PR prolongation as a predictor of atrial fibrillation onset: A state-of-the-art review.

First-degree atrioventricular block (1-AVB), characterized by a PR interval exceeding 200 milliseconds, has traditionally been perceived as a benign cardiac condition. Recently, this perception has been challenged by investigations that indicate a potential association between PR prolongation and an elevated risk of atrial fibrillation (AF). To consolidate these findings, we performed a comprehensive review to assess the available evidence indicating a relationship between these two conditions. We searched MEDLINE and EMBASE databases as well as manually searched references of retrieved articles. We selected 18 cohort studies/meta-analyses involving general and special populations. Consistent findings across expansive cohort studies reveal that incremental increases in the PR interval may serve as an independent risk factor for AF. However, our analyses underscore the need for further research into the association between 1-AVB, defined by a specified PR interval cutoff, and the risk of AF.

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: A population-based cohort study.

IMPORTANCE: The use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. DESIGN: Population-based retrospective cohort study. PARTICIPANTS: Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching. EXPOSURE: Warfarin use within 14 days of IE diagnosis. MAIN OUTCOMES AND MEASURES: Patients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up. RESULTS: The matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39-0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70-1.53]), intracranial hemorrhage (HR:1.25 [0.77-2.04]), and gastrointestinal bleeding (HR:1.04 [0.60-1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34-8.31]), but not at 90-day (sub-HR:1.63 [0.95-2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression. CONCLUSIONS AND RELEVANCE: Warfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis. KEY POINTS: Question: Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe? FINDINGS: In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding. Meaning: In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage.

Healthcare Big Data in Hong Kong: Development and Implementation of Artificial Intelligence-Enhanced Predictive Models for Risk Stratification.

Routinely collected electronic health records (EHRs) data contain a vast amount of valuable information for conducting epidemiological studies. With the right tools, we can gain insights into disease processes and development, identify the best treatment and develop accurate models for predicting outcomes. Our recent systematic review has found that the number of big data studies from Hong Kong has rapidly increased since 2015, with an increasingly common application of artificial intelligence (AI). The advantages of big data are that i) the models developed are highly generalisable to the population, ii) multiple outcomes can be determined simultaneously, iii) ease of cross-validation by for model training, development and calibration, iv) huge numbers of useful variables can be analyzed, v) static and dynamic variables can be analyzed, vi) non-linear and latent interactions between variables can be captured, vii) artificial intelligence approaches can enhance the performance of prediction models. In this paper, we will provide several examples (cardiovascular disease, diabetes mellitus, Brugada syndrome, long QT syndrome) to illustrate efforts from a multi-disciplinary team to identify data from different modalities to develop models using territory-wide datasets, with the possibility of real-time risk updates by using new data captured from patients. The benefit is that only routinely collected data are required for developing highly accurate and high-performance models. AI-driven models outperform traditional models in terms of sensitivity, specificity, accuracy, area under the receiver operating characteristic and precision-recall curve, and F1 score. Web and/or mobile versions of the risk models allow clinicians to risk stratify patients quickly in clinical settings, thereby enabling clinical decision-making. Efforts are required to identify the best ways of implementing AI algorithms on the web and mobile apps.

Secular trends of health care resource utilization and costs between Brugada syndrome and congenital long QT syndrome: A territory-wide study.

BACKGROUND: Health care resource utilization (HCRU) and costs are important metrics of health care burden, but they have rarely been explored in the setting of cardiac ion channelopathies. HYPOTHESIS: This study tested the hypothesis that attendance-related HCRUs and costs differed between patients with Brugada syndrome (BrS) and congenital long QT syndrome (LQTS). METHODS: This was a retrospective cohort study of consecutive BrS and LQTS patients at public hospitals or clinics in Hong Kong, China. HCRUs and costs (in USD) for Accident and Emergency (A&E), inpatient, general outpatient and specialist outpatient attendances were analyzed between 2001 and 2019 at the cohort level. Comparisons were made using incidence rate ratios (IRRs [95% confidence intervals]). RESULTS: Over the 19-year period, 516 BrS (median age of initial presentation: 51 [interquartile range: 38-61] years, 92% male) and 134 LQTS (median age of initial presentation: 21 [9-44] years, 32% male) patients were included. Compared to LQTS patients, BrS patients had lower total costs (2 008 126 [2 007 622-2 008 629] vs. 2 343 864 [2 342 828-2 344 900]; IRR: 0.857 [0.855-0.858]), higher costs for A&E attendances (83 113 [83 048-83 177] vs. 70 604 [70 487-70 721]; IRR: 1.177 [1.165-1.189]) and general outpatient services (2,176 [2,166-2,187] vs. 921 [908-935]; IRR: 2.363 [2.187-2.552]), but lower costs for inpatient stay (1 391 624 [1 391 359-1 391 889] vs. 1 713 742 [1 713 166-1 714 319]; IRR: 0.812 [0.810-0.814]) and lower costs for specialist outpatient services (531 213 [531 049-531 376] vs. 558 597 [558268-558926]; IRR: 0.951 [0.947-0.9550]). CONCLUSIONS: Overall, BrS patients consume 14% less health care resources compared to LQTS patients in terms of attendance costs. BrS patients require more A&E and general outpatient services, but less inpatient and specialist outpatient services than LQTS patients.

The Association Between Neutrophil-Lymphocyte Ratio and Variability with New-Onset Dementia: A Population-Based Cohort Study.

BACKGROUND: Previous studies identified that neutrophil-to-lymphocyte ratio (NLR) may be a predictor of dementia. However, the associations between NLR and dementia at the population level were less explored. OBJECTIVE: This retrospective population-based cohort study was designed to identify the associations between NLR and dementia among patients visiting for family medicine consultation in Hong Kong. METHODS: The patients were recruited from January 1, 2000, to December 31, 2003, and followed up until December 31, 2019. The demographics, prior comorbidities, medications, and laboratory results were collected. The primary outcomes were Alzheimer's disease and related dementia and non-Alzheimer's dementia. Cox regression and restricted cubic spline were applied to identify associations between NLR and dementia. RESULTS: A cohort of 9,760 patients (male: 41.08% ; baseline age median: 70.2; median follow-up duration: 4756.5 days) with complete NLR were included. Multivariable Cox regression identified that patients with NLR >5.44 had higher risks of developing Alzheimer's disease and related dementia (hazard ratio [HR]: 1.50, 95% Confidence interval [CI]: 1.17-1.93) but not non-Alzheimer's dementia (HR: 1.33; 95% CI: 0.60-2.95). The restricted cubic splines demonstrated that higher NLR was associated with Alzheimer's disease and related dementia. The relationship between the NLR variability and dementia was also explored; of all the NLR variability measures, only the coefficient of variation was predictive of non-Alzheimer's dementia (HR: 4.93; 95% CI: 1.03-23.61). CONCLUSION: In this population-based cohort, the baseline NLR predicts the risks of developing dementia. Utilizing the baseline NLR during family medicine consultation may help predict the risks of dementia.

The Role of Electrophysiological Study in the Risk Stratification of Brugada Syndrome.

Brugada syndrome (BrS) is a complex arrhythmogenic disease associated with an increased risk of sudden cardiac death (SCD). The role of electrophysiological study (EPS) for risk stratification purposes of asymptomatic BrS patients remains still controversial. This study aims to summarize the existing data about the role of electrophysiological study for arrhythmic risk stratification of BrS patients without a prior history of aborted SCD or fatal arrhythmic event. Two independent investigators (G.B. and G.T.) performed a systematic search in the MedLine database and Cochrane library from their inception until April 2022 without any limitations. The reference lists of the relevant research studies as well as the relevant review studies and meta-analyses were manually searched. Nineteen studies were included in the final analysis. The included studies enrolled 6218 BrS patients (mean age: 46.9 years old, males: 76%) while 4265 (68.6%) patients underwent an EPS. The quantitative synthesis showed that a positive EPS study was significantly associated with arrhythmic events in BrS patients (RR, 1.74 [1.23-2.45]; P = 0.002; I2 = 63%]. By including the studies that provided data on the association of EPS with arrhythmic events during follow-up in patients without a prior history of aborted SCD or fatal arrhythmic event, the association between positive EPS study and future arrhythmic events remained significant (RR, 1.60 [1.08-2.36]; P = 0.02; I2 = 19%). In conclusion, EPS is a useful invasive tool for the risk stratification of BrS patients and can be used to identify the population of BrS patients who may be candidates for primary prevention of SCD with implantable cardioverter-defibrillator (ICD) implantation.

Sodium-glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitors on new-onset overall cancer in Type 2 diabetes mellitus: A population-based study.

BACKGROUND: Cancer is currently the second leading cause of death globally. There is much uncertainty regarding the comparative risks of new-onset overall cancer and pre-specified cancer for Type 2 diabetes mellitus (T2DM) patients on sodium-glucose cotransporter 2 inhibitors (SGLT2I) versus DPP4I. METHODS: This population-based cohort study patients included patients who were diagnosed with T2DM and administered either SGLT2 or DPP4 inhibitors between 1 January 2015 and 31 December 2020 in public hospitals of Hong Kong. RESULTS: This study included 60,112 T2DM patients (mean baseline age: 62.1 ± 12.4 years, male: 56.36%), of which 18,167 patients were SGLT2I users and 41,945 patients were dipeptidyl peptidase 4 inhibitor (DPP4I) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of all-cause mortality (HR: 0.92; 95% CI: 0.84-0.99; p= 0.04), cancer-related mortality (HR: 0.58; 95% CI: 0.42-0.80; p ≤ 0.001) and new diagnoses of any cancer (HR: 0.70; 95% CI: 0.59-0.84; p ≤ 0.001). SGLT2I use was associated with a lower risk of new-onset breast cancer (HR: 0.51; 95% CI: 0.32-0.80; p ≤ 0.001), but not of other malignancies. Subgroup analysis on the type of SGLT2I, dapagliflozin (HR: 0.78; 95% CI: 0.64-0.95; p = 0.01) and ertugliflozin (HR: 0.65; 95% CI: 0.43-0.98; p = 0.04) use was associated with lower risks of new cancer diagnosis. Dapagliflozin use was also linked to lower risks of breast cancer (HR: 0.48; 95% CI: 0.27-0.83; p = 0.001). CONCLUSION: Sodium-glucose cotransporter 2 inhibitor use was associated with lower risks of all-cause mortality, cancer-related mortality and new-onset overall cancer compared to DPP4I use after propensity score matching and multivariable adjustment.

Early atrial remodeling predicts the risk of cardiovascular events in patients with metabolic syndrome: a retrospective cohort study.

Background: This study aims to assess the prevalence of atrial cardiomyopathy (ACM) in patients with new-onset metabolic syndrome (MetS) and investigate whether ACM could be a predictor of hospital admission for cardiovascular (CV) events. Methods: Patients with MetS who were free of clinically proven atrial fibrillation and other CV diseases (CVDs) at baseline were included in the present study. The prevalence of ACM was compared between MetS patients with and without left ventricular hypertrophy (LVH). The time to first hospital admission for a CV event between subgroups was assessed using the Cox proportional hazard model. Results: A total of 15,528 MetS patients were included in the final analysis. Overall, LVH patients accounted for 25.6% of all newly diagnosed MetS patients. ACM occurred in 52.9% of the cohort and involved 74.8% of LVH patients. Interestingly, a significant percentage of ACM patients (45.4%) experienced MetS without LVH. After 33.2 ± 20.6 months of follow-up, 7,468 (48.1%) patients had a history of readmission due to CV events. Multivariable Cox regression analysis revealed that ACM was associated with an increased risk of admission for CVDs in the MetS patients with LVH [hazard ratio (HR), 1.29; 95% confidence interval (CI), 1.142-1.458; P < 0.001]. Likewise, ACM was found to be independently associated with hospital readmission due to CVD-related events in MetS patients without LVH (HR, 1.175; 95% CI, 1.105-1.250; P < 0.001). Conclusion: ACM is a marker of early myocardial remodeling and predicts hospitalization for CV events in patients with MetS.

Comparing sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors on new-onset depression: a propensity score-matched study in Hong Kong.

INTRODUCTION: The risk of new onset depression associated with sodium-glucose co-transporter 2 inhibitor (SGLT2I) use in patients with type 2 diabetes mellitus (T2DM) remains unclear. This study investigated the risk of new onset depression between SGLT2I and dipeptidyl peptidase 4 inhibitor (DPP4I) users. METHODS: This was a population-based cohort study of T2DM patients in Hong Kong between January 1st, 2015, and December 31st, 2019. T2DM patients over 18 with either SGLT2I or DPP4I use were included. 1:1 propensity-score matching using the nearest-neighbour method was conducted based on demographics, past comorbidities and non-DPP4I/SGLT2I medication use. Cox regression analysis models were used to identify significant predictors for new onset depression. RESULTS: The study cohort included a total of 18,309 SGLT2I users and 37,269 DPP4I users (55.57% male, mean age: 63.5 ± 12.9 years) with a median follow-up duration of 5.56 (IQR: 5.23-5.8) years. After propensity score matching, SGLT2I use was associated with a lower risk of new onset depression compared to DPP4I use (HR: 0.52, 95% CI: [0.35, 0.77], P = 0.0011). These findings were confirmed by Cox multivariable analysis and sensitive analyses. CONCLUSION: SGLT2I use is associated with significantly lower risk of depression compared to DPP4 use in T2DM patients using propensity score matching and Cox regression analyses.

Risk of diabetes mellitus among users of immune checkpoint inhibitors: A population-based cohort study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly established cancer therapeutics, but they are associated with new-onset diabetes mellitus (DM). Such risks have not been adequately quantified, and between-class and -sex differences remain unexplored. METHODS: This was a prospective cohort study of cancer patients receiving any ICI in Hong Kong between 2013 and 2021. Patients with known DM were excluded. Due to few patients using other ICIs, only programmed cell death 1 inhibitors (PD-1i) and programmed death ligand 1 inhibitors (PD-L1i) were compared, alongside between-sex comparison. When comparing PD-1i against PD-L1i, patients with the use of other ICIs or both PD-1i and PD-L1 were further excluded. Inverse probability treatment weighting (IPTW) was used to minimize between-group covariate imbalances. RESULTS: Altogether, 3375 patients were analyzed (65.2% males, median age 62.2 [interquartile range 53.8-69.5] years old). Over a median follow-up of 1.0 [0.4-2.4] years, new-onset DM occurred in 457 patients (13.5%), with a 3-year risk of 14.5% [95% confidence interval 13.3%, 15.8%]. IPTW achieve acceptable covariate balance between sexes, and between PD-1i (N = 622) and PD-L1i (N = 2426) users. Males had significantly higher risk of new-onset DM (hazard ratio 1.35 [1.09, 1.67], p = 0.006), while PD-1i and PD-L1i users did not have significantly different risks (hazard ratio vs PD-L1i 0.81 [0.59, 1.11], p = 0.182). These were consistent in those with at least 1 year of follow-up, and on competing risk regression. CONCLUSION: Users of ICI may have a substantial risk of new-onset DM, which may be higher in males but did not differ between PD-1i and PD-L1i.

Risk stratification of sudden cardiac death in asymptomatic female Brugada syndrome patients: A literature review.

BACKGROUND AND OBJECTIVES: Risk stratification in Brugada syndrome remains a difficult problem. Given the male predominance of this disease and their elevated risks of arrhythmic events, affected females have received less attention. It is widely known that symptomatic patients are at increased risk of sudden cardiac death (SCD) than asymptomatic patients, while this might be true in the male population; recent studies have shown that this association might not be significant in females. Over the past few decades, numerous markers involving clinical symptoms, electrocardiographic (ECG) indices, and genetic tests have been explored, with several risk-scoring models developed so far. The objective of this study is to review the current evidence of clinical and ECG markers as well as risk scores on asymptomatic females with Brugada syndrome. FINDINGS: Gender differences in ECG markers, the yield of genetic findings, and the applicability of risk scores are highlighted. CONCLUSIONS: Various clinical, electrocardiographic, and genetic risk factors are available for assessing SCD risk amongst asymptomatic female BrS patients. However, due to the significant gender discrepancy in BrS, the SCD risk amongst females is often underestimated, and there is a lack of research on female-specific risk factors and multiparametric risk scores. Therefore, multinational studies pooling female BrS patients are needed for the development of a gender-specific risk stratification approach amongst asymptomatic BrS patients.

Comparison of Sodium-Glucose Cotransporter-2 Inhibitor and Dipeptidyl Peptidase-4 Inhibitor on the Risks of New-Onset Atrial Fibrillation, Stroke and Mortality in Diabetic Patients: A Propensity Score-Matched Study in Hong Kong.

OBJECTIVE: To compare the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and dipeptidyl peptidase-4 inhibitors (DPP4Is) on adverse outcomes in diabetic patients in Hong Kong. METHODS: This was a retrospective population-based cohort study of type 2 diabetes mellitus patients (n = 72,746) treated with SGLT2I or DPP4I between January 1, 2015, and December 31, 2020, in Hong Kong. Patients with exposure to both DPP4I and SGLT2I therapy, without complete demographics or mortality data, or who had prior atrial fibrillation (AF) were excluded. The study outcomes were new-onset AF, stroke/transient ischemic attack, cardiovascular mortality and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I users was performed. RESULTS: The unmatched study cohort included 21,713 SGLT2I users and 39,510 DPP4I users (total: n = 61,233 patients; 55.37% males, median age: 62.7 years [interquartile range (IQR): 54.6-71.9 years]). Over a median follow-up of 2030 (IQR: 1912-2117) days, 2496 patients (incidence rate [IR]: 4.07%) developed new-onset AF, 2179 patients (IR: 3.55%) developed stroke/transient ischemic attack, 1963 (IR: 3.20%) died from cardiovascular causes and 6607 patients (IR: 10.79%) suffered from all-cause mortality. After propensity score matching (SGLT2I: n = 21,713; DPP4I: n = 21,713), SGLT2I users showed lower incidence of new-onset AF (1.96% vs. 2.78%, standardized mean difference [SMD] = 0.05), stroke (1.80% vs. 3.52%, SMD = 0.11), cardiovascular mortality (0.47% vs. 1.56%, SMD = 0.11) and all-cause mortality (2.59% vs. 7.47%, SMD = 0.22) compared to DPP4I users. Cox regression found that SGLT2I users showed lower risk of new-onset AF (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: [0.56, 0.83], P = 0.0001), stroke (HR: 0.64, 95% CI: [0.53, 0.79], P < 0.0001), cardiovascular mortality (HR: 0.39, 95% CI: [0.27, 0.56], P < 0.0001) and all-cause mortality (HR: 0.44, 95% CI: [0.37, 0.51], P < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory tests. CONCLUSIONS: Based on real-world data of type 2 diabetic patients in Hong Kong, SGLT2I use was associated with lower risk of incident AF, stroke/transient ischemic attack, and cardiovascular and all-cause mortality outcomes compared to DPP4I use.

Predictive value of neutrophil-to-lymphocyte ratio for atrial fibrillation and stroke in type 2 diabetes mellitus: The Hong Kong Diabetes Study.

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR) is a routinely available biomarker that reflects systemic inflammation. The study evaluated the predictive value of NLR for ischemic stroke and atrial fibrillation (AF) in patients with type 2 diabetes mellitus. METHODS: This was a population-based cohort study of patients with type 2 diabetes mellitus and complete blood count tests at baseline between 1 January 1st, 2009, and 31 December, 2009, at government-funded hospitals/clinics in Hong Kong. Follow-up was until 31 December, 2019, or death. RESULTS: A total of 85,351 patients (age = 67.6 ± 13.2 years old, male = 48.8%, follow-up = 3101 ± 1441 days) were included. Univariable Cox regression found that increased NLR at quartiles 2, 3 and 4 was significantly associated with higher risks of new-onset ischemic stroke (hazard ratio [HR]: 1.28 [1.20-1.37], p < .001, HR: 1.41 [1.32-1.51], p < .001 and HR: 1.38 [1.29-1.47], p < .001) and AF (HR: 1.09 [1.02-1.17], p < .015; HR: 1.28 [1.20-1.37], p < .001; HR: 1.39 [1.31-1.49], p < .001) compared to quartile 1. On multivariable analysis, NLR remained a significant predictor of ischemic stroke risk for quartiles 2 and 3 (quartile 2: HR: 1.14 [1.05, 1.22], p = .001; quartile 3: HR: 1.14 [1.06, 1.23], p < .001) but not quartile 4 (HR: 1.08 [0.994, 1.17], p = .070). NLR was not predictive of AF after adjusting for confounders (quartile 2: HR: 0.966 [0.874, 1.07], p = .499; quartile 3: HR: 0.978 [0.884, 1.08], p = .661; quartile 4: HR: 1.05 [0.935, 1.16], p = .462). CONCLUSION: NLR is a significant predictor of new-onset ischaemic stroke after adjusting for significant confounders in Chinese type 2 diabetes patients.

P-wave durations from automated electrocardiogram analysis to predict atrial fibrillation and mortality in heart failure.

BACKGROUND: P-wave indices have been used to predict incident atrial fibrillation (AF), stroke, and mortality. However, such indices derived from automated ECG measurements have not been explored for their predictive values in heart failure (HF). We investigated whether automated P-wave indices can predict adverse outcomes in HF. METHODS: This study included consecutive Chinese patients admitted to a single tertiary centre, presenting with HF but without prior AF, and with at least one baseline ECG, between 1 January 2010 and 31 December 2016, with last follow-up of 31 December 2019. RESULTS: A total of 2718 patients were included [median age: 77.4, interquartile range (IQR): (66.9-84.3) years; 47.9 males]. After a median follow-up of 4.8 years (IQR: 1.9-9.0 years), 1150 patients developed AF (8.8/year), 339 developed stroke (2.6/year), 563 developed cardiovascular mortality (4.3/year), and 1972 had all-cause mortality (15.1/year). Compared with 101-120 ms as a reference, maximum P-wave durations predicted new-onset AF at ≤90 ms [HR: 1.17(1.11, 1.50), P < 0.01], 131-140 ms [HR: 1.29(1.09, 1.54), P < 0.001], and ≥141 ms [HR: 1.52(1.32, 1.75), P < 0.001]. Similarly, they predicted cardiovascular mortality at ≤90 ms [HR: 1.50(1.08, 2.06), P < 0.001] or ≥141 ms [HR: 1.18(1.15, 1.45), P < 0.001], and all-cause mortality at ≤90 ms [HR: 1.26(1.04, 1.51), P < 0.001], 131-140 ms [HR: 1.15(1.01, 1.32), P < 0.01], and ≥141 ms [HR: 1.31(1.18, 1.46), P < 0.001]. These remained significant after adjusting for significant demographics, past co-morbidities, P-wave dispersion, and maximum P-wave amplitude. CONCLUSIONS: Extreme values of maximum P-wave durations (≤90 ms and ≥141 ms) were significant predictors of new-onset AF, cardiovascular mortality, and all-cause mortality.