Influence of accelerated arterial ageing in growth restricted cohorts on adult-onset cardiovascular diseases.

Epidemiologists have long documented higher risk of adult-onset cardiovascular diseases (CVD) such as stroke, hypertension and coronary artery disease) and mortality from circulatory causes in low birth weight cohorts (poor substrate supply). Utero-placental insufficiency and hypoxemic state induced alterations in arterial structure and compliance are important initiating factors for adult-onset hypertension. The mechanistic links between fetal growth restriction and CVD include decreased arterial wall elastin/collagen ratio, endothelial dysfunction and heightened renin-angiotensin-aldosterone-system (RAAS). Systemic arterial thickness on fetal ultrasound and vascular changes in placental histopathology in growth restricted cohorts indicate fetal/developmental origins of adult-onset circulatory diseases. Similar findings of impaired arterial compliance have been noticed across age-groups (neonates through to adults). Such changes augment what occurs as 'normal arterial ageing', resulting in accelerated arterial ageing. Data from animal models suggest that hypoxemia-associated vascular adaptations enacted are region specific, reflecting long-term vascular pathology. In this review we explore the influence of birthweight and prematurity on blood pressure and arterial stiffness, demonstrating impaired arterial dynamics in growth restricted cohorts across age-groups, explain how early arterial ageing influences adult-onset CVDs, describe pathophysiology data from experimental models and finally, discuss interventions which may influence ageing by way of altering various cellular and molecular mechanisms of arterial ageing. Age-appropriate interventions which have noted efficacy include prolonged breastfeeding and high polyunsaturated fatty acids dietary intake. Targeting the RAAS seems a promising approach. New data indicates activation of Sirtuin 1 and maternal resveratrol may have beneficial effects.