Troponin to ID Diabetes Patients With Silent Heart Disease?

Mitchel L. Zoler, PhD

May 31, 2023

Nearly 1 in 5 US adults with type 2 diabetes but without symptoms of cardiovascular disease (CVD) have a clinically meaningful elevation of a marker of cardiac damage — namely, high sensitivity cardiac troponin T (hs-cTnT) — based on data from a representative sample of more than 10,000 US adults.

The finding suggests hs-cTnT maybe a useful marker for adults with diabetes who could benefit from more aggressive CVD risk reduction despite having no clinical indications of CVD.

The results "highlight the substantial burden of subclinical CVD in persons with diabetes and emphasize the importance of early detection and treatment of CVD for this high-risk population," say the authors of the research, published today in the Journal of the American Heart Association.

"This is the first study to examine subclinical CVD, defined by elevated cardiac biomarkers, in a nationally representative population of adults with or without diabetes. It provides novel information on the high burden of subclinical CVD [in American adults with diabetes] and the potential utility of hs-cTnT for monitoring this risk in people with diabetes," says Elizabeth Selvin, PhD, senior author and a professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

"What we are seeing is that many people with type 2 diabetes who have not had a heart attack or a history of cardiovascular disease are at high risk for cardiovascular complications," adds Selvin in an AHA press release "When we look at the whole population of people diagnosed with type 2 diabetes, about 27 million adults in the US, according to the CDC, some are at low risk and some are at high risk for cardiovascular disease, 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."

"Our results provide evidence to support use of cardiac biomarkers for routine risk monitoring in high-risk populations such as people with diabetes," Selvin noted in an interview.

Need for Aggressive CVD Risk Reduction

The findings also indicate that people with diabetes and an elevated hs-cTnT "should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins, blood pressure medications, and cardioprotective therapies such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists," Selvin adds.

"Cholesterol is often the factor that we target to reduce the risk of cardiovascular disease in people with type 2 diabetes," she observes. "However, type 2 diabetes may have a direct effect on the heart not related to cholesterol levels. If type 2 diabetes is directly causing damage to the small vessels in the heart unrelated to cholesterol plaque buildup, then cholesterol-lowering medications are not going to prevent cardiac damage," Selvin explains. "Our research suggests that additional non–statin-related therapies are needed to lower the cardiovascular disease risk in people with type 2 diabetes."

However, she notes that a necessary step prior to formally recommending such a strategy is to run clinical trials to assess the efficacy of specific treatments, such as SGLT-2 inhibitors and GLP-1 agonists, in people with diabetes and elevated hs-cTnT

"Randomized controlled trials would be best to test the relevance of measuring these biomarkers to assess risk in asymptomatic people with diabetes," as well as prospective study of the value of hs-cTnT to guide treatment, comments Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado Anschutz Medical Center in Aurora.

"I doubt measurements [of hs-cTnT] would be reimbursed [by third-party payers] if carried out without such outcome data," he added.

Eckel also highlights the need to further validate in additional cohorts the link between elevations in hs-cTnT and CVD events in adults with diabetes, and to confirm that elevated levels of another cardiac biomarker – N-terminal-pro B-type natriuretic peptide (NT-proBNP) — do not work as well as troponin as a risk marker for people with diabetes, another finding of the study.

ADA Report Already Recommends Testing These Biomarkers for HF

However, a consensus report published in 2022 by the American Diabetes Association laid out the case for routinely and regularly measuring levels of both high sensitivity cardiac troponin and natriuretic peptides in people with diabetes for early identification of incident heart failure.

"Among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure," noted the ADA consensus report on heart failure.

The new study run by Selvin and her co-authors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 from US adults who were at least 20 years old and had no history of CVD: myocardial infarction, stroke, coronary heart disease, or heart failure. This included 9273 people without diabetes and 1031 with diabetes, defined as a prior diagnosis or A1c ≥ 6.5%.

"Cardiovascular risk varies substantially in adults with type 2 diabetes, highlighting the need for accurate risk stratification," the authors observe.

All study participants had recorded measures of hs-cTnT and NT-proBNP.

The researchers considered an hs-cTnT level of greater than 14 ng/L and an NT-proBNP level of greater than 125 pg/mL as indicators of subclinical CVD.

The crude prevalence of elevated NT-proBNP was 33.4% among those with diabetes and 16.1% in those without diabetes. Elevated hs-cTnT occurred in 19% of those with diabetes and in 5% of those without diabetes. Elevated levels of both markers existed in 9% of those with diabetes and in 3% of those without diabetes.

"Approximately 1 in 3 adults with diabetes had subclinical CVD, with 19% having elevated levels of hs-cTnT, 23% having elevated NT-proBNP, and 9% having elevations in both cardiac biomarkers," the researchers note.

Diabetes Linked With a Doubled Prevalence of Elevated hs-cTnT 

After adjustment for several demographic variables as well as traditional CVD risk factors, people with diabetes had a significant 98% higher rate of elevated hs-cTnT compared with those without diabetes. But after similar adjustments, the rate of elevated NT-proBNP was significantly lower among people with diabetes compared with controls, by a relative reduction of 24%.

"Our findings suggest that in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring, as its interpretation is less complicated," said Selvin, who explained that "NT-proBNP is affected by overweight and obesity."

In people with diabetes, the age-adjusted prevalence of elevated hs-cTnT ran higher in those with longer duration diabetes, and in those with less well-controlled diabetes based on a higher level of A1c. Neither of these factors showed any significant relationship with measured levels of NT-proBNP.

Further analysis linked the NHANES findings during 1999-2004 with US national death records through the end of 2019. This showed that elevated levels of both hs-cTnT and NT-proBNP significantly linked with subsequently higher rates of all-cause mortality among people with diabetes. Elevated hs-cTnT linked with a 77% increased mortality and NT-proBNP linked with a 78% increased rate compared with people with diabetes and no elevations in these markers, after adjustment for demographic variables and CVD risk factors.

However, for the outcome of cardiovascular death, elevated hs-cTnT linked with a nonsignificant 54% relative increase, while elevated NT-proBNP linked with a significant 2.46-fold relative increase.

The study "adds new data on biomarkers that are not routinely measured in asymptomatic people with or without diabetes" and the relationships of these markers to   CVD mortality and all-cause mortality, Eckel concluded.

The study received no commercial funding, but used reagents donated by Abbott Laboratories, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. Selvin and Eckel had no disclosures.

J Am Heart Assoc. Published online May 31, 2023. Full text

Mitchel L. Zoler is a reporter with Medscape and MDedge based in the Philadelphia region. @mitchelzoler

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