Abstract
Diabetes plays an important role in the complex relationship between chronic kidney disease (CKD) and cardiovascular disease. This retrospective observational study compared the influence of estimated glomerular filtration rate (eGFR) and proteinuria on the risk of major adverse cardiovascular event (MACE; myocardial infarction or stroke) in CKD patients with and without diabetes. Data were from a linked database of UK electronic health records. Individuals with CKD and no prior MACE were classified as type 1 diabetes (T1DM; n = 164), type 2 diabetes (T2DM; n = 9,711), and non-diabetes (non-DM; n = 75,789). Monthly updated time-dependent Cox proportional hazard models were constructed to calculate adjusted hazard ratios (aHRs) for progression to MACE from first record of abnormal eGFR or proteinuria (index date). In non-DM, aHRs (95% CIs) by baseline eGFR category (referent G2) were G1: 0.70 (0.55–0.90), G3a: 1.28 (1.20–1.35), G3b: 1.64 (1.52–1.76), G4: 2.19 (1.98–2.43), and G5: 3.12 (2.44–3.99), and by proteinuria category (referent A1) were A2: 1.13 (1.00–1.28), A2/3 (severity indeterminable): 1.58 (1.28–1.95), and A3: 1.64 (1.38–1.95). In T2DM, aHRs were G1: 0.98 (0.72–1.32), G3a: 1.18 (1.03–1.34), G3b: 1.31 (1.12–1.54), G4: 1.87 (1.53–2.29), G5: 2.87 (1.82–4.52), A2: 1.22 (1.04–1.42), A2/3: 1.45 (1.17–1.79), and A3: 1.82 (1.53–2.16). Low numbers in T1DM precluded analysis. Modelling T2DM and non-DM together, aHRs were, respectively, G1: 3.23 (2.38–4.40) and 0.70 (0.55–0.89); G2: 3.18 (2.73–3.70) and 1.00 (referent); G3a: 3.65 (3.13–4.25) and 1.28 (1.21–1.36); G3b: 4.01 (3.40–4.74) and 1.65 (1.54–1.77); G4: 5.78 (4.70–7.10) and 2.21 (2.00–2.45); G5: 9.00 (5.71–14.18) and 3.14 (2.46–4.00). In conclusion, reduced eGFR and proteinuria were independently associated with increased risk of MACE regardless of diabetes status. However, the risk of MACE in the same eGFR state was 4.6–2.4 times higher in T2DM than in non-DM.
Highlights
It has been estimated that 11–13% of the global population has some degree of chronic kidney disease (CKD),[1] as defined by international criteria based on structural damage and reduced function.[2,3]A complex relationship exists between CKD and cardiovascular (CV) disease (CVD), with each being an established risk factor for the other.[4]
major adverse cardiovascular event (MACE) is a composite clinical endpoint that includes both cardiovascular and cerebrovascular disease events. This population-based study demonstrated that the risk of MACE increased with increasing disease severity within non-diabetes and type 2 diabetes cohorts in relation to renal morbidity as measured by estimated glomerular filtration rate (eGFR) and proteinuria
The observation that reduced eGFR and increased proteinuria appear synergistic with respect to risk of ischaemic cardiovascular events is of significant concern
Summary
It has been estimated that 11–13% of the global population has some degree of chronic kidney disease (CKD),[1] as defined by international criteria based on structural damage and reduced function.[2,3]A complex relationship exists between CKD and cardiovascular (CV) disease (CVD), with each being an established risk factor for the other.[4]. There is evidence that CV risk is increased at even the mildest levels of microalbuminuria,[7] and it is apparent that individuals with CKD are more likely to die of CVD than to progress to end stage renal disease.[8]. Diabetes is the leading cause of CKD in all developed and most developing countries,[9] with approximately 20% of people with type 2 diabetes showing evidence of diabetic nephropathy within 20 years of diabetes onset,[10] and diabetes itself being an independent risk factor for CVD.[11] Whilst there is a J- or U-shaped association between hyperglycaemia—as measured by glycosylated haemoglobin (HbA1c)—and cardiovascular events,[12] the association between HbA1c and CKD risk is essentially a direct, linear association.[13]
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