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

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: Hepatocyte growth factor (HGF) may act as a possible biochemical index for vascular damage, although evidence for the association between HGF and carotid intima-media thickness (CIMT) is limited. Since both HGF and circulating CD34-positive cells play an important role in endothelial repair, circulating CD34-positive cell levels may influence the association between HGF and CIMT. METHODS: We conducted a cross-sectional study of 269 elderly Japanese men aged 60-69 years who had undertaken an annual medical checkup from 2014 to 2015. RESULTS: The median value for circulating CD34-positive cells was 0.93 cells/μL. Among the study population, 135 men showed low circulating CD34-positive cell levels (≤ 0.93 cells/μL). By multivariable linear regression analysis, HGF was found to be significantly positively associated with CIMT only to participants with low circulating CD34-positive cell levels, with a multi-adjusted β of 0.26 (p = 0.005) and 0.002 (0.986) for low and high circulating CD34-positive cell levels, respectively. In addition, a significant interaction was observed between HGF and circulating CD34-positive cell levels (low and high) on CIMT (multivariable p value of 0.049). A positive association exists between HGF and CIMT in elderly Japanese men, limited to participants with low circulating CD34-positive cell levels. CONCLUSION A positive association exists between HGF and CIMT in community-dwelling elderly Japanese men, which is limited to participants with low numbers of circulating CD34-positive cells. Our findings indicate that circulating CD34-positive cell levels could determine the influence of HGF on CIMT in elderly Japanese men.
Aged ; Antigens, CD34 ; blood ; Biomarkers ; blood ; Carotid Intima-Media Thickness ; Cross-Sectional Studies ; Hepatocyte Growth Factor ; metabolism ; Humans ; Japan ; Male ; Middle Aged