May 31, 2023 – If you have type 2 diabetes, you could already be at a higher risk for heart disease without knowing it. About one-third of people with gaming diabetes in a new study had higher levels of two things in their blood linked to heart disease. These blood “biomarkers” can be detected before someone has heart disease symptoms. So they could be used to screen people for higher risk earlier, at a time when prevention efforts or treatment could be more effective, researchers said. “People with diabetes should be aware that they are at high cardiovascular risk and should work with their doctors to develop a treatment plan that can prevent the future occurrence of cardiovascular events,” said senior study author Elizabeth Selvin, PhD, MPH, a professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. Historically, bad cholesterol was blamed for higher heart disease risk in people with type 2 diabetes. This study proposes that something else is going on, and other types of treatments – beyond ones that lower cholesterol – should be considered. “Our results suggest that hypertension treatment and interventions that target microvascular or small vessel health could be particularly beneficial in people with diabetes,” Selvin said. Heart Under Stress Selvin, lead researcher Michael Fang, PhD, MHS, and their colleagues tested for two specific biomarkers. They found 33% of people with type 2 diabetes had higher blood levels of one or the other, compared to only 16% of people without diabetes. The study was published online today in the Journal of the American Heart Association. One biomarker protein, called high-sensitivity cardiac troponin (hs-troponin), indicates damage to the heart. The other, called N-terminal pro-B-type natriuretic peptide (NT-proBNP), suggests pressure is building up in the heart enough to stress or stretch the heart wall. Cardiovascular disease is linked to 40% of hospitalizations and 30% of deaths among people with type 2 diabetes, so identifying those at risk before symptoms start is important. An estimated 27 million American adults have type 2 diabetes. Large, Diverse Population These two biomarkers have been studied before, but mostly in middle-age or older White adults. They are primarily measured in hospitals to test people with chest pain and/or shortness of breath. They are not generally used to identify heart disease – but emerging data like this study suggests they may have a role for prevention or prediction of risk, said Vijay Nambi, MD, a cardiologist with Baylor College of Medicine in Houston. This current study tested stored blood samples from a more diverse, nationally representative group of 10,304 adults 20 years and older. For example, those with type 2 diabetes were 60% non-Hispanic White, 15% non-Hispanic Black, 9% Mexican American, and 16% were of another race or ethnicity. People in the study reported no heart disease when they entered the National Health and Nutrition Examination Survey (NHANES) project between 1999 and 2004. Going back to stored blood samples from about 2 decades ago allowed Selvin and colleagues to track deaths from heart disease or any cause in the National Death Index up until the end of 2019. Key Findings A greater proportion of people with diabetes had higher levels of hs-troponin – 19%, vs. 5% of those without diabetes. More muscle disease and frailty among people with diabetes could explain this difference, the researchers noted. The investigators also found the risk of heart disease was highest among people who had diabetes longer and those whose blood sugar was less well-controlled. The other biomarker, NT-proBNP, was not significantly higher in the diabetes group. But those with diabetes and either or both biomarkers were more likely to die from diabetes or from any cause. For example, the risk of cardiovascular death was 54% greater with elevated hs-troponin and 2.5 times more likely with elevated NT-proBNP levels in the blood among adults with type 2 diabetes. The risk of dying from any cause was 77% higher with hs-troponin and 78% higher with NT-proBNP in this population. The higher risk remained even after researchers controlled for other cardiovascular risk factors. The risk of death also was higher among those ages 45 to 64, vs. those 65 and older. “These strategies need to be formally tested, but these biomarkers have consistently shown to be able to identify higher-risk individuals. Hence, overall, one should seriously start considering using these biomarkers routinely,” Nambi said. Screening for Heart Risk Selvin and colleagues not only identified things driving the higher risk but suggested what could be done about it. “Our findings support the potential use of these cardiac biomarkers for routine monitoring of risk, especially in high-risk populations where we might use them to help tailor cardiovascular therapy,” Selvin said. Using biomarker results to tailor management to an individual “would be even more powerful and impactful,” Nambi agreed. Taking a blood sample from people with type 2 diabetes to test for these two things could help prioritize who gets treated with a sodium-glucose cotransporter-2 (SLGT2) inhibitor, Selvin said. Drugs in the SLGT2 class include canagliflozin, dapagliflozin, and empagliflozin. Results could also guide treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist. GLP-1 medications such as semaglutide (Ozempic) and liraglutide (Victoza 3-Pak) have received a lot of attention recently for their weight loss potential. More research is needed, Selvin said. “We need to understand how best to use cardiac biomarkers in routine practice to improve the lives of people with diabetes and other individuals who are at high risk for cardiovascular disease,” she said. “Intervention studies and clinical trials could be particularly helpful to inform best practices in this area.”
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