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. 2023 Jan 11;30(1):8-16.
doi: 10.1093/eurjpc/zwac176.

Including measures of chronic kidney disease to improve cardiovascular risk prediction by SCORE2 and SCORE2-OP

Kunihiro Matsushita  1 , Stephen Kaptoge  2 , Steven H J Hageman  3 , Yingying Sang  1 , Shoshana H Ballew  1 , Morgan E Grams  1 , Aditya Surapaneni  1 , Luanluan Sun  2 , Johan Arnlov  4 , Milica Bozic  5 , Hermann Brenner  6 , Nigel J Brunskill  7 , Alex R Chang  8 , Rajkumar Chinnadurai  9 , Massimo Cirillo  10 , Adolfo Correa  11 , Natalie Ebert  12 , Kai-Uwe Eckardt  13   14 , Ron T Gansevoort  15 , Orlando Gutierrez  16 , Farzad Hadaegh  17 , Jiang He  18 , Shih-Jen Hwang  19 , Tazeen H Jafar  20   21   22 , Simerjot K Jassal  23 , Takamasa Kayama  24 , Csaba P Kovesdy  25 , Gijs W Landman  26 , Andrew S Levey  27 , Donald M Lloyd-Jones  28 , Rupert W Major  7 , Katsuyuki Miura  29 , Paul Muntner  30 , Girish N Nadkarni  31 , Christoph Nowak  4 , Takayoshi Ohkubo  32 , Michelle J Pena  33 , Kevan R Polkinghorne  34 , Toshimi Sairenchi  35 , Elke Schaeffner  12 , Markus P Schneider  13 , Varda Shalev  36 , Michael G Shlipak  37 , Marit D Solbu  38 , Nikita Stempniewicz  39 , James Tollitt  9   40 , José M Valdivielso  5 , Joep van der Leeuw  3 , Angela Yee-Moon Wang  41 , Chi-Pang Wen  42 , Mark Woodward  1   43   44 , Kazumasa Yamagishi  45 , Hiroshi Yatsuya  46 , Luxia Zhang  47 , Jannick A N Dorresteijn  3 , Emanuele Di Angelantonio  2   48 , Frank L J Visseren  3 , Lisa Pennells  2 , Josef Coresh  1
Affiliations

Including measures of chronic kidney disease to improve cardiovascular risk prediction by SCORE2 and SCORE2-OP

Kunihiro Matsushita et al. Eur J Prev Cardiol. .

Abstract

Aims: The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an 'Add-on' to incorporate CKD measures into these algorithms, using a validated approach.

Methods: In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets.

Results: In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004-0.008) and 0.016 (0.010-0.023), respectively, for SCORE2 and 0.012 (0.009-0.015) and 0.024 (0.014-0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062-0.138) for SCORE2] compared to the qualitative approach in the ESC guideline.

Conclusion: Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.

Keywords: Cardiovascular disease; Chronic kidney disease; Meta-analysis; Risk prediction.

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Conflict of interest statement

Conflict of interest: Ku.M. reports grants from NIDDK; grants and personal fees from Kyowa Kirin, personal fees from Akebia outside the submitted work. M.G. reports grants from NIH and National Kidney Foundation outside the submitted work. J.A. reports personal fees from AstraZeneca, Novartis, and Boerhinger Ingelheim outside the submitted work. A.R.C. reports personal fees from Novartis, Reata, and Amgen; grants from Novo Nordisk outside the submitted work. N.E. reports personal fees from Bayer and AG Leverkusen outside the submitted work. K.E. reports grants from Amgen, Astra Zenceca, Bayer, Evotec, and Vifor; personal fees from Akebia, Astra Zeneca, Bayer, Otsuka, and Retrophin outside the submitted work. S.K.J reports salary support from US Government and Department of Veterans Affairs during the conduct of the study. C.K. reports personal fees from Bayer, Abbott, Astra-Zeneca, Takeda, Tricida, Akebia, Cara Therapeutics, Vifor, Rockwell, CSL Behring, Reata, Boehringer Ingelheim, and GSK outside the submitted work. A.S.L. reports grants and contracts from NIH and NKF for studies in CKD and a contract from AstraZeneca for DSMB for clinical trials of dapagliflozin. Ka.M. reports grants from Ministry of Health, Labor, and Welfare, Japan. G.N.N reports personal fees from Renalytix, Daiichi Sankyo, Menarini Medical, Qiming Capital, and Variant Bio; other fees from Pensieve Health, Nexus I Connect outside the submitted work; patent KidneyIntelX pending to Renalytix. M.G.S. reports grants from NIH- NIA/NIDDK/NHLBI during the conduct of the study; personal fees from Cricket Health, Intercept Pharmaceuticals, Bayer Pharmaceuticals, AztraZeneca, Boeringer Ingelheim; grants from Bayer Pharmaceuticals outside the submitted work. M.D.S reports a honoraria from AstraZeneca outside the submitted work. N.S. is a current employee of GSK and employed at AMGA. M.W. reports personal fees from Amgen and Freeline outside the submitted work. J.C. reports grants from National Institute of Health and National Kidney Foundation, during the conduct of the study; personal fees from Healthy.io and SomaLogic outside the submitted work. No other potential conflicts of interest relevant to this article were reported. All other authors report no potential conflicts.

Figures

Figure 1.
Figure 1.. CKD staging and risk ratio of the CKD Add-on (eGFR+ACR) in the SCORE2 and SCORE2-OP populations from the validation datasets
Figure 2.
Figure 2.. The CKD Add-on (eGFR+ACR) impact on predicted risk based on SCORE2 and SCORE2-OP in 4 hypothetical scenarios
CVD risk classification was defined as low/moderate risk (<2.5% for age <50, <5% for age 50–69 and <7.5% for age 70+), high risk (2.5–7.5% for age <50, 5–10% for age 50–69 and 7.5–15% for age 70+), very high risk (>7.5% for age <50, >10% for age 50–69 and >15% for age 70+).
See this image and copyright information in PMC

Comment in

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