To report sex specific overall attendance rate, prevalence of screen detected cardiovascular conditions, proportion of unknown conditions before screening, and proportion initiating prophylactic ...medicine among 67 year olds in Denmark.
Cross sectional cohort study.
Since 2014, all 67 year olds in Viborg, Denmark, have been invited to screening for abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD), carotid plaque (CP), hypertension, cardiac disease, and type 2 diabetes. Individuals with AAA, PAD, and or CP are recommended cardiovascular prophylaxis. Combining data with registries has facilitated estimation of unknown screen detected conditions. Up to August 2019, 5 505 had been invited; registry data were available for the first 4 826 who were invited.
The attendance rate was 83.7%, without sex difference. Screen detected prevalence was significantly lower among women than men: AAA, 5 (0.3%) vs. 38 (1.9%) (p < .001); PAD, 90 (4.5%) vs. 134 (6.6%) (p = .011); CP, 641 (31.8%) vs. 907 (44.8%) (p < .001); arrhythmia, 26 (1.4%) vs. 77 (4.2%) (p < .001); blood pressure ≥ 160/100 mmHg, 277 (13.8%) vs. 346 (17.1%) (p = .004); and HbA1c ≥ 48 mmol/mol, 155 (7.7%) vs. 198 (9.8%) (p = .019), respectively. Pre-screening proportions of unknown conditions were particularly high for AAA (95.4%) and PAD (87.5%). AAA, PAD, and or CP were found in 1 623 (40.2%), of whom 470 (29.0%) received pre-screening antiplatelets and 743 (45.8%) lipid lowering therapy. Furthermore, 413 (25.5%) started antiplatelet therapy and 347 (21.4%) started lipid lowering therapy. Only smoking was significantly associated with all vascular conditions in multivariable analysis: odds ratios (ORs) for current smoking were AAA 8.11 (95% CI 2.27 – 28.97), PAD 5.60 (95% CI 3.61 – 8.67) and CP 3.64 (95% CI 2.95 – 4.47).
The attendance rate signals public acceptability for attending cardiovascular screening. Men had more screen detected conditions than women, but prophylactic medicine was started equally frequently in both sexes. Sex specific cost effectiveness follow up is warranted.
IntroductionThe prevalence of cardiovascular disease (CVD) is increasing. Furthermore, asymptomatic individuals may not receive timely preventive initiatives to minimise the risk of further CVD ...events. Paradoxically, 80% of CVD events are preventable by early detection, followed by prophylactic initiatives. Consequently, we introduced the population-based Viborg Screening Programme (VISP) for subclinical and manifest CVD, focusing on commonly occurring, mainly asymptomatic conditions, followed by prophylactic initiatives.The aim of the VISP was to evaluate the health benefits, harms and cost-effectiveness of the VISP from a healthcare sector perspective. Furthermore, we explored the participants’ perspectives.Methods and analysisFrom August 2014 and currently ongoing, approximately 1100 men and women from the Viborg municipality, Denmark, are annually invited to screening for abdominal aortic aneurysm, peripheral arterial disease, carotid plaque, hypertension, diabetes mellitus and cardiac arrhythmia on their 67th birthday. A population from the surrounding municipalities without access to the VISP acts as a control. The VISP invitees and the controls are followed on the individual level by nationwide registries. The primary outcome is all-cause mortality, while costs, hospitalisations and deaths from CVD are the secondary endpoints.Interim evaluations of effectiveness and cost-effectiveness are planned every 5 years using propensity score matching followed by a Cox proportional hazards regression analysis by the ‘intention-to-treat’ principle. Furthermore, censoring-adjusted incremental costs, life-years and quality-adjusted life-years are estimated. Finally, the participants’ perspectives are explored by semistructured face-to-face interviews, with participant selection representing participants with both negative and positive screening results.Ethics and disseminationThe VISP is not an interventional trial. Therefore, approval from a regional scientific ethical committee is not needed. Data collection from national registries was approved by the Regional Data Protection Agency (record no. 1-16-02-232-15). We ensure patient and public involvement in evaluating the acceptability of VISP by adopting an interviewing approach in the study.Trial registration numberNCT03395509.
Lactate is traditionally recognized as a by-product of anaerobic metabolism. However, lactate is a preferred oxidative substrate for stressed myocardium. Exogenous lactate infusion increases cardiac ...output (CO). The exact mechanism underlying this mechanism has yet to be elucidated. The aim of this study was to investigate the cardiovascular mechanisms underlying the acute haemodynamic effects of exogenous lactate infusion in an experimental model of human-sized pigs.
In this randomised, blinded crossover study in eight 60-kg-pigs, the pigs received infusions with one molar sodium lactate and a control infusion of tonicity matched hypertonic saline in random order. We measured CO and pulmonary pressures using a pulmonary artery catheter. A pressure-volume admittance catheter in the left ventricle was used to measure contractility, afterload, preload and work-related parameters.
Lactate infusion increased circulating lactate levels by 9.9 mmol/L (95% confidence interval (CI) 9.1 to 11.0) and CO by 2.0 L/min (95% CI 1.2 to 2.7). Afterload decreased as arterial elastance fell by -1.0 mmHg/ml (95% CI -2.0 to -0.1) and systemic vascular resistance decreased by -548 dynes/s/cm
(95% CI -261 to -835). Mixed venous saturation increased by 11 percentage points (95% CI 6 to 16), whereas ejection fraction increased by 16.0 percentage points (95% CI 1.1 to 32.0) and heart rate by 21 bpm (95% CI 8 to 33). No significant changes in contractility nor preload were observed.
Lactate infusion increased cardiac output by increasing heart rate and lowering afterload. No differences were observed in left ventricular contractility or preload. Lactate holds potential as a treatment in situations with lowered CO and should be investigated in future clinical studies.
New Findings
What is the central question of this study?
Invasive cardiovascular instrumentation can occur through closed‐ or open‐chest approaches. To what extent will sternotomy and pericardiotomy ...affect cardiopulmonary variables?
What is the main finding and its importance?
Opening of the thorax decreased mean systemic and pulmonary pressures. Left ventricular function improved, but no changes were observed in right ventricular systolic measures. No consensus or recommendation exists regarding instrumentation. Methodological differences risk compromising rigour and reproducibility in preclinical research.
Animal models of cardiovascular disease are often evaluated by invasive instrumentation for phenotyping. As no consensus exists, both open‐ and closed‐chest approaches are used, which might compromise rigour and reproducibility in preclinical research. We aimed to quantify the cardiopulmonary changes induced by sternotomy and pericardiotomy in a large animal model. Seven pigs were anaesthetized, mechanically ventilated and evaluated by right heart catheterization and bi‐ventricular pressure–volume loop recordings at baseline and after sternotomy and pericardiotomy. Data were compared by ANOVA or the Friedmann test where appropriate, with post‐hoc analyses to control for multiple comparisons. Sternotomy and pericardiotomy caused reductions in mean systemic (−12 ± 11 mmHg, P = 0.027) and pulmonary pressures (−4 ± 3 mmHg, P = 0.006) and airway pressures. Cardiac output decreased non‐significantly (−1329 ± 1762 ml/min, P = 0.052). Left ventricular afterload decreased, with an increase in ejection fraction (+9 ± 7%, P = 0.027) and coupling. No changes were observed in right ventricular systolic function or arterial blood gases. In conclusion, open‐ versus closed‐chest approaches to invasive cardiovascular phenotyping cause a systematic difference in key haemodynamic variables. Researchers should adopt the most appropriate approach to ensure rigour and reproducibility in preclinical cardiovascular research.
Normothermic regional perfusion (NRP) allows assessment of therapeutic interventions prior to donation after circulatory death transplantation. Sodium-3-hydroxybutyrate (3-OHB) increases cardiac ...output in heart failure patients and diminishes ischemia-reperfusion injury, presumably by improving mitochondrial metabolism. We investigated effects of 3-OHB on cardiac and mitochondrial function in transplanted hearts and in cardiac organoids. Donor pigs (n = 14) underwent circulatory death followed by NRP. Following static cold storage, hearts were transplanted into recipient pigs. 3-OHB or Ringer's acetate infusions were initiated during NRP and after transplantation. We evaluated hemodynamics and mitochondrial function. 3-OHB mediated effects on contractility, relaxation, calcium, and conduction were tested in cardiac organoids from human pluripotent stem cells. Following NRP, 3-OHB increased cardiac output (P < 0.0001) by increasing stroke volume (P = 0.006), dP/dt (P = 0.02) and reducing arterial elastance (P = 0.02). Following transplantation, infusion of 3-OHB maintained mitochondrial respiration (P = 0.009) but caused inotropy-resistant vasoplegia that prevented weaning. In cardiac organoids, 3-OHB increased contraction amplitude (P = 0.002) and shortened contraction duration (P = 0.013) without affecting calcium handling or conduction velocity. 3-OHB had beneficial cardiac effects and may have a potential to secure cardiac function during heart transplantation. Further studies are needed to optimize administration practice in donors and recipients and to validate the effect on mitochondrial function.
The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) by 35% to 40% in healthy people and people with heart failure. The mechanisms underlying the effects of 3-OHB on myocardial ...contractility and loading conditions as well as the cardiovascular effects of its enantiomeric forms, D-3-OHB and L-3-OHB, remain undetermined.
Three groups of 8 pigs each underwent a randomized, crossover study. The groups received 3-hour infusions of either D/L-3-OHB (racemic mixture), 100% L-3-OHB, 100% D-3-OHB, versus an isovolumic control. The animals were monitored with pulmonary artery catheter, left ventricle pressure-volume catheter, and arterial and coronary sinus blood samples. Myocardial biopsies were evaluated with high-resolution respirometry, coronary arteries with isometric myography, and myocardial kinetics with D-
C3-OHB and L-
C3-OHB positron emission tomography. All three 3-OHB infusions increased 3-OHB levels (
<0.001). D/L-3-OHB and L-3-OHB increased CO by 2.7 L/min (
<0.003). D-3-OHB increased CO nonsignificantly (
=0.2). Circulating 3-OHB levels correlated with CO for both enantiomers (
<0.001). The CO increase was mediated through arterial elastance (afterload) reduction, whereas contractility and preload were unchanged. Ex vivo, D- and L-3-OHB dilated coronary arteries equally. The mitochondrial respiratory capacity remained unaffected. The myocardial 3-OHB extraction increased only during the D- and D/L-3-OHB infusions. D-
C3-OHB showed rapid cardiac uptake and metabolism, whereas L-
C3-OHB demonstrated much slower pharmacokinetics.
3-OHB increased CO by reducing afterload. L-3-OHB exerted a stronger hemodynamic response than D-3-OHB due to higher circulating 3-OHB levels. There was a dissocitation between the myocardial metabolism and hemodynamic effects of the enantiomers, highlighting L-3-OHB as a potent cardiovascular agent with strong hemodynamic effects.
The hemodynamic effects of aortic arch vessel (AAV) clamping during normothermic regional perfusion (NRP) in donation after circulatory death is unknown. We investigated effects of AAV clamping ...during NRP compared with no clamping in a porcine model.
In 16 pigs, hemodynamic parameters were recorded including biventricular pressure-volume measurements and invasive blood pressure. Additionally, blood gas parameters and inflammatory cytokines were used to assess the effect of AAV clamping. The animals were centrally cannulated for NRP, and baseline measurements were obtained before hypoxic circulatory arrest was induced by halting mechanical ventilation. During an 8-min asystole period, the animals were randomized to clamp (n = 8) or no-clamp (n = 8) of the AAV before commencement of NRP. During NRP, circulation was supported with norepinephrine (NE) and dobutamine. After 30 min of NRP, animals were weaned and observed for 180 min post-NRP.
All hearts were successfully reanimated and weaned from NRP. The nonclamp groups received significantly more NE to maintain a mean arterial pressure >60 mm Hg during and after NRP compared with the clamp group. There were no between group differences in blood pressure or cardiac output. Pressure-volume measurements demonstrated preserved cardiac function' including ejection fraction and diastolic and systolic function. No between group differences in inflammatory markers were observed.
AAV clamping did not negatively affect donor cardiac function or inflammation after circulatory death and NRP. Significantly less NE was used to support in the clamp group than in the nonclamp group.
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