Cardiometabolic Comorbidities Research Articles

Economic burden of generalized myasthenia gravis (MG) in the United States and the impact of common comorbidities and acute MG-events

Background This study assessed the incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG), as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. Methods Adults with gMG and without MG were identified from a large US database (2017–2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. Results The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient costs of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001. Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively. Conclusions gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over three times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.

A dynamic probabilistic model of the onset and interaction of cardio-metabolic comorbidities on an ageing adult population

Comorbidity is widespread in the ageing population, implying multiple and complex medical needs for individuals and a public health burden. Determining risk factors and predicting comorbidity development can help identify at-risk subjects and design prevention strategies. Using socio-demographic and clinical data from approximately 11,000 subjects monitored over 11 years in the English Longitudinal Study of Ageing, we develop a dynamic Bayesian network (DBN) to model the onset and interaction of three cardio-metabolic comorbidities, namely type 2 diabetes (T2D), hypertension, and heart problems. The DBN allows us to identify risk factors for developing each morbidity, simulate ageing progression over time, and stratify the population based on the risk of outcome occurrence. By applying hierarchical agglomerative clustering to the simulated, dynamic risk of experiencing morbidities, we identified patients with similar risk patterns and the variables contributing to their discrimination. The network reveals a direct joint effect of biomarkers and lifestyle on outcomes over time, such as the impact of fasting glucose, HbA1c, and BMI on T2D development. Mediated cross-relationships between comorbidities also emerge, showcasing the interconnected nature of these health issues. The model presents good calibration and discrimination ability, particularly in predicting the onset of T2D (iAUC-ROC = 0.828, iAUC-PR = 0.294) and survival (iAUC-ROC = 0.827, iAUC-PR = 0.311). Stratification analysis unveils two distinct clusters for all comorbidities, effectively discriminated by variables like HbA1c for T2D and age at baseline for heart problems. The developed DBN constitutes an effective, highly-explainable predictive risk tool for simulating and stratifying the dynamic risk of developing cardio-metabolic comorbidities. Its use could help identify the effects of risk factors and develop health policies that prevent the occurrence of comorbidities.

Deficits in brain glucose transport among younger adults with obesity.

Obesity is associated with alterations in eating behavior and neurocognitive function. In this study, we investigate the effect of obesity on brain energy utilization, including brain glucose transport and metabolism. A total of 11 lean participants and 7 young healthy participants with obesity (mean age, 27 years) underwent magnetic resonance spectroscopy scanning coupled with a hyperglycemic clamp (target, ~180 mg/dL) using [1-13C] glucose to measure brain glucose uptake and metabolism, as well as peripheral markers of insulin resistance. Individuals with obesity demonstrated an ~20% lower ratio of brain glucose uptake to cerebral glucose metabolic rate (Tmax/CMRglucose) than lean participants (2.12 ± 0.51 vs. 2.67 ± 0.51; p = 0.04). The cerebral tricarboxylic acid cycle flux (VTCA) was similar between the two groups (p = 0.64). There was a negative correlation between total nonesterified fatty acids and Tmax/CMRglucose (r = -0.477; p = 0.045). We conclude that CMRglucose is unlikely to differ between groups due to similar VTCA, and, therefore, the glucose transport Tmax is lower in individuals with obesity. These human findings suggest that obesity is associated with reduced cerebral glucose transport capacity even at a young age and in the absence of other cardiometabolic comorbidities, which may have implications for long-term brain function and health.

Are comorbidities of patients with adrenal incidentaloma tied to sex?

A recent cross-sectional study showed that both comorbidities and mortality in patients with adrenal incidentaloma (AI) are tied to sex. However, few longitudinal studies evaluated the development of arterial hypertension, hyperglycemia, dyslipidemia and bone impairment in patients with AI. The aim of this study is to analyze the impact of sex in the development of these comorbidities during long-term follow-up. We retrospectively evaluated 189 patients (120 females, 69 males) with AI, from four referral centers in Italy and Croatia. Clinical characteristics, comorbidities and cortisol after 1-mg dexamethasone suppression test (1-mg DST) were assessed at baseline and at last follow-up visit (LFUV). Median follow-up was 52 (Interquartile Range 25-86) months. The rates of arterial hypertension and hyperglycemia increased over time both in females (65.8% at baseline versus 77.8% at LFUV, p=0.002; 23.7% at baseline versus 39.6% at LFUV, p<0.001; respectively) and males (58.0% at baseline versus 69.1% at LFUV, p=0.035; 33.8% at baseline versus 54.0% at LFUV, p<0.001; respectively). Patients were stratified in two groups using 1.8 µg/dl as cut-off of cortisol following 1-mg DST: non-functional adrenal tumors (NFAT) and tumors with mild autonomous cortisol secretion (MACS). In the NFAT group (99 patients, females 62.6%), at baseline, we did not observe any difference in clinical characteristics and comorbidities between males and females. At LFUV, males showed a higher frequency of hyperglycemia than females (57.6% versus 33.9%, p=0.03). In the MACS group (89 patients, females 64.0%), at baseline, the prevalence of hypertension, hyperglycemia and dyslipidemia was similar between sexes, despite females were younger (60, IQR 55-69 versus 67.5, IQR 61-73, years; p=0.01). Moreover, females presented higher rates of bone impairment (89.3% versus 54.5%, p=0.02) than males. At LFUV, a similar sex-related pattern was observed. Patients with AI frequently develop arterial hypertension and hyperglycemia and should be periodically checked for these comorbidities, regardless of sex. In patients with MACS, the lack of difference between sexes in the frequency of cardiometabolic comorbidities despite that females are younger, and the higher frequency of bone impairment in females, suggest a sex-specific effect of cortisol.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. We enrolled 343 816 adults aged ≥30years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend<0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend<0.001). Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

Multidimensional phenotyping to distinguish among distinct obstructive sleep apnea, chronic obstructive pulmonary disease, and overlap syndrome phenotypes

Objective/backgroundChronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA) and their comorbid association called Overlap Syndrome (OS) are frequent chronic diseases with high individual and societal burdens. Precise descriptions of the respective symptoms, comorbidities, and medications associated with these three conditions are lacking. We used a multidimensional phenotyping approach to identify relevant phenotypes characterizing these 3 disorders. Patients/methods308 patients with OSA, COPD and OS were prospectively assessed using a combination of body shape measurements and multidimensional questionnaires evaluating sleep, fatigue, depression and respiratory symptoms. Comorbidities and medications were confirmed by physicians. Patients made home blood pressure self-measurements using a connected wearable device to identify undiagnosed or uncontrolled hypertension. ResultsThree distinct relevant phenotypes were identified. OSA patients were round in shape with a balanced waist-to-hip ratio, frequent witnessed apneas, nocturia, daytime sleepiness, depression, and high diastolic blood pressure. COPD patients had a thinner body shape with a high waist-to-hip ratio, complained mainly of fatigue, and exhibited a higher resting heart rate. OS patients were round in shape with a balanced waist-to-hip ratio, reported little sleepiness and depression, but had impaired sleep and the highest rate of cardio-metabolic comorbidities. Diminished fitness-to-drive was most apparent in patients with OSA and OS. Home blood pressure measurements identified undiagnosed hypertension in 80 % of patients and in nearly 80 % of those with hypertension it was uncontrolled by their current medications. ConclusionsOur systematic multidimensional phenotyping approach identified distinct body shapes, symptoms, and comorbidity profiles among patients with OSA, COPD, and OS.

Digital sleep clinic: assessing efficacy of continuous positive airway pressure through sleep staging via connected devices: a study protocol

BackgroundObstructive sleep apnea (OSA) is a multisystemic chronic disease with disabling symptoms, cardiometabolic comorbidities and reduction in physical activity. Continuous positive airway pressure (CPAP) is the standard treatment for OSA. Only a few studies have characterized trajectories of sleep parameters upon initiation of CPAP and these are limited to one or two nights of polysomnographic recording in a sleep laboratory. This is due to the cost of carrying out these studies and poor tolerance by patients of multiple nights of polysomnographic recordings. No study has characterized sleep over multiple nights before and after CPAP initiation, assessing the multidimensional efficacy of CPAP on patient reported outcomes, objective and subjective sleep quality, oximetry, glucose control and physical activity.New digital technologies enable overnight sleep studies over several nights in the patient’s home, with a reliability of sleep characterization equivalent to polysomnographic recording.The primary aim of this study is to investigate objective slow wave sleep (SWS or N3) quality before CPAP and during the first month of the treatment.Secondary objectives are to assess changes in the following parameters before CPAP and during the first month of the treatment: other objective sleep parameters and sleep stages evolution (W, N1, N2 and REM), nocturnal oxygen desaturations, 24-h blood glucose profile, daily physical activity (the daily steps count), and patient reported outcomes.MethodsSeventy patients prescribed CPAP for OSA will be recruited at Grenoble Alpes University Hospital (France) and monitored for 5 weeks using validated innovative wearable connected devices (the Dreem 3 headband, a pedometer, an oximeter, and a continuous glucose sensor) enabling them to track their own sleep and physiological parameters at home before and after CPAP initiation.DiscussionBy pooling data from the CPAP telemonitoring and other connected devices we should be able to follow the multidimensional trajectories of patients after the initiation of CPAP. This will enable us to determine whether objective changes in sleep parameters in the first few weeks of CPAP treatment are associated with improvements in daytime sleepiness, quality of life, treatment adherence, glucose control and physical activity. The data will provide integrated markers of treatment efficacy and will allow adapted personalized management of OSA in the short and long-term.Trial registrationClinicaltrials (NCT05197855).

High prevalence of diabetes among young First Nations Peoples with metabolic dysfunction-associated steatotic liver disease: a population-based study in Australia

BackgroundLiver disease is an important contributor to the mortality gap between First Nations Peoples and non-Indigenous Australian adults. Despite a high burden of metabolic comorbidities among First Nations Peoples, data about the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD) in this population is scarce.MethodsA retrospective analysis of all adults hospitalized with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) with/without cirrhosis during 2007–2019 in the state of Queensland was performed. Patients were followed from the first admission with MASLD/MASH (identified based on validated algorithms) to decompensated cirrhosis and overall mortality. We explored differences according to Indigenous status using Multivariable Cox regression.Findings439 First Nations Peoples and 7,547 non-Indigenous Australians were followed for a median of 4.6 years (interquartile range 2.7–7.2). Overall, women were overrepresented, but more so in the First Nations cohort (72.7% vs. 57.0%, p < 0.001). First Nations patients were younger, a higher proportion lived in remote and socioeconomic disadvantaged areas, and had higher comorbidity compared to non-Indigenous Australians (all p < 0.001). Diabetes, the most common comorbidity affecting both groups, was overrepresented in First Nations Peoples versus non-Indigenous Australians (43.5% vs. 30.8%, p < 0.001, respectively). Nineteen (4.3%) First Nations Peoples and 332 (4.4%) of non-Indigenous patients progressed to cirrhosis decompensation (9.0% [95%CI 4.5–17.7] vs. 7.7% [95%CI 6.6–8.9; p = 0.956] respectively within 10 years). In multivariable analysis, there was no association between Indigenous status and progression to decompensated cirrhosis (p = 0.759) and survival (p = 0.437).ConclusionsThis study provides the first population-based epidemiological data on MASLD in First Nations Australians. The high prevalence of diabetes (that is associated with advanced fibrosis and liver disease mortality) among young First Nations Peoples with MASLD raises concern about future risk of progressive liver disease in this patient population. These data highlight the importance of early identification of MASLD, and providing culturally appropriate intervention to reduce disease progression in parallel with the management of cardiometabolic comorbidities.

Genital Surgery Outcomes Using an Individualized Algorithm for Hormone Management in Transfeminine Individuals

Abstract Context Transgender and gender diverse (TGD) individuals have greater access to genital surgery (GS) with improved insurance coverage and access to trained surgeons and interdisciplinary gender-affirming providers. Objective To determine perioperative medical and behavioral health outcomes in transfeminine (TF) individuals undergoing GS, with use of a specific gender-affirming hormone therapy (GAHT) algorithm based on individualized risk factor assessment. Methods In this retrospective observational cohort study, we collected preoperative and postoperative data from 183 TF individuals at a single tertiary referral center from 2017 to 2022, grouping patients by those who continued estradiol (Group 1) vs those who had temporarily discontinued estradiol for 2 to 6 weeks preoperatively (Group 2). Data included clinical and biochemical assessment, GAHT regimens, validated behavioral health measures, and postoperative complications. Main outcomes included venous thromboembolism (VTE) incidence, non-VTE postoperative complication incidence, and change in behavioral health assessments. Results The majority of individuals continued estradiol perioperatively (Group 1; 138 [75.4%]). Individuals who temporarily held estradiol preoperatively (Group 2; 45 [24.6%]) were statistically older (P &amp;lt; .01), had higher incidence of cardiometabolic comorbidities (P &amp;lt; .01), and higher Caprini scores (P &amp;lt; .01). Group 1 was statistically more likely to use oral estradiol (P &amp;lt; .01). One episode (0.05%) of VTE occurred (Group 1). There was no significant difference in postoperative complications or behavioral health measures between groups. Conclusion An individualized algorithm for preoperative hormone management for TF GS resulted in perioperative continuation of GAHT for the majority of individuals without significantly increasing the risk for postoperative surgical complications, while maintaining stable behavioral health measures perioperatively.

Abstract 4829: Pre-diagnostic comorbid conditions and survival among black women with ovarian cancer

Abstract Introduction: Black women with epithelial ovarian cancer (EOC) have worse survival compared to other racial groups, and the causes of these poor outcomes remain unclear. Compared to other racial groups, Black women are disproportionately affected by comorbid conditions which can adversely impact cancer care and outcomes. Thus, we examined the association of pre-diagnostic comorbid conditions and their associated medications with survival among Black women with EOC. Methods: Using data from Black women with EOC in the African American Cancer Epidemiology Study, we evaluated the self-reported Charlson comorbidity index (CCI) and three cardiometabolic comorbidities (diabetes mellitus, hypertension, and hyperlipidemia). We also characterized whether women with each cardiometabolic condition were using medication for their condition. Kaplan-Meier survival curves and log-rank tests were used to examine survival by the CCI, each cardiometabolic comorbidity, and medication use. Cox proportional hazards regression models were used to examine the association of comorbid conditions and medications with survival while adjusting for age at diagnosis, stage, histotype, and study site. Results: Among 592 Black women with EOC, 35% had a CCI ≥2, and the prevalence of diabetes, hyperlipidemia, and hypertension was 19%, 31%, and 62%, respectively. Among women with each cardiometabolic condition, the prevalence of medication use for diabetes, hypertension, and hyperlipidemia was 73%, 78%, and 60%. In bivariate analyses, women with a higher CCI, diabetes, hyperlipidemia, and hypertension had worse survival compared to women without these conditions (P&amp;lt;0.05). However, when adjusting for prognostic factors, only a high CCI (≥2 vs. 0) and diabetes were significantly associated with higher hazard of death (HR=1.36, 95% CI=1.06-1.74 and HR=1.40, 95% CI=1.08-1.81, respectively). Investigating the independent associations of each condition included in the CCI with survival revealed that diabetes was largely driving the association of CCI with survival. When considering medication use, women with diabetes, irrespective of medication use, women with hypertension not on medication, and women with hyperlipidemia on medication had worse survival compared to women without these conditions in bivariate models (P&amp;lt;0.05). Compared to women without diabetes, women with diabetes on medication and women with diabetes not on medication had a statistically significant higher hazard of death in multivariable models (HR=1.39, 95% CI=1.02-1.88 and HR=1.63, 95% CI=1.04-2.57, respectively). No associations with survival were observed when considering medication use for hypertension and hyperlipidemia after adjusting for prognostic factors. Conclusion: Similar to prior studies among White women with EOC, diabetes, regardless of medication status, was strongly associated with poorer survival among Black women with EOC. Citation Format: Alicia Richards, Courtney E. Johnson, Anthony J. Alberg, Elisa V. Bandera, Melissa Bondy, Michele L. Cote, Theresa A. Hastert, Kristen Haller, Jeffrey R. Marks, Edward S. Peters, Paul D. Terry, Andrew B. Lawson, Joellen M. Schildkraut, Lauren C. Peres. Pre-diagnostic comorbid conditions and survival among black women with ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4829.

Abstract 50: Factors Associated With Obesity Pharmacotherapy Prescription Among Ambulatory Patients With Excess Weight

Background: Semaglutide, liraglutide (GLP1-RA), and tirzepatide (GLP1/GIP-RA) are potent anti-obesity pharmacotherapies resulting in marked weight loss and improved cardiometabolic outcomes. Limited insurance coverage is a well-understood barrier to these new therapies; thus, we sought to characterize additional clinical and sociodemographic factors associated with the prescription of these medications. Hypothesis: Likelihood of prescription of novel anti-obesity medications will be lower for individuals within racial and ethnic minority and lower SES subgroups. Methods: We identified adults who have obesity (BMI ≥30), existing insurance coverage for anti-obesity medications, and received outpatient care at Johns Hopkins from January 2023 to September 2023. We used multivariable logistic regression to evaluate factors associated with prescription of anti-obesity pharmacotherapies. Results: We included 18,164 patients (mean age 51 years, 64% female, 54% White, 35% Black, 5% Asian, mean BMI 36 kg/m 2 ). About 3% of eligible adults were prescribed anti-obesity medications. The likelihood of prescription was lower among Black adults (OR: 0.76, 95%CI [0.61-0.96]), males (OR: 0.54 [0.42-0.68]), and adults younger and older than 40-50 years of age; and higher for those with higher BMI (per 1-unit higher BMI, OR: 1.06 [1.05-1.07]). Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription. Clinically, those with diabetes (OR: 3.52 [2.78-4.44]) and hypertension (OR: 1.36 [1.08-1.71]) were more likely to be prescribed novel obesity pharmacotherapies. Conclusion: Among those with existing insurance coverage, the likelihood of obesity pharmacotherapy prescription differs by sociodemographic factors and cardiometabolic comorbidities. Understanding the mechanisms of these differences may have key implications for obesity management in diverse populations, and ultimately for cardiometabolic health equity.

Patients Living with Arterial Hypertension in Mexico: First Insights of The Mexican Registry of Arterial Hypertension (RIHTA Study).

Arterial hypertension is a significant cause of morbidity and mortality in Mexico. However, there is limited data available to understand blood pressure management and cardiometabolic profiles. To assess the prevalence of controlled and uncontrolled blood pressure, as well as the prevalence of cardiometabolic risk factors among patients from the Mexican Registry of Arterial Hypertension (RIHTA). We conducted a cross-sectional analysis of participants living with arterial hypertension registered on RIHTA between December 2021 and April 2023. We used both the 2017 ACC/AHA and 2018 ESC/ESH thresholds to define controlled and uncontrolled arterial hypertension. We considered eleven cardiometabolic risk factors, which include overweight, obesity, central obesity, insulin resistance, diabetes, hypercholesterolemia, hypertriglyceridemia, low-HDL-C, high-LDL-C, low-eGFR, and high CVD risk. In a sample of 5,590 participants (female: 61%, n=3,393; median age: 64 [IQR: 56-72] years), the prevalence of uncontrolled hypertension varied significantly, depending on the definition (2017 ACC/AHA: 59.9%, 95% CI: 58.6-61.2 and 2018 ESC/ESH: 20.1%, 95% CI: 19.0-21.2). In the sample, 40.43% exhibited at least 5-6 risk factors, and 32.4% had 3-4 risk factors, chiefly abdominal obesity (83.4%, 95% CI: 82.4-84.4), high-LDL-C (59.6%, 95% CI: 58.3-60.9), high-CVD risk (57.9%, 95% CI: 56.6-59.2), high triglycerides (56.2%, 95% CI: 54.9-57.5), and low-HDL-C (42.2%, 95% CI: 40.9-43.5). There is a high prevalence of uncontrolled hypertension interlinked with a high burden of cardiometabolic comorbidities in Mexican adults living with arterial hypertension, underscoring the urgent need for targeted interventions and better healthcare policies to reduce the burden of the disease in our country.

Diffuse myocardial fibrosis is uncommon in people with perinatally acquired human immunodeficiency virus infection

BackgroundCardiovascular disease (CVD) remains a leading cause of death in people living with HIV. Myocardial fibrosis is well-described in HIV infection acquired in adulthood. We evaluate the burden of fibrosis by cardiac magnetic resonance in people with perinatal HIV infection.MethodsIndividuals with perinatally acquired HIV (pnHIV) diagnosed before 10 years-old and on antiretroviral treatment for ≥ 6 months were matched with uninfected controls. Patients with significant cardiometabolic co-morbidities and pregnancy were excluded. Diffuse fibrosis was assessed by cardiac magnetic resonance (CMR) with native T1 mapping for calculation of extracellular volume fraction (ECV). Viability was assessed with late gadolinium enhancement. The normality of fibrosis was assessed using the Komogrov-Smirnov test. Fibrosis between the groups was analyzed using a Mann-Whitney U test, as the data was not normally distributed. Statistical significance was defined as a p-valve < 0.05.ResultsFourteen adults with pnHIV group and 26 controls (71% female and 86% Black race) were assessed. The average (± standard deviation) age in the study group was 29 (± 4.3) years-old. All pnHIV had been on ART for decades. Demographic data, CMR functional/volumetric data, and pre-contrast T1 mapping values were similar between groups. Diastolic function was normal in 50% of pnHIV patients and indeterminate in most of the remainder (42%). There was no statistically significant difference in ECV between groups; p = 0.24.ConclusionPerinatally-acquired HIV was not associated with diffuse myocardial fibrosis. Larger prospective studies with serial examinations are needed to determine whether pnHIV patients develop abnormal structure or function more often than unaffected controls.

Protocolo diagnóstico y terapéutico de la esteatosis hepática asociada a disfunción metabólica

Metabolic dysfunction-associated steatotic liver disease (MASLD) refers to a broad spectrum of liver manifestations that range from simple steatosis, with a generally benign course, to forms with a higher risk of progression, such as hepatic steatosis or advanced liver disease phenotypes like cirrhosis or hepatocellular carcinoma. The global prevalence of MASLD is increasing in parallel to that of the metabolic syndrome, with the main groups at risk for the disease being patients with cardiometabolic comorbidity. Advances in non-invasive diagnostic techniques allow for identifying cases with a higher risk of progression and clinical events in these at-risk populations. The management of patients with MASLD is based on lifestyle modification. There are currently no drugs with an approved indication for the management of MASLD. Therefore, it is crucial to optimize the therapeutic management of metabolic syndrome and cardiovascular risk in these patients.

Prevalence of obstructive sleep apnea after treatment for advanced T-stage head and neck cancer

PurposeTreatment of head and neck cancer (HNC) may lead to obstructive sleep apnea (OSA), but conclusive results on the prevalence of OSA are lacking. The objective of this study is to investigate the prevalence of OSA in a cohort of patients treated for advanced T-stage HNC.MethodsA cross-sectional study was conducted in two tertiary cancer care centers including patients at least 1 year after treatment with curative intent with surgery and/or (chemo)radiotherapy ((C)RT) for advanced T-staged (T3-4) cancer of the oral cavity, oropharynx, hypopharynx, or larynx. A polysomnography (PSG) was performed in all participants. OSA was defined as an apnea–hypopnea index (AHI) of 15 events/h or higher or an AHI of 5 events/h and higher with OSA related symptoms, such as sleeping problems, daytime dysfunction and/or cardiac/metabolic comorbidities collected through file review and questionnaires.ResultsOf the 67 participants, 48 (72%, 95% CI 59–82%) were diagnosed with OSA. Possible risk factors are male gender, higher BMI, greater neck circumference, more nicotine pack years, cardiometabolic comorbidities, use of medication with sleepiness as side effect, present tonsils, lower T-stage (T3 vs. T4 stage), higher AJCC stage and a HPV-negative tumor.ConclusionIn this population of advanced T-stage HNC patients, the prevalence of OSA was 72%, which is considerably higher than in the general population (2–50%). Given the high prevalence, screening of this entire subgroup for OSA may be indicated. Future studies to identify high risk factors and develop an OSA screening protocol are needed.

Influence of the HLA-Cw6 Allele and IFIH1/MDA5 Gene Variants on the Cardiometabolic Risk Profile of Patients with Psoriatic Disease

Background: Cardiovascular comorbidity is a common companion of psoriasis and psoriatic arthritis (PsA). Recently, a significant link has been found between the HLA-Cw6 allele and a better cardiometabolic profile in these patients. We aimed to check this finding in our setting. Methods: A cross-sectional observational study (n: 572 psoriasis patients, 30% with PsA) was conducted. Different study variables were collected in detail, as well as classic cardiometabolic risk factors. The distribution of the HLA-Cw6 allele and the IFIH1/MDA5 gene variants previously linked to disease risk were determined in the study cohort and stratified according to the cardiometabolic comorbidity. Linear and logistic regression models were constructed to analyze these associations. Results: The study cohort included 309 men and 263 women, with a mean age of 46.7 years (SD 14.5) and a mean disease duration of 19.4 years (SD 14.8). We confirmed the known association between HLA-Cw6 and type I psoriasis (familial, severe, and early onset). Psoriasis severity (OR: 2.14), female sex (OR: 1.63), and the IFIH1/MDA5 rs1990760 TT genotype (OR: 1.62) were significantly related to PsA, while HLA-Cw6 was protective (OR: 0.65). HLA-Cw6 carriers showed a lower waist perimeter, lower BMI, and lower risk of both hypertension (OR: 0.52, p &lt; 0.001) and diabetes (OR: 0.36, p &lt; 0.001), but these findings were no longer apparent upon adjusting the regression models. No IFIH1/MDA5 gene variant was associated with any cardiometabolic risk factor. Conclusions: The influence of HLA-Cw6 on the cardiometabolic risk profile of psoriatic patients seems to be explained by other factors (age, sex, duration of the disease or arthritis) and not by this biomarker itself.

Real world outcomes, healthcare utilisation and costs of Alzheimer's disease in England

BackgroundEvidence on health and social care resource utilisation and associated costs, and how this varies across people with Alzheimer's disease (AD) dementia is limited. MethodsRetrospective cohort, using the Discover dataset, which includes linked health and social care records for approximately 2.5 million people in North-West London. Individuals were followed up from the latter of 2010 or from diagnosis of AD dementia (index) up to 2019. Outcomes were overall survival, care home admission, health and social care utilisation and associated costs, and cardiovascular outcomes. Variation was explored in subpopulations and by stratifying by cost quintile. Generalised linear modelling was used to estimate the association between clinical and demographic characteristics and healthcare costs. ResultsThe cohort included 18,116 people diagnosed with AD dementia whose mean age at index was 81 years, 62 % were female and 65 % were of white ethnicity. Median survival from index was 4.9 years (95 %CI: 4.8–5.0). Mean healthcare costs were £4,548(£4,491–£4,604) per person year(ppy). Healthcare costs for the 48 % who used social care were £5,433ppy(£5,353–£5,514) and social care costs were £24,374ppy(£24,372–£24,376). In the overall cohort costs in the highest cost quintile were £13,665ppy(£13,420–£13,911), of which 70 % was from inpatient hospitalisation. Subpopulations admitted to care home (£7,535 £7,362–£7,709), with cardiovascular disease (£6,106;£5,990–£6,222) and with type 2 diabetes (£6,049;£5,901–£6,198) accrued the highest healthcare costs. Factors most strongly associated with cost were dying during follow up (+£2,224;£2,010–£2,493), being frail (+£1,246;£1,051–£1,440) and prior stroke (+£1,207;£908–£1,507). ConclusionCharacteristics of individuals with high healthcare costs include requirement for social care and cardiometabolic comorbidities. Identifying individuals early in their disease course may improve health outcomes and reduce the cost of AD dementia in later life.

Cardiometabolic risk comorbidities in exocrine pancreatic insufficiency compared to patients with cancer: A single centered observational retrospective cohort study.

642 Background: Exocrine pancreatic insufficiency (EPI) is characterized by inadequate secretion of digestive enzymes. EPI is associated with increased risk for pancreatic cancer as well as increased risk for diabetes and consequently cardiometabolic (CM) risk equivalents. Emerging data suggest patients with cancer also have increased CM risk equivalents. To explore the cardiovascular risk associated with both EPI and cancer, we sought to describe and compare CM comorbidities and surrogates in patients with EPI vs cancer. Methods: A retrospective observational electronic chart analysis was done at Ochsner Health, Louisiana, spanning records from January 2017-2020 comparing two cohorts: patients with EPI (n=677) and patients with Cancer (n=1432). Results: The Cancer cohort was older (65.1 ± 11.9 yrs) than the EPI cohort (54.2 ± 17.6 yrs) (p &lt; 0.05). The Cancer cohort had higher AST levels (63.2 ± 106.2 U/L [nl 8-33 U/L] at start, 84.9 ± 447.3 U/L at end) vs the EPI cohort (50.2 ± 86.9 U/L at start, 65.4 ± 368.9 U/L at end) (p &lt; 0.05). The Cancer cohort also had higher ALT levels (69 ± 111.4 U/L (nl 7-55 U/L) at start, 58.5 ± 141.2 U/L at end) vs the EPI cohort (48.7 ± 79.5 U/L at start, 41.4 ± 100.3 U/L at end) (p &lt; 0.05). No significant differences were seen in Cancer cohort vs EPI cohort for A1c, TG, amylase, lipase, cholesterol, uric acid, tobacco/alcohol use, or blood pressure levels. Within the Cancer cohort, there was an increase in neuropathy (11% at the start vs 26.9% at end [p &lt; 0.05]), CHF (3.63% at the start vs 11.5% at end [p &lt; 0.05]), and HTN prevalence (29.9% at the start vs 66.1% at end [p &lt; 0.05]). Cancer patients also had decreased weight (175.2 ± 46.5 lbs at start, 163.8 ± 43.4 lbs at end [p &lt; 0.05]) and BMI (27.3 ± 6.5 at start, 25.7 ± 6.4 at end [p &lt; 0.05]). Among the general cancer cohort, no statistically different changes were seen in hypoglycemia, DKA, retinopathy, nephropathy, ESRD, dialysis, HLD, NAFLD, OSA, CAD, CVD, PAD, hyperuricemia, or gout prevalence over the period of observation or in comparison to EPI cohort. Conclusions: Patients in the Cancer cohort in this study have some indices of greater CM risk compared to those with EPI. Though older, they had significantly higher AST and ALT levels compared to EPI cohort. Over the 3 years of observation, cancer patients developed a statistically significant increase in neuropathy, CHF, and HTN prevalence, and decrease in weight and BMI. These changes may reflect consequent morbidity related both to natural disease progression and/or effects of cancer treatments such as chemotherapy.

Obstructive sleep related breathing disorders and cardiometabolic risk factors – A Portuguese birth cohort

BackgroundPediatric obstructive sleep related breathing disorders (SRBD) are an important under-diagnosed health problem with associated cardiometabolic comorbidities, demonstrated with polysomnographic studies in selected samples. Our main goal was to assess the prevalence of SRBD in a population-based cohort and to analyze its association with cardiometabolic risk factors, in general and by sex. MethodsPediatric Sleep Questionnaire (PSQ) was applied to parents of 7-years-old children evaluated in the birth cohort, Generation XXI. Sex, anthropometrics, blood pressure (BP), lipid profile, glucose, insulin, HOMA-IR, and high-sensitivity C-reactive protein were compared among children with/without SRBD, using Chi-square, Mann-Whitney tests and logistic regression models. ResultsA total of 1931 children (51.2 % boys) were included; 17.5 % were overweight and 15.7 % obese. The prevalence of SRBD was 13.4 %, more frequent among boys (15.7 % vs.10.9 %, p = 0.002) and in overweight/obese children (22.0 % vs.13.6 % vs.11.3 % in obese, overweight and normal weight group, respectively, p < 0.001). Children with SRBD had higher systolic BP (107 ± 8 vs.105±9 mmHg; p = 0.001) and lower HDL-cholesterol levels (54 ± 11 vs.56 ± 11 mg/dL; p = 0.04) than children without SRBD. After adjustment for sex, age, birthweight-for-gestational age and maternal age, children with SRBD had higher BMI-z-score, systolic BP, insulin and HOMA-IR levels, and lower HDL-cholesterol, when compared to those without SRBD, but these associations were lost when adjusting to BMI z-score. Analyzing obese children with the same regression model, those with SRBD presented lower HDL-cholesterol than those without SRBD. ConclusionsOur results identified a male predominance of SRBD in pre-pubertal children and highlighted the potential contribution of SRBD to cardiovascular risk in obese children.

Bimekizumab Efficacy in Patients with Moderate to Severe Plaque Psoriasis and Hypertension, Elevated Body Mass Index, or Hyperglycemia: Results Through 3 years of Treatment in 5 Phase 3/3b Trials

Introduction: Patients with moderate to severe plaque psoriasis have a higher risk of cardiometabolic comorbidities than the general population.1,2 Here, response to bimekizumab (BKZ) in psoriasis patients with hypertension, elevated body mass index (BMI), or hyperglycemia at baseline is reported through 3 years of treatment.&#x0D; Procedure/study: Data were pooled from the following trials: BE SURE, BE VIVID, BE READY, their open-label extension (OLE) BE BRIGHT, and BE RADIANT.3–7 Included patients received BKZ 320 mg every 4 weeks (Q4W) to Week 16, then Q4W or Q8W in the maintenance period and on OLE entry. All received BKZ Q8W from Week 64 (BE RADIANT)/OLE Week 48 (BE BRIGHT) or next scheduled visit (dose groups were combined in this analysis). Psoriasis Area and Severity Index (PASI) ≤2, ≥90% improvement from baseline in PASI (PASI 90), and PASI 100 responses were evaluated in patients with psoriasis and concurrent hypertension (systolic &gt;130 mmHg or diastolic &gt;85 mmHg), elevated BMI (&gt;30 kg/m2), or hyperglycemia (≥140 mg/dL or ≥7.8 mmol/L), based on objective laboratory measurements at baseline. Data are reported using modified non-responder imputation: patients who discontinued due to lack of efficacy or treatment-related adverse events were considered non-responders at subsequent timepoints; multiple imputation was used for all other missing data.&#x0D; Results: Of 1,107 BKZ-randomized patients who entered the OLEs, 546, 493, and 81 had hypertension, elevated BMI, and hyperglycemia at baseline, respectively. At Week 16, 91.3% of all BKZ-treated patients had PASI ≤2; high response rates were also observed in patients with hypertension (88.9%), elevated BMI (87.8%), and hyperglycemia (87.7%). At Year 3 (OLE Week 96), PASI ≤2 response rates were 91.3% (all patients), 90.0% (hypertension), 89.4% (elevated BMI), and 91.1% (hyperglycemia). At Week 16, 90.9%/65.5% of all BKZ-treated patients achieved PASI 90/100; high responses were also observed in patients with hypertension (89.0%/62.8%), elevated BMI (87.6%/60.3%), and hyperglycemia (86.4%/64.2%). At Year 3, PASI 90/100 response rates were 90.7%/70.0% (all patients), 89.3%/66.3% (hypertension), 89.2%/66.2% (elevated BMI), and 87.9%/57.7% (hyperglycemia).&#x0D; Conclusion: High levels of complete/near-complete skin clearance achieved at Week 16 were durable through 3 years’ BKZ treatment in psoriasis patients, including those who had baseline hypertension, elevated BMI, or hyperglycemia.&#x0D; Funding: UCB Pharma.