title: Evidence for Reverse Causality in the Association Between Blood Pressure and Cardiovascular Risk in Patients With Chronic Kidney Disease.
abstract: Among those with moderate-to-advanced chronic kidney disease, the relationship between blood pressure (BP) and cardiovascular disease seems U shaped but is loglinear in apparently healthy adults. The SHARP (Study of Heart and Renal Protection) randomized 9270 patients with chronic kidney disease to ezetimibe/simvastatin versus matching placebo and measured BP at each follow-up visit. Cox regression was used to assess the association between BP and risk of cardiovascular disease among (1) those with a self-reported history of cardiovascular disease and (2) those with no such history and, based on plasma troponin-I concentration, a low probability of subclinical cardiac disease. A total of 8666 participants had a valid baseline BP and troponin-I measurement, and 2188 had at least 1 cardiovascular event during follow-up. After adjustment for relevant confounders, the association between systolic BP and cardiovascular events was U shaped, but among participants without evidence of previous cardiovascular disease, there was a positive loglinear association throughout the range of values studied. Among those with the lowest probability of subclinical cardiac disease, each 10 mm Hg higher systolic BP corresponded to a 27% increased risk of cardiovascular disease (hazard ratio, 1.27; 95% confidence interval, 1.11-1.44). In contrast, the relationship between diastolic BP and cardiovascular risk remained U shaped irrespective of cardiovascular disease history or risk of subclinical disease. In conclusion, the lack of a clear association between systolic BP and cardiovascular risk in this population seems attributable to confounding, suggesting that more intensive systolic BP reduction may be beneficial in such patients.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00125593.
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: William
authors.initials: W
authors.lastname: Herrington
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Natalie
authors.initials: N
authors.lastname: Staplin
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Parminder K
authors.initials: PK
authors.lastname: Judge
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Marion
authors.initials: M
authors.lastname: Mafham
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Emberson
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Richard
authors.initials: R
authors.lastname: Haynes
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: David C
authors.initials: DC
authors.lastname: Wheeler
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Robert
authors.initials: R
authors.lastname: Walker
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Charlie
authors.initials: C
authors.lastname: Tomson
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Larry
authors.initials: L
authors.lastname: Agodoa
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wiecek
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Sarah
authors.initials: S
authors.lastname: Lewington
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Christina A
authors.initials: CA
authors.lastname: Reith
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.).
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Landray
authors.affiliation: From the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), (W.H., N.S., P.K.J., M.M., J.E., R.H., S.L., C.A.R., M.J.L., C.B.) and Medical Research Council-Population Health Research Unit (MRC-PHRU) (P.K.J., J.E., R.H., S.L., C.B.), Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom; Centre for Nephrology, University College London, United Kingdom (D.C.W.); Dunedin School of Medicine, University of Otago, New Zealand (R.W.); Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom (C.T.); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (L.A.); and Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland (A.W.). colin.baigent@ndph.ox.ac.uk.
authors.forename: Colin
authors.initials: C
authors.lastname: Baigent
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology; D012307:Risk Factors; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000069438:Ezetimibe
keywords: blood pressure; chronic kidney disease; epidemiology; troponin; vascular disease