Socioeconomic factors and long-term mortality risk after surgical aortic valve replacement

Background There is scarce knowledge about the association between socioeconomic status and mortality in patients undergoing surgical aortic valve replacement. This study explores the associations between income, education and marital status, and long-term mortality risk. Methods In this national registry-based observational cohort study we included all 14,537 patients aged >18 years who underwent isolated surgical aortic valve replacement for aortic stenosis in Sweden 1997–2020. Socioeconomic status and comorbidities were collected from three mandatory national registries. Cox regression models adjusted for patient characteristics and comorbidities were used to estimate the mortality risk. Results Mortality risk was higher for patients in the lowest versus the highest income quintile (adjusted hazard ratio [aHR] 1.36, 95 % confidence interval [CI]: 1.11–1.65), for patients with <10 years education versus >12 years (aHR 1.20, 95 % CI:1.08–1.33), and for patients who were not married/cohabiting versus those who were (aHR 1.24, 95 % CI:1.04–1.48). Patients with the most unfavorable socioeconomic status (lowest income, shortest education, never married/cohabiting) had an adjusted median survival of 2.9 years less than patients with the most favorable socioeconomic status (14.6 years, 95 % CI: 13.2–17.4 years vs. 11.7 years, 95 % CI: 9.8–14.4). Conclusions Low socioeconomic status in patients undergoing surgical aortic valve replacement is associated with shorter survival and an increased long-term adjusted mortality risk. These results emphasize the importance of identifying surgical aortic valve replacement patients with unfavorable socioeconomic situation and ensure sufficient post-discharge surveillance.


Introduction
Low socioeconomic status (SES), especially short education, is associated with increased mortality in patients with cardiovascular disease [1][2][3].Socioeconomic disadvantages are also associated with cardiovascular risk factors such as diabetes, hypertension, smoking, and physical inactivity [4][5][6][7], and with an increased long-term mortality risk and shortened median survival in coronary artery bypass grafting patients [8].Surgical aortic valve replacement (SAVR) is recommended in younger patients with symptomatic severe aortic stenosis and low surgical risk [9,10].There is scarce knowledge about the impact of socioeconomic factors on outcome after SAVR [11,12].Bagger et al. found a moderately increased mortality risk in a mixed population of isolated heart valve surgery patients using a multifactorial socioeconomic scoring system [11], and Dalén et al. found that low income was associated with an increased risk of post-discharge bleeding and mortality in patients receiving a mechanical aortic prosthesis [12].
To our knowledge, there are no previous studies investigating associations between individual socioeconomic factors and mortality in patients with aortic stenosis undergoing SAVR, and no studies investigating if there are sex-specific differences in the associations between socioeconomic factors and mortality after SAVR.The aim of the present study was therefore to explore the association between individual socioeconomic factors and long-term mortality risk in men and women undergoing isolated SAVR due to severe aortic stenosis.

Study design, study population, and data sources
All patients ≥18 years of age (n = 14,537) who were diagnosed with aortic stenosis and underwent primary isolated SAVR in Sweden from 1997 to 2020 were included in a nationwide observational populationbased cohort study.Outcome measure was all-cause mortality.Median follow-up was 7.3 years (interquartile range: 3.9-11.4).The patients were identified from the Swedish Cardiac Surgery Registry, which is a part of the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry [13].The Swedish Cardiac Surgery Registry includes patient characteristics, intraoperative details, and early complications in all open cardiac operations in Sweden since 1992 [14].
Codes for surgical procedures were defined by the Swedish National Board of Health and Welfare (Classification of Surgery, sixth edition, 1987, and Nordic Classification of Surgical Procedures, 1997).To identify patients undergoing a first isolated SAVR, the codes FMD 00 and FMD 10 were used in combination with the diagnostic code for aortic stenosis (I35.0)according to the 10th revision of the International Classification of Diseases (ICD-10).A total of 3946 patients were excluded because of congenital heart disease (n = 623), history of endocarditis (n = 1168), or diagnosis other than aortic stenosis (n = 1532).A flowchart describing included and excluded patients is depicted in Supplemental Figure 1.
Baseline characteristics and comorbidities were obtained from SWEDEHEART and from the Swedish National Patient Register (NPR), where registration is mandatory for all hospitals in Sweden.The NPR has a complete national coverage from 1987 for all diagnoses and all patients hospitalized in Sweden, with an overall diagnosis validity of 85%-95 % for cardiovascular diseases [15].Diagnoses in the NPR are based on ICD codes, with the 9th revision (ICD-9) used from 1987 to 1997 and the 10th revision (ICD-10) from 1997 to 2015.Data for social variables were collected from the Longitudinal Integration Database for Health Insurance and Labor Market Studies register (LISA).This register is annually updated and includes all citizens in Sweden aged ≥16 years [16].

Socioeconomic status
Marital status was divided into four categories: married/cohabiting, never married, divorced, and widowed.Length of education was stratified into three levels: <10 years (compulsory school only), 10-12 years (upper school), and >12 years (college/university level).Income was measured as annual household disposable income at year of surgery, stratified into five quintiles from Q1 (lowest) to Q5 (highest).The consumer price index according to Statistics Sweden (SCB) was used to adjust for inflation rates over time.If data were missing for the year of surgery, the latest information about education, marital status, and income was imputed from records for the most recent years before the surgery.In total, 164 (1.10 %) individuals had missing data regarding education.There was no missing data for income and marital status.The study population was divided into groups for comparisons between socioeconomic conditions; the most favorable SES group was defined as being married or cohabiting, education >12 years, and highest income level (Q5), and the least favorable SES group was defined as never being married/cohabiting, education <10 years, and lowest income level (Q1).
The Swedish Cause of Death Register, which includes information on all deaths of Swedish citizens [17] was used to obtain death dates.Data from the four national registers were linked together through a personal 10-digit social security number, unique for all Swedish citizens.

Statistical methods
Baseline characteristics are presented as frequencies together with percentages for categorical variables.Continuous variables are presented as means with standard deviations (SD).Follow-up time started at date after discharge, and ended at death or end of study, whichever occurred first.Incidence rates were estimated as total follow-up in the number of deaths divided by the follow-up in years and reported as incidence rate per 100 person-years with 95 % confidence intervals (CI).
Survival probabilities were calculated using Kaplan-Meier survival curves with 95 % CI, and median survival.For all analyses, a p-value of <0.05 was considered statistically significant.
Cox proportional hazards regression was used to calculate the crude (HR) and adjusted (aHR) mortality risk, separately for marital status, education, and income.The multivariate models were adjusted for baseline characteristics (age, body mass index, estimated glomerular filtration sex, smoking, myocardial infarction, diabetes, hypertension, heart failure, left ventricular ejection fraction, atrial fibrillation, previous stroke, chronic respiratory disease, peripheral vascular disease, renal insufficiency, rate history of cancer, rheumatic aortic stenosis, depression, bicuspid aortic valve stenosis, year of surgery, urgency of surgery, type of valve prothesis and for socioeconomic factors other than the response variable (marital status, education, income).All statistical analyses were performed using version 4.2.0 of R [18].

Ethical considerations
The present study was performed in line with the Declaration of Helsinki and was approved by the Swedish Ethical Review Authority (registration number: 2021-00122).All personal identifiers were replaced by codes before analysis to ensure anonymity.The need for individual patient consent was waived by the committee.This article follows the recommendations from the statement of Strengthening the Reporting of Observational Studies In Epidemiology (STROBE) [19].
Supplemental tables 2-4 shows baselines characteristics, stratified by socioeconomic variables.Patients with low income and short education were generally older and had more comorbidities, and underwent less often mechanical prosthesis implantation, than patients with higher income or longer education.

Income
Hazard ratio adjusted for age, sex and year of surgery showed that patients with the lowest income level had an associated increased risk of mortality during follow-up (HR 1.46, 95 % CI: 1.33-1.61)compared to patients with the highest income level.This associated risk among patients with lowest income level decreased when comorbidities and educational level and marital status were included, but the risk was still significantly associated with an increased risk compared to patient with the highest income level (aHR1.36,95 % CI: 1.11-1.65)(Fig. 2).
Sex specific analysis showed that men with the lowest income level had an increased risk compared to men with the highest income level (aHR 1.61, 95 % CI: 1.24-2.09).This associated risk was not observed in women (aHR 1.17, 95 % CI: 0.86-1.59).(Supplemental figure 3).

Survival according to the most favorable versus least favorable socioeconomic status
The proportion of survival at 10 years was 70 % (95 % CI: 64-76) in patients with the most favorable SES (highest education, married, and highest income level) compared to 56 % (95 % CI: 47-65) in patients with the least favorable SES (lowest education, never married, and lowest income level).Adjusted median survival was 2.9 years shorter in patients with the least favorable SES compared to those with the most favorable SES: 14.6 years (95 % CI: 13.2-17.4)years vs. 11.7 years (95 % CI: 9.8 -14.4) (Fig. 3).
Unadjusted median survival curves are shown in Supplemental figure 4.

Discussion
In this population-based cohort study of 14,537 individuals, the main finding was that low income, short education, and never been married  were associated with shorter survival and higher adjusted mortality risk after SAVR.Patients with the least favorable socioeconomic factors (never married or being married/cohabiting, education <10 years, and lowest income level), had nearly 3 years shorter adjusted median survival after SAVR, than patients with the most favorable socioeconomic status.
To our knowledge, few previous studies have investigated the association between SES and mortality in SAVR patients.Our results demonstrate that disparities in SES conditions are associated with an increased mortality risk after SAVR and is most likely due to multiple factors.Life expectancy after SAVR has also been reported in previous studies.Glaser et al. found that SAVR patients had a higher loss of life compared to the general population [20].Martinsson et al. showed that median survival was affected by age and the presence of surgical risk factors in SAVR patients receiving a bioprosthesis [21].In line with the present study, Nielsen et al. [8] found that patients with unfavorable SES  who underwent coronary artery bypass grafting lost 4-5 years in median survival compared to patients with favorable SES, where men with low income had a stronger association for mortality than women.This disadvantageous association for risk of mortality in men compared to women with low income, was also observed in the present study.
It is a well-known association between low SES and increased mortality in patients with cardiovascular disease [1][2][3].In the present study we could observe that a large proportion of the patients had cardiovascular risk factors such as hypertension, heart failure, atrial fibrillation, and hyperlipidemia at the time of surgery.Although comorbidities at the time of surgery were taken into consideration in the multi-adjusted regression models, several of the diseases related to cardiovascular disease are progressive in a lifetime perspective.
Several previous investigations of educational and economic factors after cardiac surgery have demonstrated an increased mortality risk in patients with low educational and income level [8,11].This is in line with our finding which may suggest that low educational level have an unfavorable impact on patients' health literacy, which affects information recall and health-related knowledge [22].Low health literacy leads to less beneficial health behavior regarding exercise, smoking, and medication use [23].In the present study, about 50 % of the patients had a history of smoking before surgery.Prior studies suggests that cardiovascular-and socioeconomic risk factors, should be evaluated preoperatively, by the Heart Team in dialogue with the patients [9,10,24].Identifying patients with low SES and evaluate which resources the patients' needs, may also increase the possibilities to strengthen the health literacy [25,26].It is therefore important to provide customized and robust advice to vulnerable patients with low SES, in order to increase the possibilities for the patients to understand the importance of adhering to the recommended treatments and a healthy lifestyle after SAVR.Educational level, cultural influence, and financial strain affect the circumstances to adopt a healthy lifestyle [5,[27][28][29].
In the present study, no information of the study population's living areas was available.However, previous studies have shown that living in deprived areas is associated with an increased presence of cardiovascular risk factors [5,[27][28][29].Exploring the association with patient's living area and mortality risk after SAVR entitle further studies.
Recommended secondary prevention medications are less often dispensed to patients who undergoes coronary artery bypass grafting with low income [30].There is a scarce knowledge about the association between low SES and the use of secondary prevention medication and mortality risk in SAVR patients.However, two recent studies have showed that statins and RAAS inhibitors were associated with reduced mortality after SAVR [31,32].It is possible that low income affects the dispensation of important secondary prevention medication also in SAVR patients.In Sweden, the patients are covered by a general health care insurance which contribute to a protection for high medication costs where the patients pay the first 2600 SEK (~240 $) for medical prescriptions within a year, and the first 1300 SEK (~120 $) for in hospital care, follow up by specialist physician and contact with primary care.Still, for patients with low income this cost may be difficult to manage.This association is not clear, and further studies are warranted, exploring the association of low SES, adherence to prescribed medication and mortality risk after SAVR.
The association between marital status and mortality risk as found in the present study has previously been described with a focus on patients with cardiovascular disease [33] and patients undergoing coronary artery bypass grafting [8,34], but has not previously been reported in SAVR patients.Lack of social support, which is associated with adverse outcome and adverse health-related quality of life after cardiac surgery [35] may be one explanation.SES is a complex variable with multiple components.The result from present study analyzing different factors of SES in SAVR patients.Further studies are needed to examine if availability to medical and social support attenuates the increased long-term risk of mortality after SAVR in patients with low SES.
Strengths of this study include the large population-based cohort, high-quality registry data, and a long and complete follow-up.However, we did not have any information regarding either ethnicity, medication during the follow-up period or adherence to non-medical secondary prevention recommendations such as diet, physical activity, or smoking cessation.Another limitation is that the retrospective study design carries an inherent risk of selection bias and residual confounding.

Conclusion
In conclusion, low SES is associated with an increased adjusted mortality risk after SAVR.These results emphasize the importance of identifying SAVR patients with unfavorable socioeconomic status and

Fig. 2 .
Fig.2.Multivariable adjusted hazard ratio for all-cause mortality according to marital status, education, and income in patients who underwent isolated surgical aortic valve surgery.

Fig. 3 .
Fig. 3. Adjusted survival according to high socioeconomic status versus low socioeconomic status in patients.

Table 1
Baseline characteristics by sex in 14,537 patients who underwent isolated surgical aortic valve surgery.