Adults with Down syndrome challenge another paradigm: When aging no longer entails arterial hypertension

The paradigmatic relationship between aging and atherosclerotic cardiovascular events does not apply to all patient populations. Though trisomy 21 (T21) and its phenotypic expression, Down syndrome (DS), are conditions that involve premature aging, the cardiovascular system of adults with DS appears to be particularly spared from this early senescence. Despite a higher prevalence of some classic cardiovascular risk factors in adults with DS than in the general population, such as dyslipidemia, obesity, or sedentarism, these individuals do not develop hypertension or suffer major cardiovascular events as they age. The protective factors that prevent the development of hypertension in T21 are not well established. Genes like RCAN1 and DYRK1A, both on chromosome 21 and over-expressed in adults with DS, appear to play a major role in cardiovascular prevention. Their regulation of the renin-angiotensin-aldosterone system (RAAS) and neprilysin synthesis could underlie the constitutive protection against arterial hypertension in adults with DS and explain the absence of increased arterial stiffness in this population. A better understanding of these molecular pathways could have enormous implications for the clinical management of adults with DS and might foster the development of novel therapeutic targets in cardiovascular prevention for the general population.