ATHEROSCLEROTIC cardiovascular disease (ASCVD) remains the leading cause of death worldwide, despite major advances in low-density lipoprotein cholesterol (LDL-C)-lowering therapies.
New findings presented at the European Atherosclerosis Society (EAS) Congress suggested that chronic psychological stress may reduce the anti-inflammatory and anti-atherosclerotic benefits of lipid-lowering treatment, potentially contributing to persistent residual cardiovascular risk.
Stress and Residual Cardiovascular Risk
Psychological stress has long been recognised as a cardiovascular risk factor, but the biological mechanisms linking stress to ongoing vascular inflammation have remained unclear.
Researchers investigated whether chronic stress could impair the resolution of atherosclerosis, even after cholesterol levels were reduced.
The team used a chronic social defeat stress model in mice to induce depression-like behaviours. LDL receptor-deficient mice were first fed an atherogenic diet for 24 weeks before undergoing 10 days of stress exposure. Based on behavioural testing, the mice were categorised as either stress-susceptible or stress-resilient before being switched to a cholesterol-lowering diet.
Chronic Stress Drove Persistent Inflammation
Compared with stress-resilient and non-stressed control mice, stress-susceptible mice showed significantly increased inflammatory activity within the bone marrow and circulation.
Researchers observed expansion of monocytes in the bone marrow alongside higher levels of circulating inflammatory Ly6Chi monocytes, which demonstrated greater recruitment into atherosclerotic plaques.
After 3 weeks of cholesterol lowering, stress-susceptible mice retained higher macrophage content within plaques, indicating impaired atherosclerosis resolution despite lipid reduction.
Single-cell RNA sequencing and bone marrow transplantation experiments revealed that chronic stress reprogrammed bone marrow progenitor cells, particularly monocytes, creating what researchers described as an “inflammatory memory”. Notably, transplanted bone marrow cells from stress-susceptible mice continued to promote inflammatory and pro-atherogenic responses even in recipient mice.
Human Data Reflected the Experimental Findings
Importantly, the findings were also supported by human data. Investigators found that higher neuroimaging-derived markers of psychological stress were associated with smaller reductions in systemic and arterial inflammation during LDL-C-lowering therapy.
These translational findings suggest that chronic stress may directly interfere with the vascular benefits typically expected from cholesterol-lowering treatment.
Implications for Future ASCVD Treatment
The researchers concluded that psychosocial stress and stress-induced haematopoietic reprogramming may represent important therapeutic targets in ASCVD management.
The study also highlighted the possibility that psychological stress could be used as a stratification factor when tailoring future lipid-lowering and anti-inflammatory strategies.
While the study combined both experimental and human evidence, further research will be needed to determine whether targeted stress-reduction interventions can improve cardiovascular outcomes alongside standard lipid-lowering therapy.
Reference
Tufanli O et al. Stress susceptibility drives myelopoiesis to impair atherosclerosis resolution. 94th EAS Congress, 24-27 May, Athens.
Featured image: Andrey Popov on Adobe Stock
