Carotid Atherosclerosis shows Distinct Patterns of Atheroinflammation and Microcalcification relating to Frailty and Multimorbidity

Introduction: Atherosclerosis involves several important pathophysiological processes, in particular inflammation within the atherosclerotic plaque (atheroinflammation) and microcalcification. Not only do these processes have implications for plaque rupture and consequent thromboembolic events, but the burden of systemic atheroinflammation has also been implicated in downstream organ dysfunction. This study aimed to establish the relationships between different patterns of vascular pathophysiology, frailty, and multimorbidity. Methods: Individuals with ischaemic stroke due to symptomatic carotid atherosclerosis underwent vascular imaging using positron emission tomography with both 18F-fluorodeoxyglucose (FDG, measuring atheroinflammation) and 18F-sodium fluoride (NaF, measuring microcalcification). Pre-morbid frailty was measured using the Clinical Frailty Scale (CFS), and pre-stroke multimorbidity was assessed using the Charlson Co-morbidity Index (CCI). Results: Fifty-two carotids (26 symptomatic culprit atheroma, 26 asymptomatic non-culprit atheroma) were included. On univariable analysis, FDG uptake was associated with CFS (rs=0.68, P<0.001 for the non-culprit artery), which remained significant after adjustment for covariables (beta=1.89, P<0.001). In contrast, NaF uptake was associated with CCI (rs=0.54, P<0.01 for most-diseased segment uptake in the culprit artery), which remained significant on multivariable analysis (beta=0.81, P<0.01). There was no association between FDG uptake and CCI, nor between NaF uptake and CFS. Conclusion: We demonstrate that frailty and multimorbidity show different patterns of vascular pathophysiology. In particular, the association between diffuse atheroinflammation and frailty elucidates the inflammatory basis of frailty that may underlie its disease- and treatment-modifying effects in stroke.