One in 3 US Adults with T2D Shows Evidence of Subclinical CVD Based on Cardiac Biomarkers

Approximately 1 in 3 adults in the United States with type 2 diabetes (T2D) had evidence of subclinical cardiovascular disease (CVD) as assessed by 2 common biomarkers associated with cardiac injury, according to authors of a study published online today in the Journal of the American Heart Association (AHA).

Investigators from Johns Hopkins University and colleagues found further that subclinical CVD was strongly associated with an increased risk of mortality in adults with T2D, an association that remained after adjustment for various demographic characteristics and CV risk factors and that “highlights the urgent need for prevention,” they wrote.

“What we are seeing is that many people with T2D who have not had a heart attack or a history of CVD are at high risk for cardiovascular complications,” Elizabeth Selvin, PhD, MPH, a professor of epidemiology at Johns Hopkins Bloomberg School of Public Health said in an AHA statement. “When we look at the whole population of people diagnosed with T2D, about 27 million adults in the US, according to the CDC, some are at low risk and some are at high risk for CVD, so the open question is ‘Who is most at risk?’ These cardiac biomarkers give us a window into cardiovascular risk in people who otherwise might not be recognized as highest risk.”

The interest in using biomarkers as early evidence of subclinical CVD and to prompt treatment is “substantial,” the authors say. In the case of T2D, they cite a 2022 consensus report from the American Diabetes Association which recommended annual testing of 2 specific cardiac biomarkers, high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to enable early detection and prevention of heart failure.

Prior evidence suggests that more than one-quarter (28%) of adults with T2D may have biomarker-detected subclinical CVD and that the proportion increases with disease duration and persistence of hyperglycemia. Moreover, elevations in hs‐cTn and NT-proBNP are associated with significant risk for cardiac morbidity and mortality.

There is, however, a lack of national data and little is known regarding the burden and long-term consequences of subclinical CVD in adults with T2D in the general population.

The primary objective of the current analysis was to characterize the national prevalence of subclinical CVD, as assessed by elevated hs-cTnT and NT-proBNP, in adults in the US with and without diabetes.

The study cohort was drawn from the 1999 - 2004 National Health and Nutrition Examination Survey (NHANES) and included nonpregnant adults aged ≥20 years without self-reported CVD, and with valid measures of NT-proBNP, hs-cTnT, and covariates. The final number of participants for analysis was 10 304.

Participants were categorized as having no diabetes, newly diagnosed diabetes (≤1 year or no self-reported diagnosed diabetes and HbA1c ≥6.5%), short diabetes duration (self-reported diagnosis between 1 and 10 years), and long diabetes duration (≥10 years).

Using stored blood samples, Selvin et al defined subclinical CVD as having either elevated hs-cTnT (≥14 ng/L) or NT-proBNP (≥125 pg/mL) levels. Mortality status was determined via rough linkage to the National Death Index from baseline until December 31, 2019. CV mortality specifically was defined as heart disease or cerebrovascular disease listed as underlying cause of death.

After adjusting for age, race, income and cardiovascular risk factors, they assessed the associations among elevated NT-proBNP and hs-cTnT with risk of death from cardiovascular death or all causes.

Findings

From 1999 - 2004, 7% of US adults without a history of CVD had diabetes and were generally older and had a higher burden of CV risk factors. Distributions of both hs-cTnTand NT-proBNP were right skewed, according to the study results, and median levels of both were higher among those with vs those without T2D.

The prevalence of any subclinical CVD, the authors found, was twice as high for adults with T2D (33.4%) vs those without (16.1%). They report that differences in biomarker levels by T2D status were particularly pronounced for hs-cTnT(19% with T2D vs 5% without T2D). Although the prevalence of having elevations in both biomarkers was low, it was significantly higher in adults with (9%) vs without (3%) T2D.

In models adjusted for age, elevated hs-CTnT, but not elevated NT-proBNP, was found more common in adults with T2D, overall and across age, sex, race and ethnicity, and weight status. In contrast, after adjusting for age, NT-proBNP levels were not elevated in those with T2D compared to those without.

Further analysis found that prevalence of elevated hs-cTnT among those with T2D was significantly higher in individuals with longer disease duration and suboptimal glycemic control.

When the investigators analyzed the association between the 2 biomarkers and mortality among adults with T2D, elevated levels of hs-cTnT were independently associated with an adjusted 77% increased risk of all-cause mortality (95% CI, 1.33 - 2.34) and elevated levels of NT-proBNP with a 78% increased risk (95% CI, 1.26 - 2.51). There was also an independent association between elevated levels of both proteins and increased risk of CVD mortality, ie, 54% for hs-cTnT (95% CI, 0.83 - 2.85) and more than twice that level of heightened risk for NT-proBNP (aHR, 2.46; 95% CI, 1.31 - 4.60).

Based on these findings, the investigative team emphasized that screening for certain cardiac biomarkers should be added to the routine assessment of traditional cardiovascular risk factors.

“The biomarkers analyzed in this study are very powerful in systematically categorizing patients based on their health status,” Selvin said. “Measuring biomarkers more routinely may help us focus on cardiovascular prevention therapies for people with T2D who are at higher risk.”

Reference: Fang M, Wang D, Olive Tang, et al. Subclinical acrdiovascular disease in US adult with and without diabetes. J Am Heart Assoc. Published online May 31, 2023. doi:10.1161/JAHA.122.029083