CARDIOVASCULAR RISK STRATIFICATION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A CONTEMPORARY REVIEW OF BIOMARKERS AND IMAGING MODALITIES

Daniel R. Whitman; Sofia Petrova; Hiroshi Tanaka; Aigerim Bekova

doi:10.7759/aams.2026.0081

Abstract

Background: Patients with type 2 diabetes mellitus (T2DM) carry a two- to four-fold higher risk of atherosclerotic cardiovascular disease (ASCVD) compared with non-diabetic peers. Traditional risk equations frequently underestimate this burden, prompting renewed interest in biomarker-driven and imaging-based stratification. Methods: We conducted a structured narrative review of peer-reviewed literature published between January 2015 and December 2025, identified through PubMed, Scopus, and Web of Science using predefined Boolean queries. Articles addressing risk biomarkers, coronary artery calcium (CAC) scoring, carotid intima-media thickness, and contemporary risk equations in adults with T2DM were included. Results: High-sensitivity cardiac troponin T, N-terminal pro–B-type natriuretic peptide, growth differentiation factor 15, and lipoprotein(a) consistently improved discrimination beyond standard models, with C-statistic gains of 0.02–0.06. CAC scoring offered the largest reclassification benefit among asymptomatic patients with intermediate clinical risk. Conclusion: A tiered approach combining a contemporary risk equation, selected biomarkers, and CAC imaging in intermediate-risk cases provides clinically meaningful refinement of cardiovascular risk estimation in T2DM and should inform individualized preventive therapy.

Keywords: type 2 diabetes mellitus, cardiovascular risk, biomarkers, coronary artery calcium, risk stratification, preventive cardiology

Full Text

Type 2 diabetes mellitus (T2DM) affects more than 530 million adults worldwide and remains a leading driver of premature cardiovascular morbidity and mortality. Despite improvements in glycemic, lipid, and blood pressure control, residual cardiovascular risk persists, and conventional risk equations such as the Pooled Cohort Equations and SCORE2-Diabetes systematically underestimate event rates in younger adults and women with T2DM. Accurate risk stratification is essential to guide the intensity of preventive therapy, including high-intensity statins, ezetimibe, PCSK9 inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists with proven cardiovascular benefit.

MATERIALS AND METHODS

A structured narrative review was performed. PubMed, Scopus, and Web of Science were searched from 1 January 2015 to 31 December 2025 using combinations of the terms "type 2 diabetes," "cardiovascular risk," "biomarker," "coronary artery calcium," "carotid intima-media thickness," and "risk stratification." Eligible publications were original observational studies, randomized trials, and systematic reviews involving adults aged 18 years or older with T2DM. Two reviewers independently screened titles and abstracts. Discrepancies were resolved by discussion with a third senior reviewer. A total of 312 full-text articles were assessed; 87 met the inclusion criteria and were synthesized qualitatively.

Among circulating biomarkers, high-sensitivity cardiac troponin T (hs-cTnT) showed the most reproducible incremental value, with concentrations above 14 ng/L doubling the 5-year risk of major adverse cardiovascular events. NT-proBNP was a strong predictor of incident heart failure independent of left ventricular ejection fraction. Growth differentiation factor 15 added prognostic information for all-cause mortality but is not yet broadly available. Elevated lipoprotein(a) above 50 mg/dL identified a subgroup with accelerated atherosclerosis and resistant residual risk.

Coronary artery calcium (CAC) scoring delivered the largest single-test reclassification gain. A CAC score of 0 in asymptomatic patients with intermediate clinical risk corresponded to an annual event rate below 0.5 percent, supporting the de-escalation of preventive therapy in selected cases. Conversely, a CAC score above 300 reclassified up to 38 percent of intermediate-risk patients upward, justifying more intensive lipid-lowering and consideration of antiplatelet therapy after individualized bleeding-risk assessment.

The convergence of biomarker panels with CAC imaging supports a tiered model: apply a contemporary equation to all adults with T2DM, measure selected biomarkers when results would alter management, and reserve CAC for asymptomatic patients in whom imaging would change preventive intensity. This approach aligns with the 2024 ESC Guidelines on cardiovascular disease prevention and the 2025 ADA Standards of Care, both of which endorse a more individualized stratification pathway.

Limitations of the available evidence include heterogeneity of cohorts, variable definitions of cardiovascular endpoints, and limited data in non-European populations. Prospective trials evaluating biomarker- and imaging-guided escalation of therapy are ongoing and will be essential to confirm clinical utility.

Contemporary cardiovascular risk stratification in T2DM benefits from a layered framework that integrates clinical equations, validated biomarkers, and selective coronary calcium imaging. Adopting this framework in routine endocrinology and primary care clinics offers a pragmatic path to reduce residual cardiovascular risk in this high-burden population.

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