Distracting factors involving the high-intensity interval training as modulator of retinal microvascular phenotype and DNA methylation of SHC1 gene

This commentary refers to ‘High-intensity interval training modulates retinal microvascular phenotype and DNA methylation of p66Shc gene: a randomized controlled trial (EXAMIN AGE)’, by L. Streese et al., doi:10.1093/eurheartj/ehz196. We read with great interest the clinical trial by Streese et al.1 that investigated the effects of 12-week high-intensity interval training (HIIT) on retinal microvascular phenotype, seeking to correlate the alterations observed with SHC1 expression and DNA methylation in peripheral mononuclear cells and with plasma 3-nitrotyrosine levels in ageing subjects at increased cardiovascular risk. We sincerely congratulate the authors for their relevant work. However, we would like to address four aspects which might compromise the results interpretation. Streese et al.1 prescribed Nordic Walking training with intensities between 80% and 90% of the maximum heart rate (HRmax), which is equivalent to ∼75–85% of the maximal oxygen uptake (VO2max). However, these values do not necessarily reach the VO2max intensity zones required for characterization of HIIT, which is expected to attain an intensity of at least 90% VO2max2 for health subjects, or ≥80% VO2max (≥85% HRmax) for clinical populations.3 For 10 weeks, the sessions lasted 45 min, divided into 25 min, as the main part involving interval training (4 min at 80–90% HRmax by 3 min at 60–70% HRmax), and 20 min of warm-up and cool-down involving moderate-intensity continuous training (at 60–70% HRmax). Thus, 44% of the session’s time was performed only in moderate-intensity continuous exercise. Besides, the first 2 weeks of protocol involved only continuous training. The control group received physical activity (PA) recommendations based on the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice, which prescribes that individuals accumulate at least 30 min/day, 5 days/week of moderate-intensity PA (i.e. 150 min/week) or 15 min/day, 5 days/week of vigorous-intensity PA (75 min/week), or a combination of both.4 In addition, it also suggests the inclusion of muscle strength/resistance PA.4 Thus, there may be a very large variation in type, intensity, and duration of exercise for the control group. Besides, it is not clear if those recommendations were indeed performed by this group, stressing the results of FQPA (no changes with the intervention) and VO2max (reduction in values post-intervention) presented in the Table S1. Furthermore, a control group without exercise could contribute to better understanding the real effects of the HIIT. Although the primers described in Table S3 amplified three segments upstream the coding region, Figure 1C depicts two segments inside the coding region (+1/+676 sequence). Besides, based on the human SHC1 gene (ENST00000368445.9) described in www.ensembl.org, actually these segments are located far from the TSS, between −2900/−3900 sequence, which might compromise their transcriptional regulation. Conflict of interest: none declared.