Professional Documents
Culture Documents
Investigation
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
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
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
Characteristic
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
402 (63)
111 (49)
291 (71)
0.28 0.12
0.26 0.11
0.007
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
36 11
39 12
35 11
<0.001
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
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
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
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
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
114 46
108 42
0.322
102 34
101 33
0.703
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
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
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
Ejection fraction
<0.145
3.208
1.9665.234
<0.001
Sodium
<128.5 mEq/L
2.674
1.4165.048
0.002
525
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
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
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
526
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
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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