Cardiometabolic Comorbidities Research Articles

Neighborhood attributes and cardiovascular disease risk in breast cancer survivors: The Pathways Study.

Breast cancer survivors are at a higher risk of cardiovascular disease (CVD) morbidity and mortality compared with the general population. The impact of objective social and built neighborhood attributes on CVD risk in a cohort of female breast cancer survivors was examined. The 3975 participants came from the Pathways Study, a prospective cohort of women with invasive breast cancer from an integrated health care system in northern California. Women diagnosed with breast cancer from 2006 through 2013 were enrolled on average approximately 2 months after diagnosis. Their baseline addresses were geocoded and appended to neighborhood attributes for racial/ethnic composition, socioeconomic status (SES), population density, urbanization, crime, traffic density, street connectivity, parks, recreational facilities, and retail food environment. Incident CVD events included ischemic heart disease, heart failure, cardiomyopathy, or stroke. Cox proportional hazards models estimated associations of neighborhood attributes with CVD risk, which accounted for clustering by block groups. Fully adjusted models included sociodemographic, clinical, and behavioral factors. During follow-up through December 31, 2018, 340 participants (8.6%) had CVD events. A neighborhood racial/ethnic composition measure, percent of Asian American/Pacific Islander residents (lowest quintile hazard ratio [HR],1.85; 95% CI, 1.03-3.33), and crime index (highest quartile HR,1.48; 95% CI, 1.08-2.03) were associated with the risk of CVD events independent of individual SES, hormone receptor status, treatment, cardiometabolic comorbidities, body mass index, and physical activity. With the application of a socio-ecological framework, how residential environments shape health outcomes in women with breast cancer and affect CVD risk in this growing population can be understood.

Factors Associated With Sex Disparities in Leisure-Time Physical Activity: An Analysis of the Behavioral Risk Factor Surveillance System, 2011 to 2021

ObjectiveTo identify whether sex disparities in leisure-time physical activity (LTPA) vary across population subgroups. Participants and MethodsWe used data from the Behavioral Risk Factor Surveillance System (BRFSS) spanning 2011 to 2021. We examined subgroups by age, race/ethnicity, income, employment, education, marital status, body mass index, and cardiometabolic comorbidities (diabetes, hypertension, and cardiovascular disease) to identify where sex disparities in LTPA are most pronounced. ResultsAmong 4,415,992 respondents (57.4% [2,533,234] women and 42.6% [1,882,758] men), women were less likely than men to report LTPA (73.0% vs 76.8%; odds ratio [OR], 0.817; 95% CI, 0.809 to 0.825). The gap was widest between the youngest (OR for the 18- to 24-year age group, 0.71; 95% CI, 0.68 to 0.74) and oldest (OR for the 80 years or older age group, 0.71; 95% CI, 0.69 to 0.73) respondents but was narrower between middle-aged adults (OR for the 50- to 59-year age group, 0.95; 95% CI, 0.93 to 0.97). Disparity was greater among non-Hispanic Black participants (OR, 0.70; 95% CI, 0.68 to 0.72) and Hispanic participants (OR, 0.79; 95% CI, 0.77 to 0.81) than among non-Hispanic White participants (OR, 0.85; 95% CI, 0.84 to 0.86). Disparities were greater at the lowest income levels (OR, 0.81; 95% CI, 0.78 to 0.85) and lower at the highest income levels (OR, 0.94; 95% CI, 0.91 to 0.96). The disparity was greater in unemployed individuals (OR, 0.78; 95% CI, 0.76 to 0.80) compared with employed individuals (OR, 0.91; 95% CI, 0.90 to 0.92). Moreover, disparity was greater in individuals with a body mass index in the overweight or obese range and those with diabetes, hypertension, or cardiovascular disease. ConclusionWomen are less likely than men to engage in LTPA. These disparities are greatest among the young and elderly, Black and Hispanic individuals, lower income and unemployed individuals, and individuals with cardiometabolic disease. Targeted interventions are needed to reduce sex-related disparities.

Serum metabolomics profiling by proton nuclear magnetic resonance spectroscopy reveals sexual dimorphism and masculinization of intermediate metabolism in women with polycystic ovary syndrome (PCOS)

BackgroundThe polycystic ovary syndrome (PCOS) is associated with insulin resistance, obesity and cardiometabolic comorbidities. We here challenged the hypothesis, using state-of-the art proton nuclear magnetic resonance spectroscopy metabolomics profiling, that androgen excess in women induces also a certain masculinization of intermediate metabolism that is modulated by obesity.MethodsParticipants were 53 Caucasian young adults, including 17 women with classic PCOS consisting of hyperandrogenism and ovulatory dysfunction, 17 non-hyperandrogenic women presenting with regular menses, and 19 healthy men, selected in order to be similar in terms of age and body mass index (BMI). Half of the subjects had obesity defined by a body mass index ≥ 30 kg/m2. Subjects maintained the same diet unrestricted in carbohydrates for 3 days before sampling and maintained their lifestyle and exercise patterns prior and during the study. Plasma samples were submitted to proton nuclear magnetic resonance spectroscopy metabolomics profiling.ResultsObesity associated a metabolomics profile mainly characterized by increased branched chain and aromatic aminoacids. Regardless of obesity, this unfavorable profile also characterized men as compared with control women, and was shared by women with PCOS. Notably, the negative impact of obesity on metabolomics profile was restricted to women, with obese men showing no further deterioration when compared with their non-obese counterparts.ConclusionsSerum metabolomics profiling by proton nuclear magnetic resonance spectroscopy reveals sexual dimorphism, and masculinization of intermediate metabolism in women with PCOS, further suggesting a role for sex and sex hormones in the regulation of intermediate metabolism.

The impact of gender on the risk of cardiovascular events in older adults with advanced chronic kidney disease.

Patients with chronic kidney disease (CKD) are at a higher risk of major adverse cardiovascular events (MACE) compared with the general population, but gender differences in this risk, especially in older adults, are not fully known. We aim to identify gender differences in the risk of MACE in older European CKD patients, and explore factors that may explain these differences. The European Quality study (EQUAL) is a prospective study on stage 4-5 CKD patients, ≥65 years old, not on dialysis, from Germany, Italy, the Netherlands, Poland, Sweden and the UK. Cox regression and cumulative incidence competing risk curves were used to identify gender differences in MACE risks. Mediation analysis was used to identify variables which may explain risk differences between men and women. A total of 417 men out of 1134 (37%) and 185 women out of 602 women (31%) experienced at least one MACE, over a follow-up period of 5 years. Women had an 18% lower risk of first MACE compared with men (hazard ratio 0.82; 95% confidence interval 0.69-0.97; P=.02), which was attenuated after adjusting for pre-existing cardiometabolic comorbidities and cardiovascular risk factors. There were no significant gender differences in the risk of recurrent MACE or fatal MACE. The risk difference in MACE by gender was larger in patients aged 65-75 years, compared with patients over 75 years. In a cohort of older adults with advanced CKD, women had lower risks of MACE. These risk differences were partially explained by pre-existing cardiometabolic comorbidities and cardiovascular risk factors.

Sleep and cardiometabolic comorbidities in the obstructive sleep apnoea-COPD overlap syndrome: data from the European Sleep Apnoea Database.

The impact of obstructive sleep apnoea (OSA)-COPD overlap syndrome (OVS) on sleep quality and cardiovascular outcomes has not been fully explored. We aimed to compare clinical and polysomnographic characteristics of patients with OVS versus patients with OSA, and to explore pathophysiological links between OVS and comorbidities. This cross-sectional analysis initially included data from 5600 patients with OSA and lung function in the European Sleep Apnoea Database. Two subgroups of patients with OSA (n=1018) or OVS (n=509) were matched (2:1) based on sex, age, body mass index and apnoea-hypopnea index at baseline. After matching, patients with OVS had more severe hypoxia, lower sleep efficiency and presented with higher prevalences of arterial hypertension, ischaemic heart disease and heart failure compared with patients with OSA. OVS was associated with a significant decrease in sleep efficiency (mean difference (β) -3.0%, 95% CI -4.7 to -1.3) and in nocturnal mean peripheral oxyhaemoglobin saturation (SpO2) (β -1.1%, 95% CI -1.5 to -0.7). Further analysis revealed that a decrease in forced expiratory volume in 1 s and arterial oxygen tension was related to a decrease in sleep efficiency and in mean nocturnal SpO2. A COPD diagnosis increased the odds of having heart failure by 1.75 (95% CI 1.15-2.67) and systemic hypertension by 1.36 (95% CI 1.07-1.73). Nocturnal hypoxia was strongly associated with comorbidities; the mean nocturnal SpO2 and T90 (increase in time below SpO2 of 90%) were associated with increased odds of systemic hypertension, diabetes and heart failure but the oxygen desaturation index was only related to hypertension and diabetes. Patients with OVS presented with more sleep-related hypoxia, a reduced sleep quality and a higher risk for heart failure and hypertension.

Association between cardiometabolic comorbidities and Parkinson's disease in a Mexican population.

The prevalence of Parkinson's disease (PD) increases as the population ages. Studies have shown that some cardiometabolic comorbidities could be associated with risk or protection against developing PD. A retrospective case-control study was carried out to analyze the relationship between PD and cardiometabolic comorbidities. Subjects with PD and controls without PD were consecutively recruited. Data on type 2 diabetes mellitus, systemic arterial hypertension (SAH), dyslipidemia and body mass index were collected. Logistic regression analyses were carried out. A total of 781 subjects with PD (56.5% males) and 1,000 controls (44.4% males) were included. After adjusting for age and gender, SAH was found as an independent risk factor (OR: 1.32; 95% CI: 1.05-1.67; p = 0.02), and obesity as a protective factor (OR: 0.72; 95% CI: 0.56-0.93; p = 0.01). Subjects with SAH had a higher risk of having PD, while obese subjects had a lower risk of having PD. The relationship between cardiometabolic disease, its treatment, and PD etiopathogenesis appears to be extremely complex given the amount of contradictory data.

Clinical characteristics and severity of COVID-19 among Mexican adults.

Obesity, diabetes, hypertension and age have been pointed at as factors that influence on the progression of COVID-19; however, evidence for other conditions is inconclusive. To identify which clinical characteristics are related to COVID-19 severity and to determine whether age acts a modifier of the relationship between cardio-metabolic comorbidities (CMC) and COVID-19 progression. Data on ≥ 20-year-old confirmed cases (n = 159,017) were analyzed. Hospitalization, development of pneumonia, intubation requirement, intensive care unit admission and death were the dependent variables in Poisson regression models estimation, whereas the interaction between age and different CMCs were the independent variables. Having CMCs, as well as other comorbidities, was directly related to COVID-19 progression, whereas chronic obstructive pulmonary disease was only related to an increase in the risk of dying. The risk for COVID-19 severity was lower as age was more advanced. Asthma and smoking were not risk factors for the progression of COVID-19. In the Mexican population, the risk of COVID-19 progression associated with comorbidities was higher in young adults.

Prevalence, Cardiometabolic Comorbidities and Reporting of Chronic Kidney Disease; A Hungarian Cohort Analysis.

Objectives: Chronic kidney disease (CKD) implies increased comorbidity burden, disability, and mortality, becoming a significant public health problem worldwide, however, prevalence data are lacking in Hungary. Methods: We determined CKD prevalence, stage distribution, comorbidities using estimated glomerular filtration rate (eGFR), albuminuria, and international disease codes in a cohort of healthcare utilizing residents within the catchment area of the University of Pécs, in the County Baranya, Hungary, between 2011 and 2019 by database analysis. The number of laboratory-confirmed and diagnosis-coded CKD patients were compared. Results: Of the total 296,781 subjects of the region, 31.3% had eGFR tests and 6.4% had albuminuria measurements, of whom we identified 13,596 CKD patients (14.0%) based on laboratory thresholds. Distribution by eGFR was presented (G3a: 70%, G3b: 22%, G4: 6%, G5: 2%). Amongst all CKD patients 70.2% had hypertension, 41.5% diabetes, 20.5% heart failure, 9.4% myocardial infarction, 10.5% stroke. Only 28.6% of laboratory-confirmed cases were diagnosis-coded for CKD in 2011-2019. Conclusion: CKD prevalence was 14.0% in a Hungarian subpopulation of healthcare-utilizing subjects in 2011-2019, and substantial under-reporting of CKD was also found.

Carotid body: an emerging target for cardiometabolic co-morbidities.

What is the topic of this review? Regarding the global metabolic syndrome crisis, this review focuses on common mechanisms for high blood sugar and high blood pressure. Connections are made between the homeostatic regulation of blood pressure and blood sugar and their dysregulation to reveal signalling mechanisms converging on the carotid body. What advances does it highlight? The carotid body plays a major part in the generation of excessive sympathetic activity in diabetes and also underpins diabetic hypertension. As treatment of diabetic hypertension is notoriously difficult, we propose that novel receptors within the carotid body may provide a novel treatment strategy. The maintenance of glucose homeostasis is obligatory for health and survival. It relies on peripheral glucose sensing and signalling between the brain and peripheral organs via hormonal and neural responses that restore euglycaemia. Failure of these mechanisms causes hyperglycaemia or diabetes. Current anti-diabetic medications control blood glucose but many patients remain with hyperglycemic condition. Diabetes is often associated with hypertension; the latter is more difficult to control in hyperglycaemic conditions. We ask whether a better understanding of the regulatory mechanisms of glucose control could improve treatment of both diabetes and hypertension when they co-exist. With the involvement of the carotid body (CB) in glucose sensing, metabolic regulation and control of sympathetic nerve activity, we consider the CB as a potential treatment target for both diabetes and hypertension. We provide an update on the role of the CB in glucose sensing and glucose homeostasis. Physiologically, hypoglycaemia stimulates the release of hormones such as glucagon and adrenaline, which mobilize or synthesize glucose; however, these counter-regulatory responses were markedly attenuated after denervation of the CBs in animals. Also, CB denervation prevents and reverses insulin resistance and glucose intolerance. We discuss the CB as a metabolic regulator (not just a sensor of blood gases) and consider recent evidence of novel 'metabolic' receptors within the CB and putative signalling peptides that may control glucose homeostasis via modulation of the sympathetic nervous system. The evidence presented may inform future clinical strategies in the treatment of patients with both diabetes and hypertension, which may include the CB.

National Knowledge-Driven Management of Obstructive Sleep Apnea—The Swedish Approach

This paper describes the development of "Swedish Guidelines for OSA treatment" and the underlying managed care process. The Apnea Hypopnea Index (AHI) is traditionally used as a single parameter for obstructive sleep apnea (OSA) severity classification, although poorly associated with symptomatology and outcome. We instead implement a novel matrix for shared treatment decisions based on available evidence. A national expert group including medical and dental specialists, nurses, and patient representatives developed the knowledge-driven management model. A Delphi round was performed amongst experts from all Swedish regions (N = 24). Evidence reflecting treatment effects was extracted from systematic reviews, meta-analyses, and randomized clinical trials. The treatment decision in the process includes a matrix with five categories from a "very weak"" to "very strong" indication to treat, and it includes factors with potential influence on outcome, including (A) OSA-related symptoms, (B) cardiometabolic comorbidities, (C) frequency of respiratory events, and (D) age. OSA-related symptoms indicate a strong incitement to treat, whereas the absence of symptoms, age above 65 years, and no or well-controlled comorbidities indicate a weak treatment indication, irrespective of AHI. The novel treatment matrix is based on the effects of treatments rather than the actual frequency of respiratory events during sleep. A nationwide implementation of this matrix is ongoing, and the outcome is monitored in a prospective evaluation by means of the Swedish Sleep Apnea Registry (SESAR).

Four-year drug survival of apremilast in patients with psoriasis.

This real-world study at a single academic center retrospectively examined the drug survival of apremilast for patients with psoriasis. Retrospective information was extracted from the medical records of patients with psoriasis treated with apremilast at the Department of Dermatology, Jichi Medical University Hospital, between March 1, 2017, and June 31, 2021. In total, 281 patients were included in this study. Of these patients, 22% had psoriatic arthritis and 57% had a history of prior systemic treatment, including biologics, before the initiation of apremilast. The 1-, 2-, 3-, and 4-year drug survival rates were 54%, 41%, 32%, and 30%, respectively. Cox regression analysis revealed that sex, duration of plaque psoriasis (<10 years vs ≥10 years), presence of psoriatic arthritis, involvement of scalp lesions, involvement of palmoplantar lesion, involvement of nail lesions, having cardiometabolic comorbidities, and a history of prior systemic treatment did not have any significant impact on drug survival. The most common reason for apremilast discontinuation was inadequate efficacy (27%), followed by adverse events (12%). Approximately 49% of the patients experienced one or more adverse events. Diarrhea was the most common adverse event (24%), followed by nausea (19%) and headache (11%).

Is obstructive sleep apnea a circadian rhythm disorder?

Obstructive sleep apnea is the most common sleep-related breathing disorder worldwide and remains underdiagnosed. Its multiple associated comorbidities contribute to a decreased quality of life and work performance as well as an increased risk of death. Standard treatment seems to have limited effects on cardiovascular and metabolic aspects of the disease, emphasising the need for early diagnosis and additional therapeutic approaches. Recent evidence suggests that the dysregulation of circadian rhythms, processes with endogenous rhythmicity that are adjusted to the environment through various cues, is involved in the pathogenesis of comorbidities. In patients with obstructive sleep apnea, altered circadian gene expression patterns have been demonstrated. Obstructive respiratory events may promote circadian dysregulation through the effects of sleep disturbance and intermittent hypoxia, with subsequent inflammation and disruption of neural and hormonal homeostasis. In this review, current knowledge on obstructive sleep apnea, circadian rhythm regulation, and circadian rhythm sleep disorders is summarised. Studies that connect obstructive sleep apnea to circadian rhythm abnormalities are critically evaluated. Furthermore, pathogenetic mechanisms that may underlie this association, most notably hypoxia signalling, are presented. A bidirectional relationship between obstructive sleep apnea and circadian rhythm dysregulation is proposed. Approaching obstructive sleep apnea as a circadian rhythm disorder may prove beneficial for the development of new, personalised diagnostic, therapeutic and prognostic tools. However, further studies are needed before the clinical approach to obstructive sleep apnea includes targeting the circadian system.

IL-23/Th-17 útvonal: egy lehetséges közös nevező a pikkelysömör és kardiometabolikus társbetegségeinek kialakulásában

The systemic nature of the inflammatory processes in psoriasis is now widely accepted. It is known that the IL-23/ Th-17 axis plays a pivotal role in the development of skin and joint symptoms, which immune processes overlap with the pathways involved in the pathogenesis of cardiometabolic comorbidities at several points. IL-17 inhibitor biological therapies are frontline treatments for moderate-to-severe psoriasis and have also been the focus of interest in recent years because of their potential effects on comorbidities. In this review we aim to describe the processes of the IL-23/Th-17 axis associated with cardiometabolic pathologies and the effect of IL-17 inhibitors on these comorbidities through international data and studies conducted at the Department of Dermatology, Venereology and Dermatooncology, Semmelweis University.

Self-organized metabotyping of obese individuals identifies clusters responding differently to bariatric surgery.

Weight loss through bariatric surgery is efficient for treatment or prevention of obesity related diseases such as type 2 diabetes and cardiovascular disease. Long term weight loss response does, however, vary among patients undergoing surgery. Thus, it is difficult to identify predictive markers while most obese individuals have one or more comorbidities. To overcome such challenges, an in-depth multiple omics analyses including fasting peripheral plasma metabolome, fecal metagenome as well as liver, jejunum, and adipose tissue transcriptome were performed for 106 individuals undergoing bariatric surgery. Machine leaning was applied to explore the metabolic differences in individuals and evaluate if metabolism-based patients' stratification is related to their weight loss responses to bariatric surgery. Using Self-Organizing Maps (SOMs) to analyze the plasma metabolome, we identified five distinct metabotypes, which were differentially enriched for KEGG pathways related to immune functions, fatty acid metabolism, protein-signaling, and obesity pathogenesis. The gut metagenome of the most heavily medicated metabotypes, treated simultaneously for multiple cardiometabolic comorbidities, was significantly enriched in Prevotella and Lactobacillus species. This unbiased stratification into SOM-defined metabotypes identified signatures for each metabolic phenotype and we found that the different metabotypes respond differently to bariatric surgery in terms of weight loss after 12 months. An integrative framework that utilizes SOMs and omics integration was developed for stratifying a heterogeneous bariatric surgery cohort. The multiple omics datasets described in this study reveal that the metabotypes are characterized by a concrete metabolic status and different responses in weight loss and adipose tissue reduction over time. Our study thus opens a path to enable patient stratification and hereby allow for improved clinical treatments.

Quantifying impact of obesity on cardiometabolic comorbidities and public health implications: Insights from South Africa

IntroductionSouth Africa has the highest obesity and hypertension rates in the African region. In this cross-sectional study, we aimed to quantify the correlates and burden of obesity and their impacts on cardiometabolic conditions. MethodsThe study population was 80,270 men(41 %) and women(59 %) who participated in South African national surveys (2008-to-2017). Weighted-logistic regression models and the population attributable risk (PAR %) were used after accounting for the correlation structure of the risk factors in a multifactorial setting. ResultsOverall, 63 % of the women and 28 % of the men were either overweight or obese. Parity was identified as the most influential factor and exclusively associated with 62 % of the obesity in women; being married/cohabiting had the highest impact on obesity in men and associated with 37 % of the obesity. Overall, 69 % of them had comorbidities including hypertension, diabetes and heart disease. More than 40 % of the comorbidities were attributed to overweight/obesity. ConclusionDeveloping culturally appropriate prevention programs are urgently needed to raise awareness of obesity, hypertension and their impacts on severe cardiometabolic diseases. This approach would also significantly reduce COVID-19 related poor health outcomes and premature deaths.

HIV, Diabetes, and Cardiometabolic Comorbidities: Optimal Health Outcomes

HIV, Diabetes, and Cardiometabolic Comorbidities: Optimal Health Outcomes

Odds of Cardiometabolic Diseases and Medications in Children With Cerebral Palsy.

Individuals with cerebral palsy may be at risk of obesity, but outcomes and risk factors are understudied. The study objectives are to evaluate the frequency of body mass index (BMI) weight categories of individuals with cerebral palsy and the odds of cardiometabolic-specific diseases and medications. We hypothesize subjects with cerebral palsy and an increased body mass index will have higher odds of cardiometabolic specific diseases and medications. This is a retrospective observational cohort study utilizing TriNetX, an electronic health record database, in subjects with cerebral palsy aged 2-18 years with an available body mass index. The study population was divided into 4 body mass index percentile categories, underweight (<5th body mass index percentile), healthy weight (≥5th to <85th percentile), overweight (≥85th to <95th percentile), and obese (≥95th percentile), and the odds of the following variables were evaluated: diagnostic codes and medication codes. We computed the odds ratio to test for associations between the body mass index categories and the variables of interest. A total of 5993 subjects were included: underweight (251, 4.2%), healthy weight (2390, 39.9%), overweight (943, 15.7%), and obese (2409, 40.2%). Obese subjects had a higher odds of asthma, diabetes mellitus, hypertension, and sleep apnea when compared to the health weight group. This study found patients with cerebral palsy classified as obese had higher odds of cardiometabolic comorbidity and medication codes that influence weight. Body mass index measurements are limited in this population but may be used cautiously to evaluate the body type of children with cerebral palsy and monitor cardiometabolic-associated comorbidity occurrence.

Abstract P535: Associations of Genetically Determined Favourable and Unfavourable Adiposity Across the Phenome

Background: The large-scale investigation of the genetic architecture of favourable adiposity (FA) and unfavourable adiposity (UFA) may unravel mechanisms coupling higher adiposity and cardiometabolic comorbidities, and may in turn aid in the prevention, prediction and management of these diseases. Aims and Objectives: We aimed to interrogate FA and UFA in relation to a plethora of clinical outcomes, investigate their causality, and test whether a healthy lifestyle interacts with FA/UFA for the risk of disease. Materials and Methods: We performed a Mendelian randomisation-phenome-wide association study (MR-PheWAS) to identify health outcomes associated with FA and UFA. We first conducted a PheWAS of FA and UFA with 988 phenotypes in 426,295 UK Biobank individuals. Health outcomes passing false-discovery rate (FDR) correction for multiple testing were taken forward to MR analyses. SNP-outcome associations were extracted from external GWAS consortia data. Finally, we examined the association between FA/UFA tertiles of genetic risk and tertiles of lifestyle score and incident health outcomes using proportional hazards models. Results: Our two sample MR results suggest that a 1-SD higher genetically instrumented FA is associated with lower odds of type 2 diabetes (OR: 0.05, 95% CI: 0.02 to 0.11), hypertension (0.30, 0.18 to 0.50) and coronary atherosclerosis (0.25, 0.10 to 0.62), and with higher odds of ventral hernia (18.15, 4.22-77.97). Moreover, 1-SD higher genetically determined UFA was associated with increased odds of type 2 diabetes (5.30, 3.27-8.61), hypertension (2.40, 1.55-3.71), myocardial infarction (1.99, 1.49-2.65), cholelithiasis (2.92, 1.87-4.56), and atrial fibrillation (2.17, 1.28-3.69) at significance passing FDR q&lt;0.05. Sensitivity analyses were consistent with the main results. Our Cox regression model indicated that a favourable lifestyle is associated with a more pronounced risk reduction in cardiometabolic health outcomes and can have a more substantial impact on cardiometabolic and inflammatory conditions for individuals with either a high FA and a low UFA GRS profiles. Conclusions: Our findings offer novel insight into previously unreported effects of favourable and unfavourable adiposity, suggesting that a healthy lifestyle can benefit individuals with both favourable and unfavourable genetic risk scores. This highlights the importance of population-wide lifestyle approaches to address the problem of obesity and risk-stratifying the population according to favourable and unfavourable adiposity.

Is Clozapine-induced Weight Gain Dose-dependent? Results From a Prospective Cohort Study.

Antipsychotic-induced metabolic adverse effects are risk factors for cardiometabolic comorbidities. Whether dose lowering could mitigate such effects remains unclear. The present study aims to investigate the associations between clozapine doses and modifications of weight, blood pressure, blood glucose, and lipid levels. Linear mixed-effects models of weight changes over 1 year and of variations of other metabolic parameters over 4 months were applied to a prospective cohort of 115 patients. Age- and sex-stratified analyses of weight changes were also performed. Each 100 mg dose increment of clozapine was associated on average with a +0.48% weight increase (P = .004) over 1 year of treatment. Weight increase was greater for treatment duration ≤3 vs >3 months (+0.84% and +0.47% per month, respectively, P < .001), with a significant association with the dose for durations >3 months (+0.54%, P = .004) and a trend for durations ≤3 months (+0.33%, P = .075). Dose increments of 100 mg were also associated with weight increases of +0.71% among adults (P = .001), +1.91% among the elderly (P < .001) and +1.32% among men (P < .001) with no associations among women (P = .62). Among young adults, weight change was positively associated with doses ≤300 mg/day (+2.19% per 100 mg, P = .001), whereas no association was found with doses >300 mg/day (P = .60). No significant effect of clozapine dose on other metabolic parameters was found. This study reports a modest effect of clozapine dose increases on weight gain over 1 year with differences among age categories and sexes and no dose effect on other metabolic parameters over 4 months.

Association between pre-existing cardiometabolic comorbidities and the pathological profiles of breast cancer at initial diagnosis: a cross sectional study

Association between pre-existing cardiometabolic comorbidities and the pathological profiles of breast cancer at initial diagnosis: a cross sectional study