Geographical Variations and Predictors of Coronary Artery Disease Mortality in Turkiye: An Environmental and Behavioral Analysis Running Title: CAD Mortality Patterns in Turkiye

doi:10.21203/rs.3.rs-3953018/v1

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Geographical Variations and Predictors of Coronary Artery Disease Mortality in Turkiye: An Environmental and Behavioral Analysis Running Title: CAD Mortality Patterns in Turkiye

https://doi.org/10.21203/rs.3.rs-3953018/v1

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published 12 Oct, 2024

Read the published version in BMC Cardiovascular Disorders →

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Objective:This study aims to analyze the geographical variations and identify key environmental and behavioral predictors of coronary artery disease (CAD) mortality in Turkiye.

Methods:A 10-year longitudinal province-level data was used to identify change trajectories of CAD mortality. . Environmental determinants (such as air quality and climatic conditions) and behavioral factors of alcohol consumption and smoking were examined for their association with CAD mortality change trajectories using Ordinal Logistic Regression models.

Results:The study revealed significantly different trajectoriesof CAD mortality across Turkiye. Environmental factors, particularly air quality (Particulate Matter-10 variation) and climatic conditions (humidity and temperature variations), were heavily associated with the level of CAD mortality. Behavioral factors, notably alcohol consumption and smoking, also exhibited a significantly positive association.

Conclusion:The study underscores the importance of addressing environmental and lifestyle factors in CAD management and prevention strategies. The findings suggest the necessity for region-specific interventions and public health policies tailored to the unique characteristics of each province in Turkiye. This research contributes to a deeper understanding of the multifactorial nature of CAD mortality, providing valuable insights for healthcare planning and policy-making.

Coronary Artery Disease

Mortality

Environmental Factors

Behavioral Factors

Geographical Variations

Turkiye

Coronary artery disease (CAD), also known as ischemic heart disease, remains a leading cause of mortality worldwide. According to World Health Organization (WHO), cardiovascular diseases cause the death of 17.9 million lives each year [1]. CAD is a condition where plaque accumulates in the coronary arteries, restricting blood flow to the heart.. Plaques narrows the coronary arteries and the body's arteries over time, reducing or preventing blood flow, causing atherosclerosis. The symptoms of CAD are similar to that of a heart attack, including chest, arm, or shoulder pain or discomfort and shortness of breath. Treatments include lifestyle changes such as regular exercise, angioplasty to prevent the narrowing of the arteries, and surgery [2, 3].

The prevalence and impact of CAD vary significantly across different regions, influenced by a complex interplay of environmental and behavioral factors. Global trends indicate a shifting burden of CAD, with developing countries witnessing a surge in cases, possibly due to rapid urbanization and lifestyle changes [4]. In contrast, developed regions like Europe and North America have witnessed a relative decline in CAD mortality, attributed to improved healthcare systems and effective public health policies [5].

Environmental factors, including air pollution and urban living conditions, have emerged as critical determinants of CAD prevalence. Exposure to pollutants has been linked to increased cardiac events, emphasizing the need for environmental policies in disease management [6]. Behavioral factors such as diet, physical activity, and tobacco use also significantly contribute to CAD risk. Western diets high in saturated fats correlate with higher CAD rates, particularly in North America and parts of Europe [7]. In contrast, the traditional diets in some Asian countries, which are lower in saturated fats, may partly explain the lower incidence of CAD in these regions[8].

The Americas present a diverse picture, with South America grappling with rising CAD rates due to increasing obesity and diabetes prevalence, unlike North America, where the rates are stabilizing [9]. Europe's experience with CAD has been shaped by effective public health interventions, leading to a decline in smoking rates and better management of hypertension and hyperlipidemia[10]. In Asia, rapid urbanization and lifestyle westernization contribute to an increasing CAD burden, challenging the existing healthcare infrastructures [11].

Understanding these trends and factors is crucial for developing targeted interventions and policies to reduce the global burden of CAD. This manuscript aims to delve into these aspects, offering insights into the complex dynamics of CAD mortality in Turkiye.

The population-size standardized province-level coronary artery disease (CAD) deaths were obtained and defined as the primary outcome variable for 81 provinces of Turkiye for 10 years from 2010 to 2019. The primary predictors include Particulate Matter 10 (PM₁₀), sulfur dioxide (SO₂), Carbon Monoxide (CO), Nitrogen Dioxide (NO₂), and Ozone (O₃), air pressure, humidity, rainy days in a year, maximum-average-minimum temperatures, wind speed as well as total sunlight, sun radiation, and electromagnetic field. These markers were represented as the medians of the measurements between 2010 and 2019. To investigate the impact of the environmental variations on the CAD mortality, the variation representations of these markers were also defined as the standard deviations (SD) and coefficient of variation (CV) from 2010 to 2019. To represent the known behavioral domain, the association of smoking, alcohol consumption, and exposure to second-hand smoke with CAD mortality were also investigated.

In the first step of our analyses, we aimed to identify different change trajectories of the CAD mortality. Tthe TRAJ procedure developed by Jones, Nagin, and Roeder (2001) suggested four change-profiles for CAD mortality based on the goodness of fit diagnostics [12]. As these change-profiles are of ordered structure (e.i., low, intermediate, high, etc.), Ordinal Logistic Regression modelling framework was used to model the likelihood of being in a higher ordinal category of CAD trajectories for each unit-increase in the univariable predictor.

A total of 33 predictors were included in these univariable models. To control for the increased Type-1 Error rate due to high number of univariable testing, the multiplicity has been corrected using the False Discovery Rate (FDR) technique by Benjamini, Y., & Hochberg, Y. [13]. To graphically illustrate the association of the significant predictors on the same panel, the response variable and the predictors were standardized to have mean zero and variance one. All analysis were conducted using SAS (R) Version 9.4 (Cary, North Carolina, USA)

Analysis through SAS TRAJ procedure identified 4-trajectories in CAD mortality across the 81 provinces of Turkiye as presented in Fig. 1. The figure demonstrates a pronounced variation in CAD mortality rates, where Trajectory-1 has more stable CAD mortality while the other three trajectories have sharper increases and stabilization afterwards.

The Logistic Regression modelling revealed several key predictors of CAD mortality. In terms of environmental factors, higher median air pressure and higher median humidity levels were positively associated with increased CAD mortality, as shown in Table 1 and Figure-2 (OR estimates are 1.01 and 1.08, respectively). The positive association between these factors indicates that provinces with higher air pressure or greater humidity tend to report higher rates of CAD mortality. Behavioral factors such as ever alcohol use (OR = 1.11) and ever smoking (OR = 1.1) were likewise positively associated with higher CAD mortality, suggesting that provinces with higher rates of alcohol consumption and smoking have a greater likelihood of increased CAD mortality.

Conversely, factors like variability in maximum temperature (Coefficient of Variation, CV) and standard deviation (SD) in particulate matter-10 (PM-10) levels and rainy days indicated a negative association with CAD mortality. This implies that provinces with greater variability in temperature,PM-10 levels, and rainy days have comparatively lower CAD mortality rates. Provinces with higher sunligh and sun radiation exposures were also more likely to report lower level of CAD mortality.

Table 1

Summary of markers significantly associated with Coronary Artery Disease Mortality Profiles (CV is Coefficient of Variance, SD is Standard Deviation)
Predictor	OR (95% CI)	P-value	FDR Corrected P-value
Air Pressure (Median)	1.01 (0.99,1.02)	0.0129	0.033063
Ever Alcohol Use	1.11 (1.05,1.16)	0.0001	0.001407
Ever Smoking	1.10 (1.03,1.19)	0.0066	0.018305
Humidity (CV)	0.91 (0.87,0.95)	< .0001	0.000367
Humidity (Median)	1.08 (1.03,1.13)	0.0019	0.007451
Humidity (SD)	0.83 (0.75,0.91)	0.0002	0.001461
Maximum Temperature (CV)	0.93 (0.89,0.98)	0.0059	0.018305
Maximum Temperature (SD)	0.69 (0.54,0.89)	0.0043	0.015529
Mean Temperature (SD)	0.44 (0.30,0.64)	< .0001	0.000367
Minimum Temperature (SD)	0.50 (0.34,0.72)	0.0003	0.001572
Particulate Matter-10 (SD)	0.88 (0.82,0.94)	0.0002	0.001572
Rainy Days (CV)	0.95 (0.92,0.98)	0.0012	0.005593
Sun Radiation (Per 10-unit increase)	0.93 (0.89,0.98)	0.0008	0.004205
Sunlight (Per 10-unit increase)	0.98 (0.97,0.99)	0.0064	0.018305

Figure-2 visually represents these associations, illustrating the positive correlation between higher median air pressure, higher humidity, alcohol use, and smoking with increased CAD mortality. In contrast, the negative association of temperature variability, sunlight, sun radiation, and PM-10 levels with CAD mortality is also depicted, offering a comprehensive view of the environmental and behavioral factors influencing CAD mortality in Turkiye.

This study's findings, as presented in Figure 1, elucidate the geographical variations in coronary artery disease (CAD) mortality across Turkiye, revealing distinct mortality profiles. These profiles provide valuable insights into the different level of CAD burden, reflecting the complex interplay of environmental, lifestyle, and healthcare factors in affecting the CAD profiles over time.

As for the predictors associated with CAD, Table 1 and Figure-2 highlight several critical components. Notably, environmental markers such as air quality (Particulate Matter-10) and climatic conditions (humidity, temperature variations) were found to be significantly associated with CAD mortality. The correlation between these two markers and CAD lethality aligns with current literature emphasizing the role of environmental quality on cardiovascular health [6, 14].

Behavioral factors like alcohol consumption and smoking, as shown in Table 1, also emerged as significant predictors of CAD mortality. These findings are consistent with global research underscoring the impact of lifestyle choices on heart disease risks [5,8].

The leading strength of this study is its comprehensive analysis of various influential environmental and behavioral predictors, and their association with CAD mortality in Turkiye. The use of province-level data (Figure 3) allows for a nuanced understanding of the different levels of CAD burden.

However, the study has limitations. The reliance on secondary data sources and its overall observational nature may hinder the accuracy of some measurements, and preclude causal inferences. Additionally, the study does not account for potential genetic predispositions, which could play a role in CAD outcomes. Lack of data for diet is another restriction preventing the examination of its relation with CAD.

The findings underscore the need for region-specific public health strategies in Turkiye as illustated by Figure 3 with regional similarities in CAD mortality trajectories. Policies aimed at improving air quality, promoting healthier lifestyles, and addressing climatic impacts could substantially reduce CAD mortality. Tailoring interventions to specific regional needs, as suggested by the mortality profiles, may enhance their effectiveness.

Future research should focus on longitudinal studies to understand the causal pathways of these associations better. Investigating the genetic factors and their interplay with environmental and lifestyle factors (i.e., epigenetics) could also provide deeper insights into CAD etiology and prevention strategies.

In conclusion, this study presents a comprehensive analysis regarding the influence of the geographical and predictor-based variations on coronary artery disease (CAD) mortality rates in Turkiye. The significant associations between environmental factors, behavioral patterns, and CAD mortality emphasize the need for multifaceted public health strategies. While the study highlights essential regional disparities in CAD outcomes, it also points to universal risk factors such as air pollution and lifestyle choices. These findings call for targeted interventions that take into account both the unique regional characteristics and the shared risk factors influencing CAD mortality. Ultimately, this study contributes to a growing body of evidence that can inform public health policies and individual lifestyle choices to reduce the burden of CAD. The conclusions dervied from this study extend beyond Turkiye to include other regions with similar demographic and environmental profiles.

Funding: Partial financial support was received from TUBITAK Directorate of Science Fellowships and Grant Programmes (BIDEB)-2232 International Fellowship for Outstanding Researchers (Award No: 118C306)

Conflicts of interest/Competing interests: The authors have no relevant conflict of interest.

Availability of data and material: As the death records data utilized in this report were granted access only to the corresponding author, we do not have the permission to share these data components; however, we can share the environmental data upon request. Please contact Dr. Mehmet Kocak at [email protected] regarding such data requests.

Code availability: Not applicable

Ethics approval and Consent to participate: Our research protocol was approved by Istanbul Medipol University Ethics Committee (Application number: 10840098-604.01.01-E.53819). The Ethics Committee waived the need for Informed Consent as there is no human subject involved in this research. Data is simply province-level mortality data provided by the Turkish Statistical Institute per year.

Consent for publication: Not applicable

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No competing interests reported.

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Geographical Variations and Predictors of Coronary Artery Disease Mortality in Turkiye: An Environmental and Behavioral Analysis Running Title: CAD Mortality Patterns in Turkiye

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