Accepted Manuscript Higher serum triglyceride to high-density lipoprotein cholesterol ratio was associated with increased cardiovascular mortality in female patients on peritoneal dialysis Haishan Wu, Liping Xiong, Qingdong Xu, Juan Wu, Rong Huang, Qunying Guo, Haiping Mao, Xueqing Yu, Xiao Yang, MD, PhD PII:
S0939-4753(15)00128-3
DOI:
10.1016/j.numecd.2015.05.006
Reference:
NUMECD 1446
To appear in:
Nutrition, Metabolism and Cardiovascular Diseases
Received Date: 22 January 2015 Revised Date:
11 May 2015
Accepted Date: 12 May 2015
Please cite this article as: Wu H, Xiong L, Xu Q, Wu J, Huang R, Guo Q, Mao H, Yu X, Yang X, Higher serum triglyceride to high-density lipoprotein cholesterol ratio was associated with increased cardiovascular mortality in female patients on peritoneal dialysis, Nutrition, Metabolism and Cardiovascular Diseases (2015), doi: 10.1016/j.numecd.2015.05.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Higher serum triglyceride to high-density lipoprotein cholesterol ratio was associated with increased cardiovascular mortality in female patients on peritoneal dialysis
RI PT
Haishan Wu1,2*, Liping Xiong1,2*, Qingdong Xu1,2,Juan Wu1,2, Rong Huang1,2,
SC
Qunying Guo1,2, Haiping Mao1,2, Xueqing Yu1,2 , Xiao Yang1,2#
1.Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University.
M AN U
2. Key Laboratory of Nephrology, Ministry of Health, Guangdong China.
*Haishan Wu and Liping Xiong contributed equally to this study.
TE D
#Corresponding author: Xiao Yang, MD, PhD Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th,
EP
Zhongshan Road II, Guangzhou, 510080, China.
AC C
Email: [email protected]
ACCEPTED MANUSCRIPT Abstract Background and Aims: High serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been found to be an independent predictor for
RI PT
cardiovascular events in general population. We aimed to evaluate whether a high TG/HDL-C ratio was associated with an increased risk of mortality in continuous
SC
ambulatory peritoneal dialysis (CAPD) patients.
Methods and Results: In this single center retrospective cohort study, 1170 incident
M AN U
peritoneal dialysis (PD) patients from 1 January 2007 to 31 December 2011 were recruited and followed up until December 31, 2013. Mean age was 47.4±15.2 years and 24.7% were diabetic. During a median of 34.5-month follow-up period, 213 (18.2%) patients died, 121 (56.8%) caused by cardiovascular disease (CVD). The
TE D
serum median TG/HDL-C ratio at baseline was 2.57 (range: 0.06-39.39). On multivariate Cox regression analysis, the highest quartile of TG/HDL-C ratio (≥4.19)
EP
was associated with increased risk of all-cause mortality (HR 1.98, 95%CI, 1.17-3.36;
AC C
P=0.011) and CVD mortality (HR 2.28, 95%CI, 1.16-4.47; P=0.017). For female patients, each 1-unit higher baseline TG/HDL-C was associated with 13% (95%CI 1.06-1.22; P=0.001) increased risk of CVD mortality, while for male patients, such association was not observed (HR 1.00, 95%CI 0.92-1.08; P=0.977). Conclusions. Higher serum TG/HDL-C ratio was associated with increased risk of all-cause and CVD mortality in PD patients. Moreover, the increased risk of CVD mortality was significant higher in female than male PD patients.
ACCEPTED MANUSCRIPT Key words: Triglycerides to high-density lipoprotein cholesterol (TG/HDL-C ratio);
AC C
EP
TE D
M AN U
SC
RI PT
Cardiovascular; Mortality; Peritoneal dialysis.
ACCEPTED MANUSCRIPT Introduction Both elevated serum triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C) are well recognized as risk factors of increased cardiovascular
RI PT
disease (CVD) [1]. Recently, it was found that a greater predictive power of detecting the risk for CVD by combining high TG and low HDL-C in a single marker than
SC
individual lipids [2]. Accumulated evidence indicated that the TG/HDL-C ratio is an independent predictor of all-cause mortality [3] and major cardiovascular events [4],
M AN U
and fatal or nonfatal stoke [5] among healthy individuals, patients received coronary angiography therapy and patients with stroke history.
Disturbances of lipid transport and metabolism are common complications of peritoneal dialysis (PD)[6]. The hallmark dyslipidemias in PD population are
TE D
hypertriglyceridemia and low serum HDL-C levels [7]. Factors contributing to this phenomenon may include glucose absorption from dialysis fluid which results in
EP
increased insulin levels and enhance synthesis of TG in the liver, protein and
AC C
lipoprotein loss into the dialysis fluid stimulating hepatic very low-density lipoprotein (VLDL) synthesis, and preferential losing of smaller “protective” HDL molecules [8-9]. However, there is a paucity of data on whether TG/HDL-C ratio is an independent predictor of mortality in PD patients. In this study, we try to test the hypothesis that higher TG/HDL-C ratio are associated independently with higher risks of all-cause and CVD mortality in PD patients. Methods
ACCEPTED MANUSCRIPT Participants and study Protocol This was a retrospective observational cohort study. All incident PD patients at the First Affiliated Hospital, Sun Yat-sen University（SYSU） were recruited from
RI PT
January 1, 2007 to December 31, 2011. Inclusion criteria were aged ≥18 years old and received at least three consecutive months of CAPD therapy. Patients who were
SC
catheterized in other hospitals, transferred from permanent hemodialysis or failed renal transplantation or did not have baseline TG/HDL ratio were excluded.
M AN U
Conventional PD solutions (Dianeal 1.5%, 2.5% or 4.25% dextrose; Baxter Healthcare, Guangzhou, China), Y-sets and twin-bag systems were utilized in almost all of the CAPD patients. The study was conducted in compliance with the ethical principles
of
the
Helsinki
Declaration
TE D
(http://www.wma.net/en/30publications/10policies/b3/index.html) and approved by the Human Ethics Committees of SYSU. Written informed consent was obtained from
EP
all participants before study entry.
AC C
All patients were followed up until death, transfer to hemodialysis, kidney transplantation, transfer to other center, or censoring on December 31, 2013. Baseline data at the first 1-3 months after the initiation of CAPD were collected, including demographic [age (years), gender, cause of end-stage renal disease (ESRD), major comorbidities (CVD, hypertension, diabetes), body mass index (BMI)(kg/m2)] and
biochemical
data
[hemoglobin,
serum
albumin,
serum
creatinine,
albumin-corrected calcium, serum phosphorus, total cholesterol, TG, HDL-C,
ACCEPTED MANUSCRIPT low-density lipoprotein cholesterol (LDL-C)], which were measured in the center laboratory of the First Affiliated Hospital of SYSU. The comorbidity score was determined according to the Charlson Comorbidity Index (CCI) [10]. Glomerular
RI PT
filtration rate (GFR) was measured as the mean of urea and creatinine clearance, calculated from 24-hour urine collections and indexed for body surface area. We
SC
adapted the guideline of International Society for Peritoneal Dialysis (ISPD) to evaluate and manage patients for the dyslipidemia. Patients were required to return to
M AN U
our center at least quarterly for an overall medical evaluation or interviewed by telephone monthly with primary nurses for assessing general conditions and concomitant medications. Quarterly visits and monthly telephone contacts were
Study definitions
TE D
performed for clinical purposes not specifically for this study.
The primary outcomes were all-cause and CVD mortality. Cardiovascular events
EP
contributing to CVD mortality included acute myocardial infarction, atherosclerotic
AC C
heart disease, cardiomyopathy, cardiac arrhythmia, cardiac arrest, congestive heart failure, cerebrovascular accident, ischemic brain damage, anoxic encephalopathy, and peripheral vascular disease, determined by the PD follow-up panel composed of PD primary nurses and professors. CVD was defined as history of angina pectoris, myocardial infarction, angioplasty, coronary artery bypass, heart failure, or stroke. Patients who reported current use of insulin or oral hypoglycemic agent and/or who had a clinical diagnosis of type 1 or type 2 diabetic mellitus were considered to have
ACCEPTED MANUSCRIPT diabetes mellitus (DM). Hypertension was recorded if the patient took antihypertensive drugs or had 2 separate blood pressure measurements≥140/90 mmHg.
RI PT
Statistical Analysis TG/HDL-C was calculated as TG divided by HDL-C (expressed in mg/dl).
SC
Non-HDL-C was calculated by subtraction of HDL-C from total cholesterol, and analyzed as a continuous variable. Participants were stratified into quartiles (Qs) of
M AN U
TG/HDL ratio: Q1
S0939-4753(15)00128-3
DOI:
10.1016/j.numecd.2015.05.006
Reference:
NUMECD 1446
To appear in:
Nutrition, Metabolism and Cardiovascular Diseases
Received Date: 22 January 2015 Revised Date:
11 May 2015
Accepted Date: 12 May 2015
Please cite this article as: Wu H, Xiong L, Xu Q, Wu J, Huang R, Guo Q, Mao H, Yu X, Yang X, Higher serum triglyceride to high-density lipoprotein cholesterol ratio was associated with increased cardiovascular mortality in female patients on peritoneal dialysis, Nutrition, Metabolism and Cardiovascular Diseases (2015), doi: 10.1016/j.numecd.2015.05.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Higher serum triglyceride to high-density lipoprotein cholesterol ratio was associated with increased cardiovascular mortality in female patients on peritoneal dialysis
RI PT
Haishan Wu1,2*, Liping Xiong1,2*, Qingdong Xu1,2,Juan Wu1,2, Rong Huang1,2,
SC
Qunying Guo1,2, Haiping Mao1,2, Xueqing Yu1,2 , Xiao Yang1,2#
1.Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University.
M AN U
2. Key Laboratory of Nephrology, Ministry of Health, Guangdong China.
*Haishan Wu and Liping Xiong contributed equally to this study.
TE D
#Corresponding author: Xiao Yang, MD, PhD Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th,
EP
Zhongshan Road II, Guangzhou, 510080, China.
AC C
Email: [email protected]
ACCEPTED MANUSCRIPT Abstract Background and Aims: High serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been found to be an independent predictor for
RI PT
cardiovascular events in general population. We aimed to evaluate whether a high TG/HDL-C ratio was associated with an increased risk of mortality in continuous
SC
ambulatory peritoneal dialysis (CAPD) patients.
Methods and Results: In this single center retrospective cohort study, 1170 incident
M AN U
peritoneal dialysis (PD) patients from 1 January 2007 to 31 December 2011 were recruited and followed up until December 31, 2013. Mean age was 47.4±15.2 years and 24.7% were diabetic. During a median of 34.5-month follow-up period, 213 (18.2%) patients died, 121 (56.8%) caused by cardiovascular disease (CVD). The
TE D
serum median TG/HDL-C ratio at baseline was 2.57 (range: 0.06-39.39). On multivariate Cox regression analysis, the highest quartile of TG/HDL-C ratio (≥4.19)
EP
was associated with increased risk of all-cause mortality (HR 1.98, 95%CI, 1.17-3.36;
AC C
P=0.011) and CVD mortality (HR 2.28, 95%CI, 1.16-4.47; P=0.017). For female patients, each 1-unit higher baseline TG/HDL-C was associated with 13% (95%CI 1.06-1.22; P=0.001) increased risk of CVD mortality, while for male patients, such association was not observed (HR 1.00, 95%CI 0.92-1.08; P=0.977). Conclusions. Higher serum TG/HDL-C ratio was associated with increased risk of all-cause and CVD mortality in PD patients. Moreover, the increased risk of CVD mortality was significant higher in female than male PD patients.
ACCEPTED MANUSCRIPT Key words: Triglycerides to high-density lipoprotein cholesterol (TG/HDL-C ratio);
AC C
EP
TE D
M AN U
SC
RI PT
Cardiovascular; Mortality; Peritoneal dialysis.
ACCEPTED MANUSCRIPT Introduction Both elevated serum triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C) are well recognized as risk factors of increased cardiovascular
RI PT
disease (CVD) [1]. Recently, it was found that a greater predictive power of detecting the risk for CVD by combining high TG and low HDL-C in a single marker than
SC
individual lipids [2]. Accumulated evidence indicated that the TG/HDL-C ratio is an independent predictor of all-cause mortality [3] and major cardiovascular events [4],
M AN U
and fatal or nonfatal stoke [5] among healthy individuals, patients received coronary angiography therapy and patients with stroke history.
Disturbances of lipid transport and metabolism are common complications of peritoneal dialysis (PD)[6]. The hallmark dyslipidemias in PD population are
TE D
hypertriglyceridemia and low serum HDL-C levels [7]. Factors contributing to this phenomenon may include glucose absorption from dialysis fluid which results in
EP
increased insulin levels and enhance synthesis of TG in the liver, protein and
AC C
lipoprotein loss into the dialysis fluid stimulating hepatic very low-density lipoprotein (VLDL) synthesis, and preferential losing of smaller “protective” HDL molecules [8-9]. However, there is a paucity of data on whether TG/HDL-C ratio is an independent predictor of mortality in PD patients. In this study, we try to test the hypothesis that higher TG/HDL-C ratio are associated independently with higher risks of all-cause and CVD mortality in PD patients. Methods
ACCEPTED MANUSCRIPT Participants and study Protocol This was a retrospective observational cohort study. All incident PD patients at the First Affiliated Hospital, Sun Yat-sen University（SYSU） were recruited from
RI PT
January 1, 2007 to December 31, 2011. Inclusion criteria were aged ≥18 years old and received at least three consecutive months of CAPD therapy. Patients who were
SC
catheterized in other hospitals, transferred from permanent hemodialysis or failed renal transplantation or did not have baseline TG/HDL ratio were excluded.
M AN U
Conventional PD solutions (Dianeal 1.5%, 2.5% or 4.25% dextrose; Baxter Healthcare, Guangzhou, China), Y-sets and twin-bag systems were utilized in almost all of the CAPD patients. The study was conducted in compliance with the ethical principles
of
the
Helsinki
Declaration
TE D
(http://www.wma.net/en/30publications/10policies/b3/index.html) and approved by the Human Ethics Committees of SYSU. Written informed consent was obtained from
EP
all participants before study entry.
AC C
All patients were followed up until death, transfer to hemodialysis, kidney transplantation, transfer to other center, or censoring on December 31, 2013. Baseline data at the first 1-3 months after the initiation of CAPD were collected, including demographic [age (years), gender, cause of end-stage renal disease (ESRD), major comorbidities (CVD, hypertension, diabetes), body mass index (BMI)(kg/m2)] and
biochemical
data
[hemoglobin,
serum
albumin,
serum
creatinine,
albumin-corrected calcium, serum phosphorus, total cholesterol, TG, HDL-C,
ACCEPTED MANUSCRIPT low-density lipoprotein cholesterol (LDL-C)], which were measured in the center laboratory of the First Affiliated Hospital of SYSU. The comorbidity score was determined according to the Charlson Comorbidity Index (CCI) [10]. Glomerular
RI PT
filtration rate (GFR) was measured as the mean of urea and creatinine clearance, calculated from 24-hour urine collections and indexed for body surface area. We
SC
adapted the guideline of International Society for Peritoneal Dialysis (ISPD) to evaluate and manage patients for the dyslipidemia. Patients were required to return to
M AN U
our center at least quarterly for an overall medical evaluation or interviewed by telephone monthly with primary nurses for assessing general conditions and concomitant medications. Quarterly visits and monthly telephone contacts were
Study definitions
TE D
performed for clinical purposes not specifically for this study.
The primary outcomes were all-cause and CVD mortality. Cardiovascular events
EP
contributing to CVD mortality included acute myocardial infarction, atherosclerotic
AC C
heart disease, cardiomyopathy, cardiac arrhythmia, cardiac arrest, congestive heart failure, cerebrovascular accident, ischemic brain damage, anoxic encephalopathy, and peripheral vascular disease, determined by the PD follow-up panel composed of PD primary nurses and professors. CVD was defined as history of angina pectoris, myocardial infarction, angioplasty, coronary artery bypass, heart failure, or stroke. Patients who reported current use of insulin or oral hypoglycemic agent and/or who had a clinical diagnosis of type 1 or type 2 diabetic mellitus were considered to have
ACCEPTED MANUSCRIPT diabetes mellitus (DM). Hypertension was recorded if the patient took antihypertensive drugs or had 2 separate blood pressure measurements≥140/90 mmHg.
RI PT
Statistical Analysis TG/HDL-C was calculated as TG divided by HDL-C (expressed in mg/dl).
SC
Non-HDL-C was calculated by subtraction of HDL-C from total cholesterol, and analyzed as a continuous variable. Participants were stratified into quartiles (Qs) of
M AN U
TG/HDL ratio: Q1
