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Background Little is known whether patients with lower health literacy could retain the practice and knowledge of home blood pressure monitoring (HBPM) after an educational programme. Methods A cluster randomised controlled trial in five primary care clinics recruited participants with uncontrolled hypertension. Clinics were randomised either to a HBPM group education (Risk Assessment and Management Programme (RAMP-group), or individual counselling of self-management (RAMP-individual). Health literacy was assessed by the Chinese Health Literacy Scale for Chronic Care. Practice and knowledge of HBPM were surveyed by a 10-item HBPM knowledge checklist and patient record review 6 months after interventions. Predictors for regular HBPM and good HBPM knowledge were assessed by multivariate logistic regression models. Results 287 participants (RAMP-group: 151; RAMP-individual: 136) were follow-up for 6 months. 272 participants completed the knowledge questionnaires (response rate 94.8%). 67.8% of the participants performed HBPM regularly, and there was no statistical difference between both interventions. Age more than 65 (adjusted odds ratios (aOR) 2.58, 95% CI 1.37 to 4.86, p=0.003), not working (aOR 2.34, 95% CI 1.10 to 4.97, p=0.027)and adequate health literacy (aOR 2.25, 95% CI 1.28 to 3.95, p=0.005) predicted regular HBPM. Participants in RAMP-group demonstrated a significant lower body weight than those in RAMP-individual (−0.3±2.0 kg vs +0.7 ±1.7 kg, p Conclusion Patients could retain HBPM knowledge better after RAMP-group than RAMP-individual. Older, retired and patients with adequate health literacy were more likely to continue weekly HBPM 6 months after education. Trial registration number NCT02551393.

Introduction The present study examined the gender-specific prognostic value of blood pressure (BP) and its variability in the prediction of dementia risk and developed a score system for risk stratification. Materials and Methods This was a retrospective, observational population-based cohort study of patients admitted to government-funded family medicine clinics in Hong Kong between January 1, 2000 and March 31, 2002 with at least 3 blood pressure measurements. Gender-specific risk scores for dementia were developed and tested. Results The study consisted of 74 855 patients, of whom 3550 patients (incidence rate: 4.74%) developed dementia over a median follow-up of 112 months (IQR= [59.8–168]). Nonlinear associations between diastolic/systolic BP measurements and the time to dementia presentation were identified. Gender-specific dichotomized clinical scores were developed for males (age, hypertension, diastolic and systolic BP and their measures of variability) and females (age, prior cardiovascular, respiratory, gastrointestinal diseases, diabetes mellitus, hypertension, stroke, mean corpuscular volume, monocyte, neutrophil, urea, creatinine, diastolic and systolic BP and their measures of variability). They showed high predictive strengths for both male (hazard ratio [HR]: 12.83, 95% confidence interval [CI]: 11.15–14.33, P value Conclusion Gender-specific clinical risk scores incorporating BP variability can accurately predict incident dementia and can be applied clinically for early disease detection and optimized patient management.

Previous studies have shown that ticagrelor reduced risk of pneumonia in patients with acute coronary syndrome (ACS) compared to clopidogrel, however, its effect in patients with non-ACS cardiovascular diseases remains uncertain. The aim was to investigate the effect of ticagrelor on pneumonia and pneumonia-specific death compared to clopidogrel in non-ACS patients in Hong Kong. This was a population-based cohort study. We included consecutive patients using ticagrelor or clopidogrel admitted for non-ACS conditions in Hong Kong public hospitals from March 2012 to September 2019. Patients using both drugs were excluded. The outcomes of interest were incident pneumonia, all-cause death, and pneumonia-specific death. Multivariable survival analysis models were used to estimate the effects [hazard ratio (HR) and 95% confidence interval (CI)]. Propensity score matching, adjustment and weighting were performed as sensitivity analyses. In total, 90,154 patients were included (mean age 70.66 years, males 61.7%). The majority of them (97.2%) used clopidogrel. Ticagrelor was associated with a lower risk of incident pneumonia [0.59 (0.46–0.75)], all-cause death [0.83 (0.73–0.93)] and pneumonia-specific death [0.49 (0.36–0.67)]. Sensitivity analyses yielded similar results. Ticagrelor was associated with lower risk of all-cause death, pneumonia-specific death, and incident pneumonia in patients with non-ACS cardiovascular conditions, consistent with previous evidence in patients with ACS. This additional effect of anti-pneumonia should be considered when choosing a proper P2Y12 inhibitor for patients with high risk of pneumonia.

Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may be associated with higher susceptibility of COVID-19 infection and adverse outcomes. We compared ACEI/ARB use and COVID-19 positivity in a case-control design, and severity in COVID-19 positive patients.Consecutive patients who attended Hong Kong's public hospitals or outpatient clinics between 1 January and 28 July 2020 for COVID-19 real time-PCR (RT-PCR) tests were included. Baseline demographics, past comorbidities, laboratory tests and use of different medications were compared between COVID-19 positive and negative patients. Severe endpoints for COVID-19 positive patients were 28-day mortality, need for intensive care admission or intubation.This study included 213 788 patients (COVID-19 positive: n = 2774 patients; negative: n = 211 014). In total, 162 COVID-19 positive patients (5.83%) met the severity outcome. The use of ACEI/ARB was significantly higher amongst cases than controls (n = 156/2774, 5.62 vs. n = 6708/211014, 3.17%; P 0.0001). Significant univariate predictors of COVID-19 positivity and severe COVID-19 disease were older age, higher Charlson score, comorbidities, use of ACEI/ARB, antidiabetic, lipid-lowering, anticoagulant and antiplatelet drugs and laboratory tests (odds ratio1, P 0.05). The relationship between the use of ACEI/ARB and COVID-19 positivity or severe disease remained significant after multivariable adjustment. No significant differences in COVID-19 positivity or disease severity between ACEI and ARB use were observed (P 0.05).There was a significant relationship between ACEI/ARB use and COVID-19 positivity and severe disease after adjusting for significant confounders.

Objectives Lean mass is commonly measured by 3 modalities, dual energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and computerized tomography (CT). CT is considered the most accurate, while lean mass measured by DXA and BIA often consists of non-muscle compartment, and hence considered less accurate when compared with CT. It remains unclear if the association of lean mass with mortality would differ using different measurement modalities. Methods A systematic review and meta-analysis of lean mass and mortality was conducted. The analysis was stratified by different measurement modalities and health conditions. Pooled hazard ratios were estimated using a random effects model. Results This meta-analysis included 188 studies with 98 468 participants. Reduced lean mass measured by BIA, DXA, and CT, was associated with increased risk of mortality with a hazard ratio (HR) of 1.35 (95% CI, 1.21–1.49), 1.18 (95% CI, 1.06–1.30), and 1.44 (95% CI, 1.32–1.57), respectively. Similarly, low lean mass defined by BIA-, DXA-, and CT-measurement was associated with increased risk of mortality, with an HR of 1.81 (95% CI, 1.56–2.10), 1.44 (95% CI, 1.29–1.60), and 1.78 (95% CI, 1.64–1.93). Conclusions Reduced and low lean mass were robustly associated with increased mortality in studies using different measurement modalities.

Objectives The aim of this meta-analysis is to comprehensively evaluate the effects of lean mass on all-cause mortality across different cancer types. Methods This is a meta-analysis. Cohort studies on lean mass and mortality published before December 20, 2017 were obtained by systematic search on PubMed, Cochrane Library, and Embase. Inclusion criteria were cohort studies reporting lean mass measurements by dual-energy X-ray absorptiometry, bioimpedance analysis or computed tomography, and with all-cause mortality as the study outcome. Exclusion criteria were studies using muscle mass surrogates, anthropometric measurement of muscle, rate of change in muscle mass, and sarcopenia defined by composite criteria. Hazard ratios (HRs) and 95% confidence intervals (CIs) of low/reduced lean mass on cancer mortality were pooled with a random-effects model. Subgroup analysis stratifying studies according to cancer type and measurement index was performed. Results Altogether 100 studies evaluated the association between lean mass and cancer mortality. The overall pooled HR on cancer mortality was 1.41 (95% CI, 1.24 to 1.59) for every standard deviation decrease in lean mass and 1.69 (95% CI, 1.56 to 1.83) for patients with sarcopenia (binary cutoffs). Overall mortality was also significantly associated with sarcopenia in across various cancer types, except for hematopoietic, breast, ovarian and endometrial, and prostate cancer. Conclusions The robust association of decreased lean mass with increased mortality further justified the importance of developing clinical guidelines for managing sarcopenia in cancer patients. Public health initiatives aiming at promoting awareness of muscle health in susceptible individuals are urgently needed.

Objectives Sarcopenia has been an emerging theme in clinical oncology. Various definitions of sarcopenia have been proposed, but their prognostic performance have yet to be evaluated and compared. The aim of this meta-analysis is to comprehensively evaluate the performance of different cutoff definitions of sarcopenia in cancer mortality prognostication. Methods This is a meta-analysis. Cohort studies on lean mass and mortality published before December 20, 2017 were obtained by systematic search on PubMed, Cochrane Library, and Embase. Inclusion criteria were cohort studies reporting binary lean mass categorized according to clearly defined cutoffs, and with all-cause mortality as study outcome. Studies were stratified according to the cutoff(s) used in defining low lean mass. The cutoff-specific hazard ratios (HRs) and 95% confidence intervals (CIs) of low lean mass on cancer mortality were pooled with a random-effects model and compared. Results Altogether 81 studies that studied binary lean mass were included. The pooled HRs on cancer mortality using the 3 most used definitions were: 1.74 (95% CI, 1.46–2.07) using the definition proposed by International Consensus of Cancer Cachexia, 1.45 (95% CI, 1.21–1.75) using that by Martin, and 1.58 (95% CI, 1.35–1.84) using that by Prado. The associations between sarcopenia and cancer mortality using other definitions were all statistically significant, despite different estimates were observed. Conclusions The association of low lean mass with increased mortality was consistent across different definitions; this provides further evidence on the poorer survival in cancer patients with sarcopenia. However, further studies evaluating the performance of each definition are warranted.

Lead is a heavy metal without a biological role. High level of lead exposure is known to be associated with hypertension, but the risk at low levels of exposure is uncertain. In this study, data from US NHANES 1999–2016 were analyzed. Adults with blood lead and blood pressure measurements, or self-reported hypertension diagnosis, were included. If not already diagnosed, hypertension was defined according to the AHA/ACC 2017 hypertension guideline. Results were analyzed using R statistics version 3.5.1 with sample weight adjustment. Logistic regression was used to study the association between blood lead level and hypertension. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated. Altogether, 39,477 participants were included. Every doubling in blood lead level was associated with hypertension (OR [95%CI] 1.45 [1.40–1.50]), which remained significant after adjusting for demographics. Using quartile 1 as reference, higher blood lead levels were associated with increased adjusted odds of hypertension (Quartile 4 vs. Quartile 1: 1.22 [1.09–1.36]; Quartile 3 vs. Quartile 1: 1.15 [1.04–1.28]; Quartile 2 vs. Quartile 1: 1.14 [1.05–1.25]). In conclusion, blood lead level is associated with hypertension in the general population with blood lead levels below 5 µg/dL. Our findings suggest that reducing present levels of environmental lead exposure may bring cardiovascular benefits by reducing blood pressure.

The liver fat score (LFS) has been proposed to be a simple non-invasive marker of non-alcoholic fatty liver disease (NAFLD), which is highly prevalent in the general population. We tested its association with cardiovascular diseases (CVDs) and prognosis. 17,244 adult participants from the National Health and Nutrition Examination Survey 1999–2016 were included. LFS is calculated from variables including serum aspartate transaminase/alanine transaminase (AST/ALT) ratio, fasting serum aspartate transaminase (AST) level, fasting serum insulin level, presence of metabolic syndrome and diabetes mellitus. In cross-sectional analysis, logistic regression was used to examine the association of the LFS with coronary heart disease (CHD), myocardial infarction (MI), congestive heart failure (CHF), stroke and angina pectoris. Mortality during follow-up was analysed using Cox proportional hazard regression. LFS was associated with CHD (adjusted odds ratio [OR]: 1.09 per standard deviation [SD], 95% confidence interval [95% CI]: 1.03–1.15) (p = .003), CHF (1.11, 1.04–1.18) (p = .003) and angina pectoris (1.08, 1.02–1.13) (p = .005). LFS was not associated with MI or stroke, but was associated with increased all-cause and cardiovascular mortality with hazard ratios (HRs) of 1.10 (95% CI: 1.07–1.13) (p < .001) and 1.12 (95% CI: 1.06–1.17) (p < .001), respectively. NAFLD is usually asymptomatic, but this large study of a large general population shows that LFS is associated with CHD, CHF, angina pectoris, cardiovascular and all-cause mortality. Determining the LFS is worthwhile, as it identifies people with NAFLD, who may also be at increased cardiovascular risk.Key MessagesLiver fat score (LFS), a non-invasive marker of non-alcoholic fatty liver disease (NAFLD), is associated with coronary heart disease (CHD), congestive heart failure (CHF) and angina.LFS is also associated with increased cardiovascular and all-cause mortality.Determining the LFS is worthwhile as it identifies people with NAFLD as well as increased cardiovascular risk. Liver fat score (LFS), a non-invasive marker of non-alcoholic fatty liver disease (NAFLD), is associated with coronary heart disease (CHD), congestive heart failure (CHF) and angina. LFS is also associated with increased cardiovascular and all-cause mortality. Determining the LFS is worthwhile as it identifies people with NAFLD as well as increased cardiovascular risk.

BackgroundDepression and cardiovascular disease (CVD) are associated with each other but their relationship remains unclear. We aim to determine whether genetic predisposition to depression are causally linked to CVD [including coronary artery disease (CAD), myocardial infarction (MI), stroke and atrial fibrillation (AF)].MethodsUsing summary statistics from the largest genome-wide association studies (GWAS) or GWAS meta-analysis of depression (primary analysis: n = 500 199), broad depression (help-seeking behavior for problems with nerves, anxiety, tension or depression; secondary analysis: n = 322 580), CAD (n = 184 305), MI (n = 171 875), stroke (n = 446 696) and AF (n = 1 030 836), genetic correlation was tested between two depression phenotypes and CVD [MI, stroke and AF (not CAD as its correlation was previously confirmed)]. Causality was inferred between correlated traits by Mendelian Randomization analyses.ResultsBoth depression phenotypes were genetically correlated with MI (depression: rG = 0.169; p = 9.03 × 10−9; broad depression: rG = 0.123; p = 1 × 10−4) and AF (depression: rG = 0.112; p = 7.80 × 10−6; broad depression: rG = 0.126; p = 3.62 × 10−6). Genetically doubling the odds of depression was causally associated with increased risk of CAD (OR = 1.099; 95% CI 1.031–1.170; p = 0.004) and MI (OR = 1.146; 95% CI 1.070–1.228; p = 1.05 × 10−4). Adjustment for blood lipid levels/smoking status attenuated the causality between depression and CAD/MI. Null causal association was observed for CVD on depression. A similar pattern of results was observed in the secondary analysis for broad depression.ConclusionsGenetic predisposition to depression may have positive causal roles on CAD/MI. Genetic susceptibility to self-awareness of mood problems may be a strong causal risk factor of CAD/MI. Blood lipid levels and smoking may potentially mediate the causal pathway. Prevention and early diagnosis of depression are important in the management of CAD/MI.

Observational studies have found associations between urinary sodium (UNa) with obesity, body shape and composition; but the findings may be biased by residual confounding. The objective of this two-sample Mendelian randomization (MR) study was to analyze their causal associations in both sex-combined and sex-specific models. Genome-wide association studies of UNa, body mass index (BMI), BMI-adjusted waist-to-hip ratio (WHR), body fat (BF) percentage and estimated glomerular filtration rate (eGFR) were identified. We initially extracted fifty SNPs associated with UNa at significance level of 5 × 10–8, but further removed those SNPs with potential horizontal pleiotropy. Univariable and multivariable MR with adjustment for eGFR were performed. Inverse-variance weighted MR was performed as the primary analysis, with MR-Egger methods as sensitivity analysis. The potential bidirectional association between BMI and UNa was investigated. All exposure and outcomes were continuous, and the effect measure was regression coefficients (beta) and their 95% confidence intervals (95% CI). The total sample size was up to 322 154. UNa was causally associated with increased BMI in both men [eGFR-adjusted beta 0.443 (0.163–0.724)] and women [0.594 (0.333–0.855)]. UNa caused BF percentage increase in men [0.622 (0.268–0.976)] and women [0.334 (0.007–0.662)]. UNa significantly elevated BMI-adjusted WHR in men [0.321 (0.094–0.548)], but not in women [0.170 (− 0.052 to 0.391)]. Additionally, we found that BMI causally increased UNa [0.043 (0.023–0.063)]. UNa increased BMI and BF percentage. Salt intake affects male body shape by increasing BMI-adjusted WHR, but showed no effects on female body shape. The bidirectional association between BMI and UNa suggested that salt reduction measures and weight reduction measures should be implemented simultaneously to break the vicious cycle and gain more health benefits.

Objective To determine the incidence and prevalence of gout in the general population and the utilisation of urate-lowering therapy (ULT) among patients with gout in Hong Kong. Methods A total of 2,741,862 subjects who attended any outpatient clinics or accident and emergency department (with or without hospitalisation) in 2005 and did not die before 2006 were identified from the Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority in Hong Kong. All subjects were followed until the end of 2016 or death. Demographics, diagnosis of gout, serum urate levels, and ULT prescriptions were retrieved from CDARS. Gout was defined by the diagnosis codes in CDARS. The serum urate levels achieved after prescribing ULT were the means of all serum urate levels measured 6 months after prescriptions. Results were analysed by R version 3.3.3 with package ‘prevalence’ version 0.4.0. Results The crude incidence of gout increased from 113.05/100,000 person-years (PY) in 2006 to 211.62/100,000 PY in 2016. The crude prevalence of gout increased from 1.56% in 2006 to 2.92% in 2016. Only 25.55% of patients with gout were prescribed ULT in 2016. 35.8% of patients treated with ULT were able to achieve the target serum urate level of Conclusions Population ageing as well as other risk factors contributed to an increase in the incidence and prevalence of gout in Hong Kong. In 2016, the crude prevalence of gout in Hong Kong was comparable to that in many western countries. However, only one in four patients with gout in Hong Kong was prescribed ULT.

Aims Ticagrelor has been shown to reduce the risk of pneumonia and improve lung function, but the findings across studies were inconsistent. The objective is to investigate the relative safety of ticagrelor vs. clopidogrel on infection outcomes in patients with cardiovascular diseases. Methods and results We searched MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov up to 15 October 2019. Randomized controlled trials comparing ticagrelor and clopidogrel that reported infection outcomes were included. The primary outcome was pneumonia. Secondary outcomes were upper respiratory tract infection (URTI), urinary tract infection (UTI), and sepsis. Study quality was assessed using the Cochrane Risk of Bias tool. Study selection, data extraction, and quality assessment were conducted by independent authors. Random-effects model was used for data synthesis. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled with a random-effects model. Out of 5231 citations, 10 trials with altogether 37 514 patients were included. Ticagrelor was associated with a lower risk of pneumonia (RR 0.80, 95% CI 0.67–0.95) compared to clopidogrel. There were no statistically significant differences for URTI (RR 0.71, 95% CI 0.34–1.48), UTI (RR 1.06, 95% CI 0.73–1.64), or sepsis (RR 0.79, 95% CI 0.50–1.26). Conclusion Compared to clopidogrel, ticagrelor reduces the risk of pneumonia, but not URTI, UTI, or sepsis. Our study provides further evidence for recommending ticagrelor to patients with acute coronary syndrome at risk of pneumonia, although the mechanism by which ticagrelor reduces the risk of pneumonia merits further research.

ObjectiveTo investigate the associations of alkaline phosphatase (ALP) variability measures with new onset heart failure, cardiovascular mortality, and all-cause mortality in type 2 diabetes mellitus patients with a populational-cohort study.MethodThis study included patients with type 2 diabetes mellitus who presented to ambulatory, outpatient and inpatient facilities managed by the public sector in Hong Kong between January 1st, 2000 to December 31st, 2019. Comprehensive clinical and medical data including demographics, past comorbidities, medications, and laboratory examinations of complete blood, lipid/glycemic profile and their variability were collected. ALP and its variability measures were extracted. Univariable and multiple multivariable Cox regression were used to identify the associations of alkaline phosphatase variability with new onset heart failure and mortality risks. Patients were stratified into three subgroups based on the tertiles of baseline ALP level.ResultsThe study cohort consisted of 14289 patients (52.52% males, mean age at initial drug exposure: 74.55 years old [standard deviation (SD): 12.7]). Over a mean follow up of 2513 days [interquartile range (IQR): 1151-4173]), 10182 patients suffered from all-cause mortality (incidence rate [IR]: 71.25%), 1966 patients (IR: 13.75%) died from cardiovascular causes, and 1171 patients (IR: 8.19%) developed with new onset heart failure. Higher cumulative incidences of all three outcomes were observed for the highest tertile of ALP compared to medium/low tertiles. ALP baseline and variability level predicted new onset heart failure, cardiovascular and all-cause mortality before adjusting for subclinical biomarkers (p < 0.01). Amongst the measures of ALP variability, the hazard ratio (HR) of coefficient of variation (CV) was markedly raised in particular (new onset heart failure: HR=2.73, 95% confidence interval [CI]= [1.71-4.37], p ConclusionsRaised ALP level and variability are associated with increased risks of all-cause mortality, cardiovascular mortality and new onset heart failure amongst patients with type 2 diabetes mellitus.

ObjectivesTo compare the rates of major cardiovascular adverse events in sodium-glucose cotransporter-2 inhibitors (SGLT2I) and dipeptidyl-peptidase-4 inhibitors (DPP4I) users in a Chinese population.BackgroundSGLT2I and DPP4I are increasingly prescribed for type 2 diabetes mellitus patients. However, few population-based studies are comparing their effects on incident heart failure or myocardial infarction.MethodsThis was a population-based retrospective cohort study using the electronic health record database in Hong Kong, including type 2 diabetes mellitus patients receiving either SGLT2I or DPP4I between January 1st, 2015, to December 31st, 2020. Propensity-score matching was performed in a 1:1 ratio based on demographics, past comorbidities, non-SGLT2I/DPP4I medications with nearest-neighbor matching (caliper=0.1). Univariable and multivariable Cox models were used to identify significant predictors for new onset heart failure, new onset myocardial infarction, cardiovascular mortality, and all-cause mortality. Sensitivity analyses with competing risk models and multiple propensity score matching approaches were conducted. Subgroup age and gender analyses were presented.ResultsA total of 41994 patients (58.89% males, median admission age at 58 years old, interquartile rage [IQR]: 51.2-65.3) were included in the study cohorts with a median follow-up duration of 5.6 years (IQR: 5.32-5.82). After adjusting for significant demographics, past comorbidities, medication prescriptions and biochemical results, SGLT2I users have a significantly lower risk for myocardial infarction (hazard ratio [HR]: 0.34, 95% confidence interval [CI]: [0.28, 0.41], P < 0.0001), cardiovascular mortality (HR: 0.53, 95% CI: [0.38, 0.74], P = 0.0002) and all-cause mortality (HR: 0.21, 95% CI: [0.18, 0.25], P= 0.0001) under multivariable Cox regression. However, the risk for heart failure is comparable (HR: 0.87, 95% CI: [0.73, 1.04], P= 0.1343).ConclusionsSGLT2 inhibitors are protective against adverse cardiovascular events compared to DPP4I. The prescription of SGLT2I is preferred especially for males and patients aged 65 or older to prevent cardiovascular risks.

Context Patients with diabetes are at a higher risk of pneumonia and pneumonia mortality. Sodium glucose co-transporter 2 inhibitors (SGLT2is), the latest class of glucose-lowering agents, were shown to reduce the risk of pneumonia in clinical trials. However, the real-world effectiveness of SGLT2is on the risk of pneumonia is largely unknown. Objective To investigate the associations between SGLT2is use and the risk of pneumonia and pneumonia mortality compared with dipeptidyl peptidase-4 inhibitors (DPP4is) using an electronic medical database in Hong Kong. Design A retrospective cohort study. The “prevalent new-user” design was adopted to account for the previous exposure to the study drugs being compared. Propensity score (PS) matching (1:4) was used to balance the baseline characteristics of the 2 groups. Setting and participants Electronic health data of type 2 diabetes patients using SGLT2is and DPP4is between 2015 and 2018 was collected from the Clinical Data Analysis and Reporting System. Main Outcome Measures Pneumonia incidence and mortality. Results The PS-matched cohort consisted of 6664 users of SGLT2is and 26 656 users of DPP4is, with a mean follow-up of 3.8 years. Poisson regression showed that SGLT2is use was associated with lower risk of pneumonia compared with DPP4is with an absolute rate difference of 4.05 per 1000 person-years (95% CI, 2.61-5.51). The corresponding incidence rate ratio was 0.71 (95% CI, 0.62-0.81). Similar reduction in risk of pneumonia death was observed (hazard ratio 0.57; 95% CI, 0.42-0.77). Conclusion Compared with DPP4is, SGLT2is use was associated with a reduced risk of pneumonia and pneumonia mortality in a real-world setting.

Introduction: Obesity is a public health crisis in the USA. This study aimed to estimate the prevalence of obesity and severe obesity in US children and adolescents and identify novel targetable risk factors associated with childhood obesity. Methods: From the US National Health and Nutrition Examination Survey from 1999 to 2018, 35,907 children aged 2–19 with body mass index (BMI) data were included. Obesity and severe obesity were defined as BMI ≥95th percentile and ≥120% of 95th percentile of US Centers for Disease Control and Prevention growth charts, respectively. Trends in the prevalence of obesity and subgroup analyses according to socioeconomic factors and language used in the interview were analyzed. Results: The prevalence of obesity and severe obesity increased from 14.7 [95% confidence interval: 12.9–17.0]% to 19.2 [17.2–21.0]% and 3.9 [2.9–5.0]% to 6.1 [4.8–8.0]% in 1999–2018, respectively (p = 0.001 and p = 0.014, respectively). In 2017–2018, the prevalence of obesity among children from Spanish-speaking households was 24.4 [22.4–27.0]%, higher than children from English-speaking households (p = 0.027). Conclusion: The prevalence of childhood obesity kept increasing in 1999–2018. The problem is worse in children from Spanish-speaking households. Novel and targeted public health intervention strategies are urgently warranted to effectively halt the rising epidemic of childhood obesity.

ObjectiveTo explore the association between cardiometabolic dysregulation, an integral component of allostatic load, and health risk behaviours (HRBs) of the Hong Kong healthy adult population.DesignSecondary analysis of cross-sectional anonymous data.SettingData on sociodemographics, self-reported health status, HRBs and biomarkers were extracted from the Hong Kong Population Health Survey 2014/2015.ParticipantsOne thousand five hundred and fifty-one participants aged 18–64 years without self-reported diagnoses of hypertension, diabetes mellitus, hyperlipidaemia, cardiovascular disease, cognitive impairment or cancer.Primary outcome measuresCardiometabolic dysregulation index (CMDI), ranging from 0 to 6, was calculated by counting the number of biomarkers including systolic blood pressure, diastolic blood pressure, waist to hip ratio, glycated haemoglobin, total cholesterol to high-density lipoprotein cholesterol ratio, and triglycerides that were above the respective normal level suggested by international guidelines and literature. HRBs including smoking, dietary habits and sleeping hours were collected by self-report questionnaire. Alcohol consumption was assessed by the 10-item Alcohol Use Disorders Identification Test, while physical activity level was measured using the Global Physical Activity Questionnaire. A composite HRB score, ranging from 0 to 5, was calculated as the cumulative number of HRBs. The effect of HRB on CMDI was evaluated by negative binomial regression with adjustment for socioeconomic status, health awareness and comorbidities of the participants.ResultsThe mean CMDI of the studied population was 1.6; 29.5% had a CMDI of 0, whereas 1.5% had a CMDI of 6. Significant difference was observed in mean CMDI between gender and different age groups. Sleeping less than 6 hours (incidence rate ratio (IRR)=1.26, pConclusionSmoking, physical inactivity and inadequate sleep—an essential yet often overlooked health behaviour—were associated with higher CMDI in the Hong Kong healthy adult population.

Background Early identification of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease risk stratification and prevention. We sought to identify predictors for the long‐term absence of carotid plaque among young adults. Methods and Results We included 508 participants from the Bogalusa Heart Study without clinical atherosclerotic cardiovascular disease who were free of carotid plaque at baseline (2001–2002) and underwent ultrasound imaging at follow‐up (2013–2016). Modified Poisson regression estimated the persistent absence of plaque over 12.8 years. Participants were on average age 36.2 years at baseline, 64% were women, and 29% were Black. Although nearly all participants (97%) had a 10‐year atherosclerotic cardiovascular disease risk

Background: Metabolic syndrome (MetS) is a cluster of risk factors presaging the development of cardiovascular diseases and diabetes. It is a risk factor for severe coronavirus disease 2019 (COVID-19). This study aims to estimate the prevalence of MetS in the US National Health and Nutrition Examination Survey (NHANES) 2011-2018.Methods: This cohort study included 22370 eligible participants aged ≥20 years from the NHANES 2011-2018. MetS was defined as the presence of at least three of these components: central obesity, reduced high-density lipoprotein, elevated triglycerides, elevated blood pressure and elevated fasting blood glucose. The prevalence of MetS was estimated taking into account the complex sampling. The time trend was evaluated using logistic regression. Annual percentage changes (APC) were used to measure the trends in MetS prevalence.Results: The prevalence of MetS was 36.2% (95% CI, 32.3-40.3), 34.8% (95% CI, 32.3-37.4), 39.9% (95% CI, 36.6-43.2) and 38.3% (95% CI, 35.3-41.3) in 2011-2, 2013-4, 2015-6, 2017-8, respectively (P for trend =.08). Among the MetS components, the prevalence of elevated glucose increased from 48.7% (95% CI, 45.9-51.5) in 2011-2 to 64.3% (95% CI, 61.0-67.4) in 2017-8 [P for trend P for trend Conclusions: The prevalence of MetS remained stable from 2011 to 2018, but increased among non-Hispanic Asians. Lifestyle modification is needed to prevent metabolic syndrome and the associated risks of diabetes and cardiovascular disease.

Background Recent trials suggested that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduced cardiovascular events. Comparative effectiveness of these new antidiabetic drug classes remains unclear. We therefore performed a network meta-analysis to compare the effect on cardiovascular outcomes among GLP-1 RAs, SGLT-2 and dipeptidyl peptidase-4 (DPP-4) inhibitors. Methods MEDLINE, EMBASE, Cochrane database, ClinicalTrials.gov, and congress proceedings from recent cardiology conferences were searched up to April 20, 2019. Cardiovascular outcome trials and renal outcome trials reporting cardiovascular outcomes on GLP-1 RAs, SGLT-2 and DPP-4 inhibitors in patients with type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes were nonfatal myocardial infarction, nonfatal stroke, cardiovascular mortality, all-cause mortality, hospitalisation for heart failure (HF), and renal composite outcome. ORs and 95% CI were calculated using random-effects models. Results Fourteen trials enrolling 121,047 patients were included. SGLT-2 inhibitors reduced cardiovascular deaths and all-cause deaths compared to placebo (OR 0.82, 95% CI 0.73–0.93 and OR 0.84, 95% CI 0.77–0.92) and DPP-4 inhibitors (OR 0.83, 95% CI 0.70–0.99 and OR 0.83, 95% CI 0.73–0.94), respectively. SGLT-2 inhibitors and GLP-1 RAs significantly reduced MACE (OR 0.88, 95% CI 0.82–0.95 and OR 0.87, 95% CI 0.82–0.93), hospitalisation for HF (OR 0.68, 95% CI 0.61–0.77 and OR 0.87, 95% CI 0.82–0.93), and renal composite outcome (OR 0.59, 95% CI 0.52–0.67 and OR 0.86, 95% CI 0.78–0.94) compared to placebo, but SGLT-2 inhibitors reduced hospitalisation for HF (OR 0.79, 95% CI 0.69–0.90) and renal composite outcome (OR 0.69, 95% CI 0.59–0.80) more than GLP-1 RAs. Only GLP-1 RAs reduced nonfatal stroke (OR 0.88, 95% CI 0.77–0.99). DPP-4 inhibitors did not lower the risk of these outcomes when compared to placebo and were associated with higher risks of MACE, hospitalisation for HF, and renal composite outcome when compared to the other two drug classes. Conclusions SGLT-2 inhibitors show clear superiority in reducing cardiovascular and all-cause deaths, hospitalisation for HF, and renal events among new antidiabetic drug classes. GLP-1 RAs also have cardiovascular and renal protective effects. DPP-4 inhibitors have no beneficial cardiovascular effects and are therefore inferior to the other two drug classes. SGLT-2 inhibitors should now be the preferred treatment for type 2 diabetes mellitus.

BACKGROUND Patients who survive myocardial infarction (MI) are at risk of recurrent cardiovascular (CV) events. This study stratified post-MI patients for risk of recurrent CV events using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P). Methods and Results: This was an observational study that applied TRS 2°P to a consecutive cohort of post-MI patients. The primary outcome was a composite endpoint of CV death, non-fatal MI, and non-fatal ischemic stroke. A total of 1,688 post-MI patients (70.3±13.6 years; male, 63.1%) were enrolled. After a mean follow-up of 41.5±34.4 months, 405 patients (24.0%) had developed a primary outcome (9.3%/year) consisting of 278 CV deaths, 134 non-fatal MI, and 33 non-fatal strokes. TRS 2°P was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P 0 was 1.0%, and increased progressively to 39.9% for those with TRS 2°P ≥6 (HR, 27.6; 95% CI: 9.87-77.39, P

Background Growth differentiation factor 15 (GDF15) is a key regulator of body weight in animals by regulating food intake. Its receptor, glial cell-derived neurotrophic factor receptor alpha-like (GFRAL), was identified recently. Pre-clinical studies showed that it is a promising therapeutic target for cardiometabolic diseases and anorexia/cachexia. Although many pharmaceutical companies are developing drugs targeting GFRAL, whether the findings from animal studies can be extrapolated to man is unknown. Mendelian randomization (MR) is useful in investigating the relationship between risk factors and disease outcomes. We aimed to use a two-sample MR approach to evaluate the clinical usefulness of targeting GDF15 for cardiometabolic diseases. Methods Genetic instruments and summary statistics for MR analyses were obtained from a large genome-wide association study (GWAS) of GDF15 and cardiometabolic outcomes (n = 27,394 to 644,875), including body mass index, waist-hip ratio, waist circumference, whole-body lean mass, fat percentage, Type 2 Diabetes, fasting glucose, glycated haemoglobin, fasting insulin, LDL-cholesterol, HDL-cholesterol, total cholesterol, triglycerides, coronary artery disease, and estimated BMD (eBMD). Conventional inverse variance weighted (IVW) method was adopted to obtain the causal estimates of GDF-15 with different outcomes; weighted median and MR-egger were used for sensitivity analyses. Findings There was null association between GDF15 levels and anthropometric outcomes. One SD increase in genetically-determined GDF15 was significantly associated with reduced HDL-C (beta: -0.048SD; SE: 0.014; P = .001) but the result was not significant in sensitivity analyses. A consistent significant causal association was observed between GDF15 and eBMD in IVW (beta: 0.026 SD; SE: 0.005; P

Hong Kong is a compact territory in Southern China that enjoys a high degree of autonomy. Despite its dense population and uneven wealth distribution, infant mortality is low and life expectancy is long. The health service is more hospital and clinic based than community based. This seems cost-effective while professional standards are high and rigorously maintained. Drug registration follows American and European requirements. Hong Kong is a part of the Pharmaceutical Inspection Cooperation Scheme, which brings a high standard of drug regulation. Hong Kong is a good choice for clinical trials because the subjects are Chinese and protocols in English do not need to be translated. There are also 2 well-established clinical trials centers in university hospitals that also run Phase I and clinical pharmacology studies.

Unintentional injuries are major causes of mortality and morbidity. Although generally perceived as accidents, it is possible to identify those at higher risk and implement appropriate prevention measures. This study aims to investigate the common causes of unintentional injuries and their associated risk factors among a large representative sample. Data of 12,022 individuals who completed the Hong Kong Population Health Survey 2014/15 were extracted. The primary outcome was the prevalence of having unintentional injury(-ies) in the previous 12 months that was severe enough to limit daily activities. Multivariable logistic regression analyses were conducted to identify associations between injuries and sociodemographic, clinical and lifestyle factors. 14.5% of respondents reported episode(s) of unintentional injury in the past 12 months in the population level. The main causes of top three most severe unintentional injuries were sprains (24.0%), falls (19.9%) and being hit/struck (19.6%). 13.2% injury episodes were work-related among the most severe episode. Factors independently associated with significantly higher risks of injury included currently employed, homemaker or student, born in Hong Kong (as compared with immigrants), doctor-diagnosed chronic conditions, harmful alcohol consumption, insufficient sleep, and disturbed sleep. To summarize, unintentional injuries are highly prevalent and associated with harmful drinking, insufficient sleep, and disturbed sleep, which are potential modifiable risk factors for prevention.

Background Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD). Previous studies have shown inconsistent conclusions regarding the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing arrhythmias. This study aims to investigate the association of SGLT2i treatment with arrhythmia outcomes in clinical trials of patients with HF, DM, or CKD. Methods MEDLINE, EMBASE, and ClinicalTrials.gov were searched from inception up to 27 August 2020. Randomized controlled trials that randomized patients with DM, CKD, or HF to SGLT2i or placebo were included. The outcomes of interest include atrial fibrillation (AF), embolic stroke, atrial flutter (AFL), AF/AFL, ventricular tachycardia (VT), and cardiac arrest. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model. Results Out of 4,532 citations, 22 trials with altogether 52,115 patients were included (mean age 63.2 years; 33,747 [64.8%] of participants were men). SGLT2i were associated with a lower risk of AF (RR 0.82, 95% CI 0.70–0.96), embolic stroke (RR 0.32, 95% CI 0.12–0.85), AF/AFL (RR 0.82, 95% CI 0.71–0.95), and VT (RR 0.73, 95% CI 0.53–0.99), while the risk reductions in AFL (RR 0.83, 95% CI 0.58–1.17) and cardiac arrest (RR 0.83, 95% CI 0.61–1.14) did not reach statistical significance. The associations appeared to be consistent across different baseline conditions (DM vs CKD vs HF; atherosclerotic cardiovascular disease [ASCVD] vs no ASCVD) and the SGLT2i used. Conclusions SGLT2i reduced the risk of cardiac arrhythmias. Our study provides further evidence for recommending the use of SGLT2i in patients with DM, CKD, and HF. Further research is needed to fully elucidate the mechanism by which SGLT2i protect against arrhythmias.

Recent studies have reported numerous predictors for adverse outcomes in COVID-19 disease. However, there have been few simple clinical risk scores available for prompt risk stratification. The objective is to develop a simple risk score for predicting severe COVID-19 disease using territory-wide data based on simple clinical and laboratory variables. Consecutive patients admitted to Hong Kong’s public hospitals between 1 January and 22 August 2020 and diagnosed with COVID-19, as confirmed by RT-PCR, were included. The primary outcome was composite intensive care unit admission, need for intubation or death with follow-up until 8 September 2020. An external independent cohort from Wuhan was used for model validation. COVID-19 testing was performed in 237,493 patients and 4442 patients (median age 44.8 years old, 95% confidence interval (CI): [28.9, 60.8]); 50% males) were tested positive. Of these, 209 patients (4.8%) met the primary outcome. A risk score including the following components was derived from Cox regression: gender, age, diabetes mellitus, hypertension, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, stroke, dementia, liver diseases, gastrointestinal bleeding, cancer, increases in neutrophil count, potassium, urea, creatinine, aspartate transaminase, alanine transaminase, bilirubin, D-dimer, high sensitive troponin-I, lactate dehydrogenase, activated partial thromboplastin time, prothrombin time, and C-reactive protein, as well as decreases in lymphocyte count, platelet, hematocrit, albumin, sodium, low-density lipoprotein, high-density lipoprotein, cholesterol, glucose, and base excess. The model based on test results taken on the day of admission demonstrated an excellent predictive value. Incorporation of test results on successive time points did not further improve risk prediction. The derived score system was evaluated with out-of-sample five-cross-validation (AUC: 0.86, 95% CI: 0.82–0.91) and external validation (N = 202, AUC: 0.89, 95% CI: 0.85–0.93). A simple clinical score accurately predicted severe COVID-19 disease, even without including symptoms, blood pressure or oxygen status on presentation, or chest radiograph results.

Type 2 diabetes is among the most prevalent chronic diseases worldwide and the prevention of associated cardiovascular complications is an important treatment goal. Sodium–glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are second-line options after metformin, while cardiovascular outcome trials have been conducted to establish the cardiovascular safety of these antidiabetic drug classes. SGLT2 inhibitors have been shown to have the best overall mortality, renal and cardiovascular outcomes. Reduction in hospitalisation for heart failure is particularly consistent. GLP-1 receptor agonists have also showed some benefits, especially in stroke prevention. DPP-4 inhibitors showed neutral effects on cardiovascular outcomes, but may increase the incidence of heart failure. Favourable outcomes observed in trials of SGLT2 inhibitors mean that these should be the preferred second-line option. DPP-4 inhibitors are useful for patients with diabetes at low cardiovascular risk.

Little is still known about the clinical features associated with the occurrence of acute respiratory distress syndrome (ARDS) in hospitalized patients with Coronavirus disease 2019 (COVID-19). The aim of the present study was to describe the prevalence of pre-admission antithrombotic therapies in patients with COVID-19 and to investigate the potential association between antithrombotic therapy and ARDS, as disease clinical presentation, or in-hospital mortality. We enrolled 192 consecutive patients with laboratory-confirmed COVID-19 admitted to emergency department of five Italian hospitals. The study population was divided in two groups according to the evidence of ARDS at chest computed tomography at admission. Propensity score weighting adjusted regression analysis was performed to assess the risk ARDS at admission, and death during hospitalization, in patients treated or not with antiplatelet and anticoagulant agents. ARDS was reported in 73 cases (38 %), who showed more likely hypertension compared to those without ARDS (57.8 % vs 49.6 %; P = 0.005). Thirty-five patients (18.5 %) died during the hospitalization. Not survived COVID-19 patients showed a statistically significant increased age (77 ± 8.31 vs 65.57 ± 8.31; P = 0.001), hypertension (77.1 % vs 53.5 %; P = 0.018) and coronary artery disease prevalence (28.6 % vs 10.2 %; P = 0.009). Both unadjusted and adjusted regression analyses showed no difference in the risk of ARDS at admission, or death during hospitalization, between patients treated or not with antiplatelets or anticoagulants. Pre-admission antithrombotic therapy, both antiplatelet and anticoagulant, does not seem to show a protective effect in severe forms of COVID-19 with ARDS at presentation and rapidly evolving toward death.

The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. This study aims to identify specific lab markers, complications, and treatments that may be associated with increased mortality in COVID-19 patients. This study is retrospective in nature; it included 217 COVID-19 positive patients who were admitted to a ProMedica Health System hospital in Northwest Ohio, United States, between March 25 and June 16, 2020. We collected various laboratory values, complications, and treatment courses. T test and χ

BackgroundPulmonary hypertension, a progressive lung disorder with symptoms such as breathlessness and loss of exercise capacity, is highly debilitating and has a negative impact on the quality of life. In this study, we examined whether a multi-parametric approach using machine learning can improve mortality prediction.MethodsA population-based territory-wide cohort of pulmonary hypertension patients from January 1, 2000 to December 31, 2017 were retrospectively analyzed. Significant predictors of all-cause mortality were identified. Easy-to-use frailty indexes predicting primary and secondary pulmonary hypertension were derived and stratification performances of the derived scores were compared. A factorization machine model was used for the development of an accurate predictive risk model and the results were compared to multivariate logistic regression, support vector machine, random forests, and multilayer perceptron.ResultsThe cohorts consist of 2562 patients with either primary (n=1009) or secondary (n=1553) pulmonary hypertension. Multivariate Cox regression showed that age, prior cardiovascular, respiratory and kidney diseases, hypertension, number of emergency readmissions within 28 days of discharge were all predictors of all-cause mortality. Easy-to-use frailty scores were developed from Cox regression. A factorization machine model demonstrates superior risk prediction improvements for both primary (precision: 0.90, recall: 0.89, F1-score: 0.91, AUC: 0.91) and secondary pulmonary hypertension (precision: 0.87, recall: 0.86, F1-score: 0.89, AUC: 0.88) patients.ConclusionWe derived easy-to-use frailty scores predicting mortality in primary and secondary pulmonary hypertension. A machine learning model incorporating multi-modality clinical data significantly improves risk stratification performance.

Purpose Older adults are more likely to be vitamin D deficient. The aim of the study was to determine whether these patients have worse outcomes with COVID-19. Methods We conducted a prospective cohort study between 1 March and 30 April 2020 to assess the importance of vitamin D deficiency in older patients with COVID-19. The cohort consisted of patients aged ≥65 years presenting with symptoms consistent with COVID-19 (n=105). All patients were tested for serum 25-hydroxyvitamin D (25(OH)D) levels during acute illness. Diagnosis of COVID-19 was confirmed via viral reverse transcriptase PCR swab or supporting radiological evidence. COVID-19-positive arm (n=70) was sub-divided into vitamin D-deficient (≤30 nmol/L) (n=39) and -replete groups (n=35). Subgroups were assessed for disease severity using biochemical, radiological and clinical markers. Primary outcome was in-hospital mortality. Secondary outcomes were laboratory features of cytokine storm, thoracic imaging changes and requirement of non-invasive ventilation (NIV). Results COVID-19-positive arm demonstrated lower median serum 25(OH)D level of 27 nmol/L (IQR=20–47 nmol/L) compared with COVID-19-negative arm, with median level of 52 nmol/L (IQR=31.5–71.5 nmol/L) (p value=0.0008). Among patients with vitamin D deficiency, there was higher peak D-dimer level (1914.00 μgFEU/L vs 1268.00 μgFEU/L) (p=0.034) and higher incidence of NIV support and high dependency unit admission (30.77% vs 9.68%) (p=0.042). No increased mortality was observed between groups. Conclusion Older adults with vitamin D deficiency and COVID-19 may demonstrate worse morbidity outcomes. Vitamin D status may be a useful prognosticator.

ObjectivesTo determine whether the use of angiotensin converting enzyme inhibitors (ACEIs) was associated with a higher risk of lung cancer when compared to use of angiotensin receptor blockers (ARBs).Study DesignPopulation-based cohort study.SettingPublic hospitals under the Hospital Authority in Hong Kong, P.R. China.MethodsPatients admitted to public hospitals and first prescribed with ACEI and/or ARB between 1 January 2001 and 31 December 2018 were analyzed. The last follow-up date was 31 August 2020, or death, whichever was earlier.OutcomesThe primary outcome was the incidence of lung cancer. Logistic regression was used to calculate odds ratio [ORs] with 95% confidence intervals associated with the use of ACEIs compared to ARBs. Incidence and odds ratios were estimated for temporal analysis of incident cancer risk associated with time since the first prescription of ACEI or ARB.ResultsIn the unmatched cohort, 56,697 patients and 357,011 patients were included the ARB and ACEI cohorts, with lung cancer incidence of 2.16% and 1.29%, respectively. Using 1:3 matching for ARB to ACEI users, the incidences were 2.32% and 1.29%. ACEI use was associated with increased risks of lung cancer both before (hazard ratio: 1.30 [1.21-1.40], PConclusionsACEI use was associated with increased risk of lung cancer compared with ARB use at all time points. Additionally, incidence risk increases with the duration of exposure.

BackgroundSGLT2I and DPP4I are medications prescribed for type 2 diabetes mellitus patients. However, there are few population-based studies comparing their effects on incident atrial fibrillation or ischemic stroke.MethodsThis was a territory-wide cohort study of type 2 diabetes mellitus patients prescribed SGLT2I or DPP4I between January 1st, 2015 to December 31st, 2019 in Hong Kong. Patients with both DPP4I and SGLT2I use and patients with drug discontinuation were excluded. Patients with prior AF or stroke were excluded for the respective analysis. 1:2 propensity-score matching was conducted for demographics, past comorbidities and medications using nearest-neighbor matching method. Cox models were used to identify significant predictors for new onset heart failure (HF) or myocardial infarction (MI), cardiovascular and all-cause mortality.ResultsThe AF-free cohort included 49108 patients (mean age: 66.48 years old [SD: 12.89], 55.32% males) and the stroke-free cohort included 49563 patients (27244 males [54.96%], mean baseline age: 66.7 years old [SD: 12.97, max: 104.6 years old]). After propensity score matching, SGLT2i use was associated with a lower risk of new onset AF (HR: 0.43[0.28, 0.66]), cardiovascular mortality (HR: 0.79[0.58, 1.09]) and all-cause mortality (HR: 0.69[0.60, 0.79]) in the AF-free cohort. It was also associated with a lower risk of new onset stroke (0.46[0.33, 0.64]), cardiovascular mortality (HR: 0.74[0.55, 1.00]) and all-cause mortality (HR: 0.64[0.56, 0.74]) in the stroke-free cohort.ConclusionsThe novelty of our work si that SGLT2 inhibitors are protective against atrial fibrillation and stroke development for the first time. These findings should be validated in other cohorts.

BackgroundThe triglyceride glucose (TyG) index has been proposed to be a surrogate of insulin resistance. In the study, we aimed to examine the relationship between TyG index and the risk of new onset DM and secondary outcomes included atrial fibrillation (AF), heart failure (HF), acute myocardial infarction (AMI), ventricular tachycardia/fibrillation (VTF), cardiovascular mortality (CAD) and all-cause mortality.MethodsThe retrospective observational study analyzed patients recruited from 1st January 2000 to 31st December 2003 and followed up until 31st December 2019. Demographics, past comorbidities, medications and laboratory tests were extracted. At baseline and follow-up, DM was defined as 1) any occasion Hb1Ac ≥14 g/dL, 2) fasting glucose≥7 mmol/L on two occasions, or 3) with DM diagnosis. We excluded 1) patients with prior DM or with the use of antidiabetic medications; 2) patients with prior AMI/HF/AF or with the use of diuretic/beta blockers for HF were excluded. Univariate analysis and multivariate Cox analysis with adjustments on demographics, past comorbidities and medications were conducted to identify the significant risk predictors of primary and secondary outcomes. Optimal cutoffs of TyG index for the primary and secondary outcomes were found with maximally selected rank statistics approach.ResultLager TyG index is significantly associated with new onset DM (HR: 1.51, 95% CI: [1.47, 1.55], P vlaue1, P valueConclusionHigher TyG index remained significantly associated with the elevated risk of new onset DM, AF, HF, AMI, VTF, CAD and all-cause mortality after adjustments on demographics, past comorbidities, and medications.

BackgroundThere is a bidirectional relationship between blood pressure variability (BPV) and generalized anxiety disorder (GAD), but few studies have examined the gender- and age-specific effects of visit-to-visit BPV on GAD incidence. We examined the predictive value of BPV for the incidence of GAD in a family clinic cohort.MethodsConsecutive patients with a first attendance to family medicine clinics in Hong Kong between January 1st, 2000, and December 31st, 2002, with at least three blood pressure measurements available thereafter were included. The primary endpoint was incident GAD as identified by ICD-9 coding from the local Clinical Data Analysis and Reporting System.ResultsThis study included 48023 (50% males) patients with a median follow-up of 224 (IQR: 217-229) months. Females were more likely to develop GAD compared to males (incidence rate: 7% vs. 2%), as were patients of older age. Significant univariate predictors were female gender, older age, pre-existing cardiovascular diseases, respiratory diseases, diabetes mellitus, hypertension, and gastrointestinal diseases, various laboratory examinations and the number of blood pressure measurements. Higher baseline, maximum, minimum, SD, CV, and variability score of diastolic blood pressure significantly predicted GAD, as did all systolic blood pressure measures (baseline, latest, maximum, minimum, mean, median, variance, SD, RMS, CV, variability score).ConclusionsThe relationships between longer term visit-to-visit BPV and incident GAD were identified. Female and older patients with higher blood pressure and higher BPV were at the highest risks of GAD.

Background The present study evaluated the association between blood pressure variability and the risk of hip/vertebral fractures in middle aged and elderly patients. Methods This was a retrospective observational study of patients attending family medicine outpatient clinics, recruited from 1st January 2000 to 31st December 2003 and were followed up until 31st December 2019. Standard deviation (SD), root mean square (RMS), coefficient of variation (CV) and a variability score (defined as the number of changes in blood pressure (diastolic and systolic) of 5 mm Hg or more) were used as measures of blood pressure variability. The primary outcome was a composite of new onset hip or vertebral fractures. Results A total of 57,810 patients were included. Over a median follow-up of 5894 days (interquartile range: 3505–6487), 3285 patients (5.68%) developed new onset hip/vertebral fractures. The crude incidence rates were 4.95%, 5.31%, and 7.2% for diastolic blood pressure-CV and 5.0%, 5.28%, and 7.08% for systolic blood pressure-CV in the first, second, and third tertiles, respectively. Survival analysis demonstrated differences in hip/vertebral fracture amongst the tertiles of systolic and diastolic blood pressure variability (P Conclusions Measures of blood pressure variability were significantly associated with incident hip/vertebral fractures. They can be incorporated into existing clinical scores to improve risk stratification.

AimsRenin–angiotensin system blockers such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of adverse outcomes in COVID-19. In this study, the relationships between ACEI/ARB use and COVID-19 related mortality were examined.MethodsConsecutive patients diagnosed with COVID-19 by RT-PCR at the Hong Kong Hospital Authority between 1st January and 28th July 2020 were included.ResultsThis study included 2774 patients. The mortality rate of the COVID-19 positive group was 1.5% (n=42). Those who died had a higher median age (82.3[76.5-89.5] vs. 42.9[28.2-59.5] years old; PConclusionsWe report that an association between ACEIs/ARBs with COVID-19 related mortality even after adjusting for cardiovascular and other comorbidities, as well as medication use. Patients with greater comorbidity burden and laboratory markers reflecting deranged clotting, renal and liver function, and increased tissue inflammation, and ACEI/ARB use have a higher mortality risk.Key PointsWe report that an association between ACEIs/ARBs with COVID-19 related mortality even after adjusting for cardiovascular and other comorbidities, as well as medication use.Patients with greater comorbidity burden and laboratory markers reflecting deranged clotting, renal and liver function, and increased tissue inflammation, and ACEI/ARB use have a higher mortality risk.

IntroductionBlood pressure variability, in addition to blood pressure itself, has been used as a predictor for mortality. This study examined the predictive power of baseline/latest/mean/median blood pressure and blood pressure variability measures for all-cause mortality and adverse cardiovascular outcomes.MethodsThe retrospective observational study analyzed patients who presented to family medicine clinics between 1st January, 2000 and 31st December, 2001. Blood pressure measurements were obtained over a five-year period. Standard deviation (SD), root mean square (RMS), coefficient of variation (CV) and a variability score (number of >=5 mmHg blood pressure change) were used as measures of blood pressure variability. The primary outcome was all-cause mortality and the secondary outcomes were heart failure, acute myocardial infarction, and transient ischemic attack (TIA)/stroke, with follow-up until 31 December 2019.ResultsThis study included 37540 patients (n=29597 patients with >=3 blood pressure measurements). A nonlinear inverse U-shaped relationship was observed between baseline/latest/maximum/minimum/mean/median/RMS measures of diastolic blood pressure and time-to-death for all-cause mortality (PConclusionNonlinear inverse U-shaped relationships were observed between blood pressure and its variability measures and all-cause mortality. Higher blood pressure variability was associated with increased risk of all-cause mortality, heart failure, acute myocardial infarction and TIA/stroke.

Introduction: Apabetalone is a novel drug that reduces inflammation and thrombosis by inhibiting bromodomain and extra-terminal proteins (BET). Three phase II trials suggested benefits whereas the recent phase III BETonMACE trial did not. To reconcile these differences, we performed a meta-analysis of all trials on apabetalone. Methods: MEDLINE, EMBASE, Cochrane Library, and ClinialTrials.gov were searched for randomized controlled trials of apabetalone up to May 05, 2020. The outcomes of interest were major adverse cardiovascular events (MACE) and hospitalization for heart failure. The secondary outcomes were death, myocardial infarction (MI), coronary revascularization, high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I). Pooled risk ratios (RRs) or mean differences (MD) in a fixed-effects model were generated using the “ meta ” package in R (version 3.6.3). Results: Four trials (median follow-up 3-26.5 months) with altogether 3223 patients were included. All patients had coronary artery disease and received standard statin therapy. Apabetalone significantly reduced MACE (RR 0.78, 95% CI: 0.63-0.96) and hospitalization for heart failure (RR 0.48, 95% CI: 0.33-0.70) compared to placebo (Fig.). No significant differences were observed for death (RR 0.87, 95% CI: 0.63-1.21), MI (RR 0.82, 95% CI: 0.62-1.10), or coronary revascularization (RR 0.67, 95% CI: 0.31-1.49). Apabetalone increased ApoA-I (MD 2.82%, 95% CI: 1.36-4.28) and HDL (MD 0.04%, 95% CI: 0.02-0.07). Conclusions: Although the BETonMACE trial failed to demonstrate significant benefits, our meta-analysis shows that apabetalone reduces MACE and hospitalization for heart failure in patients with coronary artery disease. Larger outcome trials are urgently needed to investigate the benefits of epigenetic modulation through BET protein inhibition.

BackgroundRecent studies have reported numerous significant predictors for adverse outcomes in COVID-19 disease. However, there have been few simple clinical risk score for prompt risk stratification. The objective is to develop a simple risk score for severe COVID-19 disease using territory-wide healthcare data based on simple clinical and laboratory variables.MethodsConsecutive patients admitted to Hong Kong’s public hospitals between 1st January and 22nd August 2020 diagnosed with COVID-19, as confirmed by RT-PCR, were included. The primary outcome was composite intensive care unit admission, need for intubation or death with follow-up until 8th September 2020.ResultsCOVID-19 testing was performed in 237493 patients and 4445 patients (median age 44.8 years old, 95% CI: [28.9, 60.8]); 50% male) were tested positive. Of these, 212 patients (4.8%) met the primary outcome. A risk score including the following components was derived from Cox regression: gender, age, hypertension, stroke, diabetes mellitus, ischemic heart disease/heart failure, respiratory disease, renal disease, increases in neutrophil count, monocyte count, sodium, potassium, urea, alanine transaminase, alkaline phosphatase, high sensitive troponin-I, prothrombin time, activated partial thromboplastin time, D-dimer and C-reactive protein, as well as decreases in lymphocyte count, base excess and bicarbonate levels. The model based on test results taken on the day of admission demonstrated an excellent predictive value. Incorporation of test results on successive time points did not further improve risk prediction.ConclusionsA simple clinical score accurately predicted severe COVID-19 disease, even without including symptoms, blood pressure or oxygen status on presentation, or chest radiograph results.

Whether newer P2Y12 inhibitors are more efficacious and safer than clopidogrel and whether there is a superior one remain uncertain. We compared the effect of P2Y12 inhibitors on clinical outcomes in patients with acute coronary syndrome (ACS). Randomized controlled trials comparing clopidogrel, prasugrel, ticagrelor, or cangrelor, in combination with aspirin were searched. Sixteen trials with altogether 77,896 patients were included. Compared to clopidogrel, cardiovascular mortality was reduced with prasugrel (OR 0.85, 95% CI 0.75–0.97) and ticagrelor (0.82, 0.73–0.93). Myocardial infarction (0.75, 0.63–0.89) and major adverse cardiovascular events (0.80, 0.69–0.94) were reduced by prasugrel. Stent thrombosis was reduced by prasugrel (0.49, 0.38–0.63), ticagrelor (0.72, 0.57–0.90), and cangrelor (0.59, 0.43–0.81). It was reduced more by prasugrel than ticagrelor (0.69, 0.51–0.93). There were more major bleeds with prasugrel (1.24, 1.05–1.48). Thrombolysis in Myocardial Infarction (TIMI) major bleeding was increased with prasugrel compared to clopidogrel (1.36, 1.11–1.66) and ticagrelor (1.33, 1.06–1.67). TIMI minor bleeding was increased with prasugrel (1.44, 1.16–1.77) and cangrelor (1.47, 1.01–2.16) compared to clopidogrel while it was increased with prasugrel compared to ticagrelor (1.32, 1.01–1.72). Prasugrel is preferable to those ACS patients at low bleeding risk to reduce cardiovascular events whereas ticagrelor is a relatively safe antiplatelet drug of choice for most patients.

Objectives Sarcopenia is recognized to be a health problem which is as serious as obesity, but its relevance to mortality is unclear. We conducted a meta-analysis of cohort studies on lean mass and mortality in populations with different health conditions. Methods In this study, a systematic search of PubMed, Cochrane Library and Embase was performed for cohort studies published before Dec 20, 2017 which examined the relationship between lean mass and mortality. We included studies reporting lean mass measurement by dual-energy X-ray absorptiometry, bioimpedance analysis or computed tomography, as continuous (per standard deviation [SD] decrease) or binary variables (using sarcopenia cutoffs). We excluded studies which used muscle mass surrogates, anthropometric measurement of muscle, rate of change in muscle mass, and sarcopenia defined by composite criteria. The primary study outcome was all-cause mortality. Pooled hazard ratio estimates were calculated using a random effects model. Results A total of 9602 articles were identified from the systematic search, and 188 studies with 98 468 participants from 34 countries were included in the meta-analysis. Of the 68 studies included in the present meta-analysis, the pooled HR was 1.36 and 1.74 for every SD decrease in lean mass and in people with low lean mass (cutoffs), respectively. Significant associations were also observed in elderly and all disease subgroups, irrespective of the measurement modalities. Conclusions Lower lean mass is robustly associated with increased mortality, regardless of health conditions and lean mass measurement modalities. This meta-analysis highlighted low lean mass as a key public health issue.

Objectives Muscle mass is one of the key components in defining sarcopenia and is known to be important for locomotion and body homeostasis. Lean mass is commonly used as a surrogate of muscle mass and has been shown to be associated with increased mortality. However, the relationship of lean mass with mortality may be affected by different clinical conditions, modalities used, cut-off point to define low or normal lean mass, and even types of cancer among cancer patients. Thus, we aim to perform a comprehensive meta-analysis of lean mass with mortality by considering all these factors. Methods Systematic search was done in PubMed, Cochrane Library and Embase for articles related to lean mass and mortality. Lean mass measured by dual X-ray absorptiometry, bioelectrical impedance analysis, and computerized tomography were included. Results The number of relevant studies has increased continuously since 2002. A total of 188 studies with 98 468 people were included in the meta-analysis. The association of lean mass with mortality was most studied in cancer patients, followed by people with renal diseases, liver diseases, elderly, people with cardiovascular disease, lung diseases, and other diseases. The meta-analysis can be further conducted in subgroups based on measurement modalities, site of measurements, definition of low lean mass adopted, and types of cancer for studies conducted in cancer patients. Conclusions This series of meta-analysis provided insight and evidence on the relationship between lean mass and mortality in all directions, which may be useful for further study and guideline development.

Use of high-dose glucocorticoids for COVID-19 (caused by SARS-CoV-2) is controversial because of safety concerns. We examined the long-term consequences of glucocorticoid use in severe acute respiratory syndrome (caused by SARS-CoV-1) survivors. Results showed that high-dose glucocorticoids greatly increased the long-term risk of avascular necrosis but not other major diseases.

BackgroundObservational studies have found associations between salt intake with obesity, body shape and composition; but the findings may be biased by residual confounding.ObjectiveTo analyze the causal associations between salt intake and obesity measures in both sex-combined and sex-specific models.DesignsThis was a two-sample Mendelian randomization study. Genome-wide association (GWA) studies of urinary sodium secretion (UNa, a surrogate for salt intake), body mass index (BMI), BMI-adjusted waist-to-hip ratio (WHR), body fat (BF) percentage and estimated glomerular filtration rate (eGFR) were identified. We initially extracted fifty SNPs associated with UNa at GWA significance level of 5 × 10−8, but further removed those SNPs with potential horizontal pleiotropy. Univariable MR and multivariable MR with adjustment for eGFR were performed. Inverse-variance weighted MR was performed as the primary analysis, with MR-Egger methods as sensitivity analysis. The potential bidirectional association between BMI and UNa was investigated. All exposure and outcomes were continuous, and the effect measure was linear regression coefficients (beta) and their 95% confidence intervals (95%CI).ResultsUNa was causally associated with increased BMI in both men (eGFR-adjusted beta 0.443 (0.163 to 0.724)) and women (0.594 (0.333 to 0.855)). UNa caused BF percentage increase in men (0.622 (0.268 to 0.976)) and women (0.334 (0.007 to 0.662)). UNa significantly elevated BMI-adjusted WHR in men (0.321 (0.094 to 0.548)), but not in women (0.170 (−0.052 to 0.391)). Additionally, we found that BMI causally increased UNa (0.043 (0.023 to 0.063)).ConclusionsSalt intake increased BMI and BF percentage. Salt intake affects male body shape by increasing BMI-adjusted WHR, but showed no effects on female body shape. The bidirectional association between BMI and UNa suggested that salt reduction measures and weight reduction measures should be implemented simultaneously to break the vicious cycle and gain more health benefits.AbbreviationsALM: appendicular lean massBF: body fatBMI: body mass indexeGFR: estimated glomerular filtration rateGWA: genome-wide associationHC: hip circumferenceMR: Mendelian randomizationPRESSO test: Pleiotropy RESidual Sum and Outlier testSNP: single nucleotide polymorphismUNa: urinary sodium secretionWC: waist circumferenceWHR: waist-to-hip ratioWLM: whole body lean mass