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\begin{document}

\title{Prognostic value of systemic immune-inflammation index (SII) as a novel
marker in patients with atrial fibrillation}



\author[1]{Ru Jie Zheng}%
\author[1]{Yue Wang}%
\author[1]{Jun-Nan  Tang}%
\author[1]{ Jie-Ying  Duan}%
\author[1]{Ming-Yue  Yuan}%
\author[1]{Yao-Hui  Jiang}%
\author[1]{Jin-Ying Zhang}%
\affil[1]{Zhengzhou University First Affiliated Hospital}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
\let\center\flushleft
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\selectlanguage{english}
\begin{abstract}
Background Recently, inflammation plays an essential role in the
prognosis of atrial fibrillation (AF) patients. Systemic
immune-inflammation index (SII), reflecting the inflammation status,
which is measured by the formula: neutrophil count \selectlanguage{ngerman}× platelet
count/lymphocyte count, is a powerful prognostic marker in several types
of cancer and cardiovascular disease. However, no information regarding
the prognostic value of SII in patients with AF is available. Methods
and results We retrospectively enrolled 1768 AF patients in our study.
Demographic characteristics, laboratory data and echocardiography were
measured and collected on admission. The primary endpoints were death
from all causes and death from cardiovascular diseases. The secondary
endpoints were major bleeding and stroke. During a mean follow-up of
22.35 months, 155 patients occurred death from all causes. For further
analysis, patients were categorized into two groups according to the
optimal cutoff value of SII level determined by using receiver operating
characteristics curve analysis. The incidence of death from all causes
and death from cardiovascular diseases in high SII group is
significantly higher compared with that in low SII group. However, no
significant differences were detected between two groups for the
secondary endpoints (p\textgreater{}0.05). On multivariable Cox analysis
with adjustment of potential confounders, the risk of death from all
causes and death from cardiovascular diseases increased by 77.6\% and
51.2\%, respectively, in high SII group. Conclusion Systemic
immune-inflammation index was significantly associated poor outcomes and
was an independent predictor for mortality in atrial fibrillation
patients.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Prognostic value of systemic immune-inflammation index (SII) as
a novel marker in patients with atrial fibrillation}

Ru-Jie Zheng\textsuperscript{1}, Yue Wang\textsuperscript{1}, Jun-Nan
Tang\textsuperscript{1}, Jie-Ying Duan\textsuperscript{1}, Ming-Yue
Yuan\textsuperscript{1}, Yao-Hui Jiang\textsuperscript{1},Jin-Ying
Zhang\textsuperscript{1\#}

\textbf{\#} Corresponding author

Department of Cardiology, First Affiliated Hospital of Zhengzhou
University, Zhengzhou 450052 P.R., China. Key Laboratory of Cardiac
Injury and Repair of Henan Province, Zhengzhou, China.

\textbf{Corresponding author:}

Jin-Ying Zhang, MD, PhD, No. 1, Jianshe Road, Zhengzhou, China. Tel:
+86-0371- 67967641, \textbf{Email address:} jyzhang@zzu.edu.cn

\textbf{Funding statement:} This research was funded by the National
Natural Science Foundation of China (81760043 and 81560070).

\textbf{Declaration of competing interests:} None.

\textbf{Abstract}

\textbf{Background}

Recently, inflammation plays an essential role in the prognosis of
atrial fibrillation (AF) patients. Systemic immune-inflammation index
(SII), reflecting the inflammation status, which is measured by the
formula: neutrophil count \selectlanguage{ngerman}× platelet count/lymphocyte count, is a
powerful prognostic marker in several types of cancer and cardiovascular
disease. However, no information regarding the prognostic value of SII
in patients with AF is available.

\textbf{Methods and results}

We retrospectively enrolled 1768 AF patients in our study. Demographic
characteristics, laboratory data and echocardiography were measured and
collected on admission. The primary endpoints were death from all causes
and death from cardiovascular diseases. The secondary endpoints were
major bleeding and stroke. During a mean follow-up of 22.35 months, 155
patients occurred death from all causes. For further analysis, patients
were categorized into two groups according to the optimal cutoff value
of SII level determined by using receiver operating characteristics
curve analysis (low SII group \textless{}451.01 or high SII group
\selectlanguage{english}[?]451.01). The incidence of death from all causes and death from
cardiovascular diseases in high SII group is significantly higher
compared with that in low SII group, (14.3\% vs. 5.3\%,\emph{p}
\textless{}0.001; 9.3\% vs. 3.8\%, \emph{p} \textless{}0.001,
respectively). However, no significant differences were detected between
two groups for the secondary endpoints (\emph{p} \textgreater{}0.05). On
multivariable Cox analysis with adjustment of potential confounders, the
risk of death from all causes and death from cardiovascular diseases
increased by 77.6\% (hazard risk {[}HR{]}=1.776, 95\% confidence
interval {[}CI{]}: 1.109-3.065, \emph{p} = 0.018) and 51.2\% (HR=1.512,
95\%CI: 1.011-3.742, \emph{p} = 0.025), respectively, in high SII group.

\textbf{Conclusion}

Systemic immune-inflammation index was significantly associated poor
outcomes and was an independent predictor for mortality in atrial
fibrillation patients.

\textbf{Key words} systemic immune-inflammation index; atrial
fibrillation; mortality; inflammation

\textbf{Introduction}

Worldwide, atrial fibrillation (AF) is one of the most prevalent cardiac
arrhythmias in adults\textsuperscript{1}. Owing to extended longevity
and intensifying search for undiagnosed AF, approximately 4\% experience
AF in general population\textsuperscript{2} and a 2.3-fold rise is
expected\textsuperscript{3}. AF, which is associated heart
failure\textsuperscript{4} and stroke\textsuperscript{5}, worsens
patient quality of life\textsuperscript{6} and increases significant
burden to patients and societal health due to the high morbidity and
mortality. Previous studies\textsuperscript{7-11} have shown that
inflammation is associated with AF development and progression in
general population and patients after cardioversion, cardiac surgery and
catheter ablation. Increasing evidence supports the essential role of
inflammatory factors\textsuperscript{10,12-14} in predicting the onset
of AF and recurrence. Some inflammatory factors including
platelet-to-lymphocyte ratio (PLR)\textsuperscript{15,16},
IL-6\textsuperscript{17}, IL-10\textsuperscript{18} and high sensitivity
C-reactive protein\textsuperscript{19}, were proven to be simple
biomarkers to predict the incidence of AF in patients with or without
history of AF. However, these biomarkers only involve one or two types
of immune- inflammatory cells and may not accurately reflect
inflammation status.

The systemic immune-inflammation index (SII) is a novel and integrated
inflammatory index based on neutrophil, platelet and lymphocyte counts.
SII was initially demonstrated to be associated with prognosis of
various cancers, such as prostate cancer\textsuperscript{20},
hepatocellular carcinoma\textsuperscript{21} and gastric
cancer\textsuperscript{22}. Up to now, the relationships of SII and
coronary artery disease\textsuperscript{23,24}, heart
failure\textsuperscript{25} were reported by many studies. SII is now
considered to comprehensively reflect inflammation status. However, the
association between SII and AF still remains unclear. Therefore, we
conducted this study to investigate the association between SII levels
and AF to determine the prognostic value of SII in patients with AF.

\textbf{Methods}

\textbf{Study design and population}

Patients hospitalized for AF in the First Affiliated Hospital of
Zhengzhou University from January 2017 to December 2019 were registered
in this retrospective cohort study. Inclusion criteria were as follows:
(1) age \textgreater{}18 years old; (2) history of symptomatic AF for at
least 6 months and documented on electrocardiogram in the previous 1
year. Exclusion criteria were as follows: (1) patients with significant
coronary artery disease verified by coronary angiogram; (2) congenital
heart disease, valvular heart disease and serious dysfunction of kidney
and liver; (3) suffering from infectious diseases and corticosteroid or
nonsteroidal anti-inflammatory drug use in the previous 6 months; (4)
patients with incomplete clinical data and unwilling or unable to commit
to follow up requirements. The study protocol was approved by ethics
committee. Because of the retrospective design of this study, the ethics
committee waived the need of obtaining informed consent from all
participants.

\textbf{Data collection}

The demographic characteristics and laboratory data were collected by
reviewing patients' medical records. Echocardiography was performed on
admission and left atrial diameter (LAD), left ventricular ejection
fraction (LVEF) were obtained. Demographic characteristics included
gender, age, race, height, weight, body mass index (BMI), smoking
status, drinking, heart rate on admission and underlying disease.
Peripheral blood samples were obtained by vacutainer tubes at the time
of admission, after at least 12 hours of fasting. The following
hematological parameters were measured using automated hematology
analyzing devices: white blood cell count (WBC), red blood cell count
(RBC), hemoglobin (Hb), platelet count (PLT), differential white blood
cell count (neutrophils, monocytes, lymphocytes, eosinophils and
basophiles). Glucose, alanine aminotransferase (ALT), aspartic
transaminase (AST), albumin, serum creatinine (Cr), uric acid (UA),
blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG),
low-density lipoprotein (LDL), high-density lipoprotein (HDL), estimated
glomerular filtration rate (eGFR), D-dimer, C-reactive protein (CRP) and
erythrocyte sedimentation rate (ESR) were also evaluated. Neutrophils,
platelet count and lymphocytes were expressed as x10\textsuperscript{9}
cells/L. The SII was measured as neutrophil count x platelet
count/lymphocyte count.

\textbf{Outcome variables and follow-up}

The primary endpoints were death from all causes and death from
cardiovascular diseases. The secondary endpoints were major bleeding and
stroke. The major bleeding events were characterized according to the
Bleeding Academic Research Consortium
definitions\textsuperscript{26}types 2,3, or 5. Stroke was defined as a
neurological deficit attributed to an acute focal injury of the central
nervous system by vascular causes, including hemorrhage, embolism and
thrombosis\textsuperscript{5}. In our study, all participants were
contacted and followed up by telephone. The mean follow-up time was
22.35 months.

\textbf{Statistical analysis}

For analysis, patients were categorized into two groups according to the
optimal cutoff value of SII level determined by using receiver operating
characteristics curve analysis (low SII group \textless{}451.01 or high
SII group \selectlanguage{english}[?]451.01). The SPSS 22.0 software (IBM Corp., Armonk, NY) was
used to perform all analyses. Continuous variables were reported as the
mean +- standard deviation (SD) and categorical data were reported as
frequencies and percentages. Differences in baseline characteristics
between two groups were compared using a \selectlanguage{greek}χ\selectlanguage{english}2 test or Fisher's exact test
for categoric data and an independent \emph{t} -test or Kruskal-Wallis
test for continuous data, as appropriate. Kaplan-Meier survival curves
were used for cumulative incidence rates of primary and secondary
endpoints. The statistical differences between groups in Kaplan-Meier
curves were determined using the log-rank test. The predictive value of
SII level related to outcomes was assessed by the multivariable Cox
regression model with adjustment for potential confounders, including
age, diabetes mellitus, WBC, Hb, PLT, albumin, BUN, UA, Cr, HDL, eGFR,
D-dimer, CRP, ESR, LAD and LVEF. The hazard ratios (HRs) and 95\%
confidence intervals (CIs) were also determined. All tests were 2-sided
and a \emph{p} value \textless{}0.05 was considered statistically
significant.

\textbf{Results}

\textbf{Baseline characteristics and outcomes}

We initially enrolled 1851 patients with a diagnosis of atrial
fibrillation who met the inclusion criteria. 35 patients were excluded
because of incomplete SII data and 48 patients were excluded because
they were lost to follow-up. Finally, a total of 1768 patients were
selected to this study.

During a mean follow-up of 22.35 months, 155 cases of death from all
causes occurred and 105 patients died from cardiovascular diseases. The
baseline demographic characteristics and clinical data two groups are
shown in Table 1. Patients in high SII group were older and more likely
to have diabetes mellitus than patients in low SII group. Significant
differences were detected in heart rate on admission, WBC, Hb, PLT,
albumin, BUN, UA, Cr, HDL, eGFR, D-dimer, CRP, ESR, LAD and LVEF
(all\emph{p} \textless{}0.05). Besides, the incidence of death from all
causes in high SII group is 97 (14.3\%) and in low SII group, it is 58
(5.3\%) which is significantly different (\emph{p} \textless{}0.001).
The incidence of death from cardiovascular diseases between the two
groups also showed a significant difference (9.3\% vs. 3.8\%,\emph{p}
\textless{}0.001). For the secondary endpoints, we did not find any
difference in the incidence of major bleeding events and stroke
(\emph{p} = 0.094 and \emph{p} = 0.623, respectively).

Kaplan-Meier survival curves for SII level and adverse outcomes are
shown in Figure 1 and Figure 2. Compared with patients in low SII group,
patients in high SII group showed a significantly increased risk of
death from all causes and death from cardiovascular diseases (log
rank\emph{p} \textless{} 0.001 and \emph{p} = 0.001).

After adjusting for potential cofounders, including age, diabetes
mellitus, WBC, Hb, PLT, albumin, BUN, UA, Cr, HDL, eGFR, D-dimer, CRP,
ESR and LAD, multivariable Cox regression analyses were performed to
evaluate the prognostic value of SII and adverse outcomes. The risk of
death from all causes and death from cardiovascular diseases increased
by 77.6\% (95\% CI: 1.109-3.065, \emph{p} = 0.018) and 51.2\% (95\% CI:
1.011-3.742, \emph{p} = 0.025) in high SII group compared to that in low
SII group, during the long-term follow-up (Table 2 and 3).

\textbf{Discussion}

This study mainly investigated the association between SII level and
adverse outcomes in patients with AF, and tried to evaluate the
prognostic value of SII as a new inflammatory factor in AF. The major
finding was that high SII level was strongly associated with adverse
outcomes and was an independent predictor for death from all causes and
death from cardiovascular diseases in patients with AF. Our study is the
first study to report the association and prognostic value of SII in
patients with AF. This finding adds to current knowledge regarding the
predictive relationship between SII and adverse outcomes in AF patients.

Previous studies\textsuperscript{13,14,17,27} have established that
inflammation plays a key role in development and progression of AF.
Inflammatory factors, such as PLR\textsuperscript{15},
IL-6\textsuperscript{17}, IL-10\textsuperscript{18} and
CRP\textsuperscript{19}, were proven to be risk factors in AF and were
potential predictors of prognosis in patients developed AF. As for SII,
which combined neutrophil, lymphocyte and platelet count, serving as a
detectable biomarker for systemic inflammatory activity and reflecting
the inflammatory state\textsuperscript{28}. Previously, SII emerged as a
reliable and powerful predictor in various malignant diseases, including
hepatocellular carcinoma\textsuperscript{21}, gastric
cancer\textsuperscript{22} and renal cell cancer\textsuperscript{29}.
Evidence is accumulating that SII level, apart from their well-known
predictive value in cancer, were close related with in-hospital
mortality in infective endocarditis\textsuperscript{30} and the
incidence of major cardiovascular events in coronary artery
disease\textsuperscript{23,31,32}. Until now, the association between
SII level and AF is still unknown. Therefore, we utilized a novel
predictor, SII, which was demonstrated to be significantly related to
adverse outcomes in AF patients.

SII was measured based on the counts of three types of circulating
immune cells: platelets, lymphocytes, and neutrophils. Our study showed
that AF patients with high SII level had increased risk for mortality.
Neutrophils, which constitute the largest proportion of leukocyte, are
of great importance for initiating and modulating immune
processes\textsuperscript{33,34}. Lymphocytes are also an important
component of white blood cells, mediate adaptive immunity and function
in innate immunity. Both neutrophils and lymphocytes can mediate
adaptive and innate immunity. Platelets could be considered as aspecific
first line inflammatory biomarkers which bind to leukocytes, influencing
the function of inflammatory elements of these
cells\textsuperscript{35}. In several clinical studies, mediators of the
inflammatory response were supported to be associated with remodeling of
AF\textsuperscript{36,37}. Inflammation can initiate AF, which
subsequently generates an inflammatory response that further enhances
atrial electrical and structural remodeling and perpetuates the
arrhythmia.

Our study had several strengths. The sample size was relatively large to
identify the significant association between SII and adverse outcomes in
patients with AF. Moreover, we adjusted the potential confounders which
might influence the prognostic value of SII in patients with AF.
However, some limitations on this study also should be mentioned. First,
because of the retrospective study design, results of our study need to
be verified by multicenter, prospective studies. In addition, we only
collected the baseline data of SII, rather than collecting data at
multiple times.

\textbf{Conclusion}

Systemic immune-inflammation index was significantly associated poor
outcomes and was an independent predictor for mortality in atrial
fibrillation patients.

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\textbf{Data availability statement}

Due to confidentiality policies, data will not be shared.

\textbf{Figure Legends}

\textbf{Figure 1} . Cumulative Kaplan-Meier estimates of the time to the
first adjudicated occurrence of death from all causes. The X axis
represents the follow-up time and the Y axis represents the Cumulative
risk of death from all causes.

\textbf{Figure 2.} Cumulative Kaplan-Meier estimates of the time to the
first adjudicated occurrence of death from cardiovascular diseases. The
X axis represents the follow-up time and the Y axis represents the
Cumulative risk of death from cardiovascular diseases.

\textbf{Table 1 Baseline characteristics and clinical outcomes of
patients with atrial fibrillation according to the SII level.}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
Variables & low SII group (n=1091) & high SII group (n=677) & \selectlanguage{greek}χ\selectlanguage{english}2 or t &
\emph{P}\tabularnewline
\midrule
\endhead
Age, years & 65.55\selectlanguage{ngerman}±11.24 & 66.94\selectlanguage{ngerman}±11.50 & 2.552 & 0.011\tabularnewline
Heart rate, beats/min & 83.36\selectlanguage{ngerman}±22.09 & 86.66\selectlanguage{ngerman}±25.44 & 2.909 &
0.004\tabularnewline
Male, n (\%) & 514 (47.1) & 333 (49.2) & 0.053 & 0.817\tabularnewline
Smoking, n (\%) & 313 (28.7) & 201 (29.7) & 0.310 & 0.578\tabularnewline
Drinking, n (\%) & 150 (17.8\%) & 180 (19.7\%) & 1.083 &
0.298\tabularnewline
Hypertension, n (\%) & 408 (48.5) & 476 (51.9) & 2.093 &
0.148\tabularnewline
Diabetes mellitus, n (\%) & 144 (17.1) & 211 (23.1) & 9.730 &
0.002\tabularnewline
LAD, mm & 44.37\selectlanguage{ngerman}±10.04 & 45.64\selectlanguage{ngerman}±15.40 & 1.954 & 0.049\tabularnewline
LVEF, \% & 55.09\selectlanguage{ngerman}±11.81 & 53.68\selectlanguage{ngerman}±12.53 & -2.364 & 0.018\tabularnewline
WBC, 10\textsuperscript{9}/L & 5.68\selectlanguage{ngerman}±1.63 & 7.74\selectlanguage{ngerman}±6.99 & 8.704 &
\textless{}0.001\tabularnewline
RBC, 10\textsuperscript{12}/L & 4.25\selectlanguage{ngerman}±0.60 & 4.20\selectlanguage{ngerman}±0.74 & -2.005 &
0.045\tabularnewline
Hemoglobin, g/L & 131.47\selectlanguage{ngerman}±20.40 & 128.35\selectlanguage{ngerman}±22.85 & -3.038 &
0.002\tabularnewline
Platelet, 10\textsuperscript{9}/L & 159.70\selectlanguage{ngerman}±49.63 & 205.30\selectlanguage{ngerman}±88.23 & 13.533
& \textless{}0.001\tabularnewline
BUN, mmol/L & 7.03\selectlanguage{ngerman}±3.59 & 9.20\selectlanguage{ngerman}±1.17 & 6.054 &
\textless{}0.001\tabularnewline
Cr, umol/L & 80.57\selectlanguage{ngerman}±32.36 & 103.26\selectlanguage{ngerman}±83.78 & 7.598 &
\textless{}0.001\tabularnewline
UA, umol/L & 362.39\selectlanguage{ngerman}±128.89 & 398.02\selectlanguage{ngerman}±160.18 & 5.151 &
\textless{}0.001\tabularnewline
Albumin, g/L & 40.51\selectlanguage{ngerman}±4.31 & 39.55\selectlanguage{ngerman}±5.42 & -4.073 &
\textless{}0.001\tabularnewline
TC, mmol/L & 3.60\selectlanguage{ngerman}±1.04 & 3.71\selectlanguage{ngerman}±3.20 & 0.928 & 0.354\tabularnewline
TG, mmol/L & 1.29\selectlanguage{ngerman}±0.87 & 1.28\selectlanguage{ngerman}±0.72 & -0.393 & 0.695\tabularnewline
HDL, mmol/L & 1.12\selectlanguage{ngerman}±0.62 & 1.04\selectlanguage{ngerman}±0.32 & -3.402 & 0.001\tabularnewline
LDL, mmol/L & 2.26\selectlanguage{ngerman}±3.46 & 2.48\selectlanguage{ngerman}±3.78 & 0.610 & 0.542\tabularnewline
eGFR, ml/min & 80.62\selectlanguage{ngerman}±20.92 & 73.49\selectlanguage{ngerman}±31.89 & -2.268 & 0.024\tabularnewline
D-dimer, ug/L & 0.32\selectlanguage{ngerman}±1.04 & 0.65\selectlanguage{ngerman}±2.52 & 3.588 &
\textless{}0.001\tabularnewline
CRP, mg/L & 7.43\selectlanguage{ngerman}±29.31 & 23.82\selectlanguage{ngerman}±54.15 & 6.256 &
\textless{}0.001\tabularnewline
ESR, mm/h & 13.63\selectlanguage{ngerman}±15.06 & 22.50\selectlanguage{ngerman}±22.13 & 5.624 &
\textless{}0.001\tabularnewline
Stroke, n (\%) & 49 (9.8) & 43 (8.5) & 0.148 & 0.700\tabularnewline
Bleeding, n (\%) & 74 (8.7) & 57 (6.2) & 4.230 & 0.040\tabularnewline
All-cause mortality, n (\%) & 58 (5.3) & 97 (14.3) & 27.700 &
\textless{}0.001\tabularnewline
Cardiac mortality, n (\%) & 42 (3.8) & 63 (9.3) & 15.339 &
\textless{}0.001\tabularnewline
\bottomrule
\end{longtable}

Abbreviations: LAD, left atrial fibrillation; LVEF, left ventricular
ejection fraction; WBC, white blood cell; RBC, red blood cell; BUN,
blood urea nitrogen; Cr, creatinine; UA, uric acid; TG, triglyceride;
TC, total cholesterol; HDL, high-density lipoprotein cholesterol; LDL,
low-density lipoprotein cholesterol; eGFR, estimated glomerular
filtration rate; CRP, C-reactive protein; ESR, erythrocyte sedimentation
rate;

\textbf{Table 2Multivariate Cox regression analysis for death from all
causes.}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
Variables & \emph{B} & \emph{SE} & \emph{Wald} & \emph{P} & \emph{HR} &
\emph{95\% CI}\tabularnewline
\midrule
\endhead
Age & 0.001 & 0.016 & 0.001 & 0.992 & 1.000 & 0.969 -
1.033\tabularnewline
Diabetes mellitus & 0.141 & 0.386 & 0.133 & 0.715 & 1.151 & 0.540 -
2.455\tabularnewline
Heart rate & -0.012 & 0.008 & 2.623 & 0.105 & 0.988 & 0.973 -
1.003\tabularnewline
LAD & 0.033 & 0.015 & 4.877 & 0.027 & 1.033 & 1.004 -
1.063\tabularnewline
LVEF & -0.033 & 0.013 & 7.071 & 0.008 & 0.967 & 0.944 -
0.991\tabularnewline
WBC & -0.054 & 0.057 & 0.897 & 0.344 & 0.947 & 0.846 -
1.060\tabularnewline
Hemoglobin & 0.007 & 0.011 & 0.386 & 0.534 & 1.007 & 0.986 -
1.028\tabularnewline
Platelet & -0.001 & 0.002 & 0.281 & 0.596 & 0.999 & 0.995 -
1.003\tabularnewline
BUN & 0.044 & 0.036 & 1.536 & 0.215 & 1.045 & 0.975 -
1.120\tabularnewline
Cr & -0.003 & 0.004 & 0.784 & 0.376 & 0.997 & 0.989 -
1.004\tabularnewline
UA & 0.001 & 0.001 & 0.318 & 0.573 & 1.001 & 0.998 -
1.004\tabularnewline
Albumin & -0.069 & 0.037 & 3.427 & 0.064 & 0.933 & 0.868 -
1.004\tabularnewline
HDL & -0.475 & 0.627 & 0.575 & 0.448 & 0.622 & 0.182 -
2.124\tabularnewline
eGFR & -0.008 & 0.011 & 0.550 & 0.458 & 0.992 & 0.972 -
1.013\tabularnewline
D-dimer & 0.368 & 0.184 & 4.003 & 0.045 & 1.445 & 1.008 -
2.071\tabularnewline
CRP & -0.002 & 0.003 & 0.348 & 0.555 & 0.998 & 0.993 -
1.004\tabularnewline
ESR & 0.006 & 0.008 & 0.656 & 0.418 & 1.006 & 0.991 -
1.022\tabularnewline
SII & 1.789 & 0.727 & 5.621 & 0.018 & 1.776 & 1.109 -
3.065\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 3 Multivariate Cox regression analysis for death from
cardiovascular causes.}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
Variables & \emph{B} & \emph{SE} & \emph{Wald} & \emph{P} & \emph{HR} &
\emph{95\% CI}\tabularnewline
\midrule
\endhead
Age & 0.016 & 0.020 & 0.619 & 0.432 & 1.016 & 0.977 -
1.056\tabularnewline
Diabetes mellitus & 0.382 & 0.430 & 0.789 & 0.374 & 1.466 & 0.631 -
3.407\tabularnewline
Heart rate & -0.004 & 0.009 & 0.200 & 0.655 & 0.996 & 0.978 -
1.014\tabularnewline
LAD & 0.023 & 0.019 & 1.419 & 0.234 & 1.023 & 0.986 -
1.062\tabularnewline
LVEF & -0.042 & 0.016 & 7.041 & 0.008 & 0.959 & 0.930 -
0.989\tabularnewline
WBC & -0.052 & 0.070 & 0.556 & 0.456 & 0.949 & 0.828 -
1.088\tabularnewline
Hemoglobin & 0.003 & 0.013 & 0.041 & 0.839 & 1.003 & 0.978 -
1.028\tabularnewline
Platelet & -0.001 & 0.003 & 0.122 & 0.727 & 0.999 & 0.994 -
1.004\tabularnewline
BUN & 0.059 & 0.040 & 2.119 & 0.145 & 1.061 & 0.980 -
1.148\tabularnewline
Cr & -0.005 & 0.005 & 1.260 & 0.262 & 0.995 & 0.986 -
1.004\tabularnewline
UA & 0.002 & 0.002 & 1.240 & 0.266 & 1.002 & 0.999 -
1.005\tabularnewline
Albumin & -0.092 & 0.045 & 4.124 & 0.042 & 0.912 & 0.835 -
0.997\tabularnewline
HDL & 0.023 & 0.776 & 0.001 & 0.977 & 1.023 & 0.224 -
4.681\tabularnewline
eGFR & -0.001 & 0.013 & 0.004 & 0.950 & 0.999 & 0.974 -
1.025\tabularnewline
D-dimer & 0.106 & 0.302 & 0.124 & 0.725 & 1.112 & 0.615 -
2.010\tabularnewline
CRP & -0.001 & 0.003 & 0.169 & 0.681 & 0.999 & 0.992 -
1.005\tabularnewline
ESR & 0.006 & 0.009 & 0.410 & 0.522 & 1.006 & 0.988 -
1.024\tabularnewline
SII & 2.147 & 0.962 & 4.996 & 0.025 & 1.512 & 1.011 -
3.742\tabularnewline
\bottomrule
\end{longtable}

\textbf{Hosted file}

\verb`Table 1.docx`  available at \url{https://authorea.com/users/733001/articles/710988-prognostic-value-of-systemic-immune-inflammation-index-sii-as-a-novel-marker-in-patients-with-atrial-fibrillation}

\textbf{Hosted file}

\verb`Table 2.docx`  available at \url{https://authorea.com/users/733001/articles/710988-prognostic-value-of-systemic-immune-inflammation-index-sii-as-a-novel-marker-in-patients-with-atrial-fibrillation}

\textbf{Hosted file}

\verb`Table 3.docx`  available at \url{https://authorea.com/users/733001/articles/710988-prognostic-value-of-systemic-immune-inflammation-index-sii-as-a-novel-marker-in-patients-with-atrial-fibrillation}\selectlanguage{english}
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\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}

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