Abstract
Vessel wall stiffening is an important clinical parameter, but it is unknown whether platelets, key elements in the pathogenesis of arterial thrombosis, are associated with arterial stiffness. The present studies sought to determine whether mean platelet volume (MPV), a potential marker of platelet activation, is linked to vascular elasticity as assessed by the augmentation index (AIx), in 15,010 individuals from the population-based Gutenberg Health Study. Multivariable analysis showed that MPV in both males (β 0.776; 95thCI [0.250;1.16]; p = 0.0024) and females (β 0.881[0.328;1.43]; p = 0.0018) is strongly associated with AIx. Individuals with MPV and AIx above the sex-specific medians had worse survival. Association analysis between MPV-related genetic variants and arterial stiffness identified four genetic variants in males and one in females related with AIx. Cox regression analysis for mortality identified one of these joint genetic variants close to ring finger protein 145 gene (RNF145, rs10076782) linked with increased mortality (hazard ratio 2.02; 95thCI [1.35;3.02]; p = 0.00061). Thus, these population-based data demonstrate a close relation between platelet volume as a potential marker of platelet activation and arterial stiffness in both sexes. Further research is warranted to further elucidate the mechanisms underlying larger platelets‘ role in arterial stiffening including the role of shared common genetics.
Highlights
The role of platelets in causing increased vascular stiffness is much less well defined[5,6,7,8,9]
Presented augmentation index (AIx) values are estimated for the subgroups below the 5th% and above 95th% of mean platelet volume (MPV)
Individuals with cardiovascular risk factors (CVRFs) had higher AIx compared to the sample without CVRFs
Summary
The role of platelets in causing increased vascular stiffness is much less well defined[5,6,7,8,9]. It is of outmost importance to better understand the interaction between arterial stiffness and parameters of platelet activation such as mean platelet volume (MPV) with regard to underlying cellular, molecular and genetic mechanisms and their clinical impact. Several studies suggest that vessel wall stiffening is an important clinical target, but it is unknown to what extent platelets, key elements in the pathophysiology of arterial thrombosis, are associated with arterial stiffness. The Gutenberg Health Study (GHS), as a large, prospective population-based cohort study in Western Germany, offers the potential to explore this relation in depth. To the best of our knowledge, this is the first study to investigate the relation between mean platelet volume (MPV), a potential marker of platelet activation including its known genetic variants, and vascular stiffness, in a large adult general population study sample
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