EValuation Of poLygenic Scores and CT imAging In Risk Factor Modification in Patients With diabEtes

Intensification of lipid-lowering therapy at 12 months will be defined as the occurrence of any of the following:

• an increase in the intensity of statin prescribed,
• addition of ezetimibe, or
• addition of a PCSK9 inhibitor (PCSK9i).

This outcome will be assessed based on medication records at the 12-month follow-up.

Medication adherence will be assessed using a participant-reported item from a modified VOILS questionnaire at the 12-month follow-up. Participants are asked:

"In the last week, I took my tablet(s):" with response options:

• Every day
• Almost every day
• Less than half
• Rarely or not at all

Adherence will be defined as selecting "Every day", and the number of participants meeting this criterion will be reported.

Patient activation and engagement in care will be assessed using the 13-item Patient Activation Measure (PAM-13) at baseline and 12 months. Each item is scored on a 4-point Likert scale (Disagree Strongly to Agree Strongly), with responses converted into a continuous score ranging from 0 to 100.

Higher scores indicate greater activation, reflecting better self-management and engagement in health care.

Depressive symptoms will be assessed using the 9-item Patient Health Questionnaire (PHQ-9). Each item is scored from 0 (not at all) to 3 (nearly every day), producing a total score from 0 to 27. Higher scores indicate more severe depressive symptoms. A higher score represents a worse outcome.

Anxiety will be assessed using the 7-item Generalized Anxiety Disorder scale (GAD-7). Each item is scored from 0 (not at all) to 3 (nearly every day), yielding a total score from 0 to 21. Higher scores indicate greater anxiety severity. A higher score represents a worse outcome.

Diabetes distress will be assessed using the 17-item Diabetes Distress Scale (DDS-17). Each item is scored on a 6-point Likert scale from 1 (not a problem) to 6 (a very serious problem). Mean item scores range from 1 to 6, with higher scores indicating greater distress. A higher score represents a worse outcome.

Health-related quality of life will be assessed using the EQ-5D-5L questionnaire, which includes five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has five response levels, ranging from no problems to extreme problems. Responses will be converted into a health utility index score using the Australian-specific value set, ranging from <0 (worse than death) to 1 (perfect health). A higher utility score indicates better health status and quality of life.

Risk of obstructive sleep apnea will be assessed using the STOP-BANG questionnaire at baseline and 12 months. The tool includes 8 yes/no items: Snoring; Tiredness; Observed apnoea; High blood Pressure; Body mass index (BMI) >35 kg/m²; Age >50 years; Neck circumference >40 cm; Gender (male)

Each "yes" is scored as 1 point, giving a total score from 0 to 8. Scores of: 0-2 = low risk; 3-4 = intermediate risk; 5-8 = high risk

Higher scores indicate a higher risk of obstructive sleep apnea. Change in total STOP-BANG score will be reported.

Cardiovascular disease (CVD) risk will be assessed using the New Zealand Society for the Study of Diabetes (NZSSD) CVD Risk Assessment Calculator (www.nzssd.org.nz/cvd/). This tool estimates the 5-year absolute risk of a cardiovascular event based on patient characteristics, including age, sex, ethnicity, smoking status, diabetes status, blood pressure, lipids, and other clinical parameters.

The calculator produces a score between 0% and >30%, with higher scores indicating greater risk.

This composite outcome reflects the number of participants who meet all of the following three modifiable risk factor goals at 12 months:

• LDL-cholesterol < 1.8 mmol/L
• Systolic blood pressure ≤ 130 mmHg
• Smoking cessation (defined as self-reported non-smoking or validated by clinical records if available)

Total atheroma volume (in mm³) will be assessed by CTCA at baseline and 12 months. TAV quantifies plaque burden in the coronary arteries. A higher TAV indicates more atherosclerotic plaque.

Calcified plaque volume (in mm³) will be measured using CTCA at baseline and 12 months. It represents the volume of calcium-containing plaque within the coronary arteries. A higher volume indicates greater calcified atherosclerotic burden.

PCAT attenuation will be measured in Hounsfield Units (HU) using CTCA. It reflects the inflammatory status of perivascular fat. Higher values are associated with greater coronary inflammation.

Appropriateness will be assessed using a custom participant survey and focus group interviews. Participants will rate whether they found the CTCA intervention relevant and suitable for their personal health needs. Responses will be summarised using Likert scales and thematic analysis.

Feasibility will be assessed through participant survey items and focus group discussions addressing clarity of instructions. Responses will be summarised using Likert scales and thematic analysis.

Acceptability will be measured using participant survey and focus group feedback on comfort, satisfaction, and willingness to undergo CTCA again. Ratings will be reported using Likert scales and thematic analysis.

Appropriateness will be assessed using a custom participant survey and focus group interviews. Participants will rate whether they found the PRS intervention relevant and suitable for their personal health needs. Responses will be summarised using Likert scales and thematic analysis.

Feasibility will be assessed through participant survey items and focus group discussions addressing clarity of instructions. Responses will be summarised using Likert scales and thematic analysis.

Acceptability will be measured using participant survey and focus group feedback on comfort, satisfaction, and willingness to undergo PRS testing again. Ratings will be reported using Likert scales and thematic analysis.