Search

Objective: To evaluate whether estimates of risk of future cardiovascular events and death and established or unknown diabetes are significantly associated with calcified carotid artery atheromas (CCAAs) on panoramic radiographs (PRs). The main focus was on men and women without previous myocardial infarction (MI). Methods: The PAROKRANK (Periodontitis and its Relation to Coronary Artery Disease) study included patients with a first MI and matched control subjects. In this substudy, 738 patients (138 women) and 744 control subjects (144 women) with available PRs were assessed for CCAA. Cardiovascular risk estimates were determined according to the Framingham Risk Score (FRS) and Systematic COronary Risk Evaluation (SCORE). Established and previously unknown diabetes was also determined. Results: CCAA was detected on PRs in 206 control subjects (28%) and 251 patients (34%). FRS was significantly associated with CCAA among control subjects (P = .04) and patients (P = .001). SCORE was associated with CCAA among control subjects (P < .01) but not patients (P = .07). Among men, FRS and SCORE were associated with CCAA in both control subjects and patients. Diabetes was not significantly associated with CCAA after adjustments. Conclusions: Elevated cardiovascular risk scores were associated with CCAA on PRs among control subjects. Diabetes was not independently associated with CCAA, possibly owing to selection bias.

Ultrasonic echolucent carotid intima-media (IM) complex and accelerated progression of carotid intima mediathickness (cIMT) have both separately been shown to predict future cardiovascular events. The aim of this studywas to evaluate if the echogenicity of the IM-complex is associated with the 3-year progression of cIMT. B-modeultrasound images captured at baseline and 3-year follow-up in the ‘Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention’ (VIPVIZA) trial were included (n: 3154). The bilateral mean cIMT and IM-echogenicity by greyscale median (GSM) were measured in the common carotid artery. Associations between IM-GSM at baseline and the 3-year cIMT progression were investigated using linear regression models for the whole population and stratified by sex, age and VIPVIZA study group (intervention versus control). In addition, adjusted analyses for confounding factors were performed. Unadjusted analysis showed that decreased IM-GSM at baseline was associated with increased progression of cIMT (p < 0.001). Stratified by age, the association was significant among 40 (p < 0.001) and 60 years old (p < 0.001). The association was statistically significant in both sexes and on comparison of VIPVIZA study subgroups. Adjustments for confounding factors did not alter the estimated relationship between IM-GSM and cIMT progression. Echolucent carotid intima media at baseline associates with increased 3-year cIMT progression among an asymptomatic, middle-aged population. Echogenicity of the intima media may identify individuals at risk for accelerated vascular aging.

This commentary refers to 'Effects of a comprehensive lifestyle intervention on cardiovascular health: the TANSNIP-PESA trial', by I. Garcia-Lunar et al., https://doi.org/10.1093/eurheartj/ehac378 and the discussion piece 'Motivational interview and imaging of subclinical atherosclerosis for cardiovascular disease prevention: a winning combination?', by I. Garcia-Lunar et al., https://doi.org/10.1093/eurheartj/ehad126.

Objectives: The risk of cardiovascular disease is associated with the echo intensity of carotid plaques in ultrasound images and their cardiac cycle-induced intensity variations. In this study, we aimed to 1) explore the underlying origin of echo intensity variations by using simulations and 2) evaluate the association between the two-dimensional (2D) spatial distribution of these echo intensity variations and plaque vulnerability. Methods: First, we analyzed how out-of-plane motion and compression of simulated scattering spheres of different sizes affect the ultrasound echo intensity. Next, we propose a method to analyze the features of the 2D spatial distribution of interframe plaque echo intensity in carotid ultrasound image sequences and explore their associations with plaque vulnerability in experimental data. Results: The simulations showed that the magnitude of echo intensity changes was similar for both the out-of-plane motion and compression, but for scattering objects smaller than 1 mm radius, the out-of-plane motion dominated. In experimental data, maps of the 2D spatial distribution of the echo intensity variations had a low correlation with standard B-mode echo intensity distribution, indicating complementary information on plaque tissue composition. In addition, we found the existence of ∼1 mm diameter subregions with pronounced echo intensity variations associated with plaque vulnerability. Conclusions: The results indicate that out-of-plane motion contributes to intra-plaque regions of high echo intensity variation. The 2D echo intensity variation maps may provide complementary information for assessing plaque composition and vulnerability. Further studies are needed to verify this method's role in identifying vulnerable plaques and predicting cardiovascular disease risk.

Comprehensive genetic and clinical care of families with monogenic cardiovascular diseases requires competences from different medical specialties. Genetic assessment, cascade screening, risk estimation, treatment and follow-up is difficult to cover. Fourteen years ago, a center for cardiovascular diseases was created in our hospital, to improve the care of families with monogenic cardiovascular diseases. At our center, clinical geneticists, cardiologists, angiologists, pediatric cardiologists and genetic counselors work together in a seamless organization, while still having different clinic affiliations. A key feature of this organization are the family outpatient clinics, where the proband and his/her relatives at genetic risk are invited to take part. When the family or relatives live in other parts of the country, they are invited to participate through video conference. In this paper we report our experiences and working routines from more than 300 families and 2000 individuals.

AIMS: To estimate the association between long-term exposure to particulate air pollution and sub-clinical atherosclerosis based on the existence of plaque and the carotid intima-media thickness (cIMT). METHODS: Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) is a randomised controlled trial integrated within the Västerbotten Intervention Programme, an ongoing population-based cardiovascular disease (CVD) prevention programme in northern Sweden. Individuals aged 40, 50, or 60 years with one or more conventional CVD risk factors in Umeå municipality were eligible to participate. The 1425 participants underwent an ultrasound assessment of cIMT and plaque formation during the period 2013-2016 and at 3-year follow-up. Source-specific annual mean concentrations of particulate matter with aerodynamic diameter ≤10 μm (PM10) and ≤2.5 μm (PM2.5), and black carbon (BC) at the individual's residential address were modelled for the calendar years 1990, 2001 and 2011. Poisson regression was used to estimate prevalence ratios for presence of carotid artery plaques, and linear regression for cIMT. RESULTS: The plaque prevalence was 43% at baseline and 47% at follow-up. An interquartile range (IQR) increase in PM10 (range in year 2011: 7.1-13.5 μg/m3) was associated with a prevalence ratio at baseline ultrasound of 1.11 (95% CI 0.99-1.25), 1.08 (95% CI 0.99-1.17), and 1.00 (95% CI 0.93-1.08) for lag 23, 12 and 2 years, and at follow-up 1.04 (95% CI 0.95-1.14), 1.08 (95% CI 1.00-1.16), and 1.01 (95% CI 0.95-1.08). Similar prevalence ratios per IQR were found for PM2.5 and BC, but with somewhat lower precision for the later. Particle concentrations were however not associated with the progression of plaque. No cross-sectional or longitudinal associations of change were found for cIMT. CONCLUSIONS: This study of individuals with low/moderate risk for CVD give some additional support for an effect of long-term air pollution in early subclinical atherosclerosis.

Aims Visual information about subclinical atherosclerosis was provided to physicians and participants in the VIPVIZA trial, inclusion 2013–16 in northern Sweden, aiming to improve adherence to cardiovascular disease (CVD) prevention guidelines. Pictorial risk information may be more actionable. The aim of this study was to investigate the effect of intervention with pictorial risk information on time to first dispensing of statins. Methods and results Asymptomatic atherosclerotic disease was screened for by carotid ultrasound examination in 3532 participants enrolled in VIPVIZA, of those 3000 met the criteria for this study. Participants were randomly assigned to receive pictorial risk information consisting of graphical representation of atherosclerosis as compared to a control group without intervention. Time to initiation of statins was assessed during 5 years of follow-up through the National prescribed drug register. After 3 years, both groups were re-examined and received the intervention information. In the intervention group, initiation of statins increased considerably for the first 3 years and a smaller increase was also seen after re-intervention. After the cross-over, the control group showed a sharp increase in initiation of statins, almost reaching the same proportion treated at 5 years. The propensity to initiate statin treatment increased over the study period and there was no difference between men and women. Conclusions The pictorial information had an effect on time to initiation of statins, both as original and repeated intervention and also in the control group after single-arm cross-over. The current study supports pictorial information as a tool to shorten time to initiation of statins for CVD prevention. The VIPVIZA study is registered with ClinicalTrials.gov, number NCT01849575.

Lipoprotein lipase (LPL) is a key player in plasma triglyceride metabolism. Consequently, LPL is regulated by several proteins during synthesis, folding, secretion, and transport to its site of action at the luminal side of capillaries, as well as during the catalytic reaction. Some proteins are well known, while others have been identified but are still not fully understood. We set out to study the effects of the natural variations in the plasma levels of all known LPL regulators on the activity of purified LPL added to samples of fasted plasma taken from 117 individuals. The enzymatic activity was measured at 25° C using isothermal titration calorimetry. This method allows quantification of the ability of an added fixed amount of exogenous LPL to hydrolyze triglyceride-rich lipoproteins in plasma samples by measuring the heat produced. Our results indicate that, under the conditions used, the normal variation in the endogenous levels of apolipoprotein C1, C2 and C3, or the levels of angiopoietin-like proteins 3, 4, and 8 in the fasted plasma samples had no significant effect on the recorded activity of the added LPL. Instead, the key determinant for the LPL activity was a lipid signature strongly correlated to the average size of the VLDL particles. The signature involved several lipoprotein and plasma lipid parameters, but also apolipoprotein A5 levels. While the measurements cannot fully represent the action of LPL when attached to the capillary wall, our study provides knowledge on the interindividual variation of LPL lipolysis rates in human plasma.

To determine the inter-sonographer reproducibility of carotid ultrasound plaque detection using Mannheim consensus in a subclinical population and evaluate associations related to the reproducibility.Bilateral ultrasound screening for carotid plaques defined by Mannheim consensus was performed on 106 subclinical participants. Two different sonographers scanned the same participant, and reproducibility of plaque detection was measured by Cohens kappa. Associations with reproducibility were evaluated by comparing wall, and plaque characteristics between subjects with plaques identified in one and both scans. In general, the inter-sonographer reproducibility of plaque detection was substantial with a kappa value of 0·70 (95% CI 0·60-0·80). Plaques detected in only one scan had significantly lower plaque area and plaque thickness (6·82 mmMinor carotid plaques contribute to decreased reproducibility as compared to large plaques when screening for subclinical atherosclerosis using Mannheim consensus. Using an alternative plaque definition based on plaque thickness1.5 mm and plaque area10 mm

Aims Health literacy, the degree to which individuals understand and act upon health information, may have a pivotal role in the prevention of cardiovascular disease (CVD), with low health literacy potentially explaining poorer adherence to prevention guidelines. We investigated the associations between health literacy, ultrasound-detected carotid atherosclerosis and cardiovascular risk factors. Methods Baseline data (cross-sectional analysis) from a randomized controlled trial, integrated within the Västerbotten Intervention Program, Northern Sweden, was used. We included 3459 individuals, aged 40 or 50 years with ≥1 conventional risk factor or aged 60 years old. The participants underwent clinical examination, blood sampling, carotid ultrasound assessment of intima-media wall thickness (CIMT) and plaque formation, and answered a questionnaire on health literacy – the Brief Health Literacy Screen. The European Systematic Coronary Risk Evaluation and Framingham Risk Score were calculated. Results About 20% of the participants had low health literacy. Low health literacy was independently associated with the presence of ultrasound-detected carotid artery plaques after adjustment for age and education, odds ratio (95% confidence interval) 1.54 (1.28–1.85), demonstrating a similar level of risk as for smoking. Health literacy was associated with CIMT in men. Low health literacy was associated with higher CVD risk scores. Sensitivity analyses with low health literacy set to 9% or 30% of the study sample, respectively, yielded essentially the same results. Conclusions Low health literacy was independently associated with carotid artery plaques and a high level of CVD risk scores. Presenting health information in a fashion that is understood by all patients may improve preventive efforts.

Background: Transcatheter aortic valve implantation may be indicated for patients with aortic stenosis and high risk of postoperative mortality. The assessment of suitability for transcatheter aortic valve implantation requires consensus agreement of a team of cardiologists and cardiac surgeons. The burden of comorbidities, frailty and cognitive impairment are factors included when risks for transcatheter aortic valve implantation are balanced against the expected benefits. Although transcatheter aortic valve implantation is a possibility for many, there are still ineligible patients. Knowledge of their experiences of being deemed ineligible are lacking. Aim: The aim of this study was to explore patients’ experiences of being considered for transcatheter aortic valve implantation but judged ineligible. Methods: Individual in-depth interviews were performed with eight persons, and qualitative content analysis was used for the analysis. Results: Being ineligible for transcatheter aortic valve implantation may induce both hope and despair. Hope was linked to experiences of acceptance, relief of symptoms, support and control; despair was associated with feelings of being missed and abandoned, and of grief and insecurity. Some expressed great anxiety, since their incurable heart disease meant an imminent death. Others were more concerned over practical problems that affected everyday life. Conclusion: Being ineligible for transcatheter aortic valve implantation does not necessarily lead to despair. Hope is built through relationships, continuity and support. A combination of person-centred care and palliative care during the end-of-life phase should be offered to patients in order to help clients re-conceptualise hope during this stage of their illness. Cardiovascular nurses in the transcatheter aortic valve implantation team are suitable to facilitate continued care based on the patient’s needs, desires and local conditions.

Key Points Question Is provision of pictorial information on asymptomatic atherosclerosis to physicians and patients associated with prescribing of lipid-lowering or antihypertensive drugs during the following 465 days? Findings In this randomized clinical trial including 3532 participants with low to moderate cardiovascular disease risk, use of pictorial information on carotid intima-media thickness and carotid plaques based on ultrasonographic examination was evaluated. Physician prescription increased for lipid-lowering medications but not for antihypertensive drugs. Meaning The findings of this randomized clinical trial demonstrate that information on carotid intima-media thickness and the presence of carotid plaques can improve prescription of lipid-lowering drugs., Importance Preventive drugs are often underused. Carotid intima-media thickness and carotid plaques are associated with cardiovascular disease (CVD), and their detection could possibly improve estimation of the likelihood of CVD and prescription of preventive drugs. Objective To evaluate whether pictorial information on participants’ asymptomatic atherosclerosis based on carotid ultrasonographic examinations to participants and their physicians had an effect on prescribing of lipid-lowering or antihypertensive drugs during the following 465 days. Design, Setting, and Participants Visualization of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention is a pragmatic randomized clinical trial nested within the Västerbotten Intervention Program, a CVD screening and prevention program in Sweden with 60% to 70% participation rates and small social selection bias. A total of 4177 individuals aged 40, 50, or 60 years participating in the Västerbotten Intervention Program who had low to moderate risk of CVD were invited to enroll in this trial from April 29, 2013, to June 7, 2016. Prescriptions for all participants were monitored for 465 days after the intervention. Data analysis was conducted from December 6, 2019, to April 2, 2020. Interventions Participants and their family physicians were randomly assigned 1:1 to receive or not receive pictorial information from carotid ultrasonographic determination of vascular age, assessed as carotid intima-media thickness and the presence of carotid plaques, combined with a follow-up call to participants by nurses. Main Outcomes and Measures Two outcome measures of prescriptions of antihypertensive and lipid-lowering drugs within 465 days after ultrasonography was performed. Data obtained through intention-to-treat analysis are presented as proportions of individuals with a prescription among those who had no baseline prescription for agents from these drug classes. Results Of the 4177 individuals invited to enroll, 3532 participants were randomized and included in the analysis; 1870 (52.9%) were women, 2278 (64.5%) were aged 60 years, 978 (27.7%) were 50 years, and 276 (7.8%) were 40 years. First prescriptions of lipid-lowering drugs were higher in the intervention group vs the control group among men (118 of 639 [18.5%] vs 38 of 692 [5.5%]; P, This randomized clinical trial examines the effect of the use of pictorial information including carotid ultrasonographic images with explanation on prescribing of lipid-lowering and antihypertensive drugs.

Objective High-sensitivity troponin T (hs-TnT) and high-sensitivity C-reactive protein (hs-CRP) may convey prognostic information in patients with aortic stenosis (AS). However, many association studies were cross-sectional, and the presence of myocardial hypertrophy and concomitant coronary artery disease (CAD) were usually not described. This study evaluated if hs-TnT and hs-CRP relate to myocardial mass, and associate with risk of and time to future surgery for AS in patients with and without concomitant CAD. Design In total, 336 patients who underwent surgery due to AS after participation in large population surveys were identified. Median age [interquartile range] was 59.8 [10.3] years at survey and 68.3 [12.7] years at surgery, and 48% were women. The median time between survey and surgery was 10.9 [9.3] years. Preoperatively, myocardial mass and the presence of CAD were assessed. Two matched referents were allocated for each case, and hs-TnT and hs-CRP were determined in stored plasma samples from the baseline survey. Uni- and multivariable conditional logistic regression analyses were used to estimate the risk (odds ratio [95% confidence interval]) related to one (ln) standard deviation increase in hs-TnT and hs-CRP. Time to surgery was evaluated by Kaplan-Mayer analysis and Cox regression. Results Hs-TnT was independently associated with surgery for AS in patients with concomitant CAD (odds ratio [95% confidence interval]) (1.22 [1.02–1.46]) and without concomitant CAD (1.39 [1.05–1.84]). Hs-CRP was not associated with surgery for AS after adjustment for traditional cardiovascular risk factors (1.06 [0.92–1.23]). Patients with high hs-TnT levels had shorter time to surgery compared those with low levels (Figure, p Conclusions Hs-TnT – but not hs-CRP – was associated with increased risk for, and shorter time to future surgery for AS. Hs-TnT associated with myocardial mass at surgery which indicates that Hs-TnT may be used as a clinical tool and allow for identification of patients with AS who could benefit from earlier intervention. Time to surgery; tertiles of hs-TnT Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Swedish Heart–Lung Foundation

OBJECTIVES Our goal was to study long-term observed and relative survival after first-time aortic valve replacement surgery with or without concomitant coronary artery bypass surgery with reference to valve morphology (i.e. bicuspid vs tricuspid). METHODS Consecutive patients (n = 5086) from 3 Swedish hospitals, operated on between 1 January 2005 and 31 December 2016, were included. The 30-day mortality (n = 116, 2.3%) was excluded from the analysis of long-term observed and relative survival (n = 4970). Observed survival was analysed using Cox regression. Relative survival was calculated as the ratio between observed and expected survival based on data from the general Swedish population, matched for age, sex and calendar year. Risk factors for death were explored using multivariable analysis. RESULTS During the follow-up (median 4.7 years) period, 1157 (23%) patients died. Observed survival excluding 30-day mortality was 96.6%, 82.7% and 57.6% after 1, 5 and 10 years. Compared with the general Swedish population, the relative 1-, 5- and 10-year survival rates were 99.0%, 97.5% and 89.0%. Bicuspid morphology was independently associated with higher observed and relative long-term survival. Renal dysfunction, diabetes, chronic obstructive pulmonary disease, heart failure, smoking and atrial fibrillation were associated with higher long-term mortality. Combined surgery was not associated with higher observed or relative mortality. CONCLUSIONS Patients with a bicuspid morphology had better prognosis, matching that of the general population. With increased age, long-term relative survival compared favourably with survival in the general Swedish population. Adding coronary artery bypass surgery to an aortic valve replacement procedure did not affect long-term outcome., Bicuspid aortic valve is the most common congenital heart condition and leads to premature valve failure in a significant number of patients [1].

BACKGROUND: Primary prevention of cardiovascular disease often fails because of poor adherence among practitioners and individuals to prevention guidelines. We aimed to investigate whether ultrasou ...

Background: Aortic valve stenosis (AS) is the most common indication for cardiac valve surgery; untreated AS is linked to high mortality. The etiological background of AS is unknown. Previous human studies were typically based on case-control studies. Biomarkers identified in prospective studies could lead to novel mechanistic insights. Methods: Within a large population survey with blood samples obtained at baseline, 334 patients were identified who later underwent surgery for AS (median age [interquartile range], 59.9 [10.4] years at survey and 68.3 [12.7] at surgery; 48% female). For each case, 2 matched referents were allocated. Plasma was analyzed with the multiplex proximity extension assay for screening of 92 cardiovascular candidate proteins. Conditional logistic regression models were used to assess associations between each protein and AS, with correction for multiple testing. A separate set of 106 additional cases with 212 matched referents was used in a validation study. Results: Six proteins (growth differentiation factor 15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9) were associated with case status in the discovery cohort; odds ratios ranged from 1.25 to 1.37 per SD increase in the protein signal. Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Subanalyses of case-referent triplets (n=133) who showed no visible coronary artery disease at the time of surgery in the index person supported associations between AS and growth differentiation factor 15 (odds ratio, 1.40; 95% confidence interval, 1.10-1.78) and galectin-4 (odds ratio, 1.27; 95% confidence interval, 1.02-1.59), but these associations were attenuated after excluding individuals who donated blood samples within 5 years before surgery. In triplets (n=201), which included index individuals with concurrent coronary artery disease at the time of surgery, all 6 proteins were robustly associated with case status in all sensitivity analyses. In the validation study, the association of all but 1 (interleukin 17 receptor A) of these proteins were replicated in patients with AS with concurrent coronary artery disease but not in patients with AS without coronary artery disease. Conclusions: We provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.

Identification of risk markers based on quantitative ultrasound texture analysis of carotid plaques has the ability to define vulnerable components that correlate with increased cardiovascular risk. However, data describing factors with the potential to influence the measurement variability of risk markers are limited. The aim of this study was to evaluate the influence of electrocardiogram-guided image selection, plaque echogenicity and area on carotid plaque risk markers and their variability in asymptomatic carotid plaques. Plaque risk markers were measured in 57 plaques during three consecutive heartbeats at two cardiac cycle time instants corresponding to the electrocardiogram R-wave (end diastole) and end of T-wave (end systole), resulting in six measurements for each plaque. Risk marker variability was quantified by computing the coefficient of variation (CV) across the three heartbeats. The CV was significantly higher for small plaques (area 15 mm2, 6%) (p 40, 9%) (p

Cardiovascular disease is a common cause of morbidity and premature mortality. Cardiovascular disease can be prevented when risk factors are identified early. Calcified carotid artery atheromas (CCAAs), detected in panoramic radiographs, and periodontitis have both been associated with increased risk of cardiovascular disease. This case-control study aimed to 1) investigate associations between periodontitis and CCAA detected in panoramic radiographs and 2) determine the risk of future myocardial infarctions due to CCAA combined with periodontitis. We evaluated 1,482 participants (738 cases and 744 controls) with periodontitis and CCAAs recruited from the PAROKRANK study (Periodontitis and Its Relation to Coronary Artery Disease). Participants were examined with panoramic radiographs, including the carotid regions. Associations between myocardial infarction and periodontitis combined with CCAA were evaluated in 696 cases and 696 age-, sex-, and residential area–matched controls. Periodontitis was evaluated radiographically (as degree of bone loss) and with a clinical periodontal disease index score (from clinical and radiographic assessments). We found associations between CCAA and clinical periodontal disease index score among cases (odds ratio [OR], 1.51; 95% CI, 1.09 to 2.10; P = 0.02) and controls (OR, 1.70; 95% CI, 1.22 to 2.38; P < 0.01), although not between CCAA and the degree of bone loss. In a multivariable model, myocardial infarction was associated with CCAA combined with periodontitis, as assessed by degree of bone loss (OR, 1.75; 95% CI, 1.11 to 2.74; P = 0.01). When the cohort was stratified by sex, only men showed a significant association between myocardial infarction and CCAA combined with periodontitis. Participants with clinically diagnosed periodontitis exhibited CCAA in panoramic radiographs more often than those without periodontitis, irrespective of the presence of a recent myocardial infarction. Participants with combined periodontitis and CCAA had a higher risk of having had myocardial infarction as compared with participants with either condition alone. These findings implied that patients in dental care might benefit from dentists assessing panoramic radiographs for CCAA—particularly, patients with periodontitis who have not received any preventive measures for cardiovascular disease.

Background Carotid ultrasound measurements of subclinical atherosclerosis is extensively used in the research field of cardiovascular disease. Increased intima media thickness (IMT) and plaque detection have predictive value for cardiovascular events when added to traditional risk factors. However, among studies different protocols for measuring IMT (projections, mean or max values and sites) are used and methodological difficulties of plaque detection, together result in conflicting results. Recently, Deep Learning image driven classification methods, has been successfully applied in several medical imaging applications. Here we hypothesize that ultrasound image texture of the intima media complex accurately reflects the disease burden without the need to measure IMT values or detect plaques. Purpose To evaluate classification accuracy of ultrasound based deep learning approach of the intima media complex image compared to traditional risk factors for participants with no vs pronounced subclinical atherosclerosis. Methods Subjects from the VIPVIZA study (Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention, n: 3532, 40, 50 and 60 year old, 53% women) were selected for analysis. Bilateral carotid ultrasound examinations were performed according to a standardized protocol. Subjects were categorized in two groups as 1) pronounced subclinical atherosclerosis (n: 401) – bilateral plaques and estimated vascular age 10 years older, or 2) No subclinical atherosclerosis (n: 592) – no plaques and estimated ordinary vascular age. Traditional risk factors for the participants were estimated by the SCORE risk chart. A 1-cm wide region of the distal common carotid artery intima media complex was automatically segmented from the original B-mode images. The images were fed to a Deep Learning model, convolution neural network (CNN), trained using transfer learning model with 60% training data set and 40% evaluation data set. Classification performance was quantified using accuracy of ROC analysis. Results The mean age was 58 and 56 years in groups 1 and 2, respectively (with 43% and 56% women, respectively). The mean SCORE was 1.74 in group 1 and 1.09 in group 2. Classification based on SCORE had an area under the curve of 0.69 with an accuracy of 38%. The Deep learning approach had an area under the curve of 0.89 with an accuracy of 78%. Intima media image based classification Conclusion The results shows that ultrasound image texture of the intima media with Deep Learning approach can be used to detect pronounced disease without explicit measurement of IMT values or detection of plaques. With hard end-points, the approach could be used for risk stratification of subclinical atherosclerosis. Acknowledgement/Funding Västerbotten County Council, Swedish Research Council, Heart and Lung Foundation, Carl Bennet Ltd, Sweden.

Background Clinical risk factors of cardiovascular diseases (CVD) are related to atherosclerosis and cIMT and plaque are signs of early atherosclerosis. However, associations between risk factors and ultrasound variables are not fully established and comparison between studies is hampered by different imaging protocols. There is limited data regarding study population characteristics and ultrasound measurements differ regarding arterial bed, projections, and plaque definitions and inclusion Purpose 1/ To describe the distribution of asymptomatic atherosclerosis as assessed by carotid ultrasound in a middle-aged population at low/intermediate risk of CVD. 2/ To investigate the associations between clinical risk factors and a set of ultrasound variables Method Bilateral carotid ultrasound examinations were performed according to a standardized protocol in 3532 healthy VIPVIZA-participants with at least one conventional CVD risk factor. CIMT was measured in the distal far wall of CCA, 240o and 210o left and 150o and 120o right side, based on Meijer arch. For each angle, mean and max IMT was measured in a 10 mm segment. Plaques were identified according to the Mannheim consensus. Socio-economic data was also recorded. Associations between the risk factors and the set of ultrasound variables were quantified by a partial least squares (PLS) regression. A new compound ultrasound variable was computed, PLS UL, bya combining all IMT variables and plaque using the weights of the first PLS component. In a second step, to estimate how much risk factors explained the variability of the ultrasound results, associations between risk factors and both PLS UL and single cIMT variables and plaque were determined using step-wise linear regression modelling Results Mean age was 55.6 and 55.8 years among men and women (52.7% women), 13% were smokers in both sexes, and 50.8% and 39.3%, respectively, had carotid plaque. Mean of mean cIMT was 0.68 mm vs 0.64 mm (p All ultrasound variables had similar univariate associations with clinical risk factors, positive associations for all risk factors except physical activity, fruit and vegetable consumption, education and HDL-cholesterol. The strongest association between risk factors and ultrasound variables was found with PLS UL (R2=23%), compared to single cIMT variables (R2=14–18%) and plaque (R2=15%). The pattern was similar in both sexes with most risk factors shared between the sexes. The association with factors and PLS UL was stronger among 40-year olds (R2=22%) than among 50- and 60-year olds (R=12%) Conclusion A combination of ultrasound variables are stronger associated to CVD risk factors than plaque or a single CIMT measurement. The pattern is similar in men and women. These findings are relevant for development of a consensus for cIMT measurements Acknowledgement/Funding Västerbotten County Council, the Swedish Research Council, the Heart and Lung Foundation, the Swedish Society of Medicin, Carl Bennet Ltd, Sweden

Aortic stenosis is the most common valve disease in Western countries, and its prevalence is increasing because of the aging population. Some patients, denied surgery because of high risk, can be offered transcatheter aortic valve implantation (TAVI). These patients are old and have comorbidities, and it is not always easy for them to make the decision about accepting TAVI.The aim of this study was to describe the decision-making process about undergoing TAVI treatment among people with severe aortic stenosis who are denied surgery.The Swedish participants (n = 24) with a mean age of 80 years who had been offered TAVI all agreed to participate in a presurgical interview. The interviews were recorded, transcribed verbatim, and analyzed using qualitative content analysis.Three patterns in the decision-making process about TAVI treatment-ambivalent, obedient, and reconciled-were identified. The ambivalent patient is unsure of the value of treatment and aware of the risks; the obedient patient is unsure of the value of one's own decision and wants to leave the decision to others; the reconciled patient has reached a point where there is no choice anymore and is always sure that the decision to undergo TAVI is right.People with aortic stenosis who are offered TAVI need to discuss the risks and benefits in order to participate in decision making about the treatment. They have different patterns in decision making and would benefit from healthcare professionals being observant of them to support them in this process in a manner consistent with their values.

Effects of human plasma components on the activity of lipoprotein lipase: a study of samples from the VIPVIZA cohort using isothermal titration calorimetry

Publisher's version (útgefin grein), Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets. Objective: To identify novel genetic loci and pathways associated with AS. Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019. Exposures: Genetic variants (615643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples. Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography. Results: The mean (SD) age of the 44703 GERA participants was 69.7 (8.4) years, and 22019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P =.03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P =.04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]). Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target., This study was supported by grant R01 HL128550 from the NHLBI of the NIH (Dr Thanassoulis); the Ellison Medical Foundation, Robert Wood Johnson Foundation, Wayne and Gladys Valley Foundation, Kaiser Permanente Northern California, and the Kaiser Permanente National and Regional Community Benefit Programs (The Kaiser Permanente Research Program on Genes, Environment and Health); a grant from the NIH (The Genetic Epidemiology Research on Adult Health and Aging cohort); a strategic partnership between the MRC and the University of Oxford (University of Oxford MRC Population Health Research Unit); application 24281 from the UK Biobank Resource; contracts NO1-HC-25195 and HHSN268201500001I, R01 HL 089590, and the SHARe project from the NHLBI (Framingham Heart Study); the NHLBI in collaboration with Multi-Ethnic Study of Atherosclerosis (MESA) investigators (MESA and the MESA SHARe project); contracts HHSN268201500003I from the NIH, contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the NHLBI, contracts UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, and UL1-TR-001881 from the National Center for Advancing Translational Sciences, and contract DK063491 from the National Institute of Diabetes and Digestive and Kidney Diseases (MESA); contract N02-HL-64278 from the NHLBI (SHARe genotyping); shared instrumentation grant s10rr025141 from the NIH, awards UL1TR002243 and UL1TR000445 from the National Center for Clinical and Translational Science, and award UL1RR024975 from the National Center for Research Resources (Vanderbilt University Medical Center’s Vanderbilt DNA Biobank projects); and investigator-led projects U01HG004798, R01NS032830, RC2GM092618, P50GM115305, U01HG006378, U19HL065962, and R01HD07471 from the NIH (genomic data).

Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFR(cystatin C) and eGFR(creatinine) and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFR(cystatin C) and eGFR(creatinine). A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73-0.97]), especially in women (0.74 [0.60-0.92] vs. 0.93 [0.76-1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44-0.83] and 0.89 [0.65-1.23], respectively). In conclusion, a high ratio between eGFR(cystatin C) and eGFR(creatinine) was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.

BACKGROUND: People with diabetes have a higher risk for myocardial infarction (MI) than do people without diabetes. It is extremely important that patients with MI seek medical care as soon as possible after symptom onset because the shorter the time from symptom onset to treatment, the better the prognosis. OBJECTIVE: The aim of this study was to explore how people with diabetes experience the onset of MI and how they decide to seek care. METHODS: We interviewed 15 patients with diabetes, 7 men and 8 women, seeking care for MI. They were interviewed 1 to 5 days after their admission to hospital. Five of the participants had had a previous MI; 5 were being treated with insulin; 5, with a combination of insulin and oral antidiabetic agents; and 5, with oral agents only. Data were analyzed according to grounded theory. RESULTS: The core category that emerged, "becoming ready to act," incorporated the related categories of perceiving symptoms, becoming aware of illness, feeling endangered, and acting on illness experience. Our results suggest that responses in each of the categories affect the care-seeking process and could be barriers or facilitators in timely care-seeking. Many participants did not see themselves as susceptible to MI and MI was not expressed as a complication of diabetes. CONCLUSIONS: Patients with diabetes engaged in a complex care-seeking process, including several delaying barriers, when they experienced symptoms of an MI. Education for patients with diabetes should include discussions about their increased risk of MI, the range of individual variation in symptoms and onset of MI, and the best course of action when possible symptoms of MI occur.

The aim of this study was to assess the feasibility and learning curve of training novice operators in using automated ultrasound to achieve satisfactory carotid intima-media thickness (CIMT) measurements.Four novices underwent 4 weeks carotid ultrasound training using a newly developed automated ultrasonograph. A longitudinal B-mode image of the distal right common carotid artery (CCA) was acquired in 96 patients. The interoperator CIMT reproducibility was analysed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC) for every week and compared with that from an expert operator. The weekly mean CV of the measurements on the 24 patients made by all novices was consistently reduced: 0.06, 0.05, 0.03, and 0.02, respectively. For the expert, the mean CV was 0.02, 0.02, 0.03, and 0.02, respectively. The novices' standard deviation (SD) of CVs also reduced weekly from 0.04 in the first week to 0.01 in the last week (P0.05). The corresponding weekly variation in the SD for the expert was 0.02 for the first week to 0.01 in the last week (P = 0.27). The agreement between measurements made by the novices was expressed by the ICC being 0.97 (P0.001) in the first week and increased to 0.99 (P0.001) in the fourth week.CIMT assessment by novices using an automated ultrasound could be reliably achievable after a short training period. These results may have encouraging implications when designing screening programmes for primary prevention in community health service.

Purpose Carotid intima-media thickness (CIMT) is generally considered an appropriate direct vascular method for cardiovascular risk assessment. The objective of this study was to evaluate the feasi ...

Background Aortic stenosis ( AS ) has different clinical phenotypes, including AS with or without concomitant coronary artery disease ( CAD ). It is unknown whether these phenotypes share the same risk factors. In particular, lipoprotein(a) [Lp(a)] and apolipoproteins (Apo) are associated with AS , but it is unknown whether these associations differ among phenotypes. In this prospective analysis we examined the impact of Lp(a) and Apo in subgroups of patients with AS . Methods and Results We identified 336 patients (mean age at survey 56.7 years, 48% female) who underwent surgery for AS after a median 10.9 years (interquartile range 9.3 years), participants in 1 of 3 large population surveys. For each patient, 2 matched referents were allocated. Lp(a) and Apo were analyzed in the baseline samples. Uni‐ and multivariable logistic regression analyses were used to estimate risks related to a 1 (ln) standard deviation increase in Lp(a) and the ratio of Apo B to Apo A1 (Apo B/A1 ratio). High levels of Lp(a) predicted surgery for AS in 203 patients with concomitant CAD (odds ratio [95% confidence intervals]) (1.29 [1.07‐1.55]), but not in 132 patients without CAD (1.04 [0.83‐1.29]) in the fully adjusted model. Similarly, a high Apo B/A1 ratio predicted surgery in patients with concomitant CAD (1.43 [1.16‐1.76]) but not in those without CAD (0.87 [0.69‐1.10]). Conclusions High levels of Lp(a) and a high Apo B/A1 ratio were associated with surgery for AS in patients with concomitant CAD but not in those with isolated AS . This finding may lead to a new avenue of research for targeted risk factor interventions in this population.

Aortic stenosis is the most common valve disease in western countries and has poor prognosis without treatment. Surgical aortic valve replacement (SAVR) is the gold standard, and transcatheter aortic valve implantation (TAVI) is a new method that is used in high-risk patients who are denied surgery. The purpose of treatment is not only to save life, but also to reduce symptoms and increase health-related quality of life (HRQoL).The aim of this study was to describe patients' self-reported outcomes in terms of physical function, symptoms, dependence, HRQoL, and cognitive function after TAVI and SAVR.All patients treated with TAVI during 1 year ( n = 24) and age-matched patients treated with SAVR ( n = 24) were included. Data were collected on the day before and at 6 months after treatment using structural questionnaires.Self-rated function was low before treatment and increased at follow-up. A quarter of all patients reported syncope at baseline, and none reported this at follow-up. Breathlessness was reported by all patients to be the most limiting cardiac symptom, but the TAVI patients reported more severe symptoms. At 6 months' follow-up, symptoms were reduced, but breathlessness and fatigue were still common, especially in the TAVI group. HRQoL, which was very low in the TAVI group at baseline, increased in all dimensions except social function.We found no change in cognitive function or dependence at follow-up. There was no difference in the size of improvement between groups. The results could be helpful when informing future patients in order to give them realistic expectations.

Aims In transthyretin amyloid (ATTR) amyloidosis various principal phenotypes have been described: cardiac, neuropathic, or a mixed cardiac and neuropathic. In addition, two different types of amyloid fibrils have been identified (type A and type B). Type B fibrils have thus far only been found in predominantly early-onset V30M and in patients carrying the Y114C mutation, whereas type A is noted in all other mutations currently examined as well as in wild-type ATTR amyloidosis. The fibril type is a determinant of the ATTR V30M disease phenotype. (99m)Tc-DPD scintigraphy is a highly sensitive method for diagnosing heart involvement in ATTR amyloidosis. The objective of this study was to determine the relationship between ATTR fibril composition and (99m)Tc-DPD scintigraphy outcome in patients with biopsy-proven ATTR amyloidosis. Methods Altogether 55 patients with biopsy-proven diagnosis of ATTR amyloidosis and amyloid fibril composition determined were examined by (99m)Tc-DPD scintigraphy. The patients were grouped and compared according to their type of amyloid fibrils. Cardiovascular evaluation included ECG, echocardiography, and cardiac biomarkers. The medical records were scrutinized to identify subjects with hypertension or other diseases that have an impact on cardiac dimensions. Results A total of 97% with type A and none of the patients with type B fibrils displayed (99m)Tc-DPD uptake at scintigraphy (p 0.001). Findings from analyses of cardiac biomarkers, ECG, and echocardiography, though significantly different, could not differentiate between type A and B fibrils in individual patients. Conclusion In ATTR amyloidosis, the outcome of (99m)Tc-DPD scintigraphy is strongly related to the patients' transthyretin amyloid fibril composition.

Long-term survival after cardiac surgery is determined by a number of different risk factors. Central venous oxygen saturation (S(v)O(2)) measures the balance between oxygen delivery and demand. S(v)O(2) levels in the intensive care situation are reported to be associated with patient outcome. The present report explores the connection between S(v)O(2) during cardiopulmonary bypass (CPB) and survival after cardiac surgery.Retrospective analysis of one thousand consecutive cardiac surgical patients was undertaken. S(v)O(2) during CPB was monitored online. Registry data combining specific risk factors with S(v)O(2) were selected for Kaplan-Meier and Cox regression analysis to examine the influence on 30-day and 3-year survivals.Nine-hundred and thirty-two patient records were eligible for analysis. S(v)O(2) below 75% during CPB was associated with significantly shorter 30-day and 3-year survivals. Based on Kaplan-Meier statistics, the survival rate decreased by 3.1% (98.1-95.0), P = 0.011 and 6.1% (92.7-86.6), P = 0.003, respectively. The influence of S(v)O(2) on 3-year survival remained statistically significant after controlling for a series of risk factors in the Cox regression analysis. Patients with S(v)O(2)75% carried a 2-fold (odds ratio 2.1) increased relative risk of shortened 3-year survival (P = 0.003). Other risk factors statistically significantly associated with 3-year survival were age, gender, duration of CPB, blood temperature, hypertension, haematocrit and type of surgical procedure.We report decreased 30-day and 3-year survival expectancy for patients experiencing S(v)O(2) lower than 75% during CPB.

Serum metabolic phenotypes correlate with the extent of coronary artery calcification in symptomatic patients with no flow limiting lesions

Aim: To describe symptoms of a first myocardial infarction in men and women with and without diabetes.Methods: We conducted a population-based study of 4028 people aged 25-74 years, with first myoc ...

Background: Ventricular repolarization (VR) is strongly influenced by heart rate (HR) and autonomic nervous activity, both of which also are important for arrhythmogenesis. Their relative influence ...

Aim: To explore older men's prehospital experiences of their first myocardial infarction (MI). Background: The delay between the onset of symptoms to the initiation of medical care is a major det ...

The present study explored the influence of haemodilution on estimates of the glomerular filtration rate (GFR) in conjunction with cardiopulmonary bypass (CPB) and cardiac surgery. Ninety-eight patients (n = 98) undergoing coronary artery bypass grafting with the aid of CPB were examined. The serum concentration of cystatin C and creatinine was analysed prior to surgery, after completion of CPB and in the intensive care the day after surgery. The estimated GFR was calculated using standard equations based on the serum concentration of cystatin C and creatinine. It was found that haemodilution induced by CPB had significant effects on the estimated GFR. For cystatin C, the GFR increased by 50.5 ± 2.5 ml/min (P = 0.000) and for creatinine based GFR with 22.5 ± 0.9 ml/min (P = 0.000) using the 4-variable modification of diet renal disease formula and with 22.1 ± 0.93 ml/min (P = 0.000) for the Cockcroft-Gault formula, respectively. Similar effects of haemodilution on GFR were also detected postoperatively. Haemodilution induced by CPB may therefore significantly overestimate the renal function as indicated by GFR based on serum markers.

This study aimed to assess the early effect of trans-catheter aortic valve implantation (TAVI) on right (RV) and left ventricular (LV) function in severe aortic stenosis (AS) patients. Twenty AS patients (age 79±6 years) were examined before, one week and six weeks after TAVI using Doppler echocardiography. LV ejection fraction (EF), long-axis [mitral annular plane systolic excursion (MAPSE)] and RV long-axis [tricuspid annular plane systolic excursion (TAPSE)] function, septal radial motion were studied. Results were compared with 30 AS patients before and one week after aortic valve replacement (AVR) as well as 30 normals (reference group). Before TAVI, LVEF was reduced and E/A was higher than the reference and AVR groups (P0.05 for all). MAPSE, TAPSE and septal motion were equally reduced in TAVI and AVR patients (P0.05 for all). One week after the TAVI, EF increased in patients with values50% before the procedure. In contrast, AVR resulted in reversed septal motion (P0.001) and depressed TAPSE (P0.001). The extent of reversed septal motion correlated with that of TAPSE in the patients group as a whole after procedures (r=0.78, P0.001). Six weeks after TAVI, RV function remained unchanged, but LVEF increased and E/A decreased (P0.05 for both). Thus, TAVI procedure results in significant early improvement of LV systolic and diastolic function particularly in patients with reduced EF and preserves RV systolic function.