Albuminuria as a Risk Factor for Cardiovascular Events and Mortality in Patients with Type 2 Diabetes Without Apparent Cardiovascular Disease
Albuminuria in patients with type 2 diabetes is associated with a higher risk of cardiovascular (CV) events and higher mortality. However, this association has not been thoroughly investigated in diabetics without evident atherosclerotic disease. A study with a large cohort of Danish patients helped fill in the missing data.
Introduction
Atherosclerosis is the main cause of morbidity and mortality in patients with type 2 diabetes. Diabetics with CV disease are considered high-risk. For diabetics without evident atherosclerotic disease, stratification according to CV risk is recommended to choose the appropriate intensity of preventive intervention.
Micro- and macroalbuminuria are proven predictors of atherosclerotic CV events and mortality in patients with type 2 diabetes. However, their predictive significance in diabetics without evident atherosclerotic disease has not been thoroughly evaluated.
Study Methodology
The cited study included patients with type 2 diabetes over the age of 18 from the Danish registry between May 1, 2005, and June 30, 2015. They had to have two available results of the urine albumin-to-creatinine ratio (UACR) or urinary albumin excretion (UAE) within a 15-month period. Patients diagnosed with atherosclerotic disease were excluded from the study. The included individuals were categorized into three groups: normoalbuminuria, microalbuminuria (UACR 30–299 mg/g or UAE 30–299 mg/day), and macroalbuminuria (UACR ≥ 300 mg/g or UAE ≥ 300 mg/day).
The primary parameters observed were the incidence of ischemic stroke (iCMP), acute myocardial infarction (AMI), and overall mortality. The association between micro- and macroalbuminuria and the incidence of these events was evaluated using Cox proportional hazards regression analysis, adjusting for gender, age, CV risk factors (blood pressure, smoking, BMI, LDL cholesterol levels, HbA1c, duration of diabetes, heart failure, and atrial fibrillation), and medication (antiplatelet therapy, RAAS inhibitors, and anticoagulation therapy). Results were analyzed after 5 years of follow-up.
Evaluated Patient Population
The monitored population included 69,532 patients, with 58,361 having normoalbuminuria, 7,977 having microalbuminuria, and 3,194 having macroalbuminuria. The average age of the patients was 62.6 years, and 55.4% were men. Patients with micro- and macroalbuminuria were more often male, smokers, with a longer duration of disease, worse glycemic control, higher systolic blood pressure, and a higher prevalence of atrial fibrillation and heart failure. Prescription of antihypertensives, statins, and antiplatelet inhibitors increased with rising levels of albuminuria.
Results
During the 5-year period, 995 (1.4%) patients experienced iCMP, and 809 (1.2%) experienced AMI. A total of 3,735 (5.4%) enrolled individuals died.
Compared to patients with normoalbuminuria, patients with microalbuminuria had a significantly higher risk of iCMP (hazard ratio [HR] 1.28; 95% confidence interval [CI] 1.07–1.52), AMI (HR 1.34; 95% CI 1.10–1.62), and death (HR 1.48; 95% CI 1.36–1.61). Macroalbuminuria was associated with an even more pronounced increase in the risk of iCMP (HR 1.81; 95% CI 1.46–2.23), AMI (HR 1.99; 95% CI 1.59–2.48), and death (HR 1.83; 95% CI 1.64–2.04).
Conclusion
The study results indicate that both micro- and macroalbuminuria in patients with type 2 diabetes without evident atherosclerotic disease are associated with an increased risk of atherosclerotic CV events and overall mortality, with the risk rising proportionately with the level of albuminuria.
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Source: Fangel M. V., Nielsen P. B., Kristensen J. K. et al. Albuminuria and risk of cardiovascular events and mortality in a general population of patients with type 2 diabetes without cardiovascular disease: a Danish cohort study. Am J Med 2020; 133 (6): e269–e279, doi: 10.1016/j.amjmed.2019.10.042.
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