Gut-liver axis: Potential mechanisms of action of food-derived extracellular vesicles.

Food-derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non-gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non-gastrointestinal diseases via the gut-liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut-liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non-alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut-liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.

Medication and supplement pharmacokinetic changes following bariatric surgery: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements. METHODS: Systematic searches of bibliographic databases were conducted to identify studies. Pooled effect estimates from different surgical procedures were calculated using a random-effects model. RESULTS: Quantitative data were synthesized from 58 studies including a total of 1985 participants. Whilst 40 medications and 6 supplements were evaluated across these studies, heterogeneity and missing information reduced the scope of the meta-analysis to the following medications and supplements: atorvastatin, paracetamol, omeprazole, midazolam, vitamin D, calcium, zinc, and iron supplements. There were no significant differences in PK parameters post-surgery for the drugs atorvastatin and omeprazole, and supplements calcium, ferritin, and zinc supplements. Paracetamol showed reduced clearance (mean difference [MD] = -15.56 L/hr, p = 0.0002, I2 = 67%), increased maximal concentration (MD = 6.90 µg/ml, p = 0.006, I2 = 92%) and increased terminal elimination half-life (MD = 0.49 hr, p < 0.0001, I2 = 3%) post-surgery. The remaining 36 medications and 2 supplements were included in a systematic review. Overall, 18 of the 53 drugs and supplements showed post-operative changes in PK parameters. CONCLUSION: This study demonstrates heterogeneity in practice and could not reach conclusive findings for most PK parameters. Prospective studies are needed to inform best practice and enhance patient healthcare and safety following bariatric surgery.

The prognostic value of metabolic dysfunction-associated steatotic liver disease in acute myocardial infarction: A propensity score-matched analysis.

AIM: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. METHODS: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. RESULTS: In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs. 3.6%, p < .001) at 30 days, with unfavourable mortality rates sustained in the long-term (18.3% vs. 14.5%, p = .001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (hazard ratio 1.330, 95% confidence interval 1.106-1.598, p = .002). CONCLUSION: MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.

Type 2 diabetes mellitus and cardiometabolic outcomes in metabolic dysfunction-associated steatotic liver disease population.

The metabolic syndrome, characterized by type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, and obesity, collectively increases the risk of cardiovascular diseases. Nonalcoholic fatty liver disease (NAFLD) is a prominent manifestation, affecting over a third of the global population with a concerning annual increase in prevalence. Nearly 70 % of overweight individuals have NAFLD, and NAFLD-related deaths are predicted to rise, especially among young adults. The association of T2DM and NAFLD has led to the proposal of "metabolic dysfunction-associated steatotic liver disease" (MASLD) terminology, encompassing individuals with T2DM, overweight/obesity, hypertension, hypertriglyceridemia, or low HDL-cholesterol. Patients with MASLD will likely have double the risk of developing T2DM, and the combination of insulin resistance, overweight/obesity, and MASLD significantly elevates the risk of T2DM. Cardiovascular diseases remain the leading cause of mortality in the MASLD and T2DM population, with MASLD directly associated with coronary artery disease, compounded by coexisting insulin resistance and T2DM. Urgency lies in early detection of subclinical cardiovascular diseases among patients with T2DM and MASLD. Novel strategies targeting multiple pathways offer hope for effectively improving cardiometabolic health. Understanding and addressing the intertwined factors contributing to these disorders can pave the way towards better management and prevention of cardiometabolic complications.

Public acceptance of using artificial intelligence-assisted weight management apps in high-income southeast Asian adults with overweight and obesity: a cross-sectional study.

Introduction: With in increase in interest to incorporate artificial intelligence (AI) into weight management programs, we aimed to examine user perceptions of AI-based mobile apps for weight management in adults with overweight and obesity. Methods: 280 participants were recruited between May and November 2022. Participants completed a questionnaire on sociodemographic profiles, Unified Theory of Acceptance and Use of Technology 2 (UTAUT2), and Self-Regulation of Eating Behavior Questionnaire. Structural equation modeling was performed using R. Model fit was tested using maximum-likelihood generalized unweighted least squares. Associations between influencing factors were analyzed using correlation and linear regression. Results: 271 participant responses were analyzed, representing participants with a mean age of 31.56 ± 10.75 years, median (interquartile range) BMI, and waist circumference of 27.2 kg/m2 (24.2-28.4 kg/m2) and 86.4 (80.0-94.0) cm, respectively. In total, 188 (69.4%) participants intended to use AI-assisted weight loss apps. UTAUT2 explained 63.3% of the variance in our intention of the sample to use AI-assisted weight management apps with satisfactory model fit: CMIN/df = 1.932, GFI = 0.966, AGFI = 0.954, NFI = 0.909, CFI = 0.954, RMSEA = 0.059, SRMR = 0.050. Only performance expectancy, hedonic motivation, and the habit of using AI-assisted apps were significant predictors of intention. Comparison with existing literature revealed vast variabilities in the determinants of AI- and non-AI weight loss app acceptability in adults with and without overweight and obesity. UTAUT2 produced a good fit in explaining the acceptability of AI-assisted apps among a multi-ethnic, developed, southeast Asian sample with overweight and obesity. Conclusion: UTAUT2 model is recommended to guide the development of AI-assisted weight management apps among people with overweight and obesity.

The Global Epidemic of Metabolic Fatty Liver Disease.

PURPOSE OF REVIEW: The objective of this manuscript is to examine the current literature on the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD), its correlation with cardiovascular disease (CVD) outcomes, as well as to evaluate the update in nomenclature from non-alcoholic liver disease (NAFLD). RECENT FINDINGS: The update of diagnostic criteria from NAFLD to MASLD reduces the stigma associated with alcohol consumption and poor health choices. It also shines a light on the crucial role of cardiometabolic risk factors in disease pathophysiology. The incidence and prevalence of MASLD are projected to increase significantly in the future as the population burden of cardiometabolic risk factors rises. MASLD is also a potent risk factor for developing CVD that should be tackled by using a multi-disciplinary team with a holistic approach. As the new nomenclature for metabolic liver disease is adopted on a global scale, more research is needed to investigate the applicability of findings from previous trials focusing on NAFLD. It is anticipated that the epidemic of MASLD will continue to increase globally, hence the urgent need for therapeutic approaches to reverse this trend.

Efficacy and safety of tirzepatide, GLP-1 receptor agonists, and other weight loss drugs in overweight and obesity: a network meta-analysis.

OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of tirzepatide compared to glucagon-like peptide-1 receptor agonists (GLP-1 RA) and other weight loss drugs in the treatment of overweight and obesity. METHODS: MEDLINE, Embase, and Cochrane CENTRAL were searched for randomized controlled trials on tirzepatide, GLP-1 RA, and weight loss drugs approved by the US Food and Drug Administration. A network meta-analysis was performed, drawing direct and indirect comparisons between treatment groups. Network diagrams and surface under the cumulative ranking curve analysis were performed for primary (≥5%, ≥10%, ≥15%, absolute weight loss) and secondary outcomes and adverse effects. RESULTS: Thirty-one randomized controlled trials, involving more than 35,000 patients, were included in this study. Tirzepatide 15 mg ranked in the top three across weight-related parameters, glycemic profile (glycated hemoglobin), lipid parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and blood pressure. Tirzepatide 15 mg had the highest efficacy compared with placebo for achieving ≥15% weight loss (risk ratio 10.24, 95% CI: 6.42-16.34). As compared to placebo, tirzepatide and GLP-1 RA across all doses had significant increases in gastrointestinal adverse effects. CONCLUSIONS: The superiority of tirzepatide and GLP-1 RA in inducing weight loss and their ability to target multiple metabolic parameters render them promising candidates in the treatment of patients with overweight and obesity.

Anthropometric and cardiometabolic effects of polyphenols in people with overweight and obesity: an umbrella review.

CONTEXT: Polyphenols are plant-based compounds with potential anti-inflammatory, antioxidant, and anti-obesogenic properties. However, their effects on health outcomes remain unclear. OBJECTIVE: To evaluate the effects of polyphenols on anthropometric and cardiometabolic markers. DATA SOURCES: Six electronic databases-namely, EMBASE, CINAHL, PubMed, Scopus, The Cochrane Library (reviews only), and Web of Science-were searched for relevant systematic reviews with meta-analyses (SRMAs). DATA EXTRACTION: Three reviewers performed the data extraction via a data-extraction Microsoft Excel spreadsheet. DATA ANALYSIS: An umbrella review and meta-analysis of existing SRMAs was conducted. Eighteen SRMAs published from 2015 to 2023, representing 445 primary studies and 838 unique effect sizes, were identified. Meta-analyses were conducted using random-effects models with general inverse variance. Polyphenol-containing foods were found to significantly improve weight (-0.36 kg; 95% confidence interval [CI]: -0.62, 0.77 kg; P < 0.01, I2 = 64.9%), body mass index (-0.25 kg/m2; 95% CI: -0.34, -0.17 kg/m2; P < 0.001, I2 = 82.4%), waist circumference (-0.74 cm; 95% CI: -1.34, -0.15 cm; P < 0.01, I2 = 99.3%), low-density-lipoprotein cholesterol (-1.75 mg/dL; 95% CI: -2.56, -0.94; P < 0.001, I2 = 98.6%), total cholesterol (-1.23 mg/dL; 95% CI: -2.00, -0.46; P = 0.002, I2 = 94.6%), systolic blood pressure (-1.77 mmHg; 95% CI: -1.77, -0.93 mmHg; P < 0.001, I2 = 72.4%), diastolic blood pressure (-1.45 mmHg; 95% CI: -2.09, -0.80 mmHg; P < 0.001, I2 = 61.0%), fat percentage (-0.70%; 95% CI: -1.03, -0.36%; P < 0.001, I2 = 52.6%), fasting blood glucose (-0.18 mg/dL; 95% CI: -0.35, -0.01 mg/dL; P = 0.04, I2 = 62.0%), and C-reactive protein (CRP; including high-sensitivity-CRP [hs-CRP]) (-0.2972 mg/dL; 95% CI: -0.52, -0.08 mg/dL; P = 0.01, I2 = 87.9%). No significant changes were found for high-density-lipoprotein cholesterol (-0.12 mg/dL; 95% CI: -1.44, 0.69; P = 0.67, I2 = 89.4%) and triglycerides (-1.29 mg/dL; 95% CI: -2.74, 0.16; P = 0.08, I2 = 85.4%). Between-study heterogeneity could be explained by polyphenol subclass differences. CONCLUSION: The findings of this umbrella review support the beneficial effects of polyphenols on anthropometric and metabolic markers, but discretion is warranted to determine the clinical significance of the magnitude of the biomarker improvements. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews no. CRD42023420206.

The emergence of obesity in type 1 diabetes.

Obesity, a chronic low-grade inflammatory disease represented by multifactorial metabolic dysfunctions, is a significant global health threat for adults and children. The once-held belief that type 1 diabetes is a disease of people who are lean no longer holds. The mounting epidemiological data now establishes the connection between type 1 diabetes and the subsequent development of obesity, or vice versa. Beyond the consequences of the influx of an obesogenic environment, type 1 diabetes-specific biopsychosocial burden further exacerbates obesity. In the course of obesity management discussions, recurring challenges surfaced. The interplay between weight gain and escalating insulin dependence creates a vicious cycle from which patients struggle to break free. In the absence of weight management guidelines and regulatory approval for this population, healthcare professionals must navigate the delicate balance between benefits and risks. The gravity of this circumstance highlights the importance of bringing these topics to the forefront. In this Review, we discuss the changing trends and the biopsychosocial aspects of the intersection between type 1 diabetes and obesity. We highlight the evidence supporting the therapeutic means (i.e., exercise therapy, nutritional therapy, adjunct pharmacotherapy, and bariatric surgery) and directions for establishing a more robust and safer evidence-based approach.

Trends in Cardiovascular Mortality Among Patients With Alzheimer's Disease in the United States from 1999 to 2020.

This study aimed to compare the trends in cardiovascular diseases (CVDs)-related mortality in patients with Alzheimer's disease (AD) and in the general population aged ≥65 years. Data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research Multiple Cause of Death dataset were used to determine national trends in age-adjusted CVD mortality rates (AAMR) and average annual percent change (AAPC) values in patients with AD and the overall population aged ≥65 years from 1999 to 2020. Data for AAMR and AAPCs were also stratified by age, gender, ethnicity/race, geographical region, urbanization status, and subgroups of CVD. Trends in the overall AAMR stratified by gender, age, ethnicity/race, geographical region, urbanization status, and CVD subgroups were statistically different between patients with AD and the overall population (overall AAPC for CVD mortality rate in patients with AD = -3.5% [confidence interval -4.1% to -2.9%] vs -2.6% [confidence interval -2.3% to -2.9%] in overall population, p = 0.01). Differences in the decrease in the mortality rates between patients with AD and the overall population were found to be statistically different across all stratifications except for the change in the mortality rates for hypertensive diseases (p = 0.05), females (p = 0.2), and Asian or Pacific Islanders (p = 0.09). In conclusion, CVD-related mortality in patients with AD decreased over the last 2 decades, and decreases were more prominent than seen in the general population aged ≥65 years. These results may help focus public health efforts to optimize CVD health in patients with AD.

Immune Activation Mediates the Association of Advanced Hepatic Fibrosis With Adverse Outcomes in Patients With Coronary Artery Disease.

BACKGROUND: Literature suggests a bidirectional association between advanced hepatic fibrosis (AHF) and coronary artery disease (CAD). We evaluated the association of AHF with immune activation, systemic inflammation, and adverse outcomes in patients with CAD. METHODS AND RESULTS: A fibrosis-4 index cutoff value ≥2.67 was used to define AHF. Circulating levels of soluble urokinase plasminogen activator receptor and hsCRP (high-sensitivity C-reactive protein) were measured as markers for immune activation and systemic inflammation, respectively. The relationship of AHF with soluble urokinase plasminogen activator receptor, hsCRP, and adverse cardiovascular outcomes was evaluated. Among 3406 participants with CAD, 479 had AHF. Participants with AHF were older; were less likely to be Black individuals; and had a lower body mass index, worse renal function, and a prior history of heart failure. In multivariable linear regression models adjusted for clinical and demographic confounders, participants with AHF had 15.6% higher soluble urokinase plasminogen activator receptor and 24.0% higher hsCRP levels. They were more likely to experience the following adverse outcomes: all-cause death (adjusted hazard ratio [HR], 1.57 ([95% CI, 1.29-1.92]; P<0.001) and cardiovascular death: (subdistribution HR, 1.50 [95% CI, 1.14-1.95]; P=0.003). Mediation analysis showed that 47.0% (95% CI, 13.6%-81.2%]; P=0.006) of the indirect effect of AHF on cardiovascular death was mediated by circulating soluble urokinase plasminogen activator receptor levels. CONCLUSIONS: AHF is independently associated with immune activation, systemic inflammation, and adverse cardiovascular outcomes in patients with CAD. The association of AHF with adverse outcomes is partly mediated by immune activation, and targeting this pathway may help reduce the residual risk in patients with CAD.

Cardiovascular Health Metrics Differ Between Individuals With and Without Cancer.

BACKGROUND: Although individuals with cancer experience high rates of cardiovascular morbidity, there are limited data on the potential differences in cardiovascular health (CVH) metrics between individuals with and without cancer. METHODS AND RESULTS: The National Health and Nutrition Examination Survey between 2015 and 2020 was queried to evaluate the prevalence of health metrics that comprise the American Heart Association Life's Essential 8 construct of cardiovascular health among adult individuals with and without cancer in the United States. Health metric scores were also evaluated according to important patient demographics including age, sex, race and ethnicity, and socioeconomic status. Among 4370 participants representing >180 million US adults, 9.4% had a history of cancer. Individuals with cancer had lower overall cardiovascular health scores (67.1 versus 69.1, P<0.001) compared with individuals without cancer. Among individual components of the cardiovascular health score, those with cancer had better health scores on key behaviors including physical activity, diet, and sleep compared with those without cancer, although variation was noted based on age. Higher scores on these modifiable health behaviors among those with cancer compared with those without cancer were noted in older individuals, in White individuals compared with other races and ethnicities, and in individuals with higher socioeconomic status. CONCLUSIONS: We highlight important variations in simple cardiovascular health metrics among individuals with cancer compared with individuals without cancer and demonstrate differences among health metrics based on age, race and ethnicity, and socioeconomic status. These findings may explain ongoing racial, ethnic, and socioeconomic status disparities in the cancer population and provide a framework for optimizing cardiovascular health among individuals with cancer.

Biomarkers of Hepatic Dysfunction and Cardiovascular Risk.

PURPOSE OF REVIEW: The objective of this manuscript is to examine the current literature on non-alcoholic fatty liver disease (NAFLD) biomarkers and their correlation with cardiovascular disease (CVD) outcomes and cardiovascular risk scores. RECENT FINDINGS: There has been a growing appreciation for an independent link between NAFLD and CVD, culminating in a scientific statement by the American Heart Association in 2022. More recently, studies have begun to identify biomarkers of the three NAFLD phases as potent predictors of cardiovascular risk. Despite the body of evidence supporting a connection between hepatic biomarkers and CVD, more research is certainly needed, as some studies find no significant relationship. If this relationship continues to be robust and readily reproducible, NAFLD and its biomarkers may have an exciting role in the future of cardiovascular risk prediction, possibly as risk-enhancing factors or as components of novel cardiovascular risk prediction models.

Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort.

Background: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. Methods: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. Findings: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. Interpretation: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. Funding: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore.

Response to Paik et al. on the disease burden of NAFLD.

Chew and Ng et al. recently reported on the global burden of metabolic disease by utilizing estimates from the Global Burden of Disease (GBD) study. Herein, they respond to critical points highlighted by Paik et al. regarding the limitations of the GBD database as well as the definitions employed in the study.

Injectable liposomal docosahexaenoic acid alleviates atherosclerosis progression and enhances plaque stability.

Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of lipids and immune cells in plaques built up inside artery walls. Docosahexaenoic acid (DHA, 22:6n-3), an omega-3 polyunsaturated fatty acid (PUFA), which exerts anti-inflammatory and antioxidant properties, has long been purported to be of therapeutic benefit to atherosclerosis patients. However, large clinical trials have yielded inconsistent data, likely due to variations in the formulation, dosage, and bioavailability of DHA following oral intake. To fully exploit its potential therapeutic effects, we have developed an injectable liposomal DHA formulation intended for intravenous administration as a plaque-targeted nanomedicine. The liposomal formulation protects DHA against chemical degradation and increases its local concentration within atherosclerotic lesions. Mechanistically, DHA liposomes are readily phagocytosed by activated macrophages, exert potent anti-inflammatory and antioxidant effects, and inhibit foam cell formation. Upon intravenous administration, DHA liposomes accumulate preferentially in atherosclerotic lesional macrophages and promote polarization of macrophages towards an anti-inflammatory M2 phenotype, resulting in attenuation of atherosclerosis progression in both ApoE-/- and Ldlr-/- experimental models. Plaque composition analysis demonstrates that liposomal DHA inhibits macrophage infiltration, reduces lipid deposition, and increases collagen content, thus improving the stability of atherosclerotic plaques against rupture. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) further reveals that DHA liposomes can partly restore the complex lipid profile of the plaques to that of early-stage plaques. In conclusion, DHA liposomes offer a promising approach for applying DHA to stabilize atherosclerotic plaques and attenuate atherosclerosis progression, thereby preventing atherosclerosis-related cardiovascular events.

Impact of the COVID-19 Pandemic on Diabetes-Related Cardiovascular Mortality in the United States.

Background In the past few decades, diabetes-related cardiovascular mortality has been steadily declining. However, the impact of the COVID19 pandemic on this trend has not been previously defined. Methods and Results Diabetes-related cardiovascular mortality data were extracted for each year between 1999 and 2020 from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database. Regression analysis was used to calculate the trend in the 2 decades before the pandemic (1999-2019) and thereby estimate the excess cardiovascular mortality in 2020. There was a 29.2% fall in the diabetes-related cardiovascular age-adjusted mortality rate between 1999 to 2019, largely driven by a 41% decrease in ischemic heart disease deaths. In comparison to 2019, there was an overall 15.5% increase in the diabetes-related cardiovascular age-adjusted mortality rate in the first year of the pandemic, mainly due to a 14.1% rise in ischemic heart disease deaths. Younger patients (under 55 years) and the Black population experienced the greatest increase in diabetes-related cardiovascular age-adjusted mortality rate (24.0% and 25.3%, respectively). Trend analysis estimated 16 009 excess diabetes-related cardiovascular deaths in 2020, with the majority due to ischemic heart disease (8504). Black and Hispanic or Latino populations had at least one-fifth of their 2020 diabetes-related cardiovascular age-adjusted mortality rate as excess deaths (22.3% and 20.2%, respectively). Conclusions There was a sharp rise in diabetes-related cardiovascular mortality during the first pandemic year. Black, Hispanic or Latino, and young people showed the largest increases in diabetes-related cardiovascular mortality. Targeted health policies could help address the disparities observed in this analysis.