The impact of microalbuminuria and proteinuria on cardiovascular outcomes in individuals with type 2 diabetes mellitus: a population-based, electronic health records study

Abstract Background Type 2 Diabetes Mellitus (T2DM) is a prevalent condition with renal and cardiovascular complications. While urinary albumin:creatinine ratio (ACR) is used to diagnose diabetic nephropathy, its relationship with diverse cardiovascular disease (CVD) outcomes is not well understood. Aim The present study was desined to examine the impact of proteinuria on CVD outcomes, including stroke, heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF), in a large national T2DM population over 15 years follow up. Methods All individuals with T2DM aged 18 years between 1998 and 2020 with recorded ACR levels within a year of their diagnosis were included from the United Kingdom Clinical Practice Research Datalink primary care database. Patients were stratified by ACR levels into three groups: normal (no proteinuria; ACR: 2.5 mg/mmol in men, 3.5 mg/mmol in women), microalbuminuria (2.5-25 mg/mmol in men, 3.5-35 mg/mmol in women), and proteinuria (25 mg/mmol in men; 35 mg/mmol in women). Cox’s proportional hazard models were performed to assess the hazard ratio (HR) of incident CVD according to proteinuria status using the normal group as reference. Results Of 86,311 individuals, 79.4% had normal proteinuria levels, 17.9% had microalbuminuria, and 2.7% had proteinuria. Microalbuminuria and proteinuria were independently associated with an increased risk of CVD (microalbuminuria HR: 1.38 95% CI: 1.26–1.50; proteinuria HR: 2.06 95% CI: 1.76–2.42). (Figure 1) The hazard was increased across all CVD subtypes, incrementally higher in proteinuria than microalbuminuria and highest for HF in the microalbuminuria and proteinuria subgroups. (Figure 2) Conclusion Worsening proteinuria level is associated with an increased CVD risk among those with T2DM. This relationship persists for all CVD outcomes, including HF, ACS, Stroke and AF. These findings reinforce the utility of ACR as an efficacious tool for stratifying patients at higher CVD risk, thereby providing an opportunity for more aggressive CV risk modification strategies.Fig 1.Proteinuria status and CVD Hazard Fig 2.Odds of individual CVD events