High Risk of CV Event in Patients with Type 2 Diabetes Shown Despite CVD Status

September 28, 2021
Connor Iapoce

Connor Iapoce is an associate editor for HCPLive and joined the MJH Life Sciences team in April 2021. He graduated from The College of New Jersey with a degree in Journalism and Professional Writing. He enjoys listening to records, going to concerts, and playing with his cat Squish. You can reach him at ciapoce@mjhlifesciences.com.

In patients with T2D without prior CVD, chronic kidney disease was the single risk factor associated with highest risk of MACE.

A recent study compared outcomes in patients with type 2 diabetes (T2D) without established cardiovascular disease (CVD) to patients with established CVD, in order to determine the effect of selected cardiovascular (CV) risk factors on the risk of major adverse cardiovascular events (MACE).

The team of investigators, led by Kamlesh Khunti, MD, Diabetes Research Center, University of Leicester, identified risk factors including chronic kidney disease, older age, smoking and dyslipidemia had an association with a similar high risk of CV events in patients with T2D and without CVD, compared to those with established CVD.


Khunti and colleagues performed a retrospective, observational study using records from the Clinical Practice Research Datalink GOLD database, a UK-based network of primary care practices.

Patients deemed eligible for the study had T2D and were receiving both first- and second-line glucose-lowering pharmacotherapy, in the follow-up period from 2001 - 2016. During that same follow-up period, outcomes data was retrieved from Hospital Episode Statistics and the Office for National Statistics.

The study identified the index date as the first prescription of second-line glucose-lowering therapy, to determine early T2D population. Further, established CVD was defined as a record prior to the index date of CVD-related code in the GOLD database.

In addition, 9 risk factors were assessed to identify patients with T2D at high CV risk, including sex, age, obesity, hypertension, dyslipdemia, current smoking, hyperglycemia, diabetes duration ≥5 years, and chronic kidney disease.

Endpoints consisted of of 3-point major adverse cardiovascular events (MACE), a composite of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke; 3-point MACE plus hospitalization for angina, hospitalization for HF or coronary revascularization; all‐cause mortality.

Additionally, they used cox proportional hazards models in estimation of relative risks of MACE within groups defined by presence of risk factors in patients without versus with established CVD.


A total of 90,838 patients with T2D in the database between 2001 - 2016 had a prescription of second-line glucose-lowering therapy within 120 of prescription of first-line glucose-lowering therapy.

From this number, 53,182 individuals were included in the analysis, with 10,313 patients (19%) having established CVD and 42,869 (81%) having no prior CVD.

Investigators noted those without CVD were younger, with a shorter diabetes duration and higher body mass index.

During a 5-7 year follow-up period, the incidence rate of 3-point MACE was 14.0 events per 1000 person-years in patients without CVD, in comparison to 49.6 events per 1000 person-years in patients with CVD (hazard ratio 0.28; 95% CI, 0.26 - 0.29).

Overall, data show 16.9% of patients without CVD died, while 41.0% of patients with CVD died over a mean follow up of 6 years (HR 0.35; 95% CI, 0.34 - 0.37).

In comparison to a reference HR of 1.0 for patients with established CVD, chronic kidney disease (estimate glomerular filtration rate <60 mL/min) was the single risk factor associated with highest risk of MACE (HR 0.75; 95% CI, 0.70 - 0.81), followed by older age (HR 0.53; 95% CI, 0.51 - 0.56) and longer diabetes duration (HR 0.34; 95% CI, 0.32 - 0.37).

Further, chronic kidney disease was the single risk factor associated with the highest all-cause mortality (HR 1.12; 95% CI, 1.07 - 1.18).

Additionally, investigators noted the combination of chronic kidney disease with older age, smoking, or dyslipidemia had associations with a similar high risk of CV events in people with T2D and without CVD, in comparison to those with established CVD.


Investigators noted an unmet need in risk factor management, in regards to the high prevalence of CVD in patients undergoing early treatment stages of T2D.

“These findings highlight the need to control cardiovascular risk factors early in the course of type 2 diabetes in all individuals, and emphasize the need to identify people who may particularly benefit from treatments known to reduce cardiovascular risk,” investigators wrote.

The study, “Cardiovascular risk factors early in the course of treatment in people with type 2 diabetes without established cardiovascular disease: a population-based observational retrospective cohort study,” was published in Diabetic Medicine.