ART may up future risk of hypertension
Children who were conceived through assisted reproductive technologies (ART) showed premature vascular ageing which persisted over 5 years and progressed to arterial hypertension in adolescence and young adulthood, thus placing them at an increased risk of developing cardiovascular (CV) disease even though no other classical CV risk factors were present, reveals a study.
“The increased prevalence of arterial hypertension in ART participants is what is most concerning … arterial hypertension may represent the first detectable clinically relevant endpoint in humans,” said study principal investigator Dr Emrush Rexhaj from Bern University Hospital in Bern, Switzerland. “ART children [are] at a six times higher rate of hypertension than children conceived naturally.”
This begs the question: “Is the mode of conception a marker for future CV risk?”, as raised by the editorialists in an accompanying commentary. [J Am Coll Cardiol 2018;72:1275-1277]
“There is growing evidence that ART alters the blood vessels in children … It only took 5 years for differences in arterial blood pressure [BP] to show,” Rexhaj said.
What ART does to blood vessels
The current study was a follow-up of 97 participants 5 years after the initial study which assessed vascular dysfunction in children who were conceived through ART. Approximately 75 percent of the original cohort were included, comprising 54 young and apparently healthy ART-conceived participants (mean age 16.5 years) who were matched by age and sex to 43 controls (mean age 17.4 years) who were conceived naturally. [J Am Coll Cardiol 2018;72:1267-1274]
Even 5 years after the initial study, premature vascular ageing persisted in adolescents conceived through ART, as indicated by 25 percent less flow-mediated dilation of the brachial artery (p<0.001), increased carotid-femoral pulse-wave velocity (p=0.033), and greater intima-media thickness (p<0.01) compared with controls.
According to the authors, differences in vascular function between the two groups were similar in magnitude as those seen during childhood 5 years earlier and persisted in the current study.
“In adolescent and young adult ART subjects, the presence of these risk factors evolved into increased arterial BP and a significant increase in the prevalence of established arterial hypertension,” said Rexhaj and co-authors.
Measurements from 24-hour ambulatory BP monitoring (ABPM) showed that ABPM readings (systolic BP, 119.8 vs 115.7 mm Hg; p=0.03; diastolic BP, 71.4 vs 69.1; p=0.02) and BP variability were significantly greater in ART-conceived participants than controls.
This translates to a significantly higher prevalent of arterial hypertension among the ART-conceived participants, with eight out of the 52 subjects having fulfilled the ABPM criteria of arterial hypertension* vs only one out of the 43 control participants who achieved so (p=0.041).
“These data underscore the potential of ART to increase CV risk in this rapidly growing group,” stated the researchers, who believed that epigenetic modifications induced by exposure of gametes or embryos to variable physical and hormonal environments may lead to vascular changes.
A CV risk marker?
“If adolescent hypertension risk is really sixfold higher in ART patients … consequences for longevity will be vast given the millions of patients whose births were achieved by using ART methods,” wrote the editorialists.
The importance of the issue may have been understated, they said, as the relatively small study cohort excluded high-risk population such as those from multiple birth pregnancies and whose mothers had excess risk factors (for instance, diabetes, eclampsia, and chronic hypertension).
“Early study, detection, and treatment of ART-conceived individuals may be the appropriate ounce of prevention,” suggested the editorialists. “The future of precision medicine-guided approaches should incorporate emerging clinical factors, such as history of ART conception in a growing proportion of the population, in addition to an array of novel molecular markers [for assessing CV risk.]”