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Background and aims: It is unclear to what extent genetic testing improves the ability to diagnose familial hypercholesterolaemia (FH). We investigated the percentage with FH among individuals referred to Danish lipid clinics, and evaluated the impact of genetic testing for a diagnosis of FH.Methods: From September 2020 through November 2021, all patients referred for possible FH to one of the 15 Danish lipid clinics were invited for study participation and >97% (n = 1488) accepted. The Dutch Lipid Clinical Network criteria were used to diagnose clinical FH. The decision of genetic testing for FH was based on local practice.Results: A total of 1243 individuals were referred, of whom 25.9% were diagnosed with genetic and/or clinical FH. In individuals genetically tested (n = 705), 21.7% had probable or definite clinical FH before testing, a percentage that increased to 36.9% after genetic testing. In individuals with unlikely and possible FH before genetic testing, 24.4% and 19.0%, respectively, had a causative pathogenic variant.Conclusions: In a Danish nationwide study, genetic testing increased a diagnosis of FH from 22% to 37% in patients referred with hypercholesterolaemia suspected of having FH. Importantly, approximately 20% with unlikely or possible FH, who without genetic testing would not have been considered having FH (and family screening would not have been undertaken), had a pathogenic FH variant. We therefore recommend a more widespread use of genetic testing for evaluation of a possible FH diagnosis and potential cascade screening. Background and aims: It is unclear to what extent genetic testing improves the ability to diagnose familial hypercholesterolaemia (FH). We investigated the percentage with FH among individuals referred to Danish lipid clinics, and evaluated the impact of genetic testing for a diagnosis of FH. Methods: From September 2020 through November 2021, all patients referred for possible FH to one of the 15 Danish lipid clinics were invited for study participation and >97% (n = 1488) accepted. The Dutch Lipid Clinical Network criteria were used to diagnose clinical FH. The decision of genetic testing for FH was based on local practice. Results: A total of 1243 individuals were referred, of whom 25.9% were diagnosed with genetic and/or clinical FH. In individuals genetically tested (n = 705), 21.7% had probable or definite clinical FH before testing, a percentage that increased to 36.9% after genetic testing. In individuals with unlikely and possible FH before genetic testing, 24.4% and 19.0%, respectively, had a causative pathogenic variant. Conclusions: In a Danish nationwide study, genetic testing increased a diagnosis of FH from 22% to 37% in patients referred with hypercholesterolaemia suspected of having FH. Importantly, approximately 20% with unlikely or possible FH, who without genetic testing would not have been considered having FH (and family screening would not have been undertaken), had a pathogenic FH variant. We therefore recommend a more widespread use of genetic testing for evaluation of a possible FH diagnosis and potential cascade screening.

IntroductionTo enhance health and prevent secondary consequences for patients with cardiovascular disease (CVD), maintenance of an active lifestyle following participation in cardiac rehabilitation (CR) is important. However, levels of physical activity often decrease after completion of a structured CR programme. Models that support long-term behaviour change with a sustained level of physical activity are imperative. The aim of this study is to evaluate the feasibility of a mobile health intervention based on the Health Action Process Approach theoretical model of behaviour change in patients with CVD for 3 months after completion of a CR programme.Methods and analysisIn a feasibility trial design, we will recruit 40 participants from CR programmes at Slagelse Hospital, the City of Slagelse (municipality), or Holbæk Hospital. After completing the standard structured CR programme, each participant will create an action plan for physical activity together with a physiotherapist. Following that, participants are sent 2 weekly text messages for 3 months. The first text message prompts physical activity, and the second will check if the action plan has been followed. If requested by participants, a coordinator will call and guide the physical activities behaviour. The feasibility of this maintenance intervention is evaluated based on predefined progression criteria. Physical activity is measured with accelerometers at baseline and at 3 months follow-up.Ethics and disseminationStudy approval was waived (EMN-2021-00020) by the Research Ethics Committee of Region Zealand, Denmark. Study results will be made public and findings disseminated to patients, health professionals, decision-makers, researchers and the public.Trial registration numberNCT05011994.

Background Although studies have reported beneficial impact of cardiac rehabili-ta-tion in the overall population, knowledge from clinical randomized trials of the effect of cardiac rehabilitation in patients with type 2 diabetes is still sparse. Purpose In the randomized DANSUK trial, we aimed to evaluate the short- and long-term effect on cardiovascular disease, hospital readmissions, mortality and use of preventive medication in patients with type 2 diabetes referred to comprehensive cardiac rehabilitation by comparing an intensified, targeted, multifactorial intervention with standard of care. Methods From 2000 to 2004 a total of 151 patients with type 2 diabetes and with ischemic heart disease (53%), heart failure (18%), or high-risk patients with at least three risk factors for ischemic heart disease (29%) were included in the DANSUK trial. The patients were allocated to standard of care (N=76) following current guidelines or comprehensive cardiac rehabilitation during a twelve weeks program with a stepwise implementation of behaviour modification and preventive medication to reach treatment goals (N=75). Clinical outcomes were compared after three and fourteen years of follow-up using national registries. Primary composite outcome measure included overall mortality, myocardial infarction or acute first-time readmission. Results Mean age was 66 years and more than one third of the population were women. After three years of follow-up, no difference in primary outcome was obtained (HR: 0,87; 95% CI: 0,58–1,32), but when hospitalized within the first three years, mean length of stay was significantly reduced by 25% in patients who had attended comprehensive cardiac rehabilitation compared to standard of care (5,8 vs. 7,7 days; p Conclusions Although the DANSUK trial earlier has demonstrated reductions in several risk factors and in the use of preventive medication in patients with abnormal glucose metabolism attending comprehensive cardiac rehabilitation compared to standard of care, these effects did not translate into the primary composite endpoint after three and fourteen years of follow-up in patients with known type 2 diabetes at enrolment. Nevertheless, there was a significant reduction in length of stay when admitted to hospital in the cardiac rehabilitation group compared to standard of care within the first three years of follow-up. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): The Danish Heart Foundation

Objective Transoesophageal echocardiography (TEE) is the gold standard for the detection of cardiac emboli sources in ischaemic stroke patients, but new computed tomography (CT) scanners are able to visualize the heart. This pilot study aimed to compare findings on TEE with combined cardiovascular scan and cerebral CT angiography in cryptogenic ischaemic stroke patients. Methods This pilot study enrolled patients with cryptogenic ischaemic stroke who underwent a combined cardiovascular and cerebral CT angiography scan and a TEE examination, which were interpreted in a blinded manner. Results Twelve patients with cryptogenic ischaemic stroke were included (mean age 56 years). Of these, 10 patients underwent both a combined cardiovascular and cerebral CT angiography and a TEE examination. All cardiovascular CT scans were readable at sinus rhythm. None of the simultaneous cerebral angiograms were compromised. Thrombi were not detected in any patients. Patent foramen ovale was visualized in five patients by TEE, while cardiovascular CT only identified three. Cardiovascular CT revealed in addition an X-ray negative pulmonary metastasis in one patient, aortic coarctation in another and significant coronary stenosis in four patients. Conclusion The sensitivity for detecting patent foramen ovale was considerably lower for cardiovascular CT than for TEE, however the cardiovascular CT revealed several other very important clinical findings.

Recent guidelines governing anti-diabetic medications increasingly advocate metformin as first-line therapy in all patients with type 2 diabetes. However, metformin could be associated with increased risk of acute kidney injury (AKI), acute dialysis and lactate acidosis in marginal patients. In a retrospective nationwide cohort study, a total of 168 443 drug-naive patients with type 2 diabetes ≥50 years, initiating treatment with either metformin or sulphonyl in Denmark between 2000 and 2012 were included in this study (70.7% initiated treatment with metformin); calculation of 1-year risk of acute dialysis was based on g-standardization of cause-specific Cox regression models for acute dialysis, end-stage renal disease and death. One-year risks of acute dialysis were 92.4 per 100 000 (95% CI, 67.1-121.3) and 142.7 per 100 000 (95% CI, 118.3-168.0) for sulphonylurea and metformin, respectively. The metformin-associated 1-year risk of acute dialysis was increased by 50.3 per 100 000 (95% CI, 7.9-88.6), corresponding to a risk ratio of 1.53 (95% CI, 1.06-2.23), and a number needed to harm of 1988, thus providing evidence of potential concerns pertaining to the increasing use of metformin.

An increasing number of Danes are living, and dying, with cardiovascular disease. There is good evidence for the impact of cardiac rehabilitation on coronary heart disease, heart failure and symptomatic peripheral arterial disease. However, more high-quality research is needed into a wider range of cardiac diseases including rehabilitation following cardiac arrest, and palliative care for patients with advanced heart disease. In this review it is discussed how to improve the quality of care and identify the direction of future research and development.

BACKGROUND If blood pressure (BP) falls during haemodialysis (HD) [intradialytic hypotension (IDH)] a common clinical practice is to reduce the extracorporeal blood flow rate (EBFR). Consequently the efficacy of the HD (Kt/V) is reduced. However, only very limited knowledge on the effect of reducing EBFR on BP exists and data are conflicting. The aim of this study was to evaluate the effect and the potential mechanism(s) involved by investigating the impact of changes in EBFR on BP, pulse rate (PR) and cardiac output (CO) in HD patients with arteriovenous-fistulas (AV-fistulas). METHODS We performed a randomized, crossover trial in 22 haemodynamically stable HD patients with AV-fistula. After a conventional HD session each patient was examined during EBFR of 200, 300 and 400 mL/min in random order. After 15 min when steady state was achieved CO, BP and PR were measured at each EFBR, respectively. RESULTS Mean (SD) age was 71 (11) years. Systolic BP was significantly higher at an EBFR of 200 mL/min as compared with 300 mL/min [133 (23) versus 128 (24) mmHg; P < 0.05], but not as compared with 400 mL/min [133 (23) versus 130 (19) mmHg; P = 0.20]. At EBFR of 200, 300 and 400 mL/min diastolic BP, mean arterial pressure, PR and CO remained unchanged. CONCLUSION Our study does not show any consistent trend in BP changes by a reduction in EBFR. Reduction in EBFR if BP falls during IDH is thus not supported. However, none of the patients experienced IDH. Further studies are required to evaluate the impact of changes in EBFR on BP during IDH.

Udgivelsesdato: 2008-Jun BACKGROUND: Current guidelines broadly recommend comprehensive cardiac rehabilitation (CCR), although evidence for this is still limited. We investigated the 12-month effect of hospital-based CCR versus usual care (UC) for a broadly defined group of cardiac patients within the modern therapeutic era of cardiology. METHODS: We conducted a centrally randomized single-center clinical trial with blinded assessment of the primary outcome: registry-based composite of total mortality, myocardial infarction, or acute first-time readmission due to heart disease. Other outcomes were hospitalization, risk profile, and quality of life. The trial included 770 participants (20-94 years) with congestive heart failure (12%), ischemic heart disease (58%), or high risk of ischemic heart disease (30%). Comprehensive cardiac rehabilitation is composed of 6 weeks of intensive intervention and systematic follow-up for 10.5 months. RESULTS: We randomized 380 patients to CCR versus 390 to UC. Randomization was well balanced. The primary outcome occurred in 31% of both groups (relative risk 0.96, 95% confidence interval 0.78-1.26). Compared with the UC group, CCR significantly reduced length of stay by 15% (95% confidence interval 1.1%-27.1%, P = .04), mean number of cardiac risk factors above target (4.5 vs 4.1, P = .01), patients with systolic blood pressure below target (P = .003), physically inactivity (P = .01), and unhealthy dietary habits (P = .0003). Short-Form-36 and Hospital Anxiety and Depression Scale did not differ significantly. CONCLUSION: At 12 months, the CCR and UC groups did not differ regarding the primary composite outcome. Comprehensive cardiac rehabilitation significantly reduced length of hospital stay and improved cardiac risk factors.

Udgivelsesdato: 2007-Apr BACKGROUND: The DANish StUdy of impaired glucose metabolism in the settings of cardiac rehabilitation (DANSUK) examined the effect of an intensified multifactorial intervention on risk factor profile in 104 patients with type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT) attending hospital-based outpatient comprehensive cardiac rehabilitation (CCR) compared to usual care (UC). METHODS: Patients with ischemic heart disease (67%), congestive heart failure (7%), or at least 3 risk factors for ischemic heart disease (26%) discharged from 1 coronary care unit were referred to CCR. Of 473 eligible individuals, 201 agreed to participate in the study, and 52% had T2DM or IGT. Patients randomized to CCR received a stepwise implementation of behavioral modification and pharmacotherapy. RESULTS: After 1 year, patients with T2DM in the CCR group experienced a mean change in HbA1c of -0.65% +/- 0.9% compared with a mean change of -0.08% +/- 0.7% in the UC group (P < .05). Mean change in systolic and diastolic blood pressures was -8 +/- 15 and -5 +/- 9 mm Hg in the CCR group compared with a mean change of -0.8 +/- 15 and -0.2 +/- 7 mm Hg in the UC group (P < .05). Patients with IGT attending CCR obtained a significantly higher exercise capacity compared with patients in the UC group (P < .05). CONCLUSIONS: In a group of patients with impaired glucose metabolism attending CCR, an intensified multifactorial intervention with an integrated diabetes module was more efficient in improving risk factor control than UC. Besides the improvement in the exercise capacity of patients with IGT, in patients with T2DM, both HbA1c and blood pressure were lowered to a level that has been shown to reduce both cardiac and diabetic complications. These findings have important implications for patients with impaired glucose metabolism in the future settings of CCR.

Udgivelsesdato: 2006-Oct BACKGROUND: Lifestyle and pharmacological interventions can delay the progression of impaired glucose tolerance (IGT) to type 2 diabetes (T2DM), and there is growing evidence that earlier detection of T2DM and intensified risk factor management may result in improved cardiovascular morbidity and mortality. We studied the prevalence of impaired glucose metabolism (T2DM, IGT and impaired fasting glucose; IFG) in patients referred to cardiac rehabilitation, and further studied whether we could identify groups in which an oral glucose tolerance test (OGTT) need not be performed. METHODS: As part of a cardiac rehabilitation trial, 201 patients participated. Patients without a diagnosis of T2DM (N=159) underwent an OGTT 3 months after inclusion. RESULTS: Forty-two patients (21%) had known T2DM at enrolment. Based on the OGTT, 26 patients (13%) had unrecognized T2DM, 36 (18%) had IGT and 19 (9%) were diagnosed with isolated IFG according to the World Health Organization definition. Using fasting plasma glucose alone, 19% of the patients with unrecognized T2DM and two-thirds of patients with IGT would be misclassified. Using IFG as a means to detect IGT showed a sensitivity of only 33% and a positive predictive value of 39%. CONCLUSION: More than 60% of the patients (123/201) referred to cardiac rehabilitation had impaired glucose metabolism and 18% of the screened patients (29/159) would be misclassified if an OGTT was omitted. IFG and IGT did not identify the same patients or the same cardiovascular risk profile. An OGTT test should therefore be considered a constituent part of routine care management in cardiac rehabilitation settings.

The purpose of this was to investigate the effect of coenzyme Q10 (CoQ10) in patients with congestive heart failure (CHF) by measuring the possible improvement of certain relevant hemodynamic heart parameters. A statistic aggregation method know as a meta-analysis was used to measure the changes in the cardiac parameters. To begin with we collected the total number of randomized controlled trials and from a total of 14 studies published in the period of 1984–1994, eight studies met our inclusion criteria. The rest were excluded because of a lack of data which made a meta-analysis impossible. The relevant effect parameters investigated were stroke volume (SV), cardiac output (CO), ejection fraction (EF), cardiac index (CI), end diastolic volume index (EDVI), systolic time intervals ( PEP LVET ) and total work capacity (Wmax). Seven meta-analyses were performed, one for each of the parameters, and the calculated effect sizes were all positive. Statistical significance could be demonstrated for all of the parameters except the PEP LVET and Wmax thereby indicating an improvement of greater or lesser magnitude in the CoQ10 group as opposed to the placebo group. Accordingly, the average patient in the CoQ10 group had a better score with regard to SV and CO than 76 and 73% respectively of the patients in the placebo group. In conclusion, supplemental treatment of CHF with CoQ10 is consistent with an improvement of SV, EF, CO, CI and EDVI. Homogeneity could be established for SV and CO. Additional clinical trials of the effect of CoQ10 on CHF are necessary, but, on the basis of the evidence currently available, the possibility remains that CoQ10 will receive a well-documented role as an adjunctive treatment of CHF.

Introduction Dialysis-requiring acute kidney injury is a severe illness associated with poor prognosis. However, information pertaining to incidence rates and prevalence of risk factors remains limited in spite of increasing focus. We evaluate time trends of incidence rates and changing patterns in prevalence of comorbidities, concurrent medication, and other risk factors in nationwide retrospective cohort study. Materials and Methods All patients with dialysis-requiring acute kidney injury were identified between January 1st 2000 and December 31st 2012. By cross-referencing data from national administrative registries, the association of changing patterns in dialysis treatment, comorbidity, concurrent medication and demographics with incidence of dialysis-requiring acute kidney injury was evaluated. Results A total of 18,561 adult patients with dialysis-requiring AKI were identified between 2000 and 2012. Crude incidence rate of dialysis-requiring AKI increased from 143 per million (95% confidence interval, 137–144) in 2000 to 366 per million (357–375) in 2006, and remained stable hereafter. Notably, incidence of continuous veno-venous hemodialysis (CRRT) and use of acute renal replacement therapy in elderly >75 years increased substantially from 23 per million (20–26) and 328 per million (300–355) in 2000, to 213 per million (206–220) and 1124 per million (1076–1172) in 2012, respectively. Simultaneously, patient characteristics and demographics shifted towards increased age and comorbidity. Conclusions Although growth in crude incidence rate of dialysis-requiring AKI stabilized in 2006, continuous growth in use of CRRT, and acute renal replacement therapy of elderly patients >75 years, was observed. Our results indicate an underlying shift in clinical paradigm, as opposed to unadulterated growth in incidence of dialysis-requiring AKI.

An increasing number of Danes are living, and dying, with cardiovascular disease. There is good evidence for the impact of cardiac rehabilitation on coronary heart disease, heart failure and symptomatic peripheral arterial disease. However, more high-quality research is needed into a wider range of cardiac diseases including rehabilitation following cardiac arrest, and palliative care for patients with advanced heart disease. In this review it is discussed how to improve the quality of care and identify the direction of future research and development.