apoE4 allele and the natural history of cardiovascular risk factors.

The aims of the present study were to compare the longitudinal changes in traditional cardiovascular (CV) risk factors (blood pressure, BMI, total and HDL-cholesterol, triglycerides, and blood glucose) in men with and without the apolipoprotein (apo)E4 allele. Three hundred six men from the Baltimore Longitudinal Study of Aging, ranging in age from 20 to 92 yr, were studied. Repeated measurements of CV risk factors were performed over a median follow-up time of 7 yr (maximum 14.3 yr) for men. Longitudinal changes in these CV risk factors were analyzed by linear mixed-effects models. The prevalence of the apoE4 allele was 25.5%. apoE4 was independently associated with accelerated changes over time in fasting plasma glucose (+9.5% vs. no change in those without apoE4 in the 6th age-decade over 10 yr). No significant effect of apoE4 on longitudinal changes in total or HDL-cholesterol, triglycerides, or blood pressures was observed. In conclusion, apoE4 influences fasting plasma glucose and its changes over time. This could explain, in part, the increased CV risk associated with the apoE4 genotype observed in men.

[1]  M. Woodward,et al.  Blood glucose and risk of cardiovascular disease in the Asia Pacific region. , 2004, Diabetes care.

[2]  S. Laurent,et al.  Glucose level is a major determinant of carotid intima–media thickness in patients with hypertension and hyperglycemia , 2004, Journal of hypertension.

[3]  Michele Muggeo,et al.  Population-based incidence rates and risk factors for type 2 diabetes in white individuals: the Bruneck study. , 2004, Diabetes.

[4]  J. Krystal,et al.  Move over ANOVA: progress in analyzing repeated-measures data and its reflection in papers published in the Archives of General Psychiatry. , 2004, Archives of general psychiatry.

[5]  M. Hayden,et al.  Islet amyloid, metabolic syndrome, and the natural progressive history of type 2 diabetes mellitus. , 2002, JOP : Journal of the pancreas.

[6]  G. Siest,et al.  Early-glycation of apolipoprotein E: effect on its binding to LDL receptor, scavenger receptor A and heparan sulfates. , 2002, Biochimica et biophysica acta.

[7]  E. Barrett-Connor,et al.  Apolipoprotein E polymorphism and lipid levels differ by gender and family history of diabetes: the Rancho Bernardo Study , 2001, Clinical genetics.

[8]  Ana Ivelisse Avilés,et al.  Linear Mixed Models for Longitudinal Data , 2001, Technometrics.

[9]  L. Crofford,et al.  Cyclooxygenase inhibition and thrombogenicity. , 2001, The American journal of medicine.

[10]  P. Stiefel,et al.  Apolipoprotein E gene polymorphism is related to metabolic abnormalities, but does not influence erythrocyte membrane lipid composition or sodium-lithium countertransport activity in essential hypertension. , 2001, Metabolism: clinical and experimental.

[11]  J. Fleg,et al.  Is the apoE4 allele an independent predictor of coronary events? , 2001, The American journal of medicine.

[12]  B. Ahrén,et al.  Islet amyloid and type 2 diabetes mellitus. , 2000, The New England journal of medicine.

[13]  D. Singer,et al.  Apolipoprotein E isoform polymorphisms are not associated with insulin resistance: the Framingham Offspring Study. , 2000, Diabetes care.

[14]  R. Frikke-Schmidt,et al.  Apolipoprotein E genotype: epsilon32 women are protected while epsilon43 and epsilon44 men are susceptible to ischemic heart disease: the Copenhagen City Heart Study. , 2000, Journal of the American College of Cardiology.

[15]  D. Gómez-Coronado,et al.  Apolipoprotein E polymorphism in men and women from a Spanish population: allele frequencies and influence on plasma lipids and apolipoproteins. , 1999, Atherosclerosis.

[16]  Sanjay Asthana,et al.  Insulin Metabolism in Alzheimer’s Disease Differs According to Apolipoprotein E Genotype and Gender , 1999, Neuroendocrinology.

[17]  L. Bernier,et al.  Apolipoprotein E and atherosclerosis: insight from animal and human studies. , 1999, Clinica chimica acta; international journal of clinical chemistry.

[18]  J. Thijssen,et al.  Extensive islet amyloid formation is induced by development of Type II diabetes mellitus and contributes to its progression: pathogenesis of diabetes in a mouse model , 1999, Diabetologia.

[19]  J. Ordovás,et al.  The apolipoprotein E4 allele is not associated with an abnormal lipid profile in a Native American population following its traditional lifestyle. , 1999, Atherosclerosis.

[20]  Charles F. Sing,et al.  An ecological study of association between coronary heart disease mortality rates in men and the relative frequencies of common allelic variations in the gene coding for apolipoprotein E , 1998, Human Genetics.

[21]  T. Arinami,et al.  Methylenetetrahydrofolate reductase and apolipoprotein E polymorphisms are independent risk factors for coronary heart disease in Japanese: a case-control study. , 1998, Atherosclerosis.

[22]  J. Bernhagen,et al.  Contribution of advanced glycosylation to the amyloidogenicity of islet amyloid polypeptide. , 1998, European journal of biochemistry.

[23]  Christopher H. Morrell,et al.  Linear Transformations of Linear Mixed-Effects Models , 1997 .

[24]  R. T. Carroll,et al.  Cerebral lipid deposition in aged apolipoprotein-E-deficient mice. , 1997, The American journal of pathology.

[25]  M. Linton,et al.  Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[26]  F. Baralle,et al.  Polymorphism of the apolipoprotein E gene and early carotid atherosclerosis defined by ultrasonography in asymptomatic adults. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[27]  Thomas Wisniewski,et al.  The Interaction between Apolipoprotein E and Alzheimers Amyloid -Peptide Is Dependent on -Peptide Conformation (*) , 1996, The Journal of Biological Chemistry.

[28]  T. Wisniewski,et al.  The interaction between apolipoprotein E and Alzheimer's amyloid beta-peptide is dependent on beta-peptide conformation. , 1996, The Journal of biological chemistry.

[29]  J. Stengård,et al.  Apolipoprotein E polymorphism predicts death from coronary heart disease in a longitudinal study of elderly Finnish men. , 1995, Circulation.

[30]  P A Wolf,et al.  Apolipoprotein E alleles, dyslipidemia, and coronary heart disease. The Framingham Offspring Study. , 1994, JAMA.

[31]  T Vogel,et al.  Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro. , 1994, The American journal of pathology.

[32]  E. D. de Koning,et al.  Intra- and extracellular amyloid fibrils are formed in cultured pancreatic islets of transgenic mice expressing human islet amyloid polypeptide. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[33]  T. Hayek,et al.  Increased plasma and lipoprotein lipid peroxidation in apo E-deficient mice. , 1994, Biochemical and biophysical research communications.

[34]  V. Ord,et al.  ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis. Demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[35]  Y. Kesäniemi,et al.  Gallstone cholesterol content is related to apolipoprotein E polymorphism. , 1993, Gastroenterology.

[36]  L. Kuller,et al.  Relation of apolipoprotein E phenotype to myocardial infarction and mortality from coronary artery disease. , 1993, The American journal of cardiology.

[37]  J. Dallongeville Apolipoprotéine E: propriétés physiologiques, polymorphisme et athérosclérose , 1993 .

[38]  J. Hixson Apolipoprotein E polymorphisms affect atherosclerosis in young males. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.

[39]  D. T. Vernier,et al.  Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. , 1990, Journal of lipid research.

[40]  R. Mahley,et al.  Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. , 1988, Science.

[41]  C. Sing,et al.  Apolipoprotein E polymorphism and atherosclerosis. , 1988, Arteriosclerosis.

[42]  I. Rossman,et al.  Normal Human Aging: The Baltimore Longitudinal Study of Aging , 1986 .

[43]  David Arenberg,et al.  Normal Human Aging: The Baltimore Longitudinal Study on Aging , 1984 .

[44]  H. Blackburn,et al.  Cardiovascular survey methods. , 1969, Monograph series. World Health Organization.