Impact of prematurity on lifelong cardiovascular health: structural and functional considerations

Abstract

The aetiology of preterm cardiovascular disease formation appears different from that of traditional population. Within the 'traditional' population cardiovascular disease formation is driven by functional stressors (e.g., diet, smoking). Whereas preterm cardiovascular disease risk is driven by structural changes incurred at birth. Much of the proliferative growth in the developing heart and major vessels ceases at birth, leading to permanently reduced dimensions compared to their term-born cohort. These structural changes take a back seat to functional and clinical complications within the neonatal period, but become increasingly pronounced from adolescence, at which point functional decompensation can be observed. While the cause may differ from 'traditional' populations, the eventual disease outcomes do not, leading them to be an overlooked population. This means that aetiology, and thus, treatment options may be very different due to the underlying mechanisms. Here, we propose that the structural cause of preterm-associated cardiovascular disease is apparent and observable early in life. Understanding the differences in cardiovascular disease aetiology may therefore aid in the early treatment of preterm-associated cardiovascular disease risk.

Keywords: Cardiovascular diseases; Hypertension.

Fig. 1. Relative contribution of structural and functional complications in preterm cardiovascular disease risk across the lifespan.

Structural impairments (e.g., altered cardiac geometry^,, ↓ microvascular density^,) incurred with preterm birth ( < 37 weeks’ gestation) outside of clinically significant ones (e.g., patent ductus arteriosus) contribute relatively little to cardiovascular dysfunction, whereas functional complications (inotrope insensitivity, ↑ microvascular perfusion) are a significant cause of dysfunction (e.g., pulmonary hypertension^,,, ↓ cardiac output^,). Surviving graduates of neonatal intensive care exhibit little cardiovascular dysfunction following discharge and throughout infancy. By childhood, structural limitations from prematurity become apparent (↓ LV mass, ↑ RV mass), resulting in some (dys)functional changes (↓ contractility^,, ↑ BP^,,). Persistent structural limitations (altered cardiac geometry^,,, ↓ arterial diameter, ↓ microvascular density) contribute to cardiovascular remodelling (concentric hypertrophy^,,) and dysfunction in early adulthood (cardiac fibrosis^,, arterial stiffness^,, ↑ BP). In combination with ‘traditional’ cardiovascular disease risk factors, these preterm-specific risk factors fuel the onset of disease.