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

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.

[1]  P. Magni,et al.  Leptin:Adiponectin Ratio Is an Independent Predictor of Intima Media Thickness of the Common Carotid Artery , 2007, Stroke.

[2]  C. Arnaud,et al.  Association of cardiovascular risk factors with intima-media thickness of the carotid arteries in early postmenopausal women , 2004, Menopause.

[3]  M. Fujishima,et al.  Association between hyperinsulinemia and intima‐media thickness of the carotid artery in normotensive men , 1997, Journal of hypertension.

[4]  G. Stein,et al.  Serum lipids as protective factors for subarachnoid hemorrhage , 2005, Journal of Clinical Neuroscience.

[5]  M. Woodward,et al.  Serum Triglycerides as a Risk Factor for Cardiovascular Diseases in the Asia-Pacific Region , 2004, Circulation.

[6]  Yuichiro Oka,et al.  Metabolic syndrome and carotid atherosclerosis: role of elevated blood pressure. , 2005, Journal of atherosclerosis and thrombosis.

[7]  S. Ebrahim,et al.  HDL-Cholesterol, total cholesterol, and the risk of stroke in middle-aged British men. , 2000, Stroke.

[8]  G. Sesti,et al.  Carotid artery intima-media thickness is associated with insulin-mediated glucose disposal in nondiabetic normotensive offspring of type 2 diabetic patients. , 2007, American journal of physiology. Endocrinology and metabolism.

[9]  I. Holme,et al.  Risk Factors of Stroke Incidence and Mortality: A 12‐Year Follow‐up of the Oslo Study , 1993, Stroke.

[10]  G. Hallmans,et al.  Autoantibodies against oxidatively modified LDL do not constitute a risk factor for stroke: a nested case-control study. , 1999, Stroke.

[11]  N. Hattori,et al.  Polymorphism of the Lipoprotein Lipase Gene and Risk of Atherothrombotic Cerebral Infarction in the Japanese , 2001, Stroke.

[12]  Y. Friedlander,et al.  Cholesterol and other lipids predict coronary heart disease and ischaemic stroke in the elderly, but only in those below 70 years. , 2001, Atherosclerosis.

[13]  B. Fagerberg,et al.  Insulin resistance and intima–media thickness in the carotid and femoral arteries of clinically healthy 58‐year‐old men. The Atherosclerosis and Insulin Resistance Study (AIR) , 2001, Journal of internal medicine.

[14]  D. Grobbee,et al.  Cardiovascular risk factors and increased carotid intima-media thickness in healthy young adults: the Atherosclerosis Risk in Young Adults (ARYA) Study. , 2003, Archives of internal medicine.

[15]  A. Simon,et al.  Sex and topographic differences in associations between large-artery wall thickness and coronary risk profile in a French working cohort: the AXA Study. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[16]  J. Mckenney,et al.  National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) , 2002 .

[17]  S Greenland,et al.  Quantitative methods in the review of epidemiologic literature. , 1987, Epidemiologic reviews.

[18]  P Ducimetière,et al.  Relation of intima-media thickness to atherosclerotic plaques in carotid arteries. The Vascular Aging (EVA) Study. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[19]  M. Feinleib,et al.  Serum Triglyceride and Risk of Coronary Heart Disease, Stroke, and Total Mortality in Japanese‐American Men , 1983, Arteriosclerosis.

[20]  A. Fan.  Metabolic syndrome and progression of atherosclerosis among middle-aged US adults. , 2006, Journal of atherosclerosis and thrombosis.

[21]  K. Yamagishi,et al.  Metabolic Syndrome and the Risk of Ischemic Heart Disease and Stroke Among Japanese Men and Women , 2007, Stroke.

[22]  J. Oppert,et al.  Metabolic syndrome in relation to structure and function of large arteries: a predominant effect of blood pressure. A report from the SU.VI.MAX. Vascular Study. , 2005, American journal of hypertension.

[23]  W. Aronow,et al.  Three-Year Follow-Up of Risk Factors Correlated with New Atherothrombotic Brain Infarction in 708 Elderly Patients , 1988, Angiology.

[24]  A. Nicolaides,et al.  The ultrasonic evaluation of the carotid intima-media thickness and its relation to risk factors of atherosclerosis in normal and diabetic population. , 1997, International angiology : a journal of the International Union of Angiology.

[25]  M. Bond,et al.  Impact of multiple coronary risk factors on the intima-media thickness of different segments of carotid artery in healthy young adults (The Bogalusa Heart Study). , 2002, The American journal of cardiology.

[26]  D. Housman,et al.  Estrogen Receptor α Gene Variation and the Risk of Stroke , 2005 .

[27]  K. Okumura,et al.  Impact of low-density lipoprotein particle size on carotid intima-media thickness in patients with type 2 diabetes mellitus. , 2007, Metabolism: clinical and experimental.

[28]  J. Salonen,et al.  Relation of blood pressure, serum lipids, and smoking to the risk of cerebral stroke. A longitudinal study in Eastern Finland. , 1982, Stroke.

[29]  R. Sridharan.  Risk factors for ischemic stroke: a case control analysis. , 1992, Neuroepidemiology.

[30]  P. Touboul,et al.  Blood Lipids in Brain Infarction Subtypes , 2006, Cerebrovascular Diseases.

[31]  A. Simon,et al.  Erythrocyte, but not plasma, vitamin E concentration is associated with carotid intima-media thickening in asymptomatic men at risk for cardiovascular disease. , 2001, Atherosclerosis.

[32]  S Collatina,et al.  Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima–media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study , 2001, Journal of hypertension.

[33]  P. Ridker,et al.  Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. , 2007, JAMA.

[34]  L. Chambless,et al.  Plasma Lipid Profile and Incident Ischemic Stroke: The Atherosclerosis Risk in Communities (ARIC) Study , 2003, Stroke.

[35]  S. Haffner,et al.  Ultrasonographically assessed maximum carotid artery wall thickness in Mexico City residents and Mexican Americans living in San Antonio, Texas. Association with diabetes and cardiovascular risk factors. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[36]  R. Sacco,et al.  High-density lipoprotein cholesterol and ischemic stroke in the elderly: the Northern Manhattan Stroke Study. , 2001, JAMA.

[37]  E. Vicaut,et al.  Mannheim Carotid Intima-Media Thickness Consensus (2004–2006) , 2006, Cerebrovascular Diseases.

[38]  D. Tanné,et al.  Blood Lipids and First-Ever Ischemic Stroke/Transient Ischemic Attack in the Bezafibrate Infarction Prevention (BIP) Registry: High Triglycerides Constitute an Independent Risk Factor , 2001, Circulation.

[39]  T. Shoji,et al.  Antibodies against oxidized LDL and carotid artery intima-media thickness in a healthy population. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[40]  J. Dawson,et al.  Carotid Intimal-Medial Thickness Is Related to Cardiovascular Risk Factors Measured From Childhood Through Middle Age: The Muscatine Study , 2001, Circulation.

[41]  T. Lumley,et al.  The Association Between Lipid Levels and the Risks of Incident Myocardial Infarction, Stroke, and Total Mortality: The Cardiovascular Health Study , 2004, Journal of the American Geriatrics Society.

[42]  E. Arnesen,et al.  Body height, cardiovascular risk factors, and risk of stroke in middle-aged men and women. A 14-year follow-up of the Finnmark Study. , 1996, Circulation.

[43]  J. Hokanson,et al.  Plasma Triglyceride Level is a Risk Factor for Cardiovascular Disease Independent of High-Density Lipoprotein Cholesterol Level: A Metaanalysis of Population-Based Prospective Studies , 1996, Journal of cardiovascular risk.

[44]  O. Joakimsen,et al.  Age and sex differences in the relationship between inherited and lifestyle risk factors and subclinical carotid atherosclerosis: the Tromsø study. , 2001, Atherosclerosis.

[45]  F. Todua,et al.  [Effect of atherogenic risk factors on the state of complex intima-media of common carotid artery]. , 2003, Kardiologiia.

[46]  T. Wilt,et al.  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. , 1999, The New England journal of medicine.

[47]  R A Kronmal,et al.  Thickening of the carotid wall. A marker for atherosclerosis in the elderly? Cardiovascular Health Study Collaborative Research Group. , 1996, Stroke.

[48]  A. Keech,et al.  Urinary albumin levels in the normal range determine arterial wall thickness in adults with Type 2 diabetes: a FIELD substudy , 2005, Diabetic medicine : a journal of the British Diabetic Association.

[49]  R. Collins,et al.  Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. , 1999, American journal of epidemiology.

[50]  C. Ahn,et al.  Relationship of low-density lipoprotein particle size to insulin resistance and intima-media thickness in nondiabetic Koreans. , 2006, Metabolism: clinical and experimental.

[51]  Pierre Amarenco,et al.  High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: a systematic review. , 2008, Atherosclerosis.

[52]  Matthias W. Lorenz,et al.  Prediction of Clinical Cardiovascular Events With Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis , 2007, Circulation.

[53]  M. Woodward,et al.  Plasma lipids predict myocardial infarction, but not stroke, in patients with established cerebrovascular disease. , 2005, European Heart Journal.

[54]  R. Collins,et al.  Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins , 2005, The Lancet.

[55]  N. Unwin,et al.  Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Detection, Evaluation, and Treatment of High Blood Cholesterol Education Program (NCEP) Expert Panel on Executive Summary of the Third Report of the National , 2009 .

[56]  K. Matthews,et al.  Prevalence and determinants of carotid atherosclerosis in healthy postmenopausal women. , 1997, Stroke.

[57]  B. Fagerberg,et al.  Apolipoprotein B/Apolipoprotein A-I in Relation to the Metabolic Syndrome and Change in Carotid Artery Intima-Media Thickness During 3 Years in Middle-Aged Men , 2004, Stroke.

[58]  M. Fujimoto,et al.  Association between plasma homocysteine concentration and carotid atherosclerosis in hemodialysis patients. , 1999, Japanese circulation journal.

[59]  W. Kannel,et al.  Lipoproteins, cardiovascular disease, and death. The Framingham study. , 1981, Archives of internal medicine.

[60]  G. Boysen,et al.  Influence of total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease: the Copenhagen city heart study , 1994, BMJ.

[61]  Giuseppe Mancia,et al.  Risk factors associated with alterations in carotid intima—media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis , 1998, Journal of hypertension.

[62]  J. Reiber,et al.  Lipoprotein(a) and ultrasonographically determined early atherosclerotic changes in the carotid and femoral artery , 2003, Journal of thrombosis and haemostasis : JTH.

[63]  M. Hanefeld,et al.  Postprandial plasma glucose is an independent risk factor for increased carotid intima-media thickness in non-diabetic individuals. , 1999, Atherosclerosis.

[64]  M. Bond,et al.  Association of Obesity and Central Fat Distribution With Carotid Artery Wall Thickening in Middle-Aged Women , 2002, Stroke.

[65]  V. Mohan,et al.  Relationship of lipoprotein(a) with intimal medial thickness of the carotid artery in Type 2 diabetic patients in south India , 2003, Diabetic medicine : a journal of the British Diabetic Association.

[66]  M. Laakso,et al.  Predictors of stroke in middle-aged patients with non-insulin-dependent diabetes. , 1996, Stroke.

[67]  J. Michael Gaziano,et al.  Cholesterol and the Risk of Ischemic Stroke , 2003, Stroke.

[68]  J. Beilby,et al.  Angiotensin-converting enzyme gene polymorphism and carotid wall thickening in a community population. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[69]  B. Norrving,et al.  Plasma lipids and lipoproteins in subtypes of stroke , 1992, Acta neurologica Scandinavica.

[70]  M. Hennerici,et al.  High-dose atorvastatin after stroke or transient ischemic attack. , 2006, The New England journal of medicine.

[71]  Moyses Szklo,et al.  Risk factors for progression of common carotid atherosclerosis: the Atherosclerosis Risk in Communities Study, 1987-1998. , 2002, American journal of epidemiology.

[72]  J. Paramo,et al.  Validation of plasma fibrinogen as a marker of carotid atherosclerosis in subjects free of clinical cardiovascular disease. , 2004, Haematologica.

[73]  L. Brass,et al.  Reduction in Stroke With Gemfibrozil in Men With Coronary Heart Disease and Low HDL Cholesterol: The Veterans Affairs HDL Intervention Trial (VA-HIT) , 2001, Circulation.

[74]  E. Ros,et al.  Influence of HDL Cholesterol on Preclinical Carotid Atherosclerosis in Familial Hypercholesterolemia , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[75]  H. Yokoyama,et al.  Relationship between metabolic syndrome components and vascular properties in Japanese type 2 diabetic patients without cardiovascular disease or nephropathy. , 2007, Diabetes research and clinical practice.

[76]  C. Bengtsson,et al.  Triglycerides--main lipid risk factor for cardiovascular disease in women? , 2009, Acta medica Scandinavica.

[77]  H. Milionis,et al.  Risk factors for first-ever acute ischemic non-embolic stroke in elderly individuals. , 2005, International journal of cardiology.

[78]  R. Collins,et al.  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 , 2007, The Lancet.

[79]  A. Gnasso,et al.  Components of the Metabolic Syndrome and Carotid Atherosclerosis: Role of Elevated Blood Pressure , 2005, Hypertension.

[80]  C. Behre,et al.  Are serum adiponectin concentrations in a population sample of 64‐year‐old Caucasian women with varying glucose tolerance associated with ultrasound‐assessed atherosclerosis? , 2006, Journal of internal medicine.

[81]  P. Steg,et al.  The paradox of cholesterol and stroke , 2007, The Lancet.

[82]  M. Argyropoulou,et al.  Antibodies Against Various Forms of Mildly Oxidized Low-Density Lipoprotein Are Not Associated With Carotid Intima-Media Thickness in Patients With Primary Hyperlipidemia , 2006, Angiology.

[83]  J. Jamart,et al.  Lipids in ischemic stroke subtypes. , 2004, Acta neurologica Belgica.

[84]  M. Lai,et al.  4G/5G promoter polymorphism of plasminogen activator inhibitor-1, lipid profiles, and ischemic stroke. , 2003, The Journal of laboratory and clinical medicine.

[85]  P. Rizzon,et al.  Plasma leptin is independently associated with the intima-media thickness of the common carotid artery , 2001, International Journal of Obesity.

[86]  J. Woo,et al.  Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese. , 1991, Stroke.