Major adverse cardiovascular events in homozygous familial hypercholesterolaemia: a systematic review and meta-analysis.

AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a genetic condition characterized by extremely elevated levels of low-density lipoprotein cholesterol and premature atherosclerotic cardiovascular disease and death. Due to its rarity, accurate assessment of cardiovascular outcomes associated with HoFH and how they have changed over time has been challenging. The goal of this study was to assess the prevalence and age-of-onset of major adverse cardiovascular events (MACE) among patients with HoFH. METHODS AND RESULTS: We searched MEDLINE, EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, Scopus, Africa-Wide, Google Scholar, Open Grey, and various clinical trial registries from inception to February 2020 to identify studies reporting on MACE in HoFH patients. We determined the pooled prevalence and mean age-of-onset of MACE outcomes individually using a random effects inverse variance model. We identified 94 studies that met our eligibility criteria. Myocardial infarction and coronary revascularization were common with a prevalence of 15.1% [95% confidence interval (95% CI) 10.7-20.0] and 28.3% (95% CI 22.5-34.3), respectively. The mean age-of-onset was 24.5 (95% CI 19.2-29.8) years for myocardial infarction and 32.2 (95% CI 26.6-37.8) years for revascularization. Sub-group analyses based on the year of publication revealed significant delays in the onset of MACE outcomes post-1990 compared to pre-1990. Egger's regression suggested possible bias, likely due to small study effects. CONCLUSIONS: Atherosclerotic cardiovascular disease is common among HoFH patients and occurs at a young age. Age-of-onset of myocardial infarction was delayed by more than a decade from pre-1990 to post-1990, likely attributable to widespread use of statins and other therapies, reflecting substantial progress in the management of this rare but severe disorder.

The Impact of Implementing 24/7 Cardiac CTA Interpretation in the Emergency Department on Patient Care: Retrospective Analysis of a Single-Center Experience.

OBJECTIVE. The objective of our study was to provide insight on the diagnostic validity of cardiac CTA (CCTA) to identify obstructive coronary artery disease (CAD) and patients who require urgent intervention, compared with those who require same-admission coronary catheterization (CC), and to help elucidate the necessity of a 24/7 CCTA service. MATERIALS AND METHODS. We retrospectively reviewed 658 consecutive CCTA examinations performed of emergency department (ED) patients who presented with acute chest pain from October 1, 2013, to February 28, 2018. Patients were categorized by CAD severity on CCTA. Using same-admission CC as the reference standard, we assessed CCTA's validity to identify obstructive disease using PPV, NPV, sensitivity, and specificity and CCTA's validity to identify patients who require urgent intervention. The added value of the CCTA findings of subendocardial hypoattenuation and wall motion abnormality was evaluated. CCTA examinations were categorized on the basis of the time of day when scanning was performed. RESULTS. The PPV, NPV, and sensitivity of CCTA to diagnose obstructive CAD were 0.87, 0.79, and 0.95, respectively. Nine percent of the scanned patients underwent percutaneous coronary intervention (PCI) or were referred for urgent coronary artery bypass grafting (CABG). The presence of obstructive CAD on CCTA has a PPV of 0.73 to identify patients deemed to be at higher acute coronary syndrome (ACS) risk to warrant urgent PCI or CABG. Wall motion abnormality increased the PPV to 1.0; subendocardial attenuation increased the PPV to 0.9. The NPV and sensitivity were 0.89 and 0.97, respectively. Of the CCTA examinations, 54% were performed outside regular working hours. Of the patients who received urgent interventions, 62% underwent CCTA examinations performed outside regular working hours. CONCLUSION. CCTA provides high correlation with CC, helps identify individuals with high ACS risk, and is further strengthened by functional analysis; 24/7 CCTA service is warranted.

Estimating the Prevalence of Familial Hypercholesterolemia in Acute Coronary Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND: Heterozygous familial hypercholesterolemia (FH) is one of the most common monogenic conditions but remains substantially underdiagnosed. One method for increasing the diagnosis is via opportunistic screening of individuals presenting with acute coronary syndrome (ACS). The prevalence of FH in the ACS population has been assessed in numerous studies using various diagnostic criteria, resulting in wide variability of prevalence estimates. The purpose of this study was to perform a systematic review and meta-analysis to provide a more robust estimate. METHODS: We searched MEDLINE, EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews to identify peer-reviewed articles reporting the prevalence of FH in ACS. We calculated pooled prevalence using a random-effects model. When multiple diagnostic criteria were used in a single study, we gave priority to DNA-based criteria, followed by Dutch Lipid Clinic Network (DLCN) criteria. We also investigated the prevalence in subanalyses according to age and diagnostic criteria. RESULTS: The overall pooled prevalence of FH in ACS, derived from 22 studies, was 4.7% (95% confidence interval [CI], 3.0-7.3). DNA-based criteria and DLCN criteria provided similar estimates of 5.0% (95% CI, 2.6-9.3) and 5.5% (95% CI, 3.0-10.0), respectively. The prevalence was 7.3% (95% CI, 5.3-10.0) for patients aged ≤ 60 years and increased to 13.7% (95% CI, 8.2-22.1) for those aged ≤45 years. CONCLUSIONS: Approximately 1 in 21 patients with ACS has FH, and this increases to 1 in 7 among those ≤45 years. These results reinforce the importance of screening for FH in the ACS population.

Success of University Student Volunteers in Obtaining Consent for Reviewing Private Health Information for Emergency Research.

This study aimed to determine the success of university student volunteers in obtaining consent from parents to allow review of their child's personal health information (PHI) for emergency research screening. This study also aimed to examine the variables associated with successful consent. This was a prospective cross-sectional study conducted at a pediatric emergency department (ED). University students, who functioned as delegates of the health information custodian, approached parents for consent. Of 2,506 parents, 1,852 (73.9%) provided consent to allow review of their child's PHI for research screening. Variables associated with successful consent were high (≥12 months) versus low (<12 months) volunteer experience (OR = 2.0), research related (vs. unrelated) to the child's chief complaint (OR = 2.0), child treated regularly by specialists at the study institution (OR = 1.7), and ED presentation mid-week vs. weekend (OR = 1.7) and morning vs. evening presentation (OR = 1.4). When approached by a university student volunteer, about 25% of parents declined to have their child's PHI reviewed for research screening. This model of obtaining consent may put some emergency research at risk for selection bias. Variables that increase the odds of successful consent can be considered in program design to improve the effectiveness of this model.