Research project VIsualiZation of asymptomatic Atherosclerotic disease for optimum cardiovascular prevention ─ a pragmatic randomized controlled trial nested in the Västerbotten Intervention Program. Prevention of cardiovascular disease (CVD) often fails due to low adherence among physicians and individuals to prevention guidelines. Therefore, new and alternative approaches are needed. VIPVIZA evaluates the potential of visualization of silent atherosclerosis as the basis for prevention.
VIPVIZA informs patients and their physicians with graphs and pictures about subclinical atherosclerosis aiming at improved CVD risk perception and adherence to CVD prevention guidelines. After one year, a reduction of Framingham Risk Score was shown, in contrast to an increase in the control group, where no ultrasound results were given. The difference between groups was similar after three years. The CVD risk atherosclerosis and CVD morbidity and mortality up to 10 years, and the intervention impact onbiomarkers and ocial and psychological determinants of behavioral change will be evaluated.
VIPVIZA is funded by Västerbotten County Council (Central ALF, ALFVLL-298001, -643391, Spjutspets VLL-583721), the Swedish Research Council (Dnr 521-2013-2708, 2016-01891), the Heart and Lung Foundation (Dnr 20150369, 20170481), the Swedish Society of Medicine (SLS-405351, -503111), and SKANDIA Risk/Health.
In addition to major grants, VIPVIZA was funded by the Heart Foundation of Northern Sweden, STROKE-the National Association, the Foundation for Stroke Research in Northern Sweden, The Swedish Insurance Society, Visare Norr (the four Northern Regions) (465621, 561591, 741711, 931135), Foundations managed by the Faculty of Medicine Umeå University, and The Swedish and the Västerbotten Heart and Lung Associations.
An unconditional donation was received from Carl Bennet Ltd, Sweden.
Uppsala Clinical Research Center, Uppsala Universitet
Institute of Communication and Health, Faculty of Communication Sciences, University of Lugano
School of public health, Medical Faculty, University of Gothenburg, Sweden.
The main objective of this project is to contribute to improved primary prevention of cardiovascular disease above conventional CVD risk screening and prevention through the provision of a visual image and pictorial report of atherosclerosis while still asymptomatic. The image and report are seen and discussed by both physician and patient in order to improve physicians assessment of patients’ CVD risk and guideline adherence, as well as improve patients’ risk perception and enhance the motivation for performance of prevention measures. The specific objectives include: 1.To assess the prevalence of asymptomatic atherosclerotic disease in men and women through identification of carotid plaques and measurement of carotid intima-media thickness (CIMT), and to relate plaques and CIMT to clinically estimated CVD risk factors and risk scores 2.To explore the impact of pictorial representations of atherosclerosis on physicians´ adherence to prevention guidelines, and on individuals’ quality of life, preventive measures, risk factor control and progress of atherosclerotic disease over the course of three and six years, as well as on premature CVD morbidity and mortality over the course of 10 years 3.To evaluate how individuals’ social, psychological, cognitive characteristics relate to atherosclerosis and CVD risk at baseline and progression of CVD risk and atherosclerosis 4.To investigate biomarkers in relation to CIMT and plaques at baseline, changes in conventional CVD risk markers and lifestyle, and progression of atherosclerosis.
Primary prevention of CVD often fails due to poor adherence among practitioners and patients to evidence-based prevention guidelines on effective modification of risk factors by lifestyle change and pharmacological treatment. Contributory factors include poor communication about the CVD risk by the physician and inaccurate risk perception among patients. The risk message is usually communicated verbally or numerically, while potentially more effective visual tools are seldom used. For the clinical assessment of CVD risk Framingham risk score (FRS) and the European systematic coronary risk evaluation (SCORE) are most widely used. However, evidence that their use translates into reduced CVD morbidity and mortality is scarce. These risk scores focus on high-risk individuals, despite 60-70% of all CVD events occurring among individuals at low or intermediate risk for CVD. They might also be too abstract to lead to accurate risk perception and to motivate for preventive actions; information alone seldom results in rational behavior modification. VIPVIZA takes a different approach from current practice for the prevention of CVD. Instead of being based solely on indirect risk factors, this project evaluates the atherosclerotic disease itself while it still is silent, providing improved assessment, communication and perception of the CVD risk and hence greater motivation for prevention. This is achieved with ultrasonography of medium sized arteries with assessment of Carotid Intimw media thickness (CIMT) and existing atherosclerotic plaques.
The study is a pragmatic randomised open-label controlled trial with blinded evaluators (PROBE) with single-arm cross-over of the control-group at the 3-year follow-up. It is registered at https://clinicaltrials.gov/ct2/show/NCT01849575, where a detailed study protocol is presented. VIPVIZA is integrated in and added to the ordinary Västerbotten Intervention Programme (VIP). Individuals with at least one clinical CVD risk factor were invited to the VIPVIZA trial when they participated in VIP (n=4177), resulting in inclusion of of 3532 participants. Baseline visits with ultrasound examinations were carried out from April 2013 to June 2016. Participants were consecutively and randomly allocated to two groups (intervention and control group) using a computer-generated randomization list. The ultrasound examinations in VIPVIZA at baseline as well as after three years were performed at the hospitals in the three cities/towns (Umeå, Skellefteå, Lycksele), and in remote rural areas at primary health care centres. Risk factor measurements and questionnaires at follow-up after one and three years were carried out for participants living in Umeå at the Clinical Research Centre at Umeå University Hospital, and for participants in the rest of the county at their local primary health care center. The 6.5-year follow-up examinations are using the same methodology and routines, they were commenced in December 2019 and are expected to be completed December 2022. The progress of the study is according to the plan. Both groups are managed according to clinical guidelines for CVD prevention within primary care (not by the study team).
Pictorial representation of the carotid ultrasound results was given to each participant in the intervention group and their primary care physician. Atherosclerosis was presented as vascular age, with a gauge ranging from green through yellow, orange and red to illustrate the individual’s biological, compared to chronological, age. A red or a green circle, like a traffic light, illustrated detected or no detected plaque, respectively. A stylized picture of the individuals’ ultrasound image was also shown. Brief written information about atherosclerosis as a dynamic process that is modifiable by a healthy lifestyle and pharmacological treatment, as well as an interpretation of the result and general advice on CVD prevention were included. After 2-4 weeks, participants received a follow-up phone call by a research nurse in order to reassure and give additional clarification and information as needed. The same pictorial information was repeated to participants after 6 months. No information about the ultrasound result was given to the control group and their physicians, and was also not available within health care.
After the 3-year examinations, the ultrasound result is given to all study-participants and their physicians in primary care. Thus a single arm-crossover, where the intervention is provided twice to the intervention group three years apart, and for the first time to the control-group three years after baseline.
Clinical risk factors for cardiovascular disease: Measured at the baseline VIP health survey and at 1-, 3-, and 6.5 year follow-up (blood pressure, lipids, and glucose, BMI and waist circumference).
Questionnaires: The VIP questionnaire covers health, socioeconomic situation, quality of life (RAND 36), lifestyle (physical activity, tobacco and alcohol consumption, diet), working database that is managed only by the conditions, social network. Validated psychometric instruments at baseline, 3- and 6.5-year follow-up included health literacy, coping strategies, an optimism-pessimism scale, self-efficacy, HADS and self-rated risk of CVD. Perceptions about preventive medication at the 3-year follow-up. Questionnaires on stress and personality were added after 3 years, as well as questions on attitudes and norms regarding healthy life style habits and reactions to the ultrasound report.
At the 6-5-year follow-up, objective testing of physical activity with accelerometry, measurement of hand grip strength, and participants’ dental health (information from dental records and panorama x-ray images) are included.
Carotid ultrasound examinations are performed at baseline and after 3 and 6.5 years according to a standardized protocol.
Interviews: With participants after the first and second ultrasound examination, and with primary care physicians after the first ultrasound examination.
Stored samples of blood to the Medical Biobank: This was done at the baseline VIP visit and at 3- and 6.5-year follow-up visits among participants living in Umeå, to be used for analyses of novel biomarkers
Register data: Data from VIP-participation before baseline, Prescriptions, visits and risk factor measurements from the Medical records system in Region Västerbotten. The Prescribed drugs, Hospitalizations and Causes of deaths registers at the National Board of Health and Welfare, results from the physical and psychological testing at age 18 years from the Conscripts Registry (male only), highest attained education and income from Statistics Sweden and air-borne pollutants from the Swedish Meteorological and Hydrological Institute.
VIPVIZA has a separate secure database, that is managed only by the database manager. A dataportal includes metadata information about the data and a digital system for management of proposals. For further information, contact PI Ulf Näslund
VPVIZA has a post at the Swedish National Data Service https://snd.gu.se/en/catalogue/search/VIPVIZA
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Erratum in: Lancet. 2019 Jun 15;393(10189):2394
5. Lindahl B, Nordin S, Nordin M, Johansson H, Lindvall K, Vanoli D, Ng N, Näslund U, Norberg M, Schulz P. Health literacy is independently associated with carotid atherosclerotic plaque and cardiovascular risk. Eur J Prev Card 2020;27:209-15, published on-line 2019 Oct 15 DOI: 10.1177/2047487319882821
6. Nyman E, Näslund U, Grönlund C. Inter-sonographer reproducibility of carotid ultrasound plaque detection using Mannheim consensus in subclinical atherosclerosis. Clin Physiol Funct Imaging 2020;40:46-51
7. Bengtsson A, Norberg M, Ng N, Wester P, Carlberg B, Grönlund C, Hultdin J, Lindahl B, Lindahl B, Nordin S, Nyman E, Wennberg P, Näslund U for the VIPVIZA trial group. The beneficial effect over three years by pictorial information to patients and their physician about subclinical atherosclerosis and cardiovascular risk: Results from the VIPVIZA clinical trial. Am J Prev Card 2021 https://doi.org/10.1016/j.ajpc.2021.100199
8. Sjölander M, Carlberg B, Norberg M, Näslund U, Ng N. Prescription of lipid-lowering and antihypertensive drugs following pictorial information about subclinical atherosclerosis. A randomised controlled study. JAMA Network Open 2021;4(8):e2121683. doi:10.1001/jamanetworkopen.2021.21683
9. Schulz P, Lindahl B, Hartung U, Näslund U, Norberg M, Nordin S. The Right Pick: Does a Self-assessment Measurement Tool Correctly Identify Health Care Consumers with Inadequate Health Literacy? Patient Educ Couns. 2021 Jul 29:S0738-3991(21)00505-X. doi: 10.1016/j.pec.2021.07.045. Online ahead of print.PMID: 34366227
10. Kovrov O, Landfors F, Saar-Kovrov V, Näslund U, Olivecrona G. Effects of human plasma components on the activity of lipoprotein lipase: a study of samples from the VipViza cohort using isothermal titration calorimetry. J Lipid Res in press