While we examined a range of potential confounders, unmeasured confounders, or mediators that influence cardiac hypertrophy (e.g. renin–angiotensin system activity, sympathetic nervous system activity, abnormalities of lipid metabolism, inflammation, etc.)may have contributed to the associations observed.29 Echocardiography was only carried out in the most recent round of data collection and hence the possibility of reverse causality, namely that increased LVM in early-life results in raised BP and increased rate of rise in midlife BP cannot be excluded. This evidence concerns the gene REN and cardiac hypertrophy.