In young and healthy people, the aorta has a well-functioning Windkessel effect. Thereby, pulsatile blood flow is transformed into a steady flow supplying peripheral tissues, which enables a steady blood supply of the organs (esp. coronary arteries), reduces cardiac afterload and reduces pulsatile stress on the distal vasculature (3, 4). Arterial-ventricular interaction describes the effect of arterial stiffening on left ventricular function. With increased arterial stiffness, the pulse wave velocity increases. Thus, the reflected wave returns to the heart early (i.e., in late systole). This increases late systolic afterload, which affects thick-thin myofilament interactions and cross-bridge dissociation, leading to impaired relaxation, an important part of diastole (5). As a result, systolic or diastolic heart failure may evolve.

Arterial stiffness is a well-known predictor of cardiovascular morbidity and mortality in the general population (6). It has been extensively studied in adults with traditional cardiovascular risk factors such as, e.g., diabetes, dyslipidemia or hypertension, which are typically acquired as mid-aged adults. Though there is evidence that several types of CHD or genetic connective tissue disorders are associated with increased arterial stiffness, the etiology, extent, physiologic impact, changes with age and prognostic implications of vascular changes in this context are not well understood to date (7).

The most well studied congenital lesions in the field of arterial stiffness are BAV, CoA, and MFS—all of which are associated with intrinsic aortic wall abnormalities that extend beyond the actual anatomic lesion of aortic dilation vs. narrowing (8, 9). Over the last two decades, it has become evident that these histologic abnormalities translate to increased arterial stiffness on a physiologic level (10–12).

Aortic stiffening (and often dilation) in these groups starts during childhood and progresses with age. While MFS patients have general aortic stiffening together with thinning of the common carotid intima-media, this is not seen in BAV patients who have proximally increased aortic stiffness and pulse wave reflection (13–16). Similarly, on a histologic level, MFS and BAV patients have thinner intima, a lower expression of contractile vascular smooth muscle cells, and more elastic fiber thinning compared to controls (Grewal et al.). However, other features of cardiovascular ageing differed between the BAV and MFS in this study (Grewal et al.). Interestingly, there is also evidence that the risk for obstructive coronary atherosclerosis is decreased rather than increased in both MFS and BAV patients alike, supporting the above functional, structural and histologic findings (Dolmaci et al.).

Linking outcome to micro- and macro scalar arterial characteristics in CHD patients with aortopathies would be an important step to personalized medicine. Ultimately, longitudinal follow-up will be crucial in determining changes in arterial stiffness, central blood pressure and diastolic function over time and in response to changes in medical management.

Survival of patients with MFS has increased throughout the last few decades (17, 18). Likewise, improved treatment options for patients with CHD have led to an increasing number of children surviving well into adulthood, i.e., they are exposed to the adverse effects of increased arterial stiffness much longer than the average adult with atherosclerotic cardiovascular disease (19). At the same time, adults with CHD are more likely to have typical acquired cardiovascular risk factors (20). Most importantly, they have a strikingly increased risk for cardiovascular events, i.e., adults with CHD with ≤2 cardiovascular risk factors have more than twice the risk for major adverse cardiovascular events compared to non-CHD adults with ≥5 risk factors (20).

Among CoA patients, e.g., the risk for acquired cardiovascular risk factors appears particularly high (21, 22). Moreover, in MFS the body mass index may not be a good predictor of overweight and obesity as the relative muscle mass is decreased and the proportion of fat is increased (23). Additionally, overweight or obese MFS patients may be at increased risk for adverse aortic events (24).

To date, many aortopathy patients are still restriced from exercise, even though the European Society of Cardiology (ESC) has published exercise recommendations specific for the type of underlying aortopathy and degree of aortic dilation (25). In fact, limited mouse and human data suggests a beneficial effect of aerobic training on aortic root growth without major adverse events (26–28). If aortopathy patients were more physically active, this would likely increase muscle mass and lower the risk of overweight and obesity and perhaps, preventing the development of secondary cardiovascular risk factors.

Thus, over the last 50 years, the focus has shifted from improving early survival to optimizing long term outcome. Minimizing acquired cardiovascular risk factors plays an increasing role in the counseling of patients with CHD associated aortopathies.

Aortopathies in CHD and genetic aortopathies are heterogeneous with variable mechanisms for increased arterial stiffness and varying risks for aortic complications. What all aortopathy patients have in common though is that they are exposed to increased arterial stiffness for a life-time—as opposed to the typical patient with acquired cardiovascular disease. The combination of a congenital aortopathy and acquired cardiovascular risk factors may be a particularly risky combination. Further research is needed to identify personalized treatment strategies for patients with aortopathies, taking into account their individual risk factors. Perhaps most importantly, we as medical professionals need to focus more on minimizing additional cardiovascular risk factors from an early age by encouraging a healthy lifestyle and exercise.