIT is feasible and superior to moderate training in HTx recipients is unclear. A total of 120 clinically stable HTx recipients older than 18 years will be recruited from 3 Scandinavian HTx centers. Participants are randomized to HIT or moderate training, shortly after surgery. All exercises are supervised in the patients' local communities. Testing at baseline and follow-up includes the following: VO2peak (primary end point), muscle strength, body composition, quality of life, myocardial performance, endothelial function, biomarkers, and progression of cardiac allograft vasculopathy. A subgroup (n = 90) will also be tested at 3-year follow-up to assess long-term effects of exercise. So far, the HIT intervention is well tolerated, without any serious adverse events. We aim to test whether decentralized HIT is feasible, safe, and superior to moderate training, and whether it will lead to significant improvement in exercise capacity and less long-term complications.