Cardiometabolic Disorders Research Articles

Association of Christian Orthodox Fasting with Sociodemographic, Anthropometric and Lifestyle Factors and Serum Biochemical Indices: A Cross-Sectional Study on Patients with Metabolic Diseases.

Christian Orthodox fasting, a type of time-restricted diet, which presents some similarities to the Mediterranean Diet, also including certain similarities with periodic vegetarianism or other time-restricted diets (e.g., intermittent diet and Ramadan fasting), may cumulatively be related to the same or even better beneficial healthy effects as these well-recognized dietary patterns. The present study aimed to explore the potential beneficial impact of Christian Orthodox fasting in patients with metabolic disorders, such as diabetes mellitus type 2, excessive obesity, hypothyroidism and osteoporosis. This was a cross-sectional study, including 135 patients with metabolic disorders (67 fasters and 68 non-fasters). The enrolled fasters had adapted Christian Orthodox fasting recommendations for at least twelve consecutive years or even from childhood. Relevant questionnaires were used to record sociodemographic, anthropometric and lifestyle data of the study population through face-to-face interviews between the enrolled individuals and qualified personnel during a non-fasting period. Christian Orthodox fasting patients showed a significantly and independently lower prevalence of overweight/obesity and abdominal obesity, which is highly associated with cardiometabolic disease risks, as well as a significantly and independently lower incidence of hypertension, including separately lower systolic and diastolic pressure, than non-fasting patients. Fasters also had a significantly and independently increased prevalence of an advanced educational level and no smoking history, as well as a lower incidence of sedentary behavior, and a trend of a correlation with reduced c-reactive protein (CRP), an indicator of inflammation, compared to non-fasters. Fasters also exhibited higher serum albumin and high-density lipoprotein (HDL) levels, as well as lower glucose levels, than non-fasters. This is one of the few cross-sectional studies demonstrating that Christian Orthodox fasting may promote metabolic health by improving several aspects of metabolic disorders, being associated with specific sociodemographic, anthropometric and lifestyle factors. Further studies conducted on larger sample sizes from different countries and different ethnicities that include Christian Orthodox fasters are recommended to evaluate the impact of long-term religious fasting effects on human health, either as a preventative factor reducing the risk of chronic diseases and especially cardiometabolic disorders or as a nutritional intervention to ameliorate symptom severity.

Glycemic Control in Patients Living With HIV Initiated on Integrase Inhibitor-Based Three-Drug Antiretroviral Therapy.

Background: The increased risk of cardio-metabolic disorders associated with people living with human immunodeficiency virus (HIV) is of growing importance. Given the broad adoption of integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) as first-line therapy for HIV, additional data are needed regarding the metabolic effects of these regimens. Objective: The purpose of this study is to assess glycemic control in patients started on INSTI-based 3-drug regimens over a 2-year period. Methods: A retrospective study was conducted on patients seen in the Brooklyn Hospital Center. Men and nonpregnant, nonlactating women aged 18 years or older with a diagnosis of HIV who were initiated on or switched to an ART consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an INSTI were included in the analysis. The primary endpoint is change in A1C from baseline (pre-INSTI initiation) to 2 years after initiation. Results: Two hundred fifty-one patients were eligible based on specified inclusion and exclusion criteria. Overall, a statistically significant increase in A1C was seen in all patients started on INSTI-based regimen (95% CI, 0.10-0.36; P < 0.001). Primarily patients on both elvitegravir-based and bictegravir-based regimens saw the most significant increase in A1C: 0.16% (95% CI, 0.04-0.27; P = 0.006) and 0.39% (95% CI, 0.02-0.76; P = 0.038), respectively. Conclusion and Relevance: Integrase strand-transfer inhibitor-based 3-drug ART was associated with a small but statistically significant increase in A1C over a 2-year period, requiring additional monitoring by clinicians.

Erectile function in men with COVID-19 six months after recovery

Background. Based on the results of epidemiological studies, it was found that coronavirus disease 2019 (COVID-19) affects men more often than women. Among COVID-19 complications, erectile dysfunction is considered a marker of endothelial dysfunction and one of the main factors for the development of cardiovascular diseases. Lower total and free testosterone levels are predictors of adverse prognosis in males with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Testosterone deficiency syndrome is considered an independent risk factor of cardiometabolic disorders. The purpose of the study is to investigate the state of erectile function in men who suffered from COVID-19 six months after recovery. Materials and methods. Seventy-two men suffering from COVID-19 and being treated in an infectious disease hospital were examined 6.90 ± 0.29 months after recovery. Their average age was 45.23 ± 3.01 years. The control group included 18 conditionally healthy men aged 43.18 ± 2.90 years. The state of erectile function was assessed using the International Index of Erectile Function (IIEF). The concentration of testosterone was determined by the enzyme-linked immunosorbent assay with DRG (Germany) and DiaMetra (Italy) kits. All measurements were performed on the Stat Fax 3200 analyzer. Statistical comparison of the obtained results between groups was performed according to the Student’s test. A value of p &lt; 0.05 was considered to be signifi­cant. Results. In addition to erectile dysfunction, as evidenced by a reduced corresponding integrative indicator “erectile function” of IIEF-15 in men with COVID-19, a decrease in sexual desire was found, as well as a deterioration of sensations in the form of a decrease in ejaculation frequency and orgasmic sensations during sex contacts. The average serum level of total testosterone was 10.9 nmol/l and was significantly reduced compared to that in the control group. Analysis of individual indicators showed that testosterone level was decreased in 10 patients and was within the normal range in 13 men with COVID-19. The average serum concentration of total testosterone in the examined men after the disease was 10.73 ± 1.07 nmol/l and was significantly reduced compared to that of the control group. Conclusions. There was an erectile dysfunction in men who suffered COVID-19, it was confirmed by a probable decrease in IIEF-15 score and integrative indicators of erectile function. A significant decrease in the blood concentration of total testosterone was detected in the examined men, which may be one of the causes of erectile dysfunction. Large-scale prospective, randomized, controlled trials in patients infected with SARS-CoV-2 are needed to provide an understanding of the molecular mechanisms that cause erectile dysfunction.

Mental Healthcare in Pediatrics During the COVID-19 Pandemic: A Call for International Public Health Action.

Public health measures associated with coronavirus disease 2019 (COVID-19), such as lockdowns and quarantine of suspected cases, can negatively affect children's mental health status. Although the current crisis provides personal growth and family cohesion opportunities, pitfalls appear to outweigh the benefits. The magnitude and quality of its impact on children depend on several factors, including anxiety, lack of social contact, and a reduced opportunity for stress regulation, along with an increased risk for parental mental health issues, child maltreatment, and domestic violence. Children with special needs and social disadvantages like trauma experiences, disabilities, pre-existing mental illness, e.g., autism spectrum disorders and hyperactivity, and low socioeconomic status, may be at higher risk in this context. Here, the potentials social support can provide for pediatrics, both healthy children and children with special needs, are reviewed after an overview of quarantine's adverse effects on this special population during a pandemic. The most common psychological issues associated with the COVID-19 pandemic are sleep disorders, mood swings, depression, anxiety, decreased attention, stress, irritability, anger, and fear. Moreover, the impact of COVID-19 on children's physical health includes weight gain, reduced physical activity, immune dysregulation, and cardiometabolic disorders. All support systems, involving parents, teachers/school counselors, pediatricians, mental healthcare workers, and Health and Art (HEART) groups, need to enter the scene and make their share of children's mental health care.

Показатели оксидативного стресса и дисфункции эндотелия при сахарном диабете 2-го типа: риски и фокус на диетотерапию

Type 2 diabetes (T2D) is a chronic metabolic disease that poses a significant threat to public health worldwide. Carbohydrate metabolism disorders in T2D are closely related to oxidative stress. Numerous vascular complications are the main cause of disability and mortality in this disease. Objective. Comparative evaluation of the indices of oxidative stress and endothelial dysfunction with anthropometric and biochemical parameters in T2D patients. Patients and methods. The study included 55 patients with T2D and 58 patients with class 1–3 obesity without diabetes. Patients with T2D received a standard treatment with oral sugar-lowering drugs, hypolipidemic and hypotensive therapy as indicated. All patients underwent measurements of anthropometric parameters (height, weight, body mass index), indices of carbohydrate and lipid metabolism, antioxidant status and endothelial dysfunction, triglycerides-glucose index, and pulse wave velocity. Statistical processing of the results was performed using SPSS 23.0 software. Results. Several correlations were found between oxidative stress indices and clinical and metabolic parameters characterizing the state of carbohydrate and lipid metabolism and anthropometric indices in patients with T2D. The level of high-sensitivity C-reactive protein was almost twice as high in T2D patients compared to patients with obesity (11.1 ± 2.58 mg/L and 6.77 ± 1.11 mg/L, respectively). A negative correlation between the levels of superoxide dismutase and fasting blood glucose was determined (r = -0.30, p &lt; 0.005). Conclusion. The study revealed a strong correlation between oxidative stress indices, markers of endothelial dysfunction and cardiometabolic disorders in patients with T2D. The influence on oxidative stress/antioxidant defense indices may become an additional therapeutic link in the treatment of T2D patients. Key words: reactive oxygen species, endothelial dysfunction, oxidative stress, type 2 diabetes

Fecal Microbiota Transfer from Young Mice Reverts Vascular Aging Hallmarks and Metabolic Impairments in Aged Mice.

As a major risk factor for cardiometabolic diseases, aging refers to a gradual decline in physiological function, characterized with 12 conspicuous hallmarks, like telomere attrition, chronic inflammation, and dysbiosis. Common vascular aging hallmarks include endothelial dysfunction, telomere dysfunction, and vascular inflammation. In this study, we sought to test the hypothesis that young-derived gut microbiota retards vascular aging hallmarks and metabolic impairments in aged hosts. We also aimed to study the therapeutic efficacy of young microbiota in hosts of different ages. Fecal microbiota transplantation (FMT) from young to aged or middle-aged C57BL/6 mice was conducted for 6 consecutive weeks after antibiotic pretreatment. Endothelium-dependent relaxations (EDRs) in mouse arteries were determined by wire myography. Inflammation and AMPK/SIRT1 signaling in mouse aortas and intestines were studied by biochemical assays. The telomere function of aortas and intestines, in terms of telomerase reverse transcriptase expression, telomerase activity, and relative telomere length, were also studied. FMT significantly reverted vascular dysfunction and metabolic impairments in middle-aged mice than in aged mice. Besides, FMT significantly reverted inflammation and telomere dysfunction in aortas and intestines of middle-aged mice. Improved intestinal barrier function and activated AMPK/SIRT1 signaling potentially underlie benefits of FMT. The findings imply gut-vascular connection as potential target against age-associated cardiometabolic disorders, highlight crosstalk among aging hallmarks, and suggest a critical timepoint for efficacy of anti-aging interventions.

Lower regional urbanicity and socioeconomic status attenuate associations of green spaces with hypertension and diabetes mellitus: a national representative cross-sectional study in China.

High blood pressure (HBP) and diabetes mellitus (DM) are two of the most prevalent cardiometabolic disorders globally, especially among individuals with lower socio-economic status (SES). Studies have linked residential greenness to decreased risks of HBP and DM. However, there has been limited evidence on whether SES may modify the associations of residential greenness with HBP and DM. Based on a national representative cross-sectional study among 44,876 adults, we generated the normalized difference vegetation index (NDVI) at 1 km spatial resolution to characterize individuals' residential greenness level. Administrative classification (urban/rural), nighttime light index (NLI), individual income, and educational levels were used to characterize regional urbanicity and individual SES levels. We observed weaker inverse associations of NDVI with HBP and DM in rural regions compared to urban regions. For instance, along with per interquartile range (IQR, 0.26) increment in residential NDVI at 0∼5 year moving averages, the ORs of HBP were 1.04 (95%CI: 0.94, 1.15) in rural regions and 0.85 (95%CI: 0.79, 0.93) in urban regions (P = 0.003). Along with the decrease in NLI levels, there were continuously decreasing inverse associations of NDVI with DM prevalence (P for interaction <0.001). In addition, weaker inverse associations of residential NDVI with HBP and DM prevalence were found among individuals with lower income and lower education levels compared to their counterparts. Lower regional urbanicity and individual SES could attenuate the associations of residential greenness with odds of HBP and DM prevalence.

Cross-talks between perivascular adipose tissue and neighbors: multifaceted nature of nereids.

Perivascular adipose tissue (PVAT) is a unique fat depot surrounding blood vessels and plays a vital role in the progression of vascular remodeling and dysfunction. PVAT exhibits remarkable differences in structure, phenotype, origin, and secretome across anatomical locations. The proximity of PVAT to neighboring vascular beds favors a niche for bidirectional communication between adipocytes and vascular smooth muscle cells, endothelial cells, and immune cells. In this review, we update our understanding of PVAT's regional differences and provide a comprehensive exploration of how these differences impact cross-talks between PVAT and the vascular wall. Different PVAT depots show different degrees of vasoprotective function and resilience to pathological changes such as obesity and vasculopathies, shaping multifaceted interactions between PVAT depots and adjacent vasculatures. The depot-specific resilience may lead to innovative strategies to manage cardiometabolic disorders.

"High blood pressure comes from thinking too much": Understandings of illness among couples living with cardiometabolic disorders and HIV in Malawi.

Cardiometabolic disorders (CMD) such as hypertension and diabetes are increasingly prevalent in sub-Saharan Africa, placing people living with HIV at risk for cardiovascular disease and threatening the success of HIV care. Spouses are often the primary caregivers for people living with CMD, and understanding patients' and partners' conceptions of CMD could inform care. We conducted semi-structured interviews with 25 couples having a partner living with HIV and either hypertension or diabetes. Couples were recruited from HIV clinics in Malawi and were interviewed on beliefs around symptoms, causation, prevention, and treatment for CMD. Data were analyzed at the individual and dyadic levels using framework analysis and Kleinman's theory of explanatory models as a lens. On average, participants were 51 years old and married for 21 years. Approximately 57%, 14%, and 80% had hypertension, diabetes, and HIV. Couples endorsed a combination of biomedical explanatory models (beliefs around physical and mental health) and traditional explanatory models (beliefs around religion and natural remedies), although tended to emphasize the biomedical model. Half of couples believed stress was the main cause of hypertension. For diabetes, diet was believed to be a common cause. In terms of prevention, dietary changes and physical activity were most frequently mentioned. For disease management, medication adherence and diet modifications were emphasized, with some couples also supporting herbal remedies, stress reduction, and faith in God as strategies. Participants were generally more concerned about CMD than HIV due to poor access to CMD medications and beliefs that CMD could lead to sudden death. Within couples, partners often held many of the same beliefs but diverged around which etiological or preventive factors were most important (e.g., stress versus diet) and the best diet for CMD. Health education programs should involve primary partners to build knowledge of CMD and address overlap with HIV, and reinforce accurate information on lifestyle factors for the prevention and treatment of CMD.

“I too have a responsibility for my partner's life”: Communal coping among Malawian couples living with HIV and cardiometabolic disorders

RationaleHIV and cardiometabolic disorders including hypertension and diabetes pose a serious double threat in Malawi. Supportive couple relationships may be an important resource for managing these conditions. According to the theory of communal coping, couples will more effectively manage illness if they view the illness as “our problem” (shared illness appraisal) and are united in shared behavioral efforts. MethodsThis study qualitatively investigated communal coping of 25 couples living with HIV and hypertension or diabetes in Zomba, Malawi. Partners were interviewed separately regarding relationship quality, shared illness appraisal, communal coping, and dyadic management of illness. ResultsMost participants (80%) were living with HIV, and more than half were also living with hypertension. Most participants expressed high levels of unity and the view that illness was “our problem.” In some couples, partners expected but did not extend help and support and reported little collaboration. Communal coping and dyadic management were strongly gendered. Some women reported a one-sided support relationship in which they gave but did not receive support. Women were also more likely to initiate support interactions and offered more varied support than men. In couples with poor relationship quality and weak communal coping, dyadic management of illness was also weak. Partner support was particularly crucial for dietary changes, as women typically prepared meals for the entire family. Other lifestyle changes that could be supported or hindered by a partner included exercise, stress reduction, and medication adherence. ConclusionWe conclude that gendered power imbalances may influence the extent to which couple-level ideals translate into actual communal coping and health behaviors. Given that spouses and families of patients are also at risk due to shared environments, we call for a shift from an illness management paradigm to a paradigm of optimizing health for spouses and families regardless of diabetes or hypertension diagnosis.

DNA methylation as a window into female reproductive aging.

People with ovaries experience reproductive aging as their reproductive function and system declines. This has significant implications for both fertility and long-term health, with people experiencing an increased risk of cardiometabolic disorders after menopause. Reproductive aging can be assessed through markers of ovarian reserve, response to fertility treatmentor molecular biomarkers, including DNA methylation. Changes in DNA methylation with age associate with poorer reproductive outcomes, and epigenome-wide studies can provide insight into genes and pathways involved. DNA methylation-based epigenetic clocks can quantify biological age in reproductive tissues and systemically. This review provides an overview of hallmarks and theories of aging in the context of the reproductive system, and then focuses on studies of DNA methylation in reproductive tissues.

Intergenerational inheritance induced by a high-fat diet causes hyperphagia and reduced hypothalamic sensitivity to insulin and leptin in the second-generation of rats

ObjectiveThe aim was to investigate the intergenerational inheritance induced by a high-fat diet on sensitivity to insulin and leptin in the hypothalamic control of satiety in second-generation offspring, which were fed a control diet. MethodsProgenitor rats were fed a high-fat or a control diet for 59 d until weaning. The first-generation and second-generation offspring were fed the control diet until 90 d of age. Body mass and adiposity index of the progenitors fed the high-fat diet and the second-generation offspring from progenitors fed the high-fat diet were evaluated as were the gene expression of DNA methyltransferase 3a, angiotensin-converting enzyme type 2, angiotensin II type 2 receptor, insulin and leptin signaling pathway (insulin receptor, leptin receptor, insulin receptor substrate 2, protein kinase B, signal transducer and transcriptional activator 3, pro-opiomelanocortin, and neuropeptide Agouti-related protein), superoxide dismutase activity, and the concentration of carbonyl protein and satiety-regulating neuropeptides, pro-opiomelanocortin and neuropeptide Agouti-related protein, in the hypothalamus. ResultsThe progenitor group fed a high-fat diet showed increased insulin resistance and reduced insulin-secreting beta-cell function and reduced food intake, without changes in caloric intake. The second-generation offspring from progenitors fed a high-fat diet, compared with second-generation offspring from progenitors fed a control diet group, had decreased insulin-secreting beta-cell function and increased food and caloric intake, insulin resistance, body mass, and adiposity index. Furthermore, second-generation offspring from progenitors fed a high-fat diet had increased DNA methyltransferase 3a, neuropeptide Agouti-related protein, angiotensin II type 1 receptor, and nicotinamide adenine dinucleotide phosphate oxidase p47phox gene expression, superoxide dismutase activity, and neuropeptide Agouti-related protein concentration in the hypothalamus. In addition, there were reduced in gene expression of the insulin receptor, leptin receptor, insulin receptor substrate 2, pro-opiomelanocortin, angiotensin II type 2 receptor, angiotensin-converting enzyme type 2, and angiotensin-(1–7) receptor and pro-opiomelanocortin concentration in the second-generation offspring from progenitors fed the high-fat diet. ConclusionsOverall, progenitors fed a high-fat diet induced changes in the hypothalamic control of satiety of the second-generation offspring from progenitors fed the high-fat diet through intergenerational inheritance. These changes led to hyperphagia, alterations in the hypothalamic pathways of insulin, and leptin and adiposity index increase, favoring the occurrence of different cardiometabolic disorders in the second-generation offspring from progenitors fed the high-fat diet fed only with the control diet.

Metabolic status differentiates Trp53inp2 function in pressure-overload induced heart failure.

Cardiometabolic disorders encompass a broad range of cardiovascular complications associated with metabolic dysfunction. These conditions have an increasing share in the health burden worldwide due to worsening endemic of hypertension, obesity, and diabetes. Previous studies have identified Tumor Protein p53-inducible Nuclear Protein 2 (Trp53inp2) as a molecular link between hyperglycemia and cardiac hypertrophy. However, its role in cardiac pathology has never been determined in vivo. In this study, we generated a cardiac specific knockout model of Trp53inp2 (Trp53inp2-cKO) and investigated the impact of Trp53inp2 inactivation on the pathogenesis of heart failure under mechanic or/and metabolic stresses. Based on echocardiography assessment, inactivation of Trp53inp2 in heart led to accelerated onset of HFrEF in response to pressure-overload, with significantly reduced ejection fraction and elevated heart failure marker genes comparing to the control mice. In contrast, inactivation of Trp53inp2 ameliorated cardiac dysfunction induced by combined stresses of high fat diet and moderate pressure overload (Cardiometabolic Disorder Model). Moreover, Trp53inp2 inactivation led to reduced expression of glucose metabolism genes in lean, pressure-overloaded hearts. However, the same set of genes were significantly induced in the Trp53inp2-cKO hearts under both mechanical and metabolic stresses. In summary, we have demonstrated for the first time that cardiomyocyte Trp53inp2 has diametrically differential roles in the pathogenesis of heart failure and glucose regulation under mechanical vs. mechanical plus metabolic stresses. This insight suggests that Trp53inp2 may exacerbate the cardiac dysfunction during pressure overload injury but have a protective effect in cardiac diastolic function in cardiometabolic disease.

JCL roundtable: Evolution of preventive cardiology and clinical lipidology

It's a privilege to discuss preventive cardiology with 3 of the foremost U.S. leaders in this growing subspecialty. Preventive cardiology is the practice of primordial, primary, and secondary prevention of cardiovascular disease. It employs an integrated team of clinicians committed to preventing all forms of cardiovascular disease, including ischemic heart disease, heart failure, atrial fibrillation, and other conditions. Thus, contemporary preventive cardiology extends management beyond dyslipidemic risk reduction and now commonly includes treatment of hypertension, diabetes and other related cardiometabolic disorders, novel cardiovascular risk factors, thrombotic risk, some cardiac genetic disorders, and cardiac disorders specific to women's health, as well as attention to tobacco- and drug-related risks. Preventive cardiologists may simultaneously manage cardiac rehabilitation programs. Among significant innovations are the launch of the American Journal of Preventive Cardiology in 2020, increasing validation and use of coronary artery calcium scoring, prescription of obesity and diabetes pharmaceuticals by cardiologists, and focus on pregnancy as a natural cardiovascular stress test for women with implications for future cardiovascular events. A continuing major barrier is that reimbursement for preventive cardiology services currently does not match the value benefit which accrues to patients and society. Preventive care too often is added late in the course of disease management. In addition to ongoing pharmaceutical and lifestyle research, future directions include incorporation of specific training goals for preventive cardiology in general clinical cardiology training programs and support for registered dietician reimbursement for services to patients with clinically manifest atherosclerosis.

High levels of sleep disturbance across early childhood increases cardiometabolic disease risk index in early adolescence: longitudinal sleep analysis using the Health Outcomes and Measures of the Environment study.

This study examines the impact of sleep duration, bedtime, and sleep disturbance during early childhood on the risk of cardiometabolic disorder (CMD) in early adolescence. Within the Health Outcomes and Measures of Environment Study, we examined sleep patterns of 330 children from ages 2 to 8 years and the relationship of these sleep patterns with cardiometabolic risk measures at age 12 (N = 220). We used a group-based semi-parametric mixture model to identify distinct trajectories in sleep duration, bedtime timing, and sleep disturbance for the entire sample. We then examined the associations between sleep trajectories and CMD risk measures using general linear models using both an unadjusted model (no covariates) and an adjusted model (adjusting for child pubertal stage, child sex, duration of breastfeeding, household income, maternal education, and maternal serum cotinine). In the unadjusted and adjusted models, we found significant differences in CMD risk scores by trajectories of sleep disturbance. Children in the "high" disturbance trajectory had higher CMD risk scores than those in the 'low' disturbance trajectory (p's = 0.002 and 0.039, respectively). No significant differences in CMD risk were observed for bedtime timing or total sleep time trajectories in the unadjusted or adjusted models. In this cohort, caregiver-reported sleep disturbance in early childhood was associated with more adverse cardiometabolic profiles in early adolescence. Our findings suggest that trials to reduce CMD risk via sleep interventions-which have been conducted in adolescents and adults-may be implemented too late.

The risk for venous thromboembolism and cardiometabolic disorders in offspring from thrombosis-prone pedigrees

BackgroundMost family studies on venous thromboembolism (VTE) have focused on first-degree relatives. ObjectivesWe took a pedigree-based approach and examined the risk of VTE and cardiometabolic disorders in offspring from extended pedigrees according to the densities of VTE in pedigrees. MethodsFrom the Swedish population, we identified a total of 482 185 pedigrees containing a mean of 14.2 parents, aunts/uncles, grandparents, and cousins of a core full sibship that we termed the pedigree offspring (n = 751 060). We then derived 8 empirical classes of these pedigrees based on the density of cases of VTE. The risk was determined in offspring for VTE and cardiometabolic disorders as a function of VTE density in their pedigrees. Bonferroni correction for multiple comparisons was performed. ResultsVTE was unevenly distributed in the population; the Gini coefficient was 0.59. Higher VTE density in pedigrees was associated in the offspring with a higher risk of different VTE manifestations (deep venous thrombosis, pulmonary embolism, pregnancy-related VTE, unusual thrombosis, and superficial thrombophlebitis), thrombophilia, and lower age of first VTE event. Moreover, VTE density in pedigrees was significantly associated in the offspring with obesity, diabetes, gout, varicose veins, and arterial embolism and thrombosis (excluding brain and heart). No significant associations were observed for retinal vein occlusion, hypercholesterolemia, hypertension, coronary heart disease, myocardial infarction, ischemic stroke, atrial fibrillation, heart failure, primary pulmonary hypertension, cerebral hemorrhage, aortic aneurysm, peripheral artery disease, and overall mortality. ConclusionOffspring of pedigrees with a high density of VTE are disadvantaged regarding VTE manifestations and certain cardiometabolic disorders.

In situ lipid-loading activates peripheral dendritic cell subsets characterized by cellular ROS accumulation but compromises their capacity to prime naïve T cells

Background and aimsDendritic cells (DCs), professional antigen-presenting cells, play an important role in pathologies by controlling adaptive immune responses. However, their adaptation to and functionality in hypercholesterolemia, a driving factor in disease onset and progression of atherosclerosis remains to be established. MethodsIn this study, we addressed the immediate impact of high fat diet-induced hypercholesterolemia in low-density lipoprotein receptor deficient (Ldlr−/−) mice on separate DC subsets, their compartmentalization and functionality. ResultsWhile hypercholesterolemia induced a significant rise in bone marrow myeloid and dendritic cell progenitor (MDP) frequency and proliferation rate after high fat diet feeding, it did not affect DC subset numbers in lymphoid tissue. Hypercholesterolemia led to almost immediate and persistent augmentation in granularity of conventional DCs (cDCs), in particular cDC2, reflecting progressive lipid accumulation by these subsets. Plasmacytoid DCs were only marginally and transiently affected. Lipid loading increased co-stimulatory molecule expression and ROS accumulation by cDC2. Despite this hyperactivation, lipid-laden cDC2 displayed a profoundly reduced capacity to stimulate naïve CD4+ T cells. ConclusionOur data provide evidence that in hypercholesterolemic conditions, peripheral cDC2 subsets engulf lipids in situ, leading to a more activated status characterized by cellular ROS accumulation while, paradoxically, compromising their T cell priming ability. These findings will have repercussions not only for lipid driven cardiometabolic disorders like atherosclerosis, but also for adaptive immune responses to pathogens and/or endogenous (neo) antigens under conditions of hyperlipidemia.

Metabolic control of puberty: 60 years in the footsteps of Kennedy and Mitra's seminal work.

An individual's nutritional status has a powerful effect on sexual maturation. Puberty onset is delayed in response to chronic energy insufficiency and is advanced under energy abundance. The consequences of altered pubertal timing for human health are profound. Late puberty increases the chances of cardiometabolic, musculoskeletal and neurocognitive disorders, whereas early puberty is associated with increased risks of adult obesity, type 2 diabetes mellitus, cardiovascular diseases and various cancers, such as breast, endometrial and prostate cancer. Kennedy and Mitra's trailblazing studies, published in 1963 and using experimental models, were the first to demonstrate that nutrition is a key factor in puberty onset. Building on this work, the field has advanced substantially in the past decade, which is largely due to the impressive development of molecular tools for experimentation and population genetics. In this Review, we discuss the latest advances in basic and translational sciences underlying the nutritional and metabolic control of pubertal development, with a focus on perspectives and future directions.

Abstract C073: Assessing the prevalence of cardiometabolic diseases among breast cancers cases at the Howard University Cancer Center

Abstract Background: Cardiometabolic disorders encompass a spectrum of cardiovascular and metabolic system diseases including heart attack, stroke, type 2 diabetes (T2DM), insulin resistance, and metabolic syndrome. Common risk factors among these diseases include abdominal obesity, hyperlipidemia, and increased blood pressure. Cardiometabolic diseases disproportionately impact African American women, especially those with cancer. Evidence indicates that women with breast cancer are more likely to pass away from cardiometabolic diseases than cancer itself. Purpose: This study aims to investigate the prevalence of cardiometabolic diseases among female breast cancer patients diagnosed at the Howard University Cancer Center between January 2012 and December 2022. Methods: A retrospective chart review will be conducted using the cancer registry data from The Howard University Cancer Center and electronic medical records from the Howard University Faculty Practice Plan Outpatient Electronic Medical Records (Allscripts). This will be conducted in two phases. In Phase I, we will recruit women 18 to 88 years old diagnosed with breast cancer between 2012 and 2022. Howard University has approximately 70 to 100 breast cancer cases per year. It is anticipated that approximately 1,000 cases will be identified. From this sample, we will collect information regarding cancer diagnosis, treatment composite, and tumor characteristics. Assuming this generates 1,000 cases, we will randomly select 25% of this number (250 cases) to obtain the other variables of interest from the medical records. This initiates phase II, where we will use the medical record number provided by the cancer registry to identify and review records of the 250 cases. The electronic medical records will be reviewed on-site upon approval of the Director of Outpatient Medical Records. The variables assessed will include demographic data (age at diagnosis, ethnicity, geographical location, and level of education), body mass index (BMI), date of diagnosis, treatment composite (initial treatment at the time of diagnosis), menopausal status, tobacco use, cardiometabolic diseases (diabetes, heart attack, stroke, abdominal obesity), cardiometabolic risk factors (hypertension and hyperlipidemia), and tumor characteristics (number of primary sites and stages of cancer). All data will be maintained using REDCap which is a secure web-based application designed to manage online surveys and data. An electronic data abstraction form will be developed in REDCap to record all of the information listed below in Table 1. All statistical analyses will be conducted using SPSS. The quantitative data will be characterized by means, medians, modes, and frequencies in a descriptive analysis. Log-binomial regression will be used to calculate prevalence ratios. A chi-square test will be utilized to examine cardiometabolic disorders and breast cancer at diagnosis. Anticipated Deliverable: Determine the prevalence of cardiometabolic diseases among female breast cancer patients diagnosed at The Howard University Cancer Center. Citation Format: Ozioma A. Scott. Assessing the prevalence of cardiometabolic diseases among breast cancers cases at the Howard University Cancer Center [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C073.

Association of Cardiometabolic Multimorbidity with Dementia and Alzheimer’s Plasma Biomarkers in Older Adults: a population‐based study

AbstractBackgroundIndividual cardiometabolic disorders are associated with an increased dementia risk. However, the relationship of cardiometabolic multimorbidity (CMM) with dementia has not been studied in Chinese older adults and the underlying mechanisms are poorly understood.MethodThis population‐based study included 5665 rural‐dwelling adults (age ≥60 years, 57.3% women) in the baseline examination (March‐September 2018) of the Multimodal Interventions to Delay Dementia and Disability in Rural China study. Cardiometabolic diseases (CMDs), which included heart disease, stroke, type 2 diabetes, and obesity, were assessed through clinical and neurological examinations. CMM was defined as the concurrent presence of two or more CMDs. Amyloid‐β(Aβ), total tau, and neurofilament light chain (NfL) were measured using Simoa platform in a subsample (n = 1434). Dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) were clinically diagnosed following international criteria. Data were analyzed using the general linear and logistic regression and mediation models.ResultOf the 5665 participants, 1091 (19.26%) were detected with CMM, and 302 (5.33%) were diagnosed with dementia (193 with AD and 98 with VaD). The multivariable‐adjusted odds ratios of CMM (vs. no CMD) were 3.00 (95% confidence interval [CI] 2.19‐4.11) for all‐cause dementia, 1.66 (1.11‐2.47) for AD, and 12.5 (6.47‐24.18) for VaD. There was a significant interaction between CMM and sex on the likelihood of dementia and subtypes (P for interaction&lt;0.05), such that the associations of CMM with dementia and subtypes were stronger in men than in women. In the biomarker subsample, CMM was significantly associated with higher plasma NfL (demographic‐adjusted β coefficient = 0.059; 95% CI 0.028‐0.091), Aβ40 (0.034; 0.018‐0.049), and Aβ42 (1.068; 0.636‐1.501); the observed association remained significant even in the multivariable‐adjusted model (P&lt;0.001). The mediation analysis showed that plasma NfL could mediate 19.46% of the association between CMM and AD (P&lt;0.05), whereas plasma Aβ and total tau showed no significant mediation (P&gt;0.05).ConclusionCMM is associated with increased likelihoods of dementia, AD, and VaD in older adults, especially in men. Neurodegenerative pathway might play a part in the association of CMM with AD.