Immune-Cell Patterns Linked to Near-Term Plaque Formation in Older Adults

Specific patterns of immune cells were associated with the development of previously undetected arterial plaque in a three-year study of healthy older adults, according to reporting by Fight Aging! The findings point to T-cell measurements as possible markers of early vascular vulnerability, before clinical symptoms appear.

The study followed 49 adults with an average age of 63.8 years. Participants were described as healthy, medication-free and highly fit. Researchers assessed carotid arteries using ultrasound and collected data on T-cell populations, blood proteins, body composition and cardiorespiratory fitness at baseline and again during follow-up.

At the end of the study, participants were classified according to whether they had no subclinical atherosclerotic plaque, newly developed plaque or persistent plaque. Among participants who initially had no detectable plaque, 30.3% developed new subclinical plaque during the study period.

Several immune-cell patterns measured at baseline were associated with greater odds of later plaque formation. Lower frequencies of CD8+ effector memory T cells were linked with new plaque, while higher frequencies of CD8+ effector memory re-expressing CD45RA cells and regulatory T cells, or Tregs, were also associated with the outcome.

Changes over time provided a separate signal. Expansion of CD8+ effector memory T cells was the most consistently associated independent variable for new plaque formation. This increase occurred alongside declines in Tregs and in the ratio of regulatory T cells to effector T cells. Tregs help limit immune activation, while the study’s background describes T cells as important contributors to the chronic inflammation involved in plaque biology.

Higher levels of vascular cell adhesion molecule-1, or VCAM-1, at baseline were another independent predictor. Increases in visceral fat and declines in peak oxygen uptake, known as VO2peak, were also linked with new plaque, although the immune markers were reported to be more robust than metabolic measures or serum cytokines.

The research builds on earlier cross-sectional work in a similarly characterized group, in which people with subclinical plaque showed immune features associated with immunosenescence. Those included fewer naïve CD4+ T cells, more differentiated memory-cell populations, inflammatory signals and changes in regulatory T-cell subsets.

The new results are longitudinal and observational, meaning they identify relationships between baseline characteristics, changes over time and plaque development rather than proving that the immune-cell shifts caused atherosclerosis. The study was also small and focused on healthy, physically fit older adults, so the findings may not apply to other populations. The plaque measured was subclinical carotid plaque, not a clinical heart attack or stroke.