Troponin to identify diabetic patients with silent heart disease?

Nearly one in five American adults with type 2 diabetes but no symptoms of cardiovascular disease (CVD) have a clinically significant elevation of a marker of cardiac injury – namely, high-sensitivity cardiac troponin T (hs-cTnT ) – based on data from a representative sample of over 10,000 US adults.

The finding suggests that hs-cTnT may be a useful marker for adults with diabetes who may benefit from more aggressive CVD risk reduction despite the lack of clinical indications for CVD.

The findings “highlight the substantial burden of subclinical cardiovascular disease in people with diabetes and underscore the importance of early detection and treatment of cardiovascular disease for this high-risk population,” the authors state. research, published today in the Journal of the American Heart Association.

“This is the first study to examine subclinical cardiovascular disease, defined by elevated cardiac biomarkers, in a nationally representative population of adults with and without diabetes. It provides new insights into the high burden of subclinical cardiovascular disease. [in American adults with diabetes] and the potential utility of hs-cTnT to monitor this risk in people with diabetes,” says Elizabeth Selvin, PhD, lead author and professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

“What we find 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,” Selvin adds in a statement. AHA press. “When you look at the entire population of people diagnosed with type 2 diabetes, about 27 million adults in the United States, 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 might not otherwise be recognized as most at risk.”

“Our results provide evidence supporting the 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 results also indicate that people with diabetes and elevated hs-cTnT “should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins.” , antihypertensive drugs, and cardioprotective therapies such as sodium-glucose cotransporter-2 (SGLT-2) and glucagon-like peptide-1 (GLP-1) receptor agonists,” Selvin adds.

“Cholesterol is often the factor that is targeted to reduce the risk of cardiovascular disease in people with type 2 diabetes,” she observes. “However, type 2 diabetes can have a direct effect on the heart unrelated to cholesterol levels. While type 2 diabetes directly causes damage to small vessels in the heart unrelated to the buildup of cholesterol plaque, then cholesterol-lowering drugs aren’t going to prevent heart damage,” says Selvin. “Our research suggests that additional non-statin therapies are needed to reduce the risk of cardiovascular disease in people with type 2 diabetes.”

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

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

“I doubt the measures [of hs-cTnT] would be refunded [by third-party payers] if done without such outcome data,” he added.

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

ADA report already recommends testing these biomarkers for HF

However, a consensus report published in 2022 by the American Diabetes Association presented the case for routine and regular measurement of high-sensitivity cardiac troponin and natriuretic peptide levels in people with diabetes for early identification of incident heart failure.

“In people with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended at least once a year to identify the early stages of heart failure and implement strategies to prevent transition to symptomatic heart failure,” noted the ADA Consensus Report on Heart Failure.

The new study led by Selvin and his co-authors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 among American adults aged at least 20 years and without a history of CVD: myocardial infarction, stroke, coronary artery disease or heart failure. This included 9273 people without diabetes and 1031 with diabetes, defined as previously diagnosed or A1c ≥ 6.5%.

“Cardiovascular risk varies significantly among adults with type 2 diabetes, highlighting the need for accurate risk stratification,” the authors observe.

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

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

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

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

Diabetes linked to doubled prevalence of elevated hs-cTnT

After adjusting for several demographic variables as well as traditional CVD risk factors, people with diabetes had elevated hs-cTnT levels that were 98% higher than people without diabetes. But after similar adjustments, elevated NT-proBNP levels were significantly lower in people with diabetes compared to controls, by a relative reduction of 24%.

“Our results suggest that in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring because 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 was higher in people with long-lasting diabetes and in those with less well-controlled diabetes due to higher of A1c. None of these factors showed a significant relationship with the measured levels of NT-proBNP.

Further analysis linked NHANES results from 1999 to 2004 to US National Death Records through the end of 2019. This showed that elevated levels of hs-cTnT and NT-proBNP were significantly linked to later higher all-cause mortality rates in people with diabetes. . Elevated hs-cTnT linked to 77% increased mortality and NT-proBNP linked to 78% increased rate compared to people with diabetes and no elevation of these markers, after adjusting for demographic variables and risk factors of CVD.

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

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 did not disclose anything.

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

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

For more diabetes and endocrinology news, follow us on Twitter and on Facebook .