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

Background and purposeThe 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).MethodsWe 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.ResultsWe 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).ConclusionsIn 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.