People with T2D are twice as likely to develop cardiovascular disease (CVD) as those without diabetes, and they experience cardiovascular events approximately 15 years earlier, explains Elisa Dal Canto, MD, Ph.D. “They also have higher risk for microvascular disease, including nephropathy, present in about 40% of patients,” Dr. Dal Canto says. “When nephropathy develops, the risk for dying from [CVD] increases up to five-fold compared to people with diabetes but without kidney dysfunction. Early diagnosis is therefore imperative to allow for appropriate therapies.”

However, it remains unclear whether a regular assessment of kidney function, even in the presence of only mild impairment, might lessen the risk for CVD in these patients, she adds. Furthermore, whether the two measures of kidney function used in clinical practice estimated glomerular filtration rate (eGFR), based on plasma creatinine, and presence of albumin in the urine might provide different information about the occurrence of specific types of CVD were not previously studied.

Added Value of Both Kidney Function Markers in Diabetes Assessed

For a study published in Diabetologia, Dr. Dal Canto and colleagues tested the hypothesis that both manifestations of kidney disease in diabetes, decreased eGFR and a higher urinary albumin/ creatinine ratio, may increase the risk for specific CVD subtypes in adults with diabetes. “Most [previous] studies analyzed the relationship between a single baseline value of eGFR or albuminuria and the occurrence of a composite cardiovascular outcome,” Dr. Dal Canto says. “What we wanted to assess was the added value of annually repeated measurements of both kidney function markers in people with diabetes, as they pertain to refined cardiovascular risk assessment.”

The study team utilized the Hoorn Diabetes Care System Cohort, a prospective cohort representing a comprehensive dataset on the natural course of diabetes. Patients in the cohort undergo annual checkups with extensive lab work and assessment of micro- and macrovascular complications of diabetes. The researchers analyzed data of nearly 14,000 patients via repeated measures of both kidney function markers, in addition to information on multiple cardiovascular risk factors and the occurrence of cardiovascular events.

Dr. Dal Canto and colleagues observed sex-specific associations between kidney function measures and CVD. “We found that the presence of albuminuria increases the risk for heart failure [HF] in women but not in men,” Dr. Dal Canto notes. “Sex differences in [CVD] are not completely acknowledged and yet they affect each aspect [of CVD], from different risk factors, pathophysiology, different disease presentation, a predisposition to distinct forms of [CVD], and even a different response to treatment.” Physicians, she adds, particularly endocrinologists, should incorporate these differences into their daily practice.

People With Diabetes Experience Wide Range of CVD

Differential and longitudinal associations between each kidney function marker and several subtypes of CVD, including heart failure (HF), were also observed (Figure). “When we think of cardiovascular risk in diabetes, we tend to think more often about myocardial infarction, or atherosclerotic [CVD] in general,” Dr. Dal Canto says. “However, people with diabetes suffer from a wide range of [CVD], including those not related to atherosclerosis, such as heart failure with preserved ejection fraction (HFpEF). The prevalence of HFpEF in diabetes is increasing, but [fortunately] today, there are novel anti-diabetic drugs that also provide cardiovascular protection.”

Measuring albuminuria might also be a useful tool, she adds, especially if performed regularly, to help identify individuals at higher risk for developing HF, especially women. This would allow for preventive strategies and the implementation of appropriate therapies.

Conventional cardiovascular risk scores do not perform well in people with diabetes, and yet the burden of CVD prevalence further increases, especially HF, the study team points out. “A refined cardiovascular risk assessment is crucial, to help prevent [CVD] or to delay its progression,” Dr. Dal Canto says. “Future research should focus on the development of better cardiovascular risk scores, to be used even in patients with a higher cardiovascular risk, such as those with diabetes. Importantly, because comorbidities and risk factors have a different impact on the likelihood of developing certain [CVD] subtypes in both men and women, [attention to] sex differences should be implemented in every aspect of research in this area.”