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Association between change in plasma triglyceride levels and risk of stroke and carotid atherosclerosis

Systematic review and meta-regression analysis
  • Julien Labreuche
    Affiliations
    INSERM U-698 and Denis Diderot University – Paris VII, France

    Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France
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  • Dominique Deplanque
    Affiliations
    INSERM U-698 and Denis Diderot University – Paris VII, France

    Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France

    University Lille-North of France, Department of Medical Pharmacology, Faculty of Medicine, Lille, France
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  • Pierre-Jean Touboul
    Affiliations
    INSERM U-698 and Denis Diderot University – Paris VII, France

    Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France
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  • Eric Bruckert
    Affiliations
    Department of Endocrinology, Pitié-Salpêtrière University Hospital, Pierre and Marie Curie University, Paris, France
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  • Pierre Amarenco
    Correspondence
    Corresponding author at: Department of Neurology and Stroke Centre, Bichat Hospital, 46 rue Henri Huchard, 75018 Paris, France. Tel.: +331 4025 8726; fax: +331 4025 7198.
    Affiliations
    INSERM U-698 and Denis Diderot University – Paris VII, France

    Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France
    Search for articles by this author

      Abstract

      Background and purpose

      The contribution of modifying non-low-density lipoprotein cholesterol (LDL-C) levels to reduce stroke risk remains uncertain. The aim of this study was to investigate the association between treatment-induced change in plasma triglyceride levels and risk of stroke and progression of carotid intima-media thickness (CIMT).

      Methods

      We performed a systematic review and meta-regression analyses of randomized controlled trials of lipid-modifying treatments selected from a PubMed search on literature published from 1966 to 2008.

      Results

      We identified 64 randomized controlled trials (active groups, n = 96,807; control groups, n = 98,681) that tested lipid-modifying drugs and reported triglyceride levels and stroke outcome. Extracting data from placebo groups, we found a statistically significant association between baseline triglyceride levels and stroke risk (adjusted relative risk [RR], 1.05 per 10-mg/dL increase; 95% CI, 1.03–1.07). Except for a trend in fibrate and niacin trials, there was no evidence of any relationship between degree of triglyceride change and stroke incidence. In multivariable meta-regression analysis including baseline and change in LDL-C, only change in LDL-C was associated with log risk ratio of all strokes (RR reduction, 4.5% per 10-mg/dL reduction; 95% CI, 1.7–7.2; P = .003). Similarly, taking into account 26 randomized controlled trials reporting CIMT outcome, LDL-C reduction was associated with reduced CIMT progression (−3.0 μm/y per 10-mg/dL reduction; 95% CI, −5.5 to −0.4; P = .03).

      Conclusions

      In view of the limitations of meta-regression analysis and CIMT measures as surrogate endpoints in lipid-lowering drugs trials, additional studies are needed to more precisely quantify the detrimental effect of triglyceride levels on stroke risk and to establish the efficacy of triglyceride-lowering therapy in addition to LDL-C reduction.

      Keywords

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