Mediterranean diet, neutrophil count, and atherosclerosis

This commentary refers to ‘Mediterranean diet, neutrophil count, and carotid intima-media thickness in secondary prevention: the CORDIOPREV study’, by H. Boughanem et al., https://doi.org/10.1093/eurheartj/ehae836 and the discussion piece ‘Discussion on Mediterranean diet, neutrophil count, and atherosclerosis’, by J. Lopez-Miranda, https://doi.org/10.1093/eurheartj/ehaf171. Boughanem et al.1 published in a recent issue a study titled, ‘Mediterranean diet, neutrophil count, and carotid intima-media thickness in secondary prevention: the CORDIOPREV study’. This longitudinal study (baseline, follow-ups at 5 and 7 years) examined the association among neutrophil count, long-term dietary interventions, and the carotid intima-media thickness (cIMT), as a surrogate marker of pre-clinical atherosclerosis.1 The study found that patients at baseline in the highest tertile of neutrophil count had in comparison with the lowest tertile higher cIMT (P < .01).1 The study found that patients following a Mediterranean diet after 7 years had a reduced cIMT and showed also a significant decrease in neutrophil count after the same time period (P < .05), compared with baseline.1 The authors concluded that neutrophils may represent ‘a target for preventing atherosclerosis. A Mediterranean diet could serve as an effective dietary strategy to reduce neutrophil levels and potentially slow the progression of atherosclerosis, offering a new neutrophil-reducing therapy concept’.1 Some comments are needed to evaluate the results of this study in a more exhaustive manner regarding the following points [(i)–(iii)]: (i) cIMT location of measurement: the cIMT was measured at three sites of the common carotid artery (CCA).1 However, the authors did not mention at which level of the CCA measurement was performed.1 The authors missed to discuss the two major recommendations as to cIMT measurement protocols, namely a one-location vs. a multi-locations based cIMT measurement.2,3 That a one-location based cIMT measurement (i.e. within the same segment of the CA tree), generally at the far wall of the CCA, is more reliable, is vividly debated, and is contradicted as multiple studies showed.3 In contrast, a multi-locations based cIMT measurement will reflect more accurately the vessel state considering foremost that atherosclerosis, while a systemic disease presents in an asymmetric fashion.4 To measure only at one site as the authors1 performed may coincide with a normal carotid artery (CA) segment, but be still within an atherosclerotic altered section, providing consequently an inaccurate cIMT value. (ii) Follow-up visit: Related to point (i), the authors did not explain how precisely the baseline CA segment used for cIMT measurement was retrieved for the follow-up visits. If no precise baseline documentation occurred, very likely the follow-up cIMT measurements were performed in a different CCA segment with potentially different wall characteristics. The calculated rate of change will be unavoidably inaccurate. (iii) Cardiac synchronization: The authors also did not mention if cIMT measurement was synchronized with the cardiac cycle, namely the end-diastolic phase. Mean differences between the two cardiac phases up to 0.041 mm were reported.5 Without cardiac synchronization, the cIMT data are not comparable, nor cross-sectionally nor longitudinally. In conclusion: cIMT is a delicate surrogate marker of pre-clinical atherosclerosis. High-precision measurements and a detailed measurement protocol, especially for longitudinally studies, need to be in place. The cIMT is expressed at a sub-millimeter level (e.g. normal range <0.6–0.9 mm). Slightest inaccuracies will add up quickly to categorize subjects into different cIMT groups, from which important clinical and pathophysiological conclusions are drawn. Considering the multiple methodological issues in the study by Boughanem et al.,1 the cIMT results and related conclusions should be considered with caution.