American Journal of Kidney Diseases

Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women’s Health Initiative

Published:September 01, 2015DOI:


      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 isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n = 8,921), African American (n = 7,436), or Hispanic (n = 3,054) were used to calculate estimated glomerular filtration rates (eGFRs).


      Categories of eGFR (exposure); race/ethnicity (effect modifier).


      The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death.


      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.


      During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related 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 eGFRs and very few events occurring in these categories.


      Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics.


      In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.

      Index Words

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        • Coresh J.
        • Selvin E.
        • Stevens L.A.
        • et al.
        Prevalence of chronic kidney disease in the United States.
        JAMA. 2007; 298: 2038-2047
        • Grams M.E.
        • Juraschek S.P.
        • Selvin E.
        • et al.
        Trends in the prevalence of reduced GFR in the United States: a comparison of creatinine- and cystatin C-based estimates.
        Am J Kidney Dis. 2013; 62: 253-260
        • Go A.S.
        • Chertow G.M.
        • Fan D.
        • McCulloch C.E.
        • Hsu C.Y.
        Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.
        N Engl J Med. 2004; 351: 1296-1305
        • Gutierrez O.M.
        • Khodneva Y.A.
        • Muntner P.
        • et al.
        Association between urinary albumin excretion and coronary heart disease in black vs white adults.
        JAMA. 2013; 310: 706-714
        • Peralta C.A.
        • Vittinghoff E.
        • Bansal N.
        • et al.
        Trajectories of kidney function decline in young black and white adults with preserved GFR: results from the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
        Am J Kidney Dis. 2013; 62: 261-266
        • Collins A.J.
        • Foley R.N.
        • Herzog C.
        • et al.
        US Renal Data System 2012 annual data report.
        Am J Kidney Dis. 2013; 61: e1-e480
        • Peralta C.A.
        • Shlipak M.G.
        • Fan D.
        • et al.
        Risks for end-stage renal disease, cardiovascular events, and death in Hispanic versus non-Hispanic white adults with chronic kidney disease.
        J Am Soc Nephrol. 2006; 17: 2892-2899
        • Weiner D.E.
        • Tabatabai S.
        • Tighiouart H.
        • et al.
        Cardiovascular outcomes and all-cause mortality: exploring the interaction between CKD and cardiovascular disease.
        Am J Kidney Dis. 2006; 48: 392-401
        • Roderick P.J.
        • Atkins R.J.
        • Smeeth L.
        • et al.
        CKD and mortality risk in older people: a community-based population study in the United Kingdom.
        Am J Kidney Dis. 2009; 53: 950-960
        • Muntner P.
        • He J.
        • Hamm L.
        • Loria C.
        • Whelton P.K.
        Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States.
        J Am Soc Nephrol. 2002; 13: 745-753
        • Nitsch D.
        • Grams M.
        • Sang Y.
        • et al.
        Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis.
        BMJ. 2013; 346: f324
        • Hui X.
        • Matsushita K.
        • Sang Y.
        • Ballew S.H.
        • Fulop T.
        • Coresh J.
        CKD and cardiovascular disease in the Atherosclerosis Risk in Communities (ARIC) Study: interactions with age, sex, and race.
        Am J Kidney Dis. 2013; 62: 691-702
        • Jassal S.K.
        • Langenberg C.
        • von Muhlen D.
        • Bergstrom J.
        • Barrett-Connor E.
        Usefulness of microalbuminuria versus the metabolic syndrome as a predictor of cardiovascular disease in women and men > 40 years of age (from the Rancho Bernardo Study).
        Am J Cardiol. 2008; 101: 1275-1280
        • Curb J.D.
        • McTiernan A.
        • Heckbert S.R.
        • et al.
        Outcomes ascertainment and adjudication methods in the Women's Health Initiative.
        Ann Epidemiol. 2003; 13: S122-S128
        • No authors listed. Design of the Women's Health Initiative clinical trial and observational study
        The Women's Health Initiative Study Group.
        Control Clin Trials. 1998; 19: 61-109
        • Vaughan L.
        • Espeland M.A.
        • Snively B.
        • et al.
        The rationale, design, and baseline characteristics of the Women's Health Initiative Memory Study of Younger Women (WHIMS-Y).
        Brain Res. 2013; 1514: 3-11
      1. National Human Genome Research Institute. Genomics and Randomized Trials Network (GARNET). Accessed August 24, 2015.

        • Levey A.S.
        • Coresh J.
        • Greene T.
        • et al.
        Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values.
        Clin Chem. 2007; 53: 766-772
        • Matsushita K.
        • Mahmoodi B.K.
        • Woodward M.
        • et al.
        Comparison of risk prediction using the CKD-EPI equation and the MDRD Study equation for estimated glomerular filtration rate.
        JAMA. 2012; 307: 1941-1951
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Anderson G.L.
        • Manson J.
        • Wallace R.
        • et al.
        Implementation of the Women's Health Initiative study design.
        Ann Epidemiol. 2003; 13: S5-S17
        • Bohannon R.W.
        • DePasquale L.
        Physical Functioning Scale of the Short-Form (SF) 36: internal consistency and validity with older adults.
        J Geriatr Phys Ther. 2010; 33: 16-18
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin Chem. 1972; 18: 499-502
        • Shlipak M.G.
        • Matsushita K.
        • Arnlov J.
        • et al.
        Cystatin C versus creatinine in determining risk based on kidney function.
        N Engl J Med. 2013; 369: 932-943
        • Jolly S.E.
        • Burrows N.R.
        • Chen S.C.
        • et al.
        Racial and ethnic differences in mortality among individuals with chronic kidney disease: results from the Kidney Early Evaluation Program (KEEP).
        Clin J Am Soc Nephrol. 2011; 6: 1858-1865
        • Wen C.P.
        • Matsushita K.
        • Coresh J.
        • et al.
        Relative risks of chronic kidney disease for mortality and end-stage renal disease across races are similar.
        Kidney Int. 2014;
        • Muntner P.
        • Garrett E.
        • Klag M.J.
        • Coresh J.
        Trends in stroke prevalence between 1973 and 1991 in the US population 25 to 74 years of age.
        Stroke. 2002; 33: 1209-1213
        • Kaushik M.
        • Sontineni S.P.
        • Hunter C.
        Cardiovascular disease and androgens: a review.
        Int J Cardiol. 2010; 142: 8-14
        • Leuzzi C.
        • Marzullo R.
        • Modena M.G.
        [Is menopause a risk factor for ischemic heart disease in women?].
        G Ital Cardiol. 2012; 13: 401-406
        • Smulyan H.
        • Asmar R.G.
        • Rudnicki A.
        • London G.M.
        • Safar M.E.
        Comparative effects of aging in men and women on the properties of the arterial tree.
        J Am Coll Cardiol. 2001; 37: 1374-1380
        • Ma Y.
        • Hebert J.R.
        • Balasubramanian R.
        • et al.
        All-cause, cardiovascular, and cancer mortality rates in postmenopausal white, black, Hispanic, and Asian women with and without diabetes in the United States: the Women's Health Initiative, 1993-2009.
        Am J Epidemiol. 2013; 178: 1533-1541
        • McTigue K.M.
        • Chang Y.F.
        • Eaton C.
        • et al.
        Severe obesity, heart disease, and death among white, African American, and Hispanic postmenopausal women.
        Obesity. 2014; 22: 801-810
        • Shlipak M.G.
        • Simon J.A.
        • Grady D.
        • Lin F.
        • Wenger N.K.
        • Furberg C.D.
        Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease.
        J Am Coll Cardiol. 2001; 38: 705-711
        • Matsushita K.
        • van der Velde M.
        • Astor B.C.
        • et al.
        Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.
        Lancet. 2010; 375: 2073-2081
        • Waheed S.
        • Matsushita K.
        • Astor B.C.
        • Hoogeveen R.C.
        • Ballantyne C.
        • Coresh J.
        Combined association of creatinine, albuminuria, and cystatin C with all-cause mortality and cardiovascular and kidney outcomes.
        Clin J Am Soc Nephrol. 2013; 8: 434-442
        • Shlipak M.G.
        • Sarnak M.J.
        • Katz R.
        • et al.
        Cystatin C and the risk of death and cardiovascular events among elderly persons.
        N Engl J Med. 2005; 352: 2049-2060
        • Hlatky M.A.
        • Ray R.M.
        • Burwen D.R.
        • et al.
        Use of Medicare data to identify coronary heart disease outcomes in the Women's Health Initiative.
        Circ Cardiovasc Qual Outcomes. 2014; 7: 157-162
        • Lakshminarayan K.
        • Larson J.C.
        • Virnig B.
        • et al.
        Comparison of Medicare claims versus physician adjudication for identifying stroke outcomes in the Women's Health Initiative.
        Stroke. 2014; 45: 815-821
        • Stevens L.A.
        • Schmid C.H.
        • Greene T.
        • et al.
        Comparative performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study equations for estimating GFR levels above 60 mL/min/1.73 m2.
        Am J Kidney Dis. 2010; 56: 486-495