Comment on Serés-Noriega et al. Use of the Steno T1 Risk Engine Identifies Preclinical Atherosclerosis Better Than Use of ESC/EASD-2019 in Adult Subjects With Type 1 Diabetes at High Risk. Diabetes Care 2022;45:2412–2421

We read with great interest the recent study in Diabetes Care by Serés-Noriega et al. (1), which was performed in adults with type 1 diabetes (T1D) and no previous cardiovascular disease but who were selected for their high cardiovascular disease risk. They concluded that the Steno Type 1 Risk Engine seems better for identifying carotid atherosclerotic plaques detected by B-mode ultrasonography than the 2019 ESC guidelines on diabetes, prediabetes, and cardiovascular diseases, which were developed in collaboration with the European Association for the Study of Diabetes (respective C statistic 0.691 vs. 0.538). They claim in their introduction that arterial stiffness is a marker of subclinical atherosclerosis, in line with a previous study from our group (reference 12 in Serés-Noriega et al. [1]) (2). We think that this comment may cause some confusion as to what arterial stiffness means in the context of cardiovascular event prediction, with potential implications for clinical practice, clinical research, and future clinical guidelines in this area, and we believe it needs clarification.

Arterial stiffness, or arteriosclerosis, refers to the thickening and hardening of the arterial wall that usually accompanies aging. This has a major adverse effect on the macrovascular (cardiovascular events) and microvascular (e.g., chronic kidney disease) beds. Because arteriosclerosis integrates the cumulative burden of known and unknown cardiovascular risk factors on the elastic wall of large arteries along the life span of an individual (even prebirth), it is not surprising that it has utility for discriminating high-risk adults with T1D according to the Steno Type 1 Risk Engine (C statistic 0.879) (2).

Atherosclerosis is characterized by the patchy accumulation of lipids in the intima, whereas arteriosclerosis mainly affects the media. Both share several pathophysiological mechanisms, including inflammation of the artery wall and its calcification, and they often coincide. Atherosclerosis is likely a consequence rather than a cause of arteriosclerosis, although each condition may promote the other (3).

Currently, the assessment of arterial stiffness by applanation tonometry with the measurement of the carotid-femoral pulse wave velocity is at least as simple to perform as the assessment of carotid plaques by B-mode ultrasonography. It is also economical and well standardized and can be accomplished in 15–20 min. Notably, in contrast to carotid plaque assessment by ultrasonography, it can be performed by trained nonphysician personnel and is more sensitive to the effects of interventions known to reduce cardiovascular risk (e.g., SGLT2 inhibitors or statins), with significant observable improvements in only a few months. Perhaps more importantly, cross-sectional studies in people with T1D have demonstrated the association between arterial stiffness and retinopathy and nephropathy in addition to cardiovascular events (4), and there is prospective evidence that it can predict the progression of nephropathy, the development of cardiovascular events, and even all-cause mortality (5).

Finally, we agree with Serés-Noriega et al. (1) that there remains an eminently glucocentric approach to vascular complications in T1D, driven mainly by the results of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) landmark study. In this line, we believe that a hemodynamic vision of vascular complications in T1D should no longer be overlooked, aligning with the current evidence on how assessment of arterial stiffness may have utility for predicting both macro- and microvascular damage in adults with T1D.