CLINICS 2008;64:427-32

CLINICAL SCIENCE

HIGH RATIO OF TRIGLYCERIDES TO HDL-

CHOLESTEROL PREDICTS EXTENSIVE CORONARY
DISEASE

Protasio Lemos da Luz,I Desiderio Favarato,I Jose Rocha Faria-Neto Junior,II

Pedro Lemos,I Antonio Carlos Palandri ChagasI

doi: 10.1590/S1807-59322008000400003

da Luz PL, Favarato D, Faria-Neto Jr JR, Lemos P; Chagas ACP. High ratio of triglycerides to HDL-cholesterol ratio predicts
extensive coronary disease. Clinics. 2008;63:427-32.

An abnormal ratio of triglycerides to HDL-cholesterol (TG/HDL-c) indicates an atherogenic lipid profile and a risk for the devel-
opment of coronary disease.
OBJECTIVE: To investigate the association between lipid levels, specifically TG/HDL-c, and the extent of coronary disease.
METHODS: High-risk patients (n = 374) submitted for coronary angiography had their lipid variables measured and coronary
disease extent scored by the Friesinger index.
RESULTS: The subjects consisted of 220 males and 154 females, age 57.2 ± 11.1 years, with total cholesterol of 210± 50.3 mg/
dL, triglycerides of 173.8 ± 169.8 mg/dL, HDL-cholesterol (HDL-c) of 40.1 ± 12.8 mg/dL, LDL-cholesterol (LDL-c) of 137.3 ±
46.2 mg/dL, TG/HDL-c of 5.1 ± 5.3, and a Friesinger index of 6.6 ± 4.7. The relationship between the extent of coronary disease
(dichotomized by a Friesenger index of 5 and lipid levels (normal vs. abnormal) was statistically significant for the following:
triglycerides, odds ratio of 2.02 (1.31-3.1; p = 0.0018); HDL-c, odds ratio of 2.21 (1.42-3.43; p = 0.0005); and TG/HDL-c, odds
ratio of 2.01(1.30-3.09; p = 0.0018). However, the relationship was not significant between extent of coronary disease and total
cholesterol [1.25 (0.82-1.91; p = 0.33)] or LDL-c [1.47 (0.96-2.25; p = 0.0842)]. The chi-square for linear trends for Friesinger >
4 and lipid quartiles was statistically significant for triglycerides (p = 0.0017), HDL-c (p = 0.0001), and TG/HDL-c (p = 0.0018),
but not for total cholesterol (p = 0.393) or LDL-c (p = 0.0568). The multivariate analysis by logistic regression OR gave 1.3 ±
0.79 (p = .0001) for TG/HDL-c, 0.779 ± 0.074 (p = .0001) for HDL-c, and 1.234 ± 0.097 (p = 0.03) for LDL. Analysis of receiver
operating characteristic curves showed that only TG/HDL-c and HDL-c were useful for detecting extensive coronary disease, with
the former more strongly associated with disease.
CONCLUSIONS: Although some lipid variables were associated with the extent of coronary disease, the ratio of triglycerides to
HDL-cholesterol showed the strongest association with extent.

KEYWORDS: Lipids. Triglycerides. HDL. Cholesterol. Coronary disease.

INTRODUCTION cholesterol (HDL-c) and the incidence of atherosclerosis-

related diseases, such as ischemic heart disease, stroke, and
Lipid abnormalities have long been suspected to peripheral vascular disease.
contribute to atherosclerosis; several epidemiological and Recently, lipid particle subfractions have also been
cohort studies have established a strong association between implicated in the atherogenic process. Small dense LDL
total cholesterol, LDL-cholesterol (LDL-c), or low HDL- particles are more atherogenic than larger buoyant ones,
I
and different HDL subfractions play different roles in
Insituto do Coração, Faculdade de Medicina da Universidade de São Paulo
– São Paulo/SP, Brazil. atherogenesis. The larger and less dense HDL2 particles are
II
Faculdade de Medicina, Pontifícia Universidade Católica do Paraná - Pa- considered protective, while the small dense HDL3 particles
raná, Brazil.
Email: [email protected]
are atherogenic.1,2 The former correlate inversely with serum
Received for publication on January 28, 2008 triglycerides and small dense LDL.3 The ratio of triglycerides
Accepted for publication on April 06, 2008
to HDL-cholesterol ratio (TG/HDL-c) correlates inversely

427
High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease CLINICS 2008;64:427-32
da Luz PL et al.

with the plasma level of small, dense LDL particles. A independent influence of lipid variables on extent of coronary
TG/HDL-c ratio of 3.8 divides the distribution of LDL disease extension, dichotomized by a Friesinger index of 5.
phenotypes, with 79% of phenotype B greater than this
value, and 81% of phenotype A lower than this value4. We RESULTS
recently analyzed the relationship between plasma lipids and
development of coronary artery disease (CAD) as manifested The subjects included 374 patients, 165 (60.2%) men
by angina, positive ischemic tests, or significant obstructive and 109 (39.8%) women, with a mean age of 57 ± 11.5
lesions in the coronary angiogram. We found that an TG/ years. Total cholesterol was 214 ± 50.2 mg/dL; triglycerides,
HDL-c ratio >4 is the most powerful independent predictor 167.9±91.7 mg/dL; HDL-c, 38.5 ± 11.9 mg/dL; LDL-c,
of CAD development5. Thus, this ratio shows promise as an 142.9 ± 45 mg/dL; TG/HDL-c, 5.1 ± 4.0; and Friesinger
attractive surrogate index of the atherogenicity of the plasma index, 6.9 ± 4.4. Hypertensive and dyslipidemic subjects
lipid profile. However, little data exist on the association were predominantly male. Table 1 shows demographics of
between TG/HDL-c ratio and the extent or severity of lesions the patient sample, as well as the distribution of coronary
in coronary disease. lesions.
Objectives - To evaluate the correlation between lipid Extensive coronary disease, by univariate analysis,
variables, especially the TG/HDL-c ratio, and the extent presented a direct relationship with the quartiles of total
of coronary disease in patients investigated for suspected triglycerides, and TG/HDL-c, and an inverse relationship
CAD. with HDL-c quartiles (Table 2).
Study design – Eligible patients were outpatients who
underwent diagnostic coronary angiography for suspected Table 1 - Demographic characteristics of patient sample and
coronary disease. Friesinger index frequency
The presence of risk factors were defined as follows:
Characteristics Frequency (%)
hypercholesterolemia (total cholesterol >200 mg/
dL), hypertriglyceridemia (>150 mg/dL), high LDL- Gender (male/female) (%) 220/154

cholesterolemia (LDL-c) (>130 mg/dL), low HDL- Age (mean ± SD years old) 57.2 ± 11.1
cholesterolemia (HDL-c) (<40 mg/dL for male and <50 Hypertension 291 (78)
mg/dL for female), elevated TG/HDL-c ratio (>4), diabetes Hypercholesterolemia 208 (56)
mellitus (fasting glucose q126 mg/dL, casual or GTT Low HDL-cholesterol 246 (66)
over 200 mg/dL, or current use of oral hypoglycemiant or High LDL-cholesterol 194 (52)
insulin), hypertension (cutoff points were 140/90 mm Hg), Hypertriglyceridemia 176 (47)
and status as a current smoker.
High TG/HDL ratio 170 (46)
Laboratory tests for total cholesterol and fractions,
Diabetes mellitus 108 (29)
triglycerides, and glycemia were performed using standard
Smoking 86 (23)
techniques.
Friesinger Index
Coronary lesion extent was evaluated using the Friesinger
index6. This classification uses the following categories: 0, no 0 71 (19)
arteriographic abnormalities; 1, trivial irregularities (lesions 1–4 67 (17.9)
from 1-29%); 2, lesions from 30-68%; 3, multiple narrowing 5 – 10 135 (36.1)
in the same vessel, and the segment has either one lesion 11 – 15 101(27.0)
with a morphology defined as multiple, diffuse or tubular,
or two segments with stenosis of 30-68%; 4, at least one Table 2 - Frequency of extensive coronary disease (Friesinger
lesion of 69-100%, except in the proximal segment where index q5) by lipid quartile
it should be less than 100%; and 5, occlusion of a proximal
segment of a vessel. Left main lesions were counted as Q1 Q2 Q3 Q4 P (linear
trend)
proximal lesions of both left descending and circumflex
Total Cholesterol 70.2 47.9 62.8 71.7 0.393
arteries. Coronary lesions were scored by experts blinded to
patient lipid profiles. LDL-cholesterol 64.9 50.5 62.9 75 0.0568

Statistics - Statistics were calculated by univariate HDL-cholesterol 75 69.8 63.2 42.5 0.0001
analysis with chi-square and non-parametric ANOVA Triglycerides 55.3 56.8 72.8 76.7 0.0017
(Kruskal-Wallis), followed by multivariate analysis TG/HDL-c 47.9 63.0 66.7 75.3 0.0001
using stepwise forward logistic regression to assess the Q1, Q2, Q3, and Q4 are quartiles

428
CLINICS 2008;64:427-32 High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease
da Luz PL et al.

The odds ratios for the extent of coronary disease Table 3 - Results of multivariate analysis
between the fourth and first quartiles were as follows: total
cholesterol, 1.08, 95%CI (0.57-2.03), p = 0.87; LDL-c, B S.E. Sig. Exp(B)
1.62, 95%CI (0.86-3.06), p = 0.15; triglycerides, 1.7, 95%CI HDL-cholesterol -.249 .074 .001 .779
(0.94-3.08), p = 0.986; HDL-c, 0.25, 95%CI (0.13-0.46), TG/HDL-c .265 .079 .001 1.304
p = 0.0001; and TG/HDL-c, 3.31, 95%CI (1.78-6.14), p = LDL-cholesterol .211 .097 .030 1.234
0.0002 (Figure 1). This analysis showed that only HDL-c
and TG/HDL-c show statistically significant frequency
differences between the fourth and first quartiles, and that may be due to the fact that HDL-c and Triglycerides levels
the difference was larger for TG/HDL-c. The non-parametric were discordant in 35 (25%) of subjects with low extents of
ANOVA (Kruskal-Wallis) demonstrated a significant disease and in 75 (32%) of subjects with extensive coronary
association between extensive coronary disease and the disease. Thus, taking both variables into account by using
lipid variable quartiles. However, only HDL-c and TG/ the Triglycerides to HDL-c ratio increased the accuracy of
HDL-c--primarily the latter--showed statistically significant detecting extensive coronary disease.
differences in median Friesinger index between abnormal Analysis of the ROC curves showed the following areas
values and normal ones. Total cholesterol and LDL-c showed under the curves: 0.35 for HDL-c (p = 0.0001), 0.55 for
a similar distribution and Figure 2 therefore presents only the LDL-c (p = 0.131), and 0.63 for TG/HDL-c (p = 0.0001).
Friesinger distribution for the quartiles of total cholesterol,
triglycerides, HDL-c, and TG/HDL-c. DISCUSSION
The multivariate analysis by logistic regression included
these lipid variables, and it showed that the TG/HDL-c ratio We found a relationship between the extent of coronary
showed the strongest correlation [association] with extent disease and lipid variables using univariate analysis. In a
of coronary disease. Increasing the HDL-c quartile led to a multivariate model that included these variables, the ratio of
22% decrease in extent, while increasing the LDL-c or TG/ triglycerides to HDL-cholesterol was found to be a powerful
HDL-c quartiles led to a 23% and 30% increase in disease independent indicator of extensive coronary disease.
extent, respectively (Table 3). Despite the fact that small, dense LDL particles are
Of the 246 subjects with low HDL-c, 171 (69.5%) had an established risk factor for cardiovascular disease, the
extensive coronary disease, and of the 170 subjects with high assessment of their subfractions by current methods have
TG/HDL-c, 122 (72%) had extensive coronary disease. This been too technically demanding to be applicable in a routine

Figure 1 - Odds ratios between fourth and first quartiles of lipid variables for extensive coronary disease (Friesinger index >4)

429
High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease CLINICS 2008;64:427-32
da Luz PL et al.

Figure 2 - Boxplot distribution of Friesinger index by quartiles of total cholesterol, triglycerides, HDL-cholesterol, and TG/HDL-cholesterol

clinical laboratory. The usual techniques include density al,17 is an atherogenic index that has proven to be a highly
gradient ultracentrifugation,7 non-denaturing gradient gel significant independent predictor of myocardial infarction,
electrophoresis (NDGGE),8 and nuclear magnetic resonance even stronger than TC/HDL-c and LDL-c/HDL-c. The
(NMR) spectroscopy,9 which have the disadvantages of being Copenhagen Male Study showed triglycerides on their own
labor-intensive, technically demanding, expensive, or slow to be another strong risk factor, but it found that stratifying
to produce results. As a result, these precise and accurate triglyceride levels by HDL-c levels led to more accurate
techniques are not widely used in clinical settings. Thus, detection of increased risk of coronary disease.18
developing surrogate markers of lipid particle profiles are of The atherogenic link between high triglycerides and
great clinical and economic importance. HDL-c is due to the higher plasma concentration of
Several studies have attempted to determine the risk triglyceride-rich, very low-density lipoprotein that generates
levels for CAD using lipid indexes or formulas.10 The goal small, dense LDL during lipid exchange and lipolysis. These
of this work is to manage patients better in order to prevent LDL particles accumulate in the circulation and form small,
cardiac events. Of particular interest are ratios that have dense HDL particles, which undergo accelerated catabolism,
atherogenic particles in the numerator and HDL-c or its thus closing the atherogenic circle.19,20
constituents in the denominator. The ratio of total cholesterol The present study indicates that TG/HDL-c, which we
to HDL-c11,12 and, to a lesser extent, the ratio of LDL-c to previously showed to be an indicator of development of
HDL-c13 have been shown to be better predictors of CAD coronary heart disease development,5 is also related to the
than lipid alone. More recently, in the INTERHEART case- severity of vessel compromise. Thus this ratio is an easy,
control study, the apoB/apoA1 ratio was shown to be the non-invasive means of predicting the presence and extent of
strongest risk factor associated with myocardial infarction.14 coronary atherosclerosis.
This ratio had already been proposed as an accurate predictor Study limitations. We studied a high-risk subset of
of risk for major coronary events in the AFCAPS/TexCAPS15 patients, who showed a higher prevalence of coronary
and AMORIS16 studies. disease than the general population. We compared only
The ratio TG/HDL-c, initially proposed by Gaziano et lipid variables, and did not take into account the current

430
CLINICS 2008;64:427-32 High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease
da Luz PL et al.

use of medication or the inflammatory state of the patients. CONCLUSION

Since the commonly used statin and angiotensin enzyme
inhibitors and angiotensin II receptor blockers may alter Nearly all routinely assessed lipid variables were associated
the inflammatory state, they may weaken the relationship with the extent of coronary disease, but only the ratio of
between total cholesterol and LDL-cholesterol and the extent triglycerides to HDL-cholesterol or to HDL-c were robustly
of coronary disease. This is because they act more on LDL- associated with disease extent. Elevation in the ratio of TG to
cholesterol and less on HDL-cholesterol and triglycerides. HDL-c was the single most powerful predictor of extensive
coronary heart disease among all the lipid variables examined.

REFERENCES

1. Miller NE. Associations of high-density lipoprotein subclasses and 6. Rinqqvist I, Fisher LD, Mock M, Davis KB, Wedel H, Chaitman
apolipoproteins with ischemic heart disease and coronary atherosclerosis, BR, et al. The Coronary Artery Surgery Study. Prognostic Value of
Am Heart J. 1987;113:589–97. Angiographic Indices of Coronary Artery Disease from the Coronary
Artery Surgery Study (CASS), J Clin Invest. 1983;71:1854-66.
2. Robinson D, Ferns GA, Bevan EA, Stocks J, Williams PT, Galton DJ.
High density lipoprotein subfractions and coronary risk factors in normal 7. Krauss RM, Burke DJ. Identification of multiple subclasses of plasma
men, Arteriosclerosis. 1987;7:341-6. low density lipoprotein in normal humans, J Lipid Res. 1982;23:97-
104.
3. Williams PT, Krauss RM, Vranizan KM, Stefanick ML, Wood PDS,
Lindgren FT. Associations of lipoproteins and apolipoproteins with 8. Scheffer PG, Bakker SJL, Heine RJ, Teerlink T. Measurement of LDL
gradient gel electrophoresis estimates of high density lipoprotein particle size in whole plasma and serum by high performance gel-
subfractions in men and women, Arterioscler Thromb. 1992;12:332- filtration chromatography using a fluorescent lipid probe, Clin Chem.
40. 1998;44:2148-51

4. Hanak V, Munoz J, Teaque J, Stanley A Jr, Bittner V. Accuracy of the 9. Kuller L, Arnold A, Tracy R, Otvos J, Burke G, Psaty B, et al. Nuclear
triglyceride to high-density lipoprotein cholesterol ratio for prediction Magnetic Resonance Spectroscopy of Lipoproteins and Risk of Coronary
of the low-density lipoprotein phenotype B, Am J Cardiol. 2004;94:219- Heart Disease in the Cardiovascular Health Study, Arterioscler Thromb
22. Vasc Biol. 2002;22:1175-80.

5. Da luz PL, Cesena FH, Favarato D, Cerqueira ES. Comparison of serum 10. Ballantyne CM, Hoogeveen RC. Role of lipid and lipotrotein profiles
lipid values in patients with coronary artery disease at <50, 50 to 59, 60 in risk assessment and therapy, Am Heart J. 2003;146:227-33.
to 69, and >70 years of age, Am J Cardiol. 2005;96:1640-3.

431
High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease CLINICS 2008;64:427-32
da Luz PL et al.

11. Hong MK, Romm PA, Reagan K, Green CE, Rackley CE. Usefulness 16. Walldius G, Jungner I, Holme I, Astveit AH, Kolar W, Steiner E.
of the total cholesterol to high density lipoprotein cholesterol ratio in High apoliprotein B, low apolipoprotein A-I, and improvement in the
predicting angiographic coronary disease in women, Am J Cardiol prediction of fatal myocardial infarction (AMORIS Study): a prospective
1991;68:1646-50. study, Lancet. 2001;358:2026-33.

12. Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of 17. Gaziano JM, Hennekens CH, O’Donnell CJ, Breslow JL, Buring JE.
coronary heart disease. The Framingham Study, Ann Epidemiol. Fasting triglycerides, high density lipoprotein, and risk of myocardial
1992;2:23-8. infarction, Circulation. 1997; 96: 2520-5.

13. Manninen V, Tenkanen L, Koshinen P, Huttunen JK, Manttari M, 18. Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. Triglycerides
Heinonen PO, et al. Join effects of serum triglycerides and LDL concentration and ischemic heart disease: an eight-year follow-up in
cholesterol and HDL cholesterol concentrations on coronary heart the Copenhagen Male Study, Circulation. 1998;97:1029-36.
disease risk in the Helsinki Heart Sudy. Implications for treatment,
Circulation. 1992;85:37-45. 19. Packard CJ, Shepherd J. Lipoprotein heterogenity and apolipoprotein
B metabolism, Arterioscler Thromb Vasc Biol, 1999;19:2456-64.
14. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al.
Effect of potentially modifiable risk factors associated with myocardial 20. Brinton EA, Eeisenberg S, Breslow JL. Increased apo A-I and apo-AII
infarction in 52 countries (the INTERHEART study): case-control study. fractional catabolic rate in patients with low high density lipoprotein-
Lancet. 2004;363:937-52. cholesterol levels with or without hypertriglyceridemia, J Clin Invest.
1991;87:536-44.
15. Gotto AM Jr, Whitney E, Stein EA, Shapiro DR, Clearfield, Weis S,
et al. Relation between baseline and on-treatment lipid parameters
and first acute major coronary event in the Air Force/Texas Coronary
Atherosclerosis Prevention Study (AFCAPS/Tex CAPS), Circulation.
2000;101:477-84.

432