Physical activity relates to carotid plaque vulnerability in older persons with subclinical carotid atherosclerosis.

Background: Recent evidence suggests that excessive physical activity may accelerate the progression of coronary atherosclerosis. However, data on carotid atherosclerosis remains scarce. This study aimed to evaluate the association between physical activity and changes in carotid atherosclerotic plaque vulnerability, and the interaction between these two variables with the risk of first-ever stroke.

Methods: This prospective study included 1330 stroke-free persons (mean age: 71.5 years) from the population-based Rotterdam Study with carotid atherosclerosis. Carotid magnetic resonance imaging (MRI) was performed to assess intraplaque haemorrhage (IPH) and lipid-rich necrotic core (LRNC), both recognised as important vulnerable plaque components, with a follow-up MRI conducted approximately six years later in 699 participants. Physical activity was assessed using a questionnaire at baseline MRI. The association of physical activity with incident plaque components and the interaction between these two variables with the risk of stroke were analysed, adjusting for socioeconomic status and conventional cardiovascular risk factors.

Findings: Higher volumes of total, moderate-to-vigorous, and vigorous physical activity were associated with an increased risk of incident IPH and LRNC, with adjusted odds ratio (OR) ranging from 1.08 to 1.35 per 20 metabolic equivalent of task (MET)-hours/week increase. Physical activity was further categorised using literature-based cut-offs, tertiles, quartiles, and quintiles, with the lowest group as the reference. The risk of incident IPH was significantly higher exclusively in the top quintiles of total, moderate-to-vigorous, and vigorous physical activity (adjusted OR range: 1.87-2.54, all P < 0.05), with thresholds of potential harm (99, 70, and 26 MET-hours/week, respectively) substantially exceeding current guideline recommendations for cardiovascular disease prevention (15, 15, and 7.5 MET-hours/week, respectively); similar patterns were also observed for LRNC. No association was found for moderate activity. The association between physical activity and first-ever stroke differed by the presence of vulnerable plaque components at baseline (P for interaction = 0.010 for total, 0.095 for moderate-to-vigorous), and physical activity inversely associated with stroke only in individuals without vulnerable plaque components (adjusted hazard ratio range: 0.69-0.71, all P < 0.05).

Interpretation: In older individuals with pre-existing carotid atherosclerosis, the most physically active group may have a higher risk of developing vulnerable carotid plaques. Individuals with pre-existing vulnerable carotid plaques may lose the benefits of physical activity.

Funding: The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organisation for Scientific Research (NWO); the Netherlands Organisation for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. This work was further supported by the Leducq Foundation COMET Network. The funder of the study had no role in study design, data collection, data analysis, data interpretation, writing, or submission of the report.