Diabetes is a highly prevalent chronic condition and a major contributor to the global burden of disease, posing substantial challenges to health systems. Cardiovascular disease (CVD) remains its leading complication, and people with diabetes face a two- to four-fold higher risk of cardiovascular morbidity and mortality than the general population. Control of glycated hemoglobin (HbA1c), blood pressure, and low-density lipoprotein cholesterol (LDL-C), collectively referred to as ABC risk factors, is a cornerstone of cardiovascular prevention in diabetes. Yet an important question remains unresolved: do these risk factors carry the same cardiovascular significance at different ages? Emerging evidence suggests that their associations with cardiovascular outcomes may vary across age groups, but age-specific evidence remains limited, particularly in China, where diabetes prevalence continues to rise alongside population aging.

In a recent study published in Life Metabolism, investigators from Ruijin Hospital and the 4C Study Group analyzed data from the China Cardiometabolic Disease and Cancer Cohort (4C), a nationwide 10-year prospective study, to examine whether the associations of HbA1c, systolic blood pressure (SBP), and LDL-C with incident CVD differ across age groups in Chinese adults with diabetes. The aim was not simply to confirm that ABC risk factors matter, but to determine whether their relationship to future cardiovascular risk changes with age.

The study included 36,583 Chinese adults with diabetes and no history of CVD at baseline (Figure 1), classified as young (< 55 years), middle-aged (55 to < 65 years), old (65 to < 75 years), and very old (75 years or older). Over a median follow-up of 10.1 years, 4,707 incident CVD events were documented. Overall, higher HbA1c, SBP, and LDL-C were each associated with greater CVD risk, but the strength of these associations attenuated with age. Compared with HbA1c < 7.0%, HbA1c ≥ 9.0% was associated with the greatest excess risk in the young group (HR 2.42) and a weaker association in the very old group (HR 1.50). SBP ≥ 140 mmHg was strongly associated with CVD in younger adults (HR 2.41 in those < 55 years), but was not significantly associated with CVD in participants aged 75 years or older. LDL-C ≥ 4.1 mmol/L was significantly associated with CVD in the young and middle-aged groups, but not in the two older groups.

Population-attributable fraction (PAF) analyses identified SBP as the largest contributor to CVD burden in the cohort overall (28.3%), followed by HbA1c (12.0%) and LDL-C (9.2%). These attributable fractions also declined steadily with age: for example, the PAF for SBP fell from 42.6% in the young group to 16.3% in the very old group. Together, the findings indicate that ABC abnormalities carry greater cardiovascular relevance earlier in life, whereas their associations with incident CVD become less pronounced at older ages. The study therefore supports a more age-adapted approach to diabetes risk-factor management, while underscoring that treatment decisions in older adults should be individualized in the context of comorbidities, treatment burden, and competing risks rather than guided by numerical targets alone.

This large, long-term cohort study provides population-based evidence from China that age modifies the associations between glycemia, blood pressure, lipids, and cardiovascular risk in diabetes. At the same time, the findings should be interpreted in light of the study’s observational design, reliance on single baseline measurements, and the relatively small number of participants aged 75 years or older. Future studies incorporating repeated measurements and subtype-specific cardiovascular analyses will be important for refining how age should inform ABC management in diabetes.
DOI
10.1093/lifemeta/loag008