Unraveling Nesprin's Role in Dilated Cardiomyopathy#pencis#cardiology #N...

                  Unraveling Nesprin's Role in Dilated Cardiomyopathy

Nesprins (nuclear envelope spectrin repeat proteins) are crucial components of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, which helps connect the nuclear envelope to the cytoskeleton, facilitating nuclear positioning, mechanotransduction, and signal transduction. Mutations or dysfunction in nesprin proteins, particularly Nesprin-1 and Nesprin-2, have been implicated in various cardiac diseases, including dilated cardiomyopathy (DCM). Dilated cardiomyopathy is characterized by the enlargement and impaired contraction of the heart's ventricles, leading to heart failure. Nesprins play a critical role in maintaining the structural integrity of the heart's muscle cells. Mutations in nesprin genes may lead to disrupted mechanical stability of the nucleus and altered gene expression, resulting in weakened heart muscle fibers and contributing to the development of DCM. Studies have shown that nesprin mutations can impair mechanotransduction pathways, leading to defective muscle function and remodeling, which are hallmarks of dilated cardiomyopathy. Understanding the specific molecular mechanisms by which nesprins influence heart muscle function and contribute to DCM can provide potential therapeutic targets for treating the disease. More info : cardiology.pencis.com Contact : cardiology@pencis.com #Nesprin #DilatedCardiomyopathy #HeartFailure #CardiomyopathyResearch #MolecularCardiology #LINCComplex #HeartHealth #Mechanotransduction #CardiacGenetics #MedicalResearch

 

              Exploring the Genetic Link Between Cardiovascular             Disease and Psoriasis

Although genetic predictors of cardiovascular disease (CVD) were associated with an increased risk of psoriasis, there was no reciprocal effect of psoriasis on CVD, a study has found.1 Furthermore, no associations were found between cardiovascular genetic predictors and other immune-mediated inflammatory diseases (IMIDs).

These results could help guide future research into shared genetic mechanisms and treatment strategies for psoriasis and CVD.

This genetic association study is published in JAMA Dermatology.

“Our findings are consistent with genetic predictors of CVD associating with increased psoriasis risk with no reciprocal effect,” wrote the researchers of the study. “This suggests that pathways influencing CVD risk may also contribute to the causal biological pathways of psoriasis.”

Previous studies have identified a link between psoriasis and CVD. Psoriasis is an autoimmune disease, which is known to cause inflammation that is not only visibly on the skin, but with other parts of the body, including the heart.2 Researchers have identified several possible factors for this, including shared genetics and common inflammatory pathways.

In this study, the researchers aimed to determine the bidirectional relationship between genetic predictors of psoriasis with 2 major forms of CVD, coronary artery disease (CAD) and stroke, and the association between genetic predictors of CVD with 9 other IMIDs.1

The researchers utilized a 2-sample mendelian randomization (MR) approach to analyze summary-level data from large-scale genome-wide association studies, which included data on individuals of European descent and covered information on CAD, stroke, psoriasis, and 9 other IMIDs: acne, atopic dermatitis, asthma, celiac disease, Crohn disease, inflammatory bowel disease multiple sclerosis, rheumatoid arthritis, or ulcerative colitis.

The primary outcomes were the associations of genetic predictors of CAD and stroke with the risk of psoriasis and the other IMIDs using inverse-variance weighted estimation to determine the direction and strength of associations, while adjusting for potential confounding variables. Data were analyzed from January 2023 to May 2024.

The study included 181,249 cases and 1,165,690 controls with CAD; 110,182 cases and 1,503,898 controls with stroke; and 36,466 cases and 458,078 controls with psoriasis.

Contrary to prior assumptions, genetic predictors of psoriasis were not associated with an increased risk of CAD or stroke. However, in the reverse direction, genetic predictors of both CAD (OR, 1.07; 95% CI, 1.04-1.10; P = .003) and stroke (OR, 1.22; 95% CI, 1.05-1.41; P = .01) were significantly associated with a higher risk of developing psoriasis.

After adjusting for stroke, the association between CAD genetic predictors and psoriasis risk became nonsignificant, indicating a shared genetic effect between CAD and stroke that increases psoriasis risk. Importantly, no significant associations were found between cardiovascular genetic predictors and other common IMIDs, suggesting that this genetic link may be specific to psoriasis.

The researchers noted several limitations to the study, First, they were unable to empirically confirm that the second and third instrumental variable assumptions had not been violated, as this relied on the researchers’ judgment. Second, the bidirectional MR method may have led to bias estimates and reduced the power of the analysis. Third, although the study was able to identify moderate to large effects between CVD genetic predictors and other IMIDs, it may have been unable to identify smaller effect sizes.

Despite these limitations, the researchers believe the study suggests an association between genetic predictors of CVD with increased psoriasis risk with no reciprocal effect or associations with other IMIDs.

“This knowledge could help expedite biomarker discovery to improve cardiovascular risk prediction in the psoriasis population and lead to the development of novel therapeutic strategies that target common inflammatory pathways, potentially offering dual benefits in treating psoriasis and preventing CVD,” wrote the researchers.

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#PsoriasisAwareness
#GeneticsAndHealth
#HeartDisease
#PsoriasisResearch
#ChronicInflammation
#AutoimmuneDisease
#GeneticResearch
#HeartAndSkin

 

  Sex Differences in Cardiovascular Pharmacology

Cardiovascular disease (CVD) is the leading global cause of mortality, impacting individuals of all genders. Despite significant progress in understanding disease patterns in both women and men, a concerning trend of undertreatment persists due to gender-specific responses to cardiovascular drugs, resulting in diminished benefits from available therapeutic strategies. While current guidelines do not recommend differential treatment of CVD based on gender, an emerging body of research indicates sex dimorphism in the pathophysiology of CVD, resulting in varied pharmacological responses to cardiovascular agents. The pharmacodynamic mechanisms underlying gender differences are not fully elucidated, emphasizing the need for more studies focusing on women to optimize sex/gender-specific therapy and improve clinical outcomes in female CVD patients. Consequently, the present special issue aims to explore sex differences in therapeutic responses to cardiovascular drugs, a crucial step toward enhancing clinical outcomes and providing a more personalized treatment approach. This initiative aims to generate new ideas and identify potential pharmacological targets for novel drug discovery in the cardiovascular field.

The limited comprehension of pharmacological mechanisms in gender differences related to cardiovascular diseases underscores the need for more focused studies on women, aiming to optimize sex-specific therapy and enhance clinical outcomes for female CVD patients. The goal of this special issue is to focus on the investigation of sex differences in therapeutic responses to cardiovascular drugs, with the ultimate objective of improving clinical outcomes and refining personalized treatment approaches.

Specific Pharmacological Responses: Explore and elucidate the mechanisms underlying sex-specific responses to cardiovascular drugs.

Gender Dimorphism in Cardiovascular Pharmacology: Investigate and analyze sex dimorphism in the pathophysiology of cardiovascular diseases, highlighting its implications for drug responses.

Clinical Outcomes and Treatment Approaches: Examine the impact of sex differences on clinical outcomes in patients with cardiovascular diseases and animal models. Propose personalized treatment approaches based on gender-specific responses, aiming to enhance therapeutic efficacy and address the distinct needs of both male and female individuals affected by cardiovascular conditions.

Optimizing Sex-Specific Therapy: Focus on studies aiming to optimize therapy tailored to the sex of the individual, considering pharmacodynamic and pharmacokinetic factors.

Pharmacological Targets for Novel Drug Discovery: Identify and discuss potential pharmacological targets for novel drug discovery in the cardiovascular field, emphasizing sex-specific considerations.

Manuscript Types:

- Original Research Articles: Presenting novel findings and insights.

- Review Articles: Synthesizing existing knowledge and highlighting gaps.

- Clinical Studies: Investigating sex-specific responses in real-world scenarios.

- Pharmacological Mechanism Studies: Exploring the molecular basis of sex differences in drug responses.

- Perspective and Opinion Pieces: Offering unique viewpoints on the subject.

Contributors are encouraged to submit manuscripts that advance our understanding of sex differences in cardiovascular pharmacology, ultimately contributing to more effective and personalized treatment strategies.

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#SexDifferences, #CardiovascularPharmacology, #HeartHealth, #GenderMedicine, #Pharmacology, #CardiovascularDisease, #DrugResponse, #HeartMedications, #CardiacCare, #GenderDifferences, #WomenHeartHealth, #MenHeartHealth, #PrecisionMedicine, #Cardiology, #HormonalInfluence, #PersonalizedMedicine, #ClinicalPharmacology, #HeartResearch, #Pharmacokinetics, #Pharmacodynamics

 

Finerenone benefits in HFpEF may be greater in patients with recent worsening HF

Key takeaways:

• In patients with HF and LVEF 40% or greater, finerenone may have the most benefit in those with recent worsening HF.
• The trend may be due to a play of chance and more data are needed.

In patients with HF and left ventricular ejection fraction 40% or greater, the absolute risk reduction for total worsening HF events and CV death with finerenone vs. placebo was greatest in those with recent worsening HF, new data show.

However, no formal treatment interaction was observed in terms of relative risk reduction, according to a new analysis of patients from the FINEARTS-HF trial.

As Healio previously reported, in the main results of FINEARTS-HF, the nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia, Bayer) reduced risk for CV death and worsening HF by 16% compared with placebo at 32 months. Akshay S. Desai, MD, MPH, FACC, FHFSA, cardiovascular medicine specialist and director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, presented a prespecified analysis of the results stratified by recency of worsening HF during a virtual late-breaking clinical research session of the Heart Failure Society of America Annual Scientific Meeting. The in-person meeting was canceled due to Hurricane Helene.

Recent worsening HF

Akshay S. Desai

“FINEARTS-HF was unique among trials enrolling patients with HF and left ventricular EF 40% or more in that we deliberately targeted enrollment of patients with recent worsening HF events,” Desai told Healio. “Patients were eligible for enrollment during hospitalization for worsening HF or shortly after discharge from treatment for a worsening HF event, and enrollment of those without recent worsening HF was prospectively capped at about 50% of the total study enrollment. Accordingly, nearly half of the enrolled participants had experienced a recent worsening HF event (within 3 months of randomization) and about 12% were enrolled during a worsening HF event/hospitalization. These patients with worsening HF are known to be at high risk for subsequent morbidity and mortality and are a prime target for implementation of disease-modifying therapy. We therefore prespecified an analysis of the interaction between treatment and time from worsening HF to randomization as part of the study statistical analysis plan.”

The analysis, simultaneously published in the Journal of the American College of Cardiology, included 1,219 patients with a worsening HF event within 7 days before randomization, 2,028 patients with a worsening HF event between 7 days and 3 months before randomization and 2,754 patients who had a worsening HF event more than 3 months before randomization or no history of worsening HF events. The mean age was 72 years and the percentage of women ranged from 46% to 48%.

The primary outcome of CV death and total HF events (hospitalizations or urgent visits) favored the finerenone group in patients with a worsening HF event within 7 days before randomization (RR = 0.74; 95% CI, 0.57-0.95) and in patients with a worsening HF event between 7 days and 3 months (RR = 0.79; 95% CI, 0.64-0.97) but not in patients with a worsening HF event more than 3 months before randomization or no history of worsening HF events (RR = 0.99; 95% CI, 0.81-1.21), Desai said during the presentation.

However, he said, there was no formal treatment interaction (P for interaction = .07).

In a time-to-first event analysis, the treatment interaction was less pronounced (P for interaction = .46), he said.

Yet, the absolute risk reduction for the primary outcome conferred by finerenone did significantly vary by recency of worsening HF event (within 7 days, absolute RR per 100 patient-years = 7.8; 95% CI, 1.4-14.1; 7 days to 3 months, absolute RR per 100 patient-years = 4.6; 95% CI, 0.3-8.8; more than 3 months or no history, absolute RR per 100-patient years = 0.1; 95% CI, –2.2 to 2.4; P for trend = .01), he said.

High-risk population

“Patients with recent worsening HF (regardless of the treatment setting) are at high risk for subsequent readmission and mortality,” Desai told Healio. “These patients appear to derive benefit from finerenone regardless of their proximity to a worsening HF event, but those enrolled during or early after a recent worsening HF event appear to experience the greatest absolute risk reductions with finerenone, without any enhanced signal of adverse events. These data suggest that patients with recent worsening heart failure may experience a particularly favorable balance of benefit to risk from finerenone treatment and may be prime candidates for treatment with finerenone in clinical practice.”

Desai told Healio that “the lack of a compelling statistical interaction in these subgroups and the lack of consistency of this trend in other key secondary endpoints examined” mean that the researchers cannot rule out that the increased benefit of finerenone in patients with recent worsening HF is a chance finding, so more data from patients in the hospital with HF or recently discharged for it are necessary, and the REDEFINE-HF and CONFIRMATION-HF trials may provide that.

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#HeartFailure 

#HFpEF 

#Cardiology 

#Finerenone 

#ChronicKidneyDisease 

#Type2Diabetes 

#WorseningHeartFailure 

#HeartHealth 

#CardioRenal

Revolutionary Insights Cardiac MRI Radiomics in Dilated Cardiomyopathy #...

      Revolutionary Insights Cardiac MRI Radiomics in Dilated Cardiomyopathy

Revolutionary Insights: Cardiac MRI Radiomics in Dilated Cardiomyopathy Cardiac MRI radiomics is transforming the diagnostic and prognostic landscape for patients with Dilated Cardiomyopathy (DCM), a condition characterized by weakened heart muscles and enlarged ventricles. By extracting and analyzing quantitative features from MRI images, radiomics offers an unprecedented depth of understanding into tissue characteristics, fibrosis, and functional abnormalities that may not be visible to the naked eye. This advanced approach enables personalized treatment, early intervention, and precise risk stratification, making it a revolutionary tool in cardiology. In DCM, MRI radiomics helps to identify subtle changes in myocardial texture, ventricular function, and fibrosis patterns, providing critical insights into disease progression and patient outcomes. The technology can distinguish between different stages of DCM, predict response to therapies, and potentially delay the need for heart transplantation through tailored care. This leap in cardiac imaging elevates precision medicine, aiding clinicians in making data-driven decisions that enhance patient care. Related Hashtags: #CardiacMRI #Radiomics #DilatedCardiomyopathy #PrecisionMedicine #HeartHealth #MedicalImaging #CardiologyInnovation #AIInHealthcare #MRIAnalysis #HeartFailure #NonInvasiveDiagnostics #RadiologyRevolution More Info : cardiology.pencis.com Contact : cardiology@pencis.com #CardiacMRI #Radiomics #DilatedCardiomyopathy #precisionmedicine #hearthealth #MedicalImaging #cardiologyinnovation #AIInHealthcare #MRIAnalysis #HeartFailure #NonInvasiveDiagnostics #RadiologyRevolution

   

              About 6.7 million Americans older     than20 years have heart failure, report suggests

Biykem Bozkurt, M.D., Ph.D., from the Baylor College of Medicine in Houston, and colleagues updated trends in the incidence, prevalence, lifetime risk, mortality, and hospitalization rates of heart failure.

The authors note that about 6.7 million Americans older than age 20 years have heart failure, and the prevalence is expected to increase to 8.7, 10.3, and 11.4 million in 2030, 2040, and 2050, respectively. The lifetime risk for heart failure has increased to 24 percent.

Compared with the proportion of older patients, the proportion of younger patients with heart failure is increasing. About one-third of U.S. adults are at risk for heart failure, and 24 to 34 percent of the U.S. population has pre-heart failure. Individuals with obesity, hypertension, and clusters of comorbidities have an increased risk of developing heart failure.

Compared with other racial and ethnic groups, Black individuals have a higher incidence and prevalence of heart failure. Since 2012, heart failure mortality rates have been increasing, with a more pronounced acceleration from 2020 to 2021.

Compared with 1999, the age-adjusted heart failure mortality rates were higher in 2021; in 2021, heart failure accounted for 45 percent of cardiovascular deaths in the United States.

"We need to address worsening trends in heart failure, not only through medical interventions and properly implemented guideline-directed medical therapy, but by tackling the growing challenges in health care regarding access and coverage for appropriate and timely care," Bozkurt said in a statement.

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#Cardiology

#HeartHealth

#CardioCare

#HeartDisease

#CardiacCare

#Cardiovascular

#HeartFailure

#Arrhythmia

#Cardiologist

#HeartAwareness

#HeartSurgery

#InterventionalCardiology

#HeartAttack

#CardiovascularHealth

#Electrophysiology

#PreventiveCardiology

#CardiacRehab

#HeartStrong

#CongenitalHeartDisease

#HeartRhythm

Predicting Cardiac Risks in Kids New study insights #pencis #cardiology ...

        

      Predicting Cardiac Risks in Kids New study insights

A new study has provided important insights into predicting cardiac risks in children by identifying specific blood markers that can help forecast the likelihood of major cardiovascular events later in life. The study measured levels of low-density lipoprotein cholesterol (LDL-C), high-sensitivity C-reactive protein (hsCRP), and lipoprotein(a), which are key indicators of bad cholesterol, vascular inflammation, and genetic lipid factors, respectively. These markers have been associated with heart attacks and strokes in adulthood, emphasizing the importance of early detection in childhood to prevent future cardiac issues. While these tests have been available for years, the study's long-term results highlight the potential for using these markers to guide proactive health measures. Monitoring these markers could lead to early intervention, including lifestyle changes like increased physical activity and dietary improvements, which are key to reducing the risk of heart disease as children grow older. More info : cardiology.pencis.com Contact : cardiology@pencis.com #CardiacRisk #hearthealth #PediatricResearch #CardiovascularPrevention #EarlyDetection #HealthyKids #HeartDiseasePrevention