Wen-Hui Fang

Frailty and Its Impact on Health-Related Quality of Life: A Cross-Sectional Study on Elder Community-Dwelling Preventive Health Service Users

Background The purpose of this study was to identify the incidence of frailty and to investigate the relationship between frailty status and health-related quality of life (HRQoL) in the community-dwelling elderly population who utilize preventive health services. Methods People aged 65 years and older who visited a medical center in Taipei City from March to August in 2011 for an annual routine check-up provided by the National Health Insurance were eligible. A total of 374 eligible elderly adults without cognitive impairment had a mean age of 74.6±6.3 years. Frailty status was determined according to the Fried frailty criteria. HRQoL was measured with Short Form-36 (SF-36). Multiple regression analyses examined the relationship between frailty status and the two summary scales of SF-36. Models were adjusted for the participants sociodemographic and health status. Results After adjusting for sociodemographic and health-related covariables, frailty was found to be more significantly associated (p<0.001) with lower scores on both physical and mental health-related quality of life summary scales compared with robustness. For the frailty phenotypes, slowness represented the major contributing factor in the physical component scale of SF-36, and exhaustion was the primary contributing factor in the mental component scale. Conclusion The status of frailty is closely associated with HRQoL in elderly Taiwanese preventive health service users. The impacts of frailty phenotypes on physical and mental aspects of HRQoL differ.

Metabolic Syndrome and Short-Term Heart Rate Variability in Adults with Intellectual Disabilities.

Metabolic syndrome (MetS) increases the risk of cardiovascular events. Heart rate variability (HRV) represents autonomic functioning, and reduced HRV significantly increases cardiovascular mortality. The aims of the present paper are to assess the prevalence of MetS in adults with intellectual disabilities (ID), the difference in short-term HRV between the healthy and ID population, and the association of short-term HRV with MetS. In this study, we analyzed 129 ID subjects who participated in routine health check-ups in October 2010. We measured their metabolic components and evaluated the relationships of MetS with short-term HRV indices. The study found that MetS and obesity are common in persons with ID. ID subjects have significantly lower HRV than healthy adults, and persons with ID persons with MetS have significantly lower HRV than ID subjects without MetS. The individual components of MetS are differentially associated with HRV in ID men and women. Metabolic syndrome adversely affects autonomic cardiac control, and reduced autonomic cardiac control could contribute to an increased risk of subsequent cardiovascular events in individuals who exhibit metabolic syndrome. Sex differences in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in ID women compared with ID men.

Sex-specific association between nerve growth factor polymorphism and cardiac vagal modulation.

Objective Substantial research has shown that anxiety disorders are associated with decreased cardiac vagal tone, which is a known risk factor for cardiac vulnerability. A functional nerve growth factor (NGF) polymorphism (rs6330, c.104C > T, p.Ala35Val) has been associated with anxiety such that in males but not females, T-allele carriers exhibit higher levels of trait anxiety. Here we investigate whether the nonsynonymous NGF variant has an effect on cardiac autonomic control. Methods From 705 adults initially screened for medical and psychiatric illnesses, a final cohort of 580 healthy Han Chinese (352 men, 228 women; mean [standard deviation] age = 34.46 [8.45] years) was included in the NGF genotyping (C/C: 428% [73.8%] and T-allele carriers: 152% [26.2%]). Short-term heart rate variability was used to assess cardiac autonomic function. Results There were significant genotype-by-sex interaction effects (p < .05) on high-frequency power (HF) and root mean square of successive heartbeat interval differences (RMSSD), both indices of cardiac vagal control. Even after adjusting for possible confounders, men with any T allele showed lower HF and RMSSD compared with men with the C/C genotype. Women, however, showed an opposite but nonsignificant pattern. Conclusions The studied NGF polymorphism modulates autonomic outflow to the heart in a sex-dependent manner. The findings support the view that male T-allele carriers are at increased susceptibility for anxiety by association with low vagal activity and suggest a potential sex-specific genetic link between the highly comorbid anxiety disorders and cardiovascular diseases.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism affects sympathetic tone in a gender-specific way

The Val/Val genotype of the brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) has been reported to affect human anxiety-related phenotypes. Substantial research has demonstrated that anxiety is associated with sympathetic activation, while sex steroid hormones have been shown to exert differential actions in regulating BDNF expression. Thus, we examined whether the BDNF variant modulates autonomic function in a gender-dependent manner. From 708 adults initially screened for medical and psychiatric illnesses, a final cohort of 583 drug-free healthy Han Chinese (355 males, 228 females; age 34.43±8.42 years) was recruited for BDNF genotyping (Val/Val: 136, 23.3%, Val/Met: 294, 50.4%, and Met/Met: 153, 26.2%). Time- and frequency-domain analyses of heart rate variability (HRV) were used to assess autonomic outflow to the heart. Significant genotype-by-gender interaction effects were found on HRV indices. Even after adjusting for possible confounders, male participants bearing the Val/Val genotype had significant increases in low frequency (LF), LF% and LF/high frequency (HF) ratio, indicating altered sympathovagal balance with increased sympathetic modulation, compared to male Met/Met homozygotes. Females, however, showed an opposite but non-significant pattern. These results suggest that the studied BDNF polymorphism is associated with sympathetic control in a gender-specific way. The findings here support the view that male subjects with the Val/Val genotype have increased risk of anxiety by association with sympathetic activation.

Components of Metabolic Syndrome as Risk Factors for Hearing Threshold Shifts

Background Hearing loss was a common, chronically disabling condition in the general population and had been associated with several inflammatory diseases. Metabolic syndrome, which was associated with insulin resistance and visceral obesity, was considered a chronic inflammatory disease. To date, few attempts had been made to establish a direct relationship between hearing loss and metabolic syndrome. The aim of the present study was to investigate the relationship between metabolic syndrome and hearing loss by analyzing the data in the reports of the National Health and Nutrition Examination Survey 1999–2004. Methods This study included 2100 participants aged ≤ 65 years who enrolled in the National Health and Nutrition Examination Survey (1999–2004). We examined the relationship between the presence of different features of metabolic syndrome in the participants and their pure-tone air-conduction hearing thresholds, including low-frequency and high-frequency thresholds. Results After adjusting for potential confounders, such as age, medical conditions, and smoking status, the participants with more components of metabolic syndrome were found to have higher hearing thresholds than those with fewer components of metabolic syndrome (p < 0.05 for a trend). The low-frequency hearing threshold was associated with individual components of metabolic syndrome, such as abdominal obesity, high blood pressure, elevated triglycerides, and a low level of high-density lipoprotein cholesterol (HDL-C) (p < 0.05 for all parameters). Conclusions The results indicated that the presence of a greater number of components of metabolic syndrome was significantly associated with the hearing threshold in the US adult population. Among the components of metabolic syndrome, the most apparent association was observed between low HDL and hearing loss.

Factors Affecting Treatment Decisions and Outcomes of Root-Resected Molars: A Nationwide Study

BACKGROUNDnTreatment of furcation-involved molars presents a clinical challenge. This study retrospectively investigates the demographic parameters affecting treatment decisions and outcomes of root-resected molars using a nationwide population-based dataset.nnnMETHODSnDe-identified data from 471 eligible patients were obtained from a representative cohort composed of 1 million of Taiwans population. Demographic factors that influence treatment decisions and outcomes of root-resected teeth were examined. Cox regression was performed to statistically analyze the factors.nnnRESULTSnThe overall survival rate for root-resected molars was 91.1%. The survival times of the extracted and surviving teeth were 303.0 ± 274.6 and 551.8 ± 327.2 days, respectively (P <0.001). The analyzed patient-related factors, such as living district, urbanization level, medical institution, and monthly income, have remarkable influence on treatment decisions; however, there is no statistically significant difference in survival rate between root-resected molars receiving flap surgery and those that do not (P = 0.504). After adjusting for other factors, patients aged >74 years have 3.33 times (hazard ratio = 3.33; 95% CI = 1.04 to 10.66; P = 0.043) higher rates of molar extraction than younger counterparts.nnnCONCLUSIONSnThe overall survival rate of root-resected molars was satisfactory. Patients with advanced age (>74 years) had a higher risk of extraction occurrence on resected molars. Patient-related factors may influence the treatment decision of whether molars receive flap surgery. These findings suggest that demographic factors should be carefully evaluated before and after performing root-resection procedures because these factors may eventually impact the outcome of root-resected molars.

Serotonin 2A receptor (5-HT2A) gene promoter variant interacts with chronic perceived stress to modulate resting parasympathetic activity in humans

Decreased resting vagal (parasympathetic) tone is implicated in the development of stress-related disorders, including anxiety and depression. Chronic stress elevates the expression of serotonin 2A receptors (5-HT2A), while activation of 5-HT2A leads to inhibition of parasympathetic synaptic transmission. The T allele of the promoter variant, rs6311 (C>T), of the 5-HT2A gene has been shown to increase the 5-HT2A expression in vitro and to be associated with anxiety and depressive disorders. We thus hypothesized that the 5-HT2A functional polymorphism may influence resting vagal activity among persons with chronically high levels of perceived stress. A total of 1138 well-defined healthy, medication-free Han Chinese were included for 5-HT2A genotyping. The Perceived Stress Scale (PSS) was used to measure the level of perceived stress during the last month and participants were divided into low and high PSS groups. Resting-state heart rate variability (HRV) was used to assess autonomic function. No significant between-genotype difference was found in any HRV variable in the low PSS group (n=610). However, in the high PSS group (n=528), high frequency power and root mean square of successive heartbeat interval differences (both HRV indices of parasympathetic activity) were significantly reduced in T/T genotype carriers compared to C/C homozygotes. Our findings are the first to show that individuals homozygous for the high-expressing 5-HT2A (T) allele exhibit diminished resting vagal tone-an index of stress vulnerability-when experiencing chronically elevated levels of perceived stress. The present results may advance our understanding of the genetic mechanism underlying individual differences in susceptibility to stress.

Functional Ser205Leu polymorphism of the nerve growth factor receptor (NGFR) gene is associated with vagal autonomic dysregulation in humans.

Evidence indicates that reduced cardiac vagal (parasympathetic) tone, a robust cardiovascular risk factor, is a trait vulnerability marker of major depressive disorder (MDD). The Ser205/Ser205 genotype of the functional polymorphism (Ser205Leu) of the nerve growth factor receptor (NGFR), also called p75 neurotrophin receptor (p75NTR), gene is reported to increase the risk of MDD. Here, we hypothesized that the NGFR Ser205Leu polymorphism may have an effect on vagal control. A sample of 810 healthy, drug-free, unrelated Han Chinese (413 males, 397 females; mean age 35.17u2009±u20098.53 years) was included in the NGFR genotyping. Short-term heart rate variability (HRV) was used to assess vagus-mediated autonomic function. Potential HRV covariates, such as mood/anxiety status and serum metabolic parameters, were assessed. Homozygotes of the Ser205 allele had significantly lower high frequency power and root mean square of successive heartbeat interval differences, both HRV indices of vagal modulation, compared to Leu205 allele carriers. Even after adjusting for relevant confounders, these associations remained significant. Further stratification by sex revealed that the associations were observed only in males. Our results implicate that decreased parasympathetic activity is associated with the NGFR Ser205/Ser205 genotype in a gender-specific manner, suggesting a potential role of NGFR polymorphism in modulating cardiac autonomic function.

Association of neuropeptide Y promoter polymorphism (rs16147) with perceived stress and cardiac vagal outflow in humans.

Neuropeptide Y (NPY) is involved in resilience to stress, and higher vagal (parasympathetic) activity has been associated with greater stress resilience. Thus, we examined whether rs16147, a functional promoter polymorphism (C>T) of the NPY gene, could influence vagal tone during chronic high stress levels. NPY genotyping, chronic psychological stress level measurement (using the Perceived Stress Scale [PSS]), cardiac autonomic function assessment (using short-term heart rate variability [HRV]) were performed in 1123 healthy, drug-free Han Chinese participants who were divided into low- and high-PSS groups. In the high-PSS group (nu2009=u2009522), the root mean square of successive heartbeat interval differences and high frequency power (both HRV indices of parasympathetic activity) were significantly increased in T/T homozygotes compared to C/C homozygotes. However, no significant between-genotype difference was found in any HRV variable in the low-PSS group (nu2009=u2009601). Our results are the first to demonstrate that functional NPY variation alters chronic stress-related vagal control, suggesting a potential parasympathetic role for NPY gene in stress regulation.

Gender-specific association between serotonin transporter polymorphisms (5-HTTLPR and rs25531) and neuroticism, anxiety and depression in well-defined healthy Han Chinese

BACKGROUNDnA tri-allelic serotonin transporter promoter polymorphism (5-HTTLPR/rs25531) more effectively determines the levels of transcriptional efficacy than that with the bi-allelic 5-HTTLPR polymorphism in vitro. Both are reportedly associated with personality traits of negative emotionality, but with conflicting findings. One explanation for this is that a gender difference may play a role in genetic contribution. Here, we hypothesized that the tri-allelic genotype of the serotonin transporter is more closely linked to neuroticism, an anxiety- and depression-related trait, than the bi-allelic variation, particularly in a gender-dependent way.nnnMETHODSnThe genotypes of the 5-HTTLPR and rs25531 loci were determined in 1139 well-defined physically and mentally healthy Han Chinese (550 men, 589 women; mean age 38.3±10.3 years). All participants completed the neuroticism measure of the short-form Maudsley Personality Inventory (MPI). The levels of anxiety and depression were assessed by the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI), respectively.nnnRESULTSnA significant tri-allelic genotype-by-gender interaction effect was found in the MPI-neuroticism measure. SS homozygotes were associated with higher neuroticism than L allele carriers in men. Also, both the BAI and BDI scores were higher in the SS homozygotic men. In the bi-allelic analyses, however, there was only an association between SS genotype and MPI-neuroticism in men.nnnLIMITATIONSnSub-analyses by gender-stratification may reduce the statistical power.nnnCONCLUSIONSnOur findings confirm that gender differences exist in the genetic contributions of the serotonin transporter in human neuroticism, and anxiety/depression. Our data provide further support for rs25531, strengthening the effects of 5-HTTLPR.