Impact of Stress on Cardiovascular Events in Patients with Peripheral Arterial Disease

Based on the COMPASS trial MACE and MALE includes the composite of cardiovascular death, myocardial infarction, acute limb ischaemia, chronic limb ischaemia and amputation. MACE and MALE will be evaluated at baseline and after 6 and 12 months

Pychological stress is evaluated by a composite psychometric measure of stress level by using a mean rank at baseline and after 1 year. It is based on a published RCT by Blumenthal et al. and includes the Beck Depression Inventory II (BDI-II), State-Trait Anxiety inventory (STAI), Patient-Reported Outcomes Measurement Information System (PROMIS) Anger, General Health Questionnaire (GHQ) and Perceived Stress Scale (PSS). A range from 1 to 147 was present with higher scores suggestive of better function

Heart rate variability (HRV) is an indirect marker of autonomic nervous system activity and describes the oscillations between the R-R intervals in the electrocardiogram. It allows a relatively superficial insight into the heart-brain interaction and reflects the psycho-emotional status such as stress or anxiety. According to the guidelines we chose a short-time HRV with 5 minutes of recording

IL-6 is measured in pg/ml. Standard value is under 2.7 pg/ml. Higher values indicate an increased stress level

IL-1ß is measured in pg/ml. Standard value is under 5 pg/ml. Higher values indicate an increased stress level

TNFalpha is measured in pg/ml. Standard value is under 2.8 pg/ml. Higher values indicate an increased stress level

High sensitive-c-reactive protein (hsCRP) is measured in mg/dl. Standard value is under 0.02 mg/dl. Higher values indicate an increased stress level

Hair cortisol is reliable biomarker of chronic stress that offers a retrospective non-invasive measurement of long-term HPA-axis activity over several weeks or months. The cortisol concentration, measured in pg/ml, of a 3 cm hair segment using liquid chromatography tandem mass spectrometry will be analyzed. Higher values indicate an increased stress level

We will apply two instrument to measure health-related quality of life. Namely the Short Form-36 health questionnaire and the European Quality of Life 5 Dimensions 5 Level survey (EQ-5D-5L). The SF-36 is an eight-dimensional scale consisting of 36 items. It assesses health-related quality of life based on physical, social, and psychological functioning, role behavior due to physical and psychological functional impairment, physical pain, general health perception, and vitality. The EQ-5D-5L consists of five health-related dimensions that can be assessed at five levels. In addition, the questionnaire contains a visual analog scale for assessing general health

The lower systolic ankle pressure is set in relation to the systolic blood pressure of the upper extremity. The lowest calculated ABI will be used. Normal values are 0.9 to 1.2. ABI values below 0.9 are indicative of PAD, with an ABI below 0.5 showing severe limb ischaemia

Changes in functional capacity will be recorded using the established 6-minute walk test

Low density lipoprotein (LDL) is measured in mg/dl

Serum-Cortisol is measured in mol/l

The BDI-II is a self-report questionnaire comprising 21 items that assess depression severity. Its reliability and validity have been established through various studies among diverse populations and cultural backgrounds. Higher scores indicates increased depression symptoms

The STAI is the most authoritative tool for assessing anxiety in adults, precisely distinguishing between transient "state anxiety" and persistent "trait anxiety". The STAI measures anxiety with 20 items and has a range of 20 to 80. A higher score indicates more pronounced anxiety.

The PROMIS Anger scale comprises eight items that evaluate various aspects of anger. Scores on the scale range from 8 to 40, with higher scores indicating greater levels of anger

The GHQ assesses general distress and consists of 12 items. Respondents' scores range from 0 to 36, where higher scores correspond to increased distress

The Perceived Stress Scale-10 item version is a short tool for the assessment of how individuals perceive stress in their lives. The values range from 0 to 40. Higher values indicate higher perceived stress.

(l) In-treatment assessments: at the start of each intervention module (weekly), the following assessment instruments will be applied: Distress Thermometer (DT), Patient Health Questionnaire-4 (PHQ-4) and self-generated measures to assess coping skills and self-efficacy