Hellenic J Cardiol 47: 78-83, 2006

Clinical Research
Influence of Triglycerides on Other Plasma Lipids
in Middle-Aged Men Intended for Hypolipidaemic
Treatment
GENOVEFA D. KOLOVOU1, KATHERINE K. ANAGNOSTOPOULOU1, KLELIA D. SALPEA1,
IOANNIS S. HOURSALAS1, ILIAS PETROPOULOS1, HELEN I. BILIANOU2, DIMITRIS S. DAMASKOS1,
VASILIKI N. GIANNAKOPOULOU1, DENNIS V. COKKINOS1
1
Cardiology Department, Onassis Cardiac Surgery Center Athens, 2Cardiology Department, Tzanio State Hospital,
Piraeus, Greece

Key words:
Dyslipidaemia,
coronary artery
disease.

Manuscript received:
June 10, 2005;
Accepted:
December 12, 2005.

Introduction: The present investigation aimed to evaluate the influence of serum triglycerides (TG) on other
plasma lipids in male patients less than 65 years of age intended for hypolipidaemic treatment.
Methods: Lipid profiles of a cohort of 412 dyslipidaemic male patients aged 53.4 7.7 years (mean
standard deviation) were evaluated. Patients were stratified in accordance with their fasting plasma lipid levels. They were divided into multiple groups on the basis of serum TG (150 or <150 mg/dl) and high-density lipoprotein cholesterol (HDL-C 40 or <40 mg/dl).
Results: Patients with TG 150 mg/dl had higher total cholesterol and lower HDL-C levels compared with
those with TG <150 mg/dl (p=0.005 and p<0.001, respectively). Patients with HDL-C <40 mg/dl had
similar total cholesterol levels and higher TG levels compared to those with HDL-C 40 mg/dl (p<0.001). In
all patients, an inverse correlation between TG and HDL-C was found (r= -0.286, p<0.001). Additionally,
HDL-C levels were inversely correlated with the TG concentration in patients with TG <150 mg/dl (r= -0.135,
p=0.042) and TG 150 mg/dl (r= -0.188, p=0.002).
Conclusions: An inverse correlation between TG and HDL-C levels seems to exist in the sampled population,
revealing a close link between the metabolic pathways for TG and HDL-C. This inverse correlation appears to
persist even in patients with low fasting TG levels.

Address:
Genovefa D. Kolovou
Onassis Cardiac
Surgery Center
356 Sygrou Ave
176 74 Athens, Greece
e-mail:
[email protected]

ncreased levels of low-density lipoprotein cholesterol (LDL-C) are a widely

recognised risk factor for coronary artery disease.1,2 The Prospective Cardiovascular Mnster Study first unambiguously demonstrated that increased triglyceride (TG)
concentration is also an independent risk factor for major coronary artery events. Moreover, low HDL-C levels are a well established risk factor for premature cardiovascular disease, being considered as an additional recognized target for the prevention
and treatment of atherosclerosis,3 and are
now reported as the single most important

78 HJC (Hellenic Journal of Cardiology)

predictor of survival after coronary artery

bypass grafting in men.4
Epidemiological evidence based on data from western countries seems to support
the concept of an inverse relationship between plasma TG and HDL-C levels.5 In a
pathological state such as the metabolic
syndrome, the tandem high TG - low HDLC occurs in a higher frequency that cannot
readily be considered as coincidental. Also
the report from the Expert Group on HDLC points to the fact that many individuals
with low plasma levels of HDL-C also have
high levels of TG.6 Taken together, these

Inverse correlation between TG and HDL-C levels

may imply the existence of a specific metabolic relationship between the two molecules (i.e. TG and HDLC). In the present investigation, our aim was to evaluate the relationship between serum TG and HDL-C
levels in middle-aged male patients with lipidaemic disorders about to be treated with lipid lowering
agents.
Methods
Study design and population
Subjects for this investigation were selected from male
patients less than 65 years of age, who were not being
treated with lipid-lowering agents prior to referral to
our Lipid Clinic. All patients were advised of lifestyle
changes to be followed for at least 3 months. After this
interval, fasting plasma samples for routine lipid analysis were obtained in a cohort of 412 patients aged 53.4
7.7 years (mean standard deviation: SD). All subjects fulfilled one or more of the following criteria as
defined by the NCEP ATP III report:7 1) total cholesterol (TC) >240 mg/dl, or >170 mg/dl in patients with
coronary artery disease; 2) TG values >150 mg/dl; and/
or 3) HDL-C <40 mg/dl.
In addition, based on TG and HDL-C levels patients were subdivided according to: a) TG levels <150
mg/dl or 150 mg/dl; b) HDL-C levels <40 mg/dl or
40 mg/dl; c) TG 150 mg/dl and HDL-C 40 mg/dl;
d) TG 150 mg/dl and HDL-C <40 mg/dl; e) TG <150
mg/dl and HDL-C 40 mg/dl; and f) TG <150 mg/dl
and HDL-C <40 mg/dl.

and performed using Pearsons coefficient; a p value of

<0.05 was taken to be significant.
Results
Characteristics of patients
The mean values and respective SD of the various plasma lipids in the studied population were: TC = 288
63 mg/dl, LDL-C = 209 62 mg/dl, TG = 187 99
mg/dl, HDL-C = 41 11 mg/dl and the ratio TC/ HDLC = 7.5 2.7. A small percentage of the study cohort
had only one abnormal lipid parameter, i.e. 20.9% had elevated TC levels (240 mg/dl), 3.2% had elevated TG
levels (150 mg/dl) and 4.4% of the cohorts had low
HDL-C levels (<40 mg/dl). In 29.1% of the study cohort all three of the lipid parameters were abnormal.
Of the 412 subjects, 6.6% had normal TC levels with
TG levels 150 mg/dl + HDL-C <40 mg/dl, while
20.4% and 9% had abnormal TC levels with TG 150
mg/dl + HDL-C 40 mg/dl and TG <150 mg/dl +
HDL-C <40 mg/dl, respectively.
Composition of cohort based on TG levels (150 or
<150 mg/dl)
Patients with serum TG levels 150 mg/dl had lower
HDL-C levels, higher TC levels and a higher TC/HDL-C
ratio compared to those with serum TG levels <150
mg/dl. However, the two groups had similar LDL-C
levels (Table 1).

Blood chemistry
The plasma levels of TC, TG and HDL-C were measured by enzymatic colorimetric methods using a Roche
Integra Biochemical analyser with commercially available kits (Roche Diagnostics GmbH, Mannheim,
Germany). The serum LDL-C levels were calculated
in patients with fasting TG concentrations <4.5 mmol/l
(400 mg/dl) using the Friedewald formula.8
Statistical analysis
Categorical variables are presented as percentages
and numerical characteristics as mean values one
SD. The chi-square test was used for the comparison of
categorical variables, and the t-test for independent
samples or the Mann Whitney U test for the comparison of numerical values following testing for normality.
Correlation between HDL-C and TG was one-tailed

Table 1. Concentration of various lipids in subgroups according to

triglyceride levels.
TG 150 mg/dl
N
Age (years)
TC (mg/dl)
LDL-C (mg/dl)
TG (mg/dl)
HDL-C (mg/dl)
TC/HDL-C

246
53.4 7.5
294.6 60.7
207.7 61.5
240.4 94.7
38.8 10.4
8.1 2.7

TG <150 mg/dl

166
53.4 8.1
276.9 65
210.5 62
107.9 27
44.8 11.5
6.6 2.5

0.923
0.005
0.656
<0.001
<0.001
<0.001

All values are given as mean SD.

HDL-C high-density lipoprotein cholesterol; LDL-C low-density lipoprotein cholesterol; N number of patients; TC total
cholesterol; TG triglycerides.
For TC, HDL-C and LDL-C; to convert from mg/dl to mmol/L divide by 38.7.
For TG, to convert from mg/dl to mmol/L divide by 88.6.

(Hellenic Journal of Cardiology) HJC 79

G.D. Kolovou et al
Table 2. Concentration of various lipids in subgroups according to
HDL cholesterol levels.
HDL-C 40 mg/dl
N
Age (years)
TC (mg/dl)
LDL-C (mg/dl)
TG (mg/dl)
HDL-C (mg/dl)
TC/HDL-C

HDL-C <40 mg/dl

208
53.8 7.6
290.5 62
209.2 61.5
158.4 71.8
50 8.5
5.9 1.4

ratio compared to those with TG levels <150 mg/dl and

HDL-C levels <40 mg/dl (Table 3).

Correlations

204
53 7.8
0.315
284.3 64
0.323
208.4 61.9
0.892
216.8 114.2 <0.001
32.3 4.9
<0.001
9.0 2.8
<0.001

An inverse correlation between HDL-C and TG was

found to exist in the entire population studied (r=
-0.286, p<0.001). Additionally, HDL-C levels were inversely correlated with TG concentration in patients
with TG <150 mg/dl (r= -0.135, p=0.042) and TG
150 mg/dl (r= -0.188, p=0.002). When examining the
correlations between TG and HDL-C in terms of quartiles of TG, a significant inverse correlation was observed only in the fourth quartile (r= -0.171, p= 0.042).

Notes as in table 1.

Composition of cohort based on HDL-C levels (40 or

<40 mg/dl)

Discussion

Patients with HDL-C <40 mg/dl had significantly

higher TG levels and similar LDL-C and TC levels
compared to those with HDL-C 40 mg/dl. The patients with higher HDL-C levels demonstrated a significantly lower TC/HDL-C ratio (Table 2).

The data collected in the present study support the

view that, in untreated, dyslipidaemic, middle-aged
men, fasting TG levels correlate inversely with HDLC levels. This inverse correlation exists not only when
TG levels are high, but also when they are low.
Data collected over 25 years ago from the Framingham Heart Study demonstrated that TG levels could influence the coronary artery disease risk only in patients
with a low HDL-C concentration.9 After numerous reports, the association of high TG concentration with
low HDL-C levels is now well established among patients with coronary artery disease,10 diabetes mellitus,11,12 metabolic syndrome,13,14 familial combined dyslipidaemia,15 and Tangier disease.16
Our current study confirmed that patients with HDLC <40 mg/dl, a low concentration according to the
last NCEP ATP III,6 have higher serum TG levels than
do patients with HDL-C levels 40 mg/dl. The relationship between low HDL and high TG levels appears

Composition of cohort based on HDL-C (40 or <40

mg/dl) and TG (150 or <150 mg/dl)
Patients with TG levels 150 mg/dl and HDL-C
levels <40 mg/dl were the largest group (35.7% of the
study population) and those with TG levels <150 mg/dl
and HDL-C levels <40 mg/dl were the smallest group
(13.6% of the study population).
Patients with TG levels 150 mg/dl and HDL 40
mg/dl had lower TG levels and a lower TC/HDL-C ratio compared to those with TG levels 150 mg/dl and
HDL-C levels <40 mg/dl. On the other hand, patients
with TG levels <150 mg/dl and HDL-C levels 40
mg/dl demonstrated higher TC and a lower TC/HDL-C

Table 3. Concentration of various lipids in subgroups according to levels of triglycerides and HDL cholesterol.
TG 150 mg/dl
+
HDL-C40 mg/dl
N
Age (years)
TC (mg/dl)
LDL-C (mg/dl)
TG (mg/dl)
HDL-C (mg/dl)
TC/HDL-C

99
54.2 6.9
294.7 58.7
203 59.9
215.8 60.4
48.8 8.2
6.2 1.3

Notes as in table 1.

80 HJC (Hellenic Journal of Cardiology)

TG 150 mg/dl
+
HDL-C<40 mg/dl
147
52.9 7.8
294.5 62.1
210.8 62.5
257 109
32.1 4.9
9.4 2.5

0.190
0.980
0.331
<0.001
<0.001
<0.001

TG <150 mg/dl
+
HDL-C40 mg/dl

TG <150 mg/dl
+
HDL-C40 mg/dl

109
53.4 8.3
286.8 64.8
214.8 62.7
106.3 28.3
51.1 8.6
5.7 1.4

57
53.3 7.7
257.2 61.4
202 60.2
111.1 24.3
32.7 4.9
8.2 3.2

0.916
0.006
0.212
0.276
<0.001
<0.001

Inverse correlation between TG and HDL-C levels

to be independent of other plasma lipids. Additionally,

an inverse correlation was found in the entire population being studied, independently of HDL-C. Such a
correlation persists even in those patients with low TG
levels. Up to now, it was not clearly established if the
serum TG levels were correlated in any fashion with the
HDL-C levels. Evidence published in the current literature indicates that the correlation between TG and
HDL-C levels is not a simple one. For example, Le Na
and Guinsberg17 have demonstrated heterogeneity in
apolipoprotein A-I turnover in patients with different
TG and HDL-C levels, while it has been suggested that
TGs could influence HDL and apolipoprotein A-I turnover and determine HDL catabolism rate.18
One hypothesis that has been proposed by Patsch
and colleagues,19,20 to explain in part the correlation
between HDL-C and TG levels, suggests that a low concentration of HDL-C is the consequence of non-efficient postprandial clearance of TG-rich lipoproteins
and comprises a marker of postprandial hypertriglyceridaemia. A plausible mechanism to explain this inverse correlation is that in the hypertriglyceridaemic
state, the TG-rich lipoproteins being formed are more
prone to cholesteryl ester transfer protein (CETP) action, exchanging TG for HDL-cholesteryl esters. This
enhanced HDL-cholesteryl ester turnover causes a
low state of plasma HDL-C levels (Figure 1).21 However, it is likely that this relationship is bidirectional and
encompasses more than one metabolic route.22 Inhibition of CETP has been proposed as a strategy to raise
HDL-C levels. CETP inhibitors such as JTT-705 and
torcetrapid have been shown to increase plasma HDL
levels in experimental animals as well as in humans.23
Other factors besides TG that have a further influence on HDL-C levels are body mass index, adipose tissue distribution, serum glucose and insulin levels, smoking and alcohol intake.24,25 However, De Oliveirae Silva

et al26 showed that in a multiple regression analysis the

next strongest HDL-C covariate after apo A-I levels is
the log of TG concentration.
Certainly, information on the above factors could
be valuable in estimating their supplementary effect
on HDL-C and the prevalence of the metabolic syndrome in the population that we studied. Our initial
aim was to evaluate the influence of TG on the baseline lipid profile, therefore such data were not systematically collected and that lack of information could
be considered as a limitation of the present study.
A number of epidemiological studies have demonstrated an inverse correlation between HDL-C levels
and coronary artery disease.27 Thus, it has been suggested that the inverse correlation between serum TG and
HDL-C concentrations is a good marker, which may be
used to tie the state of hypertriglyceridaemia with coronary artery disease.28,29,30
In comparing our present data to other studies,
some observations on the frequency of variable HDL-C
levels in patients free of medication can be made. In the
present population, the frequency of low HDL-C levels
was 49.5%, while in the Israeli Ischemic Heart Disease
Study31 31% of the male civil servants without coronary
artery disease had HDL-C <35mg/dl. In contrast, the
prevalence of low HDL-C in the USA is only 15% among
the general male population.32 The greater discrepancy
between our study and the US is probably due to the
fact that the population we studied was dyslipidaemic
and did not represent the general Greek population.
On the other hand, the Mediterranean diet of the Greek
population differs in terms of a lower intake of saturated fatty acids when compared to the dietary habits in
the US population, a fact that should benefit the lipid
profile of the Greek population, even if that cannot
be concluded based on the present data. The higher
prevalence of low HDL observed in our patient popu-

TG: triglyceride, HDL: high-density lipoprotein cholesterol, CETP: cholesteryl ester transfer
protein, CE: cholesteryl ester, LDL: low-density lipoprotein, HL: hepatic lipase.
Figure 1. Mechanism of the inverse relation between high triglyceride and low HDL cholesterol levels.
(Hellenic Journal of Cardiology) HJC 81

G.D. Kolovou et al

lation could also be attributed to differences in the genetic background and other factors, such as the higher
tobacco smoking and lower alcohol consumption of the
Greek population in contrast to other populations.33,34
In conclusion, an inverse correlation between fasting TG and HDL-C levels was found among dyslipidaemic, untreated, middle-aged men. Of particular importance is that this inverse correlation also appears to
exist in subjects with low TG levels. This correlation
indirectly implies that TG and HDL-C levels depend
on common metabolic pathway(s), a possibility that
should be taken into consideration when the risk of
atherosclerosis is evaluated.

13.
14.

15.

16.

17.

References
18.
1. Stamler J, Wentworth D, Neaton JD, for the MRFIT RESEARCH GROUP: Is the relationship between serum cholesterol and risk of premature death from coronary heart disease
continuous and graded? Findings in 352222 primary screeners of
the Multiple Risk Factor Intervention Trial (MRFIT). JAMA
1986; 256: 2823-2828.
2. The Scandinavian Simvastatin Survival Study Group: Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival
Study (4S). Lancet 1994; 344: 1383-1389.
3. Kolovou GD, Cokkinos DV: Low serum levels of high-density lipoprotein cholesterol and hypolipidaemic treatment.
Curr Med Res Opin 2002; 18: 265-268.
4. Foody JM, Pearce GL, Ferdinand FD, et al: HDL predicts
survival in Post-CABG men: 20-year experience from The
Cleveland Clinic Foundation. Circulation 2000; 102: III90-94.
5. Anonymous: Hypertriglyceridemia and vascular risk: Report
of a Meeting of Physicians and Scientists, University College
London Medical School. Lancet 1993; 342: 781-787.
6. Sacks FM; Expert Group on HDL-C: The role of high-density lipoprotein (HDL) cholesterol in the prevention and treatment of coronary heart disease: expert group recommendations. Am J Cardiol 2002; 90: 139-143.
7. Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults: Executive Summary of
The Third Report of The National Cholesterol Education
Program (NCEP) Expert Panel on Detection, Evaluation,
and Treatment of High Blood Cholesterol In Adults (Adult
Treatment Panel III). JAMA 2001; 285: 2486-2497.
8. Friedewald WT, Levy RI, Fredrickson DS: Estimation of the
concentration of the low-density lipoprotein cholesterol in
plasma, without use of the preparative ultracentrifuge. Clin
Chem 1972; 18: 499-502.
9. Castelli WP: The triglyceride issue: a view from Framingham.
Am Heart J 1986; 112: 432-437.
10. Jeppesen J, Hein HO, Suadicani P, et al: High triglycerides/lowhigh density lipoprotein cholesterol, ischemic electrocardiogram changes, and risk of ischemic heart disease. Am Heart J
2003; 145: 103-108.
11. Wilson PW, Kannel WB, Anderson KM: Lipids, glucose intolerance and vascular disease: the Framingham study. Monogr
Atheroscler 1985; 13: 1-11.
12. Teno S, Uto Y, Nagashima H, et al: Association of postpran-

82 HJC (Hellenic Journal of Cardiology)

19.

20.
21.

22.

23.

24.

25.

26.

27.

28.

29.
30.

dial hypertriglyceridemia and carotid intima media thickness

in patients with type 2 diabetes. Diabetes Care 2000; 23: 14011406.
Reaven GM: Banting lecture 1988. Role of insulin resistance
in human disease. Diabetes 1988; 37: 1595-1607.
Jeppesen J, Hein HO, Suadicani P, et al: Relation of high
TG-low HDL-C and LDL cholesterol to the incidence of ischemic heart disease. An 8-year follow-up in the Copenhagen
Male Study. Arterioscler Thromb Biol 1997; 17: 1114-1120.
Soro A, Jauhiainen M, Ehnholm C, et al: Determinants of
low HDL levels in familial combined hyperlipidemia. J Lipid
Res 2003; 44: 1536-1544.
Kolovou G, Daskalova D, Anagnostopoulou K, et al: Postprandial hypertriglyceridaemia in patients with Tangier disease. J Clin Pathol 2003; 56: 937-941.
Le NA, Ginsberg HN: Heterogeneity of apolipoprotein A-I
turnover in subjects with reduced concentrations of plasma
high-density lipoprotein cholesterol. Metabolism 1988; 37:
614-617.
Lamarche B, Rashid S, Lewis GF: HDL metabolism in hypertriglyceridemic states: an overview. Clin Chim Acta 1999;
286: 145-161.
Patsch JR, Prasad S, Gotto AM Jr, et al: High-density lipoprotein2: relationship of the plasma levels of this lipoprotein
species to its composition, to the magnitude of postprandial
lipemia and to the activities of lipoprotein lipase and hepatic
lipase. J Clin Invest 1987; 80: 341-347.
Gotto AM Jr, Patsch JR, Yamamoto A: Postprandial hyperlipidemia. Am J Cardiol 1991, 68: 11A-12A
Murakami T, Michelagnoli S, Longhi R, et al: Triglycerides
are major determinants of cholesterol esterification/transfer
and HDL remodeling in human plasma. Arterioscler Thromb
Vasc Biol 1995; 15: 1819-1828.
Kolovou G, Anagnostopoulou K, Pilatis N, et al: Fasting serum
triglyceride and high-density lipoprotein cholesterol levels in
patients intended to be treated for dyslipidemia. Vasc Health
Risk Manage 2005; 1: 155-161.
Kolovou GD, Anagnostopoulou KK, Cokkinos DV: Pathophysiology of dyslipidaemia in the metabolic syndrome. Postgrad Med J 2005; 81: 358-366.
Ellison RC, Zhang Y, Qureshi MM, et al: Lifestyle determinants of high-density lipoprotein cholesterol: the National
Heart, Lung, and Blood Institute Family Heart Study. Am
Heart J 2004; 147: 529-535.
Goff DC Jr, DAgostino RB Jr, Haffner SM, et al: Insulin resistance and adiposity influence lipoprotein size and subclass
concentrations. Results from the Insulin Resistance Atherosclerosis Study. Metabolism 2005; 54: 264-270.
De Oliveirae Silva ER, Kong M, Han Z, et al: Metabolic and
genetic determinants of HDL metabolism and hepatic lipase
activity in normolipidemic females. J Lipid Res 1999; 40:
1211-1221.
Gordon DJ, Probstfield JL, Garrison RJ, et al: High-density
lipoprotein cholesterol and cardiovascular disease. Four prospective American Studies. Circulation 1989; 79: 8-15.
Hulley SB, Rosenman RH, Bawol RD, et al: Epidemiology as
a guide to clinical decisions. The association between triglyceride and coronary heart disease. N Engl J Med 1980; 302:
1383-1389.
Austin MA: Plasma triglycerides and coronary heart disease.
Atheroscler Thromb 1991; 11: 2-14.
Lamarche B, Desprs JP, Moorjani S, et al: Triglycerides and
HDL-cholesterol as risk factors for ischemic heart disease.

Inverse correlation between TG and HDL-C levels

Results from the Qubec Cardiovascular Study. Atherosclerosis 1996; 119: 235-245.
31. Goldbourt U, Yaari S, Medalie JH: Isolated low HDL-C as a
risk factor for coronary heart disease mortality: A 21-year follow-up of 8000 men. Arterioscler Thromb Vasc Biol 1997; 17:
107-113.
32. Maron DJ: The epidemiology of low levels of high-density
lipoprotein cholesterol in patients with and without coronary
artery disease. Am J Cardiol 2000, 86: 11L-14L.

33. Fumeron F, Betoulle D, Luc G, et al: Alcohol intake modulates the effect of a polymorphism of the cholesteryl ester
transfer protein gene on plasma high-density lipoprotein and
the risk of myocardial infarction. J Clin Invest 1995; 96: 16641671.
34. Kauma H, Savolainen MJ, Heikkila R, et al: Sex difference in
the regulation of plasma high-density lipoprotein cholesterol
by genetic and environmental factors. Hum Genet 1996; 97:
156-162.

(Hellenic Journal of Cardiology) HJC 83