Preterm-born individuals: a vulnerable population at risk of cardiovascular morbidity and mortality during thermal extremes?

Abstract

New findings: What is the topic of this review? Thermal extremes disproportionately affect populations with cardiovascular conditions. Preterm birth, across all gestational age ranges below 37 weeks, has been identified as a non-modifiable risk factor for cardiovascular disease. The hypothesis is presented that individuals born preterm are at an increased risk of cardiovascular morbidity and mortality during thermal extremes. What advances does it highlight? Cardiovascular stress tests performed in preterm-born populations, from infancy through adulthood, highlight a progression of cardiovascular dysfunction accelerating through adolescence and adulthood. This dysfunction has many similarities with populations known to be at risk in thermal extremes.

Abstract: Preterm-born individuals are a uniquely vulnerable population. Preterm exposure to the extrauterine environment and the (mal)adaptations that occur during the transitional period can result in alterations to their macro- and micro-physiological state. The physiological adaptations that increase survival in the short term may place those born preterm on a trajectory of lifelong dysfunction and later-life decompensation. Cardiovascular compensation in children and adolescents, which masks this trajectory of dysfunction, is overcome under stress, such that the functional cardiovascular capacity is reduced and recovery impaired following physiological stress. This has implications for their response to thermal stress. As the Anthropocene introduces greater changes in our environment, thermal extremes will impact vulnerable populations as yet unidentified in the climate change context. Here, we present the hypothesis that individuals born preterm are a vulnerable population at an increased risk of cardiovascular morbidity and mortality during thermal extremes.

Keywords: cardiovascular; cardiovascular dysfunction; preterm birth; thermal extremes; thermoregulation; vulnerable populations.

FIGURE 1

Relative risk of cardiovascular morbidity and mortality with exposure to increasing global temperatures. Thresholds for compensable and uncompensable thermal tolerance are altered by the presence of disease and dysfunction, for example, elderly populations (orange line) or cardiovascular disease populations (purple line). With rising global temperatures and greater severity of thermal extremes, the proportion of vulnerable populations increases (dotted line and shaded area). This cardiovascular risk may extend to apparently healthy populations, such as those born preterm. Created with BioRender.com.

FIGURE 2

Thermoeffector responses in elderly, cardiovascular disease, and ex‐preterm populations during deviations in T _C by the presence of disease and dysfunction. Elderly: vasomotor response ↓. VC↓, due to: (1) ↓ sympathetic signalling (Greaney et al., 2015); (2) ↓ transmitter synthesis and axon release (almost sole reliance on NAd; Thompson & Kenney, 2004); and (3) ↓ post‐junctional responsiveness (Frank et al., ; Thompson & Kenney, 2004). In heat, absolute Sk.BF ↓ (H. L. Martin et al., 1995), responsiveness ↓ (Holowatz & Kenney, 2010) and hepato‐splanchnic BF redistribution ↓ (Gravel et al., 2021). CIT: cold perception ↓ (Florez‐Duquet & McDonald, ; Watts, 1971), ↓ Sk.M and therefore ↓ ST (Grimby & Saltin, 1983), ↓ BAT activity (Ruiz et al., ; Yoneshiro et al., 2011) and ↓ CIT (Florez‐Duquet & McDonald, 1998). Sweat response ↓, ↓ E_sw (Balmain, Jay et al., 2018), sweat gland atrophy, sensory nerve denervation and wider thermal thresholds (Guergova & Dufour, ; Inoue, ; Inoue et al., 1999). CVD populations: vasomotor response: dysregulation of CVS in CVD ↑'s VC (Foëx & Sear, ; Greaney et al., ; Holowatz & Kenney, 2007), and ↓'s VD (Cui et al., ; Kenny et al., 2010), due to ↑ SNA, ↓ endothelial VD mediators, ↓ capillary recruitment, rarefaction and fibrosis of vasculature (↓ NOS, ↔ ET‐1; Foëx & Sear, ; Holowatz & Kenney, 2007). Experimental evidence limited in CVD, but CIT ↓, ↓ Sk.M. and therefore ↓ ST (Tyrovolas et al., 2020), BAT activity inversely correlated with BMI and visceral adiposity, and UCPs ↓ in heart failure (Laskowski & Russell, 2008). CVD sweat response ↔ (Balmain, Sabapathy et al., ; Cui et al., 2005). BV ↓ and therefore ↓ E_sw. Preterm adults: the preterm vasomotor responses are speculative as there are no published investigations in preterm thermovascular responses. Preterm adults exhibit microvascular rarefaction (Johansson et al., ; Lewandowski et al., 2015), endothelial dysfunction (Skilton et al., 2011), impaired NO sensitivity (Gray et al., unpublished results) and likely ↓ VD. ↑ VC driven by increased circulating catecholamines (Johansson et al., 2007) and narrowed arteries (Jiang et al., ; Schubert et al., 2011). CIT: BAT deposition appears comparable to term adults (Kistner et al., 2018). Abbreviations: BAT, brown adipose tissue; BF, blood flow; BV, blood volume; CIT, cold‐induced thermogenesis; E_sw, evaporative heat loss from sweating; ET‐1, endothelin 1; NAd, noradrenaline; NOS, nitric oxide synthesis; Sk.M., skeletal muscle; NST, non‐shivering thermogenesis; Sk.BF, skin blood flow; SNA, sympathetic nerve activity; ST, shivering thermogenesis; T _C, core temperature; TNZ, thermoneutral zone; UCP, uncoupling protein; VC, vasoconstriction; VD, vasodilatation.

FIGURE 3

Life course view of preterm CVD risk. Risk of CVD increases in a non‐linear trajectory due to cumulative progression of dysfunction and disease from perinatal, lifestyle‐induced or other challenges. Prematurity (grey region) elevates the starting trajectory for CVD away from term‐born low‐risk trajectory. Early interventions may lower this high‐risk trajectory, whereas adult interventions of overt CVD have limited benefits. No treatment exists to lower preterm‐born individuals to a low‐risk trajectory. Figure adapted from Hanson and Gluckman (2014). Abbreviations: BP, blood pressure; CAD, coronary artery disease; CHF, congestive heart failure; CVD, cardiovascular disease; IHD, ischaemic heart disease; ISSI, intermittent or sustained systemic inflammation; NEC, necrotising enterocolitis; NOP, nephropathy of prematurity; PDA, patent ductus arteriosus; PPH, persistent pulmonary hypertension; ROP, retinopathy of prematurity; SNS, sympathetic nervous system.