The prevalence of metabolically healthy obesity and its transition into the unhealthy state: A 5-year follow-up study.

People with metabolically healthy obesity (MHO) are at risk of developing cardiometabolic diseases. We investigated the prevalence of MHO and factors influencing its transition into a metabolically unhealthy state (MUS). This study was conducted as part of the Kerman Coronary Artery Disease Risk Factor Study (KERCADRS). From 2014 to 2018, 9997 people were evaluated. The obesity and metabolic status of the MHO participants were re-examined after 5 years of their initial participation in the study. Out of 347 MHO, 238 individuals were accessed at follow-up. Twenty-nine (12.2%) had metabolic unhealthy normal weight (MUNW), 169 (71.0%) had metabolic unhealthy obesity (MUO), and the others had healthy metabolic state. Among age, total cholesterol, diastolic blood pressure and triglyceride (TG) variables, the baseline serum TG level was associated with a significant increase in the risk of developing MUS during 5 years (p <.05). The TG level optimal cut-off point for predicting the development into MUS was 107 mg/dL with 62.1% sensitivity and 77.5% specificity (AUC = 0.734, p <.001). A high percentage of MHO people transit into MUS during 5 years. A TG level higher than 107 mg/dL can help to identify people at a higher risk of developing into MUS.

Protocol for a Study Investigating Context-Specific Sedentary Behaviors and Cardiometabolic Health in College-Based Young Adults (CONTEXT-SB).

Background: Sedentary behavior (SB) is detrimental to cardiometabolic disease (CMD) risk, which can begin in young adulthood. To devise effective SB-CMD interventions in young adults, it is important to understand which context-specific sedentary behaviors (CS-SB) are most detrimental for CMD risk, the lifestyle behaviors that co-exist with CS-SBs, and the socioecological predictors of CS-SB. Methods: This longitudinal observational study will recruit 500 college-aged (18-24 years) individuals. Two laboratory visits will occur, spaced 12 months apart, where a composite CMD risk score (e.g., arterial stiffness, metabolic and inflammatory biomarkers, heart rate variability, and body composition) will be calculated, and questionnaires to measure lifestyle behaviors and different levels of the socioecological model will be administered. After each visit, total SB (activPAL) and CS-SB (television, transportation, academic/ occupational, leisure computer, "other"; ecological momentary assessment) will be measured across seven days. Discussion: It is hypothesized that certain CS-SB will show stronger associations with CMD risk, compared to T-SB, even after accounting for coexisting lifestyle behaviors. It is expected that a range of intra-individual, inter-individual, and physical environment socioecological factors will predict CS-SB. The findings from this study will support the development of an evidence-based, multi-level intervention to target SB reduction and mitigate CMD risk in CBYA.

Mediterranean Diet Information on TikTok and Implications for Digital Health Promotion Research: Social Media Content Analysis.

BACKGROUND: The Mediterranean diet has been linked to reduced risk for several cardiometabolic diseases. The lack of a clear definition of the Mediterranean diet in the scientific literature and the documented proliferation of nutrition misinformation on the internet suggest the potential for confusion among consumers seeking web-based Mediterranean diet information. OBJECTIVE: We conducted a social media content analysis of information about the Mediterranean diet on the influential social media platform, TikTok, to examine public discourse about the diet and identify potential areas of misinformation. We then analyzed these findings in the context of health promotion to identify potential challenges and opportunities for the use of TikTok in promoting the Mediterranean diet for healthy living. METHODS: The first-appearing 202 TikTok posts that resulted from a search of the hashtag #mediterraneandiet were downloaded and qualitatively examined. Post features and characteristics, poster information, and engagement metrics were extracted and synthesized across posts. Posts were categorized as those created by health professionals and those created by nonhealth professionals based on poster-reported credentials. In addition to descriptive statistics of the entire sample, we compared posts created by professionals and nonprofessionals for content using chi-square tests. RESULTS: TikTok posts varied in content, but posts that were developed by health professionals versus nonprofessionals were more likely to offer a definition of the Mediterranean diet (16/106, 15.1% vs 2/96, 2.1%; P=.001), use scientific citations to support claims (26/106, 24.5% vs 0/96, 0%; P<.001), and discuss specific nutrients (33/106, 31.1% vs 6/96, 6.3%; P<.001) and diseases related to the diet (27/106, 25.5% vs 5/96, 5.2%; P<.001) compared to posts created by nonhealth professionals. CONCLUSIONS: Social media holds promise as a venue to promote the Mediterranean diet, but the variability in information found in this study highlights the need to create clear definitions about the diet and its components when developing Mediterranean diet interventions that use new media structures.

Contribution of circulating Mfge8 to human T2DM and cardiovascular disease.

MFGE8 is a major exosome (EV) protein known to mediate inflammation and atherosclerosis in type 2 diabetes mellitus (T2DM) in animal studies. The pathophysiological role of this protein in obesity, T2DM, and cardiovascular disease is less investigated in humans. Earlier we reported a rare Asian Indian population-specific missense variant (rs371227978; Arg148His) in the MFGE8 gene associated with increased circulating Mfge8 and T2DM. We have further investigated the role of Mfge8 with T2DM risk in additional Asian Indians (n = 4897) and Europeans and other multiethnic cohorts from UK Biobank (UKBB) (n = 455,808) and the US (n = 1150). We also evaluated the exposure of Mfge8-enriched human EVs in zebrafish (ZF) for their impact on cardiometabolic organ system. Most individual carriers of Arg148His variant not only had high circulating Mfge8 but also revealed a positive significant correlation with glucose (r = 0.42; p = 4.9 × 10-04), while the non-carriers showed a negative correlation of Mfge8 with glucose (r = -0.38; p = 0.001) in Asian Indians. The same variant was monomorphic in non-South Asian ethnicities. Even without the variant, serum Mfge8 correlated significantly with blood glucose in other non-South Asian ethnicities (r = 0.47; p = 2.2 × 10-13). Since Mfge8 is an EV marker, we tested the exposure of Mfge8-enriched human EVs to ZF larvae as an exploratory study. The ZF larvae showed rapid effects on insulin-sensitive organs, developing fatty liver disease, heart hypertrophy and exhibiting redundant growth with poor muscular architecture with and without the high-fat diet (HFD). In contrast, the control group fishes developed fatty liver disease and heart hypertrophy only after the HFD feeding. Backed with strong support from animal studies on the role of Mfge8 in obesity, insulin resistance, and atherosclerosis, the current research suggests that circulating Mfge8 may become a potential marker for predicting the risk of T2DM and cardiovascular disease in humans.

Metformin use correlated with lower risk of cardiometabolic diseases and related mortality among US cancer survivors: evidence from a nationally representative cohort study.

BACKGROUND: In the USA, the prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce. METHODS: A prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants' levels of oxidative stress. To evaluate the correlations between metformin use and the risk of cardiometabolic diseases and related mortality, survival analysis of cardiometabolic mortality was performed by Cox proportional hazards model, and cross-sectional analysis of cardiometabolic diseases outcomes was performed using logistic regression models. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin. RESULTS: Among 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47-0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44-0.97) mortality compared with metformin nonusers. Metformin use was also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28-0.59), stroke (OR, 0.44; 95% CI, 0.26-0.74), hypertension (OR, 0.27; 95% CI, 0.14-0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21-0.78). The observed inverse associations were consistent across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analyses suggested that metformin use as compared to non-use may counter-balance oxidative stress. CONCLUSIONS: In this cohort study involving a nationally representative population of US cancer survivors, metformin use was significantly correlated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.

In Utero Exposure to Maternal SARS-CoV-2 Infection Is Associated With Higher Left Ventricular Mass in Toddlers.

The intrauterine environment plays a critical role in shaping chronic disease risk over the life course. We prospectively evaluated cardiometabolic outcomes in toddlers born to mothers with versus without prenatal severe acute respiratory syndrome coronavirus 2 infection. Children with in utero severe acute respiratory syndrome coronavirus 2 exposure had higher left ventricular mass in association with altered maternal immunologic indices.

Cardiometabolic Co-morbidity Burden and Circulating Biomarkers in Patients With Chronic Coronary Disease in the ISCHEMIA Trials.

Cardiometabolic co-morbidities, diabetes (DM), hypertension (HTN), and obesity contribute to cardiovascular disease. Circulating biomarkers facilitate prognostication for patients with cardiovascular disease. We explored the relation between cardiometabolic co-morbidity burden in patients with chronic coronary disease and biomarkers of myocardial stretch, injury, inflammation, and platelet activity. We analyzed participants from the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trials biorepository with plasma biomarkers (N-terminal probrain natriuretic peptide, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, soluble CD40 ligand, and growth differentiation factor-15) and clinical risk factors (hemoglobin A1c [HbA1c], systolic blood pressure [SBP], and body mass index [BMI]) at baseline. We defined cardiometabolic co-morbidities as DM, HTN, and obesity at baseline. Co-morbidity burden is characterized by the number and severity of co-morbidities. Controlled co-morbidities were defined as HbA1c <7% for those with DM, SBP <130 mm Hg for those with HTN, and BMI <30 kg/m2. Severely uncontrolled was defined as HbA1c ≥8%, SBP ≥160 mm Hg, and BMI ≥35 kg/m2. We performed linear regression analyses to examine the association between co-morbidity burden and log-transformed biomarker levels, adjusting for age, gender, estimated glomerular filtration rate controlled for hemodialysis, and left ventricular ejection fraction. A total of 752 participants (mean age 66 years, 19% women, 84% White) were included in this analysis. Self-reported Black race, current smokers, history of myocardial infarction, and heart failure had a greater cardiometabolic co-morbidity burden. The presence of ≥1 severely uncontrolled co-morbidity was associated with significantly higher baseline levels of high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, and growth differentiation factor-15 than participants with no co-morbidities. In conclusion, increasing cardiometabolic co-morbidity burden in patients with chronic coronary disease is associated with higher levels of circulating biomarkers of myocardial injury and inflammation.

Circulating TMAO, the gut microbiome and cardiometabolic disease risk: an exploration in key precursor disorders.

BACKGROUND: Elevations in the gut metabolite trimethylamine-N-oxide (TMAO) have been linked to cardiovascular and metabolic diseases. Whether elevated TMAO levels reflect early mechanistic involvement or a sequela of evolving disease awaits elucidation. The purpose of this study was to further explore these potential associations. METHODS: We investigated relationships between circulating levels of TMAO and its pre-cursor substrates, dietary factors, gut microbiome profiles and disease risk in individuals with a Healthy BMI (18.5 < BMI < 25, n = 41) or key precursor states for cardiometabolic disease: Overweight (25 < BMI < 30 kg/m2, n = 33), Obese (BMI > 30, n = 27) and Metabolic Syndrome (MetS; ≥ 3 ATPIII report criteria, n = 39). RESULTS: Unexpectedly, plasma [TMAO] did not vary substantially between groups (means of 3-4 µM; p > 0.05), although carnitine was elevated in participants with MetS. Gut microbial diversity and Firmicutes were also significantly reduced in the MetS group (p < 0.05). Exploratory analysis across diverse parameters reveals significant correlations between circulating [TMAO] and seafood intake (p = 0.007), gut microbial diversity (p = 0.017-0.048), and plasma [trimethylamine] (TMA; p = 0.001). No associations were evident with anthropometric parameters or cardiometabolic disease risk. Most variance in [TMAO] within and between groups remained unexplained. CONCLUSIONS: Data indicate that circulating [TMAO] may be significantly linked to seafood intake, levels of TMA substrate and gut microbial diversity across healthy and early disease phenotypes. However, mean concentrations remain < 5 µM, with little evidence of links between TMAO and cardiometabolic disease risk. These observations suggest circulating TMAO may not participate mechanistically in cardiometabolic disease development, with later elevations likely a detrimental sequela of extant disease.

Polycystic ovary syndrome: A review of diagnosis and management, with special focus on atherosclerotic cardiovascular disease prevention.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy worldwide with a heterogeneous clinical presentation including reproductive, metabolic, and endocrine elements. However, the assessment and management of PCOS remains inconsistent, with many women undiagnosed and untreated. We now also understand that the management of PCOS should extend throughout a woman's lifespan as many elements of the syndrome persist after menopause. Management has traditionally focused on the treatment of hyperandrogenism and oligomenorrhea. Women with PCOS often have dyslipidemia, hypertension, obesity, and metabolic syndrome, which may be worsened by the hormonal abnormalities, and are therefore at higher risk for cardiovascular disease morbidity and mortality, a risk that increases after menopause. While treatment with hormonal therapy, in particular combined oral contraceptives, may improve cardiovascular risk factors, management plans should incorporate specific diagnosis and management of these factors, if present, because of the strong contribution to the risk for atherosclerotic cardiovascular disease (ASCVD). Given the complexities of the syndrome, optimal management often requires a multi-disciplinary approach including the lipid and cardiometabolic specialist to provide counseling and support for lifestyle modification along with pharmacologic therapy as indicated to address the full range of any reproductive, endocrine, and cardiometabolic abnormalities.

Vitamin D deficiency: A forgotten aspect in sleep disorders? A critical update.

Over the past few years, there has been a surge in interest regarding the connection between sleep duration and quality, sleep disorders, mainly Obstructive sleep apnoea (OSA) and Vitamin D. There is growing evidence to support a new role of Vitamin D in the maintenance and regulation of optimal sleep. Furthermore, a notable link has been identified between OSA and a decrease in serum Vitamin D levels, which appears to intensify as the severity of sleep apnea worsens. Vitamin D status could also potentially serve as a mediator or provide an explanation for the association between OSA and cardiometabolic morbidity, but the current state of research in this area is inadequate. Studies have indicated that the supplementation of Vitamin D can optimize sleep quality, presenting more proof of the connection between insufficient vitamin D levels and sleep disorders. However, it is unclear whether low serum Vitamin D levels are a contributing factor to OSA development or if OSA predisposes individuals to Vitamin D deficiency. As a result, various studies have endeavored to examine the complex relationship between OSA and Vitamin D deficiency. In children and adolescents, while data is limited, there seems also to be a link between sleep disorders and Vitamin D levels. Therefore, the objective of this review is to provide a comprehensive overview of the current evidence on the association between Vitamin D and sleep disorders in both adults and children.

Protocol of the HARMONY study: A culturally relevant, randomized-controlled, stress management intervention to reduce cardiometabolic risk in African American women.

BACKGROUND: African American Women (AAW) are at high risk for stress-related cardiometabolic (CM) conditions including obesity, heart disease, and diabetes. Prior interventions lack attention to culturally-nuanced stress phenomena (Superwoman Schema [SWS], contextualized stress, and network stress), which are positively and significantly associated with unhealthy eating and sedentary behavior. PURPOSE: The HARMONY Study is designed to test a culturally tailored mindfulness-based stress management intervention to address SWS, contextualized stress, and network stress as potential barriers to adherence to healthy exercise and eating goals. The study will help AAW build on their strengths to promote cardiometabolic health by enhancing positive reappraisal, self-regulation, and self-efficacy as protective factors against chronic stress-inducing biobehavioral morbidity and mortality risk. METHODS: This two-arm, randomized-controlled trial will test the effects of two group-based, online interventions. HARMONY 1 includes culturally-tailored exercise and nutrition education. HARMONY 2 includes mindfulness-based stress reduction, exercise, and nutrition education. We aim to recruit 200 AAW ≥ 18 years old with CM risk. RESULTS: Primary outcomes (actigraphy and carotenoid levels) and secondary outcomes (body composition, inflammatory markers, glucose metabolism, and stress) are being collected at baseline and 4-, 8-, and 12-months post-intervention. Intent-to-treat, data analytic approaches will be used to test group differences for the primary outcomes. DISCUSSION: This study is the first to address culturally-nuanced stress phenomena in AAW (SWS, network stress, and contextualized stress) using culturally-tailored stress management, exercise, and nutrition educational approaches to reduce biobehavioral CM risk among AAW. Quantitative and qualitative results will inform the development of scalable and sustainable CM risk-reduction programming for AAW. TRIAL REGISTRATION: The Multiple PIs registered the clinical trial (Identifier: NCT04705779) and reporting of summary results in ClinicalTrials.gov in accordance with the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information, within the required timelines.

Associations of sedentary behavior and screen time with biomarkers of inflammation and insulin resistance.

Sedentary behavior (SB) has been linked to risk factors of cardiometabolic disease, with inconsistent findings reported in the literature. We aimed to assess the associations of SB with multiple biomarkers of inflammation and insulin resistance in adults. Domain-specific SB, sitting time and moderate-to-vigorous physical activity (MVPA) were measured in 78 adults (mean ± SD 52.0 ± 10.8 y). Body fat percentage (BF%) was assessed using multi-frequency bioelectrical impedance. A blood draw assessed glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, and adiponectin. Adiponectin-leptin ratio (ALR), homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß) were calculated. Multivariable linear regression analyses, controlling for age, sex, MVPA, and BF%, were used to assess associations. After adjustment for age, sex and MVPA, total SB (7.5 ± 2.5 h/day) was positively associated with leptin, insulin, HOMA-IR, HOMA-ß (Standardized Beta (ß) range 0.21-0.32) and negatively associated with ALR (ß = -0.24, p < 0.05 for all). Similarly, total sitting time (7.2 ± 2.9 h/day) was associated with TNF-α (ß = 0.22) and ALR (ß = -0.26). These associations were attenuated to non-significance after adjustment for BF%. Leisure screen time was detrimentally associated with IL-6 (ß = 0.24), leptin (ß = 0.21), insulin (ß = 0.37), HOMA-IR (ß = 0.37), and HOMA-ß (ß = 0.34), independent of age, sex and MVPA (p < 0.05 for all). Only the associations with insulin (ß = 0.26), HOMA-IR (ß = 0.26), and HOMA-ß (ß = 0.23) remained significant after further controlling BF% (p < 0.05). Self-reported SB is associated with biomarkers of inflammation and insulin resistance, independent of MVPA, and in some cases BF%.

Substitution of Dairy Products and Risk of Death and Cardiometabolic Diseases: A Systematic Review and Meta-Analysis of Prospective Studies.

Substitution models in epidemiologic studies specifying both substitute and substituted food in relation to disease risk may be useful to inform dietary guidelines. A systematic review of prospective observational studies was performed to quantify the risks of all-cause mortality, cardiovascular disease, and type 2 diabetes (T2D) associated with the substitution of dairy products with other foods and between different dairy products. We systematically searched MEDLINE, Embase, and Web of Science until 28th June, 2023. We calculated summary relative risks (SRRs) and 95% confidence intervals (95% CI) in random-effects meta-analyses. We assessed the risk of bias with the Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool and certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach. Fifteen studies (with 34 publications) were included. There was moderate CoE that the substitution of low-fat dairy with red meat was associated with a higher risk of mortality, coronary artery disease, and T2D [SRR (95% CI): 1.11 (1.06, 1.16), 1.13 (1.08, 1.18), and 1.20 (1.16, 1.25)]. A higher risk of mortality and T2D was also observed when substituting low-fat dairy with processed meat [SRR (95% CI): 1.19 (1.11, 1.28) and 1.41 (1.33, 1.49); moderate CoE]. A lower mortality risk was associated with the substitution of dairy and yogurt with whole grains [SRR (95% CI): 0.89 (0.84, 0.93) and 0.91 (0.85, 0.97)], and butter with olive oil [SRR (95% CI): 0.94 (0.92, 0.97); all moderate CoE]. Mainly no associations were observed when substituting dairy products against each other on disease and mortality risk. Our findings indicate associations between substituting dairy with red or processed meat and higher disease risk, whereas its substitution with whole grains was associated with a lower risk. However, there is little robust evidence that substituting whole-fat with low-fat dairy is associated with disease risk. (CRD42022303198).

Heart rate variability to track autonomic nervous system health in young children: Effects of physical activity and cardiometabolic risk factors.

Evidence for a key role of dysregulated autonomic nervous system (ANS) activity in maladaptive stress response/recovery and non-communicable disease development is extensive. Monitoring ANS activity via regular heart rate variability (HRV) measurement is growing in popularity in adult populations given that low HRV has been associated with ANS dysregulation, poor stress response/reactivity, increased cardiometabolic disease risk and early mortality. Although cardiometabolic disease may originate in early life, regular HRV measurement for assessing ANS activity in childhood populations, especially those consisting of children < 6 years of age, remains largely unpractised. A greater understanding of ANS activity modifiers in early life may improve analysis and interpretation of HRV measurements, thereby optimising its usefulness. Taking into consideration that HRV and ANS activity can be improved via daily engagement in physical activity (PA), this review will discuss the ANS and HRV, ANS activity modifiers, cardiometabolic disease risk factors and PA as they relate to childhood/adolescent populations (≤ 18 years old).

Reproductive factors and cardiometabolic disease among middle-aged and older women: a nationwide study from CHARLS.

Background: Cardiometabolic disease is skyrocketing to epidemic proportions due to the high prevalence of its components and the aging of the worldwide population. More efforts are needed to improve cardiometabolic health. The aim of this nationally representative study based on the China Health and Retirement Longitudinal Study (CHARLS, 2014-2018) was to examine the association between reproductive factors and cardiometabolic disease among Chinese women aged ≥45 years. Methods: The CHARLS is an ongoing longitudinal study initiated in 2011, and the latest follow-up was completed in 2018. In total, 6,407 participants were analyzed. Effect-sizes are expressed as odds ratios (OR) and 95% confidence intervals (CI). Confounding was considered from statistical adjustment, subsidiary exploration, and unmeasured confounding assessment aspects. Results: Of 6,407 accessible participants, 60.9% were recorded as having one or more of five predefined cardiovascular or metabolic disorders. Compared to those with two children, participants who had 0-1 child were found to have a lower risk of cardiometabolic disease (OR = 0.844, 95% CI: 0.714-0.998), and those who had ≥3 children had a greater risk (OR = 1.181, 95% CI: 1.027-1.357). Age at menarche of 16-18 years was a protective factor compared with ≤16 years of age (OR = 0.858, 95% CI: 0.749-0.982). In contrast, participants with a history of abortion were 1.212 times more likely to have cardiometabolic disorders (OR = 1.212, 95% CI: 1.006-1.465). The likelihood for the presence of unmeasured confounding was low, as reflected by E-values. Conclusions: Our findings demonstrate that number of children, age at menarche, and history of abortion were associated with a significant risk of cardiometabolic disease among Chinese women aged ≥45 years.

Lipotoxicity as a therapeutic target in obesity and diabetic cardiomyopathy.

Unhealthy sources of fats, ultra-processed foods with added sugars, and a sedentary lifestyle make humans more susceptible to developing overweight and obesity. While lipids constitute an integral component of the organism, excessive and abnormal lipid accumulation that exceeds the storage capacity of lipid droplets disrupts the intracellular composition of fatty acids and results in the release of deleterious lipid species, thereby giving rise to a pathological state termed lipotoxicity. This condition induces endoplasmic reticulum stress, mitochondrial dysfunction, inflammatory responses, and cell death. Recent advances in omics technologies and analytical methodologies and clinical research have provided novel insights into the mechanisms of lipotoxicity, including gut dysbiosis, epigenetic and epitranscriptomic modifications, dysfunction of lipid droplets, post-translational modifications, and altered membrane lipid composition. In this review, we discuss the recent knowledge on the mechanisms underlying the development of lipotoxicity and lipotoxic cardiometabolic disease in obesity, with a particular focus on lipotoxic and diabetic cardiomyopathy.

Cardiometabolic Disease Staging and Major Adverse Cardiovascular Event Prediction in 2 Prospective Cohorts.

BACKGROUND: Cardiometabolic risk prediction models that incorporate metabolic syndrome traits to predict cardiovascular outcomes may help identify high-risk populations early in the progression of cardiometabolic disease. OBJECTIVES: The purpose of this study was to examine whether a modified cardiometabolic disease staging (CMDS) system, a validated diabetes prediction model, predicts major adverse cardiovascular events (MACE). METHODS: We developed a predictive model using data accessible in clinical practice [fasting glucose, blood pressure, body mass index, cholesterol, triglycerides, smoking status, diabetes status, hypertension medication use] from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study to predict MACE [cardiovascular death, nonfatal myocardial infarction, and/or nonfatal stroke]. Predictive performance was assessed using receiver operating characteristic curves, mean squared errors, misclassification, and area under the curve (AUC) statistics. RESULTS: Among 20,234 REGARDS participants with no history of stroke or myocardial infarction (mean age 64 ± 9.3 years, 58% female, 41% non-Hispanic Black, and 18% diabetes), 2,695 developed incident MACE (13.3%) during a median 10-year follow-up. The CMDS development model in REGARDS for MACE had an AUC of 0.721. Our CMDS model performed similarly to both the ACC/AHA 10-year risk estimate (AUC 0.721 vs 0.716) and the Framingham risk score (AUC 0.673). CONCLUSIONS: The CMDS predicted the onset of MACE with good predictive ability and performed similarly or better than 2 commonly known cardiovascular disease prediction risk tools. These data underscore the importance of insulin resistance as a cardiovascular disease risk factor and that CMDS can be used to identify individuals at high risk for progression to cardiovascular disease.

Increased Risk of Cardiometabolic Disease in Ideal Weight Adults With History of Overweight/Obesity in China: A Prospective Cohort Study.

BACKGROUND: Overweight and obesity represent critical modifiable determinants in the prevention of cardiometabolic disease (CMD). However, the long-term impact of prior overweight/obesity on the risk of CMD in later life remains unclear. We aimed to investigate the association between longitudinal transition of body mass index (BMI) status and incident CMD. METHODS AND RESULTS: This prospective cohort study included 57 493 CMD-free Chinese adults from the Kailuan Study. BMI change patterns were categorized according to the BMI measurements obtained during the 2006 and 2012 surveys. The primary end point was a composite of myocardial infarction, stroke, and type 2 diabetes. Cox regression models were used to evaluate the associations of transitions in BMI with overall CMD events and subtypes, with covariates selected on the basis of the directed acyclic graph. During a median follow-up of 7.62 years, 8412 participants developed CMD. After considering potential confounders, weight gain pattern (hazard ratio [HR], 1.34 [95% CI, 1.23-1.46]), stable overweight/obesity (HR, 2.12 [95% CI, 2.00-2.24]), and past overweight/obesity (HR, 1.73 [95% CI, 1.59-1.89]) were associated with the incidence of CMD. Similar results were observed in cardiometabolic multimorbidity, cardiovascular disease, and type 2 diabetes. Additionally, triglyceride and systolic blood pressure explained 8.05% (95% CI, 5.87-10.22) and 12.10% (95% CI, 9.19-15.02) of the association between past overweight/obesity and incident CMD, respectively. CONCLUSIONS: A history of overweight/obesity was associated with an increased risk of CMD, even in the absence of current BMI abnormalities. These findings emphasize the necessity for future public health guidelines to include preventive interventions for CMD in individuals with past overweight/obesity.

Intensity-specific physical activity measured by accelerometer and the risk of mortality among individuals with cardiometabolic diseases: A prospective study from the UK Biobank.

BACKGROUND: While the health benefits of physical activity for general population are well-recognized, the prospective associations of physical activity volume and intensity with mortality among cardiometabolic disease individuals remain unclear. OBJECTIVE: The objective of this study was to investigate the associations of accelerometer-measured intensity-specific physical activity with mortality risk among population with cardiometabolic disease. DESIGN: Prospective cohort study. SETTING: Participants were recruited from the United Kingdom (UK) across 22 assessment centers from 2006 to 2010. PARTICIPANTS: A total of 9524 participants from the UK Biobank (median: 67.00 years, interquartile range: 61.00-70.00 years) were included in final study. METHODS: Accelerometer-measured total volume, moderate-to-vigorous and light intensity physical activity collecting from 2013 to 2015 were quantified using a machine learning model. Multivariable restricted cubic splines and Cox proportional hazard models with hazard ratios (HRs) and 95 % confidence intervals (CIs) were employed to examine the associations of interests. RESULTS: During the follow-up period (median: 6.87 years; interquartile range: 6.32-7.39 years), there were 659 (6.92 %) death events with 218 (2.29 %) cardiovascular disease-related deaths and 441 (4.63 %) non-cardiovascular disease-related deaths separately. In the fully adjusted models, compared with participants in the lowest quartiles of total volume, moderate-to-vigorous and light physical activities, the adjusted HRs (95 % CIs) of all-cause mortality for those in the highest quartiles were 0.40 (0.31, 0.52), 0.48 (0.37, 0.61), and 0.56 (0.44, 0.71) while those for cardiovascular diseases-related mortality were 0.35 (0.22, 0.55), 0.52 (0.35, 0.78) and 0.59 (0.39, 0.88), and for non-cardiovascular diseases-related mortality, they were 0.42 (0.30, 0.59), 0.40 (0.29, 0.54) and 0.54 (0.40, 0.73), separately. The optimal moderate-to-vigorous-intensity physical activity level for cardiovascular diseases-related mortality reduction was found to be in the third quartile (17.75-35.33 min/day). Furthermore, the observed inverse associations were mainly non-linear. CONCLUSIONS: Promoting physical activity, regardless of intensity, is essential for individuals with cardiometabolic disease to reduce mortality risk. For both all-cause and cardiovascular disease-related and non-cardiovascular disease-related mortality, the observed decrease in risk seems to level off at a moderate level. The current findings deriving from precise device-based physical activity data provide inference for secondary prevention of cardiometabolic disease.

The consumption of animal products is associated with plasma levels of alpha-aminoadipic acid (2-AAA).

BACKGROUND AND AIMS: The cardiometabolic disease-associated metabolite, alpha-aminoadipic acid (2-AAA) is formed from the breakdown of the essential dietary amino acid lysine. However, it was not known whether elevated plasma levels of 2-AAA are related to dietary nutrient intake. We aimed to determine whether diet is a determinant of circulating 2-AAA in healthy individuals, and whether 2-AAA is altered in response to dietary modification. METHODS AND RESULTS: We investigated the association between 2-AAA and dietary nutrient intake in a cross-sectional study of healthy individuals (N = 254). We then performed a randomized cross-over dietary intervention trial to investigate the effect of lysine supplementation (1 week) on 2-AAA in healthy individuals (N = 40). We further assessed the effect of a vegetarian diet on 2-AAA in a short-term (4-day) dietary intervention trial in healthy omnivorous women (N = 35). We found that self-reported dietary intake of animal products, including meat, poultry, and seafood, was associated with higher plasma 2-AAA cross-sectionally (P < 0.0001). Supplementary dietary lysine (5g/day) caused no significant increase in plasma 2-AAA; however, plasma 2-AAA was altered by general dietary modification. Further, plasma 2-AAA was significantly reduced by a short-term vegetarian diet (P = 0.003). CONCLUSION: We identified associations between plasma 2-AAA and consumption of animal products, which were validated in a vegetarian dietary intervention trial, but not in a trial designed to specifically increase the 2-AAA amino acid precursor lysine. Further studies are warranted to investigate whether implementation of a vegetarian diet improves cardiometabolic risk in individuals with elevated 2-AAA.