Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials

S. Matthijs Boekholdt; G. Kees Hovingh; Samia Mora; Benoit J. Arsenault; Pierre Amarenco; Terje R. Pedersen; John C. LaRosa; David D. Waters; David A. DeMicco; R. John Simes; Antony C. Keech; David Colquhoun; Graham A. Hitman; D. John Betteridge; Michael B. Clearfield; John R. Downs; Helen M. Colhoun; Antonio M. Gotto; Paul M. Ridker; Scott M. Grundy; John J. P. Kastelein

doi:10.1016/j.jacc.2014.02.615

Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials

S. Matthijs Boekholdt, G. Kees Hovingh, Samia Mora, Benoit J. Arsenault, Pierre Amarenco, Terje R. Pedersen, John C. LaRosa, David D. Waters, David A. DeMicco, R. John Simes, Antony C. Keech, David Colquhoun, Graham A. Hitman, D. John Betteridge, Michael B. Clearfield, John R. Downs, Helen M. Colhoun, Antonio M. Gotto, Paul M. Ridker, Scott M. GrundyJohn J. P. Kastelein (Lead / Corresponding author)

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Abstract

Background

Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented.
Objectives

The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk.
Methods

This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.
Results

Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB.
Conclusions

The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.

Original language	English
Pages (from-to)	485-494
Number of pages	10
Journal	Journal of the American College of Cardiology
Volume	64
Issue number	5
DOIs	https://doi.org/10.1016/j.jacc.2014.02.615
Publication status	Published - 5 Aug 2014

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10.1016/j.jacc.2014.02.615

http://www.journals.elsevier.com/jacc-journal-of-the-american-college-of-cardiology

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Boekholdt, S. M., Hovingh, G. K., Mora, S., Arsenault, B. J., Amarenco, P., Pedersen, T. R., LaRosa, J. C., Waters, D. D., DeMicco, D. A., Simes, R. J., Keech, A. C., Colquhoun, D., Hitman, G. A., Betteridge, D. J., Clearfield, M. B., Downs, J. R., Colhoun, H. M., Gotto, A. M., Ridker, P. M., ... Kastelein, J. J. P. (2014). Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. Journal of the American College of Cardiology, 64(5), 485-494. https://doi.org/10.1016/j.jacc.2014.02.615

@article{85f2b61382ca4f69aa220033b0ed6361,

title = "Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials",

abstract = "BackgroundLevels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented.ObjectivesThe aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk.MethodsThis meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.ResultsAmong 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB.ConclusionsThe reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.",

author = "Boekholdt, {S. Matthijs} and Hovingh, {G. Kees} and Samia Mora and Arsenault, {Benoit J.} and Pierre Amarenco and Pedersen, {Terje R.} and LaRosa, {John C.} and Waters, {David D.} and DeMicco, {David A.} and Simes, {R. John} and Keech, {Antony C.} and David Colquhoun and Hitman, {Graham A.} and Betteridge, {D. John} and Clearfield, {Michael B.} and Downs, {John R.} and Colhoun, {Helen M.} and Gotto, {Antonio M.} and Ridker, {Paul M.} and Grundy, {Scott M.} and Kastelein, {John J. P.}",

year = "2014",

month = aug,

day = "5",

doi = "10.1016/j.jacc.2014.02.615",

language = "English",

volume = "64",

pages = "485--494",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier",

number = "5",

}

Boekholdt, SM, Hovingh, GK, Mora, S, Arsenault, BJ, Amarenco, P, Pedersen, TR, LaRosa, JC, Waters, DD, DeMicco, DA, Simes, RJ, Keech, AC, Colquhoun, D, Hitman, GA, Betteridge, DJ, Clearfield, MB, Downs, JR, Colhoun, HM, Gotto, AM, Ridker, PM, Grundy, SM & Kastelein, JJP 2014, 'Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials', Journal of the American College of Cardiology, vol. 64, no. 5, pp. 485-494. https://doi.org/10.1016/j.jacc.2014.02.615

TY - JOUR

T1 - Very low levels of atherogenic lipoproteins and the risk for cardiovascular events

T2 - a meta-analysis of statin trials

AU - Boekholdt, S. Matthijs

AU - Hovingh, G. Kees

AU - Mora, Samia

AU - Arsenault, Benoit J.

AU - Amarenco, Pierre

AU - Pedersen, Terje R.

AU - LaRosa, John C.

AU - Waters, David D.

AU - DeMicco, David A.

AU - Simes, R. John

AU - Keech, Antony C.

AU - Colquhoun, David

AU - Hitman, Graham A.

AU - Betteridge, D. John

AU - Clearfield, Michael B.

AU - Downs, John R.

AU - Colhoun, Helen M.

AU - Gotto, Antonio M.

AU - Ridker, Paul M.

AU - Grundy, Scott M.

AU - Kastelein, John J. P.

PY - 2014/8/5

Y1 - 2014/8/5

N2 - BackgroundLevels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented.ObjectivesThe aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk.MethodsThis meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.ResultsAmong 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB.ConclusionsThe reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.

AB - BackgroundLevels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented.ObjectivesThe aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk.MethodsThis meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.ResultsAmong 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB.ConclusionsThe reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.

U2 - 10.1016/j.jacc.2014.02.615

DO - 10.1016/j.jacc.2014.02.615

M3 - Article

C2 - 25082583

SN - 0735-1097

VL - 64

SP - 485

EP - 494

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 5

ER -

Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials

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