Heart, Lung and Circulation (2020) 29, 414–421 ORIGINAL ARTICLE

1443-9506/04/$36.00
https://doi.org/10.1016/j.hlc.2019.03.019

Elevated Triglycerides to High-Density

Lipoprotein Cholesterol (TG/HDL-C) Ratio
Predicts Long-Term Mortality in
High-Risk Patients
Rohullah Sultani, BMedSci, MD a,e*, David C. Tong, MBBS a,b,
Matthew Peverelle, MD a,e, Yun Suk Lee, MD a,e, Arul Baradi, MBBS c,d,
Andrew M. Wilson, MBBS, PhD a,d
a
Department of Cardiology, St. Vincent’s Hospital, Melbourne, Vic, Australia
b
Department of Cardiology, Peninsula Health, Melbourne, Vic, Australia
c
Department of Cardiology, Werribee Mercy Hospital, Melbourne, Vic, Australia
d
Department of Cardiology, St. Vincent’s Private Hospital, Melbourne, Vic, Australia
e
University of Melbourne, Department of Medicine, St. Vincent’s Hospital, Melbourne, Vic, Australia

Received 17 April 2018; received in revised form 25 March 2019; accepted 31 March 2019; online published-ahead-of-print 16 April 2019

Background Elevated triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been utilised as a
predictor of outcomes in patients with adverse cardiometabolic risk profiles. In this study, we examined
the prognostic value of elevated TG/HDL-C level in an Australian population of patients with high clinical
suspicion of coronary artery disease (CAD) presenting for coronary angiography.

Methods Follow-up data was collected for 482 patients who underwent coronary angiography in a prospective cohort
study. The primary endpoint was all-cause mortality and the secondary endpoint was a major adverse
cardiac event (MACE). Patients were stratified into two groups according to their baseline TG/HDL-C ratio,
using a TG/HDL-C ratio cut point of 2.5.
Results The mean follow-up period was 5.1  1.2 years, with 49 all-cause deaths. Coronary artery disease on
coronary angiography was more prevalent in patients with TG/HDL-C ratio 2.5 (83.6% vs. 69.4%,
p = 0.03). On the Kaplan-Meier analysis, patients with TG/HDL-C ratio 2.5 had worse long-term prognosis
(p = 0.04). On multivariate Cox regression adjusting for established cardiovascular risk factors and CAD on
coronary angiography, TG/HDL-C ratio 2.5 was an independent predictor of long-term all-cause mor-
tality (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.04–4.20, p = 0.04). On multivariate logistic
regression adjusting for known cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C
ratio 2.5 was strongly associated with an increased risk of long-term MACE (odds ratio [OR] 2.72, 95% CI
1.42–5.20, p = 0.002).

Conclusions Elevated TG/HDL-C ratio is an independent predictor of long-term all-cause mortality and is strongly
associated with an increased risk of MACE.
Keywords Triglycerides to high-density lipoprotein cholesterol ratio  Coronary artery disease  All-cause
mortality  Major adverse cardiovascular events  Coronary  Angiography

*Corresponding author at: Goulburn Valley Health, Graham Street, Shepparton, 3630, Victoria, Australia. Fax: +61 3 8845 7073., Email: rohullahsultani59@g
mail.com
© 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
Published by Elsevier B.V. All rights reserved.

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Triglycerides to High-Density Lipoprotein Ratio Cholesterol 415

collected from the venepuncture performed before coronary

Introduction angiography. Total cholesterol (TC) (mmol/L), TG (mmol/
Cardiovascular disease (CVD) is the leading cause of mor- L), low-density lipoprotein cholesterol (LDL-C) (mmol/L)
tality and morbidity globally. The clinical utility of hyper- and HDL-C (mmol/L) levels were measured and recorded.
triglyceridaemia to independently predict the development Baseline TG/HDL-C ratio was calculated as TG level (mmol/
of primary coronary artery disease (CAD) has been previ- L) divided by HDL-C (mmol/L) levels for all subjects with
ously established [1,2]. Patients with hypertriglyceridaemia available TG (mmol/L) and HDL-C (mmol/L) levels. Sub-
undergoing coronary angiography have more severe CAD jects were grouped according to their baseline TG/HDL-C
[3]. Similarly, low high-density lipoprotein cholesterol (HDL- ratio using the TG/HDL-C ratio cut point of 2.5. Coronary
C) level is strongly associated with CVD development and angiography was performed on all patients and reviewed
CVD-related mortality [4]. Moreover, elevated plasma tri- independently by two consultant interventional cardiolo-
glycerides (TG) to HDL-C (TG/HDL-C) ratio has been stud- gists. Coronary artery disease was defined by >50% luminal
ied as a surrogate biomarker to identify individuals with stenosis by visual assessment in at least one epicardial vessel
adverse cardiometabolic risk profiles [5]. of >2 mm luminal diameter on coronary angiography or
Elevated TG/HDL-C ratio has been shown to be associated previous PCI for a stenotic coronary artery.
with adverse long-term cardiovascular outcomes and all- Follow-up data was collected using a standard and struc-
cause mortality in high-risk populations presenting for clini- tured telephone questionnaire conducted between March
cally indicated coronary angiography [6–8]. However, these and June 2016. Data was obtained by contacting the patients,
studies were limited by gender-specific populations or those their family members and their primary care physicians.
presenting with acute coronary syndromes [6–8]. Our study From a total of 522 patients recruited in the study, 40 patients
aims to evaluate the prognostic utility of elevated TG/HDL- were lost to follow-up either because they had deceased
C levels in an Australian population of patients with a high during the study period or could not be reached due to a
clinical suspicion of CAD presenting for coronary change in their contact details.
angiography. The primary outcome of this study was death from all-
cause mortality. The secondary outcomes were MACE. The
secondary outcomes were evaluated by assessing the rela-
Methods tionship between elevated TG/HDL-C ratio and the first
MACE event. A MACE was defined as cardiac death, non-
Study Population fatal myocardial infarction, stroke or coronary revascularisa-
The study population was identified from the Biomarkers of tion. Cardiac death was defined as death due to either acute
Atherosclerosis, Vascular and Endothelial Dysfunction in myocardial infarction (AMI), heart failure or cardiac arrhyth-
Heart Disease (BRAVEHEART) Study. This was a single- mias. All responses from the participants were cross-checked
centre, prospective cohort study that included patients pre- with the relevant hospital databases to validate the exact
senting for coronary angiography/percutaneous coronary diagnosis and date of the cardiovascular event. Participants
intervention (PCI) between October 2009 and May 2013 at who deceased during the follow-up period were confirmed
St Vincent’s Hospital Melbourne, Australia. Patients with through relevant hospital records and death certificates. This
either recent or untreated malignancies, systemic inflamma- study was approved by the Human Research Ethics Com-
tory conditions, acute or chronic infections and those with mittee at St Vincent’s Hospital, Melbourne, in accordance
serum creatinine levels >160 mmol/L were excluded from with the National Health and Medical Research Council
the study cohort. guidelines. Patients were invited to participate and informed
consent was obtained before their registration into the
Study Protocol BRAVEHEART study cohort.
Baseline demographic and clinical data were collected from
patient’s medical records on admission. Obesity was defined Statistical Analysis
as a body mass index (BMI) of 30 kg/m2, calculated by For descriptive purposes, means  standard error of the
dividing a patient’s weight in kilograms (kg) by the square means (SE) were used to compare for the demographic char-
of the patient’s height in metres (m). Diabetes was defined as a acteristics, cardiovascular risk factors, baseline lipid levels,
current use of anti-diabetic medications or previous diagnosis. current medication use and outcomes data between the two
Hypertension was defined as a current use of anti-hyperten- groups. Two-samples independent T-test and Chi-Square
sive medications or previous diagnosis. Hypercholesterolae- tests were used to investigate for any statistically significant
mia was defined as a current use of cholesterol-lowering difference between the baseline characteristics of the two
medications or previous diagnosis. Smoker was defined as groups. Survival analysis was performed using the Kaplan
either active smoking or having a previous smoking history. Meier survival curves in followed up patients from the time
Patients were fasted for a minimum of 8 hours prior to of enrolment until the time of their death for the deceased,
planned or scheduled coronary angiography. Patients with and until the time of follow-up for the survivors. Multivariate
ST-elevation myocardial infarction (STEMI) who underwent Cox regression models were constructed to evaluate the
primary PCI were not fasted. A baseline blood sample was prognostic utility of elevated TG/HDL-C ratio in predicting

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416 R. Sultani et al.

long-term all-cause mortality. The models were adjusted for 69% were males, 31% were females, 74.7% had hypertension,
known cardiovascular risk factors including age, gender, 80.6% had hypercholesterolaemia, 29.6% had diabetes, 32.9%
hypertension, hypercholesterolaemia, diabetes, smoking had a history of previous AMI and 69.4% had a history of
and CAD on coronary angiography. smoking (20.1% active smokers; 49.25% ex-smokers). 70.8% of
After adjusting for conventional cardiovascular risk factors the patients had CAD that was either diagnosed at angiogra-
stated above and CAD on coronary angiography, multivari- phy or had previous PCI for stenotic coronary artery. Baseline
ate logistic regression models were constructed to assess the TG/HDL-C ratio ranged from 0.21 to 7.73 in the study cohort.
relationship between elevated TG/HDL-C levels and the first Table 1 shows the baseline characteristics between two groups
MACE outcome. The MACE outcome refers to the occur- of patients, using TG/HDL-C ratio cut point of 2.5.
rence of the first of any of the aforementioned MACE events; The proportion of patients with diabetes, hypertension and
the time to this first event was recorded. The proportional hypercholesterolaemia at baseline, were not significantly
hazards assumption of the predictor variable hazard ratios different between the two groups. Furthermore, the prescrip-
was tested and found to be met. P-values of 0.05 was set for tion of cardiac-modifying medications was similar between
statistical significance. All statistical analysis was conducted the two groups. TC (mmol/L) (4.68  0.17 vs. 4.19 0.05, p
using STATA SE (64-bit) software, version 12 (StataCorp < 0.001) and TG (mmol/L) (3.11  0.14 vs. 1.37  0.02, p
LLC, College Station, TX, USA). < 0.001) levels were higher, whilst HDL-C (mmol/L)
(0.87  0.02 vs. 1.15  0.01, p < 0.001) level was lower in the
group with TG/HDL-C ratio 2.5 compared with the group
Results with TG/HDL-C ratio <2.5. Mean TG/HDL-C ratio was
significantly higher in the group with TG/HDL-C ratio
Baseline Characteristics 2.5 (3.62  0.16 vs. 1.27  0.03, p < 0.001). A significantly
A total of 482 patients were included in the study after 40 larger proportion of patients with TG/HDL-C ratio 2.5
patients were lost during follow-up. The mean follow-up had CAD on coronary angiography, compared to patients
period was 5.1  1.2 years. The mean age was 63.4  11.0 years, with TG/HDL-C ratio <2.5 (83.64% vs. 69.40%, p = 0.03)

Table 1 Baseline characteristics according to the TG/HDL-C ratio.

Baseline Characteristics TG/HDL-C ratio TG/HDL-C ratio P-value

<2.5 (n = 427) 2.5 (n = 55)

Age (years) 63.66  10.94 61.16  11.44 0.12

Body mass index (kg/m2) 29.92  0.36 28.21  0.78 0.11
Male (%) 66.97 83.64 0.01
Diabetes (%) 29.00 34.00 0.47
Hypertension (%) 74.50 76.00 0.82
Hypercholesterolaemia (%) 79.70 88.00 0.16
Smoking (%) 68.43 70.37 0.77
Acute coronary syndromes (%) 37.00 41.82 0.49
Coronary artery disease (%) 69.40 83.64 0.03
Medications
Angiotensin-Converting Enzyme Inhibitor (%) 40.87 33.33 0.29
Angiotensin receptor blocker (%) 23.67 20.37 0.56
Beta blockers (%) 49.40 55.56 0.66
Statins (%) 71.46 72.22 0.91
Aspirin (%) 76.01 75.93 0.98
Clopidogrel (%) 33.82 38.89 0.46
Lipid measures
Total cholesterol level (mmol/L) 4.19  0.05 4.68  0.17 <0.001
Triglycerides level (mmol/L) 1.37  0.02 3.11  0.14 <0.001
Low-density lipoprotein cholesterol level (mmol/L) 2.41  0.04 2.49  0.16 0.58
High-density lipoprotein cholesterol level (mmol/L) 1.15  0.01 0.87  0.02 <0.001
TG/HDL-C (Triglycerides to high-density lipoprotein cholesterol) ratio 1.27  0.03 3.62  0.16 <0.001

Abbreviation: TG/HDL-C; triglycerides to high density lipoprotein cholesterol ratio.

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Triglycerides to High-Density Lipoprotein Ratio Cholesterol 417

Table 2 MACE and all-cause mortality events between the two groups.

Variables TG/HDL-C ratio TG/HDL-C ratio P-value

<2.5 (n = 427) 2.5 (n = 55)

All-cause mortality 39 (9.1%) 10 (18.2%) 0.04

MACE 131 (30.7%) 29 (52.7%) 0.001
Cardiac death 29 (6.8%) 8 (14.5%) 0.04
Non-fatal AMI 36 (8.4%) 12 (21.8%) <0.01
Stroke 18 (4.2%) 3 (5.5%) 0.67
Unplanned revascularisation 48 (11.2%) 6 (10.9%) 0.94

Abbreviations; MACE, major adverse cardiovascular events; AMI, acute myocardial infarction; TG/HDL-C, triglycerides to high density lipoprotein cholesterol
ratio.

Survival Analysis diabetics and obese patients were excluded from the analysis
The mean follow-up period for this study was 5.1  1.2 years. in the multivariate Cox-regression model (HR 2.07, p = 0.04),
There was a total of 39 (9.1%) deaths in group 1 (TG/HDL-C suggesting that TG-HDL-C ratio 2.5 is an independent
ratio <2.5) and 10 (18.2%) deaths in group 2 (TG/HDL-C predictor of all-cause mortality (Table 3).
ratio 2.5) (Table 2). The difference in the number of Furthermore, patients with TG/HDL-C ratio 2.5 were at
deceased between the two groups was statistically significant a significantly higher risk of suffering from MACE (HR 2.07
(p = 0.04) (Table 2). Figure 1 demonstrates the Kaplan-Meier [95% CI 1.32–3.24], p = 0.001) cardiac death (HR 2.24 [95% CI
curves for freedom from all-cause mortality across the TG/ 1.03–4.91], p = 0.04) and non-fatal AMI (HR 6.22 [95% CI 3.20–
HDL-C ratio. The Kaplan-Meier analysis (Figure 1) demon- 12.07], p < 0.001) compared to patients with TG/HDL-C ratio
strated worse long-term prognosis in patients with TG/ <2.5 (Table 3). In both groups, irrespective of their baseline
HDL-C 2.5 (log rank, p = 0.04). TG/HDL-C levels, the majority died from AMI-related death
Multivariate Cox regression models (Table 3) were con- (80% in TG/HDL-C ratio 2.5 group vs. 59% in TG/HDL-C
structed to further evaluate the association between elevated ratio <2.5 group) followed by cancer and heart failure
TG/HDL-C levels and all-cause mortality. After adjusting for (Table 4).
known cardiovascular risk factors and CAD on coronary
angiography, patients with TG/HDL-C ratio 2.5 had a
Major Adverse Cardiovascular Events
two-fold increased risk of all-cause mortality compared to Over a mean follow-up period of 5.1  1.2 years, there were
patients with TG/HDL-C ratio <2.5 (HR 2.10, p = 0.04). All- 160 major cardiovascular events; 113 (30.7%) events in the
cause mortality remained significantly elevated when group with TG/HDL-C ratio <2.5 and 29 (52.7%) events in

Figure 1 Kaplan-Meier curves showing freedom from all-cause mortality according to the TG/HDL-C ratio.
Abbreviation: TG/HDL-C, triglycerides to high density lipoprotein cholesterol ratio

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418 R. Sultani et al.

Table 3 Hazard ratio for MACE and all-cause mortality Table 5 Predictors of MACE.
for TG/HDL-C ratio 2.5.
Variables Odds Ratio 95% CI P-value
Variables Hazard Ratio 95% CI P-value
TG/HDL-C 2.5* 2.72 1.42–5.20 0.002
All-cause mortality* 2.10 1.04–4.20 0.04 Gender 1.19 0.76–1.88 0.44
All-cause mortality# 2.07 1.02–4.13 0.04 Hypertension 1.04 0.63–1.72 0.88
MACE 2.07 1.32–3.24 0.001 Hypercholesterolaemia 1.21 0.68–2.15 0.51
Cardiac death 2.24 1.03–4.91 0.04 Smoking 0.95 0.61–1.48 0.82
Non-fatal AMI 6.22 3.20–12.07 <0.001 Diabetes 1.86 1.18–2.94 0.008
Stroke 1.29 0.38–4.39 0.68 CAD on coronary 2.98 1.70–5.23 <0.001
Unplanned 0.96 0.41–2.25 0.93 angiography
revascularisation
Abbreviations: MACE, major adverse cardiovascular events; TG/HDL-C,
Abbreviations: MACE, major adverse cardiovascular events; AMI, acute triglycerides to high density lipoprotein cholesterol ratio; CI, confidence
myocardial infarction; TG/HDL-C, triglycerides to high-density lipopro- interval; CAD, coronary artery disease.
tein cholesterol ratio; CI, confidence interval. *
Adjusted for gender, age, hypertension, hypercholesterolaemia, diabetes,
*
Adjusted for age, gender, diabetes, obesity, hypertension, hypercholester- smoking and CAD on coronary angiography.
olaemia, smoking and CAD on coronary angiography.
#
Adjusted for age, gender, hypertension, hypercholesterolaemia, smoking
and CAD on coronary angiography. presenting for clinically indicated coronary angiography.
This study found that, after adjusting for established cardio-
vascular risk factors and CAD on coronary angiography,
the group with TG/HDL-C ratio 2.5 (p = 0.001) (Table 2).
elevated TG/HDL-C ratio is an independent predictor of
When the incidence of the individual components of MACE
long-term all-cause mortality and is strongly associated with
was evaluated between the two groups, the proportion of
long-term risk of MACE in patients presenting for coronary
cardiac deaths (14.5% vs. 6.8%, p = 0.04) and non-fatal AMIs
angiography.
(21.8% vs 8.4%, p < 0.01) were significantly higher in the
The relationship between TG and HDL-C levels has been
group with TG/HDL-C 2.5 (Table 2).
previously described. Elevated levels of TG and low levels of
Multivariate and univariate logistic regression models
HDL-C contribute to chronic inflammation and predisposes
were constructed to assess the relationship between elevated
to the pathophysiology of atherosclerosis [9]. HDL-C exerts
TG/HDL-C ratio and first MACE outcome. After adjusting
its cardioprotective effects predominantly through its role in
for established cardiovascular risk factors and CAD at coro-
reverse cholesterol transport (RCT) that involves the removal
nary angiography, elevated TG/HDL-C ratio was indepen-
of cholesterols from peripheral cells including macrophages
dently associated with long-term MACE (OR 2.72 [95% CI
in the arterial walls and transporting them to the liver for
1.42–5.20], p = 0.002). Moreover, CAD on coronary angiogra-
recycling [10,11]. The process of RCT can happen through
phy (OR 2.98 [95% CI 1.70–5.23], p < 0.001) and diabetes (OR
two pathways [1]: hepatic uptake of cholesteryl ester (CE)
1.86 [95% CI 1.18–2.94], p = 0.008], were strongly correlated
from HDL particles that is mediated through the scavenger
with MACE (Table 5). This association remained significant
receptor class B type 1 (SR-B1) system [12] and [2] cholesteryl
in multivariate logistic regression modelling.
ester transfer protein (CETP) that catalyses the transfer of
cholesteryl ester from HDL particles to apoB-containing lip-
oproteins (LDL and very-low-density lipoprotein (VLDL)) in
Discussion exchange for TG [13]. The RCT pathways result in LDL and
The principle objective of this study was to investigate the VLDL particles that are TG-depleted and CE-enriched and
prognostic utility of elevated TG/HDL-C ratio in patients HDL particles that are TG-enriched and CE-depleted [12,13].

Table 4 Cause of death for deceased patients.

Cause of death

Heart Failure Stroke Cancer Bowel Obstruction Sepsis Total

5 (12.8%) 3 (7.7%) 6 (15.4%) 1 (2.6%) 1 (2.6%) 39 (100%)

0 (0.0%) 0 (0.0%) 2 (20%) 0 (0.0%) 0 (0.0%) 10 (100%)
5 (10.2%) 3 (6.1%) 8 (16.3%) 1 (2.0%) 1 (2.0%) 49 (100%)

Abbreviations: TG/HDL-C, triglycerides to high-density lipoprotein cholesterol ratio; AMI, acute myocardial infarction.

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Triglycerides to High-Density Lipoprotein Ratio Cholesterol 419

However, the larger VLDL particles pool in the context of independently predict the risk of myocardial infarction.
elevated TG level, result in greater CETP-mediated transfer TG/HDL-C ratio has been reported to be a strong predictor
of CE from HDL to VLDL in exchange for TG [14]. This of CAD and CVD development [32], and men with an ele-
CETP-mediated exchange is postulated to be the underlying vated TG/HDL-C ratio are at an increased risk of ischaemic
mechanism responsible for the inverse relationship between [33] and coronary [30] heart disease. Moreover, elevated TG/
HDL-C and TG levels [15,16]. In the setting of elevated TG HDL-C ratio has been shown to be an independent predictor
levels, this pathway ultimately results in smaller and denser of extensive atherosclerotic CAD [34] and is associated with
HDL particles that are TG-enriched and rapidly catabolised significant atherosclerotic coronary artery stenosis of 50%
resulting in lower HDL-C concentrations. Consequently, [35].
smaller and denser TG-enriched HDL particles attenuates Moreover, a recent study demonstrated that, after adjust-
its cardioprotective, antioxidative and anti-inflammatory ing for conventional cardiovascular risk factors, elevated
effects [9]. Hence, lower HDL-C concentrations in the setting TG/HDL-C ratio was associated with an increased risk of
of elevated TG level increases the risk of atherosclerotic MACE and all-cause mortality in ACS patients [7]. Vega et al.
plague formation. [8] and Bittner et al. [6] also previously showed that elevated
Elevated TG/HDL-C ratio has been previously investi- TG/HDL-C ratio is an independent predictor of CHD, CVD
gated as a novel biomarker of adverse cardiometabolic risk and all-cause mortality in men and major cardiovascular
profile. It has been increasingly recognised as a potential events and all-cause mortality in women, respectively. How-
surrogate biomarker to identify individuals with insulin ever, the limitations of these studies included recruitment of
resistance [17,18]. Insulin resistance is postulated to be the gender-specific or pre-selected high-risk ACS patients. Fur-
principle feature of metabolic syndrome, which acts as a thermore, these studies lacked information on the cause of
precursor for the development of diabetes mellitus [19], death that might underlie the mechanism linking the rela-
coronary heart disease [20] and CVD [21,22]. Furthermore, tionship between elevated TG/HDL-C ratio and all-cause
it is known that LDL particles become smaller and denser as mortality.
TG/HDL-C ratio increases [23]. Relatively smaller and In contrast, our large prospective cohort study included
denser LDL particle sizes are pro-atherogenic and are well characterised patients of both genders who presented
strongly correlated with the initiation and progression of for clinically indicated coronary angiography due to high
atherosclerotic coronary artery lesions [24,25]. clinical suspicion for CAD. Utilising Cox-proportional haz-
Moreover, De Giorgis et al. [26] reported that obese pre- ard modellings and adjusting for established cardiovascular
pubertal children had elevated TG/HDL-C ratios, which was risk factors including CAD on coronary angiography, our
significantly associated with early signs of arterial vascular study affirmed that raised TG/HDL-C ratio predicts long-
damage such as increased carotid intima-media thickness term all-cause mortality. This study also found that elevated
(CIMT). Elevated TG/HDL-C ratio has been postulated to TG/HDL-C levels are independently associated with higher
be utilised as an independent determinant of CIMT in ado- risk of long-term MACE, and that patients with elevated TG/
lescents with type-2 diabetes mellitus [27]. The atherogenic- HDL-C levels were at a significantly higher risk of cardiac
ity of raised TG/HDL-C ratio is due to the role of TG-rich death and non-fatal AMI.
lipoproteins that ultimately activates the proinflammatory In addition, a large proportion of patients were taking
signalling pathways which underlies the pathophysiology statins medication in our study. Given there was no signifi-
and development of coronary atherosclerotic lesions [9]. cant difference in the number of patients on statin therapy
Thus, elevated TG/HDL-C ratio denotes a pro-atherogenic between the two groups (Table 1), it would be reasonable to
state and is strongly correlated with the pathophysiology of assume that the therapeutic effect of statin on TG levels was
atherosclerotic lesion formation. similar in both groups. Furthermore, the Fenofibrate Inter-
Furthermore, elevated TG/HDL-C ratio is independently vention and Event Lowering in Diabetes (FIELD) study [36]
associated with a higher and more severe risk of atheroscle- demonstrated that long-term fenofibrate therapy did not
rotic CAD [28–30]. Yunke et al. [29] reported that the preva- significantly reduce cardiac mortality in diabetic patients.
lence of CAD was significantly higher in patients with Therefore, an elevated TG/HDL-C ratio may have significant
elevated TG/HDL-C levels and that raised TG/HDL-C levels prognostication in selected patient populations. A TG/HDL-C
was positively associated with the extent of the atheroscle- ratio 2.5 remained a strong independent predictor of all-cause
rotic coronary artery lesions. Hadaegh et al. [30] reported that mortality and was independently associated with a higher risk of
elevated TG/HDL-C levels is an independent predictor for MACE, even after adjusting for conventional cardiovascular risk
CHD and the ratio can be utilised for CHD risk prediction in factors and CAD on coronary angiography. This indicates that a
individuals at high risk of metabolic syndromes. In congru- TG/HDL-C ratio 2.5 may offer a simpler approach compared to
ence with previous studies, our study demonstrated that the using tertiles or quartiles of TG/HDL-C levels to identify high-
prevalence of CAD on coronary angiography was signifi- risk individuals with adverse cardiometabolic risk profiles. Thus,
cantly higher in patients with raised TG/HDL-C levels. utilising this ratio would allow the clinicians to identify high-risk
The prognostic utility of raised TG/HDL-C ratio has been patients and to tailor long-term pharmacologic and non-pharma-
previously described. Gaziano et al. [31] first reported in a cologic management strategies based on risk-stratification, in
case control study, that elevated TG/HDL-C ratio can order to improve long-term outcomes in this population.

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420 R. Sultani et al.

[4] Silbernagel G, Schottker B, Appelbaum S, Scharnagl H, Kleber ME,

Limitations Grammer TB, et al. High-density lipoprotein cholesterol, coronary
This study has several limitations. First, due to inclusion of artery disease, and cardiovascular mortality. Eur Heart J 2013;34
(46):3563–71.
large numbers of rural patients in the BRAVEHEART regis-
[5] Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. Relation of high TG-low
try and choosing a pre-specified follow-up period between HDL cholesterol and LDL cholesterol to the incidence of ischemic heart
March and June 2016 due to logistical reasons, a complete disease. An 8-year follow-up in the Copenhagen Male Study. Arterioscler
Thromb Vasc Biol 1997;17(6):1114–20.
follow-up was not conducted. This would have affected the
[6] Bittner V, Johnson BD, Zineh I, Rogers WJ, Vido D, Marroquin OC, et al.
sample size, which would have affected the statistical signif- The triglyceride/high-density lipoprotein cholesterol ratio predicts all-
icance of our findings. Second, not all patients recruited in the cause mortality in women with suspected myocardial ischemia: a report
from the Women’s Ischemia Syndrome Evaluation (WISE). Am Heart J
BRAVEHEART study had their baseline TG/HDL-C levels
2009;157(3):548–55.
available, and therefore were excluded from the study. Third, [7] Wan K, Zhao J, Huang H, Zhang Q, Chen X, Zeng Z, et al. The association
the cause of death for the deceased was obtained through between triglyceride/high-density lipoprotein cholesterol ratio and all-
cause mortality in acute coronary syndrome after coronary revasculari-
death certificates and an autopsy was not performed to
zation. PLoS One 2015;10(4):e0123521.
substantiate the exact cause of death. Fourth, the prognostic [8] Vega GL, Barlow CE, Grundy SM, Leonard D, DeFina LF. Triglyceride-
utility of TG/HDL-C 2.5 was evaluated in an Australian to-high-density-lipoprotein-cholesterol ratio is an index of heart disease
mortality and of incidence of type 2 diabetes mellitus in men. J Invest
population of patients presenting for coronary angiography
Med 2014;62(2):345–9.
and this ratio needs to be further assessed in other population [9] Welty FK. How do elevated triglycerides and low HDL-cholesterol affect
groups to be generalisable. Fifth, longitudinal lipid profiles inflammation and atherothrombosis? Current Cardiol Rep 2013;15
(9):400.
were not available to assess temporal patterns and the poten-
[10] Yancey PG. Importance of different pathways of cellular cholesterol
tial impacts on long-term cardiovascular outcomes. Last but efflux. Arterioscler Thromb Vasc Biol 2003;23(5):712–9.
not least, data on other non-statin lipid-lowering agents were [11] Gadi R, Amanullah A, Figueredo VM. HDL-C: does it matter? An update
on novel HDL-directed pharmaco-therapeutic strategies. Int J Cardiol
not recorded that could potentially have an impact on TG
2013;167(3):646–55.
levels and cardiovascular outcomes. [12] Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M. Identifi-
cation of scavenger receptor SR-BI as a high density lipoprotein receptor.
Conclusions Science 1996;271(5248):518–20.
[13] Steinberg D. A docking receptor for HDL cholesterol esters. Science
An elevated TG/HDL-C ratio carries an important prognos- 1996;271(5248):460.
tic value in predicting long-term all-cause mortality and [14] Kleber ME, Grammer TB, Marz W. High-density lipoprotein (HDL) and
cholesteryl ester transfer protein (CETP): role in lipid metabolism and
MACE in a high-risk population of patients presenting for
clinical meaning. MMW Fortschritte der Medizin 2010;152(Suppl 2):
coronary angiography. Therefore, identification of this Error: FPage (47) is higher than LPage (55)!.
patient population is crucial in implementing early and [15] Klerkx AH, El Harchaoui K, van der Steeg WA, Boekholdt SM, Stroes ES,
Kastelein JJ, et al. Cholesteryl ester transfer protein (CETP) inhibition
intensive risk modification strategies to improve their
beyond raising high-density lipoprotein cholesterol levels: pathways by
long-term outcomes. which modulation of CETP activity may alter atherogenesis. Arterioscler
Thromb Vasc Biol 2006;26(4):706–15.
Disclosures [16] Hewing B, Fisher EA. Rationale for cholesteryl ester transfer protein
inhibition. Curr Opin Lipidol 2012;23(4):372–6.
No disclosures or conflicts of interest. [17] McLaughlin T, Abbasi F, Cheal K, Chu J, Lamendola C, Reaven G. Use of
metabolic markers to identify overweight individuals who are insulin
resistant. Ann Int Med 2003;139(10):802–9.
[18] Cordero A, Laclaustra M, León M, Casasnovas J, Grima A, Luengo E,
Acknowledgment et al. Comparison of serum lipid values in subjects with and without the
metabolic syndrome. Am J Cardiol 2008;102(4):424–8.
[19] Bigazzi R, Bianchi S. Insulin resistance, metabolic syndrome and endo-
Andrew M. Wilson is supported by grants from the National
thelial dysfunction. J Nephrol 2007;20(1):10–4.
Heart Foundation of Australia, Diabetes Australia Research [20] Sattar N, Gaw A, Scherbakova O, Ford I, O’Reilly DS, Haffner SM, et al.
Trust and the Australian Catholic University (Melbourne, Metabolic syndrome with and without C-reactive protein as a predictor
of coronary heart disease and diabetes in the West of Scotland coronary
Victoria, Australia). Arul Baradi is supported by an Austra- prevention study. Circulation 2003;108(4):414–9.
lian Government Research Training Program Scholarship [21] Schmidt C, Bergstrom GM. The metabolic syndrome predicts cardiovas-
and NHMRC Centre of Research Excellence in Cardiovascu- cular events: results of a 13-year follow-up in initially healthy 58-year-old
men. Metab Syndr Relat Disord 2012;10(6):394–9.
lar Outcomes Improvement (CRE-COI) PhD Scholarship
[22] McNeill AM, Rosamond WD, Girman CJ, Golden SH, Schmidt MI, East
(Melbourne, Victoria, Australia). HE, et al. The metabolic syndrome and 11-year risk of incident cardio-
vascular disease in the atherosclerosis risk in communities study. Diab
Care 2005;28(2):385–90.
[23] Hanak V, Munoz J, Teague J, Stanley A, Bittner V. Accuracy of the
triglyceride to high-density lipoprotein cholesterol ratio for prediction
References of the low-density lipoprotein phenotype B. Am J Cardiol 2004;94(2):219–
22.
[1] Morrison A, Hokanson JE. The independent relationship between tri- [24] Koba S, Hirano T, Ito Y, Tsunoda F, Yokota Y, Ban Y, et al. Significance of
glycerides and coronary heart disease. Vasc Health Risk Manag 2009;5 small dense low-density lipoprotein-cholesterol concentrations in rela-
(1):89–95. tion to the severity of coronary heart diseases. Atherosclerosis 2006;189
[2] Cullen P. Evidence that triglycerides are an independent coronary heart (1):206–14.
disease risk factor. Am J Cardiol 2000;86(9):943–9. [25] Dobiasova M, Frohlich J. The plasma parameter log (TG/HDL-C) as an
[3] Chen CY, Hwu CM, Lin MW, Tsai CH, Yeh HI. High triglyceride level is atherogenic index: correlation with lipoprotein particle size and esterifi-
associated with severe coronary artery disease in hypertensive subjects. cation rate in apoB-lipoprotein-depleted plasma (FER(HDL)). Clin Bio-
Scand Cardiovasc J 2008;42(2):146–52. chem 2001;34(7):583–8.

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Triglycerides to High-Density Lipoprotein Ratio Cholesterol 421

[26] de Giorgis T, Marcovecchio ML, Di Giovanni I, Giannini C, Chiavaroli V, [31] Gaziano JM, Hennekens CH, O’Donnell CJ, Breslow JL, Buring JE. Fast-
Chiarelli F, et al. Triglycerides-to-HDL ratio as a new marker of endo- ing triglycerides, high-density lipoprotein, and risk of myocardial infarc-
thelial dysfunction in obese prepubertal children. Eur J Endocrinol/Eur tion. Circulation 1997;96(8):2520–5.
Fed Endocr Soc 2014;170(2):173–80. [32] Asia Pacific Cohort Studies C. A comparison of lipid variables as pre-
[27] Li X, Deng YP, Yang M, Wu YW, Sun SX, Sun JZ. Triglyceride to high- dictors of cardiovascular disease in the Asia Pacific Region. Ann Epi-
density lipoprotein cholesterol ratio and carotid intima-medial thickness demiol 2005;15(5):405–13.
in Chinese adolescents with newly diagnosed type 2 diabetes mellitus. [33] Jeppesen J, Hein H, Suadicani P, Gyntelberg F. LOw triglycerides–high
Pediatr Diab 2016;17(2):87–92. high-density lipoprotein cholesterol and risk of ischemic heart disease.
[28] da Luz PL, Favarato D, Faria-Neto Jr JR, Lemos P, Chagas AC. High ratio Arc Internal Med 2001;161(3):361–6.
of triglycerides to HDL-cholesterol predicts extensive coronary disease. [34] da Luz P, Favarato D, Faria Neto J, Lemos P, Chagas ACP. High ratio of
Clin (Sao Paulo, Brazil) 2008;63(4):427–32. triglycerides to HDL-cholesterol predicts extensive coronary disease.
[29] Yunke Z, Guoping L, Zhenyue C. Triglyceride-to-HDL cholesterol ratio. Clinics 2008;63(4):427–32.
Predictive value for CHD severity and new-onset heart failure. Herz [35] Drexel H, Aczel S, Marte T, Benzer W, Langer P, Moll W, et al. Is Atheroscle-
2014;39(1):105–10. rosis in Diabetes and Impaired Fasting Glucose Driven by Elevated LDL
[30] Hadaegh F, Khalili D, Ghasemi A, Tohidi M, Sheikholeslami F, Azizi F. Cholesterol or by Decreased HDL Cholesterol? Diabe Care 2005;28(1):101–7.
Triglyceride/HDL-cholesterol ratio is an independent predictor for cor- [36] Effects of long-term fenofibrate therapy on cardiovascular events in 9795
onary heart disease in a population of Iranian men. Nutr Metab Car- people with type 2 diabetes mellitus (the FIELD study): randomised
diovasc Dis: NMCD 2009;19(6):401–8. controlled trial. The Lancet 2005;366(9500):1849–61.

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