title: Cholesterol and the risk of renal dysfunction in apparently healthy men.
abstract: Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal disease, the association between cholesterol and the development of renal dysfunction is unclear. We evaluated this association in a prospective cohort study among 4,483 initially healthy men participating in the Physicians' Health Study who provided blood samples in 1982 and 1996. Main outcome measures were elevated creatinine, defined as >/= 1.5 mg/dl (133 micromol/L), and reduced estimated creatinine clearance, defined as </=55 ml/min. Cholesterol parameters included total cholesterol (<200, 200 to 239, and >/= 240 mg/dl), HDL (<40 or >/= 40 mg/dl), total non-HDL cholesterol, and the ratio of total cholesterol to HDL. We used logistic regression to calculate age- and multivariable adjusted odds ratios as a measure for the relative risk. After 14 yr, 134 men (3.0%) had elevated creatinine and 244 (5.4%) had reduced creatinine clearance. The multivariable relative risk for elevated creatinine was 1.77 (95% confidence interval [CI], 1.10 to 2.86) for total cholesterol >/= 240 mg/dl, 2.16 (95% CI, 1.42 to 3.27) for HDL <40 mg/dl, 2.34 (95% CI, 1.34 to 4.07) for the highest quartile of total cholesterol/HDL ratio (>/= >6.8), and 2.16 (95% CI, 1.22 to 3.80) for the highest quartile of non-HDL cholesterol (>/= 196.1). Similar although smaller associations were observed between cholesterol parameters and reduced creatinine clearance. Elevated total cholesterol, high non-HDL cholesterol, a high ratio of total cholesterol/HDL, and low HDL in particular were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine <1.5 mg/dl.
authors.affiliation: Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.
authors.forename: Elke S
authors.initials: ES
authors.lastname: Schaeffner
authors.affiliation: Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kurth
authors.affiliation: Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.
authors.forename: Gary C
authors.initials: GC
authors.lastname: Curhan
authors.affiliation: Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.affiliation: Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rexrode
authors.affiliation: Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.
authors.forename: Colin
authors.initials: C
authors.lastname: Baigent
authors.affiliation: Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.|Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
mesh_terms: D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D004492:Edetic Acid / Q000737:chemistry; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis* / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D050356:Lipid Metabolism; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D011446:Prospective Studies; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D008076:Cholesterol, HDL; D002784:Cholesterol; D004492:Edetic Acid; D003404:Creatinine