Remnant cholesterol as a cause of ischemic heart disease: Evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment

doi:10.1016/j.pharmthera.2013.11.008

Pharmacology & Therapeutics

Volume 141, Issue 3, March 2014, Pages 358-367

https://doi.org/10.1016/j.pharmthera.2013.11.008 Get rights and content

Abstract

This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels are considered.

Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1 mmol/L (39 mg/dL) in levels of nonfasting remnant cholesterol associates with a 2.8-fold increased risk of IHD, independently of high-density lipoprotein cholesterol levels. Results from genetic studies also show that elevated levels of remnant cholesterol are causally associated with both low-grade inflammation and IHD. However, elevated levels of LDL cholesterol are associated with IHD, but not with low-grade inflammation. Such results indicate that elevated LDL cholesterol levels cause atherosclerosis without a major inflammatory component, whereas an inflammatory component of atherosclerosis is driven by elevated remnant cholesterol levels.

Post-hoc subgroup analyses of randomized trials using fibrates in individuals with elevated triglyceride levels, elevated remnant cholesterol levels, show a benefit of lowering triglycerides or remnant cholesterol levels; however, large randomized trials with the primary target of lowering remnant cholesterol levels are still missing.

Section snippets

Introduction including definition

Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide. An important risk factor for IHD is elevated levels of low-density lipoprotein (LDL) cholesterol, but even after lowering of LDL cholesterol to recommended levels, there is a considerable residual risk of IHD. Some of this residual risk may be explained by elevated remnant cholesterol levels (Chapman et al., 2011).

Lipoproteins transport water-insoluble triglycerides and cholesterol between tissues and organs

Remnant cholesterol levels and observational risk of ischemic heart disease

Large observational studies, and meta-analyses thereof, have shown that elevated triglycerides are associated with increased risk of cardiovascular disease (Austin, 1991, Chapman et al., 2011, Di Angelantonio et al., 2009, Freiberg et al., 2008, Hokanson and Austin, 1996, Nordestgaard et al., 2007, Varbo, Benn, Tybjaerg-Hansen and Nordestgaard, 2013); however, the association of elevated remnant cholesterol levels with cardiovascular disease risk is not as thoroughly studied. Although there has

Remnant cholesterol, genetic variation, and causal risk of ischemic heart disease

Plasma levels of remnant cholesterol (and likewise triglycerides) are partly genetically determined by common and rare genetic variants (Hegele et al., 2009, Johansen, Kathiresan and Hegele, 2011, Johansen, Wang, et al., 2011, Yuan et al., 2007), and partly determined by lifestyle factors such as diet, obesity, alcohol intake, and physical activity (Chapman et al., 2011). Several rare genetic variants are known to influence levels of triglycerides, and thus remnant cholesterol levels, such as

Measurement of remnant cholesterol

Separation of lipoproteins into different classes was first done by ultracentrifugation in the 1940's (Gofman et al., 1956). Since then, assays for measuring remnants using different methods have been developed (Hanada et al., 2012, Havel, 2000, Nakajima et al., 1993, Nakajima et al., 2011, Ooi and Nordestgaard, 2011). However, as lipoprotein remnants are different both in composition of lipids and apolipoproteins as a result of different stages of triglyceride lipolysis and exchange of

Atherogenicity of elevated remnant cholesterol

Mechanistically, the explanation for a causal effect of elevated levels of nonfasting remnant cholesterol on increased risk of IHD likely is simple and straight forward, that is, that remnant cholesterol, like LDL cholesterol, enter and is trapped in the intima of the arterial wall (Nordestgaard et al., 1992, Nordestgaard et al., 1995, Shaikh et al., 1991), leading to accumulation of intimal cholesterol, atherosclerosis and ultimately IHD (Fig. 5).

Different sizes of lipoproteins presumably play

Remnant cholesterol levels in high risk patient groups

The most common cause of elevated remnant cholesterol and triglycerides is obesity (Table 1). Likewise, poorly controlled diabetes mellitus and excessive alcohol intake are common causes of elevated remnant cholesterol levels. In some women, high estrogen levels, either endogenous during pregnancy or from exogenous sources like oral contraceptives or hormone replacement therapy, can lead to high triglycerides, and possibly high remnant cholesterol levels. Kidney and liver diseases, and a number

Lowering of remnant cholesterol levels using current approaches

In a recent consensus document (Chapman et al., 2011), therapeutic targeting of triglycerides ≥1.7 mmol/L (≥150 mg/dL) was recommended in patients at high risk of cardiovascular disease after lowering of LDL cholesterol below recommended levels, which includes lowering of remnant cholesterol. Elevated levels of remnant cholesterol can be lowered by lifestyle changes and by pharmacological therapy. Lifestyle changes that effectively lower remnant cholesterol levels include weight reduction (the

Future pharmacological approaches to lowering remnant cholesterol levels

Given the documented causal association between elevated levels of remnant cholesterol and increased risk of IHD (Jorgensen et al., 2013, Varbo, Benn, Tybjaerg-Hansen, Jorgensen, et al., 2013, Varbo, Benn, Tybjaerg-Hansen and Nordestgaard, 2013), and the lack of well documented effect in reducing IHD risk in those with elevated remnant cholesterol levels with statins, fibrates, and/or niacin, there is a clear need for new therapies to reduce remnant cholesterol as add on therapy to statins or

Conclusions and perspectives

In conclusion, evidence from observational studies, in-vitro and animal studies, and from genetic studies all support a causal association between elevated levels of remnant cholesterol and increased risk of IHD; however, even though post-hoc subgroup analyses of randomized trials using fibrates showed a benefit of lowering triglycerides or remnant cholesterol levels, large randomized clinical intervention trials with the primary target of lowering remnant cholesterol levels are still missing.

Funding sources

The research of AV, MB and BGN are supported by The Danish Council for Independent Research, Medical Sciences (FSS), The Danish Heart Foundation, Herlev Hospital, Copenhagen University Hospital, Copenhagen County Foundation, and Chief Physician Johan Boserup and Lise Boserup's Fund, Denmark.

Conflict of interest disclosures

BGN has received lecture and/or consultancy honoraria from Omthera, Sanofi-Aventis/Regeneron, Aegerion, AstraZeneca, Amgen, and ISIS Pharmaceuticals. AV and MB have no conflicts of interest.

References (110)

H.E. Bays et al.
Icosapent ethyl, a pure EPA omega-3 fatty acid: Effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study)
J Clin Lipidol
(2012)
P.L. Canner et al.
Fifteen year mortality in Coronary Drug Project patients: Long-term benefit with niacin
J Am Coll Cardiol
(1986)
M. Casula et al.
Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, double blind, placebo controlled trials
Atheroscler Suppl
(2013)
M. Cuchel et al.
Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: A single-arm, open-label, phase 3 study
Lancet
(2013)
S. Devaraj et al.
Remnant-like particle cholesterol levels in patients with dysbetalipoproteinemia or coronary artery disease
Am J Med
(1998)
R. Frikke-Schmidt et al.
Context-dependent and invariant associations between lipids, lipoproteins, and apolipoproteins and apolipoprotein E genotype
J Lipid Res
(2000)
H. Fukushima et al.
Comparison of remnant-like lipoprotein particles in postmenopausal women with and without coronary artery disease and in men with coronary artery disease
Am J Cardiol
(2001)
H. Fukushima et al.
Prognostic value of remnant-like lipoprotein particle levels in patients with coronary artery disease and type II diabetes mellitus
J Am Coll Cardiol
(2004)
A.M. Gotto et al.
Recent clinical studies of the effects of lipid-modifying therapies
Am J Cardiol
(2012)
H. Hanada et al.
Establishment of chemiluminescence enzyme immunoassay for apolipoprotein B-48 and its clinical applications for evaluation of impaired chylomicron remnant metabolism
Clin Chim Acta
(2012)

K. Higashi et al.

Remnant-like particles cholesterol is higher in diabetic patients with coronary artery disease

Metabolism

(2001)

M. Hiki et al.

Serum levels of remnant lipoprotein cholesterol and oxidized low-density lipoprotein in patients with coronary artery disease

J Cardiol

(2009)

P.N. Hopkins et al.

Plasma triglycerides and type III hyperlipidemia are independently associated with premature familial coronary artery disease

J Am Coll Cardiol

(2005)

C.T. Johansen et al.

Genetic determinants of plasma triglycerides

J Lipid Res

(2011)

M. Jun et al.

Effects of fibrates on cardiovascular outcomes: A systematic review and meta-analysis

Lancet

(2010)

F. Karpe et al.

Remnant lipoproteins are related to intima-media thickness of the carotid artery independently of LDL cholesterol and plasma triglycerides

J Lipid Res

(2001)

E. Kiss-Toth et al.

Human tribbles, a protein family controlling mitogen-activated protein kinase cascades

J Biol Chem

(2004)

P.M. Lavigne et al.

The current state of niacin in cardiovascular disease prevention: A systematic review and meta-regression

J Am Coll Cardiol

(2013)

H. Masuoka et al.

Predictive value of remnant-like particles cholesterol/high-density lipoprotein cholesterol ratio as a new indicator of coronary artery disease

Am Heart J

(1998)

H. Masuoka et al.

Association of remnant-like particle cholesterol with coronary artery disease in patients with normal total cholesterol levels

Am Heart J

(2000)

J.R. McNamara et al.

Remnant-like particle (RLP) cholesterol is an independent cardiovascular disease risk factor in women: Results from the Framingham Heart Study

Atherosclerosis

(2001)

K. Nakajima et al.

The oxidative modification hypothesis of atherosclerosis: The comparison of atherogenic effects on oxidized LDL and remnant lipoproteins in plasma

Clin Chim Acta

(2006)

K. Nakajima et al.

Postprandial lipoprotein metabolism: VLDL vs chylomicrons

Clin Chim Acta

(2011)

K. Nakajima et al.

Cholesterol in remnant-like lipoproteins in human serum using monoclonal anti apo B-100 and anti apo A-I immunoaffinity mixed gels

Clin Chim Acta

(1993)

T. Nakamura et al.

Remnant lipoproteinemia is a risk factor for endothelial vasomotor dysfunction and coronary artery disease in metabolic syndrome

Atherosclerosis

(2005)

B.G. Nordestgaard et al.

Large lipoproteins are excluded from the arterial wall in diabetic cholesterol-fed rabbits

J Lipid Res

(1988)

F.J. Raal et al.

Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: A randomised, double-blind, placebo-controlled trial

Lancet

(2010)

K. Sakata et al.

Remnant-like particle cholesterol is a major risk factor for myocardial infarction in vasospastic angina with nearly normal coronary artery

Atherosclerosis

(1998)

S. Takeichi et al.

Association of plasma triglyceride-rich lipoprotein remnants with coronary atherosclerosis in cases of sudden cardiac death

Atherosclerosis

(1999)

A. Alipour et al.

Leukocyte activation by triglyceride-rich lipoproteins

Arterioscler Thromb Vasc Biol

(2008)

M.A. Austin

Plasma triglyceride and coronary heart disease

Arterioscler Thromb

(1991)

S. Bansal et al.

Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women

JAMA

(2007)

P.J. Barter et al.

Effects of torcetrapib in patients at high risk for coronary events

N Engl J Med

(2007)

P. Benlian et al.

Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene

N Engl J Med

(1996)

W.E. Boden et al.

Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy

N Engl J Med

(2011)

J.D. Brunzell et al.

Familial lipoprotein lipase deficiency, Apo C-II deficiency, and hepatic lipase deficiency

C.P. Cannon et al.

Safety of anacetrapib in patients with or at high risk for coronary heart disease

N Engl J Med

(2010)

L.A. Carlson et al.

Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid

Acta Med Scand

(1988)

M.J. Chapman et al.

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: Evidence and guidance for management

Eur Heart J

(2011)

Clofibrate, niacin in coronary heart disease

JAMA

(1975)

M. Cuchel et al.

Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia

N Engl J Med

(2007)

M.J. Davies

Stability and instability: Two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995

Circulation

(1996)

E. Di Angelantonio et al.

Major lipids, apolipoproteins, and risk of vascular disease

JAMA

(2009)

M. Eriksson et al.

Novel small molecule lipoprotein lipase activator LP071 improves plasma lipid parameters in vivo

E. Falk et al.

Coronary plaque disruption

Circulation

(1995)

J.J. Freiberg et al.

Nonfasting triglycerides and risk of ischemic stroke in the general population

JAMA

(2008)

D. Gaudet et al.

Gene therapy for lipoprotein lipase deficiency

Curr Opin Lipidol

(2012)

C. Giannattasio et al.

Acute effect of high-fat meal on endothelial function in moderately dyslipidemic subjects

Arterioscler Thromb Vasc Biol

(2005)

J.W. Gofman et al.

Evaluation of serum lipoprotein and cholesterol measurements as predictors of clinical complications of atherosclerosis; report of a cooperative study of lipoproteins and atherosclerosis

Circulation

(1956)

T. Gotoda et al.

Diagnosis and management of type I and type V hyperlipoproteinemia

J Atheroscler Thromb

(2012)

Cited by (171)

Insulin resistance potentiates the effect of remnant cholesterol on cardiovascular mortality in individuals without diabetes
2024, Atherosclerosis
Remnant cholesterol (RC) and insulin resistance (IR) have been independently associated with cardiovascular risk. Here, we evaluated the role of IR and RC on cardiovascular disease (CVD) mortality.
We conducted an analysis of 16,113 individuals ≥20 years without diabetes from the National Health and Nutrition Examination Survey (NHANES-III/IV). RC levels were calculated using total cholesterol, non-HDL-c, and LDL-c; IR was defined as HOMA2-IR≥2.5 and CVD mortality as a composite of cardiovascular and cerebrovascular mortality. Multiple linear regression was used to assess the relationship between HOMA2-IR and RC and Cox regression models to assess their joint role in CVD mortality. Causally ordered mediation models were used to explore the mediating role of IR in RC-associated CVD mortality.
We identified an association between higher HOMA2-IR and higher RC levels. The effect of IR on CVD mortality was predominant (HR 1.32, 95%CI 1.18–1.48) and decreased at older ages (HR 0.934, 95%CI 0.918–0.959) compared to RC (HR 0.983, 95%CI 0.952–1.014). Higher risk of CVD mortality was observed in individuals with IR but normal RC (HR 1.37, 95%CI 1.25–1.50) and subjects with IR and high RC (HR 1.24, 95%CI 1.13–1.37), but not in subjects without IR but high RC. In mediation models, HOMA2-IR accounted for 78.2% (95%CI 28.11–98.89) of the effect of RC levels on CVD mortality.
Our findings suggest that RC potentiates the risk of CVD mortality through its effect on whole-body insulin sensitivity, particularly among younger individuals.
Association of serum concentrations of remnant cholesterol with incident cardiovascular disease in patients with rheumatoid arthritis: A real-world data from 2001 to 2022
2024, International Journal of Cardiology
Remnant cholesterol (RC) promotes cardiovascular disease (CVD) in the general population, but its role among rheumatoid arthritis (RA) patients remains unknown. We aimed to investigate circulating RC levels associated with incident CVD among Chinese patients with RA.
A total of 1018 RA patients free of baseline CVD were included and followed up in a prospective RA CVD cohort from 2001 to 2022. Fasting serum levels of triglycerides, total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured, while RC and Non-HDL-C levels were calculated. The primary exposure was RC levels. A LASSO Cox model was used to select covariates. The Fine-Gray competing risk model was used to estimate hazard ratios (HRs).
RA patients had a mean age of 53.9 years, and 802 (78.8%) were females. After a median follow-up of 5.54 years, 131 patients developed CVD with an incidence rate of 21.6 per 1000 person-years. Continuous and quartile-categorized RC levels were associated with incident CVD before and after multivariate adjustment and Bonferroni correction (all P < 0.001). There were no robust associations of other lipids with incident CVD. The fully adjusted HRs for RC were 2.30 (95% CI 1.58–3.35) per 1 mmol/L increase, and 2.40 (1.36–4.25) and 2.81 (1.60–4.94) for patients in the 3rd and 4th versus the 1st quartile, respectively.
Circulating RC levels are positively associated with incident CVD among Chinese RA patients independent of known risk factors, implying its clinically preferable use for improving the stratification of CVD risk in RA patients.
Discordance between remnant cholesterol and low-density lipoprotein cholesterol predicts arterial stiffness progression
2023, Hellenic Journal of Cardiology
Cross-sectional studies have shown that remnant cholesterol (RC) was associated with arterial stiffness. The present study evaluated the association of RC and the discordance between RC and low-density lipoprotein cholesterol (LDL-C) with arterial stiffness progression.
Data were derived from the Kailuan study. RC was calculated as total cholesterol – high-density lipoprotein cholesterol – LDL-C. Discordant RC with LDL-C were defined by residuals, cutoff points, and median values. Arterial stiffness progression was assessed by the brachial-ankle pulse wave velocity (baPWV) change, baPWV change rate, and increase/persistently high baPWV. Multivariable linear regression models and logistic regression models were used to explore the association of RC and discordant RC versus LDL-C with the arterial stiffness progression.
A total of 10,507 participants were enrolled in this study, with the mean age of 50.8 ± 11.8 years, 60.9% (6,396) of male. Multivariable regression analyses showed that, each 1 mmol/L increase in the RC level was associated with a 12.80 cm/s increase in baPWV change, a 3.08 cm/s/year increase in the baPWV change rate, and 13% (95% CI, 1.05-1.21) of increase in the risk for increase in/persistently high baPWV. Discordant high RC was associated with a 13.65 cm/s increase in baPWV change and 19% (95% CI, 1.06-1.33) of increase in the risk for increase in/persistently high baPWV compared to those with concordant group.
Discordantly high RC with LDL-C was associated with an increased risk of arterial stiffness progression. The findings demonstrated that RC may be an important marker of future coronary artery disease risk.
The Association Between Remnant Cholesterol and Blood Pressure: National Health and Nutrition Examination Surveys 2013-2018
2023, American Journal of Cardiology
Regulation of phospholipid peroxidation signaling by a traditional Chinese medicine formula for coronary heart disease
2023, Phytomedicine
Phospholipid peroxidation signaling was recently revealed as a novel pathological mechanism of coronary heart disease (CHD), and small molecules involved in this redox-metabolic pathway are suggested as the potential anti-CHD drugs. Danlou Tablet (DLT), a famous traditional Chinese medicine (TCM) formula characterized by multi-component and multi-target regulation, is widely used in the clinical treatment of CHD by regulating lipid metabolism. However, little information is available addressing the corresponding pharmacological mechanisms and associated active components of DLT.
To study whether phospholipid peroxidation involves a novel mechanism of DLT for the therapeutic effect of CHD and to explain the essential active components.
Firstly, the HPLC fingerprint was constructed to ensure the controllability of the quality of DLT. Then, a CHD animal model with the characteristics of lipid disorder and myocardial ischemia was established by a high-fat diet (HFD) combined with left anterior descending coronary artery (LAD) ligation. The therapeutic effect of DLT was further evaluated based on the results of the rat survival rate, cardiac function, cardiac histopathology, and myocardial ischemia indicators. Correspondingly, whether DLT can regulate the key indicators (ALOX15, GPX4, MDA, GSH, and NADPH) of the phospholipid peroxidation pathway was investigated, and Alox15^−/− mice have been applied to confirm the mechanism of DLT. Finally, the target-mediated characterization strategy based on ALOX15, including the integration of in vivo component characterization, network pharmacology, molecular docking analysis, and activity verification, has been further implemented to reveal the key bio-active components in DLT.
In this study, a high-fat diet (HFD) combined with left anterior descending coronary artery (LAD) ligation was utilized to generate a CHD model, and DLT significantly improved the cardiac dysfunction and reduced the myocardial cell death susceptibility. Further results revealed that DLT reversed the protein expression of ALOX15 and GPX4, the key proteins of phospholipid peroxidation pathways, which subsequently influenced the parameters of phospholipid peroxidation (MDA, GSH, and NADPH). The ALOX15 knockout transgenic animal model confirmed that Alox15^−/− mice lost their cardioprotective effects with DLT, suggesting that DLT exerted therapeutic effects on CHD by regulating ALOX15-mediated phospholipid peroxidation. Finally, the target-mediated characterization strategy identified that daidzein is an active component in DLT against CHD by modulating ALOX15.
Innovatively, ALOX15-mediated phospholipid peroxidation was identified as one of the critical mechanisms of DLT exerting cardioprotective effects. Our findings elucidate a novel mechanism of DLT and provide some new drug evaluation targets and therapeutic strategies for CHD.
Remnant cholesterol and risk of myocardial infarction in patients with coronary artery disease undergoing revascularization
2023, Journal of Clinical Lipidology
Despite substantial reduction in low-density lipoprotein cholesterol (LDL-C), patients develop recurrent cardiovascular events. Remnant cholesterol (RC), the cholesterol content of triglyceride-rich lipoproteins, is a potential contributor to this residual risk.
To investigate the association between RC and risk for myocardial infarction (MI) in patients with coronary artery disease, and examine whether the predictive value of RC is retained beyond non-high-density lipoprotein cholesterol (non-HDL-C).
Data on 9451 patients undergoing coronary revascularization in a single center. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus LDL-C (estimated using Martin–Hopkins equation). Cox-regression models were used to estimate the association between RC and risk for MI. Discordance analyses were performed to examine the correlation between RC and non-HDL-C (or LDL-C) in relation to MI risk.
Mean age was 65±11 years; 67% presented with acute coronary syndrome. During median follow-up of 9.6 years, 1690 patients developed MI. After multivariable adjustment including lipid-lowering therapies and non-HDL-C, RC was associated with higher MI risk: hazard ratio (95% confidence interval): 1.36 (1.20-1.56) and 1.58 (1.35-1.85) in those with RC levels ≥75th (32.6 mg/dL) and ≥90th (41.8 mg/dL) percentile, compared to RC <50th percentile (25.5 mg/dL). When RC and non-HDL-C (or LDL-C) levels were discordant, the level of RC better reflected the risk for MI.
Elevated RC is a risk factor for MI independent of lipid-lowering therapies and non-HDL-C, providing further support that RC may serve as a residual cardiovascular risk marker and potential treatment target in patients with coronary artery disease.

View all citing articles on Scopus

View full text

Associate editor: M.J. ChapmanRemnant cholesterol as a cause of ischemic heart disease: Evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment

Abstract

Section snippets

Introduction including definition

Remnant cholesterol levels and observational risk of ischemic heart disease

Remnant cholesterol, genetic variation, and causal risk of ischemic heart disease

Measurement of remnant cholesterol

Atherogenicity of elevated remnant cholesterol

Remnant cholesterol levels in high risk patient groups

Lowering of remnant cholesterol levels using current approaches

Future pharmacological approaches to lowering remnant cholesterol levels

Conclusions and perspectives

Funding sources

Conflict of interest disclosures

J Clin Lipidol

J Am Coll Cardiol

Atheroscler Suppl

Lancet

Am J Med

J Lipid Res

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

Clin Chim Acta

Metabolism

J Cardiol

J Am Coll Cardiol

J Lipid Res

Lancet

J Lipid Res

J Biol Chem

J Am Coll Cardiol

Am Heart J

Am Heart J

Atherosclerosis

Clin Chim Acta

Clin Chim Acta

Clin Chim Acta

Atherosclerosis

J Lipid Res

Lancet

Atherosclerosis

Atherosclerosis

Leukocyte activation by triglyceride-rich lipoproteins

Arterioscler Thromb Vasc Biol

Plasma triglyceride and coronary heart disease

Arterioscler Thromb

Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women

JAMA

Effects of torcetrapib in patients at high risk for coronary events

N Engl J Med

Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene

N Engl J Med

Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy

N Engl J Med

Familial lipoprotein lipase deficiency, Apo C-II deficiency, and hepatic lipase deficiency

Safety of anacetrapib in patients with or at high risk for coronary heart disease

N Engl J Med

Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid

Acta Med Scand

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: Evidence and guidance for management

Eur Heart J

JAMA

Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia

N Engl J Med

Stability and instability: Two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995

Circulation

Major lipids, apolipoproteins, and risk of vascular disease

JAMA

Novel small molecule lipoprotein lipase activator LP071 improves plasma lipid parameters in vivo

Coronary plaque disruption

Circulation

Nonfasting triglycerides and risk of ischemic stroke in the general population

JAMA

Gene therapy for lipoprotein lipase deficiency

Curr Opin Lipidol

Acute effect of high-fat meal on endothelial function in moderately dyslipidemic subjects

Arterioscler Thromb Vasc Biol

Evaluation of serum lipoprotein and cholesterol measurements as predictors of clinical complications of atherosclerosis; report of a cooperative study of lipoproteins and atherosclerosis

Circulation

Associate editor: M.J. Chapman
Remnant cholesterol as a cause of ischemic heart disease: Evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment