Amil M Shah1, Brian Claggett2, Dalane Kitzman2, Tor Biering-Sørensen2, Jan Skov Jensen2, Susan Cheng2, Kunihiro Matsushita2, Suma Konety2, Aaron R Folsom2, Thomas H Mosley2, Jacqueline D Wright2, Gerardo Heiss2, Scott D Solomon2. 1. From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., T.B.-S., S.C., S.D.S.); Wake Forest University School of Medicine, Winston-Salem, NC (D.K.); Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark (T.B.-S., J.S.J.); Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (K.M.); Cardiovascular Division, (S.K.) and Division of Epidemiology and Community Health, School of Public Health (A.R.F.), University of Minnesota, Minneapolis; Divisions of Geriatrics and Neurology, University of Mississippi Medical Center, Jackson (T.H.M.); Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD (J.D.W.); and University of North Carolina Gillings School of Global Public Health, Chapel Hill (G.H.). ashah11@partners.org. 2. From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., T.B.-S., S.C., S.D.S.); Wake Forest University School of Medicine, Winston-Salem, NC (D.K.); Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark (T.B.-S., J.S.J.); Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (K.M.); Cardiovascular Division, (S.K.) and Division of Epidemiology and Community Health, School of Public Health (A.R.F.), University of Minnesota, Minneapolis; Divisions of Geriatrics and Neurology, University of Mississippi Medical Center, Jackson (T.H.M.); Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD (J.D.W.); and University of North Carolina Gillings School of Global Public Health, Chapel Hill (G.H.).
Abstract
BACKGROUND: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk. METHODS: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67-90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e', E/e', and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors. RESULTS: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e' (4.6 and 5.2 cm/s for septal and lateral TDI e', respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e' and left atrial size demonstrated good agreement with guideline cut points. TDI e' was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement (P<0.001) and continuous net reclassification improvement (P<0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y). CONCLUSIONS: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.
BACKGROUND: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk. METHODS: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67-90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e', E/e', and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors. RESULTS: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e' (4.6 and 5.2 cm/s for septal and lateral TDI e', respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e' and left atrial size demonstrated good agreement with guideline cut points. TDI e' was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement (P<0.001) and continuous net reclassification improvement (P<0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y). CONCLUSIONS: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.
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