Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association



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Coronary Artery Disease In Young Adults: Epidemiology, Clinical Insights And Management

Early onset coronary artery disease (CAD) in individuals under 45 years old presents unique challenges, with prevalence rates of 1-2% generally, and as high as 5-10% among South Asian populations. With marked lifestyle changes and high caloric diet contributing to early occurrence of cardiovascular risk factors and associated smoking have increased the prevalence of CAD in this young population. Previous prospective long-term registries of young CAD patients in developed countries have shown it be a chronic aggressive disease with higher recurrent major adverse cardiac events (MACE) rates and worse long-term outcomes. Hence, we aim to explore the multi-faceted aspects of early onset CAD and its impact in ethnically diverse patient population.

This Research topic will focus only on early onset CAD in patients less than 45 years and study its epidemiology (CV risk factors, genetic and environmental factors), prevention (primary as well as secondary), clinical presentation (both chronic and acute coronary syndrome, ischemia related heart failure), management (non-invasive assessment including CT coronary angiogram, novel biomarkers, medical therapy, revascularisation strategies, intraprocedural coronary imaging characteristics) and subsequent clinical outcomes. Additionally, the study will scrutinize the disease's long-term impact and the effectiveness of various intervention strategies aimed at reducing its burden.

Research on early onset CAD will prioritize the following areas, with an emphasis on in-depth analyses tailored to patients under 45:1. Epidemiology of early onset CAD:- Role of emerging risk factors (e.G., metabolic disorders, inflammatory conditions,psychosocial stress, drug abuse) and genetics in early onset CAD- Disparities in the burden of early-onset CAD across different socioeconomic andethnic/racial groups2. Acute coronary syndrome (ACS) in young patients- Clinical and angiographic outcomes in young ACS patients- Utility of advanced imaging techniques (Intravascular ultrasound, opticalcoherence tomography) in young ACS3. Chronic Coronary Syndrome (CCS) in young population- Utility of early Non-invasive CAD screening (Exercise Tolerance Testing (ETT), CT-coronary calcium score & angiogram) in young patients- Exploration of novel biomarkers or risk prediction models specific to young adultswith CAD- Comparison of the efficacy and safety of different revascularization strategies(percutaneous coronary intervention/ coronary artery bypass grafting) inyoung patients.- Exploration of the long-term outcomes and factors associated with diseaseprogression in young adults with CAD4. Young individuals with ischemia related heart failure:- Impact of timely revascularization and optimal medical management on theprevention of heart failure in young CAD patients- Ischemia related heart failure burden in young CAD patients and its outcomes- Role of cardiac rehabilitation and lifestyle interventions in improving cardiacfunction and heart failure outcomes in young CAD patients.

Keywords: premature CAD, young adults, cardiovascular risk factors, myocardial infarction, heart failure

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Early onset coronary artery disease (CAD) in individuals under 45 years old presents unique challenges, with prevalence rates of 1-2% generally, and as high as 5-10% among South Asian populations. With marked lifestyle changes and high caloric diet contributing to early occurrence of cardiovascular risk factors and associated smoking have increased the prevalence of CAD in this young population. Previous prospective long-term registries of young CAD patients in developed countries have shown it be a chronic aggressive disease with higher recurrent major adverse cardiac events (MACE) rates and worse long-term outcomes. Hence, we aim to explore the multi-faceted aspects of early onset CAD and its impact in ethnically diverse patient population.

This Research topic will focus only on early onset CAD in patients less than 45 years and study its epidemiology (CV risk factors, genetic and environmental factors), prevention (primary as well as secondary), clinical presentation (both chronic and acute coronary syndrome, ischemia related heart failure), management (non-invasive assessment including CT coronary angiogram, novel biomarkers, medical therapy, revascularisation strategies, intraprocedural coronary imaging characteristics) and subsequent clinical outcomes. Additionally, the study will scrutinize the disease's long-term impact and the effectiveness of various intervention strategies aimed at reducing its burden.

Research on early onset CAD will prioritize the following areas, with an emphasis on in-depth analyses tailored to patients under 45:1. Epidemiology of early onset CAD:- Role of emerging risk factors (e.G., metabolic disorders, inflammatory conditions,psychosocial stress, drug abuse) and genetics in early onset CAD- Disparities in the burden of early-onset CAD across different socioeconomic andethnic/racial groups2. Acute coronary syndrome (ACS) in young patients- Clinical and angiographic outcomes in young ACS patients- Utility of advanced imaging techniques (Intravascular ultrasound, opticalcoherence tomography) in young ACS3. Chronic Coronary Syndrome (CCS) in young population- Utility of early Non-invasive CAD screening (Exercise Tolerance Testing (ETT), CT-coronary calcium score & angiogram) in young patients- Exploration of novel biomarkers or risk prediction models specific to young adultswith CAD- Comparison of the efficacy and safety of different revascularization strategies(percutaneous coronary intervention/ coronary artery bypass grafting) inyoung patients.- Exploration of the long-term outcomes and factors associated with diseaseprogression in young adults with CAD4. Young individuals with ischemia related heart failure:- Impact of timely revascularization and optimal medical management on theprevention of heart failure in young CAD patients- Ischemia related heart failure burden in young CAD patients and its outcomes- Role of cardiac rehabilitation and lifestyle interventions in improving cardiacfunction and heart failure outcomes in young CAD patients.

Keywords: premature CAD, young adults, cardiovascular risk factors, myocardial infarction, heart failure

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.


SCAI Publishes Expert Consensus Statement On Managing Patients With ST-elevated Myocardial Infarction

WASHINGTON —The Society for Cardiovascular Angiography & Interventions (SCAI) is pleased to announce the publication of the Expert Consensus Statement on the Management of Patients with STEMI Referred for Primary PCI.

Published in JSCAI, the consensus statement provides detailed suggestions for clinicians, particularly for nuanced situations not covered by general guidelines. It highlights the strengths and limitations of various diagnostic and therapeutic interventions for treating patients with STEMI, provides an overview of managing large thrombus burden and no reflow, and outlines best practices in managing STEMI across anatomical and clinical circumstances.  

"This document represents a collective effort to refine and advance the standards of care in STEMI management. By following these consensus statements, we can enhance the quality of care and make a meaningful difference in the lives of STEMI patients. This expert consensus statement will help interventional cardiologists make informed decisions and provide the best possible care in the cardiac catheterization laboratory. We are confident that the STEMI Consensus Statement will serve as a valuable resource for clinicians around the world," said Dr. Jacqueline Tamis-Holland, MD, FSCAI, chair of the project and an interventional cardiologist as well as Institute Director for Acute Coronary Care at Cleveland Clinic. 

Developed using a consensus process that drew from diverse viewpoints within the interventional cardiology community, the STEMI Expert Consensus Statement is the culmination of extensive collaboration among leading cardiologists, interventionalists, and researchers. It synthesizes the latest evidence-based practices and provides comprehensive suggestions to enhance patient care and outcomes. The document addresses key aspects of STEMI management, including early diagnosis, reperfusion strategies, and post-procedural care. 

The Consensus Statement delves into the technical aspects of patient care, offering practical approaches for managing thrombus and no-reflow conditions. These include using thrombectomy devices in cases with a large thrombus burden and administering vasodilators to dilate arteries. It provides clear, technical suggestions for treatment. 

Dr. Yader Sandoval, MD, FSCAI, co-chair of the project, an interventional cardiologist at the Minneapolis Heart Institute, Abbott Northwestern Hospital, and Co-Chairman for the Minneapolis Heart Institute Foundation (MHIF) Center for Coronary Artery Disease (CCAD) emphasized the importance of this consensus document in standardizing STEMI treatment protocols. 

"Our goal was to create a document that reflects the most current scientific evidence and offers practical advice for clinicians on the front lines of patient care, as well as offers input on frequently encountered clinical scenarios in STEMI patients such as microvascular obstruction, MINOCA, coronary microvascular dysfunction, including lesion subsets such as bifurcations or calcified lesions, and highlights areas with unmet needs where opportunities exist for additional research," Dr. Sandoval said. "By providing these consensus key points, we are not only helping to ensure consistency in treatment approaches but also aiming to improve the overall quality of care for STEMI patients globally. The document will be a critical resource for improving STEMI outcomes worldwide." 

The STEMI Expert Consensus Statement introduces several innovative insights and recommendations that have the potential to transform current practice. One of the key highlights is the emphasis on early and accurate diagnosis of STEMI and the need to rapidly diagnose patients with suspected STEMI so that emergency angiography can be performed. At the same time, it emphasizes the unique situations in which additional diagnostic testing may be needed.  

"Successful STEMI management should focus on the proper diagnosis and rapid treatment, and also include robust secondary prevention measures and addressing potential complications. Using this approach, we can significantly improve the quality of life and long-term survival of our patients," Dr. Tamis-Holland said. 

In addition to the Consensus Statement, an editorial published in JSCAI outlines the document's key messages.

About SCAI:

The Society for Cardiovascular Angiography & Interventions (SCAI) is the leading nonprofit medical society representing invasive and interventional cardiology. Founded in 1978, SCAI's mission is to lead the global interventional cardiovascular community through education, advocacy, research, and quality patient care. 

SCAI has dedicated its work to advancing the profession and is the designated society for guidance, representation, professional recognition, education, and research opportunities for invasive and interventional cardiology professionals. For more than 40 years, SCAI has personified professional excellence and innovation globally, fostering a trusted community of more than 4,500 members dedicated to medical advancement and lifesaving care for adults and children with cardiovascular disease.  

Article Title

SCAI Expert Consensus Statement on the Management of Patients With STEMI Referred for Primary PCI

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Ultra-rare Gene Variants Drive Coronary Artery Disease Risk In European Ancestry

In this groundbreaking study, researchers uncover how ultra-rare genetic variants, especially in heart cells, play a critical role in raising the risk of coronary artery disease among individuals of European descent.

Study: Rare variant contribution to the heritability of coronary artery disease. Image Credit: Sergey Nivens / Shutterstock.Com Study: Rare variant contribution to the heritability of coronary artery disease. Image Credit: Sergey Nivens / Shutterstock.Com

In a recent study published in the journal Nature Communications, researchers investigate the contribution of rare variants in the heritability of coronary artery disease (CAD) using whole genome sequencing.

What causes CAD?

The development of CAD, one of the major causes of mortality worldwide, is largely determined by genetic risk factors. Previous studies conducted on European populations, for example, indicate that the heritability of CAD is about 60%.

Genome-wide association studies have also identified several genetic variants that account for a significant portion of the heritability of CAD. However, many of these variants are common, with minor allele frequencies greater than 1%, which does not explain a significant portion of the genetic risk of CAD. Recent studies have found that rare genetic variants, especially those found in non-coding regions, significantly contribute to the heritability of complex diseases such as CAD.

Whole genome sequencing has identified ultra-rare variants with less than 0.1% minor allele frequencies that have gene regulatory roles, especially in heart-related tissues. In fact, single-cell epigenomic studies have also indicated that variants associated with CAD are enriched in specific heart cells.

About the study

The present study aimed to determine the contributions of rare and ultra-rare genetic variants in the heritability of CAD using whole genome sequencing and explore their roles in gene-regulatory functions and protein-altering.

Whole genome sequence data were obtained from the TOPMed Freeze 9 dataset, which consists of over 160,000 samples and approximately 800 million single nucleotide variants. Only variants with at least 10 reads were included in the analysis.

Documented coronary interventions such as angioplasty or bypass surgery, as well as cases of myocardial infarction (MI) or death due to coronary heart disease, were used to identify cases of CAD. The controls included individuals without any documented angina, CAD, or death due to coronary heart disease.

To avoid bias, any related individuals were excluded from the analysis, and stringent quality control measures were applied to all the samples. A principal component analysis was used to infer genetic ancestry, focusing on data from 22,443 individuals of European ancestry that comprised over 28 million autosomal single nucleotide variants.

The heritability of CAD was estimated using genome-based restricted maximum likelihood with linkage disequilibrium and minor allele frequency stratification (GREML-LDMS) implemented in the software genome-wide complex trait analysis (GCTA).

The linkage disequilibrium scores were calculated for each single nucleotide variant. These values were then binned according to their minor allele frequencies and linkage disequilibrium. These results were then used to calculate a genetic relatedness matrix to estimate heritability.

Single nucleotide variants were further categorized based on evolutionary constraints determined through phyloP scores, cell-specific regulatory functions, and their predicted impact on proteins. The single nucleotide variants were also annotated based on their biological importance.

To identify the genetic variants that contributed significantly to CAD risk, single-nucleotide variant comparisons based on evolutionary constraints, protein-altering impact, and cell-regulatory functions were used.

Study findings

The heritability of CAD varied considerably based on the individual's genetic ancestry and the frequency of the genetic variants, with significant contributions from ultra-rare variants. This analysis focused on individuals of European ancestry, as heritability estimates for CAD were inconsistent when the predictions were made based on self-inferred race and ethnicity as compared to genetically inferred ancestry.

The heritability of CAD among individuals of European ancestry was estimated to be 23.9%, which increased to 34.3% when the analyses were adjusted for disease prevalence. About 50% of this heritability was attributed to ultra-rare variants with a minor allele frequency of 0.1% or less with low linkage disequilibrium scores. These ultra-rare variants had a stronger effect on the risk of CAD than the common variants.

The heritability of CAD was estimated to be 25.5% among smaller groups of individuals of African ancestry. However, the contribution of ultra-rare variants to CAD heritability was lower, at 15%, among individuals of African ancestry than among individuals of European ancestry.

Protein-altering single nucleotide variants disproportionately contributed to the heritability of CAD. Furthermore, single nucleotide variants that affected regulatory elements in the coronary artery cells, such as smooth muscle and endothelial cells, were also significant contributors to the risk of CAD.

Conclusions

The study findings highlight the role of ultra-rare genetic variants in the heritability of CAD, especially among individuals of European ancestry. Single nucleotide variants with protein-altering functions or those located in gene regulatory regions significantly contributed towards CAD risk. In the future, more research is needed to examine the role of genetic variants in CAD risk among diverse populations and individuals of mixed group ancestry.

Journal reference:

  • Rocheleau, G., Clarke, S. L., Auguste, G., et al. (2024). Rare variant contribution to the heritability of coronary artery disease. Nature Communications 15(1); 8741. Doi:10.1038/s41467024529396





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