Tag: Cardiovascular Disease

A game-changer in preventing heart failure and sudden cardiac deaths

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In a trial-level meta-analysis published in the journal Circulation, researchers assessed the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) on major adverse cardiovascular events (MACE) across three patient populations: diabetes at high risk for atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or chronic kidney disease (CKD). They found that SGLT2i reduced the rate of MACE by 9% with a consistent effect across all patient populations and key subgroups, primarily driven by a reduction in cardiovascular (CV) death, particularly HF and sudden cardiac death.

Study: Sodium Glucose Co-transporter 2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis. Image Credit: Lightspring / Shutterstock

Background

SGLT2i have been extensively studied in large, randomized, placebo-controlled trials involving diverse populations of patients, including those with type 2 diabetes mellitus (T2DM) and ASCVD, HF, and CKD. While SGLT2i was primarily developed for diabetes, the trials have consistently shown these drugs to reduce HF and kidney-related issues, regardless of diabetes status. However, their impact on MACE remains unclear, with variations observed among trial results. Prior meta-analyses failed to assess the effects on MACE components definitively. Uncertainty persists, particularly in subgroups without ASCVD or diabetes and those with advanced chronic kidney disease stages. Therefore, using data from all significant placebo-controlled trials, researchers in the present study performed a collaborative meta-analysis to explore SGLT2i’s effects on MACE risk and its components and death subtypes across relevant patient subgroups.

About the study

The researchers conducted a collaborative trial-level meta-analysis within the SGLT2i Meta-Analysis Cardio-Renal Trialists Consortium (SMART-C). A systematic literature search was conducted, and the included studies were phase 3 placebo-controlled, double-blind, randomized trials with ≥ 1,000 participants in every arm and median follow-up of six months and above. Combination SGLT1/2 inhibitors studies were excluded.

The study included 11 randomized trials comparing SGLT2i to placebo, with 78,607 participants in total. Among them, 54.2%, 26.4%, and 19.5% of individuals participated in trials focused on diabetes at high ASCVD risk, established HF, or CKD, respectively. The mean age of participants was between 62 and 72 years. While 34.4% of them were females, 74.5% of them were white. At baseline, about 79.7% of the patients had diabetes, 36% had HF, and 37.2% had eGFR (short for estimated glomerular filtration rate) less than 60 mL/min/1.73 m². Established ASCVD was present in 58.9%, and 28.5% had prior MI.

The median follow-up duration ranged between 2.4 – 4.2 years, 1.3 – 2.2 years, and 2.0 – 2.6 years for trials focused on diabetes at high ASCVD risk, HF, and CKD, respectively. The primary outcome was the composite of 3-point MACE, including cardiovascular death, myocardial infarction (MI), and all types of stroke. The analysis also assessed the individual components of MI and stroke, including fatal and non-fatal events. Additionally, all-cause mortality (ACM) and death subtypes such as fatal MI, fatal stroke, HF death, sudden cardiac death, as well as other CV and non-CV deaths were examined. The analysis treated each outcome as a time-to-event event, and the effect estimates from each trial were derived from intention-to-treat analysis.

Trial effect estimates were meta-analyzed within primary patient groups using fixed-effects models and then combined as random effects for overall estimates. Sensitivity analysis was conducted using fixed effects. Heterogeneity was assessed using the Cochrane Q statistic and Higgins and Thompson’s I2.

Results and discussion

About 10.1% of participants experienced MACE, with 5.3% experiencing CV death, 3.6% experiencing MI, and 2.8% experiencing a stroke. SGLT2i was found to reduce the rate of MACE by 9% overall, with consistent effects across trial populations. The most evident effect was observed on CV death, with reductions in HF death and sudden cardiac death driving the reduction in CV death. There was no significant effect on MI or stroke overall. SGLT2i were also found to reduce ACM, with the most significant effects observed in CKD trials.

Patients with established ASCVD were found to have higher MACE incidence rates across all trial types. SGLT2i consistently reduced the risk of MACE and CV death regardless of established ASCVD status at baseline. Similarly, the effects remained consistent across subgroups stratified by diabetes status, prior HF, kidney function, and baseline eGFR. Stratification by albuminuria suggested a potential benefit primarily among those with ≥30 mg/g albuminuria. Across all the Kidney Disease Improving Global Outcomes (KDIGO) risk groups, the benefits for MACE and CV death were found to be consistent.

The study is limited by fewer trials in each drug in each disease state and variations in eligibility criteria, follow-up duration, and subgroup definitions across studies. These restrictions restrict robust comparisons within the SGLT2i class and lower the generalizability of findings to broader patient populations.

Conclusion

In conclusion, SGLT2i consistently lowers the risk of MACE across diverse patient populations, regardless of baseline ASCVD, diabetes, or kidney function. This benefit predominantly comes from reduced cardiovascular death, notably HF and sudden cardiac death, with no significant impact on MI or stroke overall. These findings suggest the potential utility of SGLT2i across the spectrum of cardiovascular-kidney-metabolic disease, aiding in therapeutic decision-making.

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April 9, 2024
How incentives and games encourage exercise
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In a recent study published in the journal Circulation, researchers evaluated the effects of gamification and financial incentives on physical activity in individuals at risk of adverse cardiovascular events.

Higher physical activity is associated with a lower risk of adverse cardiovascular events and improved control of cardiovascular risk factors. By leveraging behavioral economic concepts, such as loss-framing, immediacy, and endowment effects, shorter-term analyses have implemented financial incentives and gamification interventions and observed increased physical activity in patients at risk of or with atherosclerotic cardiovascular disease (ASCVD). Nevertheless, the effect of these interventions over the long term remains unclear.

Study: Effect of Gamification, Financial Incentives, or Both to Increase Physical Activity Among Patients at High Risk of Cardiovascular Events: The BE ACTIVE Randomized Controlled Trial. Image Credit: Alliance Images / Shutterstock

About the study

In the present study, researchers evaluated the efficacy of financial incentives, gamification, or both to improve physical activity over the long term in individuals at risk of major cardiovascular events. This randomized controlled trial was conducted between May 2019 and January 2024. Eligible participants had ASCVD or a 10-year risk of stroke, myocardial infarction, or cardiovascular death.

Eligible subjects received a wearable device to track their step count. During the two-week run-in period, a baseline step count was established. Subsequently, participants were instructed to set a goal to increase their step count relative to baseline. Next, participants were randomized to attention control, financial incentives, gamification, or financial incentives plus gamification (combination).

The control group received text messages daily for 18 months, inquiring if they had achieved their step goal the previous day. In the gamification arm, participants signed a pre-commitment pledge to reach their step goal. They received 70 points at the beginning of each week. Points were retained if they succeeded in their daily goal; otherwise, 10 points were removed.

Their levels, viz., platinum, gold, silver, bronze, and blue, changed based on points at the end of the week. All participants began at the silver level; blue- or bronze-level participants were restarted at the silver level every eight weeks. Gold- or platinum-level participants were awarded a trophy after the intervention.

On the other hand, the financial incentives group was informed that $14 would be deposited in a virtual account each week. The balance did not change if the goal was achieved; otherwise, $2 was deducted. In the combination arm, participants completed interventions from both arms. After 12 months, interventions were discontinued; however, daily text messages recording the count continued for six additional months (follow-up).

The primary outcome was the change in daily step count from baseline to the end of the intervention. Secondary outcomes were the average changes in daily step count from baseline to follow-up, weekly moderate-to-vigorous physical activity (MVPA) minutes, and the proportion of participant weeks with at least 150 MVPA minutes.

Findings

Overall, 151, 304, 302, and 304 individuals were randomized to control, gamification, financial incentives, and combination arms, respectively. The average age of participants was 66.7 years; 60.5% were female, and 25% were Black. At baseline, the average daily step count was 5081, mean MVPA minutes were 5.8, and the average step count increase was 1867.

In total, 89.8% of participants completed the 18-month study. The control, financial incentives, gamification, and combination groups achieved a mean increase of 1418, 1915, 1954, and 2297 steps from baseline to the intervention period, respectively. The corresponding figures over the follow-up period were 1245, 1576, 1708, and 1831, respectively.

Over the 12-month intervention, compared to the control arm, participants had a greater increase in average daily step count. The combination arm was superior to financial incentives during the intervention period. Weekly MVPA increased by 39.6, 56.6, 54.7, and 65.4 minutes, on average, for control, financial incentives, gamification, and combination arms from baseline to intervention.

Over the follow-up period, weekly MVPA minutes increased by 37.3 for control, 50.7 for gamification, 50.9 for financial incentives, and 57.6 for combination groups. The proportion of participant weeks with at least 150 MVPA minutes was 0.16, 0.24, 0.23, and 0.27 for control, financial incentives, gamification, and combination arms, respectively. The combination group had greater odds of a week with at least 150 minutes of MVPA.

Conclusions

Taken together, interventions with financial incentives, gamification, or both significantly improved physical activity in adults at risk of cardiovascular events compared to attention control over the 12-month intervention. This effect was sustained over the six-month follow-up period after the end of the intervention in the combination group. The combination group also increased weekly MVPA minutes more than the control group. These interventions could be helpful components of strategies aimed at alleviating cardiovascular risks.
Journal reference:

Fanaroff AC, Patel MS, Chokshi N, et al. Effect of Gamification, Financial Incentives, or Both to Increase Physical Activity Among Patients at High Risk of Cardiovascular Events: The BE ACTIVE Randomized Controlled Trial. Circulation, 2024, DOI: 10.1161/CIRCULATIONAHA.124.069531, https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.069531
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April 9, 2024
Beta-blockers show no benefit for heart attack patients with normal heart function

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In a recent study published in The New England Journal of Medicine, researchers conducted the Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) trial to determine whether long-term oral beta-blocker therapy could reduce the risk of any cause or incident MI-related mortality among individuals with acute myocardial infarction but preserved left ventricular ejection fraction compared to no beta-blocker treatment.

Study: Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction. Image Credit: aipicte / Shutterstock

Background

Beta-blockers are beneficial in treating heart failure patients and those with reducing ejection fractions; however, these findings are from 1980s trials of patients with massive myocardial infarctions and systolic dysfunction in the left ventricle. Meta-analytical research indicated that beta-blockers do not appear to lower mortality in contemporary reperfusion techniques.

There is a lack of data from recent randomized clinical studies on the efficacy of long-term use of beta-blockers among acute myocardial infarction patients with intact ejection fraction. Previous Cochrane reviews underscore the need for novel research studies in this target population. Despite the absence of convincing scientific evidence of medication benefit, current recommendations strongly advocate beta-blocker therapy following a myocardial infarction.

About the study

In the present open-label, prospective, parallel-group trial, researchers evaluated the impact of beta-blocker therapy on reducing mortality among acute MI patients.

The team conducted the registry-based trial between September 2017 and May 2023 at 45 sites across New Zealand, Sweden, and Estonia. They randomized participants with prior acute MI who underwent coronary angiographies and had ≥50% ejection fraction from the left ventricle to receive 1:1 long-term therapy with beta-blockers such as ≥100 mg/day of metoprolol or ≥5 mg/day of bisoprolol (intervention group) or no such therapy.

All participants had obstructive coronary heart disease, as determined from coronary angiographies (i.e., ≥50% stenosis, ≤0.8 fractional flow reserves, or ≤0.9 instant wave-free segment ratios) before randomization. The primary outcome was the composite measure of all-cause or incident MI-related mortality. Secondary outcomes included cardiovascular disease-related mortality and hospital admission for atrial fibrillations or heart failure.

Safety outcomes included hospital admission for hypotension, second and third-degree atrioventricular blocks, bradycardia, syncope, or pacemaker implantation, and hospital admission due to chronic obstructive pulmonary disease (COPD), asthma, or stroke. Other endpoints included dyspnea [diagnosed using the New York Heart Association (NYHA) recommendations] and angina pectoris (diagnosed using the Canadian Cardiovascular Society guidelines) six to 10.0 weeks or 11.0 to 13.0 months after treatment. The team used Cox proportional-hazards regressions to determine the hazard ratios (HR) for analysis. They performed sensitivity analyses, adjusting for age, country, diabetes, and prior myocardial infarction. The Swedish population registry provided data on death or emigration, and the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) register collected data on incident myocardial infarctions. The national cause-of-death registry provided cardiovascular-related mortality data, while the national patient registry provided data on atrial fibrillation, heart failure, and safety outcomes.

Results

The researchers enrolled 5,020 MI patients (95% from Sweden) who followed up for a median of 3.50 years until November 16, 2023. The median participant age was 65.0 years, 23% were female, and 35% had myocardial infarction with an elevation in the ST segment. Among the participants, 46% were hypertensive, 14% were diabetic, and 7.1% had a prior myocardial infarction. Of 2,508 beta-blocker recipients, 1,560 (62%) and 948 (38%) received metoprolol and bisoprolol, respectively.

Coronary angiography showed one-vessel involvement among 55% of MI patients, two vessels involved among 27%, and three vessels involved among 17% of patients. The team performed percutaneous coronary interventions in 96% of patients, with coronary artery bypass grafting (CABG) among 3.9%. At hospital discharge, 97% received aspirin, P2Y12 receptor blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins.

The researchers observed the primary endpoint among 7.9% (199 out of 2,508) of beta-blocker recipients and 8.3% (208 out of 2,512) of non-recipients (HR, 0.96). Beta-blockers did not lower the cumulative incidence rates of secondary endpoints (all-cause mortality, 3.90% and 4.10% among beta-blocker recipients and non-recipients, respectively); cardiovascular disease-related mortality, 1.50% and 1.30%, respectively; myocardial infarctions, 4.50% and 4.70%; hospital admission due to atrial fibrillations, 1.10% and 1.40%; and hospital admission due to heart failures, 0.80% and 0.90%).

Concerning safety endpoints, the researchers observed hospital admission due to atrioventricular blocks, bradycardia, syncope, hypotension, or pacemaker implantation among 3.40% of beta-blocker recipients and 3.20% of non-recipients; hospital admission due to COPD or asthma in 0.60% and 0.60%, respectively, and hospital admission due to stroke among 1.40% and 1.80% of beta-blocker recipients and non-recipients, respectively. Subgroup analyses yielded similar results.

Overall, the study findings showed that long-term use of beta-blockers did not reduce the risk of all-cause or incident myocardial infarction-related mortality in patients with an acute MI who underwent coronary angiography but retained ≥50% ejection fraction from the left ventricle compared to no treatment with beta-blockers.

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April 9, 2024
MADs show comparable blood pressure reduction to CPAP in hypertensive patients with sleep apnea

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People with hypertension and obstructive sleep apnea were no less likely to see their blood pressure drop over six months if they used a mandibular advancement device (MAD), which is inserted onto the teeth similar to a bite guard. compared to a continuous positive airway pressure (CPAP) device, according to research featured at the American College of Cardiology’s Annual Scientific Session. Hypertension, or high blood pressure, is a common risk factor for cardiovascular disease. People with obstructive sleep apnea experience frequent sleep interruptions due to the airway closing periodically during sleep. Since obstructive sleep apnea can cause or worsen hypertension, medical guidelines recommend the use of a CPAP machine to help keep airways open by delivering pressurized air through the mouth and nose.

MADs are designed to help keep the airway open by repositioning the lower jaw and moving the tongue forward. Previous studies have shown that CPAP devices outperform MADs in terms of apnea-hypopnea index, the standard metric used to measure sleep apnea severity. However, there is evidence that MADs may be better tolerated than CPAP, which some people find too uncomfortable or cumbersome for sustained use.

In this study, MADs were found non-inferior in terms of change in the average 24-hour ambulatory mean blood pressure at six months and they resulted in a larger reduction across multiple secondary blood pressure parameters compared with CPAP. According to researchers, higher adherence among people assigned to use the MAD device could help explain the findings.

Looking at the totality of evidence available in the literature, it is still reasonable to say that CPAP is the first-line treatment until we have more data on the MAD. However, for patients who truly cannot tolerate or accept using a CPAP, we should be more open minded in looking for an alternative therapy such as a MAD, which based on our study, numerically had a better blood pressure reduction in patients compared with a CPAP.”

Ronald Lee Chi-Hang, MD, professor of medicine at Yong Loo Lin School of Medicine, National University of Singapore, senior consultant in the department of cardiology at National University Heart Centre, Singapore, and one of the study authors

For the study, 321 people with uncontrolled hypertension and high cardiovascular risk underwent a sleep study to determine whether they had obstructive sleep apnea. Of these, 220 people were found to have moderate to severe obstructive sleep apnea and were randomly assigned to receive a MAD or CPAP device. Participants were instructed to use their assigned device for six months while sleeping to the degree that they could tolerate it. Both devices had built-in trackers that recorded use.

At six months, people assigned to the MAD group experienced a drop in 24-hour ambulatory mean blood pressure that was 1.64 mmHg larger, on average, than those assigned to CPAP, meeting the threshold for non-inferiority and the trial’s primary endpoint. Compared with the CPAP group, the MAD group also showed a larger between-group reduction in all ambulatory blood pressure measures, especially nighttime blood pressure when the devices were being used, and an increased proportion of patients achieving a systolic blood pressure below 120 mmHg by the end of the study. None of the participants experienced symptomatic hypotension.

The adherence data revealed that over half (56.5%) of those who were assigned to use the MAD used the device for six or more hours per night on average over the study period, while under one-quarter (23.2%) of those assigned to CPAP did so.

“The MAD patients simply used the device longer,” Chi-Hang said. “That also might explain why the blood pressure reduction at nighttime, when the patients are actually using it, had a better reduction in the MAD arm.”

Adherence to the American Academy of Sleep Medicine’s recommendation of four or more hours of use in at least 70% of nights overall was similar between groups, with 69.4% of those in the MAD group and 64.3% of those in the CPAP group meeting this recommendation. Both groups saw a reduction in daytime sleepiness and the results showed no between-group differences in cardiovascular biomarkers.

Overall, researchers said the results underscore the importance of treating sleep apnea as part of a broader effort to control hypertension and reduce cardiovascular risk.

“People should be aware that over 400 million people globally have moderate-to-severe obstructive sleep apnea, and it is underdiagnosed and may be a contributing factor to their high blood pressure,” Chi-Hang said. “Especially for patients whose blood pressure is hard to control or who have a lot of excessive daytime sleepiness, [it is important to] go see a physician about sleep apnea and get treated if necessary.”

Since the study was conducted in Singapore and most study participants were of East Asian descent, researchers said further studies in more diverse populations are necessary to determine whether the findings are generalizable to other racial and ethnic groups. Chi-Hang also said that the timing of the study, which was conducted during travel lockdowns during the COVID-19 pandemic, may have influenced the results by increasing adherence.

The researchers plan to conduct further studies focused on comparing the impacts of the different types of devices on cognition.

The study was funded by the Singapore Ministry of Health.

This study was simultaneously published online in the Journal of the American College of Cardiology at the time of presentation.

Chi-Hang will present the study, “Mandibular Advancement Device Versus CPAP for Blood Pressure Reduction in Obstructive Sleep Apnea and High Cardiovascular Risk—A Randomized Clinical Non-inferiority Trial,” on Saturday, April 6, 2024, at 4:15 p.m. ET / 20:15 UTC in the Thomas B. Murphy Ballroom 4.

Source:

American College of Cardiology

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April 8, 2024
New machine learning model achieves breakthrough in heart disease prediction with over 95% accuracy

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In a recent study published in Scientific Reports, researchers developed a machine learning-based heart disease prediction model (ML-HDPM) that uses various combinations of information and numerous recognized categorization methods.

Study: Comprehensive evaluation and performance analysis of machine learning in heart disease prediction. Image Credit: Summit Art Creations/Shutterstock.com

Background

Heart disease is a worldwide health risk that healthcare professionals must evaluate and treat with medical examinations, advanced imaging techniques, and diagnostic procedures. Promoting heart-healthy practices and early diagnosis can help minimize cardiovascular disease incidence and enhance overall health.

Current approaches such as machine learning, deep learning, and sensor-based data collection produce promising findings but have limitations such as uneven diagnostic accuracy and overfitting.

The proposed approaches use modern technology and feature selection procedures to enhance heart disease diagnosis and prognosis.

About the study

In the current study, researchers built the ML-HDPM model for accurate cardiac disease prediction.

The researchers used the Cleveland database, the Switzerland database, the Long Beach database, and the Hungary database to obtain cardiovascular data. They pre-processed clinical data followed by feature selection, feature extraction, cluster-based oversampling, and classification.

They used training data to fit the model with the feature set, compute importance scores, and remove the lowest feature scores to achieve the desired feature.

The genetic algorithm (GA) comprised population initialization, selection, crossover, and mutation to determine if the termination criterion was satisfied.

The researchers undersampled raw data samples with majority labels and clustered samples with minority labels to merge the training set and perform synthetic minority over-sampling (SMOTE) to generate model output.

The model selects relevant features using the recursive feature elimination method (RFEM) and the genetic algorithm (GA), which improves the model’s resilience. Techniques such as the under-sampling clustering oversampling technique (USCOM) correct data imbalances.

The classification task uses multiple-layer deep convolutional neural networks (MLDCNN) and the adaptive elephant herd optimization method (AEHOM).

Model classifiers were principal component analysis (PCA), support vector machine (SVM), linear discriminant analysis (LDA), decision tree (DT), random forest (RF), and naïve Bayes (NB).

The model combines supervised infinite feature selection with an upgraded weighted random forest algorithm. The ML-HDPM pre-processing step assures data integrity and model efficacy. Extensive feature selection uncovers important properties for predictive modeling.

A scalar technique achieves a consistent feature effect, while SMOTE corrects for class imbalance. The genetic algorithm employs natural selection principles to generate several solutions in a single generation.

The strategy’s performance is assessed via simulated testing and compared to existing models. The testing, training, and validation datasets comprised 80%, 10%, and 10% data, respectively.

Results

ML-HDPM performed admirably over a wide range of critical evaluation criteria, as evidenced by the comprehensive examination. Using training data, the ML-HDPM model predicted cardiovascular disease with 96% accuracy and 95% precision.

The system’s sensitivity (recall) yielded 96% accuracy, while F-scores of 92% reflected its balanced performance. The ML-HDPM specificity of 90% is noteworthy.

ML-HDPM provides accurate and reliable results. It incorporates complex technologies such as feature selection, data balance, deep learning, and adaptive elephant herding optimization (AEHOM). These strategies allow the model to reliably forecast cardiac disease, which improves clinical decisions and patient outcomes.

ML-HDPM outperforms other algorithms in training (95%) and testing (88%). The success is due to the combination of complex feature extraction, data imbalance corrections, and machine learning.

Feature selection algorithms enable finding significant qualities associated with cardiovascular health, allowing them to detect subtle patterns indicative of cardiovascular disease.

Data correction using efficient data balancing techniques guarantees model training on representative datasets, including deep learning using the MLDCNN approach and AEHOM optimization to improve model accuracy.

ML-HDPM, a deep learning model, has lower false-positive rates (FPR) in training (8.20%) and testing (15%) than other approaches due to feature selections, data balance, and improved machine learning components in ML-HDPM.

The model had high true-positive rates (TPR) in the training (96%) and testing (91%) datasets due to feature identification, data balance, and deep-learning improvements. The approach improves the model’s capacity to identify true positives.

Conclusion

The study presents a unique ML-HDPM approach that incorporates feature selections, data balance, and machine learning to improve cardiovascular disease prediction.

The balanced F-values for accuracy and recall, high accuracy and precision rates, and low false-positive rates in the training and testing datasets highlight the promising potential of the model in cardiovascular diagnostic applications.

The findings indicate that the ML-HDPM model can increase the precision and speed of identifying cardiovascular diseases, thus improving the standard of care.

However, further investigation is required to improve model optimization and data quality and investigate its use by healthcare professionals in real-world settings.

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April 5, 2024
Feeling lonely? It may affect how your brain reacts to food, new research suggests
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In a recent study published in JAMA Network Open, researchers investigated the associations between individuals’ perceived levels of social isolation and brain patterns related to food cues, psychological outcomes, and obesity.

Their results indicate that loneliness can lead to challenges in control and motivation when responding to foods and have important implications for the development of effective treatments for obesity.

Study: Social Isolation, Brain Food Cue Processing, Eating Behaviors, and Mental Health Symptoms. Image Credit: Mansoreh/Shutterstock.com

Background

Perceived social isolation, or loneliness, is known to have significant impacts on health, including mental health disorders, cardiovascular disease, and obesity. The negative health consequences of social isolation were widely documented during the coronavirus disease 2019 (COVID-19) pandemic.

The biological mechanisms that underlie loneliness include alterations in brain networks like the default mode network, executive control network, visual attention network, and reward network, which could lead to hypervigilance to perceived social threats, heightened self-rumination, and increased sensitivity to negative social cues.

They may also contribute to maladaptive behaviors like overeating and substance cravings.

Investigating the neural mechanisms that link loneliness to alterations in responses to food cues may yield important insights into what scientists have termed the ‘lonely brain’ phenomenon.

About the study

In this study, researchers hypothesized that loneliness is associated with increased activation in certain brain regions when viewing food cues, which correlates with worsened mental health, changed eating behaviors, and obesity measures.

Another key hypothesis was that sweet food-related neural alterations would show stronger associations with maladaptive eating behaviors and mental health outcomes due to the well-documented rewarding nature of sugar-rich foods.

Healthy, premenopausal female participants were recruited in Los Angeles and asked to report perceived social isolation using the Perceived Isolation Scale.

They went through functional magnetic resonance imaging (fMRI) while being exposed to various food cues to evaluate neural responses to different food types.

Various clinical and behavioral measures were examined, including body composition, eating behaviors, and mental health variables.

Statistical analyses were conducted to compare demographic and clinical characteristics between high and low-perceived isolation groups. Whole-brain analyses were performed to assess perceived isolation-related differences in neural responses to the cues.

Regions of interest (ROIs) were identified, and brain signal changes were extracted for further analysis. Multiple linear regression analyses examined associations between loneliness-related brain food cue reactivity and individual clinical and behavioral measures.

Mediation analyses were conducted to assess the mediating effect of brain food cue reactivity on the association between perceived isolation and various outcomes of interest, such as body measurements, eating behaviors, and mental health. All analyses were adjusted for age.

Findings

Overall, 93 female participants aged 18 to 50 years, with a mean age of 25.38 years, were included, with 41% self-identifying as Filipino and 59% as Mexican.

The high perceived isolation group (n=39) exhibited poorer diet quality, greater fat mass percentage, poorer mental health, and increased maladaptive eating behaviors compared to the low perceived isolation group (n=54).

The findings from whole-brain comparisons showed that the group perceiving higher levels of social isolation reacted significantly more strongly to cues when viewing foods compared to non-foods, particularly in the region of the inferior parietal lobule (IPL).

Specifically, when they viewed sweet foods compared to non-foods, increased reactivity was observed in multiple brain regions, including the lateral occipital cortex, inferior frontal gyrus, and IPL.

Conversely, when they were shown savory foods compared to non-foods, the group perceiving higher levels of isolation exhibited less reactivity to cues in the dorsolateral prefrontal cortex (dlPFC) and central praecuneus.

Brain reactivity to sweet groups only and all food groups was correlated with mental health indicators and maladaptive food consumption behaviors. However, no associations were found for the subsample of savory foods.

When participants were shown food compared to non-food, brain reactivity was observed to mediate the correlations with reward-based eating, food cravings, and generally maladaptive eating behaviors.

Similarly, when participants viewed sweet food compared to non-food, brain reactivity was seen to mediate associations with body fat percentage, reward-based eating, food cravings, and generally maladaptive eating behaviors.

The association between viewing savory food and positive affect was also mediated by brain reactivity.

Conclusions

This study reveals that loneliness is linked to obesity, mental health symptoms, and maladaptive eating behaviors.

Being lonely was associated with increased body fat; lonely individuals were also more likely to report maladaptive eating behaviors and increased vulnerability to psychological symptoms.

Brain imaging showed heightened reactivity to cues in brain regions associated with social cognition and executive control, suggesting an imbalance in sensitivity to internal states and external cues.

Sweet foods particularly influenced neural responses, potentially due to their rewarding nature and analgesic effect.

These findings underscore the role of altered brain processing in mediating the association between social isolation and adverse health outcomes, highlighting the importance of holistic interventions targeting both body and mind.
Journal reference:

Zhang, X., Ravichandran, S., Gee, G.C., Dong, T.S., Beltrán-Sánchez, H., Wang, M.C., Kilpatrick, L.A., Labus, J.S., Vaughan, A., Gupta, A. (2024) Social isolation, brain food cue processing, eating behaviors, and mental health symptoms. JAMA Network Open. doi:10.1001/jamanetworkopen.2024.4855.https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2817148
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April 5, 2024
Exploring prebiotics and probiotics as dual fighters against depression and obesity

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Depression is among the most prevalent and potentially serious mental health disorders, accounting for up to 800,000 suicides a year. The risk factors for depression have, therefore, undergone much exploration.

A recent study published online in Nutrients deals with the interactions between depression and nutrition, coupled with exercise.

Study: The Role of Gut Microbiota, Nutrition, and Physical Activity in Depression and Obesity—Interdependent Mechanisms/Co-Occurrence. Image Credit: Bits And Splits/Shutterstock.com

About depression

Depressive disorders include several categories, including persistent depressive disorder (dysthymia), premenstrual dysphoric disorder, as well as depression induced by addictive drugs or medications or by medical conditions.

All are characterized by sadness and irritability, with bodily and mental changes. The effect is a lowered quality of life and impaired functioning.

Moreover, depression is known to increase the risk for a number of metabolic diseases, such as diabetes, obesity, and ischemic heart disease.

Conversely, dietary patterns are linked to mental health as well as malnutrition. For instance, excessive fat intake leads to chronic inflammation and obesity.

Obesity

Obesity is defined as the accumulation of body fat in excess, as measured by the body mass index (BMI) and the body fat percentage. It is associated with a higher risk of cardiovascular disease (CVD), insulin resistance, cancer, and nerve damage.

Risk factors for obesity are well-known and include gender, age, smoking, apart from the consumption of excessive fat and of processed foods, which are typical of Western diets.

Obesity and depression often affect the same individual, along with anxiety disorders. They have a common mechanism of action, as seen by their bidirectional association.

People who are depressed often indulge in comfort eating, which may increase body weight, especially if the person is also inactive. The risk of obesity in people undergoing emotional stress is almost 40% higher.

Similarly, obese people are almost 20% more likely to become anxious or depressed because of negative self-image as well as adverse social perceptions that they are too lazy or undisciplined to regulate their diet and their weight. The treatment of depression with antidepressants is effective but may cause weight increase.

Unfortunately, both obesity and depression are among the most prevalent disorders globally and have a high death rate, leading to powerful scientific interest in their interrelationships.

Gut microbiota

The gut microbiota is essential to proper energy storage and metabolism, but shows marked variability in obese vs lean individuals. This includes lower diversity and fewer commensal bacteria but more pathogenic microbes in the obese. The resulting aberration in metabolism may contribute to obesity.

The need for a rational diet along with therapies like psychotherapy and medication to treat patients with depression is stressed by some scientists.

In addition, probiotics and prebiotics may be required, along with nutritional supplements, to correct dysbiosis and vitamin deficiencies.

Probiotics and gut microbiota

The researchers sought to understand how gut microbes may be useful in treating both obesity and depression and the role of probiotics and prebiotics in such therapy.

The review suggests that about 57% of the composition of the gut microbiota responds to dietary patterns.

Probiotics strengthen the gut barrier and modulate the immune system. Their use is associated with improving depressive symptoms, perhaps by supplying vitamin D and short-chain fatty acids (SCFAs), which combat inflammation.

Some strains of probiotic bacteria directly affect neural pathways. They inhibit the depression-inducing hypothalamic–pituitary–adrenal axis (HPA axis), and promote the secretion of the anti-stress neurotransmitter GABA, also known as gamma-aminobutyric acid.

Others produce gut neurotransmitters that also affect the brain, affecting the mood for the better.

Some clinical trials in humans suggest a positive effect of probiotics on depressive disorders as well as on obesity and related metabolic conditions like insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).

Further research is essential to validate these results, especially as probiotics work well on gut health and overall disease control only as part of a holistic management strategy, including proper diet, exercise, stress regulation, and adequate sleep.

Bacterial strains linked to improved neural pathways, sometimes called psychobiotics, include multiple Lactobacillus strains like Lactobacillus casei Shirota, Lactobacillus fermentum NS8 and NS9, and Lactobacillus rhamnosus JB-1, as well as Bifidobacterium strains like Bifidobacterium longum Rosell-175, Bifidobacterium longum 1714, and Bifidobacterium longum NCC3001.

Diet and mental health

The brain receives a good share of absorbed nutrients and utilizes them to keep itself healthy. For instance, regeneration, neuroplasticity, and an adequate antioxidant reserve depend on the proper supply of nutrients to the brain.

Supplementation with fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), magnesium, folate, and vitamins E and D have been suggested to be beneficial in countering or mitigating severe depression and reducing neuroinflammation.

Specific diets like the Mediterranean diet (MD), the DASH (Dietary Approaches to Stop Hypertension), or vegetarian diets have frequently been assessed for their relationship with physical and mental health.

The authors of the current study found reduced depression and obesity risk with both the DASH and the MD, but contradictory data with vegetarian and vegan diets. However, high-quality vegetarian diets were protective against depression, underlining the pivotal role of diet quality in the type of diet chosen.

Physical activity and obesity/mood disorders

There is ample evidence that weight management is aided by increasing the overall energy expenditure and improving the mood, with reduced anxiety and depression. Aerobic exercise has been recommended for its ability to build fitness and help reduce weight.

Physical exercise is linked with lengthening telomeres, a metabolic health biomarker. It is also associated with better brain health, sleep quality, and reduced depressive symptoms.

Physical exercise is also linked to better gut microbiota composition, stronger commensals, and more anti-inflammatory bacteria.

Early-life exercise may promote the development of bacteria that can help the host adapt to changing conditions and promote healthy brain development.

The broader impact of obesity and depression

Depression is associated with increased mortality and morbidity, absenteeism, severe decreases in the quality of life, and reduced productivity.

Obesity, which is currently estimated to have a prevalence of 30% in the USA, also has profound impacts on personal and social health. It reduces female fertility, promotes loss of cognitive ability, reduces the lifespan, and may increase employment difficulty.

Conclusions

Obesity and depression have common origins and act to exacerbate each other. This interrelationship significantly impacts the quality of life. One possible explanation for their connections may be via gut dysbiosis.

This has stimulated much study on the potential use of probiotics and prebiotics in depression and anxiety, as well as in obesity.

“Encouraging findings from existing research underscore the need for robust clinical trials to evaluate the therapeutic potential of microbiota modulation.”

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April 4, 2024
Earlier menopause combined with high cardiovascular risk linked to cognitive problems later

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Earlier menopause combined with higher risk of cardiovascular disease is linked to an increased risk of thinking and memory problems later, according to a new study published in the April 3, 2024, online issue of Neurology^®, the medical journal of the American Academy of Neurology. In this study, earlier menopause is defined as occurring before age 49.

As a person ages, blood vessels, including those in the brain, can be damaged by controllable cardiovascular risk factors such as high blood pressure, diabetes and smoking. These risk factors not only increase a person’s risk of cardiovascular disease, they increase the risk of dementia.

While cardiovascular risk factors are known to increase a person’s risk for dementia, what is lesser known is why women have a greater risk for Alzheimer’s disease than men. We examined if the hormonal change of menopause, specifically the timing of menopause, may play a role in this increased risk. We found that going through this hormonal change earlier in life while also having cardiovascular risk factors is linked to greater cognitive problems when compared to men of the same age.”

Jennifer Rabin, PhD, study author of the University of Toronto, Canada

The study involved 8,360 female participants and 8,360 male participants matched for age who were enrolled in the Canadian Longitudinal Study on Aging. Female participants had an average age at menopause of 50. All participants had an average age of 65 at the start of the study and were followed for three years.

Researchers divided female participants into three groups: those who experienced earlier menopause between ages 35 and 48; average menopause between ages 49 and 52; and later menopause between ages 53 and 65. Researchers also looked at whether they had used hormone therapy containing estrogens.

For all participants, researchers reviewed six cardiovascular risk factors: high LDL cholesterol, diabetes, obesity, smoking, high blood pressure, as well as prescriptions for medications to lower blood pressure.

Participants were given a series of thinking and memory tests at the start and the end of the study. Researchers calculated cognitive scores for each person.

Researchers then examined the associations of cardiovascular risk with cognitive scores in female participants in the three groups and compared them to the same association in male participants.

After adjusting for factors such as age and education, researchers found that female participants with both earlier menopause and higher cardiovascular risk had lower cognitive scores three years later. For each one standard deviation increase in cardiovascular risk score, female participants with earlier menopause showed a 0.044 standard deviation decrease in cognitive scores, compared to male participants in the same age group who showed a 0.035 standard deviation decrease in cognitive scores.

Researchers did not find a similar association for female participants with average or later menopause. Hormone therapy did not affect the results.

“Our study suggests that earlier menopause may worsen the effects of high cardiovascular risk on cognitive decline,” said Rabin. “Since our study followed participants for only three years, more research is needed over longer periods of time. Our findings highlight that age at menopause as well as cardiovascular risk should be considered when developing prevention strategies for cognitive decline.”

A limitation of the study was that the age of menopause was self-reported, and participants may not have remembered that age accurately. Another limitation was that researchers did not include participants who reported a hysterectomy since the age of the procedure was not available. Additionally, no data was available on whether participants had surgical removal of one or both ovaries.

Source:

American Academy of Neurology

Journal reference:

Alexander, M. W., et al. (2024) Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging. Neurology. doi.org/10.1212/WNL.0000000000209298.

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April 4, 2024
New research links social factors to cardiovascular risk in Asian American adults
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Having more unfavorable social determinants of health, such as being unemployed, uninsured or not having education beyond high school, was associated with an increased likelihood of having risk factors for cardiovascular disease among Asian American adults, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.

The investigation also noted that the link between these unfavorable social determinants of health variables and cardiovascular disease risk factors varied widely among people in different Asian American subgroups in this study. An association does not mean that social determinants of health directly caused the risk factor.

Despite the perception that Asian Americans may be less impacted by social determinants of health compared to people in other racial/ethnic groups, our findings indicate unfavorable social factors are associated with higher prevalence of cardiovascular risk factors among Asian American adults.”

Eugene Yang, M.D., lead study author, professor of medicine at the University of Washington School of Medicine in Seattle

“The Asian American population is the fastest growing racial/ethnic group in the United States,” Yang said. “People of South Asian heritage have higher rates of premature heart disease globally, and they recently have been found to have higher cardiovascular mortality than non-Hispanic white people. Better understanding of why differences in cardiovascular risk exist among Asian subgroups is vital to reducing risk and improving outcomes.”

Researchers examined data from the National Health Interview Survey conducted in the U.S. from 2013 to 2018, which included 6,395 adults who self-identified as Asian.

Researchers rated 27 social determinants of health factors as favorable or unfavorable in six areas: economic stability (which included employment and income status); neighborhood and social cohesion (which gauged neighborhood trust and whether homes were owned or rented); psychological distress; food security; education; and health care utilization.

The analysis found a significant relationship between unfavorable social determinants of health and cardiovascular disease risk factors. This relationship varied among people in different Asian American subgroups. Among the findings:
- For all Asian groups included in the data, a higher unfavorable social determinants of health score by one standardized unit was associated with a 14% greater risk of high blood pressure; a 17% greater risk of poor sleep; and a 24% greater risk of Type 2 diabetes -; all of which increase the risk for developing cardiovascular disease.
- Specifically, more unfavorable social determinants were associated with:
  
  a 45% greater likelihood of Type 2 diabetes among Chinese adults and a 24% greater likelihood among Filipino adults;
  
  a 28% greater risk of high blood pressure among Filipino adults;
  
  a 42% increased likelihood of insufficient physical activity among Asian Indian adults, a 58% increased likelihood among Chinese adults and a 24% increased likelihood among Filipino adults;
  
  a 20% likelihood of suboptimal sleep among Asian Indian adults; and
  
  a 56% and 50% likelihood of nicotine exposure among Chinese adults and Filipino adults, respectively.
- Compared with other Asian American subgroups, adults who identified as Filipino reported the highest prevalence -; 4 out of 7 -; cardiovascular risk factors: poor sleep, high cholesterol, high blood pressure and obesity.
Yang said many social determinants of health are often interconnected, such as neighborhood cohesion, economic stability and use of the health care system.

“It is important to understand how different Asian subgroups are affected,” he said. “When Asian people are lumped together, higher risk groups like South Asian people may not be treated aggressively enough, while groups with lower risk, like people of Korean and Japanese descent, may be overtreated for blood pressure or cholesterol.”

Study background and details:
- The large, cross-sectional study reviewed data from 2013-2018 National Health Interview Surveys -; annual, nationally representative surveys of U.S. adults.
- Of the 6,395 Asian adults in the survey, about 22% self-identified as Filipino adults; 22% as Asian Indian adults; 21% as Chinese adults; and 36% as other Asian.
- The sample size of Asian American individuals in the national survey was too small to analyze several major Asian populations, including Japanese, Korean and Vietnamese people, as well as other smaller Asian subgroups.
- Nearly 56% of the group were women, and nearly 52% were between the ages of 18 and 44. About 77% of the participants were born outside the United States.
- Participants were assigned scores for social determinants of health by categorizing 27 variables as favorable or unfavorable.
- The cardiovascular risk factors were self-reported and were similar to the American Heart Association’s Life’s Essential 8 -; eight lifestyle metrics assessing ideal cardiovascular health. These eight metrics include: following a healthy diet, maintaining a healthy weight, getting regular exercise and enough quality sleep, avoiding nicotine exposure and maintaining healthy levels of blood pressure, glucose and cholesterol. However, healthy diet was not measured in this study. Reaching optimal levels of these eight metrics improves heart health and reduces the risk for heart disease and stroke.
Limitations of the study include that its small sample size did not allow for analysis of some Asian subgroups (Japanese, Korean, Vietnamese and other Asian people). In addition, it examined self-reported survey data on social factors and cardiovascular risk factors at a single point in time. Therefore, the analysis could not assess long-term social determinants of health patterns, and it could not prove that unfavorable social factors caused the development of cardiovascular disease risk factors. Furthermore, language barriers may have been a factor for some participants because the National Heath Interview Surveys were only conducted in English and Spanish.

Study authors noted that it is vital to include more Asian Americans in national surveys to reveal potential differences in optimal social determinants of health profiles and cardiovascular risk factor prevalence and outcomes.

Co-authors, disclosures and funding sources are listed in the manuscript.

Source:

American Heart Association

Journal reference:

Zhu, A. L., et al. (2024) Social Determinants of Cardiovascular Risk Factors Among Asian American Subgroups. Journal of the American Heart Association. doi.org/10.1161/JAHA.123.032509.
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April 3, 2024
How free sugars affect human health

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In a recent review article published in Nutrients, researchers summarized the current evidence about the effect of free sugars on health outcomes in humans, including mood, cognition, cardiovascular disease, diabetes, and obesity.

They concluded that excessive consumption of added sugars may adversely affect health and overall well-being outcomes, highlighting the need for further research into how different carbohydrate forms affect diverse populations.

Study: The Impact of Free Sugar on Human Health—A Narrative Review. Image Credit: qoppi/Shutterstock.com

Background

Noncommunicable diseases (NCDs), including chronic conditions like heart disease and diabetes, are largely preventable but account for a significant portion of global deaths.

While researchers have emphasized lifestyle modifications to prevent and treat NCDs, with evidence suggesting that an improved diet yields significant benefits, the specific role of sugar consumption has been debated.

In the late 20th century, reduced fat consumption led to increased intake of carbohydrates and added sugars, notably high-fructose corn syrup. This coincided with rising obesity, diabetes, and heart disease rates.

Recent years saw a slight decline in sugar intake, prompted by health guidelines advocating limited daily sugar intake to mitigate health risks.

Some studies have linked excess consumption of sugar to various health issues. At the same time, other research indicates that sugar might not be inherently more harmful than other energy sources in the diet.

Effects of sugar on health

Global obesity rates have risen significantly over the past decades, with obesity linked to various NCDs. The debate over the primary cause of obesity—excess sugar, fat, or total calorie intake—continues, with recent declines in sugar consumption alongside persistent obesity rates suggesting generational effects.

Studies comparing low-carbohydrate and low-fat diets revealed varied results, highlighting the need for personalized dietary interventions.

Sugar consumption, particularly from fructose and sugary beverages, is associated with an increased risk of type 2 diabetes (T2DM) in numerous studies. However, findings are inconsistent, with some shorter-term studies failing to establish clear relationships.

Longer-term studies suggest a significant impact of fructose intake on insulin resistance and diabetes risk, especially in women. The protective effects of dietary fiber and certain fats on diabetes risk are also noted, indicating the complexity of dietary factors influencing T2DM.

The role of refined carbohydrates and sugary beverages in heart disease is increasingly recognized, with studies indicating their association with dyslipidemia and increased cardiovascular risk.

While some studies show a direct link between sugar consumption and heart disease, others find conflicting results, possibly due to differences in study duration and methodology.

Research suggests that sugars may play a detrimental role in cardiovascular health, although the specific types of carbohydrates and fats consumed may have different effects.

Chronic excessive sugar intake is hypothesized to impair cognitive function, with studies in animals and humans demonstrating neurological and cognitive impairments associated with high sugar consumption.

Maternal sugar consumption during pregnancy and breastfeeding may also impact offspring cognition.

While some studies suggest short-term cognitive benefits of sugar consumption, long-term effects are less clear and may be influenced by factors such as glucose control and dietary habits over time.

The impact of sugar on mood and behavior is debated, with inconsistent findings across studies. While short-term studies suggest potential mood benefits of sugar consumption, particularly following fasting, longer-term studies indicate correlations between high-sugar diets and depression, anxiety, and other mood disorders.

Confounders and methodological challenges complicate research on the relationship between added sugars and psychological health, warranting further investigation.

Underlying mechanisms

Chronic high sugar consumption is hypothesized to impact mood through neurological mechanisms. Western diets, high in sugar, are associated with inflammation, reduced BDNF in the hippocampus, and changes in dopamine signaling, resembling addictive behaviors.

Sugar consumption can dysregulate dopaminergic pathways, leading to increased sugar seeking and consumption, akin to addiction. Microbiome disruption, particularly by high sugar diets, exacerbates inflammation, contributing to obesity and neurodegeneration.

Sugar-induced dysbiosis may lead to gut permeability, triggering systemic inflammation and neuroinflammation, potentially explaining neurological and psychiatric impairments associated with sugar and obesity.

Conclusions

Minimal scientific evidence supports the claim that added dietary sugars confer health benefits; rather, a growing body of research indicates that they have negative effects, especially when consumption is excessive, prolonged, and high in fructose.

Glucose supplementation may be beneficial under certain circumstances but can also obtained from dietary sources, including whole grains, vegetables, and foods.

While not all added sugars need to be eliminated, nutritionists recommend limiting their intake to no more than 10% of total energy consumption.

The reviewers emphasized the need for further exploration of how different artificial sweeteners and macronutrients impact health outcomes and the challenges posed by sugar-related impairments.

While large-scale population studies may not be ideal for identifying individualized impacts, cohort studies and randomized controlled trials across diverse populations can yield insights into the precise effects of macronutrients and how they interact with each other to modify health outcomes.

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April 3, 2024