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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: Unique identifier: NCT00125593.

Original publication




Journal article


Hypertension (Dallas, Tex. : 1979)

Publication Date





314 - 322


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.).


SHARP Collaborative Group, Kidney, Humans, Cardiovascular Diseases, Simvastatin, Anticholesteremic Agents, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Prognosis, Drug Therapy, Combination, Risk Factors, Follow-Up Studies, Blood Pressure, Aged, Middle Aged, Female, Male, Renal Insufficiency, Chronic, Ezetimibe