Introduction

Coronary artery disease (CAD) remains one of the major causes of morbidity. An evaluation of genetic and lifetime factors can be important for public health improvement initiatives. Multivessel coronary disease can be effectively treated with surgical or percutaneous interventions. Compared with medical therapy, coronary revascularization is associated with long‑term reduction in the number of recurrent events and superior long‑term survival. However, the former is crucial to procedural outcomes. Long‑term results following surgical intervention have been related to preoperative factors, such as diabetes, hyperlipidemia, and smoking.¹ Clinical attention cannot achieve optimal results without personalized therapy for comorbidities, including arterial hypertension, diabetes mellitus, and dyslipidemia.

Currently, it is believed that environmental factors represent a group of nontraditional risk factors for morbidity and premature mortality. It has been recently postulated that air pollution has an impact on human health, including the risk of CAD.²

In their review, Miller et al³ underlined the significance of the influence of inhaled particle matter (PM) on the cardiovascular system. The relationship between traffic air pollution in metropolitan areas and the prevalence of CAD has already been presented, just as the incidence of myocardial infarction. Mena et al⁴ noted geographical differences and disparities in the incidence of cardiovascular events related to the living environment (urban vs rural). It is emphasized that in order to improve cardiovascular health, multiple strategies of tackling air pollution should be addressed. However, though it has been postulated that air pollution has a negative impact on cardiovascular morbidity and mortality, its significance in patients who have already undergone surgical coronary artery revascularization is less known.

The aim of the study was to evaluate the value of clinical and environmental factors, in terms of the place of habitation and related air pollution exposure, for long‑term mortality in patients treated with surgical coronary artery revascularization.

Patients and methods

Our single‑center retrospective analysis included 427 patients (369 [86%] men and 58 [14%] women) with a median (interquartile range [IQR]) age of 64 (59–70) years, who underwent CAD surgery with the use of off‑pump revascularization technique at our Cardiac Surgery Department in 2014 and 2016, and were followed up to September 30, 2020 (Supplementary material, Figure S1) for a median (IQR) period of 5.5 (4.8–6) years. The study group comprised 303 patients (71%) with multivessel CAD and 124 individuals (29%) with left main CAD, all of whom were qualified for surgical revascularization based on the decision of the heart team.

We analyzed the clinical characteristics and air pollution exposure of patients from western and central parts of Poland. These regions have similar population density and socioeconomic status. Main sources of air pollution include road traffic, industry, heating, and agriculture. Urban areas were classified as cities with over 50 000 citizens, and rural areas were defined as open country settlements with fewer than 5000 residents. None of the participants reported having in‑home air conditioning. The individual analysis included the time between surgery and the established follow‑up point (September 30, 2020) or time of death.

Demographic and clinical factors were collected. Blood samples were obtained for complete blood count and biochemical and lipid profiles. Dyslipidemia was diagnosed based on the current guidelines⁵ or a history of lipid‑modifying therapy.

In all patients, echocardiography was performed on admission, postoperatively, and at discharge by the same team of experienced cardiologists following the same protocol.

Mortality during follow‑up was evaluated based on the national health care database and direct contact with patients or their families, including ambulatory clinic visits and phone calls.

Results

During the median (IQR) 5.5 (4.8–6)-year follow‑up period, 56 patients (13%) died, none perioperatively. The comorbidities included arterial hypertension (n = 336; 79%), dyslipidemia (n = 238; 56%), and diabetes mellitus (n = 148; 35%). The median (IQR) body mass index was 28.4 kg/m² (26.2–30.8 kg/m²). As many as 139 patients (33%) were diagnosed as overweight.

The median (IQR) number of anastomoses was 2 (2–3). All procedures were performed through median sternotomy using the off‑pump technique (off‑pump coronary artery bypass grafting). Arterial revascularization was conducted in 19 patients (4%). None of them required intraoperative conversion to cardiopulmonary bypass. No low‑cardiac output syndrome or perioperative myocardial infarction was observed. The median (IQR) hospitalization time was 10 (8–12) days. In the perioperative period, all patients were treated with β-blockers, antiplatelets, statins, and angiotensin‑converting enzyme inhibitor / angiotensin II receptor blockers, with continued optimal medical pharmacotherapy recommended after discharge.

The patients were divided according to a prediction of long‑term mortality risk factors based on their place of residence (Figure 1). They were classified as urban residents (city over 50 000 inhabitants), representing a group of 130 patients (30%), and rural residents (297 patients; 70%).

No significant differences were observed regarding demographic and clinical profiles of the groups (Supplementary material, Table S1).

Subsequently, uni- and multivariable analyses based on demographic, clinical, and intraoperative factors combined with air pollution exposure were performed to establish the predictors of 5‑year mortality in both subgroups.

In the urban group (group 1), the multivariable analysis showed a predictive value of left ventricular ejection fraction (LVEF) of less than 50% (hazard ratio [HR], 4.4; 95% CI, 1.41–13.85; P = 0.01) and PM₁₀ exposure (HR, 1.15; 95% CI, 1–1.32; P = 0.04). Disparities between mortality and ambient PM₁₀ exposure of the urban patients are depicted in Supplementary material, Figure S1 and Table S2.

The multivariable analysis of the rural group (group 2) showed a predictive value of LVEF of less than 50% (HR, 3.59; 95% CI, 1.79–7.23; P <⁠0.001) and dyslipidemia (HR, 2.08; 95% CI, 1.04–2.83; P = 0.03; see Supplementary material, Table S3).

Discussion

The presented analysis highlights the urban / rural disparities in all‑cause long‑term mortality rates related to air pollution exposure. After adjusting for clinical and intraoperative factors, PM₁₀ exposure was shown to be a strong predictor in urban environments, distinct from its influence in the rural ones. We analyzed the median values of air pollutant exposure. Our study presents the median values of NO₂, PM_2.5, and PM₁₀ within a 5‑year period, indicating a 14% risk increase per each PM₁₀ unit growth that also distinguished urban and rural areas.

Our analysis identified possible risk factors for all‑cause mortality in 5‑year follow‑up after surgical coronary artery revascularization. Among clinical characteristics, reduced LVEF and dyslipidemia are strong predictors of fatal events. Urban citizens living in a city environment are exposed to air pollutants, which can be considered a mortality indicator. Our retrospective analysis pointed out the ominous influence of PM₁₀ exposure on late mortality.

Separate analyses for urban and rural locations showed reduced LVEF as the most significant factor for both subgroups. The relation between LV dysfunction and increased risk of hospitalization and mortality is well documented.¹¹ Despite advances in pharmacotherapy, patients with low LVEF are at a higher mortality risk due to arrhythmias and heart failure deterioration.¹² Therefore, Shen et al¹³ offered a novel approach to medical therapy, emphasizing accelerated up‑titration schedule and optimized ordering of treatment. Moreover, dyslipidemia is a well‑known morbidity and mortality predictor, which our study confirmed. Still, there is a place for other factors to explain some of the residual morbidity and mortality risks. Our study confirms the negative consequences of air pollution for human health. Chronic exposure to PM₁₀ was harmful for patients with coronary artery disease in the analysis by Occelli et al¹⁴. Proximity to high‑traffic roads increases exposure to heavy metals, pollutants such as NO₂, PM₁₀, and PM_2.5, and the risk of cardiovascular complications.

The novelty of our analysis comes from the differences in possible mortality risk after coronary revascularization in the patients living in urban and rural environments. According to our analysis, showing the 5‑year all‑cause mortality risk, PM₁₀ can be regarded as a significant risk factor in urban settings. Our previous report¹⁵ showed the progression of atherosclerotic changes in patients with CAD in response to greater air pollution exposure.

Chronic exposure to ambient air pollutants exerts complex pathophysiological effects on human organisms. These phenomena include endothelial or autonomic dysfunction and systemic reactions, such as inflammatory activation, generation of oxidative stress, impaired vegetative nervous system functioning, and increased activity of the hemostatic system.¹⁶

Choi et al¹⁷ presented the complement system activation and inflammatory reaction regulation by urban PM. They showed possible mechanisms behind the relationship between cardiovascular diseases and air pollution through the interaction between endothelial cells and dysregulation of the complement system. Importantly, there are differences in various geographic areas concerning air pollution compounds.¹⁸ Konduracka et al¹⁹ reported an increased daily number of hospital admissions related to short‑term increases in PM_2.5 levels in a large city in southern Poland, while the effect of PM₁₀ was significant during a simultaneous decrease in temperature. Kuzma et al^18,20 showed a higher incidence of hospitalizations due to acute coronary syndrome associated with air pollution in the eastern part of Poland, especially in younger individuals, women, residents of rural areas, and those with lower income. Air pollution may also aggravate the episodes of chronic obstructive pulmonary disease and increase the risk of hospital admission.²¹ Short- and long‑term exposure to air pollution may affect cardiovascular survival.^22,23