Low- and high-density lipoprotein cholesterol and ischemic cerebrovascular disease: the bezafibrate infarction prevention registry.

BACKGROUND Despite increasing evidence that beta-hydroxy-beta-methyglutaryl coenzyme A reductase inhibitors reduce the incidence of stroke in patients with coronary heart disease (CHD), the associations between blood lipid levels and cerebrovascular disease (CVD) are not clear. OBJECTIVE To evaluate whether blood cholesterol level and its fractions are risk factors for stroke in a large group of patients with CHD. METHODS We followed up 11 177 patients with documented CHD who were screened for but not included in the Bezafibrate Infarction Prevention study, a secondary prevention randomized clinical trial of lipid modification, and had no history of stroke for subsequent CVD. During a 6- to 8-year follow-up period, 941 patients were identified as having nonhemorrhagic CVD, of whom 487 had verified ischemic stroke or transient ischemic attack (TIA). RESULTS Increases in age-adjusted rates of both nonhemorrhagic CVD and verified ischemic stroke or TIA were identified with increasing cholesterol and low-density lipoprotein cholesterol levels, decreasing high-density lipoprotein cholesterol levels, and decreasing percentage of total serum cholesterol contained in the HDL moiety. In logistic regression models, adjusting for clinical covariates, the following odds ratios (95% confidence intervals) were identified for lipid values in the upper vs lower tertile for the end point of nonhemorrhagic CVD: total cholesterol, 1.43 (1.20-1.70); low-density lipoprotein cholesterol, 1.52 (1.27-1.81), high-density lipoprotein cholesterol, 0.84 (0.70-1.00); and percentage of serum cholesterol contained in HDL, 0.69 (0.58-0.83). Similar trends appeared for the end point of verified ischemic stroke or TIA. CONCLUSION These findings clearly support the role of total cholesterol and its fractions in prediction of ischemic CVD among patients with established CHD.

[1]  S L Hui,et al.  Validation techniques for logistic regression models. , 1991, Statistics in medicine.

[2]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

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

[4]  D. Tanné,et al.  Frequency and Prognosis of Stroke/TIA Among 4808 Survivors of Acute Myocardial Infarction , 1993, Stroke.

[5]  R. Collins,et al.  Blood pressure, stroke, and coronary heart disease Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias , 1990, The Lancet.

[6]  W. Landau,et al.  Is cholesterol a risk factor for stroke?: No. , 1999, Archives of neurology.

[7]  B. Davis,et al.  The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. , 1996, The New England journal of medicine.

[8]  D. Jacobs,et al.  Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial. , 1989, The New England journal of medicine.

[9]  R. Kronmal,et al.  Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. , 1999, The New England journal of medicine.

[10]  W M O'Fallon,et al.  Ischemic stroke subtypes: a population-based study of incidence and risk factors. , 1999, Stroke.

[11]  J. Mohr,et al.  Stroke : pathophysiology, diagnosis, and management , 2004 .

[12]  B. Buckley,et al.  Statins do more than just lower cholesterol , 1996, The Lancet.

[13]  C. Furberg,et al.  Relation between blood lipids, lipoproteins, and cerebrovascular atherosclerosis. A review. , 1988, Stroke.

[14]  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.

[15]  David Lee Gordon,et al.  Classification of Subtype of Acute Ischemic Stroke: Definitions for Use in a Multicenter Clinical Trial , 1993, Stroke.

[16]  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.

[17]  Scandinavian Simvastatin Survival Study Group Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) , 1994, The Lancet.

[18]  J. Velasco,et al.  After 4S, CARE and LIPID--is evidence-based medicine being practised? , 1999, Atherosclerosis.

[19]  H. Becker,et al.  Frequency and prognosis of gastric stump cancer. , 1979, Frontiers of gastrointestinal research.

[20]  G. Guyatt,et al.  Effect of HMGcoA reductase inhibitors on stroke. A meta-analysis of randomized, controlled trials. , 1998, Annals of internal medicine.

[21]  D. Reed,et al.  Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. , 1989, Stroke.

[22]  P. Allhoff,et al.  The Honolulu Heart Program , 1991 .

[23]  W. Kannel,et al.  Role of Lipids in the Development of Brain Infarction: The Framingham Study , 1974, Stroke.

[24]  Daniel B Hier,et al.  Infarcts of undetermined cause: The NINCDS stroke data bank , 1989, Annals of neurology.

[25]  D. Hosmer,et al.  A review of goodness of fit statistics for use in the development of logistic regression models. , 1982, American journal of epidemiology.

[26]  Peter W. Macfarlane,et al.  Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia , 2004 .

[27]  U. Goldbourt,et al.  A SAS program for evaluating person-years of risk in cohort studies. , 1989, Computers in biology and medicine.

[28]  W. O'Fallon,et al.  The association of stroke and coronary heart disease: a population study. , 1987, Mayo Clinic proceedings.

[29]  V. Hachinski Cholesterol as a Risk Factor for Stroke , 1999 .

[30]  C. Furberg,et al.  Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. , 1994, Circulation.

[31]  J. Slattery,et al.  Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). 1994. , 1994, Atherosclerosis. Supplements.

[32]  B. Davis,et al.  Reduction of Stroke Events With Pravastatin: The Prospective Pravastatin Pooling (PPP) Project , 2001, Circulation.

[33]  D. Kromhout Cholesterol, diastolic blood pressure, and stroke: 13 000 strokes in 450 000 people in 45 prospective cohorts , 1995, The Lancet.

[34]  U. Goldbourt,et al.  Rationale and design of a secondary prevention trial of increasing serum high-density lipoprotein cholesterol and reducing triglycerides in patients with clinically manifest atherosclerotic heart disease (the Bezafibrate Infarction Prevention Trial). , 1993, The American journal of cardiology.

[35]  A. Folsom,et al.  Relative importance of various risk factors for asymptomatic carotid atherosclerosis versus coronary heart disease incidence: the Atherosclerosis Risk in Communities Study. , 1999, American journal of epidemiology.

[36]  R. Collins,et al.  Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. , 1998, The New England journal of medicine.

[37]  R. Collins,et al.  Serum cholesterol levels and stroke mortality. , 1989, The New England journal of medicine.

[38]  R. Westendorp,et al.  Stroke, statins, and cholesterol. A meta-analysis of randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors. , 1997, Stroke.

[39]  J. Massé Effect of lovastatin on early carotid atherosclerosis. , 1995, Circulation.

[40]  H. White,et al.  Effects of Lowering Average or Below-Average Cholesterol Levels on the Progression of Carotid Atherosclerosis Results of the LIPID Atherosclerosis Substudy , 1998 .

[41]  G. Gamble,et al.  Effects of lowering average of below-average cholesterol levels on the progression of carotid atherosclerosis: results of the LIPID Atherosclerosis Substudy. LIPID Trial Research Group. , 1998, Circulation.

[42]  Katsuhiko Yano,et al.  Elevated Serum Cholesterol Is a Risk Factor for Both Coronary Heart Disease and Thromboembolic Stroke in Hawaiian Japanese Men: Implications of Shared Risk , 1994, Stroke.

[43]  A. Demchuk,et al.  Is cholesterol a risk factor for stroke?: Yes. , 1999, Archives of neurology.

[44]  D. Tanné,et al.  High-density lipoprotein cholesterol and risk of ischemic stroke mortality. A 21-year follow-up of 8586 men from the Israeli Ischemic Heart Disease Study. , 1997, Stroke.