Central arterial stiffness is associated with cognitive decline and cardiovascular disease manifestation in cancer survivors in the Framingham Heart Study

Abstract

Introduction – Cancer survivors experience disproportionate prevalence of cognitive deficits and higher risk of CVD, due to a combination of shared biological mechanisms and anticancer treatment cardiotoxicity. Central artery stiffening, which increases following cancer diagnosis, inhibits pulsatile flow damping and potentiates microvascular damage, particularly within the cerebral circulation. Associations between central arterial stiffness and the risks of incident mild cognitive impairment (MCI), CVD diagnosis, and all-cause mortality have been previously established in the general population. However, there is a paucity of evidence on the association between arterial stiffness and cognitive decline among cancer survivors. Hypothesis – We hypothesized that declines in cognitive function would be associated with a higher central arterial stiffness and that cognitive function and central arterial stiffness would predict risk of CVD diagnosis and all-cause mortality in a large cohort of diverse cancer survivors. Methods – We evaluated dementia-free cancer survivors in the Framingham Original and Offspring Cohorts (n=277, 80±12.3 years old, 56.7%women, 9.3±8.8 years from first diagnosis) with baseline carotid-femoral pulse wave velocity (cfPWV) measurements. During baseline and subsequent examinations (mean follow-up 7.7±3.9 years), the Mini-Mental State Examination (MMSE; global cognitive function) and neuropsychological exams (NP; executive function, learning and memory) were evaluated. Multivariable linear and logistic regression models determined the relationship between cfPWV and cognitive decline and MCI. Multivariate Cox Regression related cfPWV and cognitive function to the risk of CVD diagnosis and all-cause mortality. Multivariate models were adjusted for age, sex, depressive symptoms, and traditional CVD risk factors. Results – Higher cfPWV at baseline was significantly associated with a greater rate of decline in global cognitive function (ΔMMSE) (p=0.003). Higher cfPWV was also significantly associated with clinically defined MCI, whether denoted by an impaired MMSE (OR(95%CI): 9.2(2.5-33.5), p=0.001) or NP score (4.3 (1.4-13.0), p=0.009) in univariate logistic models. In the final model, there was a 3.4-fold increase in risk of CVD in cancer survivors with high cfPWV (HR (95%CI): 3.45 (1.04-11.66), p=0.04). Changes in cognitive function were not associated with CVD outcomes. Conclusion – Our findings suggest an association between central arterial stiffness, future cognitive decline, and an increased risk of CVD in a diverse cohort of cancer survivors. Our findings support the potential adverse consequences of a stiffening arterial vasculature following cancer diagnosis; specifically, those related to cognitive function and long-term CVD outcomes.