Association between change in plasma triglyceride levels and risk of stroke and carotid atherosclerosis: Systematic review and meta-regression analysis

Labreuche, Julien; Deplanque, Dominique; Touboul, Pierre-Jean; Bruckert, Eric; Amarenco, Pierre

doi:10.1016/j.atherosclerosis.2010.02.011

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Volume 212, Issue 1 , Pages 9-15, September 2010

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

Systematic review and meta-regression analysis

Julien Labreuche
- INSERM U-698 and Denis Diderot University – Paris VII, France
- Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France
Dominique Deplanque
- 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
Pierre-Jean Touboul
- INSERM U-698 and Denis Diderot University – Paris VII, France
- Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France
Eric Bruckert
- Department of Endocrinology, Pitié-Salpêtrière University Hospital, Pierre and Marie Curie University, Paris, France
Pierre Amarenco
- INSERM U-698 and Denis Diderot University – Paris VII, France
- Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France
- 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.

Received 27 November 2009; received in revised form 27 January 2010; accepted 8 February 2010. published online 11 May 2010.

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 (−3.0μm/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: Carotid atherosclerosis, Statin, Stroke, Triglyceride