Fighting Social Inequality in Cardiovascular Health I
Condition: Cardiac Disease; Vascular Diseases
MeSH terms: Vascular Diseases; Heart Diseases
Study type: Interventional

Summary: 
      This study attempts to reduce social inequality in cardiovascular health by performing an
      interventional screening trial on how best to decrease cardiovascular disease (CVD) among
      people with low social status
    

Detailed description: 
      Background

      Although CVDs have decreased, they are still among the most predominant cause of morbidity
      and mortality in the western world, incl. Denmark, where about 420,000 people have recognized
      CVD symptoms. Due to an aging population, the decline has not reduced CVD admissions and
      healthcare costs.

      In Denmark, the CVD related hospital admission costs are DKK 4.6 billion and the
      pharmaceutical cost DKK 2.4 billion. The Danish National Board of Health has reported that
      CVD carries the second largest socioeconomic difference in burden of disease. Unfortunately,
      population-based health checks and screening for risk factors has proven not efficient.
      Consequently, screening of asymptomatic CVD is discussed intensively. In the investigators
      first unique CVD screening RCT (2008-11), the VIVA trial, they randomized more than 50.000
      65-74 year old men for population-based ultrasound screening for abdominal aortic aneurysm
      (AAA), peripheral arterial disease (PAD) and hypertension. In case of positive finding,
      preventive medical actions were initiated. A significant reduction in overall mortality by 7%
      after 5 years was observed (paper submitted). Using a non-contrast CT scan, instead of the
      ultrasound based screening approach, has the opportunity to identify aneurysms in the entire
      aortic, coronary artery calcification (CAC) and arterial fibrillation, so individualized risk
      assessment and initiation of preventive actions on those with sign of early asymptomatic CVD
      is possible. The investigators therefore initiated a second trial (DANCAVAS) in 2014
      randomizing 45.000 65-74 year old men with the potential of a huge beneficial effect on
      health, quality of life (QoL) and survival. However, screening is impaired by lower social
      class, and adherence to initiated prevention could be impacted as well. Consequently, they
      want to conduct a third RCT (FISICH) to test a number of add-ons to screening that
      potentially balance the benefits across socio economic groups.

      The perspective is to establish a clear decision foundation for public health care policy
      incl. benefits, cost effectiveness and impact on social inequality of alternative variants of
      population screening for CVD.

      Hypotheses The primary hypothesis is that an extensive circulatory screening and intervention
      programme reduces social inequality in cardiovascular health and fulfills the WHO criteria
      for screening. However, this reduction can be even more pronounced, if factors reducing the
      social selection to attend screening and adherence to preventive actions initiated are
      identified.

      Aims

      The aims are to

        1. Test whether prebooking and/or supplemental informative pictures of the screening
           session and consultation improves attendance rate in general, and particular among those
           with the lowest educational level, lowest income level, and psychiatric disease.

        2. Investigate whether confrontation of imaging of own arterial lesions at consultation
           after screening and/or an e-mail 3 and 12 months after the consultation in case of
           positive findings improves adherence to suggested cardiovascular preventive actions, and
           whether it influences quality of life, in general and especially concerning those with
           the lowest educational level, lowest income level, and psychiatric disease.

      Materials and methods

      In FISICH-I 20.000 60-64 year old men are randomized to the control group, while another
      5.000 are randomized to the screening and intervention program for CAC, aortic and iliac
      aneurysms, atrial fibrillation, PAD, hypertension, diabetes and hypercholesterolaemia. There
      is no exclusion criteria. The screening setup is similar to DANCAVAS:

        1. A small questionnaire on life style, medical history, and the QoL a.o. will be enclosed
           with the invitation. Non-responders are re-invited once.

        2. The participant will be informed at attendance to the screening visit, and their consent
           will be obtained together with the questionnaire, weight, height, and waist
           circumference.

        3. The CT scan will cover the area from the mandibular bone distally to the proximal third
           of the femur. Calcium scores for the common carotids, coronary arteries, aorta, and
           common iliac, and femoral arteries will be calculated. The aorta are visualized, and the
           diameter is measured in ascending, arcus, descending and abdominal, and if possible in
           the iliac arteries. Further the heart rhythm during the CT scan is evaluated.

        4. Bilateral blood pressure will be recorded three times after 5 minutes of supine rest,
           and concurrently the ankle blood pressure are measured.

        5. The HbA1c and lipid parameters will be measured. Biobank blood samples are then taken,
           centrifuged, labelled, cooled, and stored at -80 degrees Celsius.

      Follow-up visit after screening If the CAC is above the median or if an aneurism of
      peripheral arterial disease are detected the participant is informed of the finding and its
      implications at a follow-up visit. At this visit, the patient will be recommended suitable
      prophylactic measures, including smoking cessation, walking/exercise, a lowfat diet.
      Additionally to start treatment with aspirin 75 mg/day and atorvastatin 40 mg/day. If an
      aneurism is large the patient is referred vascular surgical assessment for the repair.
      Otherwise, an annual check-up of the aneurism including a CT scan will be offered. If no
      positive findings (CAC above the median, aneurysm or PAD) are detected, the participants will
      be informed of the findings by e-mail or ordinary post as preferred.

      Independent of the above findings, the patients will be encouraged to see their GP for
      further assessment if potential undiagnosed hypertension (systolic blood pressure >160 mmHg),
      diabetes mellitus (HbA1c >48 mmol/mol), or significant isolated hypercholesterolemia
      (total-cholesterol >8.0 mmol/l) are observed, as possible continuous medical treatments will
      be better managed by the GPs.

      The GPs will be informed by a letter of all negative and positive results and the initiated
      actions. Additionally in the FISICH-I trial, four further randomizations are performed. In
      the written invitations to the screening examination two further randomizations are
      performed;

        -  prebooking versus active booking

        -  +/- addition of illustrations of the examinations during the screening session.

      Power calculations and Randomisations

      Randomisation will be performed in SPSS by providing each individual a random number from
      1-20. Those numbered +16 will be invited to participate in the screening program. Those
      numbered 17 and 18 will be prebooked, while those numbered 19 and 20 will have to book
      themselves through web-booking, email or phone.

      Those with an equal number (18 and 20) will receive supplemental informative pictures of the
      screening session.

      In case of positive finding a new random number from 1-4 is given. Those numbered 3 and 4
      will be confronted with imaging of their own arterial lesions, whilst others will receive
      standard information. Those with an equal number (2 and 4) will receive a SMS, e-mail and
      phone call 3 & 12 months after the consultation. If all groups after randomisations are
      equally sized,- 182 will only be additionally randomized to be remembered prescription
      renewal after 3 and 12 months, and 182 will only have been randomized to the standard of
      booking (Control group for all invited). If 12 months compliance to initiated preventive
      medication is 66%, then with 0.05 significance level, and 80% power, the smallest difference
      detectable is 15%, which seems clinical relevant. However, merged analyses adjusting for the
      other interventions will be performed reducing the smallest detectable difference and reveal
      potential synergistic combinations. Similar group comparisons will be performed for all
      randomized interventions.

      Baseline variables Age, smoking, previous or current stroke, ischemic heart disease, PAD,
      chronic obstructive pulmonary disease, diabetes, hypertension, use of statins, useof
      antithrombotics, body mass index, systolic- and diastolic blood pressure, ankle brachial
      index, marital status, highest educational level, personal- andin house income, psychiatric
      morbidity defined as any diagnosis and/or use of medications for mental illness, and QoL.

      Baseline and outcome variables from national registries The CPR number assigned to Danish
      citizens enables individual-level linkage to multiple nation-wide healthcare and
      administrative registries which have proved valid.

      Registry-based information on outpatient visits, hospitals admissions and procedures (The
      Danish National Patient Registry), relevant prescribed drugs dispensed (The Danish National
      Prescription Registry), socio economic status etc. (Registries at Statistics Denmark) and
      primary care service use (National Health Insurance Service Registry) will be obtained.

      Outcomes The primary outcomes are

        1. Attendance to screening

        2. One-year adherence to initiated lipid-lowering and/or antithrombotic medication.

      Secondary outcome is:

      1. QoL,

      Statistical analysis Baseline characteristics will be analysed using conventional summary
      statistics.

      Attendance rates adjusted for invitation layout and booking-method, as well as compliance one
      year after initiation (def.: received a prescription 9-12 months after the consultation)
      adjusted for image-confrontation and post-consultation phone call are compared by logistic
      regression analysis.
    

Intervention name(s): Prebooking; Pictured invitation
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Participants are receiving a prebooked appointment for CVD screening or being invited to book an appointment for CVD Screening; Participants are receiving an illustrated invitation CVD screening or a classical text-invitation to book an appointment for CVD Screening
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: 2 x factorial design regarding attendance rate to cardiovacular screening
Masking: None (Open Label)
Primary purpose: Screening
Keywords: Screening; Prevention; Cardiovascular; Public health