Tag: Cardiovascular Disease

Study suggests treating anxiety and depression significantly reduces ER visits and rehospitalizations among heart disease patients

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Ischemic heart disease (IHD) is a major cause of illness and death in developed countries. While advanced technology has boosted survival and rehabilitation odds, not much is known about the impact of anxiety or depression on the eventual outcomes. The prevalence of heart failure (HF) is predicted to increase by half in 2030. This will mean that eight million adults with HF, with almost $31 billion being required to treat them.

Study: Impact of Mental Health Treatment on Outcomes in Patients With Heart Failure and Ischemic Heart Disease. Image Credit: sitthiphong/Shutterstock.com

A new study looks at this area in order to provide evidence for key recommendations in the treatment of such patients.

Mental health and heart disease outcomes

Several previous studies have reported that anxiety and depression are independent risk factors for IHD and HF. Anxiety increases the incidence of IHD and HF by 41% and 35%, respectively, while increasing IHD-related mortality by 41%. Since anxiety and depression may originate in common factors, further research on their cross-linkage with cardiovascular disease and its outcomes is necessary.

Moreover, anxiety and depression both increase the odds of rehospitalizations and Emergency Department (ED) visits, pushing up healthcare costs. However, there is contradictory evidence for the benefits of treating anxiety or depression in IHD or HF, including recent trials like the SADHEART (Sertraline Antidepressant Heart Attack Randomized Trial).

Yet these mental and physical conditions reduce the quality of life, acting synergistically with the others due to their shared pathways. For instance, “coexistence of depression results in perception of symptom severity that exceed measures of actual functional impairment.”

About the study

The aim of the current study, published online in the Journal of the American Heart Association, aimed to examine the effect of treatment for anxiety or depression on the odds of repeated hospital admissions, ED visits, or mortality.

The researchers used a population-based cohort from the Ohio Medicaid database, exploring data retrospectively to assess the link between being treated for these conditions and future outcomes. All participants had ischemic heart disease (IHD) or heart failure, along with anxiety or depression.

There were ~1,500 participants, over 80% being White, with a mean age of 50 years. The upper age limit was 64 since people older than this are not eligible for Medicaid.

Treatment of anxiety and depression in the cohort

Over 92% were diagnosed with anxiety and 56% with depression. About half were disabled, a similar number had a history of substance use, and almost 60% had lung disease.

They were treated medically with antidepressant medication, or with psychotherapy, or both. About a quarter were on both courses of treatment, while ~30% were on antidepressants only and 15% on psychotherapy alone.

Anxiety was diagnosed in 90% of those on both therapies and depression in 70%. In the antidepressant group, 93% were anxious, and 53% were depressed. The corresponding figures in the psychotherapy group were similar.

The majority of those on treatment with antidepressants, alone or in combination with psychotherapy, were on benzodiazepines, antipsychotics, or mood stabilizers. Tricyclic antidepressants were used by a small proportion of patients.

About half the patients were on beta-blockers for their heart conditions, 36% on angiotensin-converting enzyme inhibitors (ACEIs), and 26% on calcium channel blockers.

How did treatment affect outcomes?

For all outcomes except mortality from IHD, “those who received some form of mental health treatment were significantly less likely to experience the outcome than those who received no mental health treatment.”

Those who received both psychotherapy and antidepressant therapy showed the greatest benefit in all three outcomes compared to no treatment and also when compared to either therapeutic modality alone.

The group treated with both modalities was 75% less likely to require another hospitalization or ED visit. After compensating for all known confounding factors, the risk of all-cause mortality dropped by 65% compared to those not treated for their mental ill-health.

With psychotherapy alone, there was a 40% reduction in mortality from all causes. There was no significant difference in the antidepressant-only group. None of the treatments resulted in a difference in the risk of IHD mortality, perhaps because the study was underpowered to detect this effect.

ED visits were reduced with all treatments. The combination therapy group showed a reduction of 74% compared to the no-treatment group. Psychotherapy alone, or antidepressants alone, was linked to a reduction in risk by 50%.

Hospital readmissions were also lower with combined therapy, at ~75% below the no-treatment group. With psychotherapy alone or antidepressants alone, the risk was approximately 50% and 60% lower, respectively.

Future implications

“This article is the first to show that mental health treatment may be associated with reduced risk for relevant outcomes.”

The unequivocal findings indicate the need to screen heart patients for anxiety and depression. If these conditions are diagnosed, providing appropriate treatment markedly improves the risk of rehospitalization and ED visits. Strategies must be optimized to diagnose and treat anxiety and depression in this group of patients to improve their quality of life.

Sympathetic activation occurs with anxiety and depression, along with heart disease. This results in the release of pro-inflammatory cytokines, promoting the progression of all three conditions. This may explain in part why treatment of mental ill-health improves the incidence of cardiovascular events.

This marks an advance from earlier studies that focused mostly on the safety of administering such medications to patients with IHD or HF and fills this research gap. Treating anxiety and depression in heart patients not only improves their health outcomes but may significantly reduce their healthcare costs, with a positive cost-benefit ratio.

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March 22, 2024
Transforming cardiovascular health through diet and education

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In a recent study published in BMJ Nutrition, Prevention, and Health, researchers evaluated the effectiveness of the Get Heart Smart (GHS) program in improving cardiovascular health.

Study: Evaluation of a 4-week interdisciplinary primary care cardiovascular health programme: impact on knowledge, Mediterranean Diet adherence and biomarkers. Image Credit: Sven Hansche/Shutterstock.com

Background

Cardiovascular disease is Canada’s second-leading cause of mortality. Lifestyle changes can boost cardiovascular health by improving the lipid profile and blood pressure.

Limiting alcohol use, lowering stress, increasing physical activity, managing weight, stopping smoking, and eating a well-balanced, nutrient-dense diet, such as the Mediterranean diet, can optimize cardiovascular health.

The Mediterranean Diet promotes a high diet of unsaturated fats, fruits, leafy greens, wholegrain cereals, seeds, nuts, plant-origin proteins, moderate animal-based protein consumption, and minimal sweet intake.

A two-point rise in the Mediterranean Diet score is associated with better health, including lower mortality, CVD risk, neoplastic illness, and depression. Health education and motive planning can improve cardiovascular outcomes.

According to the Planned Behavior Theory, knowledge can robustly estimate involvement, which impacts intentions and subsequent behavior change.

About the study

In the present pragmatic, longitudinal cohort study, researchers explored the impact of the GHS program on cardiovascular outcomes.

The researchers enrolled 31 adults in the four-week GHS program formulated by the East Elgin Family Health Team dieticians based on referrals from healthcare practitioners or by themselves. Due to COVID-19, 16 participants attended the program virtually.

The program comprised four weekly educational sessions of 75 minutes each to improve participant awareness of BP and cholesterol management.

In addition, the program educated the participants on grocery store navigation from a cardiovascular perspective and reviewed diets that improve cardiovascular health [like the Mediterranean Diet, Portfolio Diet, and Dietary Approaches to Stopping Hypertension (DASH) diet].

In one session, a physician answered questions concerning cardiovascular medications. After each session, participants developed their SMART (specific, measurable, achievable, realistic, and timely) goals.

The team conducted in-person sessions between May 2019 and March 2020 and provided educational handouts to the participants.

They obtained blood samples from the participants for metabolic profile analysis and used the GHS knowledge questionnaire to assess participant awareness. The primary outcome was a change in Mediterranean Diet adherence after four weeks and six months of follow-up.

Secondary study outcomes included changes in glycated hemoglobin (HbA1c), blood pressure (BP), lipid profile [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides], and an improved understanding of cardiovascular health after four weeks and six months.

In addition, the team compared cardiovascular outcomes between those attending in-person and virtually during COVID-19.

They performed two-way repeated-measures analyses of variance (RM-ANOVAs) to investigate GHS program effectiveness using data obtained between May 2019 and March 2023.

Results

The study population was primarily comprised of healthy female Caucasians, with a mean age of 61 years. GHS program participation was strong, with participants attending an average of 3.5 out of 4 sessions, with no significant differences between in-person and virtual attendance.

Knowledge ratings differed significantly between groups at baseline and after four weeks. Over six months, the team noted significantly higher Mediterranean Diet adherence and knowledge ratings in the in-person, virtual, and pooled samples. None of the biomarker alterations, except triglycerides, were statistically significant.

Following the four-week GHS course, the virtual group’s Mediterranean Diet adherence improved significantly. After a six-month follow-up, adherence to the Mediterranean Diet was remarkably higher in the virtual and in-person groups.

The effect on Mediterranean Diet adherence increased considerably with time (partial eta squared for time: 0.4).

After four-week and six-month follow-ups, the pooled, virtual, and in-person groups showed significantly higher knowledge scores than at study initiation.

After four weeks, knowledge levels differed considerably between the virtual and in-person groups; however, the team found no statistically significant difference between groups after six months. As time passed, they found a considerable influence on participant knowledge (partial eta squared for time, 0.5).

The study found that the four-week cardiovascular health program significantly increased Mediterranean diet adherence, as seen by an increase in the mean Mediterranean Diet score from 7.0 to 9.2 after six months.

Significant gains in knowledge ratings were observed in both the virtual and in-person groups, showing the adoption of virtual programs.

Future research, however, must assess the program’s effectiveness in larger sample sizes with higher gender and ethnic diversity and poor cardiovascular health to increase the generalizability and validity of the study findings.

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March 21, 2024
Exploring the role of iodine in obesity, diabetes, and other metabolic conditions

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In a recent study published in Frontiers in Nutrition, researchers reviewed recent data on the metabolic implications of iodine consumption and elucidated the underlying mechanisms.

Study: The correlation between iodine and metabolism: a review. Image Credit: Evan Lorne/Shutterstock.com

Background

Iodine is an essential nutrient that aids in producing thyroid hormones and is associated with metabolic illnesses such as diabetes, obesity, dyslipidemia, and hypertension.

However, the processes underlying these relationships are unknown. Iodine exerts immunomodulator, antioxidant, and differentiator effects in several tissues and organs, and alters the levels of thyroxine (T4) and tri-iodothyronine (T3), the primary regulators of energy metabolism.

Metabolic syndrome (MetS), which includes hypertension, abdominal obesity, hyperlipidemia, and hyperglycemia, is common globally and can lead to cardiovascular disease, malignancies, and death. Oxidative stress, chronic inflammatory diseases, and dietary changes are all risk factors for MetS.

The nutritional status of iodine may partly explain the incidence of metabolic syndrome. Further study on the relationship between iodine and metabolism will contribute to a better understanding of its role and promote an adequate and reliable iodine feeding standard.

About the study

In the present study, researchers explored the impact of iodine levels on metabolic health.

Research on the effects of iodine on metabolism

The recommended dietary allowance (RDA) of iodine ranges between 150 and 299 μg/day, with a moderately increased consumption potentially lowering the risk of prostate and breast cancer.

Cross-sectional research indicates a U-shaped association between urinary iodine concentration (UIC) and metabolic syndrome prevalence, with a low point of 300 to 499 μg/L.

In Korean postmenopausal women, consuming seaweeds and iodine showed inverse correlations with MetS incidence; however, excess seaweed intake demonstrated adverse effects among male MetS patients with TT and TG genotypes of the lipoprotein lipase gene (LPL). However, a study of school-aged children discovered associations between high UIC and MetS.

Research in China indicated central adiposity decreased when UIC levels reached ≥300 μg/L. A randomized clinical trial found that individuals who received iodine-reduced kelp tablets had a significantly lower body fat percentage.

A 28-day placebo-controlled trial discovered that fucoxanthin seaweed supplementation reduced waist circumference, fat mass, visceral fat, weight, and BMI among obese residents of Japan. However, among reproductive-age Colombian women, mUIC was shown to be positively linked with obesity.

The TIDE study demonstrated a U-shape curve for the relationship between urinary iodine concentration and diabetes prevalence, with higher UIC levels increasing the likelihood of acquiring diabetes mellitus type 2 (T2DM). Patients with diabetes mellitus have lower UIC levels than healthy individuals.

Increased iodine content in the placenta lowers gestational diabetes in pregnant women. The study also discovered a U-shaped curve in the correlation between UIC and hypertension prevalence, with individuals in iodine-excess (IE) and iodine-sufficient (IS) locations having higher blood pressure readings. Iodine deficiency is a risk factor for preeclampsia and pregnancy-related hypertension.

Research has demonstrated an inverse relationship between UIC, hyperuricemia, and gout prevalence. Longitudinal data revealed higher death rates among patients with ID (UIC <100 μg/L).

Iodine consumption can raise blood cholesterol levels in hens and cause hepatic steatosis in BaLB/c mice. In mice, higher iodine consumption enhanced lipid metabolism without affecting thyroid hormone levels or body weight.

Mechanisms underlying the metabolic effects of iodine

Iodine exerts antioxidative, antimicrobial, immunomodulatory, and molecular regulatory effects. Iodine alters the proportion of pathogenic and beneficial bacteria to restore the gut microbiome and reduce insulin resistance, obesity, and metabolic syndrome parameters.

Iodine also reduces inflammation by lowering oxidative and endoplasmic reticulum stress caused by free radicals such as reactive oxygen species (ROS).

Iodine acts on the Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) pathway to enhance the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (Cat), and glutathione peroxidase (GSH-Px).

In addition, iodine alters inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) levels, regulating mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways to reduce chronic inflammation and improve metabolic health.

The mineral acts on type 2 deiodinase (D2) receptors that convert T4 to biologically active T3 to improve weight management and adaptive thermogenesis.

Iodine also interacts with peroxisome proliferator-activated receptor-γ (PPARγ) receptors to enhance adipocyte differentiation, fatty acid uptake, and glucose metabolism by improving insulin sensitivity.

Conclusions

Overall, the review findings indicate that iodine impacts obesity, lipid metabolism, and glucose metabolism. Iodine’s antioxidant, immunomodulatory, gut-restoring, and antimicrobial effects explain the mineral’s effects.

Iodine regulates the oxidative state related to variations in insulin sensitivity or metabolism. However, iodine shortages and persistent iodine excesses may increase the risk of thyroid diseases.

Thus, it is critical to maintain iodine levels in an appropriate range at a population level. Future prospective studies and mechanism research must develop an evidence-backed and safe iodine nutrition standard.

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March 21, 2024
Socioeconomic status shapes the gut microbiome in diverse U.S. population
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Previous studies have reported an association between socioeconomic status (SES) and the gut microbiome, with various biological mechanisms potentially contributing to this relationship. A recent npj biofilms and microbiome study investigates how SES impacts the gut microbiome.

Study: Sociobiome – Individual and neighborhood socioeconomic status influence the gut microbiome in a multi-ethnic population in the US. Image Credit: Maciej Bledowski / Shutterstock.com

Background

There is a positive correlation between lower SES and mortality that is related to chronic diseases, including cardiovascular disease, cancer, and diabetes. However, the biological mechanisms involved in SES-related health disparities remain unclear.

Low SES is often associated with unhealthy eating behaviors, smoking, consumption of alcohol, and reduced access to medical services. These unhealthy SES-associated behaviors have implications for the development of chronic diseases and influence the gut microbiome.

Ample evidence exists regarding the impact of maternal and family SES on the infant and childhood gut microbiome. Furthermore, twins who experience a different SES during adulthood exhibit differences in the composition of their gut microbiome. Nevertheless, these data have typically been obtained from small cohorts, thus necessitating the need for larger samples with information on area-related measures from racially diverse populations to confirm these findings.

About the study

Data on 825 participants of diverse nativity and racial backgrounds were obtained from the Food and Microbiome Longitudinal Investigation (FAMiLI) study. SES was inferred by noting individual and neighborhood characteristics.

The researchers were primarily interested in determining whether low SES was associated with overall gut microbiota diversity and composition. Heterogeneity analyses were conducted to explore the role of race/ethnicity and nativity in the development of the gut microbiome.

Study findings

Within the study cohort, 36.7% were male, and the mean age was 59.6 years. About 38% of the participants were non-Hispanic White, 34.8% non-Hispanic Asian, 10.8% non-Hispanic Black, and 16.7% Hispanic.

Approximately 48% of the cohort were foreign-born, whereas 25% had completed high school or less education. Neighborhood- and individual-level SES were correlated with race/ethnicity and nativity.

A greater association was observed between lower individual educational attainment and microbial α-diversity, which was represented by the number of within-sample phylogenetic tree units. Participants from more deprived neighborhoods did not exhibit significant α-diversity. Moreover, β-diversity or overall composition differentials in gut microbiome correlated with neighborhood- and individual-level SES indicators.

Ten bacterial species were differentially present by SES indicators. Some taxa associated with low SES included Collinsella sp000434535, Catenibacterium sp000437715, Prevotella copri, Prevotella stercorea, and Dorea_A formigenerans.

Monoglobus pectinilyticus, Lawsonibacter asaccharolyticus, Dysosmobacter welbionis, and Frisingicoccus caecimuris were associated with high SES. Comparatively, Dorea_A formicigenerans, Catenibacterium sp000437715, and Prevotella copri were associated with social deprivation index (SDI) scores and neighborhood income. Occupation and SDI scores were associated with Dysosmobacter welbionis.

The abundance of Bacteroides and Prevotella, both of which are known biomarkers for diet and lifestyle, was compared. Consistent with previous reports, a higher abundance of Prevotella and a lower abundance of Bacteroides were associated with low SES. These differences could be attributed to varying dietary habits that entail a high consumption of animal products relative to carbohydrates.

Prior research has reported the potential role of Dysosmobacter welbionis in preventing diet-induced diabetes, obesity, and metabolic disorders in mice. In the present study, a reduced abundance of Dysosmobacter welbionis was observed among low SES participants, which could explain adverse health outcomes, such as diabetes and metabolic disorders, in this group.

Hispanic and Black participants were more likely to have lower SES, as reflected by parameters relating to education, occupation, neighborhood income, and deprivation. United States-born participants had higher SES as compared to foreign-born participants. Concerning race/ethnicity, none of the SES indicators showed marked heterogeneity. However, β-diversity varied significantly between ethnic/racial groups.

Conclusions

A significant association was observed between the gut microbiome and SES across a diverse population. Differences in the SES were associated with the abundance of bacterial species, α-diversity, β-diversity, and microbial functions. Taken together, the study findings emphasize the important role of SES in influencing the gut microbiome composition.

The term “sociobiome” describes the gut microbiota composition of residents of a particular geographic location. Socially minoritized populations are more prone to experiencing adverse health outcomes and environmental conditions. Future studies should consider the broader social context, aside from SES, while identifying microbial factors that influence health inequalities.

Despite the relatively large size of the study cohort, there was an unequal distribution of SES across ethnic/racial groups. Furthermore, the population distribution did not reflect the general American population with regard to the percentages of White, Asian, Black, and Hispanic individuals; therefore, the study findings should be generalized with caution. Residual confounding may have also been present, despite controlling for a wide array of key lifestyle variables.
Journal reference:

Kwak, S., Usyk, M., Beggs, D., et al. (2024). Sociobiome – Individual and neighborhood socioeconomic status influence the gut microbiome in a multi-ethnic population in the US. Npj Biofilms and Microbiomes 10(1);1-10. doi:10.1038/s41522-024-00491-y
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March 14, 2024
Novel tool to predict a person’s risk for cardiovascular complications after bone marrow transplant

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For thousands of Americans each year, a bone marrow transplant has the potential to cure diseases such as leukemias, lymphomas and immune deficiency disorders. While lifesaving, bone marrow transplants are taxing procedures that can affect various organs, including the cardiovascular system.

With advances in medical science and improvement in protocols, more bone marrow transplants, also known as hematopoietic stem cell transplantation, are being offered to older patients, a population at greater risk of cardiovascular disease.

Researchers led by Michigan Medicine have not only determined the contemporary prevalence of cardiovascular complications after bone marrow transplant -; they developed a novel tool to predict a person’s risk for such problems following the procedure and help guide the pre-transplant process.

“In the early era of bone marrow transplant, patients with heart disease were often excluded due to the cardiotoxicity of the conditioning regimens used at the time,” said Salim Hayek, M.D., adjunct professor of internal medicine-cardiology at U-M Medical School who specializes in cardio-oncology.

“Understanding the cardiovascular risks of modern bone marrow transplantation is crucial for selecting the right patients and to ensure that none are excluded unnecessarily. This is the first contemporary evidence that shows the risks associated with bone marrow transplant and how to assess a patient’s risk for cardiovascular complications-; which, taken together, can guide clinicians to ensure better outcomes for this procedure.”

Cardiovascular risks after transplant

Hayek and his team built the Cardiovascular Registry in Bone Marrow Transplantation, known as CARE-BMT, which compiles data of patients who underwent transplant from both University of Michigan Health and Rush University.

In a study of over 3,300 people who had a bone marrow transplant between 2008 and 2019, 4.1% of patients experienced cardiovascular events within 100 days after the procedure, and 13.9% did so after 5 years.

The results are published in JACC Cardio-Oncology.

Rare complications

Overall, cardiovascular complications during the hospitalization for bone marrow transplant were rare. The most common short and long term condition was atrial fibrillation, with 6.8% of patients diagnosed at the five-year mark, followed by 5.4% of patients experiencing heart failure. Severe cardiovascular complications, such as heart attack and stroke, were uncommon.

Investigators also found that 16.4% of allogenic transplant recipients, those who received bone marrow from another donor, developed long term cardiovascular events after five years, compared to 12.1% of autologous recipients who had damaged bone marrow replaced with their own healthy blood stem cells.

The landscape of bone marrow transplant has rapidly evolved over the last 20 years, with many improvements in the way patients are selected for and treated during bone marrow transplantation.

Our cohort allowed us to re-evaluate the incidence of cardiovascular complications in patients who received more modern treatment.”

Salim Hayek, M.D., adjunct professor of internal medicine-cardiology at U-M Medical School

Patients with preexisting cardiovascular conditions, such as diabetes and coronary artery disease, were more likely to have complications in the long term but not during the transplant process.

“Determining who is at high and low risk of cardiovascular outcomes is crucial to help guide both the pre-transplant evaluation as well as the post-transplant management -; which is why we invested so much in creating a simple risk score that health care providers can use to identify these patients,” said first author Alexi Vasbinder, Ph.D., R.N., a post-doctoral fellow at the U-M Frankel Cardiovascular Center at the time the research was conducted.

Pre-bone marrow transplant risk cardiovascular score

To develop such a tool, researchers used data from the CARE-BMT cohort. They created a simple points based risk score using clinical information that is easily accessible, including age and race, history of coronary artery disease or heart failure, and prior doses of cardiotoxic chemotherapy medications.

In an analysis of just over 2,400 adult patients, the final risk model, now known as the CARE-BMT risk score, identified a high risk group that accounted for over 30% of the patients. The five year cardiovascular complication rate was 31.9%; that rose to 55% at 10 years.

The score performed equally well in allogeneic and autologous bone marrow transplant recipients, as well as in a separate cohort of over 900 patients from Rush University.

Results are published in the Journal of the American Heart Association.

“It’s a very simple score that can be easily calculated and implemented in any health care record,” Hayek said.

“This will be easy to replicate and use during evaluations before bone marrow transplant to guide referrals of high risk patients to cardiovascular specialists who can then optimize medical and lifestyle management of their conditions.”

AHA scientific statement

The two reports formed the basis of a scientific statement published by the American Health Association geared towards the cardiovascular management of patients undergoing bone marrow transplant.

The statement covers considerations during the four steps of hematopoietic stem cell transplantation : evaluation before transplant, conditioning therapy and transplant, immediate post-transplant period and long term survivorship.

“This innovative cardiac risk assessment tool significantly improves our ability to provide a safer path throughout treatment to our cell therapy recipients possessing cardiovascular comorbidities, which in turn will have a positive effect on long term recovery and quality of life,” said co-author John Maciejewski, M.D., Ph.D., bone marrow transplant physician at U-M Health and clinical assistant professor of internal medicine at U-M Medical School.

Source:

Michigan Medicine – University of Michigan

Journal reference:

Vasbinder, A., et al. (2023). Cardiovascular Events After Hematopoietic Stem Cell Transplant: Incidence and Risk Factors. JACC: CardioOncology. doi.org/10.1016/j.jaccao.2023.07.007.

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March 13, 2024
More women experience cardiovascular disease following a depression diagnosis than men

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People with depression face an increased risk of cardiovascular disease (CVD); however, more women experience CVD following a depression diagnosis than men, according to a new study published today in JACC: Asia. The study investigates the connection between depression and CVD, shedding light on potential mechanisms that contribute to its sex-based differences and underscoring the importance of tailoring CVD prevention and management strategies according to sex-specific factors.

Depression is the third leading cause of morbidity worldwide. Prior research shows that it is associated with a heightened risk of cardiovascular events, including myocardial infarction (MI), angina, stroke and CV mortality. Women with depression are at greater relative risk of developing heart-related negative health outcomes than men, but there is still controversy over the evidence on sex differences in the impact of depression on heart health and the mechanisms underlying this are not well understood.

The identification of sex-specific factors in the adverse effects of depression on cardiovascular outcomes may help in the development of targeted prevention and treatment strategies that address the specific CVD risks faced by depressed patients. A better understanding will allow healthcare providers to optimize care for both men and women with depression, leading to improved CVD outcomes for these populations.”

Hidehiro Kaneko, MD, assistant professor at the University of Tokyo in Japan and a corresponding author of the study

Researchers in this study evaluated the association between depression and subsequent CVD events by conducting an observational cohort study using the JMDC Claims Database between 2005 and 2022. They identified 4,125,720 participants who met the study’s criteria. The median age was 44 (36-52) years, and 2,370,986 participants were men. Depression was defined as those clinically diagnosed before their initial health checkup.

Using standardized protocols, the study collected participant’s body mass index (BMI), blood pressure and fasting laboratory values at their initial health checkup. The primary outcome was a composite endpoint including MI, angina pectoris, stroke, heart failure (HF) and atrial fibrillation (AF).

Researchers analyzed the statistical significance of differences in clinical characteristics between participants with and without depression. Results indicate that the hazard ratio of depression for CVD was 1.39 in men and 1.64 in women compared with participants without depression. Models also indicate that hazard ratios of depression for MI, angina pectoris, stroke, HF, and AF were higher for women than for men.

Study authors highlight an important discussion regarding the potential mechanisms that may contribute to why depression impacts women’s heart health more than men’s. One explanation is that women may experience more severe and persistent symptoms of depression compared to men, and they may be more likely to have depression during critical periods of hormonal changes, such as pregnancy or menopause.

Other mechanisms include women’s greater susceptibility to traditional risk factors when depressed, such as hypertension, diabetes and obesity, which may contribute to the development of CVD. Differences in healthcare utilization and treatment between men and women and sex-specific differences in biological factors, such as genetics and hormonal profiles, may also increase women’s CVD risk.

“Our study found that the impact of sex differences on the association between depression and cardiovascular outcomes was consistent,” Kaneko said. “Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management. Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

Limitations of the study include the inability to establish direct causality between depression and cardiovascular events and the inability to accurately reflect the severity or duration of depressive symptoms. Potential confounding factors that may influence the association between depression and CVD were not accounted for, such as socioeconomic status. Researchers also acknowledge that COVID-19 may have been a confounder.

Source:

American College of Cardiology

Journal reference:

Senoo, K., et al. (2024) Sex Differences in the Association Between Depression and Incident Cardiovascular Disease. JACC: Asia. doi.org/10.1016/j.jacasi.2023.11.015.

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March 12, 2024
Optimizing antithrombotic treatment for individualized cardiovascular care

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Announcing a new article publication for Cardiovascular Innovations and Applications journal. Thrombosis, the process of blood clot formation in blood vessels, is an important protective mechanism for avoiding excessive blood spillage when an individual is exposed to trauma. The body has both a thrombosis inhibition and a thrombus removal system, which interact in a balanced manner. If these mechanisms become unbalanced, and too many clots form and block the lumen, thrombosis occurs.

Thrombosis is currently the leading cause of death from disease in humans and is one of the most common events leading to many cardiovascular diseases. Antithrombotic drugs are an integral part of the pharmacological treatment regimens, and interventional strategies are currently recommended for thrombotic complications in patients with thrombosis. Despite major advances in these therapies, the high risk associated with thrombosis and bleeding remains, because of the complex interplay among patient comorbidities, drug combinations, multifaceted dose adjustments, and care settings.

Detailed assessment of the effects of bleeding and thrombosis is necessary to establish optimal treatment plans for patients with thrombosis. This study retrospectively evaluated methods for assessing the risk of bleeding/ischemia in thrombosis and the individualized use of these methods.

Source:

Journal reference:

Yuan, M., et al. (2024). Precision Monitoring of Antithrombotic Therapy in Cardiovascular Disease. Cardiovascular Innovations and Applications. doi.org/10.15212/cvia.2024.0013.

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March 12, 2024
Immune cells in the liver eat up excess cholesterol, study reveals

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A new study from Karolinska Institutet in Sweden reveals that immune cells in the liver react to high cholesterol levels and eat up excess cholesterol that can otherwise cause damage to arteries. The findings, published in Nature Cardiovascular Research, suggest that the response to the onset of atherosclerosis begins in the liver.

Cholesterol is a type of fat that is essential for many functions in the body, such as making hormones and cell membranes. However, too much cholesterol in the blood can be harmful, as it can stick to the walls of the arteries and form plaques that narrow or block the blood flow. This results in atherosclerotic cardiovascular disease, the primary underlying cause of heart attacks and strokes, and the leading cause of death worldwide.

The liver responded immediately

In the current study, researchers wanted to understand how different tissues in the body react to high levels of LDL, also called ‘bad cholesterol’, in the blood. To test this, they created a system where they could quickly increase the cholesterol in the blood of mice.

Essentially, we wanted to detonate a cholesterol bomb and see what happened next. We found that the liver responded almost immediately and removed some of the excess cholesterol.”

Stephen Malin, lead author of the study and principal researcher at the Department of Medicine, Solna, Karolinska Institutet

However, it wasn’t the typical liver cells that responded, but a type of immune cell called Kupffer cells that are known for recognizing foreign or harmful substances and eating them up. The discovery made in mice was also validated in human tissue samples.

“We were surprised to see that the liver seems to be the first line of defense against excess cholesterol and that the Kupffer cells were the ones doing the job,” says Stephen Malin. “This shows that the liver immune system is an active player in regulating cholesterol levels, and suggests that atherosclerosis is a systemic disease that affects multiple organs and not just the arteries.”

Several organs could be involved

The researchers hope that by understanding how the liver and other tissues communicate with each other after being exposed to high cholesterol, they can find new ways to prevent or treat cardiovascular and liver diseases.

“Our next step is to look at how other organs respond to excess cholesterol, and how they interact with the liver and the blood vessels in atherosclerosis,” says Stephen Malin. “This could help us develop more holistic and effective strategies to combat this common and deadly disease.”

The research was supported by grants from the Swedish Heart-Lung Foundation, Leducq Foundation Networks of Excellence Program B cells in Cardiovascular Disease, EU’s Seventh Framework Program FP7, The Swedish Research Council and the Marie Skłodowska-Curie Actions Award.

Source:

Journal reference:

Di Nunzio, G., et al. (2024). Kupffer cells dictate hepatic responses to the atherogenic dyslipidemic insult. Nature Cardiovascular Research. doi.org/10.1038/s44161-024-00448-6.

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March 11, 2024
Microplastics and nanoplastics could be harming your heart health

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In a recent study published in The New England Journal of Medicine, researchers investigated whether micro- and nano-plastics (MNPs) are detectable in atherosclerotic plaques.

Study: Microplastics and Nanoplastics in Atheromas and Cardiovascular Events. Image Credit: chayanuphol/Shutterstock.com

Background

Plastic production has been constantly increasing and is likely to continue until 2050. Plastics can degrade and form MNPs, inducing toxic effects.

Studies have demonstrated the entry of MNPs into the body through skin exposure, inhalation, and ingestion, as well as their interactions with tissues/organs. Further, MNPs have been detected in the placenta, liver, lungs, urine, blood, and breast milk. Recent preclinical reports implicate MNPs as a cardiovascular risk factor.

In vitro findings indicate that some MNPs promote inflammation, oxidative stress, and apoptosis in endothelial cells. Moreover, animal studies support the role of MNPs in myocardial fibrosis, endothelial dysfunction, and cardiac function impairment.

However, their clinical relevance remains unknown. There is no evidence to suggest the infiltration of MNPs in human vascular lesions or associations between MNP burden and cardiovascular disease.

About the study

In the present study, researchers investigated the presence of MNPs in atherosclerotic plaques and the associations between MNP burden and cardiovascular disease.

Consecutive patients aged 18–75 with asymptomatic carotid artery stenosis indicated for carotid endarterectomy were screened. Patients with valvular defects, secondary causes of hypertension, malignant neoplasms, or heart failure were excluded.

Besides, patients who had complications in the postoperative period were also excluded. Baseline clinical examinations were performed, and health records were accessed for clinical, demographic, and intervention data.

Fasting blood specimens were collected for biochemical analyses. Participants were followed up after carotid endarterectomy.

Surgically excised atheromatous plaque specimens were obtained at atherectomy. MNP abundance was measured using pyrolysis–gas chromatography–mass spectrometry, and results were validated using electron microscopy (EM) and isotope analysis.

The primary endpoint was a composite of non-fatal stroke, non-fatal myocardial infarction, or death. Patients were grouped based on the presence/absence of MNPs in plaques.

Cox regression was performed to assess associations between the presence of MNPs in plaques and composite endpoint incidence.

Analyses were adjusted for sex, age, body mass index (BMI), creatinine, low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, hypertension, diabetes, and prior cardiovascular events.

Findings

The team screened 312 patients; of these, 47 were lost to follow-up or had missing data, and eight had a stroke or died before discharge.

Overall, 257 subjects were followed up for an average of 33.7 months. Polyethylene was detectable in the excised carotid plaque of 150 patients; thirty-one of these also had measurable levels of polyvinyl chloride in the plaque.

The average levels of polyethylene and polyvinyl chloride in plaques were 21.7 μg/mg and 5.2 μg/mg, respectively.

Patients with these MNPs were younger, male, smokers, had dyslipidemia, cardiovascular disease, diabetes, and higher levels of creatinine, and were less likely to have hypertension compared to those without MNPs.

Ten random plaque samples with both polyvinyl chloride and polyethylene were analyzed using EM. Transmission EM (TEM) revealed particles (foreign origin) smaller than one μm with jagged edges within foamy macrophages.

Besides, the same slices were observed with scanning EM (SEM), and spectral X-ray maps were generated from particles resembling those observed with TEM.

The maps indicated decreased carbon and oxygen in plaque samples and increased chlorine. Given the probable non-biologic nature of chlorine, this might confirm polyvinyl chloride deposits.

The researchers performed the isotope analysis on 26 random plaque samples as petroleum-derived plastics exhibit lower δ¹³C values, i.e., the ratio between carbon-13 and carbon-12, than human tissues.

This analysis revealed two distinct patient clusters. One cluster included patients with higher δ¹³C values; the other cluster showed lower values, perhaps due to MNP contamination. Lower values were more evident in plaques with MNPs.

The primary endpoint event occurred in 30 and eight patients with and without evidence of MNPs, respectively. Patients with MNPs in plaques had a higher risk of the primary endpoint events than those without MNPs.

Conclusions

In patients with high-grade asymptomatic carotid stenosis indicated for carotid endarterectomy, those with MNPs in plaques had a higher incidence of the composite endpoint than those without MNPs.

Notably, the results do not prove causality; the association between MNPs in plaques and the primary endpoint might also entail risks from exposure to unmeasured, residual, or other confounding variables.

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March 11, 2024
More steps a day keep the doctor away
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Researchers of a recent study published in the British Journal of Sports Medicine investigated the relationship between daily step count and cardiovascular disease and mortality. They also investigated whether prolonged sedentary behavior affects the ideal number of daily steps.

Healthcare specialists urge increasing daily steps to minimize mortality and morbidity since prolonged sedentary behavior is related to an increased risk of death and cardiovascular disease. However, present research on daily stepping is limited and does not address whether sedentary time influences the relationship between mortality and CVD. With the emergence of wearable devices, simplified health information may assist individuals in self-monitoring and setting objectives.

Study: Do the associations of daily steps with mortality and incident cardiovascular disease differ by sedentary time levels? A device-based cohort study. Image Credit: Joseph M. Arseneau / Shutterstock

About the study

In the present device-based cohort study, researchers investigated the effect of prolonged sedentary behavior on the dose-response of daily steps linked to any-cause mortality and CVD risk.

The researchers used United Kingdom Biobank data from individuals aged 40 to 69 years recruited from 2006 to 2010 to perform a dose-response assessment of total steps each day across high (≥10.50 hours per day) and low (less than 10.50 hours per day) inactive period (as described by the inflection point for the absolute risk of inactivity time with the study outcomes). They ascertained new-onset cardiovascular disease and mortality through October 31, 2021.

Participants completed digital questionnaires and underwent physical examinations. The researchers excluded individuals with prior CVD or cancer diagnoses, missing covariate data, or events within a year of accelerometer assessments. Between 2013 and 2015, 103,684 participants wore accelerometers on their wrists for ≥16 hours each day for ≥3.0 days to assess physical activity, classified using accelerometer-based machine learning models.

The researchers followed Welsh and English participants through September 30, 2021, and Scottish participants through October 31, 2021, using mortality data from the NHS National Records and Central Register of Scotland and NHS Digital of Wales and England. They obtained hospitalization data from the Hospital Episode Statistics (HES) database.

The researchers determined the dose-response risk for any-cause mortality and new-onset cardiovascular disease per 10,000 individual years using Cox proportional hazards regression models to estimate the hazard ratios (HRs). Study covariates included age, gender, educational level, ethnicity, smoking habits, alcohol intake, vegetable and fruit intake, parental cardiovascular disease and cancer history, and medications. In sensitivity analyses, they included clinical variables like glycated hemoglobin, waist circumference, low- and high-density lipoprotein, blood pressure, and triglyceride levels. They also performed joint association evaluations using 2,200 daily steps as the reference.

Results

Over seven years, the study of 72,174 individuals found 1,633 deaths and 6,190 cardiovascular disease events. High inactivity duration increased the likelihood of smoking, hypertension, cholesterol medication use, and waist circumference. Daily step counts among individuals with low and high sedentary times were 8,362 and 4,829, respectively. Compared to the reference of 2,200 steps per day, the optimum dose for any-cause mortality varied from 9,000 to 10,500 daily steps for the high (HR, 0.6) and low (HR, 0.7) sedentary periods.

In the high inactive duration category, fewer than 4,000 steps per day were related to a 5.4% crude death risk, whereas a step count exceeding 8,000 steps per day yielded a crude risk of 3.1%. The comparable risk for individuals with low sedentary times was 3.7% and 2.3%, respectively. Among highly inactive individuals, the curve bottom was observed at 9,000 steps per day (HR, 0.6), compared to 2,200. The minimum dosage was 4,100 steps per day (HR, 0.8).

The researchers found an attenuated step-per-day dosage-response relationship among subjects with low inactive periods, with the curve nadir at 10,300 daily steps (HR, 0.7) and the least at 4,400 steps/day. The combined dose-response evaluation revealed consistent curve nadir and least dosage values across sedentary durations, with comparable mortality risk from 6,000 to 9,500 steps per day.

For new-onset cardiovascular disease, the researchers found the least risk at 9,700 steps per day for both high (HR, 0.8) and low (HR, 0.7) sedentary times. They discovered that low-sedentary individuals had a reduced CVD risk for similar steps per day to very sedentary individuals. The lowest step count was 4,300 steps per day for low and high inactivity hours, with HRs of 0.86 and 0.9. When the daily step count exceeded 3,700, the combined dose-response analysis revealed less inactive time linked to a lower CVD and mortality risk for a similar daily step count as high inactivity time. In a cause-specific investigation, the optimal dosage was around 9600 steps per day for high-sedentary time and 9,800 steps daily for low inactive duration.

The study findings showed that doing more than 2,200 steps daily reduces mortality and cardiovascular disease risk in high- and low-sedentary individuals. Steps of 9,000 to 10,500 per day had the least mortality risk, regardless of the period of inactivity. Low inactive duration resulted in a 10% decrease in risk for the same number of daily steps. The study underlines the importance of increasing daily steps, particularly among very sedentary individuals, and determined that the optimal dosage to reduce mortality and CVD risk is between 9000 and 10,500 steps per day.
Journal reference:

Matthew Ahmadi, Rezende, Gerson Ferrari, Borja Cruz, I-Min Lee, and Emmanuel Stamataki. Leandro. Do the associations of daily steps with mortality and incident cardiovascular disease differ by sedentary time levels? A device-based cohort study, DOI: 10.1136/bjsports-2023-107221, https://bjsm.bmj.com/content/early/2024/01/24/bjsports-2023-107221
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March 8, 2024