National adult mortality trends due to chronic kidney disease-related atrial fibrillation in the United States from year 2011-2020

Abstract

BACKGROUND

Atrial fibrillation (AF) associated with chronic kidney disease (CKD) is a prevalent condition in the United States, significantly impacting global morbidity and mortality. Understanding temporal patterns in AF-related mortality among CKD patients is crucial for effective clinical and public health strategies.

AIM

To investigate AF-CKD comorbidity and mortality on the national level.

METHODS

Death certificates from the Centers for Disease Control Wide-Ranging Online Data for Epidemiologic Research database spanning 2011-2020 were analyzed to investigate AF-related CKD mortality in adults aged 35 to 85 or more years. Age-adjusted mortality rates (AAMRs) per 100000 persons and annual percent change (APC) were calculated, stratified by year, sex, race/ethnicity, and geographic region.

RESULTS

A total of 110733 deaths occurred among adults (aged 35-85 or more years) related to AF associated with CKD in the United States. Overall AAMR declined from 8.1 in 2011 to 5.5 in 2014 (APC: -14.89; 95% confidence interval (CI): -30.44 to -4.06), followed by an increase to 10.3 in 2020 (APC: 9.91; 95%CI: 6.1-19.62). Men had higher AAMRs than women (men: 7.6, 95%CI: 7.6-7.7). Non-Hispanic White adults had the highest AAMR (7.8), followed by non-Hispanic Black (5). States in the top 90^th percentile had approximately four times higher AAMRs than those in the lower 10^th percentile. AAMR also varied by region (Midwest: 7.6, West: 6.7, Northeast: 6.3, South: 5.6), with nonmetropolitan areas exhibiting higher AF-associated CKD mortality.

CONCLUSION

Temporal trends in AF-related mortality among CKD patients showed fluctuations over the study period, with notable disparities across demographic and geographic factors. Targeted interventions are warranted to mitigate the burden of AF associated with CKD and reduce mortality rates in the United States.

Key Words: Atrial fibrillation; Chronic kidney disease; Mortality; Risk factors; Disparities

Core Tip: Chronic kidney disease (CKD) could contribute to atrial fibrillation with increased mortality; our study investigates this correlation using the Centers for Disease Control’s national database over the last 2 decades. The age-adjusted mortality rate for CKD-related atrial fibrillation deaths in adults decreased from 2011 to 2014, followed by an increase from 2014 to 2020. Study noticed a variation in mortality based on gender (higher in men), race (higher in non-Hispanic White patients), Midwest states (Indiana, and Minnesota), and Nonmetropolitan areas. That result illustrates different disparities in two correlated common chronic morbidity that would guide healthcare providers and policymakers work on achieving more efficient and equitable healthcare system.

INTRODUCTION

Chronic kidney disease (CKD) and atrial fibrillation (AF) represent two significant health burdens within the United States, each associated with increased morbidity and mortality rates[1]. CKD’s prevalence has surged over decades in the US, with estimates reaching 26 million adults, up from approximately 10% to > 13% within a decade[2]. Simultaneously, AF, the prevalent cardiac arrhythmia globally, affects millions. Projections suggest 6-12 million in the United States and 17.9 million in Europe by 2050 and 2060, respectively[3]. The coexistence of AF and CKD significantly heightens the risk of adverse cardiovascular events and mortality[4]. Both conditions are prevalent, with CKD patients at heightened risk of developing AF[5].

The intersection of CKD and AF presents a formidable challenge to healthcare providers. Individuals with CKD are more prone to developing AF due to various factors, including fluid overload, electrolyte imbalances, and structural cardiac changes[6,7]. AF complicates CKD management by increasing thromboembolic events and worsening cardiovascular outcomes, elevating all-cause and cardiovascular mortality[8,9]. Therefore, this study aims to analyze the trends in mortality related to AF among CKD patients in the United States adult population from 2011 to 2020. By examining a decade of mortality data, we seek to elucidate temporal patterns, demographic disparities, and potential regional variations in mortality rates. This analysis will provide valuable insights into the evolving landscape of cardiovascular mortality in CKD patients with AF. These insights will further help in developing targeted interventions to mitigate the burden of increased mortality and morbidity associated with AF linked with CKD. Our objective was to discover patterns, disparities, and potential contributing factors by analyzing national mortality data, aiming to improve preventive measures and enhance clinical interventions for this susceptible demographic.

MATERIALS AND METHODS

Population and study setting

The comprehensive investigation uses the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research database to collect information from death certificates[10]. The study focused on instances of persons who died from CKD related to AF between 2011 and 2020. The study used the diagnostic code “I 48” “N18.0 to N18.9” from the 10^th version of the International Classification of Diseases and Related Health Problems[11]. The dataset comprises information regarding the causes of death from death certificates from all 50 states and the district of Columbia. The study examined at death records from the Multiple Causes of Death Public Use registry to find cases of CKD related AF. CKD related AF was either a contributing factor or the primary cause of death in these situations. In this study, Adults were categorized as people aged 35 to 85 and above at their demise. The research did not necessitate approval from a regional institutional review board because it relied on de-identified public use data issued by the government. The STROBE standards for reporting observational research were followed in this study[12].

Data abstraction

Our study information was obtained utilizing death certificates that included population size, demographics, location by state, urban status[13], facility type, and Census Bureau categories[14]. The differences in the coding practices over the years or the potential incorrect data found in the database could possibly skew results and have been acknowledged in the limitations of our manuscript.

Statistical analysis

We assessed mortality rates per 100000 individuals and computed both age-unadjusted and age-adjusted data during the study period. We classified these rates by year, gender, race/ethnicity, state, and urban/ rural status, with 95% confidence intervals (CIs). We calculated the crude mortality rates by dividing the total number of CKD-related AF deaths by the parallel United States population each year[15]. Age-adjusted mortality rates (AAMR) were obtained by standardizing CKD-related deaths in the United States in 2000[16]. The annual percent change (APC) and its 95%CI in AAMR were assessed using the Join-Point Regression Program (Version 5.0.2, National Cancer Institute)[17]. This study evaluated the national annual changes in both studied diseases while implementing log-linear regression models. This study evaluated the national annual changes in both studied diseases while implementing log-linear regression models. APC’s change classification relied on mortality slope depicting shift from zero, assessed via two-tailed t-testing at a significance level of P < 0.05.

RESULTS

CKD-related AF affected 110733 adults (aged 35-85 or more years) between 2011 and 2020 (Table 1). Of these, 42.5% occurred within medical facilities, 24.2% occurred in nursing homes/Long-term care facilities, 6.6% occurred in hospices, 23% occurred at home, and 3.7% at other places (Table 2).

Table 1 Chronic kidney disease related atrial fibrillation stratified by sex and race in United States, 2011 to 2020.

Year	Overall	Women	Men	NH White	NH Black or African American	NH Asian or Pacific Islander	NH American Indian or Alaska Native	Hispanic or Latino	Population
2011	10682	5237	5445	8897	1001	286	40	439	164802438
2012	12411	6048	6363	10273	1145	301	52	611	166516716
2013	7227	3407	3820	6136	637	130	34	282	168240727
2014	7694	3674	4020	6488	676	172	38	305	170292776
2015	9022	4247	4775	7682	721	189	34	367	172416615
2016	9990	4698	5292	8379	876	242	49	423	173964174
2017	11329	5309	6020	9447	1041	275	35	511	176104659
2018	12366	5764	6602	10314	1114	282	52	581	177613416
2019	13650	6475	7175	11364	1181	339	66	675	179040846
2020	16362	7466	8896	13532	1534	385	81	816	180565367
Total	110733	52325	58408	92512	9926	2601	481	5010	1729557734

NH: Non-Hispanic.

Table 2 Chronic kidney disease related atrial fibrillation, stratified by place of death in United States, 2011 to 2020.

Year	Medical facility	Nursing home/long-term care facility	Hospices	Home
2011	4691	2843	469	2241
2012	5181	3301	698	2731
2013	3222	1813	401	1472
2014	3464	1922	405	1633
2015	3832	2300	627	1953
2016	4347	2417	697	2197
2017	4797	2721	845	2549
2018	5184	2983	911	2896
2019	5542	3144	1121	3332
2020	6811	3340	1094	4495
Total	47071	26784	7268	25499

Annual trends for AF in CKD related AAMR

The overall AAMR for CKD-related AF deaths in adults was 6.2 in 2011 and increased to 7.7 in 2020. (APC: 0.82; 95%CI: -1.70 to 3.27). The overall AAMR decreased from 2011 to 2014 (APC: -15.49; 95%CI: -30.23 to -5.55) followed by an increase from 2014 to 2020 (APC: 10.12; 95%CI: 6.49-17.41) (Figure 1A, Tables 3 and 4).

Figure 1 Chronic kidney disease related atrial fibrillation in United States adults (2011-2020): Age-adjusted mortality rates per 100000 variations by sex, race, state, region, and urbanization. A: Chronic kidney disease related atrial fibrillation age-adjusted mortality rates (AAMRs) stratified by sex; B: Chronic kidney disease related atrial fibrillation AAMRs stratified by race; C: Chronic kidney disease related atrial fibrillation AAMRs stratified by state; D: Chronic kidney disease related atrial fibrillation AAMRs stratified by United States region; E: Chronic kidney disease related atrial fibrillation AAMRs stratified by urbanization. Urban areas: Large metropolitan areas with a population of 1 million or more; medium/small metropolitan areas: 50000 to 999999. Rural regions: Less than 50000 people. CI: Confidence interval; APC: Annual percent change.

Table 3 Annual percent change of chronic kidney disease related atrial fibrillation age-adjusted mortality rates per 100000, in the United States, 2011 to 2020.

Year interval	APC (95%CI)
Overall
2011 to 2014	-15.49 (-30.23 to -5.55)
2014 to 2020	10.12 (6.49-17.41)
Men
2011 to 2014	-14.89 (-30.44 to -4.06)
2014 to 2020	9.91 (6.10-19.62)
Women
2011 to 2014	-15.91 (-31.40 to -5.17)
2014 to 2020	10.09 (6.16-18.51)
NH White
2011 to 2014	-14.49 (-29.44 to -4.17)
2014 to 2020	10.63 (7.09-18.11)
NH Black or African American
2011 to 2014	-19.23 (-36.71 to -6.14)
2014 to 2020	10.28 (4.94-26.47)
NH American Indian or Alaska native
2011 to 2017	-7.17 (-21.47 to -1.42)
2017 to 2020	23.97 (8.45-51.18)
Hispanic or Latino
2011 to 2014	-22.94 (-41.00 to -7.62)
2014 to 2020	11.59 (6.08-22.08)
NH Asian or Pacific Islander
2011 to 2013	-34.76 (-47.48 to -11.50)
2013 to 2020	6.48 (2.15-19.29)
Nonmetropolitan areas
2011 to 2013	-20.90 (-29.08 to -8.27)
2013 to 2020	10.17 (7.65-14.83)
Metropolitan area
2011 to 2014	-15.59 (-30.45 to -5.43)
2014 to 2020	9.80 (6.08-17.61)
Northeast region
2011 to 2014	-13.42 (-26.72 to -4.41)
2014 to 2020	9.12 (5.94-15.48)
Midwest region
2011 to 2014	-15.05 (-30.78 to -4.00)
2014 to 2020	11.41 (7.69-19.80)
South region
2011 to 2014	-14.92 (-30.38 to -4.04)
2014 to 2020	10.67 (6.94-19.25)
West region
2011 to 2014	-16.99 (-32.90 to -6.03)
2014 to 2020	8.71 (4.51-18.15)

Indicates that the annual percentage change is significantly different from zero at α = 0.05. CI: Confidence interval; APC: Annual percent change; NH: Non-Hispanic.

Table 4 Overall and sex-stratified chronic kidney disease related atrial fibrillation age-adjusted mortality rates per 10000, in the United States, 2011 to 2020 (age-adjusted rate, 95% confidence interval).

Year	Men	Women	Overall
2011	8.1 (7.9-8.3)	4.9 (4.8-5.1)	6.2 (6.1-6.3)
2012	9.2 (9-9.4)	5.5 (5.4-5.7)	7 (6.9-7.1)
2013	5.4 (5.2-5.6)	3 (2.9-3.1)	4 (3.9-4.1)
2014	5.5 (5.3-5.7)	3.2 (3.1-3.3)	4.1 (4-4.2)
2015	6.3 (6.1-6.5)	3.6 (3.5-3.8)	4.7 (4.6-4.8)
2016	6.8 (6.6-7)	4 (3.8-4.1)	5.1 (5-5.2)
2017	7.5 (7.4-7.7)	4.4 (4.3-4.5)	5.7 (5.6-5.8)
2018	8 (7.8-8.2)	4.7 (4.6-4.8)	6 (5.9-6.1)
2019	8.5 (8.3-8.7)	5.2 (5.1-5.3)	6.6 (6.4-6.7)
2020	10.3 (10.1-10.5)	5.9 (5.7-6)	7.7 (7.6-7.8)
Total	7.6 (7.6-7.7)	4.5 (4.4-4.5)	5.8 (5.7-5.8)

AF in CKD related AAMR stratified by sex

Adult men had consistently higher AAMRs than adult women throughout the study period (overall AAMR men: 7.6, 95%CI: 7.6-7.7; women: 4.5, 95%CI: 4.4-4.5). In 2011, the AAMR for adult men was 8.1 (95%CI: 7.9-8.3), which decreased to 5.5 in 2014 (APC: -14.89; 95%CI: -30.44 to -4.06), followed by an increase to 10.3 in 2020 (APC: 9.91; 95%CI: 6.1-19.62). Similarly, the AAMR for adult women in 2011 was 4.9 (95%CI: 4.8-5.1), which decreased to 3.2 in 2014 (APC: -15.91; 95%CI: -31.4 to -5.17), followed by an increase to 5.9 in 2020 (APC: 10.09; 95%CI: 6.16-18.51). The AAMR for adult men and women at the end of the study period was 10.3 and 5.9, respectively (men: 95% Cl: 10.1-10.5; women: 95%CI: 5.7-6) (Figure 1A, Tables 3 and 4).

AF in CKD related AAMR stratified by race/ethnicity

Per race/ethnicity, AAMRs demonstrated highest values in non-Hispanic (NH) White patients, NH Black or African American, NH American Indian or Alaska native, NH Asian or Pacific Islander, and lastly Hispanic or Latino populations (overall AAMR NH White: 7.8, 95%CI: 7.7-7.8; NH Black or African American: 5, 95%CI: 4.9-5.1; NH American Indian or Alaska native: 3.8, 95%CI: 3.5-4.2; NH Asian or Pacific Islander: 2.6, 95%CI: 2.5-2.7; Hispanic or Latino: 2.2, 95%CI: 2.1-2.2).

The AAMRs for NH White and NH Black or African American exhibited similar trends over the study period. Both groups saw a decrease from 2011 to 2014 (NH White: APC: -14.49, 95%CI -29.44 to -4.17; NH Black or African American: APC: -19.23, 95%CI: -36.71 to -6.14), followed by an increase from 2014 to 2020 (NH White: APC: 10.63, 95%CI: 7.09-18.11; NH Black or African American: APC: 10.28, 95%CI: 4.94-26.47). The AAMRs for NH American Indian or Alaska Native decreased from 2011 to 2017 (APC: -7.71; 95%CI: -21.47 to -1.42), and then significantly increased from 2017 to 2020 (APC: 23.97; 95%CI: 8.45-51.18). The AAMRs for NH Asian or Pacific Islanders significantly decreased from 2011 to 2013 (APC: -34.76; 95%CI: -47.48 to -11.50) and then increased until the end of the study from 2013 to 2020 (APC: 6.48; 95%CI: 2.15-19.29). The AAMRs of Hispanic or Latino also significantly decreased from 2011 to 2014 (APC: -22.94; 95%CI: -41 to -7.62), and then increased from 2014 to 2020 (APC: 11.59; 95%CI: 6.08 to 22.08) (Figure 1B, Tables 3 and 5).

Table 5 Chronic kidney disease related atrial fibrillation age-adjusted mortality rates per 10000, stratified by races in the United States, 2011 to 2020 (age-adjusted rate, 95% confidence interval).

Year	NH White	NH Black or African American	NH American Indian or Alaska native	Hispanic or Latino	NH Asian or Pacific Islander
2011	6.3 (6.1-6.4)	6.9 (6.5-7.4)	5 (3.5-6.9)	3.8 (3.4-4.1)	4.8 (4.2-5.4)
2012	7.1 (6.9-7.2)	7.6 (7.1-8)	6.3 (4.6-8.4)	5 (4.6-5.4)	4.7 (4.2-5.2)
2013	4.1 (4-4.2)	4.2 (3.8-4.5)	4.1 (2.8-5.8)	2.2 (1.9-2.4)	1.9 (1.6-2.2)
2014	4.3 (4.2-4.4)	4.1 (3.8-4.4)	4.4 (3.1-6)	2.2 (2-2.5)	2.3 (2-2.7)
2015	5 (4.9-5.1)	4.3 (3.9-4.6)	3.2 (2.2-4.5)	2.5 (2.2-2.7)	2.4 (2-2.7)
2016	5.4 (5.3-5.5)	5 (4.7-5.4)	4.4 (3.2-5.9)	2.8 (2.5-3)	2.9 (2.5-3.3)
2017	6 (5.9-6.1)	5.7 (5.3-6.1)	3.4 (2.3-4.7)	3.1 (2.8-3.4)	3.1 (2.7-3.4)
2018	6.4 (6.3-6.6)	6 (5.6-6.3)	4.4 (3.3-5.9)	3.3 (3-3.6)	3 (2.6-3.3)
2019	7 (6.9-7.1)	6.1 (5.8-6.5)	5.6 (4.3-7.2)	3.8 (3.5-4.1)	3.4 (3-3.8)
2020	8.3 (8.1-8.4)	7.8 (7.4-8.2)	6.6 (5.2-8.2)	4.3 (4-4.6)	3.7 (3.3-4)
Total	7.8 (0-6)	5.1 (0.1-5.8)	4.2 (0.2-4.8)	2.2 (0-3.3)	2.7 (0.1-3.2)

NH: Non-Hispanic.

AF in CKD related AAMR stratified by geographic regions

A significant difference in AAMR was observed in different states, with the AAMRs ranging from 2.6 (95%CI: 2.3-2.9) in Nevada to 10.9 (95%CI: 10.6-11.3) in Minnesota. States belonging to the top 90^th percentile were Indiana, Minnesota, Nebraska, North Dakota, Oregon, Vermont, Washington, and Wisconsin which had approximately four times the AAMRs compared with states that fell into the lower 10^th percentile, namely, Alabama, Arizona, Florida, Georgia, Louisiana, Mississippi, Nevada, New York, and New Mexico. (Figure 1C, Table 6).

Table 6 Chronic kidney disease related atrial fibrillation age-adjusted mortality rates per 10000, stratified by states, in United States, 2011 to 2020.

State	Age-adjusted rate (95%CI)
Alabama	3.8 (3.6-4.1)
Alaska	5.3 (4.4-6.3)
Arizona	3.9 (3.7-4)
Arkansas	4.1 (3.8-4.4)
California	6.3 (6.2-6.5)
Colorado	7.6 (7.3-8)
Connecticut	4.7 (4.4-5)
Delaware	5.4 (4.8-6)
District of Columbia	4.5 (3.8-5.3)
Florida	3.3 (3.2-3.4)
Georgia	3.6 (3.4-3.7)
Hawaii	4.3 (3.9-4.7)
Idaho	5.8 (5.3-6.3)
Illinois	4.2 (4.1-4.4)
Indiana	8.9 (8.6-9.2)
Iowa	6.5 (6.2-6.9)
Kansas	4.2 (3.9-4.5)
Kentucky	7.7 (7.4-8.1)
Louisiana	3.4 (3.2-3.7)
Maine	5.9 (5.4-6.4)
Maryland	6.4 (6.1-6.7)
Massachusetts	5.2 (5-5.4)
Michigan	5.1 (4.9-5.3)
Minnesota	10.9 (10.6-11.3)
Mississippi	3.8 (3.5-4.1)
Missouri	4.7 (4.5-4.9)
Montana	5.6 (5.1-6.2)
Nebraska	8.7 (8.1-9.2)
Nevada	2.6 (2.3-2.9)
New Hampshire	7.3 (6.8-7.9)
New Jersey	5.2 (5-5.4)
New Mexico	3.3 (3-3.6)
New York	3.5 (3.4-3.6)
North Carolina	6.2 (6-6.4)
North Dakota	8.9 (8.1-9.8)
Ohio	6.5 (6.3-6.7)
Oklahoma	7.5 (7.1-7.8)
Oregon	9.8 (9.4-10.2)
Pennsylvania	6.9 (6.7-7)
Rhode Island	7.3 (6.7-7.9)
South Carolina	7 (6.7-7.3)
South Dakota	6.6 (6-7.3)
Tennessee	6.9 (6.7-7.2)
Texas	6.5 (6.3-6.6)
Utah	5.3 (4.9-5.7)
Vermont	8.1 (7.3-9)
Virginia	5.3 (5.1-5.5)
Washington	9 (8.7-9.3)
West Virginia	7.7 (7.2-8.2)
Wisconsin	8.4 (8.1-8.6)
Wyoming	6.2 (5.3-7)

CI: Confidence interval.

On average, throughout the study period the highest mortality was observed in the Midwestern region (AAMR: 7.6; 95%CI: 7.5-7.7), followed by the Western (AAMR: 6.7; 95%CI: 6.6-6.8), Northeastern (AAMR: 6.3; 95%CI: 6.2-6.4), and Southern (AAMR: 5.6; 95%CI: 5.6-5.7) regions (Figure 1D, Tables 3 and 7). Nonmetropolitan areas had consistently higher AAMRs than metropolitan areas throughout the study period, with overall AAMRs of 8 (95%CI: 7.9-8.1) and 6.1 (95%CI: 6.1-6.2), respectively. AAMRs of metropolitan areas decreased from 2011 to 2014 (APC: -15.59; 95%CI: -30.45 to -5.43), followed by an increase till the end of the study in 2020 (APC: 9.80; 95%CI: 6.08-17.61). While AAMRs of Nonmetropolitan significantly decreased from 2011 to 2013 (APC: -20.90; 95%CI: -29.08 to -8.27), followed by an increase till 2020 (APC: 10.17; 95%CI: 7.65 to 14.83) (Figure 1E, Tables 3 and 8).

Table 7 Chronic kidney disease related atrial fibrillation age-adjusted mortality rates per 10000, stratified by census region in United States, 2011 to 2020 (age-adjusted rate, 95% confidence interval).

Year	Northeast	Midwest	South	West
2011	5.5 (5.2-5.7)	6.7 (6.4-6.9)	5.5 (5.3-5.7)	7.3 (7-7.6)
2012	6.1 (5.9-6.4)	7.6 (7.3-7.8)	6.2 (6-6.4)	8.2 (7.9-8.5)
2013	3.7 (3.5-3.9)	4.4 (4.2-4.6)	3.6 (3.4-3.7)	4.3 (4.1-4.5)
2014	3.9 (3.7-4.1)	4.5 (4.3-4.7)	3.7 (3.6-3.9)	4.6 (4.4-4.8)
2015	4.3 (4.1-4.5)	5.3 (5.1-5.6)	4.3 (4.1-4.4)	5.1 (4.9-5.3)
2016	4.7 (4.5-5)	5.7 (5.5-5.9)	4.7 (4.5-4.8)	5.6 (5.4-5.8)
2017	5.2 (4.9-5.4)	6.4 (6.2-6.7)	5.1 (5-5.3)	6.2 (5.9-6.4)
2018	5.5 (5.2-5.7)	7 (6.7-7.2)	5.6 (5.4-5.8)	6.3 (6-6.5)
2019	5.8 (5.5-6)	7.6 (7.4-7.9)	6 (5.8-6.1)	7.1 (6.9-7.4)
2020	6.8 (6.6-7.1)	9.1 (8.9-9.4)	7.2 (7-7.4)	7.9 (7.6-8.1)
Total	5.2 (5.1-5.2)	6.5 (6.4-6.6)	5.2 (5.2-5.3)	6.3 (6.2-6.4)

Table 8 Chronic kidney disease related atrial fibrillation age-adjusted mortality rates per 10000, stratified by urban-rural classification, in United states, 2011 to 2020 (age-adjusted rate, 95% confidence interval).

Year	Metropolitan	Nonmetropolitan
2011	6.1 (6-6.2)	6.6 (6.3-6.9)
2012	6.9 (6.8-7.1)	7.3 (7-7.6)
2013	3.9 (3.8-4)	4.2 (3.9-4.4)
2014	4 (3.9-4.1)	4.5 (4.2-4.7)
2015	4.6 (4.5-4.7)	5.3 (5-5.5)
2016	5 (4.9-5.1)	5.7 (5.4-6)
2017	5.5 (5.4-5.6)	6.4 (6.2-6.7)
2018	5.9 (5.8-6)	6.7 (6.4-7)
2019	6.4 (6.2-6.5)	7.7 (7.4-7.9)
2020	7.4 (7.3-7.5)	9.2 (8.9-9.5)
Total	5.6 (5.6-5.7)	6.4 (6.3-6.5)

Our results show that the overall mortality rates for AF and CKD increased from 2011 to 2020. AMR was consistently greater for men than for women and for non-metropolitan areas than for metropolitan areas. The highest overall AAMR was reported in the Midwest region and states like Indiana and Minnesota. The lowest overall AAMR was reported in the Southern region and states like Alabama and Arizona. The values were the highest for NH white populations and lowest for Hispanic/Latino populations.

DISCUSSION

The study provides valuable insights into the temporal trends in mortality associated with AF among adults diagnosed with CKD in the United States over a decade, from 2011 to 2020. Previous investigations into CKD-related mortality have shown notable declines, indicating improvements in healthcare strategies (Figure 2)[18]. Our findings reveal a noteworthy fluctuation in AAMR attributed to AF among CKD patients throughout the study period. Initially, from 2011 to 2014, a promising decline in AAMR was seen. However, the AAMR increased from 2014 to 2020 such that the overall AAMR went from 6.2 in 2011 to 7.7 in 2020. The observed decrease in AAMR of AF among CKD patients from 2011 to 2014 likely reflects the positive impact of multidisciplinary care models, including the integration of nephrologists, nurse specialists, and professionals from other fields[19-21]. Studies such as the chronic care model and the CKD integrative care model have demonstrated the effectiveness of multidisciplinary care in improving patient outcomes and reducing mortality rates[19,21]. Furthermore, rigorous adherence to evidence-based guidelines, such as those outlined by the kidney disease: Improving Global Outcomes guidelines, may have contributed to optimized management strategies during this period[22]. However, the subsequent increase in AAMR of AF from 2014 to 2020 may be influenced by various factors, including shifts in healthcare policies, disruptions due to the coronavirus disease 2019 (COVID-19) pandemic, and changes in patient demographics and disease burden[23,24].

Figure 2  Central illustration: geographic, gender, and racial trends mortality due to chronic kidney disease related atrial fibrillation among adults in the United States from year 2011-2020.

When categorized by sex, male patients consistently showed higher AAMRs as compared to female counterparts throughout the study period. These differences can be attributed to several factors. This observation aligns with broader trends in cardiovascular and renal health, where males often face a higher burden of disease and mortality compared to females. Firstly, males tend to have a higher prevalence of risk factors for AF, such as hypertension, obesity, and coronary artery disease, which are also common comorbidities in CKD[25-27]. Additionally, biological differences between sexes, including hormonal influences and genetic predispositions, may contribute to varying susceptibilities to AF-related complications. Furthermore, disparities in healthcare access and utilization, as well as differences in adherence to treatment regimens, may result in suboptimal management of AF and CKD among males.

When analyzed according to race/ethnicity, the analysis revealed that NH White patients exhibited notably elevated AAMRs compared to their counterparts. These differences may arise from variations in socioeconomic status, healthcare access, prevalence of comorbidities, and genetic predispositions. NH Additionally, recent research also found that white males have the highest burden of AF[28]. Possible contributors include differences in comorbidity prevalence, delays in diagnosis and treatment, variations in care quality, and genetic and biological factors. Moreover, some groups may have higher rates of obesity, hypertension, and other cardiovascular risk factors known to increase the likelihood of developing AF[29].

Another significant finding of our study underscores geographic disparities, with marked variations in AAMRs observed across states and regions. With the AAMRs ranging from 2.6 to 10.9 in Nevada and Minnesota respectfully. The analysis also disclosed that the Midwestern region consistently demonstrated the highest AAMRs. These regional differences may stem from various factors distinctive to the CKD population. For example, variances in healthcare infrastructure and accessibility to specialized care might affect the proper timely diagnosis and management of AF complications. Furthermore, socioeconomic elements like income inequality and educational attainment could impact the access to healthcare services and compliance with treatment plans among CKD patients with AF[30,31]. Additionally, contextual poverty and its impact on nutrition can further exacerbate these disparities[32]. A meta-analysis further underscores the significance of socioeconomic elements, revealing their strong association with CKD[33]. Moreover, disparities in the prevalence of risk factors such as high blood pressure, diabetes, and obesity among regions might contribute to variations in mortality rates.

Persistent disparities exist between metropolitan and nonmetropolitan areas, with the latter consistently displaying higher AAMRs associated with AF among CKD patients. Contributing to this discrepancy are health behaviors, such as hypertension, diabetes, and obesity, which are not well managed and treated in rural areas compared to urban areas in the United States. These challenges are often due to barriers such as limited access to healthcare, financial constraints, and cultural differences[34]. Patients with CKD in rural areas face significant challenges in accessing kidney replacement therapy, leading to worse outcomes compared to their urban counterparts[35]. These challenges are particularly pronounced in vulnerable populations, such as the urban poor, who have a higher risk of progression to end-stage renal disease[36]. Addressing these determinants has the potential to narrow the gap in mortality rates between metropolitan and nonmetropolitan areas.

Irrespective of the stratification by sex, race/ethnicity, urbanization or United States census regions, the overall AAMRs had a concerning upward trend in the years 2014-2020. This increase in the last years of the study could be due to the COVID-19 pandemic. Its impact was wide ranging from affecting the physical health of the general population and complicating existing chronic conditions to the overuse of medical facilities for COVID-19 which could have potentially disrupted the healthcare access for general population that did not present with acute symptoms. The pandemic could be a comprehensive explanation for the elevated mortality in the final years of the study period.

Our findings have shown a significant association between AF and CKD that adds greatly to the morbidity and mortality in the United States as well as globally. This prevalence of the disease poses an inevitable burden that threatens overall national health. There is a need of development of targeted interventions and policies specifically targeting the identified high-risk demographics. This will help mitigate the burden of the disease and improve the morbidity and mortality linked with CKD and AF in the United States.

Limitations

This database might result in errors or omissions. The outcomes for patients aged 35 and older might not be generalizable to younger ages. Analyzing this data does not involve detailed clinical data, such as biomarkers and treatment modalities, and it impedes a comprehensive understanding of mortality drivers. The absence of scrutiny for the definite classification of both studied diseases impedes interpretation that would guide towards proper interventions. Furthermore, this study did not account for socioeconomic factors, potential confounders such as comorbid conditions, and medical management modalities.

CONCLUSION

In conclusion, our study underscores a notable increase in mortality linked to AF associated with CKD among adults aged 35 to 85 or more years from 2011 to 2020. Exceptionally high mortality rates were observed among NH White populations, males, residents in the Midwest United States regions, and those in non-metropolitan areas. Addressing mortality associated with AF and CKD complications demands enhanced preventive and management strategies, especially among older adults. Our results highlight a significant mortality linked to AF and CKD that needs urgent intervention to improve the overall national health outcomes in the United States.