Mayo Clinic Proceedings Home

Estimated Glomerular Filtration Rate, Activation of Cardiac Biomarkers and Long-Term Cardiovascular Outcomes: A Population-Based Cohort

Published:October 23, 2019DOI:



      To classify subjects in a general population per their renal function and characterize the cardiac biomarker levels, left ventricular function and cardiovascular outcomes over a 10.2 year follow-up period (interquartile range, 5.1–11.4 years).


      This was a retrospective review of a population-based random sample of residents aged ≥45 years. Data were collected between January 1, 1997, and December 31, 2000. One thousand nine hundred eighty-one individuals were classified based on estimated glomerular filtration rate (eGFR) into group I (>90 mL/min/1.73 m2), group II (60 to 89 mL/min/1.73 m2) and group III (<60 mL/min/1.73 m2; chronic kidney disease [CKD]). Age/sex-adjusted baseline characteristics, tertiles of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) and their interactions with eGFR were examined. Outcomes measured included incident myocardial infarction (MI), congestive heart failure, stroke, and all-cause mortality.


      Eight hundred nineteen patients were classified as group I, 1036 as group II, and 126 of 1981 (6.4%) as group III or CKD. Subjects in group III were older and had a higher incidence of hypertension, diabetes, and MI at baseline. Over a 10.2-year follow-up period, CKD was associated with an increased risk of MI (hazard ratio, 1.95; 95% CI, 1.2-3.14; P=.006) and composite cardiovascular outcomes including MI, congestive heart failure, stroke, and all-cause mortality (hazard ratio, 1.38; 95% CI, 1.05-1.83 ;P=.02). Subjects with NT-proBNP or hs-TnT in the third tertile were at greater risk of cardiovascular events without significant interactions between eGFR and levels of NT-proBNP and hs-TnT.


      Subjects with CKD had significantly elevated cardiac biomarkers and were at an increased risk of MI and adverse cardiovascular events. This warrants future studies to investigate whether these cardiac biomarkers could identify high-risk CKD patients for aggressive management of cardiovascular risk factors.

      Abbreviations and Acronyms:

      CHF (congestive heart failure), CKD (chronic kidney disease), CRP (C-reactive protein), CVD (cardiovascular disease), eGFR (estimated glomerular filtration rate), hs-TNT (high sensitivity troponin T), MI (myocardial infarction), NT-proBNP (N-terminal pro B-type natriuretic peptide)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and PersonalCorporate R&D Professionals
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Kendrick J.
        • Chonchol M.
        Cardiovascular disease in CKD in 2013: Reducing cardiovascular risk--light at the end of the tunnel.
        Nat Rev Nephrol. 2014; 10: 71-72
        • Gansevoort R.T.
        • Correa-Rotter R.
        • Hemmelgarn B.R.
        • et al.
        Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention.
        Lancet. 2013; 382: 339-352
        • Liu M.
        • Li X.C.
        • Lu L.
        • et al.
        Cardiovascular disease and its relationship with chronic kidney disease.
        Eur Rev Med Pharmacol Sci. 2014; 18: 2918-2926
        • Garcia-Gil M.
        • Parramon D.
        • Comas-Cufi M.
        • et al.
        Role of renal function in cardiovascular risk assessment: a retrospective cohort study in a population with low incidence of coronary heart disease.
        Prev Med. 2016; 89: 200-206
        • Eisen A.
        • Hoshen M.
        • Balicer R.D.
        • et al.
        Estimated glomerular filtration rate within the normal or mildly impaired range and incident cardiovascular disease.
        Am J Med. 2015; 128: 1015-1022.e2
        • Matsushita K.
        • Sang Y.
        • Ballew S.H.
        • et al.
        Cardiac and kidney markers for cardiovascular prediction in individuals with chronic kidney disease: the Atherosclerosis Risk in Communities study.
        Arterioscler Thromb Vasc Biol. 2014; 34: 1770-1777
        • Vickery S.
        • Price C.P.
        • John R.I.
        • et al.
        B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy.
        Am J Kidney Dis. 2005; 46: 610-620
        • Bjurman C.
        • Petzold M.
        • Venge P.
        • Farbemo J.
        • Fu M.L.
        • Hammarsten O.
        High-sensitive cardiac troponin, NT-proBNP, hFABP and copeptin levels in relation to glomerular filtration rates and a medical record of cardiovascular disease.
        Clini Biochem. 2015; 48: 302-307
        • Snyder J.J.
        • Collins A.J.
        Association of preventive health care with atherosclerotic heart disease and mortality in CKD.
        J Am Soc Nephrol. 2009; 20: 1614-1622
        • Levey A.S.
        • Bosch J.P.
        • Lewis J.B.
        • Greene T.
        • Rogers N.
        • Roth D.
        A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.
        Ann Intern Med. 1999; 130: 461-470
        • Inker L.A.
        • Astor B.C.
        • Fox C.H.
        • et al.
        KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD.
        Am J Kidney Dis. 2014; 63: 713-735
        • Redfield M.M.
        • Jacobsen S.J.
        • Burnett Jr., J.C.
        • Mahoney D.W.
        • Bailey K.R.
        • Rodeheffer R.J.
        Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic.
        JAMA. 2003; 289: 194-202
        • Patel P.A.
        • Scott C.G.
        • Rodeheffer R.J.
        • Chen H.H.
        The natural history of patients with isolated metabolic syndrome.
        Mayo Clinic Proc. 2016; 91: 623-633
        • Kane G.C.
        • Karon B.L.
        • Mahoney D.W.
        • et al.
        Progression of left ventricular diastolic dysfunction and risk of heart failure.
        JAMA. 2011; 306: 856-863
        • Salmasi A.M.
        • Frost P.
        • Dancy M.
        Impaired left ventricular diastolic function during isometric exercise in asymptomatic patients with hyperlipidaemia.
        Int J Cardiol. 2004; 95: 275-280
        • Contal C.
        • Oquigley J.
        An application of changepoint methods in studying the effect of age on survival in breast cancer.
        Comput Stat Data An. 1999; 30: 253-270
        • Coresh J.
        • Selvin E.
        • Stevens L.A.
        • et al.
        Prevalence of chronic kidney disease in the United States.
        JAMA. 2007; 298: 2038-2047
        • Foley R.N.
        Temporal trends in the burden of chronic kidney disease in the United States.
        Curr Opin Nephrol Hypertens. 2010; 19: 273-277
        • Murphy D.
        • McCulloch C.E.
        • Lin F.
        • et al.
        Trends in Prevalence of Chronic Kidney Disease in the United States.
        Ann Intern Med. 2016; 165: 473-481
        • Hsu R.K.
        • Powe N.R.
        Recent trends in the prevalence of chronic kidney disease: not the same old song.
        Curr Opin Nephrol Hypertens. 2017; 26: 187-196
        • Cataliotti A.
        • Malatino L.S.
        • Jougasaki M.
        • et al.
        Circulating natriuretic peptide concentrations in patients with end-stage renal disease: role of brain natriuretic peptide as a biomarker for ventricular remodeling.
        Mayo Clinic Proc. 2001; 76: 1111-1119
        • Palmer S.C.
        • Richards A.M.
        Does renal clearance differ between the B-type natriuretic peptides (BNP versus NT-proBNP)?.
        J Am Coll Cardiol. 2009; 53: 891-892
        • Srisawasdi P.
        • Vanavanan S.
        • Charoenpanichkit C.
        • Kroll M.H.
        The effect of renal dysfunction on BNP, NT-proBNP, and their ratio.
        Am J Clin Pathol. 2010; 133: 14-23
        • Anwaruddin S.
        • Lloyd-Jones D.M.
        • Baggish A.
        • et al.
        Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study.
        J Am Coll Cardiol. 2006; 47: 91-97
        • Ooi D.S.
        • Isotalo P.A.
        • Veinot J.P.
        Correlation of antemortem serum creatine kinase, creatine kinase-MB, troponin I, and troponin T with cardiac pathology.
        Clin Chem. 2000; 46: 338-344
        • Michos E.D.
        • Wilson L.M.
        • Yeh H.C.
        • et al.
        Prognostic value of cardiac troponin in patients with chronic kidney disease without suspected acute coronary syndrome: a systematic review and meta-analysis.
        Ann Intern Med. 2014; 161: 491-501
        • Gregg L.P.
        • Adams-Huet B.
        • Li X.
        • et al.
        Effect modification of chronic kidney disease on the association of circulating and imaging cardiac biomarkers with outcomes.
        J Am Heart Assoc. 2017; 6 (pii:e005235)
        • Lainchbury J.G.
        • Campbell E.
        • Frampton C.M.
        • Yandle T.G.
        • Nicholls M.G.
        • Richards A.M.
        Brain natriuretic peptide and n-terminal brain natriuretic peptide in the diagnosis of heart failure in patients with acute shortness of breath.
        J Am Coll Cardiol. 2003; 42: 728-735
        • Colbert G.
        • Jain N.
        • de Lemos J.A.
        • Hedayati S.S.
        Utility of traditional circulating and imaging-based cardiac biomarkers in patients with predialysis CKD.
        Clin J Am Soc Nephrol. 2015; 10: 515-529
        • Cleland J.G.
        • Taylor J.
        • Freemantle N.
        • Goode K.M.
        • Rigby A.S.
        • Tendera M.
        Relationship between plasma concentrations of N-terminal pro brain natriuretic peptide and the characteristics and outcome of patients with a clinical diagnosis of diastolic heart failure: a report from the PEP-CHF study.
        Eur J Heart Fail. 2012; 14: 487-494
        • Bansal N.
        • Hyre Anderson A.
        • Yang W.
        • et al.
        High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and risk of incident heart failure in patients with CKD: the Chronic Renal Insufficiency Cohort (CRIC) study.
        J Am Soc Nephrol. 2015; 26: 946-956
        • Mishra R.K.
        • Li Y.
        • Ricardo A.C.
        • et al.
        Association of N-terminal pro-B-type natriuretic peptide with left ventricular structure and function in chronic kidney disease (from the Chronic Renal Insufficiency Cohort [CRIC]).
        Am J Cardiol. 2013; 111: 432-438
        • 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
        • Sarafidis P.A.
        • Bakris G.L.
        Cardiovascular disease in CKD in 2014: new insights into cardiovascular risk factors and outcomes.
        Nat Rev Nephrol. 2015; 11: 70-72
        • 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
        • Astor B.C.
        • Yi S.
        • Hiremath L.
        • et al.
        N-terminal prohormone brain natriuretic peptide as a predictor of cardiovascular disease and mortality in blacks with hypertensive kidney disease: the African American Study of Kidney Disease and Hypertension (AASK).
        Circulation. 2008; 117: 1685-1692
        • Vinnakota S.
        • Scott C.
        • Rodeheffer R.
        • Chen H.H.
        Neurohumoral activation and long-term cardiovascular outcomes in chronic kidney disease: a population-based cohort.
        J Am Coll Cardiol. 2017; 69: 930