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Although serum uric acid (UA) has been reported to be positively associated with increased arterial stiffness as evaluated by cardio-ankle vascular index (CAVI), UA also has an antioxidative effect that prevents endothelial damage. Therefore, the status of endothelial repair induced by endothelial damage might affect the correlation between UA and CAVI. To clarify the correlation between UA and CAVI in relation to endothelial repair activity, we performed a cross-sectional study with 246 Japanese men aged 60-69 years undergoing a general health check-up. The analysis was stratified by the median circulating level of CD34-positive cells because circulating levels of CD34-positive cells could indicate the degree of endothelial repair activity. Independent of known cardiovascular risk factors, among participants with high circulating levels of CD34-positive cells (0.95 cells/µL ≤), UA was significantly positively correlated with CAVI (standardized parameter estimate ß = 0.23, p = 0.009), but not among participants with low circulating levels of CD34-positive cells (< 0.95 cells/µL) (ß = 0.07, p = 0.445). Independent of established cardiovascular risk factors, UA levels were significantly positively correlated with increased arterial stiffness only among participants with aggressive endothelial repair as evaluated by circulating levels of CD34-positive cells. These results might help clarify some background mechanisms related to endothelial activity.
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Antígenos CD34 , Índice Vascular Coração-Tornozelo , Ácido Úrico , Rigidez Vascular , Humanos , Masculino , Ácido Úrico/sangue , Antígenos CD34/metabolismo , Idoso , Estudos Transversais , Pessoa de Meia-Idade , Japão , Doenças Cardiovasculares/sangue , Fatores de Risco , População do Leste AsiáticoRESUMO
AIM: To clarify the association between genetic factors related to angiogenesis and feeling of incomplete bladder emptying among older community-dwelling individuals. METHOD: A cross-sectional study of 1762 (607 men and 1155 women) older Japanese individuals aged 60-79 years with data on rs3025020 was conducted, because vascular endothelial growth factor (VEGF), which contributes to the progression of angiogenesis, has been reported to be positively associated with the minor allele (T) of polymorphism rs3025020. RESULTS: In the study population, 155 (103 men and 52 women) had feeling of incomplete bladder emptying. With rs3025020 (C/C) as the reference group, rs3025020 (T/T) was associated with a significantly higher odds ratio (OR) for feeling of incomplete bladder emptying. The adjusted ORs and 95% confidence intervals were 3.01(1.53, 5.93) in men and 2.48 (1.09, 5.66) in women, respectively. CONCLUSION: VEGF polymorphism rs3025020 was associated with feeling of incomplete bladder emptying among older community-dwelling individuals. Development of angiogenesis could be associated with feeling of incomplete bladder emptying in older individuals. Geriatr Gerontol Int 2024; 24: 1039-1044.
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Vida Independente , Fator A de Crescimento do Endotélio Vascular , Humanos , Masculino , Feminino , Idoso , Estudos Transversais , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/genética , Japão , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Genótipo , AngiogêneseRESUMO
Although fast eating speed has been associated with cardiovascular risk factors, no studies have reported an association between fast eating speed and atherosclerosis as evaluated by carotid intima-media thickness (CIMT). Rapid glucose ingestion is known to cause glucose spikes, which may accelerate atherogenesis and increase levels of growth differentiation factor 15 (GDF-15). Therefore, GDF-15 levels may influence the association between fast eating speed and atherosclerosis. To evaluate the association between eating speed and atherosclerosis in relation to GDF-15, this cross-sectional study analyzed 742 Japanese aged 60-69 years. They were required to have normal thyroid hormone levels, because both GDF-15 levels and atherosclerosis (CIMT ≥ 1.1 mm) can be influenced by thyroid dysfunction. Participants were stratified by the median GDF-15 level. A significant positive association was observed between fast eating speed and atherosclerosis, but only among participants with a high GDF-15 level: the sex- and age-adjusted odds ratios (95% confidence intervals) were 1.95 (1.09, 3.48) in participants with a high GDF-15 level, and 0.83 (0.37, 1.88) in those with a low GDF-15 level. This association remained even after further adjustment for thyroid function and metabolic factors. Serum concentrations of GDF-15 may mediate the association between fast eating speed and atherosclerosis.
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Aterosclerose , Espessura Intima-Media Carotídea , Fator 15 de Diferenciação de Crescimento , Humanos , Fator 15 de Diferenciação de Crescimento/sangue , Masculino , Feminino , Aterosclerose/sangue , Aterosclerose/etiologia , Estudos Transversais , Idoso , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Patients with primary focal hyperhidrosis (hyperhidrosis) are known to have higher levels of anxiety induced by sweating than those who do not. However, in hyperhidrosis, no scale has been developed to measure anxiety specific to hyperhidrosis symptoms. Therefore, this study aimed to develop an anxiety scale specific to hyperhidrosis symptoms (ASSHS) and to verify its reliability and validity. METHODS: Based on previous studies on hyperhidrosis and a preliminary survey conducted with 26 university students who met the diagnostic criteria for hyperhidrosis, 40 items that adequately reflected anxiety specific to hyperhidrosis symptoms were obtained. A survey was done to examine the internal consistency and validity of the our developed ASSHS. In total, 1,207 participants (680 male and 527 female; mean age ± standard deviation 18.7 ± 0.9 years) were included. A second survey (re-survey) was conducted three weeks later to verify the reliability. It included 201 participants (85 male and 116 female; mean age ± standard deviation 18.6 ± 0.7 years). The survey items included (1) the diagnostic criteria for hyperhidrosis, (2) our anxiety scale developed for primary focal hyperhidrosis symptoms (ASSHS), (3) Hyperhidrosis Disease Severity Scale (HDSS), (4) State-Trait Anxiety Inventory (STAI), (5) Hospital Anxiety and Depression Scale (HADS), (6) Dermatology Life Quality Index (DLQI), and (7) presence of anxiety induced by sweating. RESULTS: The results of the factor analysis revealed 10 items with one factor, "anxiety specific to hyperhidrosis symptoms." The alpha coefficient of the ASSHS was α = 0.94. The correlation coefficient between the scores at re-test was r = 0.75. A moderate positive correlation was found between the ASSHS, HDSS (r = 0.53), and anxiety induced by sweating (r = 0.47) (all p < 0.001). Additionally, participants with hyperhidrosis symptoms had significantly higher ASSHS scores than did those without hyperhidrosis symptoms (p < 0.001). Those with mild/moderate hyperhidrosis and those with severe hyperhidrosis had significantly higher the ASSHS scores than did those without hyperhidrosis (p < 0.001). CONCLUSIONS: This scale has sufficient reliability and validity as an instrument to measure anxiety specific to hyperhidrosis symptoms.
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Atherosclerosis and height loss are each reportedly associated with cardiovascular disease. However, no studies have found an association between atherosclerosis and height loss. A retrospective study of 2435 individuals aged 60-89 years who underwent annual health check-ups was conducted. Atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥ 1.1 mm. Height loss was defined as being in the highest quintile of height decrease per year, as in our previous studies. Among study participants, 555 were diagnosed as having atherosclerosis. Independent of known cardiovascular risk factors, atherosclerosis was positively associated with height loss. The adjusted odds ratio (OR) was 1.46 (95% confidence interval, 1.15, 1.83). Essentially the same associations were observed for men and women. The adjusted OR (95% CI) was 1.43 (1.01, 2.04) for men and 1.46 (1.07, 1.99) for women. Among older individuals, atherosclerosis is associated with height loss. This result can help clarify the mechanism underlying the association between height loss and cardiovascular disease.
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Aterosclerose , Doenças Cardiovasculares , Masculino , Humanos , Feminino , Espessura Intima-Media Carotídea , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Retrospectivos , Fatores de Risco , Aterosclerose/epidemiologia , Aterosclerose/diagnósticoRESUMO
To maintain normal level of thyroid hormone, especially for free thyroxine (FT4), individuals with latent thyroid gland damage might have required higher thyroid stimulating hormone (TSH) than those without latent thyroid gland damage. Anti-thyroid peroxidase antibody (TPO-Ab) is a main cause of auto-immune thyroiditis, and therefore euthyroid individuals positive for TPO-Ab might have latent damage to the thyroid gland. Therefore, the association between TSH values and TPO-Ab positivity may be useful to determine the influence of latent thyroid gland damage on requirement of TSH. Furthermore, because latent damage of thyroid might elevate TSH level but not FT4 level, those associations should be observed independent from FT4. This cross-sectional study analyzed 1431 Japanese with normal ranges of free triiodothyronine (FT3) and FT4. Since TPO-Ab is associated with atherosclerosis in euthyroid individuals, cardiovascular risk factors might underlie the association between TPO-Ab and TSH values. After adjusting for FT4 and known cardiovascular risk factors, the adjusted odds ratio (95% confidence interval) of TPO-Ab positivity for logarithmic value of TSH was 1.53 (1.20, 1.95). Essentially the same association was observed when the analysis was restricted to individuals without subclinical hypothyroidism (1.54 [1.15, 2.13]). Euthyroid individuals with latent thyroid gland damage might have increased the requirement of TSH.
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Hipotireoidismo , Tireotropina , Humanos , Estudos Transversais , PeroxidasesRESUMO
Cryptococcosis has become a major health problem worldwide and caused morbidity and mortality in immunocompromised patients, especially those infected with human immunodeficiency virus (HIV). Despite the global distribution of cryptococcosis, the number and types of the available antifungals are limited, and the treatment outcomes in HIV patients are generally poor. In this study, we screened a compound library and identified one tetrazole derivative as an efficient inhibitor of Cryptococcus neoformans and Cryptococcus gattii. We further designed and synthesized a series of tetrazole derivatives and determined their structure-activity relationship, demonstrating that tetrazole backbone-containing compounds could be developed as novel antifungal drugs with distinct mechanisms against Cryptococcus spp. Our findings provide a starting point for novel target identification and structural optimization to develop a distinct class of therapeutics for patients with cryptococcosis.
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Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Infecções por HIV , Humanos , Criptococose/tratamento farmacológico , Antifúngicos/farmacologiaRESUMO
Growth differentiation factor 15 (GDF-15), which modulates cellular energy balance, is reported to be positively associated with cardiovascular disease. However, there have been no reports about the association between serum GDF-15 concentration and atherosclerosis as evaluated by carotid intima-media thickness (CIMT) among the general population. A cross-sectional study of 536 Japanese individuals aged 60 to 69 years was conducted. To avoid the influence of abnormal cellular energy balance, this study only included participants who had a normal body mass index (BMI) and normal thyroid hormone (free thyroxine and free triiodothyronine) levels. A significant positive association between serum GDF-15 concentration and atherosclerosis was observed. In the sex- and age-adjusted model (Model 1), the odds ratio (OR) (95% confidence interval (CI)) for the logarithmic value of GDF-15 and atherosclerosis was 2.62 (1.67, 5.87). This association remained after adjusting for thyroid function and renal function (Model 2) and further adjusting for known cardiovascular risk factors (Model 3). The corresponding values were 2.61 (1.15, 5.93) for Model 2 and 2.49 (1.08, 5.71) for Model 3, respectively. Serum GDF-15 concentrations could help us to estimate the risk of atherosclerosis by indicating the status of cellular energy balance, which is related to mitochondrial activity among comparative healthy older individuals.
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AIM: This study aimed to clarify the influence of functional atherosclerosis on the association between periodontitis and chronic kidney disease (CKD). MATERIALS AND METHODS: A cross-sectional study of 998 older Japanese individuals aged 60-99 years who participated in an oral health check-up was conducted. Early and advanced periodontitis were defined as periodontal pocket depth of 4.0-5.9 mm and ≥6.0 mm, respectively. Functional atherosclerosis was defined as cardio-ankle vascular index ≥9.0. RESULTS: Of the 998 study participants, 238 (23.8%) had CKD. No significant associations between periodontitis and CKD were observed in participants without functional atherosclerosis. After adjusting for known cardiovascular risk factors, the odds ratio (OR) (95% confidence interval [CI]) was 1.31 (0.81-2.11) for early periodontitis and 0.74 (0.41-1.34) for advanced periodontitis. Significant positive associations were observed for participants with functional atherosclerosis; the adjusted ORs (95% CIs) were 1.76 (1.04-3.01) for early periodontitis and 1.95 (1.05-3.63) for advanced periodontitis. CONCLUSIONS: A significant positive association between periodontitis and CKD was established for older participants with functional atherosclerosis. No significant associations were observed for those without functional atherosclerosis. These results can help clarify the influence of periodontitis on systemic circulation.
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Aterosclerose , Periodontite , Insuficiência Renal Crônica , Humanos , Estudos Transversais , População do Leste Asiático , Periodontite/complicações , Periodontite/epidemiologia , Aterosclerose/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fatores de RiscoRESUMO
Height is inversely associated with inflammation that stimulates endothelial repair. In our previous study involving elderly men aged 60-69 years, we found that active arterial wall thickening, which is known as the process of endothelial repair, requires CD34-positive cells. As thyroid hormone regulates CD34-positive cell production and as the absence of thyroid cysts might indicate latent damage in the thyroid, the status of thyroid cysts possibly influences the association between height and active arterial wall thickening. We conducted a 2-year follow-up study of Japanese aged 60-69 years. For participants with thyroid cysts, height was significantly inversely associated with active arterial wall thickening (thyroid function and baseline CIMT adjusted odds ratio of active arterial wall thickening for one increment of standard deviation of height (5.7 cm for men and 4.8 cm for women), 0.66 [0.49, 0.89]), while for those without thyroid cysts, a positive tendency between the two parameters was observed (1.19 [0.96, 1.50]). An inverse association between height and active arterial wall thickening was observed only for elderly participants with thyroid cysts possibly because of a supportive role of thyroid hormone, as the absence of thyroid cysts might indicate latent damage in the thyroid.
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Previous studies have reported a close correlation between vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, and human T-cell leukemia virus 1 (HTLV-1). However, an association between genetic characteristics related to VEGF and HTLV-1 infection has not yet been reported. Because the VEGF polymorphism rs3025039 is inversely associated with serum concentrations of VEGF, we focus on rs3025039 in the present study. To clarify the association between the VEGF polymorphism rs3025039 and HTLV-1 infection, a cross-sectional study of 1924 Japanese individuals aged 60-79 years who participated in general health check-ups was conducted. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for HTLV-1 infection in relation to rs3025039 genotype were calculated with adjustment for known confounders. Compared with rs3025039 CC-homozygotes, (T) allele carriers had a significantly lower OR for HTLV-1 infection. The adjusted OR and 95% CI for HTLV-1 infection was 0.70 (0.54-0.91) (p = 0.009). Genetic characteristics related to lower angiogenesis activity might be associated with a lower chance of establishing HTLV-1 infection. Although further investigation is necessary, angiogenesis might play a crucial role in the establishment of HTLV-1 infection.
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Reactivation of Epstein-Barr virus (EBV) is associated with the etiopathogenesis of a broad spectrum of diseases. This study aimed to investigate the association between psychological distress and EBV serological reactivation among community-dwelling older people and assess the role of sex differences in this association. This population-based cross-sectional survey was conducted among individuals who underwent annual health checkups (N = 2,821; median age 72.4 years). EBV serological reactivation was defined as elevation of EBV early antigen immunoglobulin G titers, and psychological distress was defined as Kessler 6 scores ≥5. Multivariable logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (CI) for EBV serological reactivation and psychological distress. EBV serological reactivation and psychological distress were detected in 16.4% and 8.7% of participants, respectively. Women accounted for 71% (328/463) of those with EBV serological reactivation. Multivariable logistic regression analysis showed psychological distress was not significantly associated with EBV serological reactivation among all participants (OR 1.31, 95% CI: 0.95, 1.82; P = 0.102). A sex-stratified multivariable analysis showed a positive association among women (OR 1.45, 95% CI: 1.01, 2.08; P = 0.043), but no association among men. EBV serological reactivation was independently associated with psychological distress in community-dwelling older women. The sex difference in our results warrants further investigation to clarify the physiological mechanisms underlying the association.
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Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Feminino , Humanos , Masculino , Idoso , Infecções por Vírus Epstein-Barr/complicações , Estudos Transversais , Vida Independente , Anticorpos Antivirais , Japão/epidemiologia , Imunoglobulina GRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) and Japanese spotted fever (JSF; a spotted fever group rickettsiosis) are tick-borne zoonoses that are becoming a significant public health threat in Japan and East Asia. Strategies for treatment and infection control differ between the two; therefore, initial differential diagnosis is important. We aimed to compare the clinical characteristics of SFTS and JSF based on symptomology, physical examination, laboratory data, and radiography findings at admission. This retrospective study included patients with SFTS and JSF treated at five hospitals in Nagasaki Prefecture, western Japan, between 2013 and 2020. Data from 23 patients with SFTS and 38 patients with JSF were examined for differentiating factors and were divided by 7:3 into a training cohort and a validation cohort. Decision tree analysis revealed leukopenia (white blood cell [WBC] < 4000/µL) and altered mental status as the best differentiating factors (AUC 1.000) with 100% sensitivity and 100% specificity. Using only physical examination factors, absence of skin rash and altered mental status resulted in the best differentiating factors with AUC 0.871, 71.4% sensitivity, and 90.0% specificity. When treating patients with suspected tick-borne infection, WBC < 4000/µL, absence of skin rash, and altered mental status are very useful to differentiate SFTS from JSF.
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Exantema , Leucopenia , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Rickettsiose do Grupo da Febre Maculosa , Animais , Humanos , Japão/epidemiologia , Leucopenia/diagnóstico , Estudos Retrospectivos , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Rickettsiose do Grupo da Febre Maculosa/diagnósticoRESUMO
The postoperative increase in glucagon-like peptide-1 (GLP-1) is the main factor to improve glucose metabolism following sleeve gastrectomy (SG) in obese patients with type 2 diabetes. We investigated whether the ß-cell responsiveness to an injection of exogenous GLP-1 in the preoperative period could determine the postoperative glucose tolerance in 18 patients underwent SG. In the preoperative period, a regular oral glucose tolerance test (OGTT) and an exenatide-challenge during OGTT (Ex-OGTT) were performed to evaluate the ß-cell function and its responsiveness to GLP-1. The postoperative glucose tolerance was evaluated by another regular OGTT performed at 3 months after SG. The significant decrease in glucose levels with enhanced secretions of insulin and GLP-1 was observed in OGTT at 3 months after SG. The area under the curve of glucose from 0 to 120 minutes (AUC glucose0-120 min) and the insulinogenic index (I.I.) in OGTT at 3 months post-SG were significantly improved compared to those in preoperative period, but comparable with those in Ex-OGTT. AUC glucose0-120 min and I.I. in OGTT at 3 months post-SG were significantly correlated with not only those in Ex-OGTT, but also those in the preoperative regular OGTT. Conversely, the correlations calculated by the Spearman's ρ were stronger in the latter than the former. This exenatide-challenge protocol might be useful to estimate glucose tolerance and insulin secretion after SG, however, it may be insufficient to improve predictability of a patient who is likely to achieve a significant benefit on glucose metabolism from receiving SG.
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Diabetes Mellitus Tipo 2 , Peptídeo 1 Semelhante ao Glucagon , Humanos , Teste de Tolerância a Glucose , Secreção de Insulina , Exenatida , Projetos Piloto , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/complicações , Obesidade/cirurgia , Insulina/metabolismo , Glucose , Gastrectomia/métodos , Glicemia/metabolismoRESUMO
Structural arterial stiffness can be evaluated with carotid intima-media thickness (CIMT). Functional arterial stiffness can be evaluated with cardio-ankle vascular index (CAVI). A positive association between CIMT and tooth loss has been reported, but no studies have evaluated the association between CIMT and tooth loss in relation to functional arterial stiffness (functional atherosclerosis). A cross-sectional study of 1235 Japanese individuals aged 40-89 years was conducted. Tooth loss was defined as being in the lowest tertile for the number of remaining teeth (≤20 in men and ≤19 in women). Functional atherosclerosis was defined as CAVI ≥ 9.0. Independent of known confounding factors, CIMT was positively associated with tooth loss only in participants without functional atherosclerosis. Adjusted odds ratios for tooth loss and a 1 standard deviation increment in CIMT were 1.27 (1.04-1.55) for participants without functional atherosclerosis and 0.99 (0.77-1.26) for participants with functional atherosclerosis. CIMT and functional atherosclerosis had a significant effect on tooth loss; the fully adjusted p-value for the interaction on tooth loss was 0.019. Independent of known confounding factors, CIMT is positively associated with tooth loss only in participants without functional atherosclerosis. This finding helps clarify the influence of the progression of arterial stiffness on tooth loss because the progression of structural atherosclerosis might have a beneficial influence on the maintenance of the microcirculation.
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Height loss starting in middle age is reportedly significantly associated with death due to cardiovascular disease. Impaired blood flow is the main pathology in cardiovascular disease. Hematopoietic stem cells such as CD34-positive cells play an important role in maintaining the microcirculation and preventing impaired blood flow by activating endothelial repair and angiogenesis. Therefore, circulating CD34-positive cell count could be associated with height loss. To clarify the association between circulating CD34-positive cell count and height loss, we conducted a follow-up study of 363 Japanese men aged 60-69 years over 2 years. Height loss was defined as being in the highest quartile of height decrease per year. Independent of known cardiovascular risk factors, circulating CD34-positive cell count was significantly inversely associated with height loss. The fully adjusted odds ratio (OR) and 95% confidence interval (CI) of height loss for circulating CD34-positive cell count (logarithmic values) was 0.49 (0.32, 0.74). This study suggests that a lower capacity to maintain the microcirculation due to a fewer CD34-positive cells might affect height loss.
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Doenças Cardiovasculares , Idoso , Antígenos CD34 , Contagem de Células , Estudos Transversais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The ratio of free triiodothyronine (FT3) to free thyroxine (FT4) (FT3/FT4), a maker of peripheral thyroxin deiodination, could indicate activity of thyroid hormone. Since positive association between subclinical hypothyroidism (SCH) and chronic kidney disease (CKD) was reported, clarifying the association among FT3/FT4, SCH, and CKD could be an efficient tool to make a strategy for preventing CKD. A cross-sectional study with 1724 Japanese with normal thyroid hormone was conducted. Significant positive association between SCH and CKD was observed; the adjusted odds ratio (OR) and 95% confidence interval (95% CI) was 2.23 (1.38, 3.59). Even though, FT3/FT4 was found to be inversely associated with CKD whereas positively associated with SCH; the adjusted ORs and 95% CIs for 1 standard deviation (SD) increment of FT3/FT4 were 0.51 (0.35, 0.74) for CKD and 2.40 (1.34, 4.29) for SCH, respectively. FT3/FT4 was also found to be positively associated with SCH without CKD but not those with CKD; 1 SD increment of FT3/FT4 were 3.44 (1.72, 6.91) for SCH without CKD and 1.11 (0.40, 3.06) for SCH with CKD, respectively. Although further investigation is necessary, present study indicates that higher activity of peripheral thyroxin deiodination might have beneficial association on absence of CKD even among SCH which is positively associated with CKD.
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Subclinical hypothyroidism (SCH) was reported to be associated with accelerating endothelial dysfunction, which is recognized as one of the upstream mechanisms that leads to glomerular injury (lower glomerular filtration rate (GFR)). SCH was also reported to be associated with hyperglycemia, which is associated with higher hemoglobin A1c (HbA1c) levels and induces endothelial dysfunction. Therefore, SCH status could influence the association between HbA1c and reduced eGFR. To clarify those associations, we conducted a prospective study of 1580 Japanese individuals who participated in an annual health check-up in 2014 with 2.8 years of follow-up. All participants had free triiodothyronine (T3) and free thyroxine (T4) levels in the normal range. Among study participants, 88 were diagnosed as having SCH. Even though no significant correlation was observed between HbA1c and annual change in estimated GFR among participants without SCH (multi-adjusted standardized parameter estimate (ß) = 0.03, p = 0.250), a significant inverse association was observed among participants with SCH (ß = -0.26, p = 0.014). When those analyses were performed among participants who were not taking glucose lowering medication, the observed associations were essentially the same: ß = 0.03, p = 0.266 for participants without SCH and ß = -0.32, p = 0.006 for participants with SCH, respectively. Therefore, SCH status could influence the association between HbA1c and renal function.
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Among euthyroid individuals, having an anti-thyroid peroxidase antibody (TPO-Ab) titer in the normal range (negative) is positively associated with atherosclerosis as evaluated based on carotid intima-media thickness (CIMT). Atherosclerosis is an established risk factor for cardiovascular disease, but no significant association between yearly progression in CIMT and cardiovascular disease has been reported. Therefore, clarifying the association between having a TPO-Ab titer in the normal range and yearly progression in CIMT (i.e., active arterial wall thickening) among euthyroid individuals could help inform strategies for preventing cardiovascular disease. We conducted a prospective study of 1069 Japanese subjects with free triiodothyronine and free thyroxine levels within the normal range. Having a TPO-Ab titer in the normal range was significantly positively associated with baseline atherosclerosis and significantly inversely associated with active arterial wall thickening. After adjusting for known confounding factors, the adjusted odds ratio (OR) and 95% confidence interval (CI) of log (TPO-Ab titer) for baseline atherosclerosis and active arterial wall thickening was 2.16 (1.07, 4.35) and 0.59 (0.37, 0.93), respectively. Since progression in CIMT is a process of aggressive endothelial repair, deficient endothelial repair inhibits active arterial wall thickening. Therefore, high-normal TPO-Ab titers might induce a deficiency in endothelial repair.
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Aggressive endothelial repair results in the progression of both structural and functional atherosclerosis, while insufficient endothelial repair worsens functional but not structural atherosclerosis. Aging increases the risk of inadequate endothelial repair. Since low-density lipoprotein cholesterol (LDLc) activates endothelial repair, LDLc may be positively associated with structural atherosclerosis but inversely associated with functional atherosclerosis in older individuals. This cross-sectional study analyzed 1458 participants aged 60 to 79 years. We defined structural atherosclerosis as a carotid intima-media thickness (CIMT) of at least 1.1 mm and functional atherosclerosis as a cardio-ankle vascular index (CAVI) of at least 9.0. LDLc was significantly positively associated with structural atherosclerosis and significantly inversely associated with functional atherosclerosis, independently of known cardiovascular risk factors. For 1 standard increment of LDLc (28 mg/dL for men and 29 mg/dL for women), the odds ratios and 95% confidence intervals after adjustment for known cardiovascular risk factors were 1.28 (1.10, 1.50) for structural atherosclerosis and 0.85 (0.75, 0.96) for functional atherosclerosis. LDLc activates endothelial repair, which results in the development of structural atherosclerosis but maintains endothelial function in older individuals. To evaluate atherosclerosis in clinical practice, the combination of structural and functional assessment of atherosclerosis could be informative.