Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

Emanuele Di Angelantonio; Pei Gao; Hassan Khan; Adam S Butterworth; David Wormser; Stephen Kaptoge; Sreenivasa Rao Kondapally Seshasai; Alex Thompson; Nadeem Sarwar; Peter Willeit; Paul M Ridker; Elizabeth L M Barr; Kay-Tee Khaw; Bruce M Psaty; Hermann Brenner; Beverley Balkau; Jacqueline M Dekker; Debbie A Lawlor; Makoto Daimon; Johann Willeit; Inger Njølstad; Aulikki Nissinen; Eric J Brunner; Lewis H Kuller; Jackie F Price; Johan Sundström; Matthew W Knuiman; Edith J M Feskens; W M M Verschuren; Nicholas Wald; Stephan J L Bakker; Peter H Whincup; Ian Ford; Uri Goldbourt; Agustín Gómez-de-la-Cámara; John Gallacher; Leon A Simons; Annika Rosengren; Susan E Sutherland; Cecilia Björkelund; Dan G Blazer; Sylvia Wassertheil-Smoller; Altan Onat; Alejandro Marín Ibañez; Edoardo Casiglia; J Wouter Jukema; Lara M Simpson; Simona Giampaoli; Børge G Nordestgaard; Randi Selmer; Emerging Risk Factors Collaboration

doi:10.1001/jama.2014.1873

Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

Emanuele Di Angelantonio, Pei Gao, Hassan Khan, Adam S Butterworth, David Wormser, Stephen Kaptoge, Sreenivasa Rao Kondapally Seshasai, Alex Thompson, Nadeem Sarwar, Peter Willeit, Paul M Ridker, Elizabeth L M Barr, Kay-Tee Khaw, Bruce M Psaty, Hermann Brenner, Beverley Balkau, Jacqueline M Dekker, Debbie A Lawlor, Makoto Daimon, Johann WilleitInger Njølstad, Aulikki Nissinen, Eric J Brunner, Lewis H Kuller, Jackie F Price, Johan Sundström, Matthew W Knuiman, Edith J M Feskens, W M M Verschuren, Nicholas Wald, Stephan J L Bakker, Peter H Whincup, Ian Ford, Uri Goldbourt, Agustín Gómez-de-la-Cámara, John Gallacher, Leon A Simons, Annika Rosengren, Susan E Sutherland, Cecilia Björkelund, Dan G Blazer, Sylvia Wassertheil-Smoller, Altan Onat, Alejandro Marín Ibañez, Edoardo Casiglia, J Wouter Jukema, Lara M Simpson, Simona Giampaoli, Børge G Nordestgaard, Randi Selmer, Emerging Risk Factors Collaboration

Institut for Klinisk Medicin

134 Citationer (Scopus)

Abstract

IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA_1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA_1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5%to <7.5%), and high (≥7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA_1c values and CVD risk. The association between HbA_1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA_1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (−0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA_1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA_1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

Originalsprog	Engelsk
Tidsskrift	J A M A: The Journal of the American Medical Association
Vol/bind	311
Udgave nummer	12
Sider (fra-til)	1225-1233
Antal sider	9
ISSN	0098-7484
DOI	https://doi.org/10.1001/jama.2014.1873
Status	Udgivet - 26 mar. 2014

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Di Angelantonio, E., Gao, P., Khan, H., Butterworth, A. S., Wormser, D., Kaptoge, S., Kondapally Seshasai, S. R., Thompson, A., Sarwar, N., Willeit, P., Ridker, P. M., Barr, E. L. M., Khaw, K-T., Psaty, B. M., Brenner, H., Balkau, B., Dekker, J. M., Lawlor, D. A., Daimon, M., ... Emerging Risk Factors Collaboration (2014). Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease. J A M A: The Journal of the American Medical Association, 311(12), 1225-1233. https://doi.org/10.1001/jama.2014.1873

Di Angelantonio, E, Gao, P, Khan, H, Butterworth, AS, Wormser, D, Kaptoge, S, Kondapally Seshasai, SR, Thompson, A, Sarwar, N, Willeit, P, Ridker, PM, Barr, ELM, Khaw, K-T, Psaty, BM, Brenner, H, Balkau, B, Dekker, JM, Lawlor, DA, Daimon, M, Willeit, J, Njølstad, I, Nissinen, A, Brunner, EJ, Kuller, LH, Price, JF, Sundström, J, Knuiman, MW, Feskens, EJM, Verschuren, WMM, Wald, N, Bakker, SJL, Whincup, PH, Ford, I, Goldbourt, U, Gómez-de-la-Cámara, A, Gallacher, J, Simons, LA, Rosengren, A, Sutherland, SE, Björkelund, C, Blazer, DG, Wassertheil-Smoller, S, Onat, A, Marín Ibañez, A, Casiglia, E, Jukema, JW, Simpson, LM, Giampaoli, S, Nordestgaard, BG, Selmer, R & Emerging Risk Factors Collaboration 2014, 'Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease', J A M A: The Journal of the American Medical Association, bind 311, nr. 12, s. 1225-1233. https://doi.org/10.1001/jama.2014.1873

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title = "Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease",

abstract = "IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5%to <7.5%), and high (≥7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (−0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.",

keywords = "Aged, C-Reactive Protein, Cholesterol, HDL, Coronary Disease, Diabetes Mellitus, Female, Hemoglobin A, Glycosylated, Humans, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Risk Assessment, Stroke",

author = "{Di Angelantonio}, Emanuele and Pei Gao and Hassan Khan and Butterworth, {Adam S} and David Wormser and Stephen Kaptoge and {Kondapally Seshasai}, {Sreenivasa Rao} and Alex Thompson and Nadeem Sarwar and Peter Willeit and Ridker, {Paul M} and Barr, {Elizabeth L M} and Kay-Tee Khaw and Psaty, {Bruce M} and Hermann Brenner and Beverley Balkau and Dekker, {Jacqueline M} and Lawlor, {Debbie A} and Makoto Daimon and Johann Willeit and Inger Nj{\o}lstad and Aulikki Nissinen and Brunner, {Eric J} and Kuller, {Lewis H} and Price, {Jackie F} and Johan Sundstr{\"o}m and Knuiman, {Matthew W} and Feskens, {Edith J M} and Verschuren, {W M M} and Nicholas Wald and Bakker, {Stephan J L} and Whincup, {Peter H} and Ian Ford and Uri Goldbourt and Agust{\'i}n G{\'o}mez-de-la-C{\'a}mara and John Gallacher and Simons, {Leon A} and Annika Rosengren and Sutherland, {Susan E} and Cecilia Bj{\"o}rkelund and Blazer, {Dan G} and Sylvia Wassertheil-Smoller and Altan Onat and {Mar{\'i}n Iba{\~n}ez}, Alejandro and Edoardo Casiglia and Jukema, {J Wouter} and Simpson, {Lara M} and Simona Giampaoli and Nordestgaard, {B{\o}rge G} and Randi Selmer and {Emerging Risk Factors Collaboration}",

year = "2014",

month = mar,

day = "26",

doi = "10.1001/jama.2014.1873",

language = "English",

volume = "311",

pages = "1225--1233",

journal = "J A M A: The Journal of the American Medical Association",

issn = "0098-7484",

publisher = "American Medical Association",

number = "12",

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TY - JOUR

T1 - Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

AU - Di Angelantonio, Emanuele

AU - Gao, Pei

AU - Khan, Hassan

AU - Butterworth, Adam S

AU - Wormser, David

AU - Kaptoge, Stephen

AU - Kondapally Seshasai, Sreenivasa Rao

AU - Thompson, Alex

AU - Sarwar, Nadeem

AU - Willeit, Peter

AU - Ridker, Paul M

AU - Barr, Elizabeth L M

AU - Khaw, Kay-Tee

AU - Psaty, Bruce M

AU - Brenner, Hermann

AU - Balkau, Beverley

AU - Dekker, Jacqueline M

AU - Lawlor, Debbie A

AU - Daimon, Makoto

AU - Willeit, Johann

AU - Njølstad, Inger

AU - Nissinen, Aulikki

AU - Brunner, Eric J

AU - Kuller, Lewis H

AU - Price, Jackie F

AU - Sundström, Johan

AU - Knuiman, Matthew W

AU - Feskens, Edith J M

AU - Verschuren, W M M

AU - Wald, Nicholas

AU - Bakker, Stephan J L

AU - Whincup, Peter H

AU - Ford, Ian

AU - Goldbourt, Uri

AU - Gómez-de-la-Cámara, Agustín

AU - Gallacher, John

AU - Simons, Leon A

AU - Rosengren, Annika

AU - Sutherland, Susan E

AU - Björkelund, Cecilia

AU - Blazer, Dan G

AU - Wassertheil-Smoller, Sylvia

AU - Onat, Altan

AU - Marín Ibañez, Alejandro

AU - Casiglia, Edoardo

AU - Jukema, J Wouter

AU - Simpson, Lara M

AU - Giampaoli, Simona

AU - Nordestgaard, Børge G

AU - Selmer, Randi

AU - Emerging Risk Factors Collaboration

PY - 2014/3/26

Y1 - 2014/3/26

N2 - IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5%to <7.5%), and high (≥7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (−0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

AB - IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5%to <7.5%), and high (≥7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (−0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

KW - Aged

KW - C-Reactive Protein

KW - Cholesterol, HDL

KW - Coronary Disease

KW - Diabetes Mellitus

KW - Female

KW - Hemoglobin A, Glycosylated

KW - Humans

KW - Male

KW - Middle Aged

KW - Predictive Value of Tests

KW - Prospective Studies

KW - Risk Assessment

KW - Stroke

U2 - 10.1001/jama.2014.1873

DO - 10.1001/jama.2014.1873

M3 - Journal article

C2 - 24668104

SN - 0098-7484

VL - 311

SP - 1225

EP - 1233

JO - J A M A: The Journal of the American Medical Association

JF - J A M A: The Journal of the American Medical Association

IS - 12

ER -

Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

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