Vascular Endothelial Function Assessed by Flow-Mediated Vasodilatation in Young Adults Born Very Preterm or With Extremely Low Birthweight: A Regional Cohort Study

Abstract

Background: Preterm birth and low birthweight have been associated with increased risk of cardiovascular disease in young adults. Endothelial dysfunction is established as an early marker for development of atherosclerotic cardiovascular disease. Previous studies of endothelial function in young adults born very preterm or with extremely low birthweight have, however, shown diverging results. Objective: We aimed to evaluate the risk of cardiovascular disease as measured by vascular endothelial function in young adults born very preterm (<29 weeks of gestation) or with extremely low birthweight (<1,000 g), compared with term-born controls. Methods: This study included 50 young adults born very preterm or with extremely low birthweight and 49 term-born controls born in Norway in the periods 1982-1985, 1991-1992, and 1999-2000 at mean age 28 (±6) years. The endothelial function was assessed by ultrasound measured flow-mediated dilatation (FMD) of the right brachial artery. The arterial diameter was measured at baseline, after release of 5 min of occlusion, and after sublingual administration of nitroglycerine. FMD was reported as absolute and percentage diameter change from baseline and relative to nitroglycerine-induced dilatation. Results: The participants were mainly normal weight non-smokers, without hypertension, diabetes, or established cardiovascular disease. The cases and controls had mean blood pressure 112/71 (SD 12/9) and 112/69 (SD 11/8) mmHg, body mass index 24.0 (SD 4.2) and 24.4 (SD 4.5) kg/m², and HbA1c 32.7 (SD 2.5) and 33.0 (SD 2.6) mmol/mol, respectively. For both groups, 4 (8%) were smokers. Mean FMD for the adults born very preterm or with extremely low birthweight was 0.17 mm (95% CI 0.14, 0.21) vs. 0.24 mm (95% CI 0.20, 0.28) for the controls (p = 0.01), corresponding to a percentage increase of 5.4% (95% CI 4.2, 6.6) and 7.6% (95% CI 6.2, 8.9), respectively (p = 0.02). The FMD relative to maximal nitroglycerine-induced dilatation was 20% and 31%, respectively (p = 0.001). Conclusions: Young adults born very preterm or with extremely low birthweight have significantly lower FMD compared with the term-born controls suggesting an increased risk of cardiovascular disease.

Keywords: cardiovascular risk; endothelial function; extremely low birthweight; flow-mediated dilatation; very preterm.

Figure 1

Flow chart of the study population in the study of vascular endothelial function in young adults born very preterm or with extremely low birthweight (PB/ELBW) and term-born controls, part of the Project Extreme Prematurity in Norway.

Figure 2

The artery diameter was first measured at baseline after 10 min of rest. Thereafter, occlusion of the right brachial artery was done with a blood pressure cuff on the forearm, inflated at least 50 mmHg above systolic blood pressure for 5 min. The next measurements were done at peak artery dilatation after release of occlusion. After a second 10-min resting period followed by sublingual nitroglycerine administration, the last measurements were done at peak artery dilatation.

Figure 3

Brachial artery diameter at baseline (blue), after flow-mediated dilatation (red), and after nitroglycerine induced dilatation (green) in young adults born very preterm or with extremely low birthweight (PB/ELBW) and term-born controls, presented as mean with 95% CI. Absolute flow-mediated dilatation was 0.17 mm (95% CI 0.14, 0.21) in the PB/ELBW group and 0.24 mm (95% CI 0.20, 0.28) in the control group. Dbaseline: brachial artery diameter at baseline; Dflowmediated: brachial artery diameter after flow-mediated dilatation; Dpeaknitro: brachial artery diameter after nitroglycerine induced dilatation.

Figure 4

Percentage flow-mediated dilatation (FMD) of the brachial artery from baseline in young adults born very preterm or with extremely low birthweight (PB/ELBW) and term-born controls, presented as mean with 95% CI. Percentage FMD was 5.4% (95% CI 4.2, 6.6) for PB/ELBW and 7.5% (95% CI 6.2, 8.9) for controls.

Figure 5

Endothelial-dependent dilatation capacity measured as flow-mediated dilatation in percent of nitroglycerine induced dilatation of the brachial artery in young adults born very preterm or with extremely low birthweight (PB/ELBW) and term-born controls presented as mean with 95% CI. Endothelial-dependent capacity was 20.1% (95% CI 16.1, 24.5) for PB/ELBW and 30.8% (95% CI 25.9, 35.6) for controls.

Figure 6

Percentage flow-mediated dilatation of the brachial artery in young adults born very preterm or with extremely low birthweight (PB/ELBW) born in year 1982–1985 (cohort 1, n = 21), 1991–1992 (cohort 2, n = 16), and 1999–2000 (cohort 3, n = 13), presented as mean with 95% CI. Percentage FMD was 5.8% (95% CI 4.0, 7.7) in cohort 1, 5.2% (95% CI 2.6, 7.4) in cohort 2, and 5.2% (95% CI 2.3, 8.2) in cohort 3.

Figure 7

Percentage flow-mediated dilatation (FMD) of the brachial artery in 24 men and 26 women born very preterm or with extremely low birthweight, and term-born controls (20 men and 29 women), presented as mean with 95% CI. In women, percentage FMD was 5.0% (95% CI 3.1, 7.0) for PB/ELBW vs. 8.6% (95% CI 7.0, 10.3) for controls. In men, percentage FMD was 5.8% (95% CI 4.2, 7.4) for PB/ELBW vs. 6.0% (95% CI 3.9, 8.1) for controls.