Primary prevention of cardiovascular disease often fails because of poor adherence among practitioners and individuals to prevention guidelines. We aimed to investigate whether ultrasound-based ...pictorial information about subclinical carotid atherosclerosis, targeting both primary care physicians and individuals, improves prevention.
Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) is a pragmatic, open-label, randomised controlled trial that was integrated within the Västerbotten Intervention Programme, an ongoing population-based cardiovascular disease prevention programme in northern Sweden. Individuals aged 40, 50, or 60 years with one or more conventional risk factors were eligible to participate. Participants underwent clinical examination, blood sampling, and ultrasound assessment of carotid intima media wall thickness and plaque formation. Participants were randomly assigned 1:1 with a computer-generated randomisation list to an intervention group (pictorial representation of carotid ultrasound plus a nurse phone call to confirm understanding) or a control group (not informed). The primary outcomes, Framingham risk score (FRS) and European systematic coronary risk evaluation (SCORE), were assessed after 1 year among participants who were followed up. This study is registered with ClinicalTrials.gov, number NCT01849575.
3532 individuals were enrolled between April 29, 2013, and June 7, 2016, of which 1783 were randomly assigned to the control group and 1749 were assigned to the intervention group. 3175 participants completed the 1-year follow-up. At the 1-year follow-up, FRS and SCORE differed significantly between groups (FRS 1·07 95% CI 0·11 to 2·03, p=0·0017 and SCORE 0·16 0·02 to 0·30, p=0·0010). FRS decreased from baseline to the 1-year follow-up in the intervention group and increased in the control group (−0·58 95% CI −0·86 to −0·30 vs 0·35 0·08 to 0·63). SCORE increased in both groups (0·13 95% CI 0·09 to 0·18 vs 0·27 0·23 to 0·30).
This study provides evidence of the contributory role of pictorial presentation of silent atherosclerosis for prevention of cardiovascular disease. It supports further development of methods to reduce the major problem of low adherence to medication and lifestyle modification.
Västerbotten County Council, the Swedish Research Council, the Heart and Lung Foundation, the Swedish Society of Medicine, and Carl Bennet Ltd, Sweden.
•VIPVIZA is a pragmatic randomized controlled trial performed within the regular primary health care and targeting both individuals and physicians.•Beneficial effects on risk for cardiovascular ...disease regardless of sex and education level 3 years after providing pictorial information of subclinical atherosclerosis in addition to regular preventive information.•The results indicate that the intervention effect is a combined effect of pharmacological treatment and lifestyle modification.•The intervention effect was observed in the intermediate risk group, the group where most CVD events occur and in which sufficient prevention is often overlooked.
Non-adherence to guidelines and preventive measures is a major challenge, particularly so to obtain long-term adherence to lifestyle changes and recommended medication. The objective was to investigate if pictorial information regarding subclinical carotid atherosclerosis provided to individuals and physicians gave sustained effects on cardiovascular risk beyond the previously reported effect after 1 year and up to 3 years.
A Prospective Randomized Open Blinded End-point (PROBE) trial. Within a CVD prevention program in Västerbotten County, Sweden, 3532 healthy individuals aged 40, 50 or 60 years were enrolled and 1:1 randomized to intervention (n = 1749; pictorial information with additional prevention materials to participants and physicians) or control group (n = 1783; no pictorial information to participants and physicians). Preventive measures were managed within primary care. Participants were investigated at baseline during 2013–2016 and at follow-up after 1 and 3 years.
A beneficial effect on cardiovascular risk was observed at 3-year follow-up; Framingham Risk Score (FRS) was 13.38 for the intervention group and 14.08 for the control group (p = 0.047) and SCORE was 1.69 vs. 1.82 (p = 0.022). The effect observed at 1-year was sustained over 3 years after adjustment for sex and education and more pronounced among participants with a severe atherosclerotic picture at baseline.
This study provides evidence of sustained beneficial effects on the adherence to prevention guidelines over 3 years of pictorial information about subclinical carotid atherosclerosis, resulting in lower cardiovascular risk regardless of sex and educational level. Direct visualization of the underlying still subclinical atherosclerotic disease, rather than just indirect information about risk factors and statistical risk of future myocardial infarction, stroke and death, is one way to tackle the problem of non-adherence to prevention of cardiovascular diseases.
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Abstract
Aims
Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS ...and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS.
Methods and results
A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51 and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS.
Conclusion
Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.
Structured Graphical Abstract
Structured Graphical Abstract
Genetic etiology of aortic stenosis. This study meta-analyzed 13 765 AS cases vs. 640 102 controls and confirmed 15 genetic loci associated with AS. Downstream analyses implicated additional candidate genes involved in dyslipidemia, inflammation, calcification, and adiposity. The Manhattan plot shows variants with P ≥ 1 × 10−25, for improved visualization. Genetic loci in grey were previously identified, and those in gold are new discoveries. Abbreviations: AS, aortic stenosis; GWAS, genome-wide association study; LDL, low-density lipoprotein.
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.
Sweden has an ambitious plan to fully decarbonise district heating by 2030 and to contribute with negative emissions of greenhouse gases in 2050. The vagaries of the energy market associated with ...climate, political, and social changes entail cross-sectoral integration that can fulfill these national targets. Fifth-generation district heating and cooling (5GDHC) is a relatively new concept of district energy systems that features a simultaneous supply of heating and cooling using power-to-heat technologies. This paper presents best practices for developing 5GDHC systems in Sweden to reach a consensus view on these systems among all stakeholders. A mixed-method combining best practice and roadmapping workshops has been used to disseminate mixed knowledge and experience from middle agents representing industry professionals and practitioners. Four successful implementations of 5GDHC systems are demonstrated and the important learned lessons are shared. The best practices are outlined for system planning, system modeling and simulation, prevailing business models for energy communities, and system monitoring. A roadmap from the middle agents’ point of view is composed and can be utilised to establish industry standards and common regulatory frameworks.
•Middle agents interact with all stakeholders and can induce a sociotechnical change.•A roadmap is delineated by system planners, DH companies, and HP experts.•Four different technical solutions for the shared energy concept are demonstrated.•Best practices for system planning, modeling, ownership, and monitoring are proposed.•Four topics for future development of 5GDHC systems are identified.
The ABO blood group system has previously been associated with cardiovascular disease (CVD), where non-O blood group individuals have shown an increased risk. Studies assessing early atherosclerotic ...disease while also including RhD are few. We aimed to determine whether the ABO and RhD blood groups are associated with subclinical atherosclerosis in a healthy population.
We included 3532 participants from the VIPVIZA trial with available carotid ultrasonography results to assess subclinical disease. Information about blood groups was obtained from the SCANDAT-3 database, where 85% of VIPVIZA participants were registered.
RhD- individuals aged 40 years showed increased carotid intima-media thickness (B 1.09 CI 95% 1.03; 1.14) compared to RhD+ individuals. For ABO, there were no differences in ultrasonography results when assessing the whole study population. However, 60-year-old individuals with heredity for CVD and a non-O blood group had decreased odds for carotid plaques (OR 0.54 CI 95% 0.33; 0.88).
RhD blood group is associated with subclinical atherosclerosis in younger individuals, indicating a role as a mediator in the atherosclerotic process. In addition, a non-O blood group was associated with decreased subclinical atherosclerosis in individuals aged 60 and with heredity (corresponding to the group with the highest atherosclerotic burden).
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, whereas 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 not only 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.
Pictorial communication about subclinical atherosclerosis can improve cardiovascular disease (CVD) risk, but whether it leads to long-term shifts in self-rated CVD risk (risk perception) and beliefs ...about possibility to influence personal risk (efficacy beliefs) is unknown.
To study the impact of personalized color-coded and age-related risk communication about atherosclerosis and motivational conversation, compared to traditional risk factor-based communication, on risk perception and efficacy beliefs. Also, whether risk perception increases with message severity.
The effect of the pragmatic RCT Visualization of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention (VIPVIZA) was analyzed using a linear mixed effects model with risk perception and efficacy believes at 1-year and 3-year follow up as dependent variables. Participants' (n = 3532) CVD risk perception and efficacy beliefs were assessed with visual analog scales (0-10). Fixed effects were group (intervention vs control), time point (1 year or 3 years) and interaction between group and time point. Further, the models were adjusted for corresponding baseline measurement of the dependent variable and a baseline × time point interaction. Effect of pictorial color-coded risk in the intervention group was investigated using a corresponding mixed effects model, but with pictorial risk group (message severity) as exposure instead of intervention group.
After one year, the intervention group rated their CVD risk as higher (m = 0.46, 95% CI 0.32-0.59), with an effect also after 3 years (m = 0.57, 95% CI 0.43-0.70). The effect was consistent in stratified analyses by sex and education. Overall, no effect on efficacy beliefs was observed. In the intervention group, differences in CVD risk perception were found between participants with different color-coded risk messages on atherosclerosis status.
Personalized, color-coded and age-related risk communication about atherosclerosis had an effect on risk perception with an effect also after 3 years, whereas overall, no effect on efficacy beliefs was observed.
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.
The aim of this study was to explore patients' experiences of being considered for transcatheter aortic valve implantation but judged ineligible.
Individual in-depth interviews were performed with eight persons, and qualitative content analysis was used for the analysis.
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.
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.
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.
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