Arterial stiffness linked to small-, large-fiber neuropathy

A recent study has shown the association of greater arterial stiffening with both ocular (small) and peripheral (large) fiber neuropathies.

A team of investigators explored the associations of arterial stiffness with retinal nerve layer thickness, retinal sensitivity, corneal nerve measures, peripheral nerve conduction velocities, amplitudes, and vibration perception thresholds using population-based cross-sectional data from The Maastricht Study, which included 9,188 participants (mean age 59.5 years, 50.2 percent women, 21 percent had diabetes).

Linear regression analyses were performed, adjusting for potential confounders and testing for interactions by sex and glucose metabolism status (prediabetes and type 2 diabetes vs normal glucose metabolism). [J Hypertens 2025;43:1945-1952]

Following adjustments, increased arterial stiffness correlated with lower Z scores for retinal nerve layer thickness (standardized beta coefficient [SBC], ‒0.04, 95 percent confidence interval [CI], ‒0.07 to 0.00), mean retinal sensitivity (SBC, ‒0.06, 95 percent CI, ‒0.09 to ‒0.03), corneal nerve measures (SBC, ‒0.05, 95 percent CI, ‒0.09 to ‒0.01), peripheral nerve conduction velocities (SBC, ‒0.05, 95 percent CI, ‒0.08 to ‒0.03), and tibial nerve amplitude (SBC, ‒0.05, 95 percent CI, ‒0.08 to ‒0.01).

Furthermore, greater arterial stiffness also correlated with higher Z scores for mean peripheral vibration perception thresholds (SBC, 0.06, 95 percent CI, 0.03‒0.08).

Similar associations were noted for individual components, but no significant association was found between the Z score for peroneal nerve amplitude (SBC, 0.00, 95 percent CI, ‒0.04 to 0.04) and that for sural nerve amplitude (SBC, 0.00, 95 percent CI, ‒0.04 to 0.03). These findings were comparable between men and women, as well as in people across different glucose metabolism strata.

“These results were independent of important confounders, such as diabetes, hypertension, renal insufficiency, and prior cardiovascular disease,” the investigators said. “Future longitudinal research is needed to clarify whether arterial stiffening is a direct cause of neuropathy.”

Mechanism

It remains unclear how arterial stiffness and neuropathy are connected, but a potential explanation involves microvascular dysfunction, which may result from mechanical stress exerted by increased pulsatile energy on endothelial cells. [J Appl Physiol (1985) 2018;125:1871-1880]

“Endothelial dysfunction involves impaired regulation of vasodilation and vasoconstriction as well as impairment of antithrombotic and anti-inflammatory properties, setting the stage for a chronic inflammatory response, creating a … cycle that further exacerbates endothelial dysfunction,” the investigators said. [J Mol Cell Cardiol 2022;168:58-67; Neurology 2021;97:e329-e340]

Moreover, blood flow may be obstructed by localized thrombosis within the microcirculation, which then results in inadequate nutrient delivery to the nerves while simultaneously promoting heightened permeability of adjacent blood vessels. [Curr Pharm Des 2012;18:1478-1493]

“Interestingly, we found that greater arterial stiffness was associated with lower peripheral nerve conduction velocities but was only partially associated with lower peripheral nerve amplitudes,” the investigators said.

“This may be because the process of demyelination (ie, lower peripheral nerve conduction velocity) occurs first, while axonal loss (ie, lower peripheral nerve amplitude) manifests at a more advanced stage, as has been reported in previous studies,” they added. [Hand Clin 2002;18:231-241; Proc Natl Acad Sci U S A 1990;87:9828-9832]