Effects of endothelin-related gene polymorphisms and aerobic exercise habit on age-related arterial stiffening: a 10-yr longitudinal study

Increased arterial stiffness has emerged as a strong predictor of future cardiovascular events and all-cause mortality. The aim of this study was to elucidate influences of endothelin (ET)-related genetic polymorphisms and regular physical activity on age-related arterial stiffening through a 10-yr longitudinal study. A decadal change in brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, was evaluated retrospectively among 92 volunteers (63？±？14 yr, 51 men). The targeted single-nucleotide polymorphisms were ET-A receptor SNP rs5333 (ET-A) and ET-B receptor SNP rs5351 (ET-B). Subjects with either ET-A TC or CC genotypes exhibited significantly greater increases in baPWV (+15.3？±？11.7 and +16.6？±？15.7%/dec, respectively) than ET-A TT genotype holders (+9.2？±？9.0%/dec), whereas subjects with the ET-B GG genotype showed a significantly greater increase in baPWV (+17.7？±？14.1%/dec) than other ET-B genotype holders (AA: +9.5？±？10.0%/dec; AG: +11.2？±？9.6%/dec). The combination of these ET-related genetic risks was associated with a 2.4 times greater decadal increase in baPWV compared with no genetic risk (+8.1？±？8.4 vs. 19.5？± 16.0%/dec). In contrast, individuals engaging in >15 METs·h/wk of aerobic exercise showed substantially smaller increases in baPWV (+5.0？±？9.7%/dec) compared with their physically inactive peers (approximately +13%/dec). These differences remained significant after adjusting for confounding factors, including baseline baPWV and ET-related genotype risk. Our current longitudinal study found that ET-related gene polymorphisms contribute to diverse age-related changes in arterial stiffness, and that regular sufficient aerobic exercise attenuates the age-related arterial stiffening independently of ET-related gene polymorphisms. NEW & NOTEWORTHY This 10-yr longitudinal study suggests that endothelin-related gene polymorphisms contribute to divergent increases in arterial stiffness with advancing age, whereas regular sufficient aerobic exercise attenuates age-related arterial stiffening independently of ET-related gene polymorphisms. This notion partly supports prevailing evidence that regular aerobic exercise contributes to a lower incidence of cardiovascular disease.