Major adverse cardiovascular events in people with chronic kidney disease in relation to disease severity and diabetes status

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.

2022 update to the position statement by Primary Care Diabetes Europe: a disease state approach to the pharmacological management of type 2 diabetes in primary care

“…History of established CVD is one of the most widely recognised and important predictors of future major adverse cardiovascular events (MACE) [80]. Similarly, both decreased estimated glomerular filtration rate (eGFR) and albuminuria are strong independent predictors of MACE in patients with T2D [81]. Finally, there is evidence to suggest that early-onset T2D represents an aggressive form of the disease in terms of cardiovascular risk [82], reflected in the fact that patients with a younger age at diagnosis have a much higher cardiovascular risk than that of age-matched controls [83].…”

Advances in chronic kidney disease pathophysiology and management

“…10 Albuminuria is an independent risk factor for cardiovascular disease, conferring an increased risk at every stage of CKD. 11 Reduction in the amount of albuminuria is associated with improved outcomes. 12 Strategies include reducing sodium intake and blood pressure, especially through prescription of an ACE inhibitor or ARB.…”

“…Reduced GFR and elevated urinary albumin are both independent risk factors for cardiovascular disease. 11 Interventions to reduce this Statins also play an important part in cardiovascular risk reduction. Dyslipidemia is common in patients with CKD and typically includes increased triglyceride levels in conjunction with decreased levels of high-density lipoprotein.…”

Predisposing factors and uremic pericardial effusion among ESRD patients undergoing dialysis

“…Adverse cardiovascular events are commonly reported causes of mortality among end-stage renal disease (ESRD) patients [ 1 , 2 ] such as; coronary heart disease, stroke, cardiometabolic disorders, myocardial infarction [ 3 ], heart failure, ischemic heart disease, heart failure, and cardiac arrhythmia [ 4 ]. Uremic pericarditis, defined as presentation of clinical signs and symptoms before or within 8 days of renal replacement therapy [ 5 ], and is reported in 16–41% patients undergoing dialysis.…”