BACKGROUND: Low-density lipoprotein cholesterol (LDLc) is regarded as a risk factor for endothelial dysfunction. However, LDLc stimulates the proliferation of hematopoietic stem cells (CD34-positive cells), which contribute to endothelial repair. Therefore, LDLc may have a beneficial influence on the endothelium of individuals with lower endothelial repair activity. METHODS: This cross-sectional study included 245 men aged 60-69 years. Endothelial repair activity was categorized by the circulating levels of CD34-positive cells based on median values. The status of endothelium was evaluated using the cardio-ankle vascular index (CAVI). RESULTS: Among individuals with low levels of circulating CD34-positive cells, LDL-c levels were significantly inversely correlated with CAVI and positively correlated with circulating CD34-positive cells. No significant correlations were observed among the participants with high levels of circulating CD34-positive cells. Among low levels of CD34-positive cells, the adjusted standardized parameter (β) and p value were -0.24 (p = 0.021) for CAVI and 0.41 (p < 0.001) for CD34-positive cells, whereas among high levels of CD34-positive cells, the corresponding values were 0.03 (p = 0.738) and -0.09 (p = 0.355). CONCLUSION LDLc has a beneficial influence on endothelial health among individuals with low endothelial repair activity, possibly by stimulating the proliferation of hematopoietic stem cells.
Humans ; Middle Aged ; Male ; Aged ; Cross-Sectional Studies ; Cholesterol, LDL/blood* ; Endothelium, Vascular/physiology* ; Antigens, CD34/blood* ; Hematopoietic Stem Cells

BACKGROUND: Epstein-Barr (EB) virus infection stimulates the production of vascular endothelial growth factor (VEGF), which contributes to the progression of angiogenesis. Angiogenesis plays an important role in the development of atherosclerosis. Since serum anti-early antigen EB virus IgG (EBV EA-IgG) titer is a sign of active EB virus infection, EBV EA-IgG titer could be associated with atherosclerosis. The number of minor (T) alleles in VEGF polymorphism rs3025039 has been reported to be inversely associated with serum VEGF concentration, suggesting that rs3025039 might have a strong influence on the association between EBV EA-IgG titer and atherosclerosis. By focusing on the role of VEGF in the development of atherosclerosis, this study aimed to investigate the association between active EB virus infection and atherosclerosis. METHODS: A cross-sectional study of 2,661 older Japanese individuals aged 60-89 years who participated in annual health check-ups during 2017-2019 was conducted. Logistic regression was used to evaluate the association between EBV EA-IgG titer and atherosclerosis in relation to rs3025039 genotype. The influence of rs3025039 (T) allele carrier status on the association between EBV EA-IgG titer and atherosclerosis was also evaluated by using logistic regression. RESULTS: Among rs3025039 CC-homozygotes, with the lowest EBV EA-IgG titer tertile as the reference, the multivariable odds ratio (95% confidence interval) was 1.11 (0.82, 1.50) for the medium tertile and 1.07 (0.78, 1.47) for the high tertile. Among rs3025039 (T) allele carriers, the corresponding values were 1.44 (0.88, 2.36) and 1.88 (1.15, 3.05), respectively. There was a significant interaction between rs3025039 (T) allele carrier status and the association between EBV EA-IgG titer and atherosclerosis (adjusted p = 0.0497). CONCLUSION EBV EA-IgG titer was significantly positively associated with atherosclerosis only among participants who are genetically less likely to have progressive angiogenesis. An angiogenesis-related genetic factor was revealed as a determinant of the association between EBV EA-IgG titer and atherosclerosis. These findings introduce a novel concept that could explain the association between viral infection and atherosclerosis.
Humans ; Aged ; Male ; Middle Aged ; Female ; Japan/epidemiology* ; Atherosclerosis/virology* ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/genetics* ; Epstein-Barr Virus Infections/virology* ; Polymorphism, Single Nucleotide ; Cross-Sectional Studies ; Herpesvirus 4, Human ; Antigens, Viral/immunology* ; Antibodies, Viral/blood* ; Immunoglobulin G/blood* ; Genotype ; East Asian People

BACKGROUND: Subclinical hypothyroidism (SCH) has been reported to be associated with lower endothelial progenitor (CD34-positive) cell count, whereas an inverse association between circulating CD34-positive cell count and height loss is documented. Reports indicate height loss to be associated with all-cause mortality, and a higher CD34-positive cell count has been shown to predict longer life. Therefore, evaluating the association between SCH and height loss provides mechanistic insights underlying the association between height loss and mortality risk. METHODS: A prospective study involving 1,599 participants with normal free triiodothyronine (T3) and free thyroxine (T4) levels was conducted to determine the association between SCH and height loss.Since the free T4 level influences the supply of active thyroid hormone (free T3), the analysis was stratified by the median free T4 level. Height loss was defined as the highest quintile of annual height decrease. RESULTS: SCH was positively associated with height loss in participants with low-normal free T4 levels (below the median), but not in those with high-normal free T4 levels (at or above the median). After adjusting for sex, age, free T3 level, atherosclerosis, and known cardiovascular risk factors, the adjusted odds ratios (95% confidence interval) for height loss were 1.88 (1.02, 3.47) and 1.92 (1.02, 3.62) in the low-normal free T4 group. The corresponding values in the high-normal free T4 group were 0.37 (0.08, 1.69) and 0.43 (0.09, 1.97). CONCLUSION SCH could influence height loss, and free T4 might influence the association between SCH and height loss in euthyroid individuals. These results clarify the mechanisms underlying the association between height loss and mortality risk.
Humans ; Hypothyroidism/epidemiology* ; Thyroxine/blood* ; Male ; Female ; Prospective Studies ; Middle Aged ; Body Height ; Adult ; Aged ; Risk Factors

Based on the social context of an aging society and surveys conducted since 2020, the need for comprehensive perspectives and approaches that consider patients'psychosocial background and a cross-organ perspective has been identified. As a result, a new quality and ability, namely comprehensive attitudes toward patients, has been established as part of the core curriculum for medical education in FY2022. Specific learning objectives include "holistic perspectives and approaches," "community perspectives and approaches," "life perspectives and approaches," and "social perspectives and approaches". An educational design that draws on multiple learning theories to enable reflection on one's own way of being has been proposed to integrate abstract and concrete, conceptual and experiential, and self and others perspectives. It is expected that this medical education will lead to improvement in the well-being of individuals, families, and communities.

BACKGROUND: Aging is a process that increases oxidative stress. Increased oxidative stress leads to the development of atherosclerosis and mitochondrial dysfunction. Mitochondria contribute to energy production that might have a beneficial influence on maintaining muscle strength. Therefore, the height-related single nucleotide polymorphism (SNP) rs17081935, which is also reported to be associated with mitochondrial metabolism, might be associated with reduced muscle strength and this association might be affected by atherosclerosis status. To clarify those associations, a cross-sectional study of 1374 elderly Japanese individuals aged 60-89 years was conducted. METHODS: Logistic regression was used to clarify the association between rs17081935 and reduced handgrip strength. Since atherosclerosis might affect handgrip strength, participants were stratified by atherosclerosis status. Reduced handgrip strength was defined as being in the lowest quintile of handgrip strength (< 25.6 kg for men and < 16.1 kg for women). RESULTS: No significant associations were found between a minor allele of rs17081935 and reduced handgrip strength among elderly participants without atherosclerosis. A significant inverse association was observed among elderly participants with atherosclerosis. After adjusting for known cardiovascular risk factors and height, the adjusted odd ratio (OR) and 95% confidence interval (CI) for reduced handgrip strength and a minor allele of rs17081935 were 1.13 (0.86, 1.43) for elderly participants without atherosclerosis and 0.55 (0.36, 0.86) for those with atherosclerosis, respectively. CONCLUSION A minor allele of the height-related SNP rs17081935 was significantly inversely associated with reduced handgrip strength among older individuals with atherosclerosis, but not among those without atherosclerosis.
Aged ; Aged, 80 and over ; Atherosclerosis/epidemiology* ; Body Height ; Cross-Sectional Studies ; Female ; Hand Strength ; Humans ; Japan/epidemiology* ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Prevalence

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway. The minor allele of single nucleotide polymorphism (SNP) in breast cancer suppressor BRCA1-associated protein (BRAP), which has a common etiology with HTLV-1 infection, has been reported to be positively associated with carotid atherosclerosis, but inversely associated with hypertension. Therefore, HTLV-1 infection may be inversely associated with hypertension by activating endothelial maintenance, including atherosclerosis. To clarify these associations, a cross-sectional study was conducted using 2989 Japanese individuals aged 60-99 years participating in a general health check-up. METHODS: Logistic regression models were used to clarify the association between HTLV-1 and hypertension. Platelet levels stratified analyses were also performed since platelet production, which plays a crucial role in endothelium maintenance, can be stimulated by activating the NF-κB pathway. RESULTS: HTLV-1 infection was found to be significantly inversely associated with hypertension, particularly in subjects with high platelet levels (≥ second tertiles of platelet levels); the fully adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.75 (0.62, 0.92) for total and 0.64 (0.50, 0.82) for high platelet levels, respectively. Further analysis of the non-hypertensive subjects demonstrated that HTLV-1 infection was significantly positively associated with atherosclerosis in subjects with the highest tertile of platelet levels (2.11 [1.15, 3.86]) but not in subjects with low platelet levels (first and second tertiles of platelet level) (0.89 [0.57, 1.39]). CONCLUSION Asymptomatic HTLV-1 infection is inversely associated with hypertension, possibly by activating endothelial maintenance, including atherosclerosis progression.
Aged ; Aged, 80 and over ; Carotid Artery Diseases/virology* ; Cross-Sectional Studies ; Female ; HTLV-I Infections/complications* ; Human T-lymphotropic virus 1/physiology* ; Humans ; Hypertension/virology* ; Japan/epidemiology* ; Male ; Middle Aged

BACKGROUND: A positive association between handgrip strength and blood pressure has been reported. Since these factors are linked to the condition of the endothelium, the activity of endothelial repair might influence the association between handgrip strength and hypertension. METHODS: A cross-sectional study was conducted with 257 Japanese men aged 60-69 years who underwent an annual health checkup. As individuals with high level of circulating CD34-positive cells might show active endothelial repair, which plays an important role in vascular homeostasis, participants were stratified by circulating CD34-positive cell levels, using the median value of this population (0.96 cells/μL) as the cutoff. RESULTS: Independent of known cardiovascular risk factors, for participants with a high CD34-positive cell, handgrip strength is significantly positively associated with hypertension (odds ratio and 95% confidence interval of hypertension for 1 standard deviation increment of handgrip strength were 1.85 (1.19, 2.88) but not for participants with a low CD34-positive cell (0.91 (0.61, 1.37)). CONCLUSION The positive association between handgrip strength and hypertension is limited to high CD34-positive cells. This result may help clarify the role of vascular homeostasis in maintaining muscle strength.

BACKGROUND: We investigated the association between psychological distress and oral health status/oral health-related quality of life (OHQoL) in Japanese community-dwelling people. METHODS: We conducted a cross-sectional study using data from the Nagasaki Islands Study. A total of 1183 (455 men and 728 women) has been analyzed in this study. Psychological distress was measured using the Kessler Psychological Distress Scale (K6). Oral health status was measured by dental examination. The OHQoL was measured using the General Oral Health Assessment Index (GOHAI). We defined the total score of ≥5 points on the K6 as high psychological distress (high-K6 group). RESULTS: The multiple linear regression analysis to identify the GOHAI showed that gender, K6, the total number of teeth, the number of dental caries, and visiting a dental clinic within the past 6 months significantly associated with the GOHAI. Among all of these variables, high-K6 (≥ 5) was a substantial contributing factor of the GOHAI (β = - 0.23, 95% Cl - 2.31 to -1.41, p < 0.0001). CONCLUSIONS It is likely that the individual with high psychological distress was strongly related to poor OHQoL even in the general population.
Aged ; Cross-Sectional Studies ; Dental Caries/epidemiology* ; Female ; Humans ; Independent Living/statistics & numerical data* ; Japan/epidemiology* ; Linear Models ; Male ; Middle Aged ; Oral Health/statistics & numerical data* ; Quality of Life/psychology* ; Sex Factors ; Stress, Psychological/epidemiology*

BACKGROUND: Human T cell leukemia virus type-1 (HTLV-1) stimulates inflammation activity. Our previous study revealed a positive association between asymptomatic HTLV-1 infection and advanced periodontitis among elderly Japanese individuals with low levels of hematopoietic activity (reflected by reticulocyte levels). Since low hematopoietic activity has been correlated with low-grade inflammation and low-grade inflammation is associated with atherosclerosis, the status of atherosclerosis could, in turn, determine the nature of this association. METHODS: To this end, a cross-sectional study of 907 elderly Japanese individuals (aged 60-99 years), who had participated in dental health check-up during the period 2016-2018, was conducted. Advanced periodontitis was defined as periodontal pocket ≥ 6.0 mm. RESULTS: Among the study population, 295 (32.5%) were found to have atherosclerosis defined as a carotid intima-media thickness (CIMT) of ≥ 1.1 mm. HTLV-1 infection was positively associated with advanced periodontitis in participants with atherosclerosis, but no significant associations were observed among the participants without atherosclerosis. The known risk factors' (including reticulocyte and CIMT) adjusted odds ratio (OR) and 95% confidence interval (CI) of advanced periodontitis were OR 2.01 and 95% CI 1.06-3.81 for participants with atherosclerosis and OR 0.61 and 95% CI 0.34-1.12 for participants without atherosclerosis. CONCLUSION This study found a significant association between HTLV-1 infection and advanced periodontitis among elderly Japanese with atherosclerosis. However, this association is absent in individuals without atherosclerosis, suggesting that atherosclerosis might act as a determinant in the association between HTLV-1 infection and advanced periodontitis among elderly Japanese.

BACKGROUND: Even 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. METHODS: We 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. RESULTS: In 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)). CONCLUSIONS γ-GTP revealed to have ambivalent association with hypertension and atherosclerosis. Active endothelial repair that is associated with atherosclerosis might have beneficial association with hypertension.