 |
|
Total Cholesterol/HDL Cholesterol Ratio vs LDL Cholesterol/HDL Cholesterol Ratio as Indices of Ischemic Heart Disease Risk in Men
The Quebec Cardiovascular Study
Isabelle Lemieux, MSc;
Benoît Lamarche, PhD;
Charles Couillard, PhD;
Agnès Pascot, MSc;
Bernard Cantin, MD, PhD;
Jean Bergeron, MD, MSc;
Gilles R. Dagenais, MD;
Jean-Pierre Després, PhD
Arch Intern Med. 2001;161:2685-2692.
ABSTRACT
Background Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C)
and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratios are used to predict
ischemic heart disease risk. There is, however, no consensus on which of these
2 indices is superior. The objective of the present study was to present evidence
that the LDL-C/HDL-C ratio may underestimate ischemic heart disease risk in
overweight hyperinsulinemic patients with high triglyceride (TG)–low
HDL-C dyslipidemia.
Methods A total of 2103 middle-aged men in whom measurements of the metabolic
profile were performed in the fasting state were recruited from 7 suburbs
of the Quebec metropolitan area.
Results The relationship of LDL-C/HDL-C to TC/HDL-C ratios was examined among
men in the Quebec Cardiovascular Study classified into tertiles of fasting
TG levels. For any given LDL-C/HDL-C ratio, the TC/HDL-C ratio was higher
among men in the top TG tertile (>168 mg/dL [>1.9 mmol/L]) than in men in
the first and second TG tertiles. Adjustment of the TC/HDL-C ratio for LDL-C/HDL-C
by covariance analysis generated significant differences in average TC/HDL-C
ratios among TG tertiles (P<.001). Greater differences
in features of the insulin resistance syndrome (insulinemia, apolipoprotein
B, and LDL size) were noted across tertiles of the TC/HDL-C ratio than tertiles
of the LDL-C/HDL-C ratio.
Conclusion Variation in the TC/HDL-C ratio may be associated with more substantial
alterations in metabolic indices predictive of ischemic heart disease risk
and related to the insulin resistance syndrome than variation in the LDL-C/HDL-C
ratio.
INTRODUCTION
DESPITE considerable advances during the past 40 years, there is increasing
awareness among scientists, epidemiologists, and clinicians that current approaches
to evaluation of coronary heart disease (CHD) risk in asymptomatic individuals
remain suboptimal.1 There is also controversy
around recommending widespread use of additional metabolic markers, such as
apolipoprotein (APO) levels, indices of fibrinolytic activity and of susceptibility
to thrombosis (eg, plasminogen activator inhibitor–1 and lipoprotein[a]
levels), markers of inflammation (eg, C-reactive protein levels), and markers
of insulin resistance (waist circumference and fasting insulin levels).2-9
Although all of these markers have been shown to predict CHD events, whether
these variables contribute to CHD risk independently of the variation in traditional
risk factors and lipid variables remains a matter of debate.
Regarding the traditional fasting plasma lipid profile (triglycerides
[TGs], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C]
[which is most often calculated rather than measured directly], and high-density
lipoprotein cholesterol [HDL-C]), there is no universal acceptance of how
this information should be used and interpreted, although several consensus
documents have been produced.2, 10-13
Because there is overwhelming evidence14-15
that an elevated LDL-C concentration in plasma is atherogenic, whereas a high
HDL-C level is cardioprotective,15-17
the measurement and interpretation of LDL-C and HDL-C levels is emphasized
in the US National Cholesterol Education Program guidelines.11
According to these guidelines,11 LDL-C concentration
should be considered the primary therapeutic target, whereas HDL-C levels
may also be critical in the assessment of CHD risk. Thus, because TG levels
are ignored in the National Cholesterol Education Program algorithm, the clinician
is left with LDL-C and HDL-C levels to assess risk while considering the presence
or absence of other important risk factors, such as family history of early
CHD, age, smoking, hypertension, diabetes mellitus, low physical activity,
and obesity. On this basis, the LDL-C/HDL-C ratio is often calculated to estimate
CHD risk.
Results of prospective studies18-19
have suggested that a high LDL-C/HDL-C ratio combined with hypertriglyceridemia
is associated with highest CHD risk. Thus, algorithms have been produced showing
that an elevated LDL-C/HDL-C ratio combined with elevated TG is associated
with high CHD risk. This dyslipidemic state (lipid triad) has been described
as atherogenic dyslipidemia.20 We believe that
this approach could be further simplified by using the TC/HDL-C ratio. Because
there is more cholesterol in the very LDL (VLDL) fraction in individuals with
elevated TG concentrations, the LDL-C/HDL-C ratio may underestimate the magnitude
of the dyslipidemic state in these patients. On that basis, we propose that
the high prevalence of moderate hypertriglyceridemia among patients with CHD
explains why the TC/HDL-C ratio was the best predictor of ischemic heart disease
(IHD) risk in several observational prospective studies, including the Quebec
Cardiovascular Study.5 However, reduction of
this ratio and of the LDL-C/HDL-C ratio in patients initially free of IHD
who were treated with a lipid-lowering drug (lovastatin) was found to predict
a decreased risk of a first IHD event.21
Therefore, the objective of this article was to present evidence from
the Quebec Cardiovascular Study that supports the notion that the TC/HDL-C
ratio may be a better and simpler cumulative marker of the presence of atherogenic
dyslipidemia and of increased IHD risk than the LDL-C/HDL-C ratio.
PARTICIPANTS AND METHODS
THE QUEBEC CARDIOVASCULAR STUDY
The population and evaluation procedures of the Quebec Cardiovascular
Study have been described previously.22-23
Briefly, 2443 men were evaluated in 1985 for IHD risk factors, including familial
history of IHD, history of smoking, diabetes mellitus, blood pressure measurement,
height and weight, determination of the fasting plasma lipid and lipoprotein
profile, and an electrocardiogram. Each participant completed a standardized
questionnaire administered by trained nurses. After exclusion of men with
fasting TG levels greater than 399 mg/dL (>4.5 mmol/L) and patients with clinical
signs of IHD, 2103 middle-aged men who were asymptomatic for IHD were followed
for 5 years for the occurrence of IHD events. During this period, 114 men
developed a first ischemic event, which included typical effort angina, coronary
insufficiency, nonfatal myocardial infarction, and coronary death.24 Logistic regression analysis using the Cox proportional
hazards model revealed that diabetes mellitus, LDL-C level, age, systolic
blood pressure, HDL-C level, smoking, and medication use at baseline ( -adrenergic
blocking agents and diuretics) were the best independent predictors of IHD
in this cohort.25
LABORATORY ANALYSES
After participants had fasted for 12 hours, blood samples were obtained
from an antecubital vein while participants were sitting. A tourniquet was
used, but it was released before withdrawal of blood into Vacutainer tubes
(Becton Dickinson, Mountain View, Calif) containing EDTA. Plasma was separated
from blood cells by centrifugation and immediately used for measurement of
lipoprotein-lipid and APOB levels. Aliquots of fasting plasma were frozen
at the time of collection for subsequent assessment of insulin levels. Plasma
TC and TG concentrations were determined using a Technicon RA-500 analyzer
(Bayer Corp, Tarrytown, NY), as previously described.26
The HDL-C level was measured in the supernatant after precipitation of APOB-containing
lipoproteins with heparin–manganese chloride.27
The LDL-C concentration was estimated using the equation of Friedewald et
al28 because men with TG concentrations greater
than 399 mg/dL (>4.5 mmol/L) were excluded from the analyses. Plasma APOB
concentrations were measured using the rocket immunoelectrophoretic method
of Laurell,29 as previously described.26 Serum standards for the APOB assay were prepared
in our laboratory (Lipid Research Center, Sainte-Foy, Quebec) and calibrated
against serum samples obtained from the Centers for Disease Control and Prevention
(Atlanta, Ga). The standards were lyophilized and stored at -80°C
until use. The coefficients of variation for TC, HDL-C, and TG levels were
all less than 3%, and for APOB measurements were less than 5%.
Fasting insulin concentrations were measured using a commercial double-antibody
radioimmunoassay (human insulin–specific radioimmunoassay method; LINCO
Research, St Louis, Mo). This insulin assay shows little cross-reactivity
with human proinsulin (<0.2%).30 The coefficients
of variation were 3.5% for lower insulin concentrations and 5.2% for higher
concentrations.
The LDL peak particle diameter was obtained from the nondenaturing 2%
to 16% polyacrylamide gel electrophoresis of whole plasma, which was kept
at -80°C before use, according to the procedure described by Krauss
and Burke31 and by McNamara et al.32 Gels were cast in our laboratory using acrylamide
and bisacrylamide (30.0:0.8) obtained from Bio-Rad (Hercules, Calif). A volume
of 7.5 µL of plasma samples was applied on lanes in a final concentration
of 20% sucrose and 0.25% bromophenol blue. Electrophoresis was performed in
a refrigerated cell (10°C-15°C) for a prerun of 15 minutes at 125
V and for the entry of samples into stacking at 70 V, followed by migration
at 200 V for 12 to 16 hours and finally at 400 V for 2 to 4 hours. Gels were
stained for lipids overnight with sudan black (Lipostain, Paragon electrophoresis
system; Beckman, Montreal, Quebec) in 55% ethanol. Gels were destained in
a 45% ethanol solution, and original gel size was restored in a 9% acetic
acid, 20% methanol solution. A plasma pool was used as an internal standard.
Gels were analyzed using an optical densitometer image analyzer (Bio-Image
Visage 110) coupled to a SPARC Station 2 Sun computer (Millipore, Ville St-Laurent,
Quebec) and using GEL 1D software. Low-density lipoprotein peak particle size
was obtained using the migration of standards of known diameter, such as ferritin
(122 Å), thyroglobulin (170 Å), and 380-Å latex beads (Duke
Scientific Corp, Palo Alto, Calif), and plasma standards of known diameter.
Analyses of pooled plasma standards revealed that identification of the major
LDL peak was highly reproducible, with an interassay coefficient of variation
of less than 3% (B. Lamarche, PhD, A. Tchernof, PhD, S. Moorjani, PhD, et
al, unpublished data, 1997).
STATISTICAL PROCEDURES
All analyses were conducted using the SAS statistical computer program
package (SAS Institute, Cary, NC). Prevalence odds ratios for quintiles of
the LDL-C/HDL-C or TC/HDL-C ratios were assessed using logistic regression
procedures. Group differences for continuous variables were examined using
either the t test or the general linear model, and
the Duncan post-hoc test was used in situations in which a significant group
effect was observed. Pearson product moment correlation coefficients were
used to quantify associations between variables. Statistical adjustment of
data was performed using the general linear model procedure, with adjustment
for the LDL-C/ HDL-C ratio.
RESULTS
Table 1 gives the baseline
characteristics of the 114 men who developed IHD compared with those who remained
IHD free during 5-year follow-up. Overall, men with IHD were characterized
by an unfavorable metabolic profile compared with asymptomatic men. When the
TC/HDL-C ratio was included in a multivariate model, it was found to be the
best single predictor of IHD risk in the Quebec Cardiovascular Study.5 Neither TG nor HDL-C levels further contributed to
IHD risk once the TC/HDL-C ratio had been considered in the analysis. These
observations are concordant with results from the Copenhagen Male Study,33 where it was found that after adjustment for age
and nonlipid risk factors, the TC/HDL-C ratio was the strongest predictor
of IHD risk. Results presented in Figure 1 indicate that there was a progressive increase in the IHD odds
ratio across quintiles of the TC/HDL-C ratio, whereas only men in quintiles
4 and 5 of the LDL-C/HDL-C ratio were characterized by increased IHD risk.
We believe that there is a metabolic rationale underlying this finding. It
is well documented that high TG–low HDL-C dyslipidemia, which is often
linked to abdominal obesity and insulin resistance, is associated with marginal
or even no change in LDL-C levels.34 Furthermore,
LDL-C concentrations are often estimated from 3 measurements (TG, TC, and
HDL-C) rather than measured directly. Thus, a variation that may reach 25%
in estimated LDL-C levels could be explained by these 3 components.35 This variation may therefore have a major effect
on the calculated LDL-C/HDL-C ratio. On the other hand, the 2 components of
the TC/HDL-C ratio are measured directly, and this ratio can be used in men
with TG levels greater than 399 mg/dL (>4.5 mmol/L).
|
|
|
|
Table 1. Characteristics of 114 Men in the Quebec Cardiovascular Study
Who Developed IHD Compared With 1989 Men Who Remained IHD Free During 5-Year
Follow-up*
|
|
|
|
|
|
|
Figure 1. Odds ratios for ischemic heart
disease (IHD) during 5-year follow-up in 2103 men in the Quebec Cardiovascular
Study classified according to quintiles of low-density lipoprotein cholesterol
(LDL-C)/high-density lipoprotein cholesterol (HDL-C) (A) and total cholesterol
(TC)/HDL-C (B) ratios. Numbers below the bars indicate the mean LDL-C/HDL-C
or TC/HDL-C ratios for each quintile, whereas numbers above the bars indicate
the relative odds ratio compared with the first quintile.
|
|
|
As given in Table 2, men
in the Quebec Cardiovascular Study with high TG–low HDL-C dyslipidemia
(TG,  177 mg/dL [2.0 mmol/L]; and HDL-C, <35 mg/dL [<0.9 mmol/L])
were characterized by a higher body mass index (calculated as weight in kilograms
divided by the square of height in meters) and by elevated fasting insulin
concentrations compared with normolipidemic men despite identical LDL-C levels
in the 2 groups. Moreover, the IHD event rate was 2 times higher among these
men. Thus, when the LDL-C/HDL-C ratio was computed in these overweight hyperinsulinemic
patients with high TG–low HDL-C dyslipidemia, its increase resulted
only from the reduced HDL-C levels associated with this condition (Figure 2). However, the increased TC/HDL-C
ratio obtained in overweight hyperinsulinemic men with high TG–low HDL-C
dyslipidemia not only resulted from the decreased HDL-C level but also from
the slight increase in the TC level as more TC was associated with the calculated
VLDL fraction in hypertriglyceridemic individuals than in normolipidemic men
(Figure 2). Thus, the relative difference
in the TC/HDL-C ratio in overweight patients with high TG–low HDL-C
dyslipidemia vs normotriglyceridemic men (62%) was greater than the difference
in the LDL-C/HDL-C ratio between these 2 groups (54%).
|
|
|
|
Table 2. Characteristics of 1426 Men in the Quebec Cardiovascular Study
Classified on the Basis of TG and HDL-C Levels*
|
|
|
|
|
|
|
Figure 2. Relative differences in the total
cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and low-density
lipoprotein cholesterol (LDL-C)/HDL-C ratios between normolipidemic men and
men of the Quebec Cardiovascular Study with high triglyceride (TG)–low
HDL-C dyslipidemia. VLDL indicates very low-density lipoprotein; ellipses,
not applicable. To convert cholesterol from milligrams per deciliter to millimoles
per liter, multiply milligrams per deciliter by 0.02586. To convert insulin
from microunits per milliliter to picomoles per liter, multiply microunits
per milliliter by 6.945. Body mass index is calculated as weight in kilograms
divided by the square of height in meters.
|
|
|
This phenomenon is further illustrated in Figure 3, in which participants in the Quebec Cardiovascular Study
were stratified into tertiles of fasting TG levels. In all TG tertiles, significant
correlations were observed between LDL-C/HDL-C and TC/HDL-C ratios (r = 1.00, 0.99, and 0.96 in the 3 TG tertiles, respectively; P<.001), a finding that would, at first glance, suggest
that both ratios essentially provide similar information. However, the intercept
of the relationship between the 2 ratios was different among the 3 TG tertiles.
Thus, among men in the top TG tertile (TG, >168 mg/dL [>1.9 mmol/L]), higher
TC/HDL-C ratios were found for any given LDL-C/HDL-C value than in the 2 other
tertiles. Accordingly, results in Figure 4 indicate that the difference in the TC/HDL-C ratio in the top tertile
vs the first tertile of fasting TG levels was greater than the difference
in the LDL-C/HDL-C ratio. Our results are in accordance with those of Leroux
et al,36 who demonstrated that the relative
cholesterol content of the calculated VLDL fraction increased across TG quintiles,
whereas there was also relatively less cholesterol associated with the HDL
fraction as a function of increasing triglyceridemia. Moreover, a study conducted
by McNamara et al37 demonstrated that the difference
between the estimated LDL-C concentrations and values obtained by measuring
cholesterol in the LDL fraction isolated by ultracentrifugation was substantially
greater in hypertriglyceridemic individuals than in those with normal TG levels.
|
|
|
|
Figure 3. Relationships between the low-density
lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C)
and total cholesterol (TC)/HDL-C ratios among men in the Quebec Cardiovascular
Study divided into tertiles of fasting plasma triglyceride (TG) levels. To
convert TG from milligrams per deciliter to millimoles per liter, multiply
milligrams per deciliter by 0.01129.
|
|
|
|
|
|
|
Figure 4. Low-density lipoprotein cholesterol
(LDL-C)/high-density lipoprotein cholesterol (HDL-C) and total cholesterol
(TC)/HDL-C ratios according to triglyceride (TG) tertiles in men in the Quebec
Cardiovascular Study. Asterisk indicates significantly different from the
first tertile; dagger, significantly different from the second tertile (P<.001). The relative difference between the third and
first tertiles of LDL-C/HDL-C or TC/HDL-C ratios is indicated above the bar.
Numbers within parentheses indicate the mean TG level for each tertile. Error
bars represent SE. To convert TG from milligrams per deciliter to millimoles
per liter, multiply milligrams per deciliter by 0.01129.
|
|
|
To quantify potential differences in the TC/HDL-C ratio and in the risk
profile beyond what could be explained by the LDL-C/HDL-C ratio, we adjusted
the TC/HDL-C ratio for the concomitant variation in LDL-C/HDL-C ratio by covariance
analysis (Table 3). Thus, when
the TC/HDL-C ratios across TG tertiles were standardized for an LDL-C/HDL-C
ratio of 3.99, the first TG tertile (TG, <115 mg/dL [<1.3 mmol/L]) had
an adjusted TC/HDL-C ratio of 5.49, the second TG tertile (TG, 115-168 mg/dL
[1.3-1.9 mmol/L]) had a TC/HDL-C ratio of 5.73, whereas the top TG tertile
(TG, >168 mg/dL [>1.9 mmol/L]) had a TC/HDL-C ratio that reached 6.33. Thus,
the results indicate that individuals with similar LDL-C/HDL-C ratios may
have markedly different TC/HDL-C ratios depending on their fasting TG levels.
|
|
|
|
Table 3. Characteristics of Men in the Quebec Cardiovascular Study
Classified on the Basis of Tertiles of TG Levels After Adjustment for LDL-C/HDL-C
Ratio by Covariance Analysis*
|
|
|
Lamarche et al38 also previously reported
that patients with high TG–low HDL-C are characterized by clustering
metabolic abnormalities described as the atherogenic metabolic triad of nontraditional
risk factors, which included hyperinsulinemia, elevated APOB level, and small,
dense LDL particles. Thus, a higher proportion of men with elevated TG levels
were also characterized by the features of the atherogenic metabolic triad. Figure 5 shows that men with high TG concentrations
had elevated APOB and insulin levels and smaller LDL particles than men characterized
by low TG levels.
|
|
|
|
Figure 5. Fasting apolipoprotein B and insulin
levels and low-density lipoprotein (LDL) peak particle size among triglyceride
(TG) tertiles in men in the Quebec Cardiovascular Study. Asterisk indicates
significantly different from the first tertile; dagger, significantly different
from the second tertile (P<.001). Numbers within
parentheses indicate the mean TG level for each tertile. Error bars represent
SE. To convert TG from milligrams per deciliter to millimoles per liter, multiply
milligrams per deciliter by 0.01129. To convert insulin from microunits per
milliliter to picomoles per liter, multiply microunits per milliliter by 6.945.
|
|
|
Accordingly, Figure 6 compares
these features of the atherogenic metabolic triad (insulin, APOB, and LDL
size) across tertiles of TC/HDL-C and LDL-C/HDL-C ratios. There was a progressive
increase in plasma APOB (+47 mg/dL; +50%) and insulin (+3 µU/mL [+21.3
pmol/L]; +32%) levels from the first to the third TC/HDL-C tertiles, which
was accompanied by a significant decrease in LDL peak particle size (-4.65
Å; -2%). There was also a progressive increase in APOB (+48 mg/dL;
+52%) and insulin (+2 µU/mL [+14.7 pmol/L]; +21%) concentrations and
a decrease in LDL peak particle diameter (-3.52 Å; -1%)
in the first vs third tertiles of the LDL-C/HDL-C ratio. However, there was
a greater deterioration in 2 of the 3 features of the atherogenic metabolic
triad (insulin and LDL size) across TC/HDL-C ratio tertiles than among tertiles
of the LDL-C/HDL-C ratio. Therefore, although both LDL-C/HDL-C and TC/HDL-C
ratios were significantly correlated with the features of the atherogenic
metabolic triad related to the insulin resistance syndrome (hyperinsulinemia,
elevated APOB level, and small, dense LDL particles), variation in the TC/HDL-C
ratio seems to better reflect underlying metabolic alterations in the features
of the insulin resistance syndrome than the LDL-C/HDL-C ratio.
|
|
|
|
Figure 6. Fasting apolipoprotein B and insulin
levels and low-density lipoprotein (LDL) peak particle size among tertiles
of total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) or
LDL-C/HDL-C ratios in men in the Quebec Cardiovascular Study. Asterisk indicates
significantly different from the first tertile; dagger, significantly different
from the second tertile (P<.005). The absolute
and relative differences between the top and first tertiles of TC/HDL-C or
LDL-C/HDL-C ratios are indicated above the bars. Numbers below the bars indicate
the mean TC/HDL-C or LDL-C/HDL-C ratios for each tertile. Error bars represent
SE. To convert insulin from microunits per milliliter to picomoles per liter,
multiply microunits per milliliter by 6.945.
|
|
|
COMMENT
An elevated TC/HDL-C ratio in men is observed among overweight, hyperinsulinemic,
and hypertriglyceridemic individuals. Additional metabolic alterations found
in these individuals include, among others, elevated APOB levels, an exaggerated
postprandial lipemia, and small, dense LDL particles.39-43
Results of the present study suggest that these atherogenic metabolic disturbances
may not always be adequately reflected by the variation in the LDL-C/HDL-C
ratio.
In the Quebec Cardiovascular Study, Lamarche et al38
previously reported that variables such as APOB and fasting insulin levels
and LDL size could provide a more refined evaluation of IHD risk than traditional
lipid variables. In clinical practice, however, these markers are not measured,
and we propose that, in addition to the well-established conventional risk
factors, the TC/HDL-C ratio may represent an important cumulative index of
the presence of an atherogenic dyslipidemic profile associated with insulin
resistance. Because the high TG–low HDL-C dyslipidemia associated with
small, dense LDL particles has been suggested to represent the most prevalent
lipoprotein phenotype among patients with CHD,44
the importance of measuring and properly interpreting the TC/HDL-C ratio (rather
than the LDL-C/HDL-C ratio) is emphasized.
In summary, the TC/HDL-C ratio was a useful and simple index of IHD
risk in men in the Quebec Cardiovascular Study. It is proposed that the ability
of this ratio to predict risk is explained by the fact that it is a relevant
cumulative marker of the cluster of metabolic abnormalities found in individuals
with high TG–low HDL-C dyslipidemia. This condition has been shown to
be the consequence of abdominal obesity and insulin resistance and is also
commonly associated with an increased concentration of small, dense LDL particles.
Because little variation is found in plasma LDL-C levels in overweight hyperinsulinemic
men compared with normolipidemic individuals, we propose that calculation
of the LDL-C/HDL-C ratio may underestimate IHD risk in some patients compared
with the quality of the estimation achieved with the simple use of the TC/HDL-C
ratio.
AUTHOR INFORMATION
Accepted for publication April 18, 2001.
This study was supported in part by the Canadian Institutes of Health
Research, the Quebec Heart and Stroke Foundation, and an unrestricted grant
from Fournier Pharma Inc, Montreal, Quebec. Dr Després is chair professor
of human nutrition and lipidology, which is supported by Pfizer, Provigo,
and the Foundation of the Quebec Heart Institute. Dr Lamarche is chair professor
at Laval University. Ms Lemieux is a research fellow of the Heart and Stroke
Foundation of Canada. Dr Bergeron is a clinical research scholar from the
Fonds de la Recherche en Santé du Québec.
Corresponding author and reprints: Jean-Pierre Després, PhD,
Quebec Heart Institute, Laval Hospital Research Center, 2725, chemin Sainte-Foy,
Pavilion Mallet, Second Floor, Sainte-Foy, Quebec, Canada G1V 4G5
(e-mail: jean-pierre.despres{at}crchul.ulaval.ca).
From the Quebec Heart Institute, Laval Hospital Research Center Mss
Lemieux and Pascot and Drs Couillard, Cantin, Dagenais, Després), and
the Lipid Research Center, CHUL Research Center (CHUQ) (Drs Lamarche, Couillard,
Cantin, Bergeron, and Després and Mss Lemieux and Pascot), Sainte-Foy,
Quebec.
REFERENCES
1. Superko HR. The new thinking on lipids and coronary artery disease. Curr Opin Cardiol. 1997;12:180-187.
WEB OF SCIENCE
| PUBMED
2. Assmann G, Cullen P, Jossa F, Lewis B, Mancini M for the International Task Force for the Prevention of Coronary Heart
Disease. Coronary heart disease: reducing the risk: the scientific background
to primary and secondary prevention of coronary heart disease: a worldwide
view. Arterioscler Thromb Vasc Biol. 1999;19:1819-1824.
FREE FULL TEXT
3. Koenig W, Sund M, Frohlich M, et al. C-reactive protein, a sensitive marker of inflammation, predicts future
risk of coronary heart disease in initially healthy middle-aged men: results
from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease)
Augsburg Cohort Study, 1984 to 1992. Circulation. 1999;99:237-242.
FREE FULL TEXT
4. Sniderman AD, Genest JJ. The measurement of apolipoprotein B should replace the conventional
lipid profile in screening for cardiovascular risk. Can J Cardiol. 1992;8:133-140.
WEB OF SCIENCE
| PUBMED
5. Lamarche B, Moorjani S, Lupien PJ, et al. Apolipoprotein A-I and B levels and the risk of ischemic heart disease
during a five-year follow-up of men in the Québec Cardiovascular Study. Circulation. 1996;94:273-278.
FREE FULL TEXT
6. Juhan Vague I, Alessi MC, Vague P. Increased plasma plasminogen activator inhibitor 1 levels: a possible
link between insulin resistance and atherothrombosis. Diabetologia. 1991;34:457-462.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
7. Després JP, Lamarche B, Mauriège P, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med. 1996;334:952-957.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
8. Lemieux S, Prud'homme D, Bouchard C, Tremblay A, Després JP. A single threshold value of waist girth identifies normal-weight and
overweight subjects with excess visceral adipose tissue. Am J Clin Nutr. 1996;64:685-693.
FREE FULL TEXT
9. Cantin B, Gagnon F, Moorjani S, et al. Is lipoprotein(a) an independent risk factor for ischemic heart disease
in men? the Quebec Cardiovascular Study. J Am Coll Cardiol. 1998;31:519-525.
FREE FULL TEXT
10. Final report: Canadian Consensus Conference on the prevention of heart
and vascular disease by altering serum cholesterol and lipoprotein risk factors. CMAJ. 1988;139:1-8.
11. National Cholesterol Education Program. Second report of the Expert Panel on Detection, Evaluation and Treatment
of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation. 1994;89:1333-1445.
PUBMED
12. Joint British recommendations on prevention of coronary heart disease in clinical practice. Heart. 1998;80:S1-S29.
13. Fodor JG, Frohlich JJ, Genest JJ Jr, McPherson PR. Recommendations for the management and treatment of dyslipidemia: report
of the Working Group on Hypercholesterolemia and Other Dyslipidemias. CMAJ. 2000;162:1441-1447.
FREE FULL TEXT
14. Kannel WB, Neaton JD, Wenworth D, et al. Overall and coronary heart disease mortality rates in relation to major
risk factors in 325,348 men screened for the MRFIT. Am Heart J. 1986;112:825-836.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
15. Castelli WP, Garrison RJ, Wilson PWF, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels:
the Framingham Study. JAMA. 1986;256:2835-2838.
FREE FULL TEXT
16. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart
disease: the Framingham study. Am J Med. 1977;62:707-714.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
17. Miller GJ, Miller NE. Plasma high density lipoprotein concentration and development of ischaemic
heart disease. Lancet. 1975;1:16-19.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
18. Assmann G, Schulte H, Funke H, von Eckardstein A. The emergence of triglycerides as a significant independent risk factor
in coronary artery disease. Eur Heart J. 1998;19(suppl M):M8-M14.
19. Manninen V, Tenkanen L, Koshinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol
concentrations on coronary heart disease risk in the Helsinki Heart Study:
implications for treatment. Circulation. 1992;85:37-45.
FREE FULL TEXT
20. Grundy SM. Small LDL, atherogenic dyslipidemia, and the metabolic syndrome. Circulation. 1997;95:1-4.
FREE FULL TEXT
21. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men
and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998;279:1615-1622.
FREE FULL TEXT
22. Dagenais GR, Robitaille NM, Lupien PJ, et al. First coronary heart disease event rates in relation to major risk
factors: Québec Cardiovascular Study. Can J Cardiol. 1990;6:274-280.
WEB OF SCIENCE
| PUBMED
23. Lamarche B, Després JP, Moorjani M, Cantin B, Dagenais GR, Lupien PJ. Prevalence of dyslipidemic phenotypes in ischemic heart disease (prospective
results from the Québec Cardiovascular Study). Am J Cardiol. 1995;75:1189-1195.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
24. Gillum RF, Fortmann SP, Prineas RJ, Kottke TE. International diagnostic criteria for acute myocardial infarction and
acute stroke. Am Heart J. 1984;108:150-158.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
25. Després JP, Lemieux I, Dagenais GR, Cantin B, Lamarche B. HDL-cholesterol as a marker of coronary heart disease risk: the Québec
Cardiovascular Study. Atherosclerosis. 2000;153:263-272.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
26. Moorjani S, Dupont A, Labrie F, et al. Increase in plasma high density lipoprotein concentration following
complete androgen blockage in men with prostatic carcinoma. Metabolism. 1987;36:244-250.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
27. Albers JJ, Warnick GR, Wiebe D, et al. Multi-laboratory comparison of three heparin-MnCl2 precipitation
procedures for estimating cholesterol in high-density lipoproteins. Clin Chem. 1978;24:853-856.
FREE FULL TEXT
28. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low density lipoprotein cholesterol
in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502.
FREE FULL TEXT
29. Laurell CB. Electroimmunoassay. Scand J Clin Lab Invest Suppl. 1972;124:21-27.
PUBMED
30. Orchard TJ, Becker DJ, Bates M, Kuller LH, Drash AL. Plasma insulin and lipoprotein concentrations: an atherogenic association? Am J Epidemiol. 1983;118:326-337.
FREE FULL TEXT
31. Krauss RM, Burke DJ. Identification of multiple subclasses of plasma low density lipoproteins
in normal humans. J Lipid Res. 1982;23:97-104.
ABSTRACT
32. McNamara JR, Campos H, Ordovas JM, Peterson J, Wilson PWF, Schaefer EJ. Effect of gender, age, and lipid status on low density lipoprotein
subfraction distribution: results from the Framingham Offspring Study. Arteriosclerosis. 1987;7:483-490.
FREE FULL TEXT
33. Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. Relation of high TG–low HDL cholesterol and LDL cholesterol to
the incidence of ischemic heart disease: an 8-year follow-up in the Copenhagen
Male Study. Arterioscler Thromb Vasc Biol. 1997;17:1114-1120.
FREE FULL TEXT
34. Lamarche B, Després JP, Moorjani S, Cantin B, Dagenais GR, Lupien PJ. Triglycerides and HDL-cholesterol as risk factors for ischemic heart
disease: results from the Québec Cardiovascular Study. Atherosclerosis. 1996;119:235-245.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
35. Schectman G, Sasse E. Variability of lipid measurements: relevance for the clinician. Clin Chem. 1993;39:1495-1503.
FREE FULL TEXT
36. Leroux G, Lemieux I, Lamarche B, et al. Influence of triglyceride concentration on the relationship between
lipoprotein cholesterol and apolipoprotein B and A-I levels. Metabolism. 2000;49:53-61.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
37. McNamara JR, Cohn JS, Wilson PW, Schaefer EJ. Calculated values for low-density lipoprotein cholesterol in the assessment
of lipid abnormalities and coronary disease risk. Clin Chem. 1990;36:36-42.
FREE FULL TEXT
38. Lamarche B, Tchernof A, Mauriège P, et al. Fasting insulin and apolipoprotein B levels and low-density lipoprotein
particle size as risk factors for ischemic heart disease. JAMA. 1998;279:1955-1961.
FREE FULL TEXT
39. Couillard C, Bergeron N, Prud'homme D, et al. Postprandial triglyceride response in visceral obesity in men. Diabetes. 1998;47:953-960.
ABSTRACT
40. Tchernof A, Lamarche B, Prud'homme D, et al. The dense LDL phenotype: association with plasma lipoprotein levels,
visceral obesity, and hyperinsulinemia in men. Diabetes Care. 1996;19:629-637.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
41. Lemieux I, Pascot A, Couillard C, et al. Hypertriglyceridemic waist: a marker of the atherogenic metabolic triad
(hyperinsulinemia, hyperapoB, small, dense LDL) in men? Circulation. 2000;102:179-184.
FREE FULL TEXT
42. Björntorp P. Abdominal obesity and the metabolic syndrome. Ann Med. 1992;24:465-468.
WEB OF SCIENCE
| PUBMED
43. Després JP. Abdominal obesity as important component of insulin-resistance syndrome. Nutrition. 1993;9:452-459.
WEB OF SCIENCE
| PUBMED
44. Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype: a proposed genetic marker for coronary
heart disease risk. Circulation. 1990;82:495-506.
FREE FULL TEXT
 CiteULike  Connotea  Delicious  Digg  Facebook  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Tocilizumab Monotherapy Reduces Arterial Stiffness as Effectively as Etanercept or Adalimumab Monotherapy in Rheumatoid Arthritis: An Open-label Randomized Controlled Trial
KUME et al.
The Journal of Rheumatology 2011;38:2169-2171.
ABSTRACT
| FULL TEXT
Lipid re-screening: what is the best measure and interval?
Takahashi et al.
Heart 2010;96:448-452.
ABSTRACT
| FULL TEXT
Beyond Low-Density Lipoprotein Cholesterol: Respective Contributions of Non-High-Density Lipoprotein Cholesterol Levels, Triglycerides, and the Total Cholesterol/High-Density Lipoprotein Cholesterol Ratio to Coronary Heart Disease Risk in Apparently Healthy Men and Women
Arsenault et al.
J Am Coll Cardiol 2010;55:35-41.
ABSTRACT
| FULL TEXT
Soy Protein Reduces Serum LDL Cholesterol and the LDL Cholesterol:HDL Cholesterol and Apolipoprotein B:Apolipoprotein A-I Ratios in Adults with Type 2 Diabetes
Pipe et al.
J. Nutr. 2009;139:1700-1706.
ABSTRACT
| FULL TEXT
Prospective studies on the relationship between high-density lipoprotein cholesterol and cardiovascular risk: a systematic review
Chirovsky et al.
European Journal of Cardiovascular Prevention & Rehabilitation 2009;16:404-423.
ABSTRACT
| FULL TEXT
Lipid profiles in middle-aged men and women after famine exposure during gestation: the Dutch Hunger Winter Families Study
Lumey et al.
Am J Clin Nutr 2009;89:1737-1743.
ABSTRACT
| FULL TEXT
Mathieu et al.
Heart 2009;95:938-939.
FULL TEXT
Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor
Chechi et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009;296:R1029-R1040.
ABSTRACT
| FULL TEXT
Association of serum lipid indices with large artery atherosclerotic stroke
Bang et al.
Neurology 2008;70:841-847.
ABSTRACT
| FULL TEXT
Glycemic index and glycemic load in relation to food and nutrient intake and metabolic risk factors in a Dutch population
Du et al.
Am J Clin Nutr 2008;87:655-661.
ABSTRACT
| FULL TEXT
Site-Specific Reduction of Oxidative and Lipid Metabolism in Adipose Tissue of 3'-Azido-3'-Deoxythymidine-Treated Rats
Deveaud et al.
Antimicrob. Agents Chemother. 2007;51:583-590.
ABSTRACT
| FULL TEXT
Fish-oil esters of plant sterols improve the lipid profile of dyslipidemic subjects more than do fish-oil or sunflower oil esters of plant sterols
Demonty et al.
Am J Clin Nutr 2006;84:1534-1542.
ABSTRACT
| FULL TEXT
Association of total cholesterol versus other serum lipid parameters with the short-term prediction of cardiovascular outcomes: Tehran Lipid and Glucose Study
Hadaegh et al.
European Journal of Cardiovascular Prevention & Rehabilitation 2006;13:571-577.
ABSTRACT
| FULL TEXT
Metabolic Syndrome Negatively Influences Disease Progression and Prognosis in Aortic Stenosis
Briand et al.
J Am Coll Cardiol 2006;47:2229-2236.
ABSTRACT
| FULL TEXT
A Cholesterol-Rich Diet Accelerates Bacteriologic Sterilization in Pulmonary Tuberculosis
Perez-Guzman et al.
Chest 2005;127:643-651.
ABSTRACT
| FULL TEXT
Lipid Profiles in HIV-Infected Patients Receiving Combination Antiretroviral Therapy: Are Different Antiretroviral Drugs Associated with Different Lipid Profiles?
Fontas et al.
The Journal of Infectious Disease 2004;189:1056-1074.
ABSTRACT
| FULL TEXT
A Comparison of the Effects of Nevirapine and Nelfinavir on Metabolism and Body Habitus in Antiretroviral-Naive Human Immunodeficiency Virus-Infected Patients: A Randomized Controlled Study
Fisac et al.
J. Clin. Endocrinol. Metab. 2003;88:5186-5192.
ABSTRACT
| FULL TEXT
Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis
Boers et al.
Ann Rheum Dis 2003;62:842-845.
ABSTRACT
| FULL TEXT
Calcium intake, body composition, and lipoprotein-lipid concentrations in adults
Jacqmain et al.
Am J Clin Nutr 2003;77:1448-1452.
ABSTRACT
| FULL TEXT
Impact of Protease Inhibitor Substitution With Efavirenz in HIV-Infected Children: Results of the First Pediatric Switch Study
McComsey et al.
Pediatrics 2003;111:e275-e281.
ABSTRACT
| FULL TEXT
Nonfasting Apolipoprotein B and Triglyceride Levels as a Useful Predictor of Coronary Heart Disease Risk in Middle-Aged UK Men
Talmud et al.
Arterioscler. Thromb. Vasc. Bio. 2002;22:1918-1923.
ABSTRACT
| FULL TEXT
|
