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Original Research |

Blood Pressure and Mortality in U.S. Veterans With Chronic Kidney Disease: A Cohort Study

Csaba P. Kovesdy, MD; Anthony J. Bleyer, MD; Miklos Z. Molnar, MD, PhD; Jennie Z. Ma, PhD; John J. Sim, MD; William C. Cushman, MD; L. Darryl Quarles, MD; and Kamyar Kalantar-Zadeh, MD, PhD
[+] Article and Author Information

From Memphis Veterans Affairs Medical Center and University of Tennessee Health Science Center, Memphis, Tennessee; Wake Forest School of Medicine, Winston-Salem, North Carolina; University Health Network, University of Toronto, Toronto, Ontario, Canada; Semmelweis University, Budapest, Hungary; University of Virginia, Charlottesville, Virginia; Kaiser Permanente Los Angeles Medical Center, Los Angeles, California; and University of California, Irvine, Orange, California.

Parts of this material were presented at Kidney Week 2011, American Society of Nephrology, Philadelphia, Pennsylvania, 8–13 November 2011.

Disclaimer: Opinions expressed in this article are those of the authors and do not necessarily represent the opinions of the U.S. Department of Veterans Affairs.

Grant Support: By the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK078106-01), National Institutes of Health, and the U.S. Department of Veterans Affairs.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0460.

Reproducible Research Statement: Study protocol and data set: Not available. Statistical code: Available from Dr. Kovesdy (e-mail, csaba.kovesdy@va.gov).

Requests for Single Reprints: Csaba P. Kovesdy, MD, Division of Nephrology (111B), Memphis Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104; e-mail, csaba.kovesdy@va.gov.

Current Author Addresses: Dr. Kovesdy: Division of Nephrology (111B), Memphis Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104.

Dr. Bleyer: Section of Nephrology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157.

Dr. Molnar: Semmelweis University, Institute of Pathophysiology, Nagyvarad ter 4, H-1089, Budapest, Hungary.

Dr. Ma: Division of Biostatistics, Department of Public Health Sciences, University of Virginia, PO Box 800717, Charlottesville, VA 22908-0717.

Dr. Sim: 4700 Sunset Boulevard, Los Angeles, CA 90027.

Dr. Cushman: Preventive Medicine (111Q), Memphis Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104.

Dr. Quarles: Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, College of Medicine, 956 Court Avenue, Suite B226, Memphis, TN 38163.

Dr. Kalantar-Zadeh: Harold Simmons Center at University of California, Irvine, Veterans Affairs Long Beach Healthcare System, 5901 East 7th Street, Long Beach, CA 90822.

Author Contributions: Conception and design: C.P. Kovesdy, A.J. Bleyer, W.C. Cushman, K. Kalantar-Zadeh.

Analysis and interpretation of the data: C.P. Kovesdy, A.J. Bleyer, M.Z. Molnar, J.Z. Ma, K. Kalantar-Zadeh.

Drafting of the article: C.P. Kovesdy, A.J. Bleyer, W.C. Cushman.

Critical revision of the article for important intellectual content: A.J. Bleyer, M.Z. Molnar, J.Z. Ma, J.J. Sim, W.C. Cushman, L.D. Quarles, K. Kalantar-Zadeh.

Final approval of the article: A.J. Bleyer, M.Z. Molnar, J.Z. Ma, W.C. Cushman, K. Kalantar-Zadeh.

Statistical expertise: C.P. Kovesdy, A.J. Bleyer, J.Z. Ma, K. Kalantar-Zadeh.

Obtaining of funding: C.P. Kovesdy, K. Kalantar-Zadeh.

Administrative, technical, or logistic support: C.P. Kovesdy, M.Z. Molnar, K. Kalantar-Zadeh.

Collection and assembly of data: C.P. Kovesdy.


Ann Intern Med. 2013;159(4):233-242. doi:10.7326/0003-4819-159-4-201308200-00004
Text Size: A A A

Chinese translation

Background: The ideal blood pressure (BP) to decrease mortality rates in patients with non–dialysis-dependent chronic kidney disease (CKD) is unclear.

Objective: To assess the association of BP (defined as the combination of systolic BP [SBP] and diastolic BP [DBP] at the individual level) with death in patients with CKD.

Design: Historical cohort between 2005 and 2012.

Setting: All U.S. Department of Veterans Affairs health care facilities.

Patients: 651 749 U.S. veterans with CKD.

Measurements: All possible combinations of SBP and DBP were examined in 96 categories from lowest (<80/<40 mm Hg) to highest (>210/>120 mm Hg), in 10–mm Hg increments. Associations with all-cause mortality were examined in time-dependent Cox models with adjustment for relevant confounders.

Results: Patients with SBP of 130 to 159 mm Hg combined with DBP of 70 to 89 mm Hg had the lowest adjusted mortality rates, and those in whom both SBP and DBP were concomitantly very high or very low had the highest mortality rates. Patients with moderately elevated SBP combined with DBP no less than 70 mm Hg had consistently lower mortality rates than did patients with ideal SBP combined with DBP less than 70 mm Hg. Results were consistent in subgroups of patients with normal and elevated urinary microalbumin–creatinine ratios.

Limitation: Mostly male patients, inability to establish causality, and large number of patients missing proteinuria measurement.

Conclusion: The optimal BP in patients with CKD seems to be 130 to 159/70 to 89 mm Hg. It may not be advantageous to achieve ideal SBP at the expense of lower-than-ideal DBP in adults with CKD.

Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and U.S. Department of Veterans Affairs.

Figures

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Appendix Figure 1.

Study flow diagram.

BP = blood pressure; CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease.

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Grahic Jump Location
Figure 1.

Multivariable-adjusted relative hazards (hazard ratios [95% CIs]) of all-cause mortality associated with SBP and DBP relative to a hypothetical patient with the mean time-varying SBP (133 mm Hg) and DBP (71 mm Hg).

Calculated in time-dependent Cox models using restricted cubic splines, adjusted for age, sex, race, diabetes mellitus, cardiovascular and cerebrovascular disease, chronic heart failure, Charlson Comorbidity Index scores, medication use (angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers; α-blockers, β-blockers, and calcium-channel blockers; loop and thiazide diuretics; and cholesterol-lowering agents), estimated glomerular filtration rates, and blood cholesterol levels. DBP = diastolic blood pressure; SBP = systolic blood pressure.

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Grahic Jump Location
Appendix Figure 2.

Multivariable-adjusted relative hazards (hazard ratios [95% CIs]) of all-cause mortality associated with baseline SBP and DBP relative to a hypothetical patient with the mean SBP (135 mm Hg) and DBP (72 mm Hg).

Calculated in Cox models using restricted cubic splines, adjusted for age, sex, race, diabetes mellitus, cardiovascular and cerebrovascular disease, chronic heart failure, Charlson Comorbidity Index scores, baseline medication use (angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers; α-blockers, β-blockers, and calcium-channel blockers; loop and thiazide diuretics; and cholesterol-lowering agents), baseline estimated glomerular filtration rates, and baseline blood cholesterol levels. DBP = diastolic blood pressure; SBP = systolic blood pressure.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Multivariable-adjusted mortality hazard ratios (95% CIs) associated with blood pressure categories defined according to cutoffs established by the JNC 7.

The group with systolic blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg served as reference. Estimates are from time-dependent Cox models adjusted for age, sex, race, diabetes mellitus, cardiovascular and cerebrovascular disease, chronic heart failure, Charlson Comorbidity Index scores, medication use (angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers; α-blockers, β-blockers, and calcium-channel blockers; loop and thiazide diuretics; and cholesterol-lowering agents), eGFRs, and blood cholesterol levels. CAD = coronary artery disease; CHF = chronic heart failure; eGFR = estimated glomerular filtration rate; HTN = hypertension; UACR = urinary microalbumin–creatinine ratio.

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