Effectiveness of letters to patients with or without Cochrane blogshots on 10-year cardiovascular risk change among women in menopausal transition: 6-month three-arm randomized controlled trial | BMC Medicine

Trial design

This parallel, three-arm randomized controlled trial (RCT) tested the effect of a 6-month educational intervention in a form of letters in decreasing the 10-year CVD risk in women aged 45 to 65 with one or more known CVD risk factors. The letters reminded the participants of their own 10-year CVD risk, with or without included Cochrane blogshots.

Participants

The inclusion criteria were (1) female sex; (2) age 45 to 65 years, which is the age of menopause transition, including postmenopause [15]; and (3) one or more CVD risk factors: overweight or obesity (body mass index (BMI) ≥ 25 kg/m², and/or central obesity, i.e., waist circumference ≥ 88 cm), high blood pressure (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg), high blood cholesterol (≥ 5.2 mmol/L), and active smoking. The participants on antihypertensive therapy were eligible for the study.

Current CVD (ischemic heart disease, peripheral artery disease, and stroke), malignant diseases, serious systemic diseases, and/or mental diseases were the exclusion criteria.

The trial took place in family medicine offices in Croatia from February 1, 2018, to September 1, 2020. Family medicine offices are primary health care offices, i.e., the first step for patients to seek help for their health problems in the Croatian health care system, which ensures full national health coverage. Physicians working in family medicine offices are specialists in family medicine. One office was in the city of Split, the capital of the Split-Dalmatia County; one in the city of Osijek, the capital of the Osijek-Baranja County; and one in the city of Rijeka, the capital of the Primorje-Gorski Kotar County. An office from each of the following towns was the recruitment sites: Supetar (the island of Brač, Split-Dalmatia County), Bijelo Brdo (Vukovar-Srijem County), Kotoriba (Međimurje County), and Kutina (Sisak-Moslavina County). In each family medicine office, 30 participants were recruited. All participants involved in this trial had access to their family medicine office according to their place of residence. The first participant was recruited in February 2018, and the last participant was recruited in February 2020. The recruitment was performed by family medicine doctors in their medical offices. They also performed clinical measurements at the baseline and 6 months after the intervention, after sending the notification to the participants about their check-up appointment. The data from the two time points were sent to the primary investigator.

The Ethics Committee of the University of Split, School of Medicine, approved the study, No. 2181-198-03-94/10-11-0038 and No. 2181-198-03-04/19-0044. Written informed consent was obtained from all participants after they received the information about the study. The data were processed as pseudonymized (coded) data, following the General Data Protection Regulation (GDPR).

Intervention

The participants were randomized into three parallel groups:

1. 1.

   Control group: A month after recruitment, the participants received a letter that included the list of their own CVD risk factors and their 10-year risk of CVD, based on the data provided by the participants during recruitment. This was the only letter this group received.

2. 2.

   Passive intervention group: The participants first received a letter with the same information as the control group. After this letter, the participants received a letter every 2 months, which reminded them of their own CVD risk factors and their 10-year risk of CVD. In total, this group received four letters at their home address during the trial.

3. 3.

   Active intervention group: The participant first received the same letter as the other two groups. Every 2 months after that letter, they received a reminder about their own CVD risk factors and their 10-year risk of CVD, together with a Cochrane systematic review summary in the form of a blogshot. The topics in the blogshots were the following: (1) the effect of calcium in the prevention of high blood pressure [16], (2) the effect of reducing saturated fat acids in eating habits [17], and (3) the effects of green and black tea in the prevention of CVD [18]. In total, this group received four letters at their home address during the trial.

The examples of all types of letters sent to the participants in each group (in Croatian) are available in Additional file 1: Letters 1–5, including the Cochrane blogshots (in Croatian) used in the letters.

Outcomes

At recruitment and at 6 months after the intervention, we measured the following clinical parameters: height, weight, BMI, waist and hips circumference, systolic and diastolic blood pressure, total serum cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, triglycerides, and glucose.

The primary outcome measure was the change in the score between the 10-year risk of CVD at the beginning of the study and the 10-year risk of CVD after 6 months. The 10-year risk of fatal CVD was estimated using an online tool (https://www.cvriskcalculator.com/) based on the American College of Cardiology/American Heart Association (ACC/AHA) guidance [19]. The calculation is based on the following data collected from the study participants: age, gender, race, total and HDL cholesterol, systolic blood pressure, data about antihypertensive therapy, diabetes mellitus, and smoking status. The 10-year risk of fatal CVD was expressed as a percentage and was calculated at the beginning of the trial and at 6 months, after the participants received the last letter.

The secondary outcome measures were the changes in weight (in kg), body mass index (BMI), waist circumference (in cm), hip circumference (in cm), and smoking status (related to continued or excessive smoking) at 6 months post-intervention. The number of participants who changed their CVD risk category—low, moderate, and high [19]—was also calculated.

After recruitment, the participants first completed the pre-study questionnaire (in Croatian), which included (a) demographic data (available in Additional file 2), (b) Decisional Conflict Scale (DCS) [20,21,22], and (c) future time perspective (FTP) [23].

The DCS consists of 16 items rated on a 5-point Likert scale and measures an individual’s uncertainty toward a course of action. The score is calculated as a sum of items, divided by the number of items and multiplied by 25, allowing for a score range from 0 (no decisional conflict) to 100 points (extreme decisional conflict) [20, 21]. The Croatian version of the scale was previously validated [22].

The FTP is a 13-item scale from the Time Perspective Inventory [23]. It assesses how respondents focus on planning and achievement of future goals. The respondent answers using a 5-point Likert scale from 1 (does not refer to me) to 5 (refers to me completely), maximum score of 65. Higher scores indicate a greater future time perspective.

Sample size

As there were no previous studies on this topic, we hypothesized that in the intervention group at the end of the trial, the mean CVD risk would be 6.0 and 8.0 in the control group, with a standard deviation of 3. With a study strength of 0.8 and alpha level of 0.01 (to take multiple comparisons into account), we used an online sample size calculator (https://epitools.ausvet.com.au/twomeansone), to estimate that we would need at least 53 participants per group (159 in total). To compensate for potential dropouts, we aimed to recruit 70 participants per trial arm.

Randomization and blinding

Trial groups were formed by a random assignment, so that each respondent had one probability of falling into one of the three research groups (1:1:1) and each group of participants was exposed to only one of the study interventions. The generation of the random sequence was performed by a statistician who was not involved in the conduct of the trial, using https://www.randomizer.org/. Only the main investigator was aware of the allocation of participants into the study groups, and the participants, the family medicine doctors, or the statistician were not aware of the allocation of participants to trial arms. The family medicine doctors made physical exams and took all measurements of each eligible participant. The main investigator prepared all letters, sealed them in opaque envelopes, and sent them to the addresses collected from the medical records of the participants.

Statistical analysis

Categorical data are presented as frequencies and percentages. Numerical variables did not follow a normal distribution and were presented as medians with IQR or with 95% confidence intervals (CIs). Due to the asymmetrical distribution of the variables, a parametric 2 × 2 factorial analysis could not be performed. As there is no non-parametric analog, the post-intervention differences between the three groups were compared by using the Kruskal-Wallis test with post hoc Conover-Iman test. To address multiple comparisons, we applied the Bonferroni correction to avoid type I error. The differences in CVD risk were made by subtracting the scores at the end of the trial with the ones from the baseline assessment, which sometimes resulted in negative scores. The results were expressed as a median difference in the score (with 95% CI). The changes in the number of participants who changed the category of their 10-year CVD risk after the interventions were tested using the McNemar χ² test. The risk ratios and numbers needed to treat (NNTs) were calculated based on the number of participants who had a decrease in CVD risk after the interventions. We used linear regression to determine the variables that predicted the pre- and post-assessment changes. The results were expressed as unstandardized coefficients and R². All analyses were performed by the R programming software (R Core Team, 2021).

Trial registration

The trial was retrospectively registered on ClinicalTrials.gov on October 19, 2020 (trial registration number NCT04601558). The trial was retrospectively registered because of the lack of timely official access to the registry by the first author from the University Hospital of Split.