Clinical

Investigation

Low Serum Triglyceride

Levels as Predictors of
Cardiac Death in Heart
Failure Patients

Guliz Kozdag, MD
Gokhan Ertas, MD
Ender Emre, MD
Yasar Akay, MD
Umut Celikyurt, MD
Tayfun Sahin, MD
Gozde Gorur, MD
Kurtulus Karauzum, MD
Irem Yilmaz, MD
Dilek Ural, MD
Mira Sarsekeyeva, MD

Understanding the influence of sex differences on predictors of cardiac mortality rates in

chronic heart failure might enable us to lengthen lifetimes and to improve lives. This study
describes the influence of sex on cardiovascular mortality rates among chronic heart failure patients.
From January 2003 through December 2009, we evaluated 637 consecutive patients
(409 men and 228 women) with chronic heart failure, who ranged in age from 18 through
94 years (mean age, 64 13 yr) and ranged in New York Heart Association (NYHA) functional class from II through IV. The mean follow-up period was 38 15 months, the mean
age was 64 13 years, and the mean left ventricular ejection fraction was 0.27 0.11.
By the end of the study, both sexes had similar cardiovascular mortality rates (36%
men vs 37% women, P=0.559). In Cox regression analysis, NYHA functional class, triglyceride level, and history of coronary artery disease were independent predictors of cardiovascular death for women with chronic heart failure. For men with chronic heart failure, the
patients age, ejection fraction, and sodium level were independent predictors of cardiovascular death.
In a modern tertiary referral heart failure clinic, decreased triglyceride levels were, upon
univariate analysis, predictors of poor outcomes for both men and women. However, upon
Cox regression analysis, reduced triglyceride levels were independent predictors of cardiac death only in women. (Tex Heart Inst J 2013;40(5):521-8)

Key words: Cachexia/

blood; chronic disease; heart
failure/mortality; female;
follow-up studies; male;
predictive value of tests;
prognosis; risk assessment;
sex factors; survival
analysis; triglycerides/blood;
univariate analysis
From: Departments of
Cardiology (Drs. Akay,
Celikyurt, Emre, Ertas,
Karauzum, Kozdag, Sahin,
Ural, and Yilmaz) and
Nuclear Medicine (Dr.
Gorur), Faculty of Medicine,
Kocaeli University, 41300
Kocaeli, Turkey; and Charles
E. Schmidt College of
Medicine (Dr. Sarsekeyeva),
Florida Atlantic University,
Boca Raton, Florida 33431
Address for reprints:
Gokhan Ertas, MD,
Department of Cardiology,
Istanbul Dr. Siyami Ersek
Thoracic and Cardiovascular
Surgery Training and
Research Hospital, Tibbiye
St., Haydarpasa-Kadikoy,
34710 Istanbul, Turkey
E-mail: drgokhanertas@
yahoo.com.tr
2013 by the Texas Heart
Institute, Houston

Texas Heart Institute Journal

he 5-year survival rate for chronic heart failure (CHF) remains at 50%, with
mortality rates higher for men than for women (relative risk=1.33, P <0.001).
After diagnosis with heart failure, women tend to have a better prognosis and
to survive longer than men.1 Given the greater life expectancy of women in the developed world, the overall impact of heart failure is still very important for them.2
Although the CHF death rate seems to be lower or the same in women, most available scientific evidence regarding the influence of male versus female sex on the prognosis of CHF patients derives from observational studies and retrospective analyses,
and women are known to be underrepresented in clinical trials.3 These studies report
divergent findings concerning the prognosis of CHF patients according to sex, mainly attributable to the study characteristics, the cause of the heart failure, and the type
of population studied.2,4-6 Few reports deal with the differences between men and
women in specialized heart failure clinics or units.
Chronic heart failure can lead to a catabolic state and eventually to cachexia in advanced cases. There is preferential loss of fat but also a decline in lean body mass.
Reduced efficiency of adenosine triphosphate production by mitochondria, reduced
appetite, malabsorption, and reduced levels of anabolic steroids might play a role.7 Patients with advanced heart failure have severe symptoms, a high mortality rate, and a
low cholesterol level.8 This can be due to inflammation, endotoxins, adrenergic activation, oxidative stress, tissue injury, and cachexia.9,10
Liver-function abnormalities are most commonly seen in patients with low cardiac
indices and resolve with compensation of heart failure; they are not associated with
clinically apparent hepatic disease.11 It has been determined that liver dysfunction is
frequent in CHF and is characterized by a predominantly cholestatic enzyme profile
that worsens with disease severity.12 Functional liver mass was significantly decreased
in New York Heart Association (NYHA) functional class IV patients, in comparison with NYHA II and III patients and with subjects in a control group. The funcLow Serum Triglycerides as Predictors of Cardiac Death

521

tional liver mass in patients with systolic CHF did not

show any correlations with left ventricular ejection fraction (LVEF), but it did correlate strongly with left atrial
diameter.13 Dysfunction of the liver during heart failure
syndrome can be another explanation of decreased cholesterol level in CHF.
Triglycerides are neutral lipids consisting of a glycerol backbone and 3 long-chain fatty acids. These molecules are a major source of stored energy in such diverse
tissues as adipose tissue and skeletal muscle, and they
are integral components of lipoprotein particles synthesized by the liver and small intestine.14
In advanced heart failure, mechanisms similar to
those that cause low cholesterol levels might cause low
triglyceride levels. It seems that heart failure might alter
both the production and the storage of triglycerides.
Loss of a major energy source can adversely affect the
survival of patients with CHF. The aim of this study
was to determine the prognostic significance of triglyceride levels for both men and women who have CHF.

Patients and Methods

From January 2003 through December 2009, we evaluated 637 patients (409 men and 228 women) who
ranged in age from 18 through 94 years (mean age, 64
13 yr) and in NYHA functional class from II through
IV. They had been admitted for worsening of heart failure: either ischemic or nonischemic dilated cardiomyopathy. Dilated cardiomyopathy was diagnosed on the
basis of transthoracic echocardiographic (TTE) findings of left ventricular (LV) end-diastolic diameter >56
mm and LVEF <0.45. All patients who had not undergone diagnostic coronary angiography were so evaluated to determine the cause of the heart failure (Table I).
In patients who had symptoms of decompensated heart
failure, the criteria for exclusion from the study were
malignancy, the concomitant presence of any predominant severe systemic illness, acute coronary syndrome,
pericardial tamponade, hypertrophic cardiomyopathy,
restrictive cardiomyopathy, right-sided heart failure due
to chronic obstructive pulmonary disease, severe aortic
stenosis, and mitral stenosis.
This study was conducted in accordance with the
Declaration of Helsinki and approved by our institutional ethics committee. All patients gave written informed consent before entry into the study.
Echocardiographic and Clinical Evaluation

A detailed medical history and physical examination

were obtained for each patient, along with a baseline
electrocardiogram and chest radiograph. All participants underwent TTE by means of an echocardiograph
equipped with a Vivid 7 broadband transducer (GE
VingMed Ultrasound AS; Horten, Norway). Measurements of the left atrium, left ventricle, and right ventri522

Low Serum Triglycerides as Predictors of Cardiac Death

cle were obtained from parasternal long-axis and apical

4-chamber views, in accordance with standard criteria.
The LVEF was calculated by means of the modified
Simpson rule, in the apical 2- and 4-chamber views.
Mitral flow was measured from the apical 4-chamber
view with pulsed-wave Doppler by placing the sample
volume at the tips of the mitral leaflets. Right ventricular systolic pressure was determined by continuouswave Doppler study of the tricuspid regurgitation jet.
If tricuspid regurgitation was mild and right atrial size
was normal, right atrial pressure was assumed to be 5
mmHg. For moderate tricuspid regurgitation with mild
or no right atrial enlargement, we assumed a constant
pressure of 10 mmHg. When tricuspid regurgitation
was severe and was observed in the presence of a dilated right atrium, we assumed a constant pressure of 15
mmHg.
Blood Samples

Fasting blood samples were drawn from a large antecubital vein in each patient for determination of biochemical
and hemostatic values during the first 1 to 3 days of hospitalization. Brain natriuretic peptide (BNP) levels were
measured with the Triage BNP test (Biosite Incorporated; San Diego, Calif ), which is a fluorescence immunoassay for the quantification of BNP in 24 hours. Serum
high-sensitivity C-reactive protein (hs-CRP) was measured by means of a sensitive nephelometric assay. Sedimentation rate, albumin, creatinine, hemoglobin, and
lipid levels were measured by standard methods.
Follow-Up of Patients

Clinical follow-up was done by telephone contact and

periodic examination of outpatients. All patients were
followed for a mean duration of 38 15 months (range,
382 mo). The primary endpoint of the study was cardiac death, including sudden death and death attributable to advanced heart failure.
Statistical Analysis

All statistical analyses were performed with the SPSS

13.0 statistical software package (IBM Corporation;
Armonk, NY). Results are presented as mean SD
or, for categorical data, as number and percentage. In
comparing patients with and without study endpoints,
normally distributed continuous variables were analyzed with the 2-tailed t test, and unequally distributed variables were analyzed with the Mann-Whitney U
test. Categorical data and proportions were analyzed by
means of the c2 test. Correlations between triglyceride
and echocardiographic or biochemical values were determined by Spearman correlation analysis. A P value
of less than 0.05 was considered statistically significant.
During the follow-up period, the clinical and laboratory values of patients with and without study endpoints
were compared. The resulting values (as evaluated in the
Volume 40, Number 5, 2013

TABLE I. Baseline Characteristics of the Patients

Characteristic

Mean age (yr)

All Patients
(n=637)

Women
(n=228)

Men
(n=409)

P Value

64 13

63 14

64 12

0.72

26.8 5.5

26.7 4.1

0.788
<0.001

Body mass index (kg/m ) 26.7 4.6

2

Coronary artery disease

402 (63)

LVEF 0.27 0.11

111 (49)

291 (71)

0.28 0.12

0.26 0.11

0.007

NYHA functional class

2.8 0.5

2.8 0.5

2.8 0.5

0.601

SBP (mmHg)

125 18

125 20

124 18

0.499

DBP (mmHg)

76 11

76 12

76 11

0.764

12 8

13 2

1,155 980

Hemoglobin (g/dL)

12.6 2

1,238 2,191

0.931

hs-CRP (pg/mL)

2.6 4.3

2.67 4.85

2.60 3.97

0.844

Creatinine (mg/dL)

1.4 1.2

1.4 1.3

1.5 1.14

0.533

Triglycerides (mg/dL)

129 69

136 68

125 69

0.017

Cholesterol (mg/dL)

BNP (pg/mL)

1,208 1,249

<0.001

168 47

178 55

162 41

<0.001

HDL cholesterol (mg/dL)

36 11

39 12

35 11

<0.001

LDL cholesterol (mg/dL)

105 38

112 45

102 34

0.004

Albumin (mg/dL)

3.8 0.5

3.8 0.6

3.8 0.5

0.725

Hypertension

463 (73)

180 (79)

283 (70)

0.008

Diabetes mellitus

223 (35)

88 (39)

135 (34)

0.156

443 (70)

163 (71)

280 (70)

0.425

ACEI/ARB

522 (82)

176 (77)

346 (85)

0.02

Spironolactone

289 (45)

118 (52)

171 (43)

0.016

Loop diuretic

513 (81)

191 (84)

228 (57)

0.123

Comorbidities

Medications
-Blockers

Digitalis

118 (19)

70 (31)

71 (17)

<0.001

Nitrates

258 (41)

79 (35)

179 (45)

0.023

Aspirin

564 (89)

197 (84)

367 (91)

0.206

ACEI/ARB = angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers; BNP = brain natriuretic peptide; DBP =
diastolic blood pressure; HDL = high-density lipoprotein; hs-CRP = high sensitivity C-reactive protein; LDL = low-density lipoprotein;
LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; SBP = systolic blood pressure
Values are expressed as mean SD or as number and percentage. P <0.05 was considered statistically significant.

model) were significantly different between cardiovascular death-positive and death-negative patient groups.
The values of triglycerides, LVEF, and sodium levels
that were predictors of cardiovascular death were detected via receiver operating characteristic (ROC) curve
analysis by using the SPSS statistical software package.
Cox proportional hazard analysis was used to arrive at
the independent predictors of survival. Coronary artery
disease, age, NYHA functional class, body mass index,
LVEF <0.145, BNP levels, hs-CRP levels, triglyceride
levels <70.5 mg/dL, triglyceride levels <150 mg/dL, and
sodium levels <128.5 mEq/L were studied via Cox reTexas Heart Institute Journal

gression analysis as possible independent predictors of

cardiac death. The Kaplan-Meier method was used to
analyze the timing of events during follow-up.

Results
The cardiovascular mortality rates of men (143; 36%)
and women (85; 37%) were similar, P=0.559. Upon
univariate analysis, histories of coronary artery disease,
diabetes mellitus, and hypertension were not predictors of cardiovascular death in either sex. On the other
hand, older age, worse NYHA functional status, and
Low Serum Triglycerides as Predictors of Cardiac Death

523

lower triglyceride levels were important determinants

of cardiovascular death in both sexes, upon univariate
analysis. In both sexes, surviving patients had higher triglyceride levels than nonsurviving patients (in women,
147 70 vs 119 62 mg/dL, P=0.001; in men, 130
74 vs 116 57 mg/dL, P=0.038) (Table II). Although
increased hs-CRP level was a predictor of cardiovascular death in women (4.19 6.51 vs 1.77 3.22 mg/dL,
P <0.001), its level was not an important predictor in
men (Table II).
In men, surviving patients had higher LVEFs, increased hemoglobin levels, higher sodium levels, and
lower BNP levels, compared with nonsurviving patients
in univariate analysis (Table II).
One hundred fifty mg/dL was accepted as a cutoff
value for triglycerides. A triglyceride level of <150 mg/
dL, in accordance with the ATP III guidelines,15 was accepted as normal. Patients were divided into 2 different
groups, according to triglyceride level. One group comprised patients who had triglyceride levels <150 mg/dL,
and the other group comprised patients who had triglyceride levels 150 mg/dL. Of the 458 patients whose triglyceride levels were <150 mg/dL, 179 (39%) died, and
of the 179 patients whose triglyceride levels were 150
mg/dL, 48 (27%) died (P=0.005). We found no statistically significant difference between men whose tri-

glyceride levels were <150 mg/dL and men whose levels

were 150 mg/dL: of 307 men whose triglyceride levels
were <150 mg/dL, 110 (36%) died; and of 101 whose
triglyceride levels were 150 mg/dL, 32 (32%) died
(P=0.448). However, of 151 women whose triglyceride levels were <150 mg/dL, 69 (46%) died; and of 75
whose triglyceride levels were 150 mg/dL, 16 (21%)
died (P <0.001) (Fig. 1).
Cutoff Values of Triglycerides for Predicting
Cardiovascular Death in Women

To define the predictor level in the study population,

we used ROC curve analysis to detect the predictive
cutoff values of triglyceride level for the occurrence of
cardiovascular death in women (area under the curve
[AUC]=0.363; 95% confidence interval [CI], 0.289
0.437; P=0.001).
The ROC curves showed that the best cutoff value for
predicting cardiovascular death in women was a triglyceride level of <70.5 mg/dL (79% sensitivity and 91%
specificity). There were 31 women with triglyceride levels of <70.5 mg/dL, 18 (58%) of whom died during the
follow-up period. There were 197 women with triglyceride levels of >70.5 mg/dL, 67 (34%) of whom died
due to cardiovascular reasons during the study period
(P=0.01).

TABLE II. Comparison of the Clinical, Echocardiographic, and Laboratory Values among Men and Women

Women

Men

Variable

Surviving Nonsurviving
Surviving Nonsurviving
Patients Patients Patients Patients
(n=144)
(n=84)
P Value
(n=270)
(n=139)
P Value

Mean age (yr)

59.8 11

69.4 11.5

<0.001

61.6 12.2

68 11.6

<0.001

2.68 0.48

2.98 0.46

<0.001

2.7 0.52

3.03 0.46

<0.001

NYHA functional class

Body mass index (kg/m ) 27 5.9

26.5 4.6

0.464

27 4.1

12 1.8

11.8 1.7

0.548

13.3 1.9

Hemoglobin (mg/dL)
Creatinine (mg/dL)

1.41 1.44

1.4 0.88

26.1 4.1

0.044

12.6 2

0.002

0.928

1.4 1.08

1.6 1.24

1,119 2,572

1,456 1,194

2.36 3.55

3.04 4.63

0.086

1,124 986

1,206 974

0.545

hs-CRP (mg/dL)

1.77 3.22

4.19 6.51

<0.001

Triglycerides (mg/dL)

147 70

119 62

0.002

130 74

116 57

Cholesterol (mg/dL)

183 57

170 51

0.086

164 41

159 42

0.334

LDL cholesterol (mg/dL)

114 46

108 42

0.322

102 34

101 33

0.703

HDL cholesterol (mg/dL)

39 12

38 12

0.369

35 10

36 12

0.526

BNP (pg/mL)

Sodium (mEq/L)

137.7 5.2

LVDD (mm)

60 6.5

LVSD (mm)

46.4 7.3

LVEF 0.29 0.12

137.8 4.8

0.887

0.001
0.13
0.038

137.8 4.5

136.2 6.2

0.006

61 7

NS

61.7 7.4

63.9 7.7

0.004

47.7 7.9

NS

48.3 8.4

50.8 8.8

0.003

0.27 0.11

0.12

0.27 0.1

0.23 0.11

0.013

BNP = brain natriuretic peptide; HDL = high-density lipoprotein; hs-CRP = high-sensitivity C-reactive protein; LDL = low-density
lipoprotein; LV = left ventricular; LVDD = left ventricular diastolic diameter; LVEF = left ventricular ejection fraction; LVSD = left
ventricular systolic diameter; NS = not significant; NYHA = New York Heart Association
Values are expressed as mean SD. P <0.05 was considered statistically significant.

524

Low Serum Triglycerides as Predictors of Cardiac Death

Volume 40, Number 5, 2013

Fig. 1 Cumulative survival rate in women, in accordance with

triglyceride level (P <0.001).

Fig. 2 Cumulative survival rate in men, in accordance with

ejection fraction (P=0.011).

Cutoff Values of Ejection Fraction for

Predicting Cardiovascular Death in Men

TABLE III. Cox Regression Analysis for Cardiovascular

Death in Chronic Heart Failure Patients

As determined by ROC curve analysis (AUC=0.42;

95% CI, 0.3610.479; P=0.008), the cutoff value of
LVEF for cardiovascular death was <0.145 in men
(84% sensitivity and 92% specificity) . There were
44 men with LVEFs of <0.145, 23 (52%) of whom
died during the follow-up period. There were 365
men with LVEFs of >0.145; 67 (33%) of whom died
due to cardiovascular reasons during the study period
(P=0.011) (Fig. 2).
Cutoff Values of Sodium for Predicting
Cardiovascular Death in Men

As determined by ROC curve analysis (AUC=0.427;

95% CI, 0.3690.496; P=0.018), the cutoff value of
sodium that predicted cardiovascular death was <128.5
mEq/L in men, with 92% sensitivity and 97% specificity. There were 21 men with sodium levels of <128.5
mEq/L, 12 (57%) of whom died during the followup period. There were 388 men with sodium levels of >128.5 mEq/L, 131 (34%) of whom died due
to cardiovascular reasons during the follow-up period (P=0.029).
Cox Regression Analysis

In Cox regression analysis, NYHA functional class,

triglyceride level <150 mg/dL, and history of coronary artery disease were independent predictors of cardiovascular death in women with CHF (Table III).
The NYHA functional class had a 95% CI of 2.002
(range, 1.1473.494; P=0.015); history of coronary artery disease had a 95% CI of 1.608 (range, 1.033
Texas Heart Institute Journal

Variable

Hazard Ratio

95% CI

P Value

Women
NYHA functional
class

2.002

1.1473.494

0.015

Triglyceride level
<150 mg/dL

1.995

1.1423.487

0.015

Coronary artery
disease

1.608

1.0332.504

0.035

Men
Age

1.057 1.0391.075 <0.001

Ejection fraction
<0.145

3.208

1.9665.234

<0.001

Sodium
<128.5 mEq/L

2.674

1.4165.048

0.002

CI = confidence interval; NYHA = New York Heart Association

P <0.05 was considered statistically significant.

2.504; P=0.035); and triglyceride level <150 mg/dL

had a 95% CI of 1.995 (range, 1.1423.487; P=0.015)
(Table III).
Patients age, LVEFs of <0.145, and sodium levels of
<128.5 mEq/L were independent predictors of cardiovascular death in men with CHF. Age had a 95% CI of
1.057 (range, 1.0391.075; P <0.001); LVEF of <0.145
had a 95% CI of 3.208 (range, 1.9665.234; P <0.001);
and sodium levels of <128.5 mEq/L had a 95% CI of
2.674 (range, 1.4165.048; P=0.002) (Table III).
Low Serum Triglycerides as Predictors of Cardiac Death

525

Correlations between Triglyceride

Levels and Other Values

In women, significant negative correlations were found

between triglyceride levels and left atrial dimensions,
right ventricular dimensions, pulmonary artery pressures, and grades of mitral regurgitation and tricuspid
regurgitation (Table IV).

Discussion
Higher NYHA functional class, older age, and reduced
triglyceride levels were important prognostic markers
for cardiovascular death in both sexes in the presented study. Besides those factors, increased hs-CRP level
was another indicator of poor prognosis in women. In
men, poor prognosis was indicated by such factors as
lower body mass index, decreased hemoglobin levels,
and reduced sodium levels, and higher creatinine and
BNP levels. Decreased LVEF was a significant echocardiographic factor associated with a poor prognosis
in men. In Cox regression analysis, older age, history of
coronary artery disease, and triglyceride level <150 mg/
dL were important predictors in women, but older age,
LVEF <0.145, and sodium levels <128.5 mEq/L were
significant predictors in men.
Before our study, it was known that higher functional class,16,17 increased hs-CRP levels,18,19 higher BNP levels,20,21 lower hemoglobin levels,22 lower LVEFs, and
decreased sodium levels23,24 were prognostic markers in
heart failure patients.
It has also been reported25 that, in CHF patients, a
higher body mass index is associated with a better prognosis independently of other clinical variables. The risk
of death due to progressive heart failure was 3.4-fold
higher in underweight than in obese patients. Normal
weight, overweight, and obese patients had lower risk

of death, compared with underweight patients.25 In

fact, a paradox between decreased total cholesterol levels and prognosis has been confirmed: lower cholesterol levels predicted significantly worse clinical outcomes
in CHF patients. These findings imply that the classic
risk profile should not apply in patients once CHF is
established. Rauchhaus and colleagues10 observed a relationship between lower cholesterol levels, higher cytokine levels, and increased mortality rates. They found
that triglyceride levels were lower in cachectic heart failure patients than in noncachectic heart failure patients
(P=0.04).10
It has been suggested that cholesterol levels in stable
mild-to-moderate CHF patients are an indicator of nutritional status, because cholesterol levels correlate closely with prealbumin levels.26 Some investigators conclude
that higher total cholesterol might represent a greater
metabolic reserve to deal with heart failure syndrome
and that the cholesterol could limit the production of
harmful cytokines.8
Low triglyceride levels might be merely a consequence
of advanced heart failure. Kato and colleagues27 showed
that both glucose and insulin levels were lower in CHF
rats than in control rats in fed condition. The amount
of glycogen in the liver was decreased, and the level of
triglycerides was increased in CHF rats. Metabolome
analysis revealed that levels of some metabolites of glycolysis increased, whereas some metabolites in the Krebs
cycle, such as acyl coenzyme A (acetyl-CoA) and citrate,
decreased. Overall, these results might suggest that hepatic lipogenesis is increased and that acetyl-CoA is
used for the synthesis of triglycerides and cholesterol.
Plasma levels of cholesterol and triglycerides were increased, and free fatty acids (FFAs) were decreased in
Dahl salt-sensitive rats with CHF. Kato and colleagues27
concluded that the animals decreased food intake, in

TABLE IV. Related Values with Triglycerides in Patients with Congestive Heart Failure

Women

Variable

Correlation
of Estimates (r)
P Value

Men
Correlation
of Estimates (r)

P Value

Cholesterol

0.52 <0.001

0.41 <0.001

LDL cholesterol

0.35

<0.001

0.11

0.028

Left atrial dimension

0.25

<0.001

0.01

0.067

RV dimension

0.16

0.021

0.09

0.09

Mitral regurgitation

0.16

0.014

0.09

0.068

Tricuspid regurgitation

0.3

<0.001

0.14

0.004

RV systolic pressure

0.24

0.001

0.18

<0.001

Albumin

0.23 0.027

0.12 0.15

CHF = chronic heart failure; LDL = low-density lipoprotein; RV = right ventricular

P <0.05 was considered statistically significant.

526

Low Serum Triglycerides as Predictors of Cardiac Death

Volume 40, Number 5, 2013

association with lower glucose and insulin levels, suggested starvation. However, the plasma level of FFAs
was decreased and that of triglycerides increased, which
is not consistent with a starved condition.27
Acyl-coenzyme A:diacylglycerol acyltransferase
(DGAT) is the enzyme that catalyzes the final step in
triglyceride synthesis. In states of energy excess, hepatic DGAT activity increases triglyceride synthesis. These
triglycerides are exported from the liver in lipoprotein
particles and delivered to extrahepatic adipose depots
for storage. Within adipose tissue, lipoprotein lipase
hydrolyzes liver-derived triglycerides to liberate FFAs,
which are then transported into adipocytes. Adipocyte
DGAT catalyzes the esterification of these FFAs to regenerate triglycerides.14
Congestion of the liver secondary to congestive heart
failure results in elevation of hepatic venous pressure;
in fact, the close relationship between elevated venous
pressure and elevated serum levels of transaminases can
be seen as a measure of hepatic dysfunction.28 In CHF
rats compared with control-group rats, liver weight (corrected by body weight) was found to be higher.27 The
increase in liver weight was most likely due to congestion, because venous dilation in liver tissue was reported in their model.29 It is of interest that increased right
atrial pressure has been reported to indicate malnutrition in CHF patients.30
During cancer cachexia in mice bearing an experimental colon adenocarcinoma (MAC16), Briddon and
colleagues31 studied the effect of weight loss on plasma
levels of FFAs and triglycerides, and on tissue levels of
lipoprotein lipase (LPL). They found that plasma levels
of triglycerides were reduced despite extensive mobilization of host body-fat reserves and regardless of weight
loss. The plasma levels of FFA also showed an initial decrease with weight loss, followed by an increase, which
peaked at a weight loss of about 2 g; thereafter, the levels
decreased with increasing weight loss. The level of LPL
in both heart and adipose tissue showed an initial rise
with increasing weight loss, which peaked at a weight
loss of approximately 2.5 g, followed by a decrease upon
further weight loss. The increased LPL would provide
an increased level of fatty acids for oxidation in the cachectic state and would account for the effect on plasma FFAs and triglycerides.31
Although it might be assumed that increased triglyceride levels serve the human body as a compensatory
mechanism against starvation during CHF, this mechanism would not raise triglyceride levels enough during
an advanced stage of starvation in CHF. Lower levels
of triglycerides might therefore be a sign of the more advanced stages of starvation in CHF.
Although a triglyceride level of <150 mg/dL has been
accepted as normal in the general population, it seemed
to us, in view of this studys results, that such a level
could not be used as normal in CHF patients. This is
Texas Heart Institute Journal

the first report of low triglyceride level as a predictor of

poor outcomes in both sexes. In Cox regression analysis,
that triglyceride level (<150 mg/dL) was an independent
predictor of cardiovascular death in women with CHF.
In this study, we found that negative correlations between triglyceride levels and pulmonary artery pressure,
tricuspid regurgitation, and right-sided heart dimension
can show impaired biosynthetic function of the liver, due
to the failure of the right side of the heart in CHF. Repeated states of hepatic congestion during decompensation episodes of CHF could have negative effects on
biosynthetic processes of the liver. In advanced stages of
CHF, the liver could lose its ability to synthesize. Cardiac cirrhosis, a liver condition characterized by chronic
venous congestion and caused by right-sided heart failure, could be a signal for the end stage of CHF.32
Reduced triglyceride levels might be the consequence
of associated factors during CHF: advanced states of
congestion in the gastrointestinal system and liver, decreased food intake, increased cachexia, and increased
levels of inflammation.
Conclusion

Although decreased serum triglyceride levels are predictors of cardiovascular death in patients with heart
failure, the reasons for the low triglyceride levels are unknown and require further investigation.

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Volume 40, Number 5, 2013