© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Apolipoprotein Concentrations During Treatment and Recurrent Coronary Artery Disease Events
From the Department of Cardiology (J.E.R.v.L., E.E.v.d.W.) and Department of Medical Statistics (A.H.Z.), Leiden University Medical Center, Leiden; Department of Internal Medicine (H.T.W., D.W.E.), University Medical Center Utrecht, Utrecht and Oosterschelde Hospital (H.W.O.R.v.L), Goes, the Netherlands. Correspondence to Ernst E. van der Wall, MD, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
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Abstract—The effect of untreated total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) as cardiovascular risk factors in both primary and secondary prevention has been extensively investigated. The predictive value of on-treatment lipid and apolipoprotein levels on subsequent cardiovascular events is as yet uncertain. Eight hundred forty-eight patients (675 men and 173 women) with angiographically proven coronary artery disease (CAD) who received effective statin therapy (
30% decrease of baseline TC) were
studied. We analyzed the predictive value of on-treatment
levels of TC, LDL-C, triglycerides (TG), apolipoprotein A-I
(apoA-I) and apolipoprotein B (apoB) on subsequent myocardial
infarction (MI) and all cause mortality. On-treatment LDL-C levels were
2.55±0.55 mmol/L and 2.58±0.62 mmol/L for men and women
respectively. Age-adjusted Cox regression analysis showed that
only on-treatment apoA-I was predictive for future CAD events in both
men and women, whereas on-treatment HDL-C was exclusively predictive in
women. On-treatment apoB levels were predictive for recurrent CAD
events in the total population but not after separate analysis
for men and women. On-treatment levels of TC, LDL-C, and TG did not
predict subsequent events. Multivariate
analysis showed that on-treatment apoA-I and apoB were the only
significant predictors for future cardiovascular
events. On-treatment levels of TC, LDL-C, and TG were no longer
associated with increased risk of recurrent
cardiovascular events in CAD patients treated to target
levels, which justifies the current guidelines. However, on-treatment
levels of apoB and in particular apoA-I (and HDL-C in women) were
significantly predictive for MI and all-cause mortality and may
therefore be more suitable for cardiovascular risk
assessment in this population.
Key Words: lipids • apolipoproteins • risk factors • coronary disease
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Introduction |
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Major randomized lipid intervention trials have convincingly demonstrated the clinical benefit of lipid lowering therapy in both primary and secondary prevention.1 2 3 4 5 Therefore, elevated levels of total cholesterol (TC), and more specifically elevated levels of low density lipoprotein cholesterol (LDL-C), have become highly modifiable risk factors. Besides TC and LDL-C, elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels are other important lipid factors associated with an increased risk on coronary heart disease.6 7 Furthermore, apolipoprotein B (apoB) and A-I (apoA-I), the major apolipoproteins of LDL-C and HDL-C particles, have been suggested as better markers than LDL-C and HDL-C in the assessment of risk on coronary artery disease (CAD).8 9 10
Because of their safety and efficacy, statin therapy plays a major role in the management of patients who are at risk for CAD events. An increasing number of patients with hyperlipidemia will therefore achieve target lipid levels as recommended by international guidelines. The National Cholesterol Education Program (NCEP) guidelines recommend target levels of LDL-C of <2.6 mmol/L (100 mg/dL) in patients with established CAD.11 However, the risk on recurrent coronary events in patients with LDL-C levels treated to these targets has never been established. In addition, the predictive value of lipid and apolipoprotein levels during lipid lowering therapy on subsequent cardiovascular events has not sufficiently been investigated.
Accordingly, the aim of this study was to investigate the effect of both lipids and apolipoproteins A-I and B on myocardial infarction (MI) and all-cause mortality in men and women with documented CAD who were adequately treated with lipid lowering therapy.
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Methods |
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Patient Population and Follow-Up
The study population derived from a population of 3095 consecutive patients who underwent a first diagnostic coronary angiogram between July 1981 and January 1998 at the Oosterschelde Hospital in Goes, the Netherlands. Patients who were referred for coronary angiography for reasons other than suspicion of CAD (eg, valve pathology, cardiomyopathy) were excluded from analysis (n=365). We next excluded patients without hemodynamically significant coronary artery disease (defined as
60% luminal narrowing, n=682). We then excluded
1200 patients who did not show a 30% reduction of TC by lipid
lowering therapy (statin therapy either alone or in combination with
cholestyramine or gemfibrozil) or in whom no complete lipid profile was
known. As a result 848 patients (675 men and 173 women) could be
included for final analysis. To acquire mortality data, the computerized hospital system was screened. Subsequently, all family practitioners in the region were asked to verify whether patients who underwent coronary angiography and belonged to their practice were currently alive.
Using this information, we sent a questionnaire containing questions
about clinical and lifestyle characteristics to all patients who were
known to be alive. Letters were submitted to population registers and
family members to obtain information about patients who could not be
located or who did not return their questionnaires. Through these
procedures, 3084 (99.7%) of all patients could be traced. The
questionnaires were returned by 2285 (93.0%) of the 2457 eligible
patients. Medical records were consulted to obtain clinical and
lifestyle characteristics of the remaining patients. Myocardial
infarction was enzymatically diagnosed. The follow-up period of each
patient was calculated from the date of the first complete lipid
profile that showed a 30% decrease of baseline TC level until death,
non-fatal myocardial infarction, or until September 1, 1999.
Coronary Angiography
Coronary angiography was performed according to the
standard Judkins technique. An obstruction in 1 of the 3 major
epicardial coronary arteries of 60% on visual examination
was considered hemodynamically
significant.8 12 The coronary angiograms were
evaluated visually and independently by 2 experienced cardiologists. In
case of disagreement, a third observer was consulted to reach
consensus.
Lipids and Apolipoproteins
All plasma lipid and apolipoprotein concentrations were
determined from overnight fasting blood samples. TC and TG
concentrations were measured enzymatically (Vitros analyzer,
Johnson & Johnson). HDL-C fractions were prepared by precipitation from
plasma of the apoB containing lipoproteins with the use of dextran
sulfate and MgCl2. Plasma LDL-C was calculated
with the Friedewald formula
(TC-[HDL-C]-[0.45xTG]).13 ApoA-I and apoB were
measured by immunonephelometry on a Beckman array protein system:
Beckman reagents, calibrators, and standards were used. All patients in
this study were on statin therapy(simvastatin,
atorvastatin, fluvastatin, or pravastatin). For
each patient, a baseline TC level without statin therapy was used as
reference value. Additionally, baseline HDL-C level was known of 290
men and 81 women, LDL-C level of 270 men and 76 women, TG of 297 men
and 80 women, and apoA-I/apoB level of 188 men and 54 women. There were
no important differences between baseline total cholesterol
levels in patients with or without complete baseline lipid profile. The
first complete lipid profile (TC, HDL-C, LDL-C, TG, apoA-I, and apoB)
that demonstrated a 30% decrease of baseline TC level was used for
analysis. Previous studies have shown that a 30% lowering of
TC can be considered effective lipid treatment.4 5
Statistical Analysis
Changes in lipids and apolipoproteins were described as average
percent decrease from baseline values. Continuous and categorical
variables were analyzed by Student’s t test and
2 analysis respectively. A Cox proportional-hazards
regression model was used to estimate the effect of various
age-adjusted risk factors as independent predictors of MI and all-cause
mortality. A multivariate Cox proportional-hazards
regression analysis was performed to measure the combined
effect of the variables on MI and all-cause mortality. All lipid
and apolipoprotein variables were analyzed as continuous
variables unless stated otherwise. Because of interdependency of
several lipid factors, LDL-C and HDL-C could not enter the
multivariate model.Therefore a ridge regression
analysis was performed for these variables. Values were
expressed as hazard ratios (HR) with 95% confidence intervals (CI).
Cut-off levels for high versus low HDL, apoB, and apoA-I were based to
the values that divide the subjects into 2 equal groups. A P
value <0.05 was considered statistically significant.
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Baseline Characteristics and Follow-Up
Baseline characteristics of the study population for men and women are shown in Table 1
. Age
ranged from 33 to 84 years for men and 30 to 87 years for women. Women
were older than men (66.9±9.9 years versus 64.2±9.5 years,
P<0.001, respectively). Diabetes was more prevalent in
women than in men (20.7% versus 11.9%, P=0.005,
respectively). Fewer women than men were current smokers (7.1% versus
20.1%, P<0.001, respectively). Results of coronary
angiography were similar for men and women in terms of extent of
coronary artery disease. Mean follow-up of the 675 men and 173
women was 2.95 years (0–6.61) and 3.03 years (0.1 to 6.55),
respectively. The 1-, 2-, and 3-year event-free survival rates were
93.8%, 91.0%, and 88.6% for men and 92.9%, 90.1%, and 87.6% for
women.
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Serum Lipids
Baseline lipids and apolipoprotein levels before lipid lowering
therapy for men and women showed that both sexes had similar mean
levels of TG and LDL-C (Table 2). Women had significantly
higher baseline TC and higher HDL-C levels than men (TC: 7.46±1.19
versus 6.99±1.01 mmol/L, and HDL-C: 1.32±0.31 versus
1.07±0.25 mmol/L, both P<0.0001, respectively). Also,
baseline apoA-I and apoB levels were higher for women than for men
(apoA-I: 1.55±0.22 versus 1.32±0.21 g/L, P<0.0001, and
apoB: 1.64±0.37 versus 1.52±0.28 g/L). On-treatment lipid levels
after successful lipid lowering therapy defined as the first complete
lipid profile showing a 30% reduction of baseline TC are
presented in Table 2. Compared with men, women had
higher on-treatment TC levels (4.54±0.71 versus 4.32±0.65
mmol/L, P<0.0001), higher HDL-C levels (1.22±0.31 versus
1.06±0.27 mmol/L, P<0.0001), and higher on-treatment
apoA-I levels (1.42±0.26 versus 1.28±0.22 g/L, P<0.0001).
However, because of the greater reduction in apoB in women,
on-treatment apoB levels reached similar levels for men and women. The
effects of lipid treatment showed no major differences between men and
women except for the average decrease in apoB, which was somewhat
greater in women than in men (-44.00±8.3% versus -40.99±9.6%,
P=0.04, respectively). Overall, HDL-C levels did not
increase on statin treatment, however a considerable standard deviation
was observed. Cox regression analysis adjusted for age showed
that of all classical lipid variables (TC, LDL-C, HDL-C, and TG)
only on-treatment HDL-C levels were significantly correlated with a
decrease in recurrent cardiovascular event-rate (HR
0.37, CI 0.17 to 0.80, P=0.0012). Both on-treatment apoA-I
and apoB were significantly associated with the incidence of events in
the total study population (P=0.0005 and P=0.033,
respectively) (Table 3).
This is also illustrated in cumulative events curves that show that
patients with low HDL-C (<1.1 mmol/L) (Figure 1), high apoB (0.89 g/L) (Figure 2), and in particular low apoA-I (<1.3
g/L) (Figure 3) had an increased risk on
subsequent myocardial infarction or all-cause mortality. The predictive
value of lipids and apolipoproteins and the incidence of events as
calculated by Cox regression analysis, adjusted for in men and
women separately, is shown in Table 3. For both sexes, low
levels of on-treatment apoA-I were the most significant predictors for
primary events (P=0.026 and P=0.002 for men and
women, respectively). The predictive value of HDL-C
(P=0.004) was only seen in women. A
multivariate Cox regression model was performed to
study the effect of individual variables (TC, TG, apoA-I, apoB,
male sex, diabetes, age, angiographic results, and smoking status) on
all-cause mortality and non-fatal MI, adjusted for concomitant lipid
levels and clinical variables (Table 4). Age
(P=<0.001), ApoA-I (P=0.044), and apoB
(P=0.041) were the only significant predictors for
subsequent future events. LDL-C could not be included in the model
because of collinearity with TC. The effect of HDL-C could not be
estimated due to collinearity between apoA-I and TC. When using a ridge
regression approach, the HR of HDL-C was 0.99, CI 0.37 to 2.62
(P=NS).
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Our study revealed that only on-treatment levels of apoB and especially apoA-I were significantly predictive for MI and all-cause mortality in CAD patients receiving effective statin therapy, whereas on-treatment HDL-C level was a significant risk factor exclusively for women. On-treatment levels of TC, LDL-C, and TG were no longer associated with increased risk of recurrent cardiovascular events in this population.
LDL Metabolism and Recurrent Cardiovascular
Events
Clinical intervention trials have shown that lowering LDL-C plasma
levels with statins reduces the relative risk on major coronary
events by 
30% dependent on baseline risk.14 The
National Cholesterol Education Program (NCEP) guidelines
recommend target levels of LDL-C of <2.6 mmol/L (100 mg/dL) in
patients with established CAD.11 However, the risk on
recurrent coronary events in patients with LDL-C levels treated
to these targets have never been established. In our population,
patients were on aggressive lipid lowering therapy, resulting in
average levels of LDL-C of 2.55 mmol/L for men and 2.58
mmol/L for women. We found that neither TC nor LDL-C levels during
statin therapy were predictive for all-cause mortality and non-fatal
myocardial infarction. This finding has several implications. First,
the value of lipid lowering therapy is once more confirmed, because we
showed that effective treatment of elevated LDL-C levels eliminates
LDL-C as risk factor for recurrent cardiovascular
events. Second, our results imply that it is unlikely that further
lowering of LDL-C has any effect when treated to NCEP standards. This
is consistent with several previous studies that showed that
the magnitude of beneficial clinical effects is
diminished15 16 or even eliminated17 18 at
lower LDL-C and TC levels. Results from the Multiple Risk Factor
Intervention Trial (MRFIT)16 and the Scandinavian
Simvastatin Survival Study (4S)15 support a
curvilinear model showing a continuous but progressive decrease of
benefit on CHD risk with increased reduction of TC levels. The
Cholesterol and Recurrent Events (CARE)
study17 demonstrated that no further decline in CHD events
was to be expected with LDL-C levels below 3.2 mmol/L (125 mg/dL).
Accordingly, our findings along with these the current results provide
evidence for justification of the current guidelines.
Nevertheless, as Superko previously emphasized19 , CAD risk management cannot be simplified to LDL-C reduction. We found that apoB was a better predictor for recurrent coronary events than LDL-C. This finding is biologically plausible. Atherogenic lipoproteins including LDL-C particles and remnants of triglyceride-rich particles each contain 1 molecule of apoB.20 Consequently, apoB gives an accurate estimation of the total number of atherogenic particles.21 The composition of LDL-C particles, each containing 1 molecule of apoB, is heterogeneous because of the variable content of cholesterol. Smaller, denser LDL-C are more atherogenic than larger ones.22 23 Therefore apoB is superior compared with LDL-C in determining CAD risk. A great number of studies have confirmed that apoB is a better marker for atherogenicity and CAD than LDL-C and TC both in men9 10 and women.8 10 Recently Gotto et al24 showed in data from the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TEXCAPS) that on-treatment apoB was the only significant predictor for subsequent cardiovascular events for primary prevention. This study24 is as yet the only large study that evaluated the predictive value of on-treatment lipid and apolipoprotein levels. As our study provides information on secondary prevention our data are complementary to their results on primary prevention. In agreement with their findings, we showed that, in patients with effectively treated lipid levels, measurement of apoB seems more appropriate than LDL-C and TC plasma levels as predictor of recurrent cardiovascular events
HDL Metabolism and Recurrent Cardiovascular
Events
Low levels of plasma HDL-C are directly associated with a
significantly increased risk of CAD.25 26 27 Compared with
the knowledge of the LDL-C metabolism, our insight of HDL-C
metabolism including reverse cholesterol
transport, is incomplete. Judged by the number of recently published
studies dedicated to HDL-C, it appears that lipid research has
‘discovered’ HDL-C, due to the remarkable progress in unraveling the
HDL-C metabolism. Major breakthroughs include the discovery
of the HDL-C receptor, the scavenger receptor B-1 (SR-B1), which is
expressed at high levels at the main sites of selective uptake of
HDL-C.28 In addition, along with epidemiologic
evidence,25 29 recent major clinical intervention
trials3 30 have shown the importance of HDL-C on CAD, in
particular in patients without elevated LDL-C levels. Miller et
al29 demonstrated the significance of low HDL-C as risk
factor on the incidence of recurrent cardiovascular
events in a follow-up study of patients with angiographically proven
CAD and desirable TC levels. The AFCAPS/TexCAPS study3
showed that, in a population without a history of CAD and with normal
TC and LDL-C levels, a below-average HDL-C level (0.94 mmol/L for
men and 1.03 mmol/L for women) forms an important risk factor for
a first major coronary event. The recently published Veterans
Affairs Cooperative Studies Program High-Density Lipoprotein
Cholesterol Intervention Trial (VA-HIT)30
proved that a modest increase in HDL-C levels in CAD patients with
normal LDL-C levels (
3.6 mmol/L) resulted in a significant
reduction of risk on major cardiovascular events.
In our study, we found that only in women, on-treatment plasma HDL-C was inversely correlated with the risk for recurrent events. This is consistent with some other studies that found that the impact of HDL-C on coronary risk was greater in women than in men.26 27
ApoA-I, the major apolipoprotein of HDL-C, showed a predictive value for CHD events similar to HDL-C in women and was the only significant predictor in men. Similar to our findings, Kwiterovich et al10 found that the level of apoA-I, but not the level of HDL-C, was an indicator of future CAD for men. ApoA-I has previously been reported as a better indicator of CHD than HDL-C.10 31 32 Biologically, this finding can be explained because not all HDL-C particles are equally protective. Two predominant classes of HDL-C can be recognized; HDL-C particles that only contain apoA-I (lipoprotein A-I) and particles that contain both apoA-I and apoA-II (lipoprotein A-I:A-II). In general, lipoprotein A-I is considered to be more protective against CHD than lipoprotein A-I:A-II.33 Therefore, apoA-I levels may be a better marker for functional reverse cholesterol transport than HDL-C.
Considerations of the Study
Recently it has been stated that clinical investigators should
rely on all-cause death as an objective, unbiased end-point, rather
than rely on cardiovascular mortality alone. Therefore,
we chose to assess total mortality because of the bias existing in the
use of cardiovascular mortality, especially in a
population with known CAD.34 In our institution, all
patients had complete lipid profiles measured after 1993 and we do not
expect to create a bias in outcome by excluding patients with
incomplete profiles. We analyzed patients with 1 or more
significant coronary artery stenosis and, therefore,
our results only apply to this group and cannot be generalized.
Furthermore, we cannot answer the question whether patients with <30%
reduction in total cholesterol should be a given a higher
dose of statins as we did not assess these patients. In our opinion,
the current guidelines are appropriate as far as it concerns LDL-C
target levels as we showed that on-treatment LDL-C levels do not have
prognostic relevance anymore. To establish the prognostic value of
on-treatment apolipoproteins, large prospective trials are necessary.
Therefore, we do not think that the current guidelines should be
changed directly as a result of our study.
Conclusion
On-treatment levels of TC, LDL-C, and TG were no longer associated
with increased risk of recurrent cardiovascular events
in CAD patients treated to target levels, which justifies the current
guidelines. However, on-treatment levels of apoB and in particular
apoA-I (and HDL-C in women) were significantly predictive for MI and
all-cause mortality and may therefore be more suitable for
cardiovascular risk assessment in this population.
Received May 4, 2000; accepted August 17, 2000.
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  J. H. Contois, J. P. McConnell, A. A. Sethi, G. Csako, S. Devaraj, D. M. Hoefner, and G. R. Warnick Apolipoprotein B and Cardiovascular Disease Risk: Position Statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices Clin. Chem., March 1, 2009; 55(3): 407 - 419. [Abstract] [Full Text] [PDF]
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 J. D. Brunzell, M. Davidson, C. D. Furberg, R. B. Goldberg, B. V. Howard, J. H. Stein, and J. L. Witztum Lipoprotein Management in Patients With Cardiometabolic Risk: Consensus Conference Report From the American Diabetes Association and the American College of Cardiology Foundation J. Am. Coll. Cardiol., April 15, 2008; 51(15): 1512 - 1524. [Full Text] [PDF]
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 J. D. Brunzell, M. Davidson, C. D. Furberg, R. B. Goldberg, B. V. Howard, J. H. Stein, and J. L. Witztum Lipoprotein Management in Patients With Cardiometabolic Risk: Consensus statement from the American Diabetes Association and the American College of Cardiology Foundation Diabetes Care, April 1, 2008; 31(4): 811 - 822. [Full Text] [PDF]
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 K.-L. Chien, H.-C. Hsu, T.-C. Su, M.-F. Chen, Y.-T. Lee, and F. B. Hu Apolipoprotein B and non-high density lipoprotein cholesterol and the risk of coronary heart disease in Chinese J. Lipid Res., November 1, 2007; 48(11): 2499 - 2505. [Abstract] [Full Text] [PDF]
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J. O. Mudd, B. A. Borlaug, P. V. Johnston, B. G. Kral, R. Rouf, R. S. Blumenthal, and P. O. Kwiterovich Jr Beyond Low-Density Lipoprotein Cholesterol: Defining the Role of Low-Density Lipoprotein Heterogeneity in Coronary Artery Disease J. Am. Coll. Cardiol., October 30, 2007; 50(18): 1735 - 1741. [Abstract] [Full Text] [PDF]
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 W. A. van der Steeg, S. M. Boekholdt, E. A. Stein, K. El-Harchaoui, E. S.G. Stroes, M. S. Sandhu, N. J. Wareham, J. W. Jukema, R. Luben, A. H. Zwinderman, et al. Role of the Apolipoprotein B-Apolipoprotein A-I Ratio in Cardiovascular Risk Assessment: A Case-Control Analysis in EPIC-Norfolk Ann Intern Med, May 1, 2007; 146(9): 640 - 648. [Abstract] [Full Text] [PDF]
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 T. Pischon, C. J. Girman, F. M. Sacks, N. Rifai, M. J. Stampfer, and E. B. Rimm Non-High-Density Lipoprotein Cholesterol and Apolipoprotein B in the Prediction of Coronary Heart Disease in Men Circulation, November 29, 2005; 112(22): 3375 - 3383. [Abstract] [Full Text] [PDF]
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 P. M Ridker, N. Rifai, N. R. Cook, G. Bradwin, and J. E. Buring Non-HDL Cholesterol, Apolipoproteins A-I and B100, Standard Lipid Measures, Lipid Ratios, and CRP as Risk Factors for Cardiovascular Disease in Women JAMA, July 20, 2005; 294(3): 326 - 333. [Abstract] [Full Text] [PDF]
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N. Sattar, K. Williams, A. D. Sniderman, R. D'Agostino Jr, and S. M. Haffner Comparison of the Associations of Apolipoprotein B and Non-High-Density Lipoprotein Cholesterol With Other Cardiovascular Risk Factors in Patients With the Metabolic Syndrome in the Insulin Resistance Atherosclerosis Study Circulation, October 26, 2004; 110(17): 2687 - 2693. [Abstract] [Full Text] [PDF]
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 A. M. Wagner, O. Jorba, R. Bonet, J. Ordonez-Llanos, and A. Perez Efficacy of Atorvastatin and Gemfibrozil, Alone and in Low Dose Combination, in the Treatment of Diabetic Dyslipidemia J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3212 - 3217. [Abstract] [Full Text] [PDF]
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A. M. Wagner, A. Perez, E. Zapico, and J. Ordonez-Llanos Non-HDL Cholesterol and Apolipoprotein B in the Dyslipidemic Classification of Type 2 Diabetic Patients Diabetes Care, July 1, 2003; 26(7): 2048 - 2051. [Abstract] [Full Text] [PDF]
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F. F. Ribeiro-Filho, A. N. Faria, N. E.B. Kohlmann, M.-T. Zanella, and S. R.G. Ferreira Two-Hour Insulin Determination Improves the Ability of Abdominal Fat Measurement to Identify Risk for the Metabolic Syndrome Diabetes Care, June 1, 2003; 26(6): 1725 - 1730. [Abstract] [Full Text] [PDF]
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S. Rashid, K. D. Uffelman, P. H. R. Barrett, and G. F. Lewis Effect of Atorvastatin on High-Density Lipoprotein Apolipoprotein A-I Production and Clearance in the New Zealand White Rabbit Circulation, December 3, 2002; 106(23): 2955 - 2960. [Abstract] [Full Text] [PDF]
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 S. S. Levinson High Density- and Beta-Lipoprotein Screening for Risk of Coronary Artery Disease in the Context of New Findings on Reverse Cholesterol Transport Ann. Clin. Lab. Sci., April 1, 2002; 32(2): 123 - 136. [Abstract] [Full Text] [PDF]
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P. N. Durrington Can Measurement of Apolipoprotein B Replace the Lipid Profile in the Follow-up of Patients with Lipoprotein Disorders? Clin. Chem., March 1, 2002; 48(3): 401 - 402. [Full Text] [PDF]
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S. Miremadi, A. Sniderman, and J. Frohlich Can Measurement of Serum Apolipoprotein B Replace the Lipid Profile Monitoring of Patients with Lipoprotein Disorders? Clin. Chem., March 1, 2002; 48(3): 484 - 488. [Abstract] [Full Text] [PDF]
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 J. Frohlich, A. Sniderman, and R. H. Eckel Familial Combined Hyperlipidemia and Insulin Resistance Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 2100 - 2101. [Full Text] [PDF]
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A. D. Sniderman, T. Scantlebury, and K. Cianflone Hypertriglyceridemic HyperapoB: The Unappreciated Atherogenic Dyslipoproteinemia in Type 2 Diabetes Mellitus Ann Intern Med, September 18, 2001; 135(6): 447 - 459. [Abstract] [Full Text] [PDF]
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J. R. Crouse III and C. D. Furberg Treatment of Dyslipidemia : Room for Improvement? Arterioscler. Thromb. Vasc. Biol., November 1, 2000; 20(11): 2333 - 2335. [Full Text] [PDF]
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