Aortic stiffness increases markedly with age and is associated with hypertension, heart failure and accelerated brain aging. Abnormal hemodynamic coupling between left ventricle (LV) and aorta contributes to pathogenesis of target organ damage. However, the LV is also mechanically coupled to and stretches the proximal aorta during systole. The force associated with stretch of the `aortic spring' is considerable, comparable to the force required for LV pressure generation. `Mechanical coupling' loads the LV but also stores energy in the aortic spring, which contributes to the recoil of the base of the heart during diastole, producing the suction that facilitates early diastolic filling. Aortic stiffening disrupts this mechanical coupling and imposes an asymmetric load on the LV long axis that impairs global longitudinal strain (GLS) and early diastolic filling. Impaired mechanical coupling contributes to left atrial (LA) enlargement and dysfunction, which increases pulmonary artery (PA) pressure and stiffness, leading to abnormal right ventricular (RV)-PA hemodynamic coupling, and an age-related increase in PA systolic pressure. An associated increase in PA pulse pressure could contribute to remodeling of resistance vessels in the lung, leading to combined pre- and post-capillary pulmonary hypertension. The resulting combination of right and left heart abnormalities limits cardiac output and contributes to the syndrome of heart failure with preserved LV ejection fraction (HFpEF). In young, healthy adults, the low impedance of a compliant aorta interfaces with normally stiff conduit arteries, creating impedance mismatch and wave reflection that limits the transmission of excessive pulsatile energy into the microcirculation, resulting in optimal `hemodynamic coupling' between the left heart and target organs, such as the brain. Aortic stiffening increases aortic impedance, reduces impedance mismatch, and results in an increased transmission of harmful pulsatile energy into the microcirculation, resulting in microvascular damage, accumulation of amyloid fibrils in brain parenchyma, premature brain aging and cognitive impairment. We will use tonometry and echocardiography in the elderly Framingham Offspring cohort to test the hypothesis that aortic stiffness impairs mechanical coupling between the aorta and LV, reduces LV GLS and impairs LV diastolic function and LA function. We will assess RV structure and function and RV-PA coupling with echocardiography to test the hypothesis that an increase in LA pressure increases PA pressure, stiffness and impedance, impairs RV-PA coupling and contributes to the age-related increase in pulmonary artery systolic pressure. Finally, we will assess carotid input impedance and aorta-carotid coupling to test the hypothesis that a disproportionate increase in aortic as compared to common carotid and cerebrovascular input impedances reduces the impedance gradient and increases penetration of pulsatile flow into the cerebral circulation, resulting in microvascular tissue damage, accumulation of amyloid and impaired cognitive function.

Public Health Relevance

Aortic stiffness increases markedly with age, particularly after midlife, and is associated with high blood pressure, reduced pumping and filling of the heart, faster brain aging and impaired memory. The high frequency of and risk posed by aortic stiffness in the elderly places increased load on the heart, the lungs and on the blood vessels supplying the brain, which contributes to malfunction of these vital organs. Results of the proposed research will inform development and implementation of strategies that will reduce and prevent aortic stiffening and lower the burden of heart and lung disease, and memory problems in the elderly.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cancer, Heart, and Sleep Epidemiology B Study Section (CHSB)
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Minear, Mollie A
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Boston University
Internal Medicine/Medicine
Schools of Medicine
United States
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