HHS Public Access Author manuscript Author Manuscript
Am J Kidney Dis. Author manuscript; available in PMC 2017 February 01. Published in final edited form as: Am J Kidney Dis. 2016 February ; 67(2): 198–208. doi:10.1053/j.ajkd.2015.07.020.
Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women’s Health Initiative
Author Manuscript
Cristina M. Arce, MD, MSc1,2,*, Jinnie J. Rhee, MSc, ScD1,*, Katharine L. Cheung, MD, MSc, FRCPC1,3, Haley Hedlin, PhD1, Kristopher Kapphahn, MSc1, Nora Franceschini, MD4, Roberto S. Kalil, MD5, Lisa W. Martin, MD6, Lihong Qi, PhD7, Nawar M. Shara, PhD8, Manisha Desai, PhD1, Marcia L. Stefanick, PhD1, and Wolfgang C. Winkelmayer, MD, ScD1,9 on behalf of the Women’s Health Initiative Investigators** 1Stanford 2Ohio
University School of Medicine, Palo Alto, CA
State University, Columbus, OH
3University
of Vermont, Burlington, VT
4University
of North Carolina Gillings School of Global Public Health, Chapel Hill, NC
5University
of Iowa Carver College of Medicine, Iowa City, IA
6George
Washington University, Washington, D.C.
7University
Author Manuscript
8MedStar 9Baylor
of California, Davis, Davis, CA
Health Research Institute, Hyattsville, MD
College of Medicine, Houston, TX
Abstract Correspondence to: Wolfgang C. Winkelmayer, MD, MPH, ScD; Section of Nephrology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030; Tel: 713-798-2625; Fax 713-798-5010; [email protected]. *C.M.A. and J.J.R. contributed equally to this work. **Information about the WHI Investigators and centers appears in the Financial Disclosure: The authors declare that they have no other relevant financial interests.
Author Manuscript
Contributions: Research idea and study design: CMA, JJR, WCW; data acquisition: MLS; data analysis/interpretation: all authors; statistical analysis: HH, KK, MD; supervision or mentorship: WCW. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. WCW takes responsibility that this study has been reported honestly, accurately, and transparently; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned and registered have been explained. Supplementary Material: Table S1: HRs for composite CV outcome by eGFR category and race/ethnicity. Table S2: HRs for MI by eGFR category and race/ethnicity. Table S3: HRs for stroke events by eGFR category and race/ethnicity. Table S4: HRs for CV deaths by eGFR category and race/ethnicity. Item S1: WHI clinical trial and observational study design and adjudication of CV events. Note: The supplementary material accompanying this article (doi:_______) is available at www.ajkd.org Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Arce et al.
Page 2
Author Manuscript
Background—Kidney disease disproportionately affects minority populations including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women’s Health Initiative. Study Design—Prospective cohort study Setting & Participants—Baseline serum creatinine concentrations (assay traceable to isotopedilution mass spectrometry standard) of 19,411 postmenopausal women aged 50–79 years who self-identified as either non-Hispanic white (n=8921), African American (n=7436), or Hispanic (n=3054) were used to calculate estimated glomerular filtration rates (eGFRs). Predictors—Categories of eGFR (exposure); race/ethnicity (effect modifier).
Author Manuscript
Outcomes—The primary outcome was the composite of three physician-adjudicated CV events: myocardial infarction (MI), stroke, or CV-related death. Measurements—We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity.
Author Manuscript
Results—Over a mean follow-up of 7.6 years, 1424 CV events (653 MI, 627 strokes, 297 CVrelated deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship with lower eGFR being associated with higher CV risk and higher eGFR with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFR and very few events occurring in these categories. Limitations—Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics. Conclusions—In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women. INDEX WORDS cardiovascular disease (CVD); CV risk; CV events; myocardial infarction (MI); stroke; CV death; renal function; estimated glomerular filtration rate (eGFR); serum creatinine; race/ethnicity; Hispanic; African American; kidney disease; Women’s Health Initiative (WHI)
Author Manuscript
Chronic kidney disease (CKD), defined by a glomerular filtration rate (GFR)
Am J Kidney Dis. Author manuscript; available in PMC 2017 February 01. Published in final edited form as: Am J Kidney Dis. 2016 February ; 67(2): 198–208. doi:10.1053/j.ajkd.2015.07.020.
Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women’s Health Initiative
Author Manuscript
Cristina M. Arce, MD, MSc1,2,*, Jinnie J. Rhee, MSc, ScD1,*, Katharine L. Cheung, MD, MSc, FRCPC1,3, Haley Hedlin, PhD1, Kristopher Kapphahn, MSc1, Nora Franceschini, MD4, Roberto S. Kalil, MD5, Lisa W. Martin, MD6, Lihong Qi, PhD7, Nawar M. Shara, PhD8, Manisha Desai, PhD1, Marcia L. Stefanick, PhD1, and Wolfgang C. Winkelmayer, MD, ScD1,9 on behalf of the Women’s Health Initiative Investigators** 1Stanford 2Ohio
University School of Medicine, Palo Alto, CA
State University, Columbus, OH
3University
of Vermont, Burlington, VT
4University
of North Carolina Gillings School of Global Public Health, Chapel Hill, NC
5University
of Iowa Carver College of Medicine, Iowa City, IA
6George
Washington University, Washington, D.C.
7University
Author Manuscript
8MedStar 9Baylor
of California, Davis, Davis, CA
Health Research Institute, Hyattsville, MD
College of Medicine, Houston, TX
Abstract Correspondence to: Wolfgang C. Winkelmayer, MD, MPH, ScD; Section of Nephrology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030; Tel: 713-798-2625; Fax 713-798-5010; [email protected]. *C.M.A. and J.J.R. contributed equally to this work. **Information about the WHI Investigators and centers appears in the Financial Disclosure: The authors declare that they have no other relevant financial interests.
Author Manuscript
Contributions: Research idea and study design: CMA, JJR, WCW; data acquisition: MLS; data analysis/interpretation: all authors; statistical analysis: HH, KK, MD; supervision or mentorship: WCW. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. WCW takes responsibility that this study has been reported honestly, accurately, and transparently; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned and registered have been explained. Supplementary Material: Table S1: HRs for composite CV outcome by eGFR category and race/ethnicity. Table S2: HRs for MI by eGFR category and race/ethnicity. Table S3: HRs for stroke events by eGFR category and race/ethnicity. Table S4: HRs for CV deaths by eGFR category and race/ethnicity. Item S1: WHI clinical trial and observational study design and adjudication of CV events. Note: The supplementary material accompanying this article (doi:_______) is available at www.ajkd.org Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Arce et al.
Page 2
Author Manuscript
Background—Kidney disease disproportionately affects minority populations including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women’s Health Initiative. Study Design—Prospective cohort study Setting & Participants—Baseline serum creatinine concentrations (assay traceable to isotopedilution mass spectrometry standard) of 19,411 postmenopausal women aged 50–79 years who self-identified as either non-Hispanic white (n=8921), African American (n=7436), or Hispanic (n=3054) were used to calculate estimated glomerular filtration rates (eGFRs). Predictors—Categories of eGFR (exposure); race/ethnicity (effect modifier).
Author Manuscript
Outcomes—The primary outcome was the composite of three physician-adjudicated CV events: myocardial infarction (MI), stroke, or CV-related death. Measurements—We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity.
Author Manuscript
Results—Over a mean follow-up of 7.6 years, 1424 CV events (653 MI, 627 strokes, 297 CVrelated deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship with lower eGFR being associated with higher CV risk and higher eGFR with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFR and very few events occurring in these categories. Limitations—Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics. Conclusions—In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women. INDEX WORDS cardiovascular disease (CVD); CV risk; CV events; myocardial infarction (MI); stroke; CV death; renal function; estimated glomerular filtration rate (eGFR); serum creatinine; race/ethnicity; Hispanic; African American; kidney disease; Women’s Health Initiative (WHI)
Author Manuscript
Chronic kidney disease (CKD), defined by a glomerular filtration rate (GFR)
