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Platelets and circulating CD34-positive cells have been reported to contribute to vascular repair (endothelial repair and developing atherosclerosis). And because hypertension is known to be a strong vascular impairment factors, it should also influence the respective numbers of these factors. To clarify the clinical importance of platelets on vascular repair, we conducted a cross-sectional study of 567 Japanese men aged 60-69 who underwent an annual health check-up between 2013 and 2015. Multiple linear regression analysis of non-hypertensive subjects adjusting for classical cardiovascular risk factors showed that although platelet count did not significantly correlate with carotid intima media thickness (β = −0.05, p = 0.356), it did positively correlate significantly with the natural log of the number of circulating CD34-positive cells (β = 0.26, p < 0.001). In hypertensive subjects, a significant positive correlation was seen between platelets and intima media thickness (β = 0.19, p = 0.008), whereas no significant correlation was seen between platelet count and the natural log of the number of circulating CD34-positive cells (β = 0.11, p = 0.119). Our results indicate that platelet count is an indicator of vascular repair activity (endothelial repair and developing atherosclerosis). Additionally, hypertension might mask the beneficial effects of circulating CD34-positive cells.

BackgroundEven though there is bidirectional association between hypertension and atherosclerosis, atherosclerosis itself is involved in the process of endothelial repair. To clarify the association of endothelial repair with hypertension, a cross-sectional study was conducted.MethodsWe conducted a cross-sectional study of 562 elderly Japanese men aged 60–69. As gamma-glutamyl transpeptidase (γ-GTP) could act as a marker of oxidative stress that injures endothelial cell and higher levels of CD34-positive cell indicate a higher activity of endothelial repair, we therefore performed a CD34-positive level specific analysis of γ-GTP on atherosclerosis and hypertension.ResultsIn the present study population, hypertension was independently and positively associated with atherosclerosis (multivariable odds ratio (OR) = 2.09 (1.30, 3.35)). Among participants with high CD34-positive cells, γ-GTP showed significant and positive association with atherosclerosis (OR of the log-transformed value of γ-GTP (OR) = 2.26 (1.32, 3.86)) but not with hypertension (OR = 0.77 (0.51, 1.17)). Among participants with low CD34-positive cells, even γ-GTP showed no significant association with atherosclerosis (OR = 0.92 (0.51, 1.68)), but was significantly and positively associated with hypertension (OR = 1.99 (1.27, 3.12)).Conclusionsγ-GTP revealed to have ambivalent association with hypertension and atherosclerosis. Active endothelial repair that is associated with atherosclerosis might have beneficial association with hypertension.

Age-related disruption of microvascular endothelium exacerbates hypertension and sarcopenia; and atherosclerosis is a well-known biological response to vascular endothelial injury. Therefore, prevalence of atherosclerosis among hypertensive elderly subjects may partly indicate the presence of an appropriate response to endothelial injury. We conducted a cross-sectional study of 795 elderly hypertensive Japanese subjects aged 60-89 years. Since platelet level is an indicator of vascular repair activity, subjects were stratified by platelet counts. No significant association between handgrip strength and subclinical carotid atherosclerosis (carotid intima-media thickness (CIMT) ≥1.1mm) was observed for subjects with lower platelet counts, while a significant positive association was observed for subjects with higher platelets. Adjusted odds and 95% confidence intervals of subclinical carotid atherosclerosis for 1 standard deviation increments in handgrip strength were 0.86 (0.61, 1.22) for subjects with lower platelets and 1.82 (1.26, 2.64) for subjects with higher platelets. A positive association between handgrip strength and subclinical carotid atherosclerosis exists in hypertensive elderly subjects with higher, but not lower, platelet counts. These results lead us to speculate that subjects with a beneficial influence on prevention of sarcopenia (maintenance of handgrip strength) may possess the capacity of active endothelial repair that causes atherosclerosis.

Age-related physical changes, such as low-grade inflammation and increased oxidative stress, induce endothelial repair and cause active arterial wall thickening by stimulating the production of CD34+ cells (the principal mediators of atherosclerosis). Despite this, aggressive endothelial repair (progressing atherosclerosis) might cause a wasting reduction in CD34+ cells, which could result in a lower capacity of endothelial repair and hypertension. As yet, no prospective study has clarified the association of circulating CD34+ cells with active arterial wall thickening. We conducted a prospective study of 363 men aged 60-69 years who participated in a general health checkup at least twice from 2014-2017. The circulating CD34+ cell count was significantly positively associated with active arterial wall thickening among subjects without hypertension (n = 236), but not among subjects with hypertension (n = 127). The fully adjusted odds ratios (ORs) of active arterial wall thickening for the logarithmic circulating CD34+ cell count were 1.83 (1.19, 2.84) and 0.69 (0.36, 1.32) for subjects without and with hypertension, respectively. Circulating CD34+ cells are positively associated with active arterial wall thickening in subjects without hypertension. this study demonstrates a means to clarify the mechanisms of endothelial repair in elderly subjects. Recently, bone marrow-derived hematopoietic stem cells (immature cells, such as CD34+ cells) have been revealed to play a major role in vascular homeostasis 1-3. It is likely that the number of circulating CD34+ cells could indicate the capacity of endothelial maintenance 4-6. However, it is known that hematopoietic bone marrow activity declines with age 7-10 , which might induce a lower capacity of endothelial maintenance in elderly subjects. Furthermore, aging is a well-known cause of endothelial injury 11,12 which subsequently induces endothelial repair. In addition, the aggressive endothelial repair that causes atherosclerosis might induce a wasting reduction of circulating CD34+ cells 6,13 which result in a shortage of the mediators of endothelial repair. Moreover, inadequate endothelial repair might cause hypertension in elderly individuals 14. These previous studies indicate that there are close connections among the age-related decline of bone marrow activity, age-related endothelial injury, and the wasting reduction of circulating CD34+ cells. Platelets are also known to play an important role in vascular inflammation and vessel wall remodeling 15,16. Indeed, platelets promote the mobilization of bone marrow-derived CD34+ cells into the peripheral blood 17-21 , and CD34+ cells also induce platelet elevation 22,23. Furthermore, platelets have been reported to play an important role in the initial development of atherosclerotic lesions 24 , and not only induce the differentiation of human CD34+ cells into endothelial cells, but also into foam cells, which contribute to the development of atherosclerosis 25. Therefore, platelets also play an important role in the a...

Aim: The cardio-ankle vascular index (CAVI) reflects functional arterial stiffness, which is related to endothelial dysfunction. CD34-positive cells carry out an important function in endothelial repair. However, there have been no reports assessing the association between CAVI and the number of circulating CD34-positive cells.Methods: We carried out a cross-sectional study of 249 Japanese men, aged 60-69 years, who underwent annual health checkups between 2013 and 2015. As individuals with high levels of circulating CD34-positive cells might indicate the influence of consumptive reduction of circulating CD34-positive cells as a result of aggressive endothelial repair, participants were stratified by circulating CD34-positive cell levels, using the median value in this population (0.95 cells/μL) as the cut-off.Results: For participants with low circulating CD34-positive cell levels, logarithmic values of circulating CD34-positive cells were inversely associated with CAVI (multivariable standardized parameter estimate [β] = −0.22, P = 0.014), but not for participants with high levels (β = −0.04, P = 0.638). In addition, even when no significant associations between CAVI and carotid intima-media thickness were detected for participants with low circulating CD34-positive cell levels (β = −0.02, P = 0.865), significant positive associations were identified for participants with high levels (β = 0.22, P = 0.028). Conclusions:As circulating CD34-positive cell count might indicate endothelial repair activity, the present results show that CAVI is affected by insufficient endothelial repair in individuals with low circulating CD34-positive cell counts. Our results also show that a positive association between CAVI and carotid intima-media thickness exists only in individuals with aggressive endothelial repair, which indicates the presence of organic arterial disease, such as atherosclerosis.

AimAlthough several risk factors contribute to the development of sarcopenia, whether preclinical atherosclerosis contributes to the risk of sarcopenia is not established. The present cross‐sectional study aimed to investigate if there is an association between preclinical atherosclerosis and muscle strength among two ethnic populations.MethodsParticipants included individuals aged ≥40 years and enrolled in the third follow‐up examination of the Andhra Pradesh Children and Parents Study, India, and in the baseline assessments of the Nagasaki Islands Study, Japan. Preclinical atherosclerosis was evaluated by carotid intima‐media thickness, brachial‐ankle pulse wave velocity, cardio‐ankle vascular index. The association of carotid intima‐media thickness and pulse wave velocity/cardio‐ankle vascular index with handgrip strength (HGS) was analyzed separately in the sexes and for hypertensive status from the two cohorts using a multivariable linear regression model.ResultsData on a total of 1501 participants in India and 3136 participants in Japan were analyzed. Carotid intima‐media thickness was negatively associated with HGS in non‐hypertensive Indian men (B coefficient = −5.38, P = 0.036). Arterial stiffness was also associated with HGS in non‐hypertensive Indian men (B = −0.97, P = 0.001), but not in hypertensive Indian men. Same as Indian men, we found the significant associations between arterial stiffness and HGS in non‐hypertensive women in both India and Japan (B = −0.44, P = 0.020, B = −0.63, P = 0.016, respectively), but not in hypertensive women.ConclusionsThe negative association between preclinical atherosclerosis and HGS was dominantly found in non‐hypertensive participants. Geriatr Gerontol Int 2018; 18: 1071–1078.

Height is reported to be inversely associated with cardiovascular disease. And platelets play an important role in vascular remodeling by supporting CD34-positive cells. To clarify the association between height and platelet, we conducted a cross-sectional study of 219 elderly Japanese men. Since hemoglobin concentration is influenced by vascular remodeling activity, an analysis stratified by hemoglobin level was performed. An inverse association was seen between height and platelet count in subjects with a high hemoglobin concentration (≥ 14.5 g/dL), but not in subjects with a low hemoglobin concentration (< 14.5 g/dL). The standardized parameter estimates (β) were β = −0.22, p = 0.019 for subjects with high hemoglobin, and β = −0.01, p = 0.931 for subjects with low hemoglobin. We also found a positive association between platelets and carotid intima media thickness (CIMT) and circulating CD34-positive cells in subjects with high hemoglobin (partial correlation coefficient (r) = 0.21, p = 0.037 and r = 0.40, p =< 0.001), but not in subjects with low hemoglobin (r = 0.04, p = 0.710 and r = 0.06, p = 0.544). In subjects with a high hemoglobin concentration, platelets were inversely associated with height, and positively associated with CIMT and circulating CD34-positive cells. These results indicate that subjects with a short stature activate vascular remodeling to a much greater extent than subjects with a tall stature.