Approaches to Comparing the Impact of Socioeconomic Disadvantage on Acute Myocardial Infarction Care Within and Across Countries: A Scoping Review.

BACKGROUND: Understanding how cardiovascular disease treatment and outcomes differ for socioeconomically disadvantaged patients across countries may reveal insights into the impact of countries' policy initiatives on health equity. However, methods of undertaking these studies are poorly characterized. METHODS: We performed a scoping review to identify studies describing between-country comparisons of socioeconomic inequalities in the care of acute myocardial infarction (AMI). We sought to determine the extent to which such comparisons have been conducted, the methodologies used, and outcomes assessed. We searched Medline from January 1, 2013 to September 30, 2023 for peer-reviewed English-language publications. Studies were included if they stratified patients by a measure of socioeconomic disadvantage (eg, race, ethnicity, income, education, occupation, immigrant status) and made comparisons between 2 or more countries. RESULTS: Our search yielded 4861 articles focused on patients with AMI, of which 7 met our inclusion criteria. Common individual-level proxies for disadvantage were self-reported income or education. In contrast, we found no cross-country comparisons focused on other measures of disadvantage such as race and ethnicity. There was marked heterogeneity in methods and thresholds used to define socioeconomic disadvantage at the individual level. All included studies found that patients with higher income and higher educational attainment had improved AMI outcomes. CONCLUSIONS: Between-country comparisons of socioeconomic disparities in AMI outcomes are scarce and heterogeneous, but all identified studies relied on metrics of disadvantage including income and education that could be uniformly measured across countries. We found no articles addressing other types of inequities, likely because of significant methodologic challenges.

Association of Neighborhood-Level Marginalization With Health Care Use and Clinical Outcomes Following Hospital Discharge in Patients Who Underwent Coronary Catheterization for Acute Myocardial Infarction in a Single-Payer Health Care System.

BACKGROUND: Canadian data suggest that patients of lower socioeconomic status with acute myocardial infarction receive less beneficial therapy and have worse clinical outcomes, raising questions regarding care disparities even in universal health care systems. We assessed the contemporary association of marginalization with clinical outcomes and health services use. METHODS: Using clinical and administrative databases in Ontario, Canada, we conducted a population-based study of patients aged ≥65 years hospitalized for their first acute myocardial infarction between April 1, 2010 and March 1, 2019. Patients receiving cardiac catheterization and surviving 7 days postdischarge were included. Our primary exposure was neighborhood-level marginalization, a multidimensional socioeconomic status metric. Neighborhoods were categorized by quintile from Q1 (least marginalized) to Q5 (most marginalized). Our primary outcome was all-cause mortality. A proportional hazards regression model with a robust variance estimator was used to quantify the association of marginalization with outcomes, adjusting for risk factors, comorbidities, disease severity, and regional cardiologist supply. RESULTS: Among 53 841 patients (median age, 75 years; 39.1% female) from 20 640 neighborhoods, crude 1- and 3-year mortality rates were 7.7% and 17.2%, respectively. Patients in Q5 had no significant difference in 1-year mortality (hazard ratio [HR], 1.08 [95% CI, 0.95-1.22]), but greater mortality over 3 years (HR, 1.13 [95% CI, 1.03-1.22]) compared with Q1. Over 1 year, we observed differences between Q1 and Q5 in visits to primary care physicians (Q1, 96.7%; Q5, 93.7%) and cardiologists (Q1, 82.6%; Q5, 72.6%), as well as diagnostic testing. There were no differences in secondary prevention medications dispensed or medication adherence at 1 year. CONCLUSIONS: In older patients with acute myocardial infarction who survived to hospital discharge, those residing in the most marginalized neighborhoods had a greater long-term risk of mortality, less specialist care, and fewer diagnostic tests. Yet, there were no differences across socioeconomic status in prescription medication use and adherence.

Prevalence and Treatment of Familial Hypercholesterolemia and Severe Hypercholesterolemia in Older Adults in Ontario, Canada.

Background: A simplified Canadian definition was recently developed to enable identification of individuals with familial hypercholesterolemia (FH) and severe hypercholesterolemia in the general population. Our objective was to use a modified version of this new definition to assess contemporary disease prevalence, treatment patterns, and low-density lipoprotein cholesterol (LDL-C) control in Ontario, Canada. Methods: We identified individuals aged 66 to 105 years who were alive as of January 1, 2011, using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) database, which was created by linking 19 population-based health databases in Ontario. Hypercholesterolemia was identified using LDL-C values. Cholesterol reduction and lipid-lowering treatment were assessed at time of diagnosis and after at least 2 and 5 years' follow-up. Results: Among 922,464 individuals, 2440 (0.26%) met criteria for definite or probable FH, and 72,893 (7.90%) for severe hypercholesterolemia. At diagnosis, mean LDL-C concentration was 9.52 mmol/L for those with definite FH, 5.83 mmol/L for those with probable FH, 5.73 mmol/L for those with severe hypercholesterolemia, and 3.33 mmol/L for all other individuals. After > 5 years, LDL-C concentration remained elevated at 3.58 mmol/L for those with definite FH, 2.72 mmol/L for those with probable FH, and 2.93 mmol/L for those with severe hypercholesteremia. Use of statin therapy was initially high (83% of those with definite FH, 78% of those with probable FH, 62% of those with severe hypercholesterolemia); however, fewer patients remained on statins at follow-up at > 5 years (62% of those with definite FH, 67% of those with probable FH, 58% of those with severe hypercholesterolemia). Conclusions: Among older Ontarians, we estimated that 1 in 378 individuals had FH, and 1 in 13 had severe hypercholesterolemia. Despite being at substantially increased cardiovascular risk, these patients acheived suboptimal LDL-C level control and fewer were on medical therapy at follow-up.

Introduction: Une définition canadienne simplifiée a récemment été élaborée pour permettre la détection des personnes atteintes d'hypercholestérolémie familiale (HF) et d'hypercholestérolémie grave au sein de la population générale. Notre objectif était d'utiliser la version modifiée de cette nouvelle définition pour évaluer la prévalence contemporaine de la maladie, les schémas de traitement et la maîtrise du cholestérol à lipoprotéines de faible densité (cholestérol LDL) en Ontario, au Canada. Méthodes: Nous avons recensé les individus âgés de 66 à 105 ans qui étaient en vie au 1er janvier 2011 à partir de la base de données Cardiovascular Health in Ambulatory Care Research Team (CANHEART), qui a été créée par la liaison de 19 bases de données populationnelles de l'Ontario. L'hypercholestérolémie a été définie par les valeurs du cholestérol LDL. Nous avons évalué la diminution du cholestérol et le traitement hypolipémiant au moment du diagnostic et après au moins les suivis après 2 ans et après 5 ans. Résultats: Parmi les 922 464 personnes, 2 440 (0,26 %) répondaient aux critères de diagnostic définitif ou de diagnostic probable d'HF, et 72 893 (7,90 %), aux critères d'hypocholestérolémie grave. Au diagnostic, les concentrations moyennes de cholestérol LDL étaient de 9,52 mmol/l chez ceux qui avaient un diagnostic définitif d'HF, de 5,83 mmol/l chez ceux qui avaient un diagnostic probable d'HF, de 5,73 mmol/l chez ceux qui avaient un diagnostic d'hypercholestérolémie grave et de 3,33 mmol/l chez toutes les autres personnes. Après > 5 ans, les concentrations de cholestérol LDL étaient demeurées élevées : 3,58 mmol/l chez ceux qui avaient un diagnostic définitif d'HF, 2,72 mmol/l chez ceux qui avaient un diagnostic probable d'HF et 2,93 mmol/l chez ceux qui avaient un diagnostic d'hypercholestérolémie grave. L'utilisation du traitement par statines était initialement élevée (83 % de ceux qui avaient un diagnostic définitif d'HF, 78 % de ceux qui avaient un diagnostic probable d'HF, 62 % de ceux qui avaient un diagnostic d'hypercholestérolémie grave). Toutefois, moins de patients avaient conservé les statines au suivi > 5 ans (62 % de ceux qui avaient un diagnostic définitif d'HF, 67 % de ceux qui avaient un diagnostic probable d'HF, 58 % de ceux qui avaient un diagnostic d'hypercholestérolémie grave). Conclusions: Parmi les Ontariens âgés, nous avons estimé que 1 sur 378 personnes avaient une HF, et que 1 sur 13 avaient une hypercholestérolémie grave. Malgré le fait qu'ils sont exposés à un risque cardiovasculaire substantiellement élevé, ces patients ont atteint une maîtrise sous-optimale du taux de cholestérol LDL et moins d'entre eux étaient sous traitement médical au suivi.

Aortic stenosis in homozygous familial hypercholesterolaemia: a paradigm shift over a century.

AIMS: Homozygous familial hypercholesterolaemia (HoFH) is an orphan disease defined by extreme elevations in low-density lipoprotein cholesterol, cutaneous xanthomas, and pre-mature atherosclerotic cardiovascular disease. Survival has more than doubled over the past three decades. Aortic stenosis (AS) [supravalvular aortic stenosis (SVAS) or valvular aortic stenosis (VAS)] is commonly encountered. There are no medical treatments available and complex high-risk surgeries represent the only available option in severe cases. A systematic review was performed to summarize the current evidence on AS in HoFH and to determine whether pharmacological treatment (statins) have had an impact on clinical presentation, phenotype and clinical course over the past nine decades (PROSPERO CRD42021250565). METHODS AND RESULTS: MEDLINE, Embase Classic + Embase, Cochrane Central Register of Controlled Trials, PubMed, AfricaWide, and Scopus were searched from inception to 10 November 2021. Searches identified 381 publications, of which 19 were retained; they were cross-sectional or retrospective studies. Separately, 108 individual case reports were described. Within the 424 HoFH cases, AS was identified in 57% of patients in the pre-statin era vs. 35% in patients reported more recently (>2000, long-term statin period). With an increase in longevity due to statins and lipoprotein apheresis, a change in the proportion of patients with SVAS and VAS with a SVAS:VAS ratio of 47:53 and 10:90 for HoFH patients not on statin and on long-term statin, respectively, was noted. CONCLUSION: These data suggest that SVAS and VAS are frequent in HoFH and that the phenotype has shifted towards calcific VAS as statins and lipoprotein apheresis improve survival in these patients.

Association of Neighborhood-Level Material Deprivation With Atrial Fibrillation Care in a Single-Payer Health Care System: A Population-Based Cohort Study.

BACKGROUND: There are limited data on the association of material deprivation with clinical care and outcomes after atrial fibrillation (AF) diagnosis in jurisdictions with universal health care. METHODS: This was a population-based cohort study of individuals ≥66 years of age with first diagnosis of AF between April 1, 2007, and March 31, 2019, in the Canadian province of Ontario, which provides public funding and prohibits private payment for medically necessary physician and hospital services. Prescription medications are subsidized for residents >65 years of age. The primary exposure was neighborhood material deprivation, a metric derived from Canadian census data to estimate inability to attain basic material needs. Neighborhoods were categorized by quintile from Q1 (least deprived) to Q5 (most deprived). Cause-specific hazards regression was used to study the association of material deprivation quintile with time to AF-related adverse events (death or hospitalization for stroke, heart failure, or bleeding), clinical services (physician visits, cardiac diagnostics), and interventions (anticoagulation, cardioversion, ablation) while adjusting for individual characteristics and regional cardiologist supply. RESULTS: Among 347 632 individuals with AF (median age 79 years, 48.9% female), individuals in the most deprived neighborhoods (Q5) had higher prevalence of cardiovascular disease, risk factors, and noncardiovascular comorbidity relative to residents of the least deprived neighborhoods (Q1). After adjustment, Q5 residents had higher hazards of death (hazard ratio [HR], 1.16 [95% CI, 1.13-1.20]) and hospitalization for stroke (HR, 1.16 [95% CI, 1.07-1.27]), heart failure (HR, 1.14 [95% CI, 1.11-1.18]), or bleeding (HR, 1.16 [95% CI, 1.07-1.25]) relative to Q1. There were small differences across quintiles in primary care physician visits (HR, Q5 versus Q1, 0.91 [95% CI, 0.89-0.92]), echocardiography (HR, Q5 versus Q1, 0.97 [95% CI, 0.96-0.99]), and dispensation of anticoagulation (HR, Q5 versus Q1, 0.97 [95% CI, 0.95-0.98]). There were more prominent disparities for Q5 versus Q1 in cardiologist visits (HR, 0.84 [95% CI, 0.82-0.86]), cardioversion (HR, 0.80 [95% CI, 0.76-0.84]), and ablation (HR, 0.45 [95% CI, 0.30-0.67]). CONCLUSIONS: Despite universal health care and prescription medication coverage, residents of more deprived neighborhoods were less likely to visit cardiologists or receive rhythm control interventions after AF diagnosis, even though they exhibited higher cardiovascular disease burden and higher risk of adverse outcomes.

Association between sex and survival after non-traumatic out of hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Existing studies have shown conflicting results regarding the relationship of sex with survival after out of hospital cardiac arrest (OHCA). This systematic review evaluates the association of female sex with survival to discharge and survival to 30 days after non-traumatic OHCA. METHODS: We searched Medline, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from inception through June 2021 for studies evaluating female sex as a predictor of survival in adult patients with non-traumatic cardiac arrest. Random-effects inverse variance meta-analyses were performed to calculate pooled odds ratios (ORs) with 95% confidence intervals (CI). The GRADE approach was used to assess evidence quality. RESULTS: Thirty studies including 1,068,788 patients had female proportion of 41%. There was no association for female sex with survival to discharge (OR 1.03, 95% CI 0.95-1.12; I2 = 89%). Subgroup analysis of low risk of bias studies demonstrated increased survival to discharge for female sex (OR 1.20, 95% CI 1.18-1.23; I2 = 0%) and with high certainty, the absolute increase in survival was 2.2% (95% CI 0.1-3.6%). Female sex was not associated with survival to 30 days post-OHCA (OR 1.02, 95% CI 0.92-1.14; I2 = 79%). CONCLUSIONS: In adult patients experiencing OHCA, with high certainty in the evidence from studies with low risk of bias, female sex had a small absolute difference for the outcome survival to discharge and no difference in survival at 30 days. Future models that aim to stratify risk of survival post-OHCA should focus on sex-specific factors as opposed to sex as an isolated prognostic factor.

Health-related quality of life in homozygous familial hypercholesterolemia: A systematic review and meta-analysis.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by extreme elevations of low-density lipoprotein cholesterol (LDL-C) and extremely premature atherosclerotic cardiovascular disease. To date, impacts of HoFH and its treatment on the psychosocial wellbeing of patients have been poorly characterized. OBJECTIVES: We performed a systematic review of the association between HoFH and health-related quality of life (HRQL). METHODS: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) consensus guidelines. We searched MEDLINE, Embase, The Cochrane Controlled Register of Trials (CENTRAL), Pubmed, Scopus, AfricaWide (via EBSCO), and six trial registries and grey-literature databases from inception to May 2021 for published English-language literature examining HRQL and its determinants in HoFH. Studies were eligible if they included patients with confirmed HoFH and evaluated HRQL using validated tools. We performed a narrative synthesis of qualitative findings from included studies and, where data permitted, random-effects meta-analysis reporting standardized mean differences (SMD) and 95% confidence intervals (CIs). RESULTS: Our review identified seven eligible studies examining HRQL in HoFH participants. Pooling data from two included studies, we found that relative to the general population, HoFH patients demonstrated significantly poorer HRQL in multiple dimensions of the 36-item Short-Form Health Survey (SF-36) with lower scores in physical functioning (SMD -0.37; 95% CI: -0.60, -0.15), role limitations due to physical health (SMD -0.63; 95% CI: -1.24, -0.02), social functioning (SMD -0.61; 95% CI: -1.19, -0.03), bodily pain (SMD -0.24; 95% CI: -0.46, -0.01), and general health (SMD -1.55; 95% CI: -1.80, -1.31). No differences were observed in domains of energy and vitality, mental health and emotional well-being, or role limitations due to emotional problems. Patients suffered high treatment burdens related to lipoprotein apheresis that compromised educational attainment and employment. However, few patients received psychological support in navigating their treatment challenges. No studies evaluated the association of HoFH with incident anxiety, depression, or other psychopathology. CONCLUSIONS: Limited data are available on quality of life for patients with HoFH. The available data suggest that these patients may suffer disease-related impairments in quality of life. Future work should aim to elucidate relationships between HoFH and mental health outcomes and develop interventions to improve quality of life in this population.

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.

New Frontiers in the Treatment of Homozygous Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder. The most common cause is a mutation in both alleles of the gene encoding for the low-density lipoprotein (LDL) receptor, although other causative mutations have been identified. Complications of atherosclerotic cardiovascular disease are common in these patients; therefore, reducing the elevated LDL-cholesterol burden is critical in their management. Conventionally, this is achieved by patients initiating lipid-lowering therapy, but this can present challenges in clinical practice. Fortunately, novel therapeutic strategies have enabled promising innovations in HoFH treatment. This review highlights recent and ongoing studies examining new therapeutic options for patients with HoFH.

Mycobacterium chimaera After Aortic Valve Replacement Causing Aortic Rupture and Prosthetic Valve Endocarditis.

A 20-year-old man with severe aortic insufficiency received a mechanical aortic valve replacement. Afterward he subsequently presented with an aortic root dissection, pseudoaneurysm, and prosthetic valve endocarditis requiring surgical reinterventions twice with a positive Mycobacterium chimaera tissue culture despite prolonged antimycobacterial therapy. This is the first reported clinical case of M chimaera in Western Canada and the first with M chimaera-associated aortic dissection and pseudoaneurysm.

Evidence for improved survival with treatment of homozygous familial hypercholesterolemia.

PURPOSE OF REVIEW: Homozygous familial hypercholesterolemia (HoFH) is an orphan disease caused by biallelic mutations at the LDL receptor (LDLR) gene, with a prevalence estimated at 1 : 250 000 to 1 : 630 000. HoFH is characterized by extremely elevated plasma levels of LDL-C greater than 10 mmol/l (>387 mg/dl), tendinous and cutaneous xanthomas in youth and premature atherosclerotic cardiovascular disease (ASCVD). The expected prevalence varies from country to country depending on the presence of founder effects, genetic probability and life expectancy. Untreated, HoFH is a fatal condition before age 30. Plasma levels of LDL-C are the major cause of mortality and the therapeutic target. Statin therapy led to a remarkable improvement in survival but is of limited use in loss-of-function LDLR gene variants or 'null' mutations. Inhibitors of PCSK9 are a useful adjunct in patients with LDLR mutations with residual activity. Extracorporeal LDL filtration has improved survival since its introduction three decades ago. RECENT FINDINGS: Novel therapies, not dependent on a functioning LDLR include lomitapide and mipomersen, which decrease hepatic apolipoprotein B secretion, and evinacumab, directed at the angiopoietin like-3 protein (ANGPLT-3). SUMMARY: Over the past 3-4 decades, the survival of patients with HoFH has increased markedly. New therapeutic options offer new hope.

Risk of Ischemic Stroke and Peripheral Arterial Disease in Heterozygous Familial Hypercholesterolemia: A Meta-Analysis.

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder predisposing affected individuals to lifelong low-density lipoprotein cholesterol (LDL-C) elevation and coronary heart disease. However, whether HeFH increases the risk of peripheral arterial disease (PAD) and ischemic stroke is undetermined. We examined associations between HeFH and these outcomes in a comprehensive systematic review and meta-analysis. We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed (for ahead-of-print publications) for relevant English-language studies. Maximally adjusted risk estimates were pooled under random- and fixed-effects meta-analysis to derive odds ratios (ORs) and 95% confidence intervals (CIs). We included 6 studies representing 183 388 participants. Heterozygnous familial hypercholesterolemia was associated with a higher risk of PAD (OR: 3.59 [95% CI: 1.30-9.89]). This trend was nonsignificantly preserved (OR: 2.96 [95% CI: 0.68-12.88]) in sensitivity analyses of genetically defined HeFH. Genetic HeFH was not associated with increased ischemic stroke risk (OR: 0.76 [95% CI: 0.37-1.58]) although possessing an LDL-C >4.9 mmol/L (190 mg/dL) was (OR: 1.42 [95% CI: 1.06-1.89]). We found clinical and genetic diagnoses of HeFH to be associated with increased PAD risk. Genetically confirmed HeFH may not confer an increased risk of ischemic stroke. Modest associations may exist between LDL-C and ischemic stroke risk in HeFH.

Genetic testing for familial hypercholesterolemia: Impact on diagnosis, treatment and cardiovascular risk.

AIMS: Familial hypercholesterolemia (FH) is the most common genetic disorder in medicine, with a prevalence of 1/250. Affected individuals have elevated low-density lipoprotein cholesterol (LDL-C) and an increased lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The diagnosis of FH is based on algorithms that include LDL-C levels, physical manifestations, family history of high LDL-C and premature ASCVD, and, more recently, genetic testing. We sought to determine the impact of genetic testing on the: 1) diagnosis of 'definite familial hypercholesterolemia', 2) initiation and adherence of lipid-lowering therapy and 3) risk of ASCVD. METHODS: We performed a systematic review and meta-analysis, pooling odds ratios and 95% confidence intervals for ASCVD from studies comparing risk estimates in individuals harboring FH-causing variants and unaffected individuals. RESULTS: After screening 3304 unique publications, 56 studies were included in the analysis. 1) Genetic testing provided confirmation of FH in 28-80%, over clinical criteria alone, depending on the diagnostic algorithm and the method of analysis. In two large population-based studies comprising 76,751 individuals, an FH-causing variant was identified in only 1.7-2.5% of subjects with an LDL-C > 4.9 mmol/L (190 mg/dL). 2) A confirmed molecular diagnosis increased lipid-lowering therapy adherence (five studies, n = 4181 definite FH). 3) Loss-of-function variant of the LDLR were at a markedly increased risk of myocardial infarction (odds ratio 6.77, 95% confidence interval 4.75-9.66), and patients with a milder (hypomorphic) pathogenic LDLR change had a 4.4-fold increase in risk (odds ratio 4.4, 95% confidence interval 2.34-8.26), compared with controls. CONCLUSION: DNA sequencing confirms the diagnosis of FH but has a poor yield in unselected patients whose sole criterion is an elevated LDL-C. Initiation and adherence to treatment is improved. The risk of ASCVD is 4.4- to 6.8-fold increased in patients with an FH-causing variant compared with controls, depending on the severity of the DNA change.

Risk factors for cardiovascular disease in heterozygous familial hypercholesterolemia: A systematic review and meta-analysis.

BACKGROUND: Current data from individual studies present conflicting evidence about the relationship between risk factors and cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (FH). OBJECTIVES: We conducted a systematic review and meta-analysis to quantify the association between various CVD risk factors and CVD in FH. METHODS: We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed for English-language studies reporting adjusted-associations between cardiovascular, behavioral, or clinical risk factors and CVD with ≥ 100 participants. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) for selected risk factors with random-effects meta-analysis, from which we derived attributable risk estimates. RESULTS: We identified 27 studies representing 41,831 unique participants and 6629 CVD events. Age (OR: 1.07; 95% CI: 1.03, 1.10), male sex (OR: 1.95; 95% CI: 1.68, 2.23), hypertension (OR: 2.11; 95% CI: 1.64, 2.58), diabetes (OR: 1.95; 95% CI: 1.33, 2.57), body mass index (OR: 1.04; 95% CI: 1.03, 1.05), smoking (OR: 1.71; 95% CI: 1.30, 2.12), elevated lipoprotein(a) (OR: 1.90; 95% CI: 1.10, 2.71), low high-density lipoprotein cholesterol (OR: 1.39; 95% CI: 1.24, 1.53), and a family history of CVD (OR: 1.83, 95% CI: 1.58, 2.07) were found to be significant CVD risk factors in FH. Smoking, hypertension, and diabetes accounted for more than a quarter of CVD risk in FH individuals, whereas low-density lipoprotein cholesterol > 4.0 mmol/L accounted for 1 in 3 CVD cases. Meta-regression analyses found associations between low-density lipoprotein cholesterol (P = .045) and total cholesterol (P < .001) and CVD. Results were broadly consistent in sensitivity analyses. CONCLUSION: Several clinical risk factors are significantly and independently associated with CVD risk in patients with FH and should be targeted for modification. These data can also inform the selection of variables for prediction models to aid in risk stratifying patients.

Anxiety, depression, and health-related quality of life in heterozygous familial hypercholesterolemia: A systematic review and meta-analysis.

BACKGROUND: Heterozygous familial hypercholesterolemia (FH) is a common genetic disease predisposing affected individuals to a high risk of cardiovascular disease. Yet, considerable uncertainty exists regarding its impact on psychosocial wellbeing. OBJECTIVES: We performed a systematic review and meta-analysis of the association between FH and symptoms of anxiety and depression, and health-related quality of life (HRQL). METHODS: We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO, and PubMed for peer-reviewed literature published in English between January 1, 1990 and January 1, 2018. Quantitative and qualitative studies were eligible if they included patients with confirmed FH and evaluated its association with symptoms of anxiety or depression, or HRQL. We performed a narrative synthesis of studies, including thematic analysis of qualitative studies, and where data permitted, random-effects meta-analysis reporting standardized mean differences (SMD) and 95% confidence intervals. RESULTS: We found 10 eligible studies measuring HRQL, depression and anxiety. Random-effects meta-analysis of 4 (n = 4293) and 5 studies (n = 5098), respectively, showed that patients with FH had slightly lower symptoms of anxiety (SMD: -0.29 [95% CI: -0.53, -0.04]) and mental HRQL (SMD: -0.10 [95% -0.20, -0.00]) relative to general population controls. No significant differences existed in depressive symptoms (SMD: 0.04 [95% CI: -0.12, 0.19]) or physical HRQL scores (SMD: 0.02 [95% CI: -0.09, 0.12]). CONCLUSIONS: Our systematic review suggests that patients with FH may report small but measurable differences in anxiety symptoms and mental HRQL.

Comparative Efficacy of Angiotensin II Antagonists in Essential Hypertension: Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Evidence on the long-term clinical benefits of individual members of angiotensin II receptor blockers is limited given the lack of head-to-head studies. We conducted a network meta-analysis to determine the comparative efficacy of different members within this drug class with respect to outcomes of (i) blood pressure reduction (at 24 and 52 weeks) and (ii) prevention of cardiovascular disease (>104 weeks). METHODS: A systematic literature review was conducted - Protocol registration: (PROSPERO - CRD42014007067) - to identify relevant literature from the following databases: Cochrane Library, PubMed, Medline and EMBASE; searched from inception to July 2016. Randomised controlled trials (RCTs) were included if they reported long-term effectiveness relating to blood pressure, mortality, myocardial infarction or stroke. Eligible studies included those with placebo or specific active-treatment comparators (either another angiotensin II receptor blockers or hydrochlorothiazide). A Bayesian random-effects network model was used to combine direct within-trial comparisons between treatment groups with indirect evidence from other trials. RESULTS: Thirty-six studies were identified, representing 28 unique trials. Blood pressure reduction, based on 12 studies (n=807) with fixed dosing regimen, was found to be similar amongst members of the angiotensin receptor blocker drug class at both 24 and 52 weeks. A network meta-analysis of five studies (n=16,716) with a treat-to-target approach found that prevention of all-cause mortality, stroke and myocardial infarction was similar across the angiotensin-receptor blockers therapies initiated. CONCLUSIONS: Current evidence is insufficient to show differences in any members within the angiotensin II receptor blocker drug class with respect to blood pressuring lowering effects or a reduction in cardiovascular diseases.

Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis.

OBJECTIVES: Heterozygous familial hypercholesterolaemia (FH) confers a significant risk for premature cardiovascular disease (CVD). However, the estimated prevalence of FH varies substantially among studies. We aimed to provide a summary estimate of FH prevalence in the general population and assess variations in frequency across different sociodemographic characteristics. SETTING, PARTICIPANTS AND OUTCOME MEASURES: We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO and PubMed for peer-reviewed literature using validated strategies. Results were limited to studies published in English between January 1990 and January 2017. Studies were eligible if they determined FH prevalence using clinical criteria or DNA-based analyses. We determined a pooled point prevalence of FH in adults and children and assessed the variation of the pooled frequency by age, sex, geographical location, diagnostic method, study quality and year of publication. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were investigated through subgroups, meta-regression and sensitivity analyses. RESULTS: The pooled prevalence of FH from 19 studies including 2 458 456 unique individuals was 0.40% (95% CI 0.29% to 0.52%) which corresponds to a frequency of 1 in 250 individuals. FH prevalence was found to vary by age and geographical location but not by any other covariates. Results were consistent in sensitivity analyses. CONCLUSIONS: Our systematic review suggests that FH is a common disorder, affecting 1 in 250 individuals. These findings underscore the need for early detection and management to decrease CVD risk.

Effects of depression pharmacotherapy in fertility treatment on conception, birth, and neonatal health: A systematic review.

OBJECTIVES: While antidepressant medications are currently used during conception, gestation and post-partum, considerable uncertainty exists regarding the benefits and harms conferred to mothers and their offspring. A significant body of evidence has focused on antidepressant use during pregnancy and post-partum. However, it is difficult to know if this translates to specific populations. Women receiving treatment for infertility are especially vulnerable to symptoms of depression and adverse perinatal outcomes. This systematic review aimed to determine the effects of antidepressants taken during the perinatal period by women receiving fertility treatment on conception, birth, and long-term maternal and child health outcomes. METHODS: We searched MEDLINE, EMBASE, CINAHL, the Cochrane Library, PsycINFO, ProQuest Dissertation & Theses, and Pubmed databases from January 1950 to November 2015. Articles were screened for inclusion independently by two reviewers. Studies were included if they enrolled women of reproductive age exposed to pharmacotherapy for depression and infertility at any point during the perinatal period. RESULTS: A total of 8587 unique citations, and 83 full-text articles were reviewed. Of these, two randomized controlled trials and two retrospective chart reviews were included in the narrative synthesis. While most studies reported on assisted reproduction processes and birth outcomes, none examined long-term impacts on maternal-child health. The few included studies did not find that antidepressant use by women receiving fertility therapy impacted gamete quality or pregnancy success. CONCLUSIONS: Currently, no studies address whether pharmacotherapy for the treatment of depression in women undergoing assisted reproduction affects their health or that of their offspring long-term. It appears that much like antidepressant use in fertile women, there are risks associated with both antidepressant use and untreated depression. Decisions regarding the treatment of depression should be made taking into account clinical presentation and illness severity. Given the complexities of conducting research in this population, future research should attempt to leverage health registry data, to increase sample sizes and follow mothers and children longitudinally.

Cardiovascular and cerebrovascular outcomes of long-term angiotensin receptor blockade: meta-analyses of trials in essential hypertension.

Angiotensin receptor blockers (ARBs) are widely used in managing essential hypertension, with considerable evidence available on their short-term efficacy in lowering blood pressure (BP). However, there currently exists limited "pooled" data examining the long-term efficacy of ARB treatment in controlling BP or mitigating cardiovascular and cerebrovascular events. The purpose of this study was to conduct a systematic review and meta-analysis assessing the long-term effects of ARBs as a class on BP control, myocardial infarction, hospitalization for heart failure, cerebrovascular events (ie, stroke), cardiovascular mortality, and all-cause mortality. MEDLINE, EMBASE, PubMed, and the Cochrane Library databases were searched from inception to March 2015. Two evaluators independently reviewed studies for eligibility. Randomized controlled hypertension trials were included if they reported on ARB efficacy in either BP control (relative to placebo for periods ≥ 6 months) or cardiovascular/cerebrovascular outcomes (relative to non-ARB antihypertensive therapies for periods ≥ 24 months). Studies were pooled with a random-effects model using weighted mean differences (WMDs) and relative risks for continuous and dichotomous outcomes, respectively. A total of 11 articles were included in the narrative synthesis, representing seven unique trials (16,864 participants). Six ARB agents were studied: candesartan, eprosartan, irbesartan, olmesartan, losartan (each represented by one trial arm), and telmisartan (represented by two arms). ARB therapy significantly reduced mean systolic BP (WMD: -4.86; 95% CI: -6.19, -3.53 mm Hg) and diastolic BP (WMD: -2.75; 95% CI: -3.65, -1.86 mm Hg] compared to placebo. The risk of stroke was reduced by 21% in the ARB group compared with alternative antihypertensives (risk ratio: 0.79; 95% CI: 0.66, 0.96). ARBs did not, however, produce statistically significant reductions in the risk of myocardial infarction, heart failure hospitalization, or mortality. Our findings suggest that ARBs, as a class, are more effective than placebo therapy in long-term BP lowering in patients with essential hypertension. Long-term ARB treatment may also confer enhanced protection against stroke but not other cardiovascular outcomes relative to placebo.