Baseline and On-Treatment High-Density Lipoprotein Cholesterol and the Risk of Cancer in Randomized Controlled Trials of Lipid-Altering Therapy

ObjectivesWe sought to examine the relationship between high-density lipoprotein cholesterol (HDL-C) levels and the risk of the development of cancer in large randomized controlled trials (RCTs) of lipid-altering interventions.BackgroundEpidemiologic data demonstrate an inverse relationship between serum total cholesterol levels and incident cancer. We recently reported that lower levels of low-density lipoprotein cholesterol are associated with a significantly higher risk of incident cancer in a meta-analysis of large RCTs of statin therapy. However, little is known about the relationship between HDL-C levels and cancer risk.MethodsA systematic MEDLINE search identified lipid intervention RCTs with ≥1,000 person-years of follow-up, providing baseline HDL-C levels and rates of incident cancer. Using random-effects meta-regressions, we evaluated the relationship between baseline HDL-C and incident cancer in each RCT arm.ResultsA total of 24 eligible RCTs were identified (28 pharmacologic intervention arms and 23 control arms), with 625,477 person-years of follow-up and 8,185 incident cancers. There was a significant inverse association between baseline HDL-C levels and the rate of incident cancer (p = 0.018). The inverse association persisted after adjusting for baseline low-density lipoprotein cholesterol, age, body mass index (BMI), diabetes, sex, and smoking status, such that for every 10-mg/dl increment in HDL-C, there was a 36% (95% confidence interval: 24% to 47%) relatively lower rate of the development of cancer (p < 0.001).ConclusionsThere is a significant inverse association between HDL-C and the risk of incident cancer that is independent of LDL-C, age, BMI, diabetes, sex, and smoking

Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer Insights From Large Randomized Statin Trials

ObjectivesWe sought to assess the relationship between the magnitude of low-density lipoprotein cholesterol (LDL-C) lowering and rates of elevated liver enzymes, rhabdomyolysis, and cancer.BackgroundAlthough it is often assumed that statin-associated adverse events are proportional to LDL-C reduction, that assumption has not been validated.MethodsAdverse events reported in large prospective randomized statin trials were evaluated. The relationship between LDL-C reduction and rates of elevated liver enzymes, rhabdomyolysis, and cancer per 100,000 person-years was assessed using weighted univariate regression.ResultsIn 23 statin treatment arms with 309,506 person-years of follow-up, there was no significant relationship between percent LDL-C lowering and rates of elevated liver enzymes (R2<0.001, p = 0.91) or rhabdomyolysis (R2= 0.05, p = 0.16). Similar results were obtained when absolute LDL-C reduction or achieved LDL-C levels were considered. In contrast, for any 10% LDL-C reduction, rates of elevated liver enzymes increased significantly with higher statin doses. Additional analyses demonstrated a significant inverse association between cancer incidence and achieved LDL-C levels (R2= 0.43, p = 0.009), whereas no such association was demonstrated with percent LDL-C reduction (R2= 0.09, p = 0.92) or absolute LDL-C reduction (R2= 0.05, p = 0.23).ConclusionsRisk of statin-associated elevated liver enzymes or rhabdomyolysis is not related to the magnitude of LDL-C lowering. However, the risk of cancer is significantly associated with lower achieved LDL-C levels. These findings suggest that drug- and dose-specific effects are more important determinants of liver and muscle toxicity than magnitude of LDL-C lowering. Furthermore, the cardiovascular benefits of low achieved levels of LDL-C may in part be offset by an increased risk of cancer

Inflammatory cytokines and atrial fibrillation: current and prospective views

Atrial fibrillation (AF) is the most common sustained arrhythmia and a challenging clinical problem encountered in daily clinical practice. There is an increasing body of evidence linking inflammation to a broad spectrum of cardiovascular conditions including AF. Historical evidence supports an association between AF and inflammation and is consistent with the association of AF with inflammatory conditions of the heart, such as myocarditis and pericarditis. AF has been associated with myocardial oxidative stress, and antioxidant agents have demonstrated antiarrhythmic benefit in humans. Increased plasma interleukin (IL)-6, C-reactive protein (CRP), and plasma viscosity support the existence of an inflammatory state among “typical” populations with chronic AF. These indexes of inflammation are related to the prothrombotic state and may be linked to the clinical characteristics of the patients (underlying vascular disease and comorbidities), rather than simply to the presence of AF itself. It has been suggested that inflammation may have a role in the development of atrial arrhythmias after cardiac surgery, and that a genetic predisposition to develop postoperative complications exists. Cytokines can have a prognostic significance; IL-6 levels, CRP, and other cytokines may have prognostic value in AF. Cytokine lowering therapies, statins, angiotensin converting enzyme inhibitors and other anti-inflammatory agents may have a role in the treatment of AF. The present article provides an overview of the evidence linking inflammatory cytokines to AF and their therapeutic and prognostic implications

Commotio Cordis

Sudden arrhythmic death as a result of a blunt chest wall blow has been termed Commotio Cordis (CC). CC is being reported with increasing frequency with more than 180 cases now described in the United States Commotio Cordis Registry. The clinical spectrum is diverse; however young athletes tend to be most at risk, with victims commonly being struck by projectiles regarded as standard implements of the sport. Sudden death is instantaneous and victims are most often found in ventricular fibrillation (VF). Chest blows are not of sufficient magnitude to cause any significant damage to overlying thoracic structures and autopsy is notable for the absence of any structural cardiac injury. Development of an experimental model has allowed for substantial insights into the underlying mechanisms of sudden death. In anesthetized juvenile swine, induction of VF is instantaneous following chest impacts that occur during a vulnerable window before the T wave peak. Other critical variables, including the impact velocity and location, and the hardness of the impact object have also been identified. Rapid left ventricular pressure rise following chest impact likely results in activation of ion channels via mechano-electric coupling. The generation of inward current through mechano-sensitive ion channels results in augmentation of repolarization and non-uniform myocardial activation, and is the cause of premature ventricular depolarizations that are triggers of VF in CC. Currently available chest protectors commonly used in sport are not adequately designed to prevent CC. The development of more effective chest protectors and the widespread availability of automated external defibrillators at youth sporting events could improve the safety of young athletes

Case-finding of chronic obstructive pulmonary disease with questionnaire, peak flow measurements and spirometry : a cross-sectional study

Peer reviewedPublisher PD

Unveiling the dynamics of antimicrobial utilization and resistance in a large hospital network over five years: Insights from health record data analysis

Antimicrobial Resistance (AMR) presents a pressing public health challenge globally which has been compounded by the COVID-19 pandemic. Elucidation of the impact of the pandemic on AMR evolution using population-level data that integrates clinical, laboratory and prescription data remains lacking. Data was extracted from the centralized electronic platform which captures the health records of 60,551 patients with a confirmed infection across the network of public healthcare facilities in Dubai, United Arab Emirates. For all inpatients and outpatients diagnosed with bacterial infection between 01/01/2017 and 31/05/2022, structured and unstructured Electronic Health Record data, microbiological laboratory data including antibiogram, molecular typing and COVID-19 testing information as well as antibiotic prescribing data were extracted curated and linked. Various analytical methods, including time-series analysis, natural language processing (NLP) and unsupervised clustering algorithms, were employed to investigate the trends of antimicrobial usage and resistance over time, assess the impact of prescription practices on resistance rates, and explore the effects of COVID-19 on antimicrobial usage and resistance. Our findings identified a significant impact of COVID-19 on antimicrobial prescription practices, with short-term and long-lasting over-prescription of these drugs. Resistance to antimicrobials increased the odds ratio of all mortality to an average of 2.18 (95% CI: 1.87–2.49) for the most commonly prescribed antimicrobials. Moreover, the effects of antimicrobial prescription practices on resistance were observed within one week of initiation. Significant trends in antimicrobial resistance, exhibiting fluctuations for various drugs and organisms, with an overall increasing trend in resistance levels, particularly post-COVID-19 were identified. This study provides a population-level insight into the evolution of AMR in the context of COVID-19 pandemic. The findings emphasize the impact of COVID-19 on the AMR crisis, which remained evident even two years after the onset of the pandemic. This underscores the necessity for enhanced antimicrobial stewardship to address the evolution of AMR

The “obesity paradox” in patients with atrial fibrillation:Insights from the Gulf SAFE registry

BACKGROUND: The prognostic impact of obesity on patients with atrial fibrillation (AF) remains under-evaluated and controversial. METHODS: Patients with AF from the Gulf Survey of Atrial Fibrillation Events (Gulf SAFE) registry were included, who were recruited from six countries in the Middle East Gulf region and followed for 12 months. A multivariable model was established to investigate the association of obesity with clinical outcomes, including stroke or systemic embolism (SE), bleeding, admission for heart failure (HF) or AF, all-cause mortality, and a composite outcome. Restricted cubic splines were depicted to illustrate the relationship between body mass index (BMI) and outcomes. Sensitivity analysis was also conducted. RESULTS: A total of 1,804 patients with AF and recorded BMI entered the final analysis (mean age 56.2 ± 16.1 years, 47.0% female); 559 (31.0%) were obese (BMI over 30 kg/m(2)). In multivariable analysis, obesity was associated with reduced risks of stroke/systematic embolism [adjusted odds ratio (aOR) 0.40, 95% confidence interval (CI), 0.18–0.89], bleeding [aOR 0.44, 95%CI, 0.26–0.74], HF admission (aOR 0.61, 95%CI, 0.41–0.90) and the composite outcome (aOR 0.65, 95%CI, 0.50–0.84). As a continuous variable, higher BMI was associated with lower risks for stroke/SE, bleeding, HF admission, all-cause mortality, and the composite outcome as demonstrated by the accumulated incidence of events and restricted cubic splines. This “protective effect” of obesity was more prominent in some subgroups of patients. CONCLUSION: Among patients with AF, obesity and higher BMI were associated with a more favorable prognosis in the Gulf SAFE registry. The underlying mechanisms for this obesity “paradox” merit further exploration

Saliva as an Alternative Specimen for Molecular COVID-19 Testing in Community Settings and Population-Based Screening.

PURPOSE: With the easing of restriction measures, repeated community-based sampling for tracking new COVID-19 infections is anticipated for the next 6 to 12 months. A non-invasive, self-collected specimen like saliva will be useful for such public health surveillance. Investigations on the use of saliva for SARS-CoV-2 RT-PCR have largely been among COVID-19 in-pa\tients and symptomatic ambulatory patients with limited work in a community-based screening setting. This study was carried out to address this paucity of data and reported discrepancies in diagnostic accuracy for saliva samples. PATIENTS AND METHODS: From 29th June to 14th July 2020, adults presenting for COVID-19 testing at a community-based screening facility in Dubai, United Arab Emirates were recruited. Clinical data, nasopharyngeal swab in universal transport media and drooling saliva in sterile containers were obtained. Reverse transcriptase PCR amplification of SARS-CoV-2 RdRp and N genes was used to detect the presence of the SARS-CoV-2 virus. RESULTS: Of the 401 participants, 35 (8.7%) had viral detection in at least one specimen type and the majority (n=20/35; 57.1%) were asymptomatic. Both swab and saliva were positive in 19 (54.2%) patients, while 7 (20.0%) patients had swab positive/saliva negative results. There were 9 (25.7%) patients with saliva positive/swab negative result and this included 5 asymptomatic COVID-19 patients undergoing repeat screening. Using the swab as the reference gold standard, the sensitivity and specificity of saliva were 73.1% (95% CI 52.2-88.4%) and 97.6% (95% CI 95.5-98.9%) while the positive and negative predictive values were 67.9% (95% CI 51.5-80.8%) and 98.1% (95% CI 96.5-99.0%), respectively. CONCLUSION: The findings suggest good diagnostic accuracy for saliva and feasibility of utilization of specimen without transport media for SARS-CoV-2 RT-PCR. Saliva represents a potential specimen of choice in community settings and population-based screening