BACKGROUND Previous studies have linked gut dysbiosis to the acute coronary syndrome (ACS) and sympathetic nervous system disturbances. However, the relationship between skin sympathetic nerve activity (SKNA) and gut microbiota in ACS patients remains largely unexplored. We hypothesize that elevated SKNA may interact with specific microbial profiles in ACS. METHODS AND RESULTS Fifteen ACS patients with age- and sex-matched controls were enrolled in the cross-sectional study. Subjects with type 2 diabetes or on antibiotics, proton pump inhibitors, or metformin were excluded. Demographic and clinical data were recorded, and SKNA was measured by neuECG. Gut microbial profiles were analyzed by sequencing the V3-V4 region of the 16S rRNA gene. Significant differences in alpha diversity, including Chao 1 index and Faith’s phylogenetic diversity, were observed between the ACS and control groups ( P <0.001). Distinct beta diversity between the two groups was also identified using unweighted normalized UniFrac analysis ( P =0.001). Redundancy analysis and Mantel test revealed a significant relationship between SKNA and microbial profiles. Several butyrate-producing bacteria were decreased in the ACS group, while the genus Hungatella , a trimethylamine producer, showed a significant increase and was positively correlated with SKNA. Additionally, predicted microbial functional analysis indicated an elevation in branched-chain amino acid biosynthesis in the ACS group. CONCLUSIONS This study is the first to establish an association between SKNA and gut microbial profiles in ACS patients. SKNA can serve as a biomarker for ACS, offering a simple and non-invasive tool to explore the interaction between the nervous system and gut microbiota in cardiovascular diseases. WHAT IS NEW? The Skin sympathetic nerve activity (SKNA) is a novel and non-invasive recording of the sympathetic nervous system from the skin of patients. The NEW findings in our study from acute coronary syndrome (ACS) patients are (1) to establish the correlation between SKNA, heart rate variability and microbiota, (2) the Hungatella is correlated with SKNA and standard deviation of NN intervals (SDNN). WHAT ARE THE CLINICAL IMPLICATIONS? Since microbiota and sympathetic nervous system (SNS) might be essential factors of ACS, it is important to assess the abundance of microbiota and SNS activity for accurate management of ACS. The Hungatella , one of the microbiota involved in atherosclerotic cardiovascular disease, heart failure, inflammatory process, and anxiety disorder, might be the link between SNS and ACS. In our study, we prove the positive association between Hungatella and SKNA. Therefore, by checking the SKNA of patients with ACS, we might discover the SNS activity and also the underlying microbiota etiology of ACS. Then, it is critical and accurate to target Hungatella in ACS patients with high SKNA to reduce the risk of ACS. ### Competing Interest Statement The authors have declared no competing interest.

Background: Reduced-dose prasugrel is widely used in East Asia for acute coronary syndrome (ACS), but real-world data in diverse Asian populations are limited. This study evaluated its effectiveness and safety in Taiwanese patients. Methods: The PROMISE-TW Registry was a multicenter, retrospective study including 1167 patients with ACS or chronic coronary syndrome (CCS) treated with reduced-dose prasugrel (20 mg loading, 3.75 mg maintenance) across 13 hospitals in Taiwan from 2018 to 2022. The primary endpoint was 1-year major adverse cardiovascular events (MACEs: cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke). Secondary outcomes included composite ischemic events and major bleeding (BARC 3-5). Results: Among enrolled patients (mean age 63.9 years; 81.2% male; 83% ACS), percutaneous coronary intervention was performed in 90.8%. At one year, MACEs occurred in 1.9%, composite ischemic events in 8.2%, and major bleeding in 0.8%. Subgroup analysis identified prior stroke, diabetes, and chronic total occlusion intervention as predictors of bleeding. Male sex, chronic kidney disease, and left circumflex artery intervention predicted higher ischemic risk. Conclusions:Reduced-dose prasugrel provided effective ischemic protection and low bleeding rates in Taiwanese patients, especially those with ACS. These findings support the clinical utility of dose-adjusted prasugrel in East Asian populations and highlight the importance of individualized risk assessment.

ABSTRACT A lower blood pressure threshold (≥130/80 mmHg) to define hypertension has been proposed in several hypertension guidelines. This study assessed the relationship between hyperuricemia and incident hypertension, examining serum uric acid (SUA) cut‐offs using both traditional and new definitions in a large Taiwanese cohort. This observational cohort study enrolled 26 973 participants from the Taiwan Biobank (TWB), followed for a median of 4 years. Regarding traditional definition (140/90 mmHg), hyperuricemia (odds ratio [OR], 1.297), quartile 3 of SUA (OR, 1.211), quartile 4 of SUA (OR, 1.495), and high SUA (OR, 1.127) were significantly associated with incident hypertension in males, and hyperuricemia (OR, 1.198), quartile 4 of SUA (OR, 1.359), and high SUA (OR, 1.099) were significantly associated with incident hypertension in females. As for new definition (130/80 mmHg), hyperuricemia (OR, 1.376), quartile 3 of SUA (OR, 1.229), quartile 4 of SUA (OR, 1.554), and high SUA (OR, 1.139) were associated with incident hypertension in males, and hyperuricemia (OR, 1.249), quartile 3 of SUA (OR, 1.253), quartile 4 of SUA (OR, 1.429), and high SUA (OR, 1.096) were associated with incident hypertension in females. The interaction between hyperuricemia and sex on incident hypertension was significant for both traditional (140/90, p < 0.001) and new (130/80, p = 0.001) definitions. Hyperuricemia was significantly associated with incident hypertension under both traditional and new definitions. A significant interaction between hyperuricemia and sex was noted, although the differences were not so great.

Background: Acute myocardial infarction (AMI) is a critical cardiovascular disease with high morbidity and mortality. Identifying practical parameters for predicting long-term mortality is crucial in this patient group. The percentage of mean arterial pressure (%MAP) is a useful parameter used to assess peripheral artery disease. It can be easily calculated from ankle pulse volume recording. Previous studies have shown that %MAP is a useful predictor of all-cause mortality in specific populations, but its relationship with mortality in AMI patients is unclear. Methods: In this observational cohort study, 191 AMI patients were enrolled between November 2003 and September 2004. Ankle-brachial index (ABI) and %MAP were measured using an ABI-form device. All-cause and cardiovascular mortality data were collected from a national registry until December 2018. Cox proportional hazards model and Kaplan-Meier survival plot were used to analyze the association between %MAP and long-term mortality in AMI patients. Results: The median follow-up to mortality was 65 months. There were 130 overall and 36 cardiovascular deaths. High %MAP was associated with increased overall mortality after multivariable analysis (HR = 1.062; 95% CI: 1.017-1.109; p =0.006). However, high % MAP was only associated with cardiovascular mortality in the univariable analysis but became insignificant after the multivariable analysis. Conclusions: In conclusion, this study is the first to evaluate the usefulness of %MAP in predicting long-term mortality in AMI patients. Our study shows that %MAP might be an independent predictor of long-term overall mortality in AMI patients and has better predictive power than ABI.

Both hepatitis C virus (HCV) infection and end-stage renal disease are associated with an increased risk of developing peripheral arterial disease (PAD). Our objective was to explore the relationship between HCV infection and PAD in hemodialysis patients, using brachial-ankle pulse wave velocity (baPWV) as the assessment method. Since 2016, we have actively been recruiting patients undergoing regular hemodialysis three times a week. All baPWV assessments for our patients were performed before the implementation of direct-acting antiviral treatment. Furthermore, none of the uremic patients with HCV infection had received interferon-based treatment in the past. An elevated baPWV measurement surpassing 2100 cm/s is indicative of an increased susceptibility to potential PAD. Our analysis utilized multivariate linear and logistic regression analysis. Individuals with HCV infection exhibited higher baPWV levels compared with those without HCV infection (2006.0 +/- 687.4 vs. 1809.3 +/- 466.1 cm/s, p = .039). The presence of HCV infection (beta = 199.56, 95% CI: 10.56-388.56, p = .039) demonstrated a significantly positive correlation with baPWV levels. In the multivariate logistic regression analysis, HCV infection (OR = 2.67, 95% CI: 1.07-6.68, p = .036) significantly associated with baPWV >2100 cm/s. Furthermore, individuals with a higher viral load (HCV RNA >= 60 x 10(3) IU/mL) (OR = 4.45, 95% CI: 1.12-17.68, p = .034) demonstrated a significant association with baPWV >= 2100 cm/s when compared with non-HCV infection patients. Additionally, patients with genotype I exhibited a significant association with baPWV >= 2100 cm/s (OR = 8.13, 95% CI: 2.04-32.42, p = .003) in comparison to non-HCV patients. The presence of HCV infection has been demonstrated to markedly increase baPWV levels. Particularly, HCV infection with higher viral load and genotype I is significantly linked to an elevated risk of PAD. It emphasizes the importance of HCV elimination in the specific population.

Background: Acute limb ischemia (ALI) is a medical emergency necessitating immediate action to avert irreversible tissue harm and limb loss. Rotarex mechanical thrombectomy (RMT) has become an efficient treatment alternative for ALI. However, there is a lack of data on RMT in Taiwan. Methods: We retrospectively analyzed 61 ALI patients treated with RMT at our hospital between January 2016 and January 2022. We collected baseline characteristics, laboratory and angiographic data. We also examined the outcomes at 30 days, 6 months, and 1 year, including major amputations, minor amputations, all-cause mortality, and major adverse limb events (MALEs). Results: Among the 61 RMT-treated patients, the average age was 70 +/- 14 years. ALI affected the upper extremities in 9 cases and lower extremities in 52 cases. One-year outcomes revealed 2 major amputations (3.3%), 2 minor amputations (3.3%), 6 all-cause deaths (9.8%), and 10 MALEs (16.4%). After multiple logistic regression analysis, hemoglobin drop was significantly associated with 1-year all-cause mortality, and a history of peripheral artery disease (PAD) was significantly associated with MALEs. Conclusions: Our research is the first investigation into the application of RMT for ALI in Taiwan. The short- and mid-term outcomes after RMT for ALI revealed reductions in amputation, mortality, and MALE rates. In addition, a decline in hemoglobin level was a significant predictor of increased mortality, and a history of PAD was a significant predictor of increased MALEs following RMT.

Background: Left atrial strain can usefully reflect left atrial function. The follow-up periods in previous studies assessing left atrial strain as a survival predictor have been relatively short, and few studies have examined the ability of left atrial strain to predict mortality in patients with borderline diastolic function. This study sought to investigate the survival predictive value of left atrial strain with a longer follow-up duration. In addition, we also evaluated the survival predictive value of left atrial strain in patients with borderline diastolic function. Methods: In total, 652 participants who received routine echocardiography underwent 2-D speckle tracking echocardiography to evaluate left atrial reservoir function by peak atrial longitudinal strain. The study endpoints were all-cause and cardiovascular mortality. Results: The mean left atrial strain was 27.6%, and the median follow-up duration was 92 months. During followup, 72 patients died of cardiovascular causes and 181 died of all causes. Univariable Cox regression analysis revealed that lower left atrial strain significantly predicted an increase in all-cause and cardiovascular mortality. After adjusting for common clinical and echocardiographic parameters, lower left atrial strain was still associated with a higher risk of all-cause mortality [hazard ratio (HR) = 0.942, p = 0.011] and cardiovascular mortality (HR = 0.915, p = 0.018) in multivariable Cox-regression analysis. In addition, 293 patients had borderline left ventricular diastolic function. Multivariable analysis still revealed that left atrial strain could predict cardiovascular mortality in this population. Conclusions: Our data showed that left atrial strain could predict all-cause and cardiovascular mortality, even after adjusting for general clinical and echocardiographic parameters.

An elevated white blood cell (WBC) count has been linked to incident diabetes. WBC count has been positively associated with body mass index (BMI), and elevated BMI has been reported to be a strong predictor of future diabetes. Hence, the association of increased WBC count with the subsequent development of diabetes may be mediated by increased BMI. This study was designed to address this issue. We selected subjects from the 104,451 participants enrolled from 2012 to 2018 in the Taiwan Biobank. We only included those with complete data at baseline and follow-up and those without diabetes at baseline. Finally, 24,514 participants were enrolled in this study. During an average 3.88 years of follow-up, 248 (1.0%) of the participants had new-onset diabetes. After adjusting for demographic, clinical, and biochemical parameters, increased WBC count was associated with new-onset diabetes in all of these participants (p ≤ 0.024). After further adjustment for BMI, the association became insignificant (p = 0.096). In addition, subgroup analysis of 23,430 subjects with a normal WBC count (range: 3500-10500/µl) demonstrated that increased WBC count was significantly associated with new-onset diabetes after adjusting for demographic, clinical, and biochemical parameters (p ≤ 0.016). After further adjustment for BMI, this association was attenuated (p = 0.050). In conclusion, our results showed that BMI had a significant impact on the relationship between increased WBC count and new-onset diabetes in all study participants, and BMI also attenuated the association in those with a normal WBC count. Hence, the association between increased WBC count and the future development of diabetes may be mediated by BMI.

Hyperuricemia has been linked with the development of diabetes, gout, kidney, and cardiovascular diseases. Although obesity is associated with hyperuricemia, data on sex differences in this association are scarce. Therefore, this study was conducted to explore sex differences in the correlations among various indices of obesity with hyperuricemia in Taiwan. Data were obtained from the Taiwan Biobank and included 122,067 participants. After excluding 179 participants with missing data, the remaining 121,888 participants (men: 43,790; women: 78,098) were enrolled. The prevalence rates of hyperuricemia (defined as serum uric acid >7.0/6.0 mg/dL in men/women) were 29.8% and 13.6%, respectively (p < 0.001). Multivariable analysis revealed high values of body shape index (ABSI), waist-to-height ratio (WHtR), waist-hip ratio (WHR), lipid accumulation product (LAP), conicity index (CI), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), body mass index (BMI), and body roundness index (BRI) were significantly associated with hyperuricemia in both the male and female participants (all p < 0.001). The interactions between sex and all 10 of these indices were significant (all p < 0.001) for hyperuricemia. In men, LAP had the highest area under the curve (0.669), followed by BMI (0.655), VAI (0.645), AVI (0.642), BRI (0.640), WHtR (0.633), BAI (0.605), WHR (0.599), CI (0.574), and ABSI (0.510). In women, LAP also had the highest area under the curve (0.754), followed by BMI (0.728), VAI (0.724), WHtR (0.721), BRI (0.720), AVI (0.713), WHR (0.676), BAI (0.673), CI (0.626), and ABSI (0.544). In conclusion, obesity-related indices were associated with hyperuricemia in this large Taiwanese study, and sex differences were found in these associations, with stronger associations in women than in men.

The incidence of chronic kidney disease (CKD) is increasing worldwide; however, the association between CKD and anemia and hyperuricemia has yet to be clarified. In addition, whether anemia and hyperuricemia only influence renal damage in combination with other comorbidities or whether they are direct causative factors is also controversial. Therefore, the aim of this longitudinal study was to investigate these issues in a large Taiwanese cohort. We enrolled 26,631 participants from the Taiwan Biobank (TWB) after excluding those with CKD at the baseline, all of whom had follow-up data for a median of 4 years. In this study, CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2, incident new-onset CKD was defined as the development of CKD during follow-up, anemia was defined as a hemoglobin level <13 mg/dL in males and <12 mg/dL in females, and hyperuricemia was defined as a serum uric acid (UA) level >7 mg/dL in males and >6 mg/dL in females. The participants were divided into four groups according to whether or not they had anemia and hyperuricemia. Multivariable analysis showed that low hemoglobin (per 1 g/dL; odds ratio [OR], 0.760; p < 0.001) and high serum UA (per 1 mg/dL; OR, 1.444; p < 0.001) in model 1 and anemia (OR, 2.367; p < 0.001) and hyperuricemia (OR, 2.516; p < 0.001) in model 2 were significantly associated with new-onset CKD. Furthermore, compared to the group without anemia or hyperuricemia, the groups with anemia without hyperuricemia (OR, 2.502; p < 0.001), without anemia with hyperuricemia (OR, 2.559; p < 0.001), and with anemia and hyperuricemia (OR, 5.505; p < 0.001) were significantly associated with new-onset CKD. There was a significant interaction between hemoglobin and serum UA and new-onset CKD (p < 0.001). In conclusion, we found that anemia and hyperuricemia were associated with new-onset CKD, respectively, and also had a synergetic effect on new-onset CKD.

BACKGROUND:Previous studies investigating the relationship between hypertension (HT) and hematological parameters report inconsistent results, and most them included a small number of participants or only conducted a cross-sectional analysis of 1 or 2 hematological factors. Moreover, no large cohort follow-up studies have investigated this topic. The aim of this longitudinal study was to explore associations between components of the complete blood count (CBC) and incident HT using data from a large Taiwanese biobank. METHODS AND RESULTS:Hematological parameters including white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, hematocrit (HCT), and platelet count were evaluated. We included 21,293 participants who did not have HT at baseline and followed them for a mean period of 3.9 years. During follow-up, 3,002 participants with new-onset HT (defined as incident HT) were identified. Univariable analysis revealed that high WBC count, high RBC count, high hemoglobin, high HCT, and low platelet count were associated with incident HT. Multivariable analysis after adjusting potential confounding factors found high WBC count (odds ratio [OR], 1.057; 95% confidence interval [CI], 1.028 to 1.087; P<0.001) and high HCT (OR, 1.023; 95% CI, 1.010 to 1.036; P<0.001) were still significantly associated with incident HT. CONCLUSIONS:High WBC count and high HCT were associated with incident HT.

The prevalence rate of hyperuricemia remains high in Taiwan, at 21.6% in men and 9.57% in women. Both metabolic syndrome (MetS) and hyperuricemia can cause many complications; however, few studies have evaluated the correlation between MetS and hyperuricemia. Therefore, in this observational cohort study, we explored associations between metabolic syndrome (MetS) and its components and new-onset hyperuricemia. Of 27,033 individuals in the Taiwan Biobank who had complete follow-up data, we excluded those with hyperuricemia at baseline (n = 4871), those with gout at baseline (n = 1043), those with no data on baseline uric acid (n = 18), and those with no data on follow-up uric acid (n = 71). The remaining 21,030 participants (mean age 50.8 ± 10.3 years) were enrolled. We found a significant association between new-onset hyperuricemia with MetS and the components of MetS (hypertriglyceridemia, abdominal obesity, low high-density lipoprotein cholesterol, hyperglycemia, and high blood pressure). Furthermore, compared to those without any MetS components, those with one MetS component (OR = 1.816), two MetS components (OR = 2.727), three MetS components (OR = 3.208), four MetS components (OR = 4.256), and five MetS components (OR = 5.282) were significantly associated with new-onset hyperuricemia (all p < 0.001). MetS and its five components were associated with new-onset hyperuricemia in the enrolled participants. Further, an increase in the number of MetS components was associated with an increase in the incidence rate of new-onset hyperuricemia.

Gut dysbiosis can induce chronic inflammation and contribute to atherosclerosis and vascular calcification. The aortic arch calcification (AoAC) score is a simple, noninvasive, and semiquantitative assessment tool to evaluate vascular calcification on chest radiographs. Few studies have discussed the relationship between gut microbiota and AoAC. Therefore, this study aimed to compare the microbiota composition between patients with chronic diseases and high or low AoAC scores. A total of 186 patients (118 males and 68 females) with chronic diseases, including diabetes mellitus (80.6%), hypertension (75.3%), and chronic kidney disease (48.9%), were enrolled. Gut microbiota in fecal samples were analyzed by sequencing of the 16S rRNA gene, and differences in microbial function were examined. The patients were divided into three groups according to AoAC score, including 103 patients in the low AoAC group (AoAC ≤ 3), 40 patients in the medium AoAC group (3 < AoAC ≤ 6), and 43 patients in the high AoAC group (AoAC > 6). Compared to the low AoAC group, the high AoAC group had a significantly lower microbial species diversity (Chao1 index and Shannon index) and increased microbial dysbiosis index. Beta diversity showed that the microbial community composition was significantly different among the three groups (p = 0.041, weighted UniFrac PCoA). A distinct microbial community structure was found in the patients with a low AoAC, with an increased abundance at the genus level of Agathobacter, Eubacterium coprostanoligenes group, Ruminococcaceae UCG-002, Barnesiella, Butyricimonas, Oscillibacter, Ruminococcaceae DTU089, and Oxalobacter. In addition, there was an increased relative abundance of class Bacilli in the high AoAC group. Our findings support the association between gut dysbiosis and the severity of AoAC in patients with chronic diseases.

Aims Metabolic syndrome (MetS) is associated with arrhythmias and cardiovascular mortality. Arrhythmogenesis in MetS results from atrial structural and electrical remodelling. The small-conductance Ca2+-activated K+ (SK) currents modulate atrial repolarization and may influence atrial arrhythmogenicity. This study investigated the regulation of SK current perturbed by a high-fat diet (HFD) to mimic MetS. Methods and results Thirty mice were divided into two groups that were fed with normal chow (CTL) and HFD for 4 months. Electrocardiography and echocardiography were used to detect cardiac electrical and structure remodelling. Atrial action potential duration (APD) and calcium transient duration (CaTD) were measured by optical mapping of Langendorff-perfused mice hearts. Atrial fibrillation (AF) inducibility and duration were assessed by burst pacing. Whole-cell patch clamp was performed in primarily isolated atrial myocytes for SK current density. The SK current density is higher in atrial myocytes from HFD than in CTL mice (P <= 0.037). The RNA and protein expression of SK channels are increased in HFD mice (P <= 0.041 and P <= 0.011, respectively). Action potential duration is shortened in HFD compared with CTL (P <= 0.015). The shortening of the atrial APD in HFD is reversed by the application of 100 nM apamin (P <= 0.043). Compared with CTL, CaTD is greater in HFD atria (P <= 0.029). Calcium transient decay (Tau) is significantly higher in HFD than in CTL (P = 0.001). Both APD and CaTD alternans thresholds were higher in HFD (P <= 0.043), along with higher inducibility and longer duration of AF in HFD (P <= 0.023). Conclusion Up-regulation of apamin-sensitive SK currents plays a partial role in the atrial arrhythmogenicity of HFD mice.

Osteoporosis results in reduced bone strength and an elevated risk of fractures. Both overweight and underweight have been associated with osteoporosis; however, few studies have examined associations between osteoporosis and indices related to obesity. Therefore, the aim of this study was to investigate the associations of obesity-related indices, including body mass index (BMI), waist–hip ratio (WHR), waist-to-height ratio (WHtR), body roundness index (BRI), body adiposity index (BAI), abdominal volume index (AVI), lipid accumulation product (LAP), and visceral adiposity index (VAI), with baseline and change in calcaneus ultrasound T-score between baseline and follow-up (ΔT-score). T-score was measured using ultrasound. A total of 26,983 subjects were enrolled (mean age 51.2 ± 10.4 years). Multivariable analysis showed significant associations between low BMI (per 1 kg/m2; β, 0.065), WHR (per 1%; β, 0.012), WHtR (per 1%; β, 0.024), BRI (per 1; β, 0.079), BAI (per 1; β, 0.032), AVI (per 1; β, 0.049), and LAP (per 1; β, 0.005) with low baseline T-scores (all p < 0.001). Furthermore, there were significant associations between low BMI (per 1 kg/m2; β, 0.005; p = 0.036), BAI (per 1; β, 0.010; p < 0.001), and VAI (per 1; β, 0.017; p = 0.002) with low ΔT-scores. A low baseline T-score was significantly associated with low values of LAP, AVI, BAI, BMI, BRI, WHR, and WHtR but not VAI. In addition, low BMI, BAI, and VAI were significantly associated with low ΔT-scores, representing a rapidly decreasing T-score. Consequently, avoiding being underweight may help prevent osteoporosis in the Taiwanese population.

Previous studies demonstrated inconsistent results regarding the association between liver function and hypertension. In addition, large cohort follow-up studies are lacking. Therefore, this longitudinal study aimed to investigate the association between liver function and incident hypertension using data from the Taiwan Biobank (TWB). We evaluated liver biomarkers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, alpha-fetoprotein (AFP), total bilirubin, and gamma-glutamyl transferase (GGT) in this study. A total of 21,293 participants without hypertension at baseline were analyzed. During the mean 3.9-year follow-up, 3002 participants developed hypertension (defined as incident hypertension). Multivariable analysis revealed that high AST (odds ratio [OR], 1.004; 95% confidence interval [CI], 1.001–1.007; p = 0.014), high ALT (OR, 1.004; 95% CI, 1.002–1.006; p < 0.001), high albumin (OR, 1.897; 95% CI, 1.573–2.286; p < 0.001), and high GGT (OR, 1.004; 95% CI, 1.003–1.005; p < 0.001) were significantly associated with incident hypertension in all study participants. In subgroup analysis of the participants with an ALT level ≤2 times the normal limit (80 u/l) ( n = 20,983), multivariable analysis demonstrated that high ALT (OR, 1.009; 95% CI, 1.005–1.012; p < 0.001) and high GGT (OR, 1.005; 95% CI, 1.003–1.006; p < 0.001) were significantly associated with incident hypertension. In conclusion, we found that elevated AST, ALT, albumin, and GGT were associated with incident hypertension in a large Taiwanese cohort. A greater understanding of potential risk factors for hypertension may help to reduce the burden of hypertension in this Taiwanese population.

Hyperuricemia is the chief cause of gout and has been linked with hypertension, cardiovascular and renal disease, diabetes and metabolic syndrome. Liver with the highest protein expression of xanthine oxidase, the main enzyme responsible for uric acid formation, is the primary site of uric acid biosynthesis. However, there are few studies that examine the association between liver function and new-onset hyperuricemia. Hence, using the Taiwan Biobank dataset, we aimed to explore the capability of liver function parameters, including gamma-glutamyl transferase, total bilirubin, albumin, alanine aminotransferase and aspartate aminotransferase in association with the subsequent development of hyperuricemia. We analyzed 21,030 participants without hyperuricemia at baseline. Hyperuricemia was defined as a uric acid concentration > 6.0 mg/dL in women or >7.0 mg/dL in men. New-onset hyperuricemia was defined as participants without baseline hyperuricemia having developed hyperuricemia upon subsequent exam. Overall, 1804 (8.6%) of the study subjects developed new-onset hyperuricemia. After multivariable analysis, significant associations were found between the male sex (odds ratio [OR], 4.412; p < 0.001), high values of systolic blood pressure (SBP) (OR, 1.006; p = 0.012), body mass index (BMI) (OR, 1.064; p < 0.001), fasting glucose (OR, 1.005; p < 0.001), triglycerides (OR, 1.001; p = 0.003), uric acid (OR, 5.120; p < 0.001), low values of estimated glomerular filtration rates (eGFR) (OR, 0.995; p < 0.001), total bilirubin (OR, 0.616; p < 0.001) and new-onset hyperuricemia. The cutoff level of total bilirubin, according to the Youden index, of receiver operating characteristic curve for identifying new-onset hyperuricemia was 0.65 mg/dL. Low total bilirubin was defined as ≤0.65 mg/dL. After multivariable analysis, we found a significant association between low total bilirubin level (≤0.65 mg/dL) (OR = 0.806; p < 0.001) and new-onset hyperuricemia. Our present study demonstrated that in addition to male sex, high SBP, BMI, fasting glucose, triglycerides, and uric acid and low eGFR, the serum’s total bilirubin levels were negatively associated with new-onset hyperuricemia in a large Taiwanese cohort.

To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD) to better understand their nosology, this study explored the independent and joint effects of polygenic liabilities for SCZ and BPD on cognitive aging and educational attainment among a collection of 80318 unrelated community participants from the Taiwan Biobank. Using the Psychiatric Genomics Consortium meta-analysis as a discovery sample, we calculated the polygenic risk score (PRS) for SCZ (PRSSCZ) and BPD (PRSBPD), shared PRS between SCZ and BPD (PRSSCZ+BPD), and SCZ-specific, differentiated from BPD, PRS (PRSSCZvsBPD). Based on the sign concordance of the susceptibility variants with SCZ and BPD, PRSSCZ was split into PRSSCZ_concordant and PRSSCZ_discordant and PRSBPD was split into PRSBPD_concordant and PRSBPD_discordant. Linear regression models were used to estimate the association with cognitive aging as measured by the Mini-Mental State Examination (MMSE) in individuals aged [≥] 60 years. Ordinal logistic regression models were used to estimate the association with educational attainment. PRSSCZ was negatively associated with MMSE (beta=-0.063, p<0.001), while PRSBPD was positively associated with MMSE (beta=0.04, p=0.01). A larger difference between PRSSCZ and PRSBPD was associated with lower MMSE scores (beta=-0.052, p<0.001). Both PRSSCZ_concordant and PRSSCZ_discordant were negatively associated with MMSE scores, without a synergistic effect. There was a complex interaction between PRSBPD_concordant and PRSBPD_discordant on the MMSE scores. PRSSCZ+BPD (beta=-0.09, p=0.01) and PRSSCZvsBPD (beta=-0.13, p<0.001) predicted a decrease in MMSE scores during the follow-up. PRSSCZ, PRSBPD, and PRSSCZ+BPD were positively associated with educational attainment, whereas PRSSCZvs BPD was negatively associated with educational attainment. This study provides evidence for the contrasting effect of polygenic liabilities for SCZ and BPD on cognitive aging and partially supports the hypothesis that the heterogeneity of SCZ and the positive association of polygenic liability for SCZ with education might be attributed to the shared part with BPD.

BACKGROUND Acute coronary syndrome (ACS) is major cause of ventricular arrhythmias (VAs) and sudden death. neuECG is a noninvasive method to simultaneously record skin sympathetic nerve activity (SKNA) and electrocardiogram. OBJECTIVE The purpose of this study was to test the hypotheses that (1) ACS increases average SKNA (aSKNA), (2) the magnitude of aSKNA elevation is associated with VAs during ACS, and (3) there is a gender difference in aSKNA between patients without and with ACS. METHODS We prospectively studied 128 ACS and 165 control participants. The neuECG was recorded with electrodes at Lead I configuration at baseline, during mental math stress, and during recovery (5 minutes for each phase). All recordings were done in the morning. RESULTS In the control group, women have higher aSKNA than do men at baseline (0.82 +/- 0.25 mu V vs 0.73 +/- 0.20 mu V; P = .009) but not during mental stress (1.21 +/- 0.36 mu V vs 1.16 +/- 0.36 mu V; P = .394), suggesting women had lower sympathetic reserve. In comparison, ACS is associated with equally elevated aSKNA in women vs men at baseline (1.14 +/- 0.33 mu V vs 1.04 +/- 0.35 mu V; P = .531), during mental stress (1.46 +/- 0.32 mu V vs 1.33 +/- 0.37 mu V; P = .113), and during recovery (1.30 +/- 0.33 mu V vs 1.11 +/- 0.30 mu V; P = .075). After adjusting for age and gender, the adjusted odds ratio for VAs including ventricular tachycardia and ventricular fibrillation is 1.23 (95% confidence interval 1.05-1.44) for each 0.1 mu V aSKNA elevation. aSKNA is positively correlated with plasma norepinephrine level. CONCLUSION ACS is associated with elevated aSKNA, and the magnitude of aSKNA elevation is associated with the occurrence of VAs. Women have higher aSKNA and lower SKNA reserve than do men among controls but not among patients with ACS. (C) 2022 Heart Rhythm Society. All rights reserved.

AIM:Abnormal ankle-brachial index (ABI) is regarded as peripheral artery disease and can be used to predict cardiovascular (CV) outcomes. However, the usefulness of ABI for the prediction of CV outcome in patients with normal ABI is limited. Upstroke time per cardiac cycle (UTCC) is recently reported to be associated with mortality in patients with acute myocardial infarction and the elderly. Therefore, we aimed to evaluate UTCC, left ventricular ejection fraction (LVEF), brachial-ankle pulse wave velocity (baPWV), and ABI for the prediction of mortality in patients with normal ABI. METHODS:Patients arranged for echocardiographic examinations were enrolled, and 1076 patients with normal ABI were included. ABI, baPWV, and UTCC were measured by an ABI-form device. RESULTS:The median follow-up to mortality was 95 months. There were 88 CV and 244 all-cause deaths. After multivariate analysis, UTCC was associated with increased CV and all-cause mortality (P ≤ 0.004). Age, diabetes, heart failure, left ventricular hypertrophy, baPWV, and LVEF were also independent predictors of CV and all-cause mortality, but ABI was not. Furthermore, UTCC had a better additive predictive value than ABI, baPWV, and LVEF for CV mortality ( P ≤ 0.012). It also had a better additive predictive value than ABI and LVEF for all-cause mortality (P ≤ 0.013). CONCLUSIONS:UTCC is an independent predictor for CV and all-cause mortality in patients with normal ABI. It also has a better additive predictive value of CV and all-cause mortality than ABI and LVEF. Therefore, UTCC is a simple, novel, and useful parameter for identifying high-risk patients with normal ABI.