The impact of age on endothelial dysfunction measured by peripheral arterial tonometry in a healthy population-based cohort - the Malmo offspring study

Background/Aims The reactive hyperaemia index (RHI) assesses endothelial function, with a proposed cut-off of <1.67 for prevalent endothelial dysfunction (ED). However, uncertainties remain about whether this cut-off is age-dependent and applicable in healthy individuals. We aimed to explore ED in relation to age within a large population-based cohort of young to middle-aged, healthy individuals. Methods Within the Malmo Offspring Study, a total of 1812 subjects (50.9% women, mean age 48 & PLUSMN; 11 years) were included. Post-occlusion/pre-occlusion ratio of the pulsatile signal amplitudes in the non-dominant upper arm was used to calculate RHI by EndoPat & REG;. ED was defined as RHI < 1.67. Multivariable regression models were used to explore associations between ED and age. Results Prevalent ED was found in 534 (29.5%) participants. In subjects aged & LE;30 years, ED was present in 47.4% compared to 27.6% in subjects & GE;30 years (p < 0.001). In multivariable logistic regression analyses, ED was associated with younger age (p < 0.001), higher BMI (p < 0.001) and current smoking (p < 0.001). No sex differences were observed. Conclusion In a large healthy population, RHI < 1.67, an early marker of endothelial dysfunction, was more prevalent in younger individuals, implying that RHI might not be a suitable measure of endothelial function in individuals under 30 years of age. Our findings suggest that low RHI in young, healthy individuals may not necessarily indicate true ED but rather an artefact of the limited ability of young and healthy arteries to dilate post-occlusion. Therefore, the term pseudo-ED may be applicable to young individuals with low RHI values. PLAIN LANGUAGE SUMMARY What is the context? The endothelium is a thin layer of cells that lines the inside of blood vessels, and its proper function is crucial for the maintenance of vascular health. Endothelial dysfunction (ED) is an early marker of cardiovascular disease and is characterised by impaired dilation of blood vessels, which can lead to reduced blood flow and increased risk of heart attacks and strokes. The reactive hyperaemia index (RHI) is a widely used non-invasive test that measures endothelial function by evaluating the dilation of blood vessels in response to temporary occlusion. What is new? This study aimed to investigate the relationship between age and ED in a large population-based cohort of young to middle-aged healthy individuals. The results showed that prevalent ED was more common in younger individuals, with 47.4% of participants aged & LE;30 years having ED, compared to 27.6% in those & GE;30 years. The study also found that ED was associated with higher BMI and current smoking, but no sex differences were observed. What is the impact? The findings suggest that the proposed RHI cut-off of <1.67 for prevalent ED may not be applicable to individuals under the age of 30, as young and healthy arteries may have limited ability to dilate post-occlusion, resulting in low RHI values that do not necessarily indicate true ED. Therefore, the term pseudo-ED may be more appropriate for young individuals with low RHI values.

Automated summary

This study investigates the relationship between age and endothelial dysfunction (ED) in a large population-based cohort. The study finds that the proposed cut-off of RHI < 1.67 for prevalent ED may not be applicable to individuals under the age of 30, as young and healthy arteries may have limited ability to dilate post-occlusion, resulting in low RHI values that do not necessarily indicate true ED.