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Midlife ICAM-1 levels may predict cardiovascular disease and cognitive decline in latelife: Insights from the
Khaled Abdoun1, Justin Swanson2, Ian Pollack1
1University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Insights
Midlife inflammation, particularly intracellular Adhesion Molecule 1 (ICAM-1), predicts long-term risk for atherosclerotic cardiovascular disease (ASCVD) and cognitive decline. ICAM-1 serves as a dual marker for both conditions, aiding early intervention strategies.
Area of Science:
- Cardiovascular disease research
- Neuroscience
- Inflammation and immunology
Background:
- Systemic inflammation is a known risk factor for atherosclerotic cardiovascular disease (ASCVD) and neuroinflammation.
- The combined risk of ASCVD and cognitive decline, especially during midlife to late life transition, is not well understood.
- Identifying shared inflammatory markers can facilitate early intervention for individuals at risk.
Purpose of the Study:
- To investigate the relationship between baseline inflammatory markers and their changes over one year with long-term risks of ASCVD and cognitive decline.
- To identify a potential shared inflammatory marker for both ASCVD and cognitive impairment.
- To assess the predictive value of inflammatory markers for major adverse cardiovascular events (MACE) and cognitive function.
Main Methods:
- Analysis of baseline and one-year changes in high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), intracellular Adhesion Molecule 1 (ICAM-1), and CD40 ligand (CD40L) in the Heart SCORE study.
- Longitudinal assessment using Cox regression models for MACE, coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and Montreal Cognitive Assessment (MoCA) scores.
- Risk prediction models adjusted for Pooled Cohort Equation (PCE) risk factors, with calculation of area under the receiver operating characteristic curve (AUC).
Main Results:
- Among 673 participants followed for 12 years, hs-CRP and IL-6 were associated with MACE, while ICAM-1 predicted both long-term MACE and lower MoCA scores.
- ICAM-1 showed a significant association with MACE (HR 2.34) and cognitive decline (β: 0.47).
- Inflammatory biomarkers improved risk prediction for MACE and MoCA scores compared to the PCE model alone.
Conclusions:
- Midlife levels of hs-CRP, IL-6, and ICAM-1 predict late-life ASCVD.
- ICAM-1 emerged as a significant dual marker for both ASCVD and cognitive impairment.
- Further research into ICAM-1's role as a prognostic marker for cardiovascular and cognitive health is warranted.
Introduction:
Systemic inflammation is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD) and has also been implicated in the progression of neuroinflammation. However, the relationship between inflammation and the combined risk of ASCVD and cognitive decline-particularly during the critical transition from midlife to late life-remains poorly understood. Identifying a shared inflammatory marker that signals vulnerability to both conditions may be an important tool for early intervention. In this study, we examined how baseline inflammatory markers, as well as their changes over one year, relate to long-term risk of ASCVD and cognitive outcomes.
Methods:
We analyzed baseline and one-year change (1y-Δ) in an inflammatory biomarker panel [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), intracellular Adhesion Molecule 1 (ICAM-1) and CD40 ligand (CD40L_)] in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Using logistic and linear Cox regression models, the association of inflammatory markers and 1y-Δ, cognitive assessment by MoCA score, coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and major adverse cardiovascular events (MACE) events were assessed longitudinally. All data were adjusted for the pooled cohort equation (PCE) risk factors and area under the receiver operating characteristic curve (AUC) were calculated for incremental risk prediction.
Results:
Among 673 participants (mean age 59 ± 6.8 years; 63.9 % female; 31.6 % Black) were followed for 12 years. While both hs-CRP and IL-6 were associated with MACE events at 12 years, only ICAM-1 was linked with long-term MACE (HR 2.34 [1.02-5.37], p < 0.05) as well as lower MoCA scores (β: 0.47 [95 % CI: 0.93 to -0.02], p < 0.05). Compared to the PCE model, inflammatory biomarkers improved risk prediction indices for MACE (0.812, ΔAUC +0.056, p = 0.02) and MoCA (0.664, ΔAUC +0.04, p = 0.048). One-year biomarker changes were not significant for endpoint association.
Conclusions:
In a community cohort of adults, midlife levels of three inflammatory markers (hs-CRP, IL-6, and ICAM-1) were predictive of late life ASCVD; however, only ICAM-1 was identified as a dual marker for ASCVD and cognitive impairment. The role of ICAM-1 as a prognostic marker for adverse cardiovascular and cognitive health should be explored in future studies.
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