Plasma triglyceride levels and risk of stroke and carotid atherosclerosis: A systematic review of the epidemiological studies

doi:10.1016/j.atherosclerosis.2008.08.040

Atherosclerosis

Volume 203, Issue 2, April 2009, Pages 331-345

https://doi.org/10.1016/j.atherosclerosis.2008.08.040 Get rights and content

Abstract

Objective

The contribution of lipids to stroke risk remains uncertain; little attention has been paid to the effect of triglyceride levels, an emerging risk factor.

Methods

We performed two independent systematic PubMed literature searches for epidemiological studies that examined the association of triglyceride levels with stroke and carotid intima-media thickness (CIMT).

Results

We identified 31 studies on the relationship between triglyceride levels and stroke risk and 38 on triglyceride levels and CIMT. Although study designs varied widely, nine of the 17 prospective cohort studies (n = 140,788) and six of the 14 case-control studies (n = 3458 cases, 4089 controls) supported a positive association between elevated triglyceride levels and increased risk of stroke. Combining all available data from prospective studies (n = 9) produced a pooled relative risk of main stroke outcome per 1 standard-deviation increase of 1.10 (95% confidence interval, 1.07–1.13) without evidence of heterogeneity. One prospective study and one case-control study reported a negative relationship with haemorrhagic stroke. Of the 38 studies on CIMT (n = 43,161), 11 reported a significant correlation between CIMT and triglyceride levels, of which three were unadjusted, and one reported an inverse relationship. All of the three studies with longitudinal analysis, two of which were restricted to women, reported a positive association between baseline triglyceride levels and progression of CIMT.

Conclusions

The weight of evidence in prospective cohort studies favours a positive association between triglyceride levels and stroke, and supports the evaluation of triglyceride-lowering therapy to prevent stroke. However, this review shows the need for additional large prospective studies, especially in stroke subtypes, to establish firmly the independent detrimental effect of triglyceride levels in stroke risk.

Introduction

Blood cholesterol is a well-established risk factor for cardiovascular disease [1], whereas its relationship with fatal stroke is more controversial [2], [3] despite the benefit of lipid-lowering therapy in preventing stroke events [4], [5]. Although blood total cholesterol and low-density lipoprotein cholesterol (LDL-C) are the most frequent lipid components reported in clinical and epidemiological studies, little attention has been paid to levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides. A recent systematic review showed epidemiological evidence of an inverse association between HDL-C levels and stroke risk [6]. To date, no systematic reviews have addressed the effect of triglyceride plasma levels on stroke risk. In the VA-HIT trial (Veterans Affairs High-density lipoprotein cholesterol Intervention Trial), lowering triglyceride plasma levels by 31% with gemfibrozil was associated with a reduction in stroke risk of 31% (95% confidence interval [CI], 2–52%) [7], [8].

Lowering triglyceride levels pharmacologically or by lifestyle modification may be an effective additional strategy in the primary and secondary prevention of vascular disease and stroke. A recent meta-analysis of prospective cohort studies conducted in the Asia–Pacific region [9], which confirmed the strong independent association between triglyceride levels and cardiovascular disease previously reported [10], showed a positive association with ischaemic stroke but not with haemorrhagic stroke (fatal and non-fatal events). Several previous epidemiological studies have shown no consistent association. A number of methodological issues could explain these controversial findings. We therefore conducted a systematic review to summarize the epidemiological evidence for triglyceride levels exerting a detrimental effect by increasing stroke risk. Since carotid intima-media thickness (CIMT) is a marker for early atherosclerosis strongly associated with stroke [11], and is a surrogate efficacy endpoint in randomized controlled trials, we also reviewed the epidemiological association between triglyceride levels and CIMT.

Section snippets

Search strategy and study selection

We performed two independent computerized PubMed literature searches of studies published between January 1966 and September 2007 to identify observational epidemiological studies that examined the association of triglyceride levels with stroke risk and CIMT. Searches were restricted to studies conducted in humans, and one author (JL) selected potentially relevant articles based on the title and abstract, and obtained the full text of these articles for detailed review.

Epidemiologic literature on the relationship between triglyceride levels and stroke

We used the search terms

Triglycerides and stroke risk

The computerized literature search identified 5657 citations. After a review of the titles and abstracts, 73 full articles were read and 31 were judged to be eligible for inclusion (Fig. 1A) [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43].

Discussion

This systematic review shows that uncertainties remain regarding the positive association between triglyceride levels and stroke risk; even more uncertainties are apparent when considering the possible impact of CIMT on stroke risk. Prospective cohort studies support a weak detrimental effect of higher triglyceride levels on stroke risk, whereas there is little corroborating evidence in case-control studies and in CIMT studies. It is possible that some relevant studies were not included in our

Acknowledgements

This work was funded by SOS-ATTAQUE CEREBRALE association. The authors thank Dr Sophie Rushton-Smith who provided editorial assistance in the preparation of this manuscript and was funded by SOS-ATTAQUE CEREBRALE association.

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Citation Excerpt :
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ReviewPlasma triglyceride levels and risk of stroke and carotid atherosclerosis: A systematic review of the epidemiological studies

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Search strategy and study selection

Epidemiologic literature on the relationship between triglyceride levels and stroke

Triglycerides and stroke risk

Discussion

Acknowledgements

Lancet

Atherosclerosis

Atherosclerosis

J Clin Neurosci

Int J Cardiol

J Lab Clin Med

Metabolism

Diab Res Clin Pract

Metabolism

Am J Hypertens

J Thromb Haemost

Am J Cardiol

Atherosclerosis

Atherosclerosis

Atherosclerosis

Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report

Circulation

Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths.

Lancet

Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.

Lancet

High-dose atorvastatin after stroke or transient ischemic attack

N Engl J Med

Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group.

N Engl J Med

Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT)

Circulation

Serum triglycerides as a risk factor for cardiovascular diseases in the Asia-Pacific region

Circulation

Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies

J Cardiovasc Risk

Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis

Circulation

Quantitative methods in the review of epidemiologic literature

Epidemiol Rev

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

JAMA

Metabolic syndrome and the risk of ischemic heart disease and stroke among Japanese men and women

Stroke

Estrogen receptor alpha gene variation and the risk of stroke

Stroke

The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: the cardiovascular health study

J Am Geriatr Soc

Plasma lipid profile and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study

Stroke

Blood lipids and first-ever ischemic stroke/transient ischemic attack in the Bezafibrate Infarction Prevention (BIP) registry: high triglycerides constitute an independent risk factor

Circulation

HDL-cholesterol, total cholesterol, and the risk of stroke in middle-aged British men

Stroke

Predictors of stroke in middle-aged patients with non-insulin-dependent diabetes

Stroke

Body height, cardiovascular risk factors, and risk of stroke in middle-aged men and women. A 14-year follow-up of the Finnmark study.

Circulation

Influence of total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease: the Copenhagen City Heart Study

BMJ

Risk factors of stroke incidence and mortality. A 12-year follow-up of the Oslo Study

Stroke

Three-year follow-up of risk factors correlated with new atherothrombotic brain infarction in 708 elderly patients

Angiology

Triglycerides--main lipid risk factor for cardiovascular disease in women?

Acta Med Scand

Serum triglyceride and risk of coronary heart disease, stroke, and total mortality in Japanese-American men

Arteriosclerosis

Relation of blood pressure, serum lipids, and smoking to the risk of cerebral stroke. A longitudinal study in Eastern Finland.

Stroke

Lipoproteins, cardiovascular disease, and death the Framingham study.

Arch Intern Med

Review
Plasma triglyceride levels and risk of stroke and carotid atherosclerosis: A systematic review of the epidemiological studies