Childhood height inversely associated with ischaemic stroke, intracerebral haemorrhage
Children aged 7 to 13 years with shorter stature appear to be at increased risks of ischaemic stroke (IS) or intracerebral haemorrhage (ICH), a study has found. Importantly, the association of childhood height with these stroke subtypes persists regardless of a substantial increase in the average height among the children.
“Our results support the potential role of early-life exposures associated with growth before midchildhood in stroke genesis,” the authors said.
The study included 311,009 Danish schoolchildren (49 percent female) who had their height measured from 7–13 years. Average height increased by 4.1 cm in girls and 4.2 cm in boys at 7 years and by 7.3 cm in girls and 8.8 cm in boys at 13 years.
During a median follow-up of 31.1 years, 5,313 women and 7,645 men developed IS (80.4 percent) or ICH (19.6 percent). [Stroke 2018;49:579-585]
Cox proportional hazards regressions showed that height at 7 years was inversely and significantly associated with IS in both sexes. Specifically, each z-score increase in height (equivalent to about 5.2 cm in girls and 5.1 cm in boys) reduced the risk of developing IS by 11 percent in women (hazard ratio [HR], 0.89; 95 percent CI, 0.87–0.92) and by 10 percent in men (HR, 0.90; 0.88–0.92).
A similar pattern of association was observed for ICH in men (HR, 0.89; 0.84–0.94) but not in women (HR, 0.97; 0.91–1.04). Men in the lowest height quintile had an elevated risk of ICH.
The observed associations between childhood height and the two stroke subtypes were consistent across all childhood ages (up to 13 years). However, growth between 7 and 13 years (expressed per 0.5 z-score change) showed no significant association with the risk of IS (women: HR, 1.03; 1.00–1.66; men: HR, 1.02; 0.99–1.50) or ICH (women: HR, 0.98; 0.92–1.04; men: HR, 0.99; 0.94–1.05).
Findings of the present study are consistent with those reported in three previous studies and have implications for understanding disease pathogenesis rather than for clinical risk prediction, the authors said. [Stroke 2000;31:869-874; Stroke 2007;38:264-270; J Epidemiol Community Health 2012;66:18-23]
“Attained adult height is an indicator of growth conditions during childhood, timing of puberty and genetic height potential,” they continued. The strong inverse associations between height at 7 years and IS in both sexes, as well as with ICH in men, and the limited indications of childhood growth being associated with these two stroke subtypes suggest that the main effects of height on stroke are initiated before 7 years, already well before entering puberty.
Because some strokes occur relatively early in adult life, the authors pointed out that it is likely that early-life exposures have a greater influence on stroke early in adulthood compared with stroke diagnosed later in life.
The above hypothesis is supported by evidence from the Emerging Risk Factors Collaboration, which showed that the inverse associations of height with stroke were not appreciably altered after controlling for long-term smoking, adiposity, inflammation biomarkers, blood pressure, lipids and diabetes mellitus, thus reducing the likelihood that these well-known adult risk factors are mediators of the inverse associations. [Int J Epidemiol 2012;41:1419–1433]
Despite the strengths of the study, including its prospective design and mandatory height assessments, the authors admitted that they were unable to evaluate the magnitude of the inverse associations for childhood height against corresponding measurements in adulthood, or to attempt to disentangle the independent effects of childhood vs adult measures on stroke risk.
“Future studies should focus on the mechanisms underlying the relationship between childhood height and later stroke,” they said.