Association between body weight and tocilizumab effectiveness in rheumatoid arthritis: results from the BSRBR-RA.

OBJECTIVES: Tocilizumab is an IL-6 receptor humanised monoclonal antibody for the treatment of rheumatoid arthritis (RA) with intravenous (IV) and subcutaneous (SC) preparations available. Only IV tocilizumab is dosed adjusting for weight. Therefore, we aimed to study the association between body weight and the effectiveness of tocilizumab by the route of administration. METHODS: Patients with RA administered tocilizumab in the BSRBR-RA were included in the analysis and stratified by route of administration. Outcomes included the 6 month change in DAS28, the proportion of patients achieving DAS28 remission, 6-month EULAR response and persistence of the first route of tocilizumab administration. The exposure was every increase in 10 kg of body weight. Adjusted regression models appropriate to outcome were used to study the associations between body weight and outcomes. Multiple imputations accounted for missing data. RESULTS: 2612 patients were included. Body weight was associated with reduced response to SC tocilizumab measured by change in DAS28: adjusted regression coefficient (95% CI) all patients 0.01 (-0.04, 0.07); IV: -0.03, (-0.1, 0.5); SC: 0.1 (0.02, 0.2) but not odds in achieving DAS28 remission or EULAR response. There was no significant association between body weight and the persistence of IV or SC tocilizumab. CONCLUSION: Body weight was associated with the initial response to SC tocilizumab, although the difference in response was small, but not drug persistence. Physicians should monitor the body weight of patients and consider interventions to promote maintenance of a healthy weight.

Outcomes following switching from etanercept originator to etanercept biosimilar in 1024 RA patients: A matched-analysis of the BSRBR-RA.

OBJECTIVES: Adults with RA are being switched from etanercept originator to biosimilar in non-medical/cost-saving switching. This analysis aims to investigate outcomes in these patients, including (a) drug survival and (b) disease activity at six and 12-month, compared with those who remain on originator. METHODS: Using BSRBR-RA, those who switched directly from etanercept originator to biosimilar were identified and matched to patients receiving originator, based on gender, age, disease duration, originator start year. Drug survival was calculated; Cox-proportional hazard models assessed differences in drug persistence between those who switched versus remaining on originator. Change in DAS28 after six and 12-months was compared between cohorts. Multiple imputation was used. RESULTS: 1024 adults with RA switching from etanercept originator to biosimilar were included, with a matched cohort of patients remaining on originator. Patients who switched onto a biosimilar product were no more likely to discontinue etanercept treatment versus those who remained on originator; hazard ratio 1.06 (95%CI 0.89-1.26), with 65% of patients remaining on treatment at three years. Ninety-five (9%) patients switched back to originator within the first year. After six and 12-months, biosimilar patients were no more likely to have a worsening of DAS28 (>0.6units) compared with those who remained on originator. CONCLUSIONS: This is the largest matched comparative effectiveness analysis showing patients switched from etanercept originator to biosimilar appear to do just as well with regards to disease activity and drug persistence compared with those who remained on originator. These data will be reassuring to clinicians and patients regarding non-medical switching.

Etanercept originator versus etanercept biosimilar for the treatment of rheumatoid arthritis as a first biologic: results from the BSRBR-RA.

OBJECTIVES: Etanercept biosimilars show comparable efficacy to their originators among biologic-naïve patients with RA in randomized controlled trials. Nationwide guidelines have obligated prescribing of etanercept biosimilars from 2016, resulting in significant cost savings. This analysis aimed to compare the effectiveness of etanercept originator vs etanercept biosimilar amongst biologic-naïve RA patients treated in routine clinical practice in the UK. METHODS: Biologic-naïve RA patients starting etanercept in the British Society for Rheumatology Biologics Register in Rhematoid Arthritis (BSRBR-RA) cohort study from 2010 were included. Data collected at start of therapy includes patient demographics and disease activity. Follow-up data includes changes in disease activity and anti-rheumatic therapy. Six- and 12-month primary outcomes include DAS for 28-joints (DAS28) remission, EULAR response and minimal clinically important difference in function. Etanercept drug survival was assessed using Kaplan-Meier and Cox regression, including reasons for treatment withdrawal. Multiple imputation accounted for missing data. Propensity-decile adjustment was used to account for confounding by indication. RESULTS: A total of 1806 biologic-naïve RA patients started etanercept: 1009 originator, 797 biosimilar. At 6 and 12 months, the proportion of patients achieving DAS28 remission and EULAR response were similar between treatments. During follow-up, 19% of originator patients switched onto etanercept biosimilar. Patients were censored at time of switch. Patients on originator were no more likely to stop therapy vs biosimilar; 71% of originator and 76% of biosimilar patients remained on therapy at 1 year. CONCLUSIONS: In one of the largest analyses of patients with RA, biologic-naïve RA patients treated with etanercept originator showed similar outcomes vs biosimilar using real-world data. Drug survival, and disease activity after 6 and 12 months of therapy, was similar between cohorts.

Cancer Risk of Angiotensin II Receptor Blocker Valsartan: A Population-based Study.

ABSTRACT: Nitrosamine contamination of generic valsartan was found in 2018. This study aimed to investigate whether long-term use of valsartan increases cancer risk. Patients prescribed valsartan or amlodipine (control group) from 1 January 1, 2003, to June 30, 2010, were identified using the Clinical Data Analysis and Reporting System of the Hong Kong Hospital Authority, a territory-wide database in Hong Kong. Patients previously diagnosed with cancer, prescribed both medications, taking the medication, or followed up for <1 year were excluded. Cancer incidence, adjusted for age, sex, and Charlson Comorbidity Index, was the primary outcome and was estimated using Poisson regression in R version 3.6.1. Among 5023 valsartan users and 3692 amlodipine users, 887 and 740 were diagnosed with cancers during median follow-up periods of 10.97 and 12.12 years, respectively. The adjusted incidence of cancer in valsartan and amlodipine users was 165.29 (95% confidence interval 154.76-175.53) and 180.12 (167.35-193.67) per 10,000 person-years, respectively. The cancer incidence rate ratio of valsartan relative to amlodipine was 0.94 (0.88-1.01). Adjusted incidence rate ratios of valsartan relative to amlodipine were significant for breast cancer (0.63, 0.46-0.86) only. Our findings do not suggest an increase in incidence of cancer with long-term valsartan use. The duration of follow-up of more than 10 years of the study provides the reassurance that an increase in cancer risk is unlikely. Further studies are needed to elucidate the long-term effect of valsartan use on the risk of specific types of cancer.

The seroprevalence and kinetics of IgM and IgG in the progression of COVID-19.

BACKGROUND: SARS-CoV-2 is a novel coronavirus first recognized in late December 2019 that causes coronavirus disease 19 (COVID-19). Due to the highly contagious nature of SARS-CoV-2, it has developed into a global pandemic in just a few months. Antibody testing is an effective method to supplement the diagnosis of COVID-19. However, multicentre studies are lacking to support the understanding of the seroprevalence and kinetics of SARS-CoV-2 antibodies in COVID-19 epidemic regions. METHOD: A multicentre cross-sectional study of suspected and confirmed patients from 4 epidemic cities in China and a cohort study of consecutive follow-up patients were conducted from 29/01/2020 to 12/03/2020. IgM and IgG antibodies elicited by SARS-CoV-2 were tested by a chemiluminescence assay. Clinical information, including basic demographic data, clinical classification, and time interval from onset to sampling, was collected from each centre. RESULTS: A total of 571 patients were enrolled in the cross-sectional study, including 235 COVID-19 patients and 336 suspected patients, each with 91.9%:2.1% seroprevalence of SARS-CoV-2 IgG and 92.3%:5.4% seroprevalence of SARS-CoV-2 IgM. The seroprevalence of SARS-CoV-2 IgM and IgG in COVID-19 patients was over 70% less than 7 days after symptom onset. Thirty COVID-19 patients were enrolled in the cohort study and followed up for 20 days. The peak concentrations of IgM and IgG were reached on the 10th and 20th days, respectively, after symptom onset. The seroprevalence of COVID-19 IgG and IgM increased along with the clinical classification and treatment time delay. CONCLUSION: We demonstrated the kinetics of IgM and IgG SARS-CoV-2 antibodies in COVID-19 patients and the association between clinical classification and antibodies, which will contribute to the interpretation of IgM and IgG SARS-CoV-2 antibody tests and in predicting the outcomes of patients with COVID-19.

Comparative cardiovascular risk in users versus non-users of xanthine oxidase inhibitors and febuxostat versus allopurinol users.

OBJECTIVES: The aim of this study is to determine major adverse cardiovascular events (MACE) and all-cause mortality comparing between xanthine oxidase inhibitors (XOIs) and non-XOI users, and between allopurinol and febuxostat. METHODS: This is a retrospective cohort study of gout patients prescribed anti-hyperuricemic medications between 2013 and 2017 using a territory-wide administrative database. XOI users were matched 1:1 to XOI non-users using propensity scores. Febuxostat users were matched 1:3 to allopurinol users. Subgroup analyses were conducted based on colchicine use. RESULTS: Of the 13 997 eligible participants, 3607 (25.8%) were XOI users and 10 390 (74.2%) were XOI non-users. After propensity score matching, compared with non-users (n = 3607), XOI users (n = 3607) showed similar incidence of MACE (hazard ratio [HR]: 0.997, 95% CI, 0.879, 1.131; P>0.05) and all-cause mortality (HR = 0.972, 95% CI 0.886, 1.065, P=0.539). Febuxostat (n = 276) users showed a similar risk of MACE compared with allopurinol users (n = 828; HR: 0.672, 95% CI, 0.416, 1.085; P=0.104) with a tendency towards a lower risk of heart failure-related hospitalizations (HR = 0.529, 95% CI 0.272, 1.029; P=0.061). Concurrent colchicine use reduced the risk for all-cause mortality amongst XOI users (HR = 0.671, 95% 0.586, 0.768; P<0.001). CONCLUSION: In gout patients, XOI users showed similar risk of MACE and all-cause mortality compared with non-users. Compared with allopurinol users, febuxostat users showed similar MACE and all-cause mortality risks but lower heart failure-related hospitalizations.

The lipid-lowering effect of once-daily soya drink fortified with phytosterols in normocholesterolaemic Chinese: a double-blind randomized controlled trial.

PURPOSE: Phytosterols reduce intestinal cholesterol absorption and help to lower LDL-cholesterol. Many Chinese adults are lactose-intolerant and cannot tolerate bovine milk enriched with phytosterol. Soya-milk is a common beverage in Asia and it has beneficial effects on general health. We therefore conducted a randomized double-blind controlled trial to assess the effectiveness of a phytosterols-enriched soya drink in lowering serum LDL-cholesterol level (primary outcome) and other cardiovascular parameters (secondary outcomes). METHODS: One hundred and fifty-nine normocholesterolaemic participants (85 men and 74 women; aged 19-79) were randomized to daily intake of one serving of phytosterols-enriched soya drink (N = 82), equivalent to 2 g of phytosterol per day, or a matched soya drink without phytosterols (N = 77) for 3 weeks. Adverse events, withdrawal and compliance were documented. RESULTS: Among the treatment group (N = 82), phytosterols-enriched soya drink significantly decreased LDL-cholesterol by 5.96% (SE 1.48, 95% CI - 8.91%, - 3.00%) with a median of 6.74% compared with baseline, resulting in a significant reduction of 4.70% (95% CI - 8.89%, - 0.51%; p = 0.028) with a median of 5.20% compared with placebo (N = 77). In contrast, there were no significant changes in other lipid parameters, blood glucose, blood pressure, body weight or waist circumference. Remarkably, 95% of the participants randomized to the fortified drink reported no adverse events at all. CONCLUSIONS: Daily consumption of a phytosterols-enriched soya drink may be a simple and cost-neutral means of lowering LDL-cholesterol in individuals in China, with massive population and rising incidence of coronary heart disease (ClinicalTrials.gov identifier: NCT02881658; date of registration: 14 Aug 2016).

Vancomycin-associated acute kidney injury in Hong Kong in 2012-2016.

BACKGROUND: To study the incidence of vancomycin-associated acute kidney injury (VA-AKI) in Hong Kong and identify risk factors for VA-AKI. METHOD: Patients with vancomycin prescription and blood level measurement in 2012-2016 were identified using the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System. Acute kidney injury was defined using KDIGO criteria. Patients without creatinine measurements, steady-state trough vancomycin level or who had vancomycin treatment < 3 days were excluded. Results were analyzed using SPSS version 22.0. Logistic regression was used to identify the predictors for VA-AKI. Odds ratio and 95% confidence interval were estimated. RESULTS: One thousand four hundred fifty patients were identified as VA-AKI from 12,758 records in Hong Kong in 2012-2016. The incidence was respectively 10.6, 10.9, 11.3, 12.2, 11.2% from 2012 to 2016. The incidence of VA-AKI was 16.3, 12.2, 11.3 and 6.2% in patients aged 1-12, 12-60, elderly aged > 60 and newborn and infants, respectively. Baseline creatinine, serum trough vancomycin level, systematic disease history including respiratory failure, hypertension, congestive heart failure, chronic renal failure, anemia and type II diabetes, and concomitant diuretics, piperacillin-tazobactam (PTZ) and meropenem prescription were significantly higher in VA-AKI patients older than 12 years. Logistic regression showed that older age group, higher baseline creatinine, serum trough vancomycin level, respiratory failure, chronic renal failure and congestive heart failure, concomitant diuretics, PTZ and meropenem prescription, and longer hospital stay were all associated with increased risk of VA-AKI. CONCLUSION: The incidence of VA-AKI in Hong Kong is low but shows no decline. Patients with higher baseline creatinine, multi-organ diseases and multiple drugs administration should have their vancomycin level monitored to decrease the risk of VA-AKI.

Prevalence of metabolic syndrome among ethnic groups in China.

BACKGROUND: Metabolic syndrome (MetS) is common in China, which has a multi-ethnic population of 1·3 billion. We set out to determine the prevalence of MetS and its components in different ethnic groups. METHODS: This nationwide cross-sectional survey involved 24,796 participants from eight ethnicities in six provinces in China from 2008 to 2011. MetS was defined using the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Results were analysed using SPSS version 22·0 in 2018. Logistic regression was used for deriving odds ratios and 95% confidence intervals of risk factors for the MetS. RESULTS: The prevalence of MetS increased with age from 3·60% to 21·68%. After age standardization, the prevalence of MetS, in descending order, was 35·42% (Korean), 22·82% (Hui), 19·80% (Han), 13·72% (Miao), 12·90% (Tujia), 12·04% (Li), 11·61% (Mongolian), 6·17% (Tibetan). Korean ethnicity was associated with a higher prevalence in five components of MetS, while Tibetan ethnicity was associated with lower prevalence except decreased HDL cholesterol. Logistic regression analyses showed that age, drinking and being non-Tibetan were associated with a higher risk of MetS. CONCLUSIONS: Within one country, albeit a large one, the prevalence of MetS can vary greatly. Chinese of Korean ethnicity had a much higher prevalence than Tibetan ethnicity. Measures to tackle MetS should be tailored to the ethnic groups within a population.

Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis.

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.

Hypokalaemia associated with hydrochlorothiazide used in the treatment of hypertension in NHANES 1999-2018.

Hydrochlorothiazide is the most common thiazide diuretic used for hypertension in the US. Yet, hypokalaemia is a well-recognised adverse effect. To evaluate the prevalence and factors associated with hypokalaemia (serum potassium < 3.5 mmol/L) among hydrochlorothiazide users, we included US adults aged ≥20 years in the 1999-2018 National Health and Nutrition Examination Survey. Participants were categorised according to the use of hydrochlorothiazide and other antihypertensive agents. Factors associated with hypokalaemia, including demographics and prescription patterns (monotherapy vs single-pill fixed-dose combination vs polytherapy) were studied using multivariable logistic regression. Hypokalaemia was present in 12.6% of the hydrochlorothiazide users, equivalent to ~2.0 million US adults. Women (adjusted OR, 2.22; 95% CI, 1.74-2.83), non-Hispanic blacks (adjusted OR, 1.65; 95% CI, 1.31-2.08), underweight (adjusted OR, 4.33; 95% CI, 1.34-13.95), and participants taking hydrochlorothiazide for five years or more (adjusted OR, 1.47; 95% CI, 1.06-2.04) had a higher risk of hypokalaemia. Compared to monotherapy, fixed-dose combination therapy (adjusted OR, 0.32; 95% CI, 0.21-0.48) was associated with the lowest risk. Among those taking potassium supplements, hypokalaemia was found in 27.2% of participants on monotherapy and 17.9% on polytherapy. The prevalence of hypokalaemia among hydrochlorothiazide users was considerable, even among participants who also took potassium supplements. Women, ethnic minorities, underweight, monotherapy, and participants with long-term therapy are more likely to have hypokalaemia. Regular monitoring of potassium and combination with potassium-sparing drugs are needed.

Incidence of severe hypokalaemia in patients taking indapamide.

BACKGROUND: Diuretics are commonly used for the treatment of hypertension. Yet, hypokalaemia is a well-recognised adverse effect. We conducted a retrospective study to evaluate the incidence of severe hypokalaemia, defined as requiring hospitalisation, among patients on indapamide. METHODS: We searched a territory-wide database, Clinical Data Analysis and Reporting System of the Hong Kong Hospital Authority. We traced all hypertensive patients who had been prescribed indapamide in 2007-2016 and all admissions due to hypokalaemia in 2007-2018. Factors associated with hospitalisation were studied using multivariable logistic regression. RESULTS: During the period studied, 62,881 patients were started on indapamide and 509 (0.8%) were hospitalised for hypokalaemia. 53% of these hospitalisations occurred within the first year of treatment, and half of those in the first year occurred during the first 16 weeks. Female sex (adjusted OR, 1.75; 95%CI, 1.45-2.12) and immediate-release formulation (adjusted OR, 1.41; 95%CI, 1.14-1.75) were associated with hospitalisation. In the multivariable model, advanced age was not a significant predictor. There were no deaths during hospitalisation and the median length of hospital stay was one day. CONCLUSIONS: In this large population-based study with 147,319 person-years of follow-up, severe hypokalaemia requiring hospitalisation was uncommon among hypertensive patients on indapamide. The risk is higher in women and in the initial weeks and months after starting therapy. The use of the sustained-release formulation reduces the risk. We conclude that using indapamide to treat hypertension is safe, even in the elderly, especially if the sustained-release formulation is used and electrolytes are monitored periodically.

Real-World Study on Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Unvaccinated Patients with Chronic Respiratory Diseases with Confirmed SARS-CoV-2 Infection Managed in Out-Patient Setting.

While molnupiravir (MOV) and nirmatrelvir-ritonavir (NMV-r) were developed for treatment of mild to moderate COVID-19 infection, there has been a lack of data on the efficacy among unvaccinated adult patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. A territory-wide retrospective cohort study was conducted in Hong Kong to investigate the efficacy of MOV and NMV-r against severe outcomes of COVID-19 in unvaccinated adult patients with chronic respiratory diseases. A total of 3267 patients were included. NMV-r was effective in preventing respiratory failure (66.6%; 95% CI, 25.6-85.0%, p = 0.007), severe respiratory failure (77.0%; 95% CI, 6.9-94.3%, p = 0.039) with statistical significance, and COVID-19 related hospitalization (43.9%; 95% CI, -1.7-69.0%, p = 0.057) and in-hospital mortality (62.7%; 95% CI, -0.6-86.2, p = 0.051) with borderline statistical significance. MOV was effective in preventing COVID-19 related severe respiratory failure (48.2%; 95% CI 0.5-73.0, p = 0.048) and in-hospital mortality (58.3%; 95% CI 22.9-77.4, p = 0.005) but not hospitalization (p = 0.16) and respiratory failure (p = 0.10). In summary, both NMV-r and MOV are effective for reducing severe outcomes in unvaccinated COVID-19 patients with chronic respiratory diseases.

Prevalence of Childhood Obesity in the United States in 1999-2018: A 20-Year Analysis.

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.

Use of ticagrelor and the risks of pneumonia and pneumonia-specific death in patients with non-acute coronary syndrome conditions: a population-based cohort study.

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.

Risk of infections in patients treated with ticagrelor vs. clopidogrel: a systematic review and meta-analysis.

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.

Blood lead level and risk of hypertension in the United States National Health and Nutrition Examination Survey 1999-2016.

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.

Association between the liver fat score (LFS) and cardiovascular diseases in the national health and nutrition examination survey 1999-2016.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Blood and Urine Inorganic and Organic Mercury Levels in the United States from 1999 to 2016.

BACKGROUND: Mercury is an environmental hazard. Organic mercury is biologically more toxic than inorganic mercury. Therefore, we studied recent trends in the blood levels of organic and inorganic mercury in the United States. METHODS: A total of 56,445 participants that had blood mercury and urine mercury measurements in National Health and Nutrition Examination Survey (NHANES) 1999-2016 were included. The organic mercury level was obtained by subtracting the inorganic mercury level from the total mercury level. Results were analyzed using SPSS complex sample module version 25. Pregnant women, children ages <20 years, and different ethnicities were analyzed as subgroups. RESULTS: Blood organic mercury level increased from (geometric mean [95% confidence interval]) 0.08 [0.07-0.10] to 0.17 [0.16-0.18] µg/L during 1999-2016. It increased significantly (P <0.001) from 0.03 [0.02-0.03] to 0.07 [0.06-0.07] µg/L in children ages <20 and from 0.14 [0.09-0.21] to 0.36 [0.16-0.83] µg/L in pregnant women in this period (P <0.001). In 2013-2016, non-Hispanic Asians had the highest blood organic mercury level among different ethnicities, 0.93 [0.82-1.05] µg/L (P <0.001). Blood inorganic mercury level decreased from 0.31 [0.31-0.31] in 1999-2000 to 0.21 [0.21-0.22] µg/L in 2015-2016 (P <0.001). Urine mercury level decreased from 0.75 [0.71-0.80] in 1999-2000 to 0.16 [0.16-0.17] µg/L in 2015-2016 (P <0.001). CONCLUSION: Blood organic mercury increased over the period 1999-2016 in the US population, including children and pregnant women, whereas there was a steady decline in both blood inorganic mercury and urine mercury levels.

A 2020 Vision of Hypertension.

Hypertension is a common chronic disease affecting a large section of the general population. Hypertension is highly prevalent in the elderly because blood pressure (BP) rises with age. The risk of developing hypertension increases with predisposing genes, intrauterine growth retardation, prematurity and childhood obesity. BP is easier to control in the young. Non-pharmacological treatment through lifestyle changes, such as weight control and leisure-time physical activity, is more likely to be successful in young people. Hypertension in older adults is more difficult to control, requiring the use of more than one antihypertensive drug. Adverse effects and compliance become problematic. Much research is now directed at novel ways of controlling BP such as denervation. The change in definition of hypertension in the American guideline highlights the need to identify and manage hypertension early, at a stage when it is potentially reversible.