Study design, Setting, Participants
This study was approved by the Regional Ethics Committee (TuKEB 250/2013) and registered at ClinicalTrials.gov (NCT02224222). The inclusion criteria were as follows: age over 18 years, native Hungarian speaker and undergoing elective vascular surgery. Exclusion criteria were pregnant women and patients with a legal incapacity or considered to have a limited capability to understand the study procedures and provide ethical consent. All clients were capable of making decisions regarding their participation in this study, and accordingly, written consent was obtained. A study nurse, a medical student or a postdoctoral fellow invited patients to participate in the study during their outpatient anaesthesiology visit. Every person of the enrolled staff was trained by a psychologist to perform correct cognitive mapping and assessments. Baseline questionnaires were completed 5-30 days before surgery. After signing the informed consent form, 199 adult patients were enrolled prospectively at the Department of Vascular Surgery of the Heart and Vascular Center of Semmelweis University in Budapest between September 2014 and August 2017. Thirty-two patients were excluded because of cancelled surgery. Three patients withdrew their consent. Finally, data from 164 patients were used for the statistical analysis.
Definitions and measurements (variables, data sources, and grouping)
Wide ranges of clinical and psychosocial factors were assessed as potential determinants of the outcome. Clinical factors included perioperative laboratory parameters (blood counts, renal function measures, ion levels, etc.), intraoperative parameters (operation time, cross-clamp time, blood loss, need for transfusions and fluid balance medications), postoperative parameters (blood loss, medications, etc.), outcomes, the incidence and severity of postoperative complications (major cerebrovascular or neurological event; acute or chronic heart failure defined as pulmonary oedema, atrial fibrillation, arrhythmias, cyanosis, metabolic disorders, need for inotropes, respiratory failure; infection; acute renal failure/need for renal replacement therapy; length of mechanical ventilation; length of ICU and in-hospital stay and in-hospital mortality rate). The American Society of Anesthesiologists risk score (ASA score) [9] and the Vascular Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (vascular POSSUM) [10-13] were also calculated. The vascular-POSSUM consists of two parts, a physiological score and an operative score. The physiological score includes age and major vital parameters (cardiac, renal, haematological and neurological function), and the operative score focuses on intraoperative blood loss, peritoneal contamination, possible malignancy and the length and urgency of the procedure.
Psychosocial factors
Psychosocial and demographic data were collected, e.g., age, sex, living conditions, smoking, alcohol consumption and education. Then, participants were asked to complete many questionnaires measuring psychosocial factors: the Beck Depression Inventory (BDI), the Spielberger State and Trait Anxiety Inventory (STAI-S and STAI-T), the Mini Mental State Examination (MMSE), the Geriatric Depression Scale, the Somatic Symptom Severity Scale, the Devins Illness Intrusiveness Rating Scale, the Caldwell Social Support Dimension Scale, and specific parts of the Hungarostudy Query (a representative national study conducted in 2013 that was used as a control group and measured the health status, illnesses, biopsychosocial background and health-related quality of life (HRQ)).
For mapping, the Mini-Mental State Examination (MMSE) was applied to assess cognitive function. The MMSE is a well-established scale to screen cognitive deficits and signs of dementia. It contains simple questions and problems in many areas, including temporal-spatial orientation, short-term memory, arithmetic computation such as decreasing serial sevens, language use and comprehension, as well as basic visual-motor skills. The questionnaire score ranged from 0 to 30 points. Cut-off values are 23, 18 and 9 points for mild, moderate and severe cognitive impairment, respectively. [14, 15] In addition to an assessment of the raw MMSE results, adjustment for age and education level was performed. Patients with cognitive impairment were defined when a difference greater than 2 standard deviations between expected (age and education level adjusted) and MMSE scores was observed. [14] Modified cut-off values were used to detect the mildest cognitive impairment, according to previous publications. [16-18] In these studies, a cut-off value of 27 or lower indicated mild cognitive impairment, and a score of 23 or lower indicated a severe cognitive impairment.
Patients were asked to estimate self-reported happiness and satisfaction using a 1 to 10 point scale. These self-reported parameters were reported as an important aspect determining the long-term mortality of healthy adult volunteers. [19]
The State-Trait Anxiety Inventory (STAI) was used to characterize the anxiety of patients. The inventory consists of two parts, the STAI-S and the STAI-T. The first 20 questions refer to the transitional emotional status evoked by a stressful situation (STAI-S), e.g., a hospital admission or a surgical intervention. The STAI-T score reflects personal differences in chronic anxiety susceptibility. Each group is scored from 20 to 80 points based on four-level Likert items. [20, 21] The STAI, a test with high reliability and validity, is well documented in the Hungarian population. [22] (STAI-T and S Cronbach’s α=0.638 and 0.763, respectively)
The Beck Depression Inventory (BDI) was used for affective disorders. The BDI, a 21-item questionnaire, is an established tool for screening depression, with each item evaluating different symptoms of depression, such as a bad mood, pessimistic outlook, feelings of guilt and loss of appetite. Each item contains four sentences indicating the degree of severity for that particular symptom. Answers are four-level Likert items; the whole inventory is scored from 0 to 60 points.[23-25] The validity and reliability of the BDI are also well documented in the Hungarian population (Cronbach’s α=0.787). [26]
The Geriatric Depression Scale is a yes-or-no question-based, 30-item inventory for the assessment of depression occurring in the older population. In our study, the short form of the GDS was used, which includes 15 questions. Every question is scored either 0 or 1, and the sum normally ranges from 0 to 9 points (Cronbach’s α=0.704). [27]
The Somatic Symptom Severity Scale (Patient Health Questionnaire – PHQ15) refers to different symptoms, e.g., gastrointestinal dysfunction, dizziness, chest pain and dyspnoea. It is calculated by assigning scores of 0, 1 and 2 to the response categories of “not at all”, “bothered a little”, and “bothered a lot”, respectively, for all 13 somatic symptoms. Additionally, 2 items from the mood module (fatigue and sleep) are scored 0 (“not at all”), 1 (“several days”) or 2 (“more than half the days” or “nearly every day”). We did not use questions regarding pain caused by menstruation or dysmenorrhea for better comparability. Thus, the inventory is scored from 0 to 28 points. Scores of 5, 10, and 15 represent cut-off points for low, medium, and high somatic symptom severity, respectively (Cronbach’s α=0.730). [28-30]
The Devins Illness Intrusiveness Rating Scale measures the effect of illness on different social issues. The 13-item questionnaire was introduced to screen for illness-induced disruptions in lifestyle, activities and interests that may compromise psychosocial well-being and contribute to emotional distress in patients with chronic diseases. Answers are seven-level Likert items; the inventory is scored from 13 to 91 points (Cronbach’s α=0.854). [31, 32]
For the analysis of the patient’s social web structure, the Caldwell Social Support Dimension Scale was used. This scale is a novel version of the Social Support Questionnaire published originally in 1987. [33] The intensity of different interpersonal relationships and supports, such as direct relatives, neighbours, workmates and friends, are represented in the questionnaire. After the first summary of scores, a distinct familial (parents, spouse, grandparents, children and other relatives) and nonfamilial (neighbour, schoolmate, workmate, other social or sacral company) support score was created. Answers are provided as four-level Likert items (Cronbach’s α=0.570). [34-36]
Finally, the shortened form of the Athens Insomnia Scale Inventory (AIS-5) was also recorded to detect mild or severe insomnia. The cut-off score of the AIS-5 is ≥4, which is related to potential insomnia (Cronbach’s α=0.630). [37]
The data were compared to the Hungarostudy (HS) population. Free-access, nationally representative, face-to-face household surveys are conducted in Hungary every 10 years, and the last survey was conducted in 2013 (n=2,000). [38, 39] Hungarostudy is built from the inventories listed above and contains the BDI, STAI, CSSDS, Devins Illness Intrusiveness Rating Scale, PHQ15 and AIS, along with basic questions about age, sex, education, marital status, religion, and physical status. In HS, further questions about smoking, drinking alcoholic beverages and some questions about the income of the participant are asked. In our inventory, a shorter form from HS 2013 was used; in this manner, the two populations became comparable. Identical questions were compared using the propensity score matching method.
Our results were adjusted to a comprehensive frailty score published by Shi et al. to characterize the relationship between traditional frailty syndrome and cognitive decline. [40] The modified frailty index based on our data included the presence of recurrent angina pectoris, atrial fibrillation, congestive heart failure, chronic coronary disease, diabetes mellitus, hypertension, past myocardial infarction, peripheral vascular disease, stroke or TIA, anxiety (defined by the STAI score), asthma or COPD, depression (defined by the GDS score), cognitive impairment (defined by the MMSE score), malnutrition (BMI<21) and medication (using ≥5 medications daily). The MMSE categories used in the comprehensive frailty score were applied accordingly with the following cut-off values: 27 points and above, 24-26 points, 21-23 points and less than 21 points.
Outcomes
The primary outcome of the study was the overall mortality rate. As secondary outcomes, one-year and two-year mortality rates were examined.
Statistical analysis
Descriptive statistics (means, standard deviations, medians and interquartile ranges) were calculated for all continuous variables. Means and SDs were used for variables with a normal distribution, and the Kolmogorov-Smirnov test and the Shapiro-Wilk test were used to ascertain the type of distribution. For categorical variables, Pearson χ2-test was used; nonparametric tests were used for continuous variables, with the Mann-Whitney U test as the default. Categorical variables were calculated from continuous scales, with well-proven cut-off values. Univariate and multivariable logistic regression (Cox regression) models were also used. A Kaplan-Meier analysis with the log-rank and Breslow tests were used to investigate differences in short- and mid-term survival rates. P < 0.05 was considered statistically significant. For the statistical analysis, IBM SPSS Statistics 24.0 (SPSS Inc., Chicago, Illinois) with the R plugin (version 3.2.1) for PS matching was used. Forest plots were generated using GraphPad Prism version 8.0.1 software for Windows, GraphPad Software, San Diego, California, USA, www.graphpad.com.
A propensity-matching analysis was performed to compare the vascular population and the Hungarian patient cohort. During propensity score matching, pairs were generated from the HS representative group and the vascular surgical group according to age, sex and place of residence. The balance of baseline covariates between the treated and control groups was evaluated using absolute standardized differences. A value less than 0.1 was considered an acceptable standardized bias. As the pairs were created, identical questions were compared to analyse the differences in psychological attitudes and social states between the general and surgical populations.