Associations of different types of statins with the risk of open-angle glaucoma: a systematic review and network meta-analysis.

PURPOSE: Previous studies implied that different types of statins may pose divergent impacts on the risk of glaucoma onset. This study aimed to comprehensively evaluate the effects of various statins on the risk of glaucoma occurrence. METHODS: PubMed, Cochrane CENTRAL, Embase, and Web of Science were searched from February 1994 to February 2024. We included studies that investigated the effects of various types of statins, fibrates, ezetimibe, cholestyramine, niacin, PCSK9 inhibitors, omega-3 fatty acids, and any cholesterol-lowering medications on glaucoma onset or progression. The revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) and the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-1) tool were used to assess the quality of randomized controlled trials (RCTs) and non-RCTs, respectively. The frequentist network meta-analysis framework was utilized to evaluate the comparative effectiveness, with the random effects model applied. RESULTS: This network meta-analysis comprised 12 studies, encompassing 262,217 individuals and including cholesterol-lowering medications such as statins, fibrates, ezetimibe, cholestyramine, niacin, and omega-3 fatty acids. Our findings demonstrate that comparing to the placebo, rosuvastatin (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.03 to 1.46), simvastatin (RR, 1.21; 95% CI, 1.02 to 1.43), and pravastatin (RR, 1.20; 95% CI, 1.01 to 1.43) increased the risk of glaucoma onset with statistical significance. CONCLUSION: Rosuvastatin, simvastatin, and pravastatin were each associated with a significantly increased risk of glaucoma onset. We advise medical practitioners to exercise caution when prescribing these specific statins for patients who are at risk of developing glaucoma. KEY MESSAGES: What is known Previous studies have suggested a link between statins and the risk of developing glaucoma. However, there is still ongoing debate regarding the specific effects of each type of statin on the onset of glaucoma. What is new This network meta-analysis comprehensively evaluated the effects of various statins on the risk of glaucoma onset. Rosuvastatin, simvastatin, and pravastatin were associated with a significantly increased risk of glaucoma onset.

Systolic blood pressure as a critical mediator in the association between adult height and 25-year risk of stroke.

BACKGROUND: Adult height is associated with the risk of stroke. However, the underlying mechanism remains unclear. We explored the mediating role of metabolic factors in the association between adult height and stroke incidence. METHODS: We used data from 3306 community-dwelling participants with complete information on adult height, metabolic factors, and 25-year cardiovascular outcomes. Participants were classified into three adult height groups based on sex-specific height quartiles: short (Q1), average (Q2-Q3), and tall (Q4). The primary endpoint was the occurrence of cardiovascular disease, including coronary artery disease and stroke. RESULTS: Taller adult height was associated with a lower risk of stroke. Compared with the short group the risk of stroke reduced with taller height with a hazard ratio (HR) of 0.68 in the average group (95% confidence interval [CI]: 0.50-0.93), and 0.45 in the tall group (95% CI: 0.31-0.65). Low systolic blood pressure was considered as a protective mediator in the effect of adult height on the risk of stroke in the average (HR: 0.86; 95% CI: 0.82-0.93) and the tall group (HR: 0.85; 95% CI: 0.78-0.91). Systolic blood pressure significantly contributed to height-related stroke risk (proportion mediated: 0.41; 95% CI: 0.19-1.56). CONCLUSIONS: This study found an inverse association between adult height and stroke risk, which is partly driven by lower systolic blood pressure. These findings highlight the importance of systolic blood pressure management as a potential preventive strategy against stroke.

Sodium Glucose Transporter 2 Inhibitors Versus Metformin on Cardiovascular and Renal Outcomes in Patients With Diabetes With Low Cardiovascular Risk: A Nationwide Cohort Study.

BACKGROUND: This study investigated whether initial SGLT2 (sodium-glucose cotransporter 2) inhibitor-based treatment is superior to metformin-based regimens as a primary prevention strategy among low-risk patients with diabetes. METHODS AND RESULTS: In this nationwide cohort study, a total of 38 496 patients with diabetes with low cardiovascular risk were identified (age 62.0±11.6 years, men 50%) from January 1 to December 31, 2016. Patients receiving SGLT2 inhibitors-based and metformin-based regimens were 1:2 matched by propensity score. Study outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, stroke, and progression to end-stage renal disease. Compared with 1928 patients receiving metformin-based regimens, 964 patients receiving SGLT2 inhibitor-based regimens had similar all-cause mortality (hazard ratio [HR], 0.75 [95% CI, 0.51-1.12]), cardiovascular death (HR, 0.69 [95% CI, 0.25-1.89]), hospitalization for heart failure (HR, 1.06 [95% CI, 0.59-1.92]), stroke (HR, 0.78 [95% CI, 0.48-1.27]), and progression to end-stage renal disease (HR, 0.88 [95% CI, 0.32-2.39]). However, SGLT2 inhibitors were associated with a lower risk of all-cause mortality (HR, 0.47 [95% CI, 0.23-0.99]; P for interaction=0.008) and progression to end-stage renal disease (HR, 0.22 [95% CI, 0.06-0.82]; P for interaction=0.04) in patients under the age of 65. CONCLUSIONS: In comparison to metformin-based regimens, SGLT2 inhibitor-based regimens showed a similar risk of all-cause mortality and adverse cardiorenal events. SGLT2 inhibitors might be considered as first-line therapy in select low-risk patients, for example, younger patients with diabetes.

The impact of sodium-glucose co-transporter-2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation.

AIMS: The effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase-4 inhibitors (DPP4i). MATERIALS AND METHODS: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. RESULTS: After up to 5 years of follow-up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51-0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24-0.82). SGLT2i was related to reduced risks of AF-related hospitalisation (HR: 0.72, 95% CI: 0.56-0.93), stroke (HR: 0.75, 95% CI: 0.60-0.94), and all-cause death (HR: 0.33, 95% CI: 0.24-0.44). The protective effects were consistent irrespective of the concurrent use of non-vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. CONCLUSIONS: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF-related hospitalisation, stroke, and all-cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Efficacy and Safety of a High-Energy, Low-Protein Formula Replacement Meal for Pre-Dialysis Chronic Kidney Disease Patients: A Randomized Controlled Trial.

High-energy, low-protein formulas (HE-LPFs) are commonly used as oral nutritional supplements (ONSs) to help provide extra calories to patients who are adhering to a low-protein diet (LPD) after diagnosis with chronic kidney disease (CKD). This randomized controlled trial aimed to evaluate the efficacy and safety of an HE-LPF as either a partial or a total replacement for one meal in pre-dialysis CKD patients. Stage 4-5 CKD patients received either a once-daily HE-LPF (HE-LPF group) or normal food (control group) for a period of 4 weeks while following an LPD. Overall, 73 patients who completed the study were included in the intention-to-treat population. After analyzing the 3-day food records, the HE-LPF group experienced a significant decrease in the percentage of energy derived from protein (p < 0.05) and an increase in the percentage of energy derived from fat (p < 0.05) compared to the control group. The two groups had no significant differences in body weight, body composition, grip strength, renal function, electrolytes, or metabolic markers. The HE-LPF group had a high adherence (94.9% at week 4), and no adverse effects were observed. HE-LPFs are safe to employ as meal replacements for pre-dialysis CKD patients adhering to an LPD.

Catheter Ablation With Morphologic Repetitiveness Mapping for Persistent Atrial Fibrillation.

Importance: Catheter ablation for persistent atrial fibrillation (AF) has shown limited success. Objective: To determine whether AF drivers could be accurately identified by periodicity and similarity (PRISM) mapping ablation results for persistent AF when added to pulmonary vein isolation (PVI). Design, Setting, and Participants: This prospective randomized clinical trial was performed between June 1, 2019, and December 31, 2020, and included patients with persistent AF enrolled in 3 centers across Asia. Data were analyzed on October 1, 2022. Intervention: Patients were assigned to the PRISM-guided approach (group 1) or the conventional approach (group 2) at a 1:1 ratio. Main Outcomes and Measures: The primary outcome was freedom from AF or other atrial arrhythmia for longer than 30 seconds at 6 and 12 months. Results: A total of 170 patients (mean [SD] age, 62.0 [12.3] years; 136 men [80.0%]) were enrolled (85 patients in group 1 and 85 patients in group 2). More group 1 patients achieved freedom from AF at 12 months compared with group 2 patients (60 [70.6%] vs 40 [47.1%]). Multivariate analysis indicated that the PRISM-guided approach was associated with freedom from the recurrence of atrial arrhythmia (hazard ratio, 0.53 [95% CI, 0.33-0.85]). Conclusions and Relevance: The waveform similarity and recurrence pattern derived from high-density mapping might provide an improved guiding approach for ablation of persistent AF. Compared with the conventional procedure, this novel specific substrate ablation strategy reduced the frequency of recurrent AF and increased the likelihood of maintenance of sinus rhythm. Trial Registration: ClinicalTrials.gov Identifier: NCT05333952.

Ablation of atrial fibrillation and dementia risk reduction during long-term follow-up: a nationwide population-based study.

AIMS: This study investigated the epidemiological characteristics of new-onset dementia in patients with atrial fibrillation (AF) and the association of catheter ablation with different subtypes of dementia. METHODS AND RESULTS: We conducted a population-based, retrospective cohort study using data from the Taiwan National Health Insurance Research Database. In total, 136 774 patients without a history of dementia were selected after 1:1 propensity score matching based on age (with AF vs. without AF). A competing risk model was used to investigate the three subtypes of dementia: Alzheimer's disease, vascular dementia, and other/mixed dementia. Inverse probability of treatment weighting (IPTW) was performed to minimize the impact on dementia risk due to the imbalanced baseline characteristics. After a median follow-up period of 6.6 years, 8704 events of new-onset dementia occurred. Among all AF patients developing dementia, 73% were classified as having Alzheimer's disease, 16% as having vascular dementia, and 11% as having other/mixed dementia. The cumulative incidence of dementia in AF patients was higher than those without AF (log-rank test: P < 0.001 for both before and after IPTW). In patients with AF undergoing catheter ablation, the total dementia risk decreased significantly [P = 0.015, hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.58-0.94] after multivariable adjustment, but not for the subtype of vascular dementia (P = 0.59, HR: 0.86, 95% CI: 0.49-1.50). CONCLUSION: Patients with AF have a higher incidence of all types of dementia, including Alzheimer's disease, vascular dementia, and a mixed type of dementia. Alzheimer's disease is less likely to occur in patients with AF undergoing catheter ablation.

Atrial fibrillation as a contributor to the mortality in patients with dementia: A nationwide cohort study.

Background: Knowledge of the risk of death in patients with dementia is essential for planning preventive strategies. This study aimed to evaluate the effect of atrial fibrillation (AF) on death risks and other factors associated with death in patients with dementia and AF. Methods: We conducted a nationwide cohort study using Taiwan's National Health Insurance Research Database. We identified subjects with dementia diagnosed for the first time and AF diagnosed concomitantly between 2013 and 2014. Subjects under the age of 18 years were excluded. Age, sex, and CHA2DS2-VASc scores were 1: 4 matched for AF patients (N = 1,679) and non-AF controls (N = 6,176) using the propensity score technique. The conditional Cox regression model and competing risk analysis were applied. The risk of mortality was tracked till 2019. Results: AF history was associated with higher risks of all-cause death (hazard ratio [HR]: 1.208; 95% confidence interval [CI]: 1.142-1.277) and cardiovascular death (subdistribution HR: 1.210; 95% CI: 1.077-1.359) in dementia patients than patients without a diagnosis of AF. For patients with both dementia and AF, they had a higher risk of death due to higher age, diabetes mellitus, congestive heart failure, chronic kidney disease, and prior stroke. Anti-arrhythmic drugs and novel oral anticoagulants significantly reduced the risk of death in patients with AF and dementia. Conclusion: This study found that AF is a risk factor for mortality in patients with dementia and explored several risk factors for AF-related mortality. This study highlights the importance of controlling AF especially in patients with dementia.

Corrigendum: Systolic blood pressure as the mediator of the effect of early menarche on the risk of coronary artery disease: A Mendelian randomization study.

[This corrects the article DOI: 10.3389/fcvm.2022.1023355.].

Hypertension as a Novel Link for Shared Heritability in Age at Menarche and Cardiometabolic Traits.

CONTEXT: Extremely early age at menarche, also called precocious puberty, has been associated with various cardiometabolic traits, but their shared heritability remains unclear. OBJECTIVES: This work aimed to identify new shared genetic variants and their pathways for age at menarche and cardiometabolic traits and to investigate the influence of central precocious puberty on childhood cardiometabolic traits. METHODS: Using the conjunction false discovery rate method, this study analyzed genome-wide association study data from the menarche-cardiometabolic traits among 59 655 females of Taiwanese ancestry and systemically investigated pleiotropy between age at menarche and cardiometabolic traits. To support the novel hypertension link, we used the Taiwan Puberty Longitudinal Study (TPLS) to investigate the influence of precocious puberty on childhood cardiometabolic traits. RESULTS: We discovered 27 novel loci, with an overlap between age at menarche and cardiometabolic traits, including body fat and blood pressure. Among the novel genes discovered, SEC16B, CSK, CYP1A1, FTO, and USB1 are within a protein interaction network with known cardiometabolic genes, including traits for obesity and hypertension. These loci were confirmed through demonstration of significant changes in the methylation or expression levels of neighboring genes. Moreover, the TPLS provided evidence regarding a 2-fold higher risk of early-onset hypertension that occurred in girls with central precocious puberty. CONCLUSION: Our study highlights the usefulness of cross-trait analyses for identifying shared etiology between age at menarche and cardiometabolic traits, especially early-onset hypertension. The menarche-related loci may contribute to early-onset hypertension through endocrinological pathways.

Epidemiological Characteristics and Meteorological Factors of Sudden Death among General Population of Ethnic Chinese in Taiwan: An Eighteen-Year Follow-Up Report in a Community.

Background: The epidemiological characteristics of sudden death may vary according to ethnicity and country. This study aimed to analyze the distribution of sudden deaths in Taiwan, as well as their epidemiological characteristics and the associated meteorological factors. Methods: The Chin-Shan Community Cardiovascular Cohort is a longitudinal study conducted in a community in Taipei County since July 1990. A total of 3,602 individuals aged 35 years and older were included in the study. Sudden deaths were prospectively recorded and analyzed. Results: Eighty-two (68.3% men) sudden deaths (8.56% of all deaths) were reported from July 1990 to December 2008, of which 87.8% were caused by cardiovascular disease. However, only 36.6% were attributed to coronary artery disease. There was a higher incidence of sudden death in the winter [incidence rate ratio (IRR): 1.91, 95% confidence interval (CI): 1.42-2.56], compared to fall, and the highest peak of sudden death occurred between 16:00-20:00 (IRR: 3.00, 95% CI: 1.72-5.22) compared to 00:00-04:00 as the reference group. Additionally, a relatively higher mean temperature was associated with a lower risk of sudden death (IRR: 0.96, 95% CI: 0.93-0.98). On the other hand, higher humidity (IRR: 1.09, 95% CI: 1.02-1.16) and discomfort index (IRR: 1.03, 95% CI: 1.003-1.05) were associated with increased risks of sudden death. Conclusions: Meteorological factors and circadian patterns were associated with sudden death among our Taiwanese cohort. Our study findings may support potential protective behavior for sudden death via weather forecasting.

Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts.

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). DESIGN: Pooled analysis. DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020. STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate. DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis. MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2 and <75% of baseline rate. RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I2=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m2), hypertension, diabetes, and coronary heart disease at baseline. CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.

Discriminative Ability of Left Ventricular Strain in Mildly Reduced Ejection Fraction Heart Failure.

Background: Left ventricular (LV) systolic strain is presumably a more sensitive myocardial indicator than LV ejection fraction (LVEF). Data regarding the use of LV strain in clinical risk stratification and in identifying angiotensin receptor-neprilysin inhibitor (ARNi) responders remain scarce in heart failure with mildly reduced ejection fraction (HFmrEF). Objectives: The authors aimed to examine whether assessing LV strain may provide prognostic insight beyond LVEF and help discriminate the therapeutic efficacy of ARNi in HFmrEF patients. Methods: LVEF and LV strain were quantified among 1,075 first-time hospitalized HFmrEF patients (mean age: 68.1 ± 15.1 years, 40% female). The MAGGIC (Meta-analysis Global Group in Chronic Heart Failure) risk score and its components were calculated. A Cox proportional hazard model was constructed for time-to-event analysis. Restrictive cubic spline curves were used to model the therapeutic effects of ARNi against renin-angiotensin system inhibitor according to baseline LVEF or LV strain. Results: LV strain showed a statistically significant inverse association with MAGGIC cardiac risk (coefficient: -0.14, P < 0.001). LV strain was independently associated with clinical outcomes after accounting for LVEF. MAGGIC-LV strain strata outperformed MAGGIC-LVEF strata in overall survival (Harrell's C-index: 0.71 and 0.56, P for difference <0.001; category-free net reclassification index: 0.44, P < 0.001). Lower LV strain but not LVEF consistently showed the beneficial therapeutic effects of ARNi against renin-angiotensin system inhibitor by Cox models and restrictive cubic spline (all P interaction <0.05). Conclusions: Among HFmrEF patients, LV strain may serve as an attractive systolic marker and provide a better prognostic and therapeutic discriminative measure for ARNi treatment than conventional LVEF.

Comparison of Aspergillus-specific antibody cut-offs for the diagnosis of aspergillosis.

Background: Aspergillus diseases are frequently encountered in patients who are immunocompromised. Without a prompt diagnosis, the clinical consequences may be lethal. Aspergillus-specific antibodies have been widely used to facilitate the diagnosis of Aspergillus diseases. To date, universally standardized cut-off values have not been established. This study aimed to investigate the cut-off values of Aspergillus-specific antibodies and perform a narrative review to depict the geographic differences in the Taiwanese population. Methods: We analyzed enrolled 118 healthy controls, 29 patients with invasive aspergillosis (IA), chronic pulmonary aspergillosis (CPA), and allergic bronchopulmonary aspergillosis (ABPA) and 99 with disease control, who were tested for Aspergillus fumigatus and Aspergillus niger-specific IgG and IgE using ImmunoCAP. 99 participants not fulfilling the diagnosis of IA, CPA, and ABPA were enrolled in the disease control group. The duration of retrieval of medical records from June 2018 to September 2021. Optimal cut-offs and association were determined using receiver operating characteristic curve (ROC) analysis. Results: We found that patients with CPA had the highest A. fumigatus-specific IgG levels while patients with ABPA had the highest A. fumigatus-specific IgE, and A. niger-specific IgG and IgE levels. In patients with CPA and ABPA, the optimal cut-offs of A. fumigatus-specific IgG and A. niger-specific IgG levels were 41.6, 40.8, 38.1, and 69.9 mgA/l, respectively. Geographic differences in the cut-off values of A. fumigatus-specific IgG were also noted. Specifically, the levels were different in eco-climatic zones. Conclusion: We identified the optimal cut-offs of Aspergillus-specific antibodies to facilitate a precise diagnosis of aspergillosis. The observed geographic differences of the antibody levels suggest that an eco-climatic-specific reference is needed to facilitate a prompt and accurate diagnosis of aspergillosis.

Exploring the Risk Factors of Sudden Cardiac Death Using an Electrocardiography and Medical Ultrasonography for the General Population Without a History of Coronary Artery Disease or Left Ventricular Ejection Fraction <35% and Aged >35 Years　- A Novel Point-Based Prediction Model Based on the Chin-Shan Community Cardiovascular Cohort.

BACKGROUND: Most of the factors and prediction models of sudden cardiac death (SCD) have been developed without considering the Asia population. The purpose of this study is to construct a point-based prediction model for the general population in Asia.Methods and Results: Chin-Shan Community Cardiovascular Cohort (CCCC) is a community-based longitudinal cohort initiated between 1990 and 1991, enrolling participants aged ≥35 years and following them up until 2005. Participants with coronary artery disease (CAD) or a left ventricular ejection fraction (LVEF) of 35% were excluded from this study. The Framingham risk score function was used to derive a simple point-based prediction model. Based on bootstrapping, a novel model (CCCC-SCD-Score) was validated. A total of 2,105 participants were analyzed. The incidence rate of SCD was 0.406 per 1,000 person-years. The CCCC-SCD-Score score was calculated using age groups (maximal points=4), left ventricular hypertrophy, hypertension, left ventricular ejection fraction <40%, aortic flow rate >190 cm/s, and carotid plaque scores ≥5 (point=1 for each risk factor). The C-index of the CCCC-SCD-Score in predicting SCD risks was 0.888 (95% confidence interval: 0.807-0.969). CONCLUSIONS: For the general Asian population without a history of CAD or a LVEF <35% and who are aged >35 years, the novel model-based scoring system effectively identifies the risk for SCD using the clinical factors, electrocardiographic and echocardiographic data.

Measuring the frequency and distribution of meiotic crossovers in homozygous barley inbred lines.

We report a novel approach for establishing the number and position of CO events in individual homozygous inbred plants by combining low level EMS mutagenesis, speed breeding, whole genome shotgun sequencing and sliding window analysis of the induced molecular variant data. We demonstrate the approach by exploring CO frequency and distribution in self-fertilised progeny of the inbred barley cultivar Bowman and compare these observations to similar data obtained from a Bowman nearly isogenic line (BW230 Hvmlh3) containing a mutation in the DNA mismatch repair gene HvMLH3. We have previously shown that Hvmlh3 decreases both plant fertility and recombination by ~50%. We compare our results to those from previously published traditional genetic analysis of F3 families derived from multiple F2 lines containing WT or mutant alleles of HvMLH3, revealing a high level of correspondence between analyses. We discuss possible applications of the approach in streamlining the assessment of recombination in plant meiosis research.

The evolutionary patterns of barley pericentromeric chromosome regions, as shaped by linkage disequilibrium and domestication.

The distribution of recombination events along large cereal chromosomes is uneven and is generally restricted to gene-rich telomeric ends. To understand how the lack of recombination affects diversity in the large pericentromeric regions, we analysed deep exome capture data from a final panel of 815 Hordeum vulgare (barley) cultivars, landraces and wild barleys, sampled from across their eco-geographical ranges. We defined and compared variant data across the pericentromeric and non-pericentromeric regions, observing a clear partitioning of diversity both within and between chromosomes and germplasm groups. Dramatically reduced diversity was found in the pericentromeres of both cultivars and landraces when compared with wild barley. We observed a mixture of completely and partially differentiated single-nucleotide polymorphisms (SNPs) between domesticated and wild gene pools, suggesting that domesticated gene pools were derived from multiple wild ancestors. Patterns of genome-wide linkage disequilibrium, haplotype block size and number, and variant frequency within blocks showed clear contrasts among individual chromosomes and between cultivars and wild barleys. Although most cultivar chromosomes shared a single major pericentromeric haplotype, chromosome 7H clearly differentiated the two-row and six-row types associated with different geographical origins. Within the pericentromeric regions we identified 22 387 non-synonymous SNPs, 92 of which were fixed for alternative alleles in cultivar versus wild accessions. Surprisingly, only 29 SNPs found exclusively in the cultivars were predicted to be 'highly deleterious'. Overall, our data reveal an unconventional pericentromeric genetic landscape among distinct barley gene pools, with different evolutionary processes driving domestication and diversification.