Phenomics and Robust Multiomics Data for Cardiovascular Disease Subtyping.

The complex landscape of cardiovascular diseases encompasses a wide range of related pathologies arising from diverse molecular mechanisms and exhibiting heterogeneous phenotypes. This variety of manifestations poses significant challenges in the development of treatment strategies. The increasing availability of precise phenotypic and multiomics data of cardiovascular disease patient populations has spurred the development of a variety of computational disease subtyping techniques to identify distinct subgroups with unique underlying pathogeneses. In this review, we outline the essential components of computational approaches to select, integrate, and cluster omics and clinical data in the context of cardiovascular disease research. We delve into the challenges faced during different stages of the analysis, including feature selection and extraction, data integration, and clustering algorithms. Next, we highlight representative applications of subtyping pipelines in heart failure and coronary artery disease. Finally, we discuss the current challenges and future directions in the development of robust subtyping approaches that can be implemented in clinical workflows, ultimately contributing to the ongoing evolution of precision medicine in health care.

Machine learning-based diagnosis and risk factor analysis of cardiocerebrovascular disease based on KNHANES.

The prevalence of cardiocerebrovascular disease (CVD) is continuously increasing, and it is the leading cause of human death. Since it is difficult for physicians to screen thousands of people, high-accuracy and interpretable methods need to be presented. We developed four machine learning-based CVD classifiers (i.e., multi-layer perceptron, support vector machine, random forest, and light gradient boosting) based on the Korea National Health and Nutrition Examination Survey. We resampled and rebalanced KNHANES data using complex sampling weights such that the rebalanced dataset mimics a uniformly sampled dataset from overall population. For clear risk factor analysis, we removed multicollinearity and CVD-irrelevant variables using VIF-based filtering and the Boruta algorithm. We applied synthetic minority oversampling technique and random undersampling before ML training. We demonstrated that the proposed classifiers achieved excellent performance with AUCs over 0.853. Using Shapley value-based risk factor analysis, we identified that the most significant risk factors of CVD were age, sex, and the prevalence of hypertension. Additionally, we identified that age, hypertension, and BMI were positively correlated with CVD prevalence, while sex (female), alcohol consumption and, monthly income were negative. The results showed that the feature selection and the class balancing technique effectively improve the interpretability of models.

Cost analysis of treating cardiovascular diseases in a super-specialty hospital.

Cardiovascular care is expensive; hence, economic evaluation is required to estimate resources being consumed and to ensure their optimal utilization. There is dearth of data regarding cost analysis of treating various diseases including cardiac diseases from developing countries. The study aimed to analyze resource consumption in treating cardio-vascular disease patients in a super-specialty hospital. An observational and descriptive study was carried out from April 2017 to June 2018 in the Department of Cardiology, Cardio-Thoracic (CT) Centre of All India Institute of Medical Sciences, New Delhi, India. As per World Health Organization, common cardiovascular diseases i.e. Coronary Artery Disease (CAD), Rheumatic Heart Disease (RHD), Cardiomyopathy, Congenital heart diseases, Cardiac Arrhythmias etc. were considered for cost analysis. Medical records of 100 admitted patients (Ward & Cardiac Care Unit) of cardiovascular diseases were studied till discharge and number of patient records for a particular CVD was identified using prevalence-based ratio of admitted CVD patient data. Traditional Costing and Time Driven Activity Based Costing (TDABC) methods were used for cost computation. Per bed per day cost incurred by the hospital for admitted patients in Cardiac Care Unit, adult and pediatric cardiology ward was calculated to be Indian Rupee (INR) 28,144 (US$ 434), INR 22,210 (US$ 342) and INR 18,774 (US$ 289), respectively. Inpatient cost constituted almost 70% of the total cost and equipment cost accounted for more than 50% of the inpatient cost followed by human resource cost (28%). Per patient cost of treating any CVD was computed to be INR 2,47,822 (US $ 3842). Cost of treating Rheumatic Heart Disease was the highest among all CVDs followed by Cardiomyopathy and other CVDs. Cost of treating cardiovascular diseases in India is less than what has been reported in developed countries. Findings of this study would aid policy makers considering recent radical changes and massive policy reforms ushered in by the Government of India in healthcare delivery.

Docosahexaenoic fatty acid nanoencapsulated with Anti-PECAM-1 as strategy to increase atherosclerotic plaque stability / Ácido graxo docosahexaenoico nanoencapsulado com anti-PECAM-1 como uma estratégia para aumentar a estabilidade de placas ateroscleróticas

Cardiovascular diseases (CVDs) are the main cause of mortality worldwide, being the ischemic heart disease responsible for 85% of deaths. Atherosclerosis is a chronic inflammation of the arteries that underlies ischemic forms of CVD and involves the innate and adaptive immune systems, from initial fatty streak formation to atherosclerotic plaque ruptures, which defines the beginning and end stages of disease, respectively. Recent research on the reduction of systemic inflammation in order to treat CVD is controversial, since results show that this reduced inflammation can also increase patient susceptibility to general infection. Therefore, new tissue-targeting strategies are necessary. Docosahexaenoic fatty acid (DHA) is a natural bioactive precursor of pro-resolving oxylipins that can reduce inflammation. Based on these factors, the objective of this study was to develop a nanocapsule containing algae oil as a DHA source and apply anti-PECAM-1 on its surface to drive it to the inflamed endothelium. Initially, a surface-functionalized metal-complex multi-wall nanocapsule containing algae oil in its nucleus (MLNC-DHA-a1) was developed. This nanocapsules presented a mean diameter of 163 ± 5 nm, was spherical in shape, showed 94.80% conjugation efficiency using 200 µg/mL of anti-PECAM-1 on the surface, and did not show significant toxicity toward HUVECs at concentrations from 0.14 to 2.90x1011 nanocapsules/mL. The nanocapsules were also stable for 2 h, sufficient time to allow for clinical applications. In cell viability assays, concentrations of 0.14 to 1.40x1011 nanocapsules/mL did not significantly affect the viability of immortalized murine macrophages (RAW 264.7) and U-937 cells after 24, 48, and 72 h of treatment. Finally, macrophages were incubated with 0.75x1011 MLNC-DHA-a1 nanocapsules/mL for 4 h and showed a significant uptake, observed using dark-field hyperspectral microscopy (CytoViva®). Once inside murine macrophages (RAW 264.7), MLNC-DHA-a1 nanocapsules promoted a strong increase in M2 phenotype polarization compared to non-treated control cells. Our results suggest that DHA-enriched algae oil, as part of a lipid core nanocapsules, does not reduce cell viability and improves macrophage phenotype, making it a promising potential therapy for controlling chronic inflammation and healing or stabilizing atherosclerotic plaques

As doenças cardiovasculares (DCVs) são a principal causa de mortalidade no mundo, sendo os eventos isquêmicos responsáveis por 85% das mortes. A aterosclerose é uma inflamação crônica das artérias associada aos eventos isquêmicos das DCVs, na qual o sistema imunológico inato e adaptativo estão envolvidos desde a formação inicial das estrias gordurosas até a ruptura das placas ateroscleróticas. Pesquisas recentes direcionadas à redução da inflamação sistêmica têm mostrado resultados controversos, pois essa abordagem pode aumentar a susceptibilidade do paciente a infecções. Nesse sentido, novas estratégias direcionadas ao tecido lesionado são necessárias. No que se refere a medicamentos anti-inflamatórios ou suplementos alimentares, o ácido docosaexaenóico (DHA) tem sido relatado como um precursor natural de oxilipinas pró- resolutivas. Baseado nesse contexto, o objetivo deste estudo foi desenvolver nanocápsulas contendo óleo de alga como fonte de DHA e vetorizar essas nanopartículas com o anticorpo antiPECAM-1 em sua superfície, visando direcioná-las ao endotélio inflamado. Inicialmente, a nanocápsula multiparede metal-complexa funcionalizada contendo óleo de alga em seu núcleo (MLNC-DHA-a1) foi desenvolvida, apresentando um diâmetro médio de 163 ± 5 nm, formato esférico, onde a eficiência de conjugação do anti-PECAM-1 (200 µg/mL) foi de 94,80% sem toxicidade significativa em HUVECs nas concentrações de 1.14 a 2.9 x 1011 nanocápsulas/mL. As nanocápsulas apresentaram uma estabilidade de 2h, o que representa tempo suficiente para a sua aplicação clínica. A seguir, ensaios de viabilidade celular foram realizados em outras linhagens de células para avaliar a toxicidade das nanocápsulas. As concentrações de 0.14 a 1.40 x 1011 de nanocápsulas/mL não afetaram significativamente a viabilidade celular de macrófagos murinos imortalizados (RAW 264.7) e U-937 após 24, 48 e 72 h de tratamento. Por fim, os macrófagos (RAW 264.7) foram incubados com 0.75 x 1011 MLNC-DHA-a1/mL durante 4 h e apresentam uma captação significativa das nanocápsulas, observada por microscopia hiperespectral de campo escuro (CytoViva®). Uma vez captadas pelos macrófagos murinos imortalizados (RAW 264.7), as nanoformulações MLNC-DHA-a1 promoveram um forte aumento da polarização do fenótipo M2 em comparação com as células controle não tratadas. Nossos resultados sugerem que o óleo de alga rico em DHA presente no núcleo lipídico das nanocápsulas, não reduziu a viabilidade celular e estimulou uma maior polarização de macrófagos para o tipo M2, sendo assim uma terapia potencial para controlar a inflamação crônica e cicatrizar ou estabilizar placas ateroscleróticas

Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy.

BACKGROUND: Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs). OBJECTIVES: This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy. METHODS: In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR). RESULTS: The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythmias (n = 74 [2.8%], adj.ROR = 2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n = 69 [2.6%], adj.ROR = 3.51 [2.42-5.09]), pleural disorders (n = 46 [1.7%], adj.ROR = 3.91 [2.92-5.23]), and pericardial diseases (n = 11 [0.4%], adj.ROR = 2.26 [1.25-4.09], all IC025 >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC025 >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age- and sex-adjusted model (adj.ROR = 1.82 [1.04-3.18] and adj.ROR = 2.86 [1.18-6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%. CONCLUSIONS: In this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients.

Risk of cardiovascular disease in patients with fatty liver disease as defined from the metabolic dysfunction associated fatty liver disease or nonalcoholic fatty liver disease point of view: a retrospective nationwide claims database study in Japan.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction associated fatty liver disease (MAFLD) have important associations with cardiovascular disease (CVD). The main objective of this study was to compare the frequency of incidence rate of CVD in the NAFLD or MAFLD patients utilizing a large claims database. METHODS: Using the JMDC database from April 2013 to March 2019, we retrospectively analyzed data for 1,542,688 and 2,452,949 people to estimate the relationship between CVD and NAFLD, MAFLD, respectively. RESULTS: The incidence rates of CVD were 0.97 (95% CI 0.94-1.01) and 2.82 (95% CI 2.64-3.01) per 1000 person-years in the non-NAFLD and NAFLD groups, respectively, and 1.01 (95% CI 0.98-1.03) and 2.69 (95% CI 2.55-2.83) per 1000 person-years in the non-MAFLD and MAFLD groups, respectively. The overall prevalence of hypertriglyceridemia and diabetes mellitus (DM) was 13.1, and 4.2%, respectively, in the non-NAFLD group and 63.6, and 20.2%, respectively, in the NAFLD group. The overall prevalenceof hypertriglyceridemia and DM was 13.6 and 4.3%, respectively, in the non-MAFLD group and 64.1, and 20.6%, respectively, in the MAFLD group. HRs for CVD increased with hypertriglyceridemia and DM. CONCLUSIONS: Results indicated that incident rate of CVD increased with NAFLD/MAFLD; the complication rate of DM and hypertriglyceridemia among NAFLD/MAFLD patients is high and may affect the development of CVD.

DXA Versus Clinical Measures of Adiposity as Predictors of Cardiometabolic Diseases and All-Cause Mortality in Postmenopausal Women.

OBJECTIVE: To investigate whether dual-energy x-ray absorptiometry (DXA) estimates of adiposity improve risk prediction for cardiometabolic diseases over traditional surrogates, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) in older women. PATIENTS AND METHODS: We analyzed up to 9744 postmenopausal women aged 50 to 79 years participating in the Women's Health Initiative who underwent a DXA scan and were free of cardiovascular disease and diabetes at baseline (October 1993 to December 1998) and followed through September 2015. Baseline BMI, WC, WHR, and DXA-derived percent total-body and trunk fat (%TrF) were incorporated into multivariable Cox proportional hazards models to estimate the risk of incident diabetes, atherosclerosis-related cardiovascular diseases (ASCVDs), heart failure, and death. Concordance probability estimates assessed the relative discriminatory value between pairs of adiposity measures. RESULTS: A total of 1327 diabetes cases, 1266 atherosclerotic cardiovascular disease (ASCVD) cases, 292 heart failure cases, and 1811 deaths from any cause accrued during a median follow-up of up to 17.2 years. The largest hazard ratio observed per 1 standard deviation increase of an adiposity measure was for %TrF and diabetes (1.77; 95% CI, 1.66-1.88) followed by %TrF and broadly defined ASCVD (1.22; 95% CI, 1.15-1.30). These hazard ratios remained significant for both diabetes (1.47; 95% CI, 1.37-1.57) and ASCVD (1.22; 95% CI, 1.14-1.31) even after adjusting for the best traditional surrogate measure of adiposity, WC. Percentage of trunk fat was also the only adiposity measure to demonstrate statistically significant improved concordance probability estimates over BMI, WC, and WHR for diabetes and ASCVD (all P<0.05). CONCLUSION: DXA-derived estimates of abdominal adiposity in postmenopausal women may allow for substantially improved risk prediction of diabetes over standard clinical risk models. Larger DXA studies with complete lipid biomarker profiles and clinical trials are needed before firm conclusions can be made.

Coronavirus disease 2019 in patients with cardiovascular disease: clinical features and implications on cardiac biomarkers assessment.

INTRODUCTION: Previous cardiovascular disease (CVD) and myocardial involvement are common in coronavirus disease-19 (COVID-19). We investigated relationships between CVD, cardiac biomarkers and outcome in COVID-19. METHODS: We analyzed n = 252 patients from a multicenter study and provided comparison according to the presence or absence of underlying CVD. Cardiac biomarkers high-sensitivity Troponin [upper reference of normality (URN) 35 pg/ml for Troponin I and 14 pg/ml for Troponin T] and natriuretic peptides (Nt-pro-B-type natriuretic peptide, URN 300 pg/ml and B-type natriuretic peptide, URN 100 pg/ml) were both available in n = 136. RESULTS: Mean age was 69 ±â€Š16 years (56% men, 31% with previous CVD). Raised hs-Troponin and natriuretic peptides were detected in 36 and 50% of the cases respectively. Age, chronic obstructive pulmonary disease, hemoglobin, hs-Troponin and natriuretic peptides were independently associated with underlying CVD (P < 0.05 for all). Compared with the normal biomarkers subgroups, patients with isolated hs-Troponin elevation had higher in-hospital mortality (31 vs. 4%, P < 0.05), similar CVD prevalence (15 vs. 11%) and trend towards higher D-dimer (930 vs. 397 ng/ml, P = 0.140). Patients with both biomarkers elevated had higher age, D-dimer, CVD and in-hospital mortality prevalence compared with other subgroups (all P < 0.05 for trend). Outcome analysis revealed previous CVD [model 1: OR 2.72 (95% CI 1.14-6.49), P = 0.024. model 2: OR 2.65 (95% CI 1.05-6.71), P = 0.039], hs-Troponin (log10) [OR 2.61 (95% CI 1.21-5.66), P = 0.015] and natriuretic peptides (log10) [OR 5.84 (95%CI 2.43-14), P < 0.001] to be independently associated with in-hospital mortality. CONCLUSION: In our population, previous CVD was part of a vulnerable phenotype including older age, comorbidities, increased cardiac biomarkers and worse prognosis. Patients with isolated increase in hs-Troponin suffered higher mortality rates despite low prevalence of CVD, possibly explained by higher COVID-19-related systemic involvement.

Mendelian randomization study on atrial fibrillation and cardiovascular disease subtypes.

Atrial fibrillation (AF) has been associated with numerous diseases. However, whether AF is a cause or consequence of these diseases is uncertain. To clarify, we assessed the causal role of AF on ischemic heart disease (IHD), stroke, other cardiovascular disease (CVD) subtypes, type 2 diabetes mellitus (T2DM), and late-onset AD using bi-directional two-sample Mendelian randomization (MR) among people primarily of European descent. Genetically predicted log odds of AF was associated with any stroke (odds ratio (OR) 1.22, 95% CI 1.18 to 1.27), particularly cardioembolic stroke and possibly subdural hemorrhage, with sensitivity analyses showing similar positive findings. Genetically predicted AF was also associated with arterial thromboembolism (1.32, 1.13 to 1.53), and heart failure (1.26, 1.21 to 1.30). No association of genetically predicted AF with IHD, T2DM, cognitive function, or late-onset AD was found. Conversely, genetically predicted IHD, heart failure and possibly ischemic stroke, particularly cardioembolic stroke, were positively associated with AF. Atrial fibrillation plays a role in any stroke, arterial thromboembolism, and heart failure, corroborating current clinical guidelines on the importance of preventing these complications by effective AF management. In addition, patients with IHD, heart failure or possibly ischemic stroke might be predisposed to developing AF, with implications for management.

Manejo de la hipercolesterolemia desde dos ángulos diferentes / Hypercholesterolemia management from two different points of view

RESUMEN La cardiopatía isquémica y los accidentes cerebrovasculares son la primera causa de muerte en el mundo. La enfermedad cardiovascular de origen ateroesclerótico es un problema internacional de salud, que constituye una carga social, sanitaria y económica. Se realizó un análisis de las principales guías internacionales sobre dislipoproteinemias y su manejo, como las de la Sociedad Europea de Cardiología y las del Colegio Americano de Cardiología/Asociación Americana del Corazón. También, de los principales artículos publicados en los últimos cinco años sobre el manejo de la hipercolesterolemia, de los cuales se tomaron 20 publicaciones en Medline, Google Académico y SciELO. Las mencionadas guías reúnen las recomendaciones de sus respectivas organizaciones y las combinan con nuevas. Ambas mantienen el uso de scores de riesgo y discrepan sobre la imagenología en la determinación del tratamiento, al igual que en el uso de drogas no estatinas. Se plantea que la mejor intervención para prevenir la enfermedad cardiovascular es la promoción de un estilo de vida saludable (AU).

ABSTRACT Ischemic cardiomyopathy and cerebrovascular stroke are the first causes of death in the world. Cardiovascular disease of atherosclerotic origins is an international health problem that is also a social, sanitary and economic burden. The authors analyzed the main international guidelines on dyslipoproteinemia, like the ones from the European Society of Cardiology and the American College of Cardiology/American Heart Association. They also considered the main articles published in the last five years on the management of hypercholesterolemia and chose 20 of them available in Medline, Google Scholar and SciELO. The before-mentioned guidelines gather the recommendations of their own organizations, and combine them with new ones. They both keep using risk scores on and differ on medical imaging determining the treatment, and also in the use of non-statin drugs. It is stated that the better intervention to prevent cardiovascular disease is the promotion of a healthy lifestyle (AU).

Trends in Use of Cardioprotective Medication in Peripheral Artery Disease: A Nationwide Study.

Background Guideline-based cardioprotective medical therapy is intended to reduce the burden of adverse cardiovascular and limb outcomes in patients with peripheral artery disease (PAD). However, contemporary data describing trends in use of medication remains limited. The present study, therefore, aims to investigate changes in use of cardioprotective medication in PAD. Methods and Results By using Danish national healthcare registries, we identified all patients with first-time diagnosis of PAD (1997-2016) and classified them into two groups: (1) PAD+ that includes all patients with PAD with a history of cardiovascular disease, ie, myocardial infarction, atrial fibrillation, and stroke (n=162 627); and (2) PAD (n=87 935) that comprise patients without a history of cardiovascular disease. We determined the use of medication in the first 12 months after the incident diagnosis of PAD and estimated age standardized 1-year mortality rates. Our results showed increase in use of cardioprotective medication throughout the study period in both groups. However, PAD+ had a higher use of medication (acetylsalicylic acid, 3.5%-48.4%; Clopidogrel, 0%-17.6%; vitamin K antagonists, 0.9%-7.8%; new oral anticoagulants, 0.0%-10.1%; Statins, 1.9%-58.1%; angiotensin-converting enzyme inhibitors, 1.2%-20.6%), compared with PAD (acetylsalicylic acid, 2.9%-54.4%; Clopidogrel, 0%-11.9%; vitamin K antagonists, 0.9%-2.4%; new oral anticoagulants, 0.0%-3.4%; Statins, 1.5%-56.9%; angiotensin-converting enzyme, 0.9%-17.2%), respectively. Furthermore, 1-year mortality rates in PAD declined with increased use of medications during study. Conclusions In this nationwide study, use of cardioprotective medication increased considerably with time, but compared to patients with other atherosclerotic diseases, there remains an underuse of guideline-based medical therapy in patients with PAD.

Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews.

AIMS: To consolidate evidence to determine (i) the association between cardiovascular risk factors and health outcomes with coronavirus 2019 (COVID-19); and (ii) the impact of COVID-19 on cardiovascular health. METHODS AND RESULTS: An umbrella review of systematic reviews was conducted. Fourteen medical databases and pre-print servers were searched from 1 January 2020 to 5 November 2020. The review focused on reviews rated as moderate or high-quality using the AMSTAR 2 tool. Eighty-four reviews were identified; 31 reviews were assessed as moderate quality and one was high-quality. The following risk factors were associated with higher mortality and severe COVID-19: renal disease [odds ratio (OR) (95% confidence interval) for mortality 3.07 (2.43-3.88)], diabetes mellitus [OR 2.09 (1.80-2.42)], hypertension [OR 2.50 (2.02-3.11)], smoking history [risk ratio (RR) 1.26 (1.20-1.32)], cerebrovascular disease [RR 2.75 (1.54-4.89)], and cardiovascular disease [OR 2.65 (1.86-3.78)]. Liver disease was associated with higher odds of mortality [OR 2.81 (1.31-6.01)], but not severe COVID-19. Current smoking was associated with a higher risk of severe COVID-19 [RR 1.80 (1.14-2.85)], but not mortality. Obesity associated with higher odds of mortality [OR 2.18 (1.10-4.34)], but there was an absence of evidence for severe COVID-19. In patients hospitalized with COVID-19, the following incident cardiovascular complications were identified: acute heart failure (2%), myocardial infarction (4%), deep vein thrombosis (7%), myocardial injury (10%), angina (10%), arrhythmias (18%), pulmonary embolism (19%), and venous thromboembolism (25%). CONCLUSION: Many of the risk factors identified as associated with adverse outcomes with COVID-19 are potentially modifiable. Primary and secondary prevention strategies that target cardiovascular risk factors may improve outcomes for people following COVID-19.

Age-Specific Associations Between Habitual Snoring and Cardiovascular Diseases in China: A 10-Year Cohort Study.

BACKGROUND: Limited convincing evidence is available of the relationship between habitual snoring and cardiovascular diseases (CVDs). RESEARCH QUESTION: Is habitual snoring associated with total CVD and CVD subtypes in different age groups of Chinese adults? STUDY DESIGN AND METHODS: The China Kadoorie Biobank study enrolled more than 0.5 million adults aged 30 to 79 years from 10 regions in China. Snoring status and other baseline characteristics were collected from 2004 to 2008, using an interviewer-administered laptop-based questionnaire. The current analysis included 489,583 participants without stroke or coronary heart disease at baseline. Cox proportional hazards models were used to calculate the adjusted hazard ratios (HRs) and 95% CIs of cardiovascular diseases (CVDs) for habitual snoring vs nonhabitual snoring. RESULTS: During a median follow-up of 9.6 years, 130,935 participants developed CVDs. Associations between habitual snoring and CVDs varied with age. Among participants aged younger than 50 years at baseline, habitual snoring was associated with an increased risk of total CVD (HR, 1.11; 95% CI, 1.07-1.14) after adjustment for known CVD risk factors, including systolic BP. The corresponding HRs (95% CIs) for ischemic heart disease, ischemic stroke, and hemorrhagic stroke were 1.18 (1.12-1.24), 1.12 (1.05-1.19), and 1.05 (0.92-1.19), respectively. However, such associations in adults aged 50 to 64 years were much weaker, and no statistically significant association was observed among individuals aged ≥65 years. Age-specific risk estimates were generally similar across sex and obesity subgroups. INTERPRETATION: Habitual snoring was associated with increased risks of total CVD, ischemic heart disease, ischemic stroke, but not hemorrhagic stroke in Chinese, and these associations were mainly limited to those aged <50 years. Clinicians in China are encouraged to identify snoring, particularly in younger adults.

Temporal trends and sex differences in sudden cardiac death in the Copenhagen City Heart Study.

OBJECTIVE: More knowledge about the development of sudden cardiac death (SCD) in the general population is needed to develop meaningful predictors of SCD. Our aim with this study was to estimate the incidence of SCD in the general population and examine the temporal changes, demographics and clinical characteristics. METHODS: All participants in the Copenhagen City Heart Study were followed from 1993 to 2016. All death certificates, autopsy reports and national registry data were used to identify all cases of SCD. RESULTS: A total of 14 562 subjects were included in this study. There were 8394 deaths with all information available, whereof 1335 were categorised as SCD. The incidence of SCD decreased during the study period by 41% for persons aged 40-90 years, and the standardised incidence rates decreased from 504 per 100 000 person-years (95% CI 447 to 569) to 237 per 100 000 person-years (95% CI 195 to 289). The incidence rate ratio of SCD between men and women ≤75 years was 1.99 (95% CI 1.62 to 2.46). The proportion of SCD of all cardiac deaths decreased during the observation period and decreased with increasing age. Men had more cardiovascular comorbidities (OR 1.34, 95% CI 1.07 to 1.68, p<0. 01), and SCD was the first registered manifestation of cardiac disease in 50% of all cases. CONCLUSION: The incidence of SCD in the general population has declined significantly during the study period but should be further investigated for more recent variations as well as novel risk predictors for persons with low to medium risk of SCD.

NHLBI-CMREF Workshop Report on Pulmonary Vascular Disease Classification: JACC State-of-the-Art Review.

The National Heart, Lung, and Blood Institute and the Cardiovascular Medical Research and Education Fund held a workshop on the application of pulmonary vascular disease omics data to the understanding, prevention, and treatment of pulmonary vascular disease. Experts in pulmonary vascular disease, omics, and data analytics met to identify knowledge gaps and formulate ideas for future research priorities in pulmonary vascular disease in line with National Heart, Lung, and Blood Institute Strategic Vision goals. The group identified opportunities to develop analytic approaches to multiomic datasets, to identify molecular pathways in pulmonary vascular disease pathobiology, and to link novel phenotypes to meaningful clinical outcomes. The committee suggested support for interdisciplinary research teams to develop and validate analytic methods, a national effort to coordinate biosamples and data, a consortium of preclinical investigators to expedite target evaluation and drug development, longitudinal assessment of molecular biomarkers in clinical trials, and a task force to develop a master clinical trials protocol for pulmonary vascular disease.

Long-Term Cardiovascular Outcomes in Systemic Lupus Erythematosus.

BACKGROUND: Data on long-term cardiovascular outcomes in systemic lupus erythematosus (SLE) are sparse. OBJECTIVES: This study sought to examine the long-term risk and prognosis associated with cardiovascular outcomes, including heart failure (HF), in patients with SLE. METHODS: Using Danish administrative registries, risks of outcomes were compared between SLE patients (diagnosed 1996 to 2018, no history of cardiovascular disease) and age-, sex-, and comorbidity-matched control subjects from the background population (matched 1:4). Furthermore, mortality following HF diagnosis was compared between SLE patients developing HF and age- and sex-matched non-SLE control subjects with HF (matched 1:4). RESULTS: A total of 3,411 SLE patients (median age: 44.6 years [25th to 75th percentile: 31.9 to 57.0 years]; 14.1% men) were matched with 13,644 control subjects. The median follow-up was 8.5 years (25th to 75th percentile: 4.0 to 14.4 years). Absolute 10-year risks of outcomes were: HF, 3.71% (95% confidence interval [CI]: 3.02% to 4.51%) for SLE patients, 1.94% (95% CI: 1.68% to 2.24%) for control subjects; atrial fibrillation, 4.35% (95% CI: 3.61% to 5.18%) for SLE patients, 2.82% (95% CI: 2.50% to 3.16%) for control subjects; ischemic stroke, 3.75% (95% CI: 3.06% to 4.54%) for SLE patients, 1.92% (95% CI: 1.66% to 2.20%) for control subjects; myocardial infarction, 2.17% (95% CI: 1.66% to 2.80%) for SLE patients, 1.49% (95% CI: 1.26% to 1.75%) for control subjects; venous thromboembolism, 6.03% (95% CI: 5.17% to 6.98%) for SLE patients, 1.68% (95% CI: 1.44% to 1.95%) for control subjects; and the composite of implantable cardioverter-defibrillator implantation/ventricular arrhythmias/cardiac arrest, 0.89% (95% CI: 0.58% to 1.31%) for SLE patients, 0.30% (95% CI: 0.20% to 0.43%) for control subjects. SLE with subsequent HF was associated with higher mortality compared with HF without SLE (adjusted hazard ratio: 1.50; 95% CI: 1.08 to 2.08). CONCLUSIONS: SLE patients had a higher associated risk of HF and other cardiovascular outcomes compared with matched control subjects. Among patients developing HF, a history of SLE was associated with higher mortality.

Team-Based Care of Women With Cardiovascular Disease From Pre-Conception Through Pregnancy and Postpartum: JACC Focus Seminar 1/5.

The specialty of cardio-obstetrics has emerged in response to the rising rates of maternal morbidity and mortality related to cardiovascular disease (CVD) during pregnancy. Women of childbearing age with or at risk for CVD should receive appropriate counseling regarding maternal and fetal risks of pregnancy, medical optimization, and contraception advice. A multidisciplinary cardio-obstetrics team should ensure appropriate monitoring during pregnancy, plan for labor and delivery, and ensure close follow-up during the postpartum period when CVD complications remain common. The hemodynamic changes throughout pregnancy and during labor and delivery should be considered with respect to the individual cardiac disease of the patient. The fourth trimester refers to the 12 weeks after delivery and is a key time to address contraception, mental health, cardiovascular risk factors, and identify any potential postpartum complications. Women with adverse pregnancy outcomes are at increased risk of long-term CVD and should receive appropriate education and longitudinal follow-up.

Management of Women With Congenital or Inherited Cardiovascular Disease From Pre-Conception Through Pregnancy and Postpartum: JACC Focus Seminar 2/5.

Maternal morbidity and mortality continue to rise in the United States, with cardiovascular disease as the leading cause of maternal deaths. Congenital heart disease is now the most common cardiovascular condition encountered during pregnancy, and its prevalence will continue to grow. In tandem with these trends, maternal cardiovascular health is becoming increasingly complex. The identification of women at highest risk for cardiovascular complications is essential, and a team-based approach is recommended to optimize maternal and fetal outcomes. This document, the second of a 5-part series, will provide practical guidance from pre-conception through postpartum for cardiovascular conditions that are predominantly congenital or heritable in nature, including aortopathies, congenital heart disease, pulmonary hypertension, and valvular heart disease.

Management of Women With Acquired Cardiovascular Disease From Pre-Conception Through Pregnancy and Postpartum: JACC Focus Seminar 3/5.

Acquired cardiovascular conditions are a leading cause of maternal morbidity and mortality. A growing number of pregnant women have acquired and heritable cardiovascular conditions and cardiovascular risk factors. As the average age of childbearing women increases, the prevalence of acute coronary syndromes, cardiomyopathy, and other cardiovascular complications in pregnancy are also expected to increase. This document, the third of a 5-part series, aims to provide practical guidance on the management of such conditions encompassing pre-conception through acute management and considerations for delivery.

Diagnostic Cardiovascular Imaging and Therapeutic Strategies in Pregnancy: JACC Focus Seminar 4/5.

The prevalence of cardiovascular disease (CVD) in pregnancy, both diagnosed and previously unknown, is rising, and CVD is a leading cause of maternal morbidity and mortality. Historically, women of child-bearing potential have been underrepresented in research, leading to lasting knowledge gaps in the cardiovascular care of pregnant and lactating women. Despite these limitations, clinicians should be familiar with the safety of frequently used diagnostic and therapeutic interventions to adequately care for this at-risk population. This review, the fourth of a 5-part series, provides evidence-based recommendations regarding the use of common cardiovascular diagnostic tests and medications in pregnant and lactating women.