Cardiometabolic Risk Factors Research Articles

The association of steatotic liver disease with recurrent ischemic events in patients with chronic coronary syndrome: a multicenter cohort study

Abstract Background/introduction A panel of multi-society experts has proposed new subcategories under the term steatotic liver disease (SLD), replacing the exclusive term non-alcoholic fatty liver disease with the new nomenclature metabolic dysfunction-associated steatotic liver disease (MASLD). However, the prognostic impact of SLD subtypes in patients with chronic coronary syndrome (CCS) remains unknown. Purpose We aimed to investigate the associations between SLD subtypes and recurrent event risks in CCS patients. Methods Our analysis included a total of 9,448 patients with CCS from a large multicenter nationwide cohort. Hepatic steatosis was defined as hepatic steatosis index ≥36 and ultrasound evidence. Patients were categorized into four groups based on the evidence of steatosis, cardiometabolic risk factors and alcohol intake: 1) no SLD; 2) MASLD; 3) MASLD with increased alcohol intake (MetALD) and 4) SLD with other causes. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality, myocardial infarction, stroke and unplanned revascularization. Results The prevalence of no SLD, MASLD, MetALD and SLD with other causes in our population was 37.3%, 47.7%, 14.7% and 0.3%, respectively. During a median follow-up of 2.0 years, 759 (8.0%) MACCE events occurred. After multivariable adjustment, MASLD (HR 1.25, 95%CI 1.06-1.48), MetALD (HR 1.31, 95%CI 1.04-1.65) and SLD with other causes (HR 2.81, 95%CI 1.04-7.57) were all significantly associated with higher MACCE risks compared to no SLD. Conclusions A significant proportion of SLD was observed in CCS patients. Patients with various SLD subcategories all had higher risks of recurrent events.

Cardiometabolic risk factor clusters in older adults using latent class analysis on the Bushehr elderly health program

Metabolic syndrome (MetS), comprising obesity, insulin resistance, hypertension, and dyslipidemia, increases the risk of type II diabetes mellitus and cardiovascular disease. This study aimed to identify the prevalence and determinants of specific clusters of the MetS components and tobacco consumption among older adults in Iran. The current study was conducted in the second stage of the Bushehr Elderly Health (BEH) program in southern Iran—a population-based cohort including 2424 subjects aged ≥ 60 years. Latent class analysis (LCA) was used to identify MetS and tobacco consumption patterns. Multinomial logistic regression was conducted to investigate factors associated with each MetS class, including sociodemographic and behavioral variables. Out of 2424 individuals, the overall percentage of people with one or more components of MetS or current tobacco use was 57.8% and 20.8%, respectively. The mean (SD) age of all participants was 69.3(6.4) years. LCA ascertained the presence of four latent classes: class 1 (“low risk”; with a prevalence of 35.3%), class 2 (“MetS with medication-controlled diabetes”; 11.1%), class 3 (“high risk of MetS and associated medication use”; 27.1%), and class 4 (“central obesity and treated hypertension”; 26.4%). Compared to participants with a body mass index (BMI) < 30, participants with BMI ≥ 30 were more likely to belong to class 3 (OR 1.91, 95% CI 1.31–2.79) and class 4 (OR 1.49, 95% CI 1.06–2.08). Polypharmacy was associated with membership in class 2 (OR 2.07, 95% CI 1.12–3.81), class 3 (OR 9.77, 95% CI 6.12–15.59), and class 4 (OR 1.76, 95% CI 1.07–2.91). The elevated triglyceride-glucose index was associated with membership in class 2 (OR 12.33, 95% CI 7.75–19.61) and class 3 (OR 12.04, 95% CI 8.31–17.45). Individuals with poor self-related health were more likely to belong to class 3 (OR 1.43; 95% CI 1.08–1.93). Four classes were identified among older adults in Iran with distinct patterns of cardiometabolic risk factors. Segmenting elderly individuals into these cardiometabolic categories has the potential to enhance the monitoring and management of cardiometabolic risk factors. This strategy may help reduce the severe outcomes of metabolic syndrome in this susceptible population.

Comorbidity neural network model for personalised recommendations in cardiometabolic risk factor management: towards early precision medicine in routine clinical practice

Abstract Background and Aims Hypertension and hypercholesterolaemia often develop in tandem to confer a risk of cardiovascular disease that may be more than additive. The present study explored early comorbid therapeutic intervention, i.e., beyond individual disease silos, while minimising data bias to provide clinical decision support tools that are portable across clinics. Methods A neural network was created to reproduce UK national clinical guidelines with an accuracy higher than 95%. Relying on real-world evidence from the UK primary care Clinical Practice Research Datalink electronic health record resource, a transfer learning methodology was then applied to achieve recommended risk factor goal attainment after two years. Shapley values derived from game theory were used to define similar digital twin cohorts, and to evaluate individualised recommendations that deviated from national clinical guidelines by rejecting a no-benefit hypothesis retrospectively in a classical proportion test. The methodology was ported to an independent hold-out dataset with anonymized records from six primary care clinics in the South of England. Results The adult patient population (n=469,496, mean+SD age 61+11yr; M 56% vs F 44%; primary 84% vs secondary prevention 16%) included 101,255 diagnosed for hypertension and 112,180 for cholesterol management. While a majority of the 52,504 therapeutic decisions in a test set agree with single morbidity guidelines, for 4639 deviations from the guidance, a significant minority was identified for whom alternative therapy was recommended. Rejecting a no-clinical benefit hypothesis at the 95% confidence level in a retrospective analysis, 1367 decisions showed statistically significant better outcomes over guidelines, for example by escalating anti-hypertensive therapies for patients receiving statin therapy (1085) or by complementing anti-hypertensive therapy with a statin (158). Similar findings were obtained when tested in a hold-out dataset with 13,725 decisions for 6531 patients. Conclusions The results support the contention that machine learning can identify patient subgroups for whom comorbid intervention deviating from clinical guidelines may be appropriate. A novel aspect of the study is the demonstration of clinically portable and actionable application of machine learning in the context of comorbid cardiometabolic diseases. The results represent practical steps towards personalised precision medicine for cardiovascular comorbidity in routine clinical practice.

Generalised and visceral obesity metrics and ankle-brachial systolic blood pressures during pregnancy

Abstract Background Increased body mass index (BMI) (generalised obesity) and waist-to-height ratio (WHtR) (visceral obesity) are associated differently with brachial and ankle blood pressures in the general population. Ankle blood pressures are associated with blood glucose in pregnancy. This study investigates the relationship between BMI and WHtR with the brachial and ankle blood pressures separately during pregnancy. Methods Pregnant women were recruited during antenatal visits at an antenatal clinic in Bradford Royal Infirmary, UK, and their BMI, waist circumference, systolic, and diastolic blood pressure were clinically measured by staff in the second trimester. Additionally, blood pressure readings from both arms (left and right brachial arteries) and ankles [dorsalis pedis artery (DP) and posterior tibial artery (PT) on both sides] were obtained using Doppler by research staff. Results A total of 179 women participated, with an average BMI of 28.5 Kg/m2 (SD = 4.97) and average WHtR of 0.61 (SD = 0.08). BMI exhibited a positive correlation with all blood pressure measurements (r = 0.165 to 0.419, p &amp;lt; 0.05), while WHtR demonstrated significant correlations only with the right brachial, left PT, systolic and diastolic blood pressures (r: 0.170 to 0.271, p &amp;lt; 0.05). Moreover, BMI significantly associated with all blood pressure measurements in linear regression models, after adjusting for various sociodemographic and other factors, whereas WHtR significantly predicted only right brachial and left PT and some of the other blood pressure measurements. Conclusions BMI, and to a lesser extent WHtR, are associated with both brachial and ankle blood pressure measurements during pregnancy. These findings underscore the importance of recognizing the varying impacts of cardiometabolic risk factors for early detection and management of potential complications in pregnancy and the postpartum period. Key messages • BMI &amp; WHtR are associated differently with brachial and ankle blood pressures in pregnancy. • Further exploration of combined non-invasive measurements like BMI, WHtR, brachial, and ankle blood pressures in early pregnancy for gestational diabetes mellitus and other co-morbidities is needed.

Long-term prognostic impact of fasting plasma glucose and myocardial flow reserve beyond other risk factors and heart disease phenotypes

Abstract Background Cardiometabolic risk factors, including high fasting plasma glucose (hFPG), are emerging determinants of residual mortality risk in patients with coronary artery disease (CAD) or heart failure (HF). Coronary microvascular dysfunction, encompassing a broad spectrum of traditional and emerging risk factors, might be a comprehensive risk predictor in these patients. Purpose To assess whether hFPG and global myocardial blood flow (MBF) reserve measured by positron emission tomography (PET), expressing global coronary function, may predict long-term prognosis beyond other risk factors and the presence of obstructive CAD or left ventricular (LV) dysfunction associated with HF. Methods Among 281 consecutive patients undergoing cardiac PET/CT because of stable chest pain or dyspnea we retrospectively collected long-term follow-up data in 103 patients (mean age 61±10 years, 74 males) in whom MBF measurements, coronary angiography and clinical data were available. Disease phenotypes included obstructive CAD (35%), LV dysfunction without obstructive CAD (43%) or none (22%). Results The mean age was 61±10 years (74 males, 72%). Among CVD risk factors, high LDL-cholesterol (hypercholesterolemia under treatment or LDL-C&amp;gt; 130 mg/dL) was present in 72%, high systemic blood pressure (hypertension under treatment or SBP&amp;gt;130/85 mmHg) in 51%, smoking habits in 49%, obesity (BMI&amp;gt;30 Kg/m2) in 22%, type 2 diabetes under treatment in 17%, low HDL-cholesterol (HDL-C&amp;lt; 40 mg/dL in males and &amp;lt;50 mg/dL in females) in 51%, high triglycerides (TG&amp;gt;150 mg/dL) in 27% and high fasting plasma glucose (FPG&amp;gt;100 mg/dL) in 33%. Global MBF reserve was &amp;lt;2 in 68% of patients. In a median follow-up of 10.9 years (7.8-13.9 IQR), 39 patients (37.8%) died (13.6% cardiac death). At multivariable Cox analyses including all risk factors and MBF reserve, age (HR 1.06, 95% CI 1.02-1.11), high FPG (HR 2.28, 95% CI 1.09-4.79) and depressed MBF reserve (HR 4.79, 95% CI 2.14-10.69) were the only independent predictors of death (Global χ2 36.74, P=0.0001). When disease phenotypes were added to the model, age (HR 1.07, 95% CI 1.02-1.12), high FPG (HR 2.18, 95% CI 1.02-4.63) and depressed MBF reserve (HR 4.47, 95% CI 1.96-10.18) remained independent predictors of death (Global χ2 37.41, P=0.0004) (Figure 1). Figure 2 plots the observed all cause death rate in patients with different disease phenotypes stratified for absence/presence of high FPG or MBF reserve &amp;lt;2. Death rate progressively increases according to disease phenotypes and is significantly associated with high FPG (P=0.049) or impaired MBF reserve (P=0.012) in each patient group. Conclusions These results suggest a strong long-term prognostic role of high FPG and depressed MBF reserve in a selected high-risk population of patients with high prevalence of obstructive CAD or HF.Figure 1 Figure 2

Applicability of VICTORION-1 PREVENT Criteria to the US Population

Abstract Background VICTORION-1 PREVENT (V-1P) is an ongoing randomized clinical trial comparing inclisiran sodium 300mg every six months with placebo for primary prevention in patients with high cardiovascular (CV) risk. Purpose We evaluated the generalizability of V-1P trial enrollment criteria to the US population to understand the demographic and CV health characteristics of the trial target population. Methods We included data from the National Health and Nutrition Examination Survey (N=25,531, 2015-March 2020), a nationally representative sample of the US population. Enrollment criteria similar to V-1P were applied. Nonpregnant adults 40-79 years with low-density lipoprotein cholesterol (LDL-C) of 70-189 mg/dL were included. 10-year risk for CV disease was determined using the American Heart Association race-free 10-year PREVENT risk equations. Individuals with 10-year risk &amp;gt;20% or 7.5%-19.9% with two risk enhancing factors at baseline were included. Risk enhancing factors included elevated high sensitivity C-reactive protein (≥2 mg/L), inflammatory arthritis, estimated glomerular filtration rate &amp;lt;60 ml/min/1.73 m2, metabolic syndrome, or early family history of CV disease. Patients with history of atherosclerotic CV disease or liver disease were excluded. Estimates of demographics and health characteristics were nationally representative using survey weights. Results Among US adults, 21,576,506 (standard error [SE]: ±1,258,255) meet eligibility criteria for V-1P (weighted estimate). This represents 8.8% of all US adults or 15.1% of US adults 30-79 years. The V-1P eligible population had a mean age of 65.3 years (SE: ±0.5 years), and 55.0% (SE: ±2.5%) were female. Compared with the US adult population (≥18 years), V-1P eligible population had a higher mean body mass index (32.6 ± 0.3 kg/m2 vs 29.5 ± 0.2 kg/m2) and higher rates of obesity (61.0% ± 2.1% vs 40.0% ± 1.1%) (Table). V-1P eligible population also had higher mean systolic blood pressure (133.9 ± 1.0 mmHg vs 121.7 ± 0.3 mmHg), similar mean diastolic blood pressure (72.6 ± 0.8 mmHg vs 71.8 ± 0.2 mmHg), and higher rates of hypertension (85.8% ± 2.0% vs 45.9% ± 1.1%). Mean hemoglobin A1c percent (6.3 ± 0.1 vs 5.7 ± 0.02), fasting blood sugar (127.7 ± 1.9 mg/dL vs 109.2 ± 0.6 mg/dL), and diabetes rates (39.7% ± 2.6% vs 13.1% ± 0.7%) were higher in the V-1P eligible population. Mean low-density lipoprotein cholesterol (115.8 ± 1.5 mg/dL vs 110.2 ± 0.8 mg/dL) and fasting triglycerides (137.6 ± 5.0 mg/dL vs 110.4 ± 1.7 mg/dL) were higher, while mean high-density lipoprotein cholesterol was lower (49.9 ± 0.8 mg/dL vs 54.8 ± 0.4 mg/dL). The distribution of key CV risk factors is shown in the Figure. Conclusion V-1P enrollment criteria apply to many patients. These patients have significant cardiometabolic risk factor burden, and effective preventive therapies could have substantial health impact.

Traditional medicine use to manage hypercholesterolemia, hyperglycaemia and hypertension in Ecuador

Abstract Background Although the use of traditional medicine (TM) to manage health issues is frequently reported, clinical guidelines often overlook this practice. This study aimed to describe the frequency of TM use to control 3 cardiometabolic risk factors for non-communicable diseases (arterial hypertension, hypercholesterolemia, and hyperglycaemia, collectively referred to as CMRF here); and associated sociodemographic, economic, and clinical characteristics. Methods Descriptive cross-sectional study with a representative population of two health districts in Ecuador, one urban in southern Quito and one in a forested rural area with diverse ethnic groups in Esmeraldas. We included 602 individuals with at least one CMRF and calculated the proportion of those who reported regular use of TM (herbal or traditional remedies) to control their CMRF. We used a multivariable logistic regression model to calculate Odds Ratios for TM use according to sociodemographic, economic, and clinical characteristics. Results TM was commonly used to control CMRF in both sociocultural contexts (39.4% Esmeraldas, 31.1% Quito), often in combination with conventional medicine (CM). A notable percentage of people (33.9% Esmeraldas, 39.0% Quito) did not take any treatment for their CMRF, and the rest used CM alone. In both settings, education was significantly associated with TM use. While in Quito people with higher education were more likely to use TM (aOR 2.04, 95%CI 1.03-3.90), in Esmeraldas, it was more common among people without formal schooling (aOR 3.76; 95%CI 1.59-8.88) as well as those of younger age (aOR per year 0.97; 95%CI 0.95-0.99) and from Afro-Ecudorian ethnicity (aOR 2.13; 95%CI 1.02-4.45). Conclusions Traditional medicine is used by a significant portion of Ecuador’s population, highlighting the need for a more accessible and intercultural approach to healthcare. Key messages • The use of traditional medicine to address hypertension, hypercholesterolemia, and hyperglycaemia appears to be widespread in different sociocultural and economic contexts of Ecuador. • To promote intercultural health, understanding the diverse sociocultural patterns associated with the use of traditional medicine, often combined with conventional medicine, is crucial.

The Influence of GLP1 on Body Weight and Glycemic Management in Patients with Diabetes—A Scientometric Investigation and Visualization Study

Diabetes medications can affect weight and cardiovascular health. Some medications can aid in weight management, while others may lead to weight gain. Patients must be monitored and receive appropriate care to manage weight and prevent cardiovascular complications. Despite advancements in diabetes treatments that can influence weight and cardiovascular outcomes, ongoing research is necessary in this intricate field. Long-term effects, individual variations, and combination therapies are still subjects of uncertainty and ongoing investigation. The major objective of the research is to evaluate the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on body weight in diabetic patients through a scientometric assessment. Methodology: Research data were gathered from the Web of Science Core Collection (WoSCC) database by searching for the keywords “Body Weight”, dulaglutide, and semaglutide, identifying 60 relevant articles in the field. While there are advantages in managing diseases in which the cardiovascular system is implicated, there are also clinical considerations for personalized medicine and shared decision-making. The scientometric analysis of the articles revealed important insights into how dulaglutide and semaglutide impact weight management and their potential benefits for managing cardiovascular diseases in individuals with diabetes. Conclusions: Semaglutide shows superior outcomes compared to other commercially available GLP-1RAs, particularly in improving blood sugar control, lowering body weight, and addressing other cardio-metabolic risk factors in individuals with type 2 diabetes (T2DM). The findings suggest that GLP-1 RAs have the potential to provide cardiovascular protection by influencing various physiological factors such as blood pressure, pulse rate, glycated hemoglobin (HbA1c) levels, and the urinary albumin-to-creatinine ratio (RAC). The development and validation of the 4GI model provides a sophisticated tool for evaluating the complex interactions involved in diabetes treatments, offering insights into the mechanisms of action of various medications.

Cardio-metabolic disorders in a patient with non-alcoholic fatty liver disease and normal body weight

The relationship between the formation of non-alcoholic fatty liver disease (NAFLD) in obese individuals has been proven, which increases the patient’s cardio-metabolic risk. A number of studies have demonstrated that patients with normal body weight (NBW) have comparable risks of developing cardiovascular disease and progression to NAFLD compared to obese patients. Purpose of the study: To assess the incidence of cardio-metabolic disorders in patients with NAFLD and NBW. Materials and methods: 225 patients of both sexes (18–65 years old) with confirmed NAFLD were included. Patients were divided into 3 groups according to body mass index (BMI) values. Results: In patients of group 1, an increased risk of developing coronary heart disease (CHD), arterial hypertension (AH), type 2 diabetes mellitus and progression of liver fibrosis was revealed with an increase in the level of the triglyceride index. Conclusions: The study demonstrated the need for early identification of NAFLD in NBW individuals and assessment of existing cardiometabolic risk factors.

New nomenclature and subclassification of steatotic liver disease and loss of skeletal muscle mass: A longitudinal cohort study.

Identifying risk factors for sarcopenia is important due to its significant effect on health. The association between sarcopenia and the newly proposed steatotic liver disease (SLD) and its subclassification has largely been unexplored. This longitudinal cohort study included 67905 adults who underwent at least two health checkup examinations. SLD participants were categorized as cryptogenic SLD, metabolic dysfunction-associated SLD, metabolic dysfunction-associated alcoholic liver disease, or alcoholic liver disease. Appendicular skeletal muscle mass (ASM) was evaluated by bioelectrical impedance analysis. The average duration of follow-up was 5.9years. The annual ASM change was -31.0g (95% CI -32.3, -29.6) and -38.3g (-40.3, -36.3) in participants without and with SLD, respectively. When assessed based on SLD severity, annual ASM loss was fastest in SLD participants with Fibrosis-4 score ≥1.3, followed by those with Fibrosis-4 score <1.3 and those without SLD. In multivariable adjusted analysis, annual ASM loss was fastest in participants with metabolic dysfunction-associated alcoholic liver disease (-49.8g; -93.1, -6.5), followed by those with metabolic dysfunction-associated SLD (-24.7g; -60.4, 11.1), and alcoholic liver disease (-24.4g; -91.1, 42.3), and slowest in those with cryptogenic SLD (reference). This pattern was more pronounced in participants with Fibrosis-4 score ≥1.3. The loss of skeletal muscle mass was fastest in the participants with metabolic dysfunction-associated alcoholic liver disease, followed by participants with metabolic dysfunction-associated SLD, alcoholic liver disease, and cryptogenic SLD. Particular attention to prevent sarcopenia should be given to SLD patients with cardiometabolic risk factors or alcohol consumption, especially in patients with advanced fibrosis.

Gestational diabetes and future cardiovascular diseases: associations by sex-specific genetic data.

Observational studies have highlighted that gestational diabetes mellitus is associated with a higher risk of cardiovascular diseases, but the causality remains unclear. Herein, the causality between genetic predisposition to gestational diabetes mellitus and the risk of cardiovascular diseases was investigated using sex-specific Mendelian randomization analysis. Linkage disequilibrium score regression analysis and two-sample Mendelian randomization analysis were applied to infer the genetic correlation and causality, respectively. Mediation analysis was conducted using a two-step Mendelian randomization approach. Sensitivity analyses were performed to differentiate causality from pleiotropy. The genome-wide association study summary statistics for gestational diabetes mellitus were obtained from FinnGen consortium, while for cardiovascular diseases were generated based on individual-level genetic data from the UK Biobank. Linkage disequilibrium score regression analyses revealed that gestational diabetes mellitus had a significant genetic correlation with coronary artery disease and myocardial infarction after Benjamini-Hochberg correction in ever-pregnant women. In Mendelian randomization analyses, odds ratios (95% confidence interval) for coronary artery disease and myocardial infarction were 1.09 (1.01-1.17) and 1.12 (.96-1.31) per unit increase in the log-odds of genetic predisposition to gestational diabetes mellitus in ever-pregnant women, respectively. Further, Type 2 diabetes and hypertension were identified as mediators for the causality of genetic predisposition to gestational diabetes mellitus on coronary artery disease. In sensitivity analyses, the direction of odds ratio for the association between instrumental variables with gestational diabetes mellitus-predominant effects and the risk of coronary artery disease was consistent with the primary results in ever-pregnant women, although not statistically significant. This study demonstrated a suggestive causal relationship between genetic predisposition to gestational diabetes mellitus and the risk of coronary artery disease, which was mainly mediated by Type 2 diabetes and hypertension. These findings highlight targeting modifiable cardiometabolic risk factors may reduce the risk of coronary artery disease in women with a history of gestational diabetes mellitus.

Primary and residual cardiometabolic risk factors among young adults in a Russian city

BackgroundCardiovascular diseases are a leading cause of mortality and a significant contributor to temporary and permanent disabilities worldwide. This study aimed to investigate the burden of primary and residual cardiometabolic risk factors in a sample of young adults in the Russian city of Kazan.MethodsThis case-control study used the Cardiometabolic Disease Staging (CMDS) classification system, which has been validated in several countries. The study included 191 individuals aged 25–44 years who met the inclusion criteria but did not meet any exclusion criteria. Data collection involved a patient card with questions from the World Health Organization’s STEPS instrument, face-to-face patient interviews, and a physical examination. Anthropometric assessments included height, weight, and waist circumference measurements. Body composition was evaluated using bioelectrical impedance measurements. Patients also underwent in-depth laboratory biochemical analyses.ResultsThe study cohort was comprised of 97 females (50.8%) and 94 males (49.2%). The median age of participants was 35.00 years [IQR: 30.00–39.00]. The study cohort showed an increase in all anthropometric parameters, with abdominal obesity and overweight reaching 100% in the CMDS 3. Apart from atherogenic lipids and raised blood pressure, other risk factors that precipitate residual risk and were not part of CMDS, such as insulin levels, insulin resistance, leptin values, and hyperuricemia, increased as CMDS levels increased.ConclusionsThe prevalence of cardiometabolic risk factors was high in young adults in Kazan. This study highlights the need for the early identification and management of cardiometabolic risk factors in young adults to prevent the development of cardiovascular diseases later in life.

20-HETE, Blood Pressure, and Vascular Stiffness in Young Adults.

Cytochrome-P450 eicosanoids from arachidonic acid, including vasodilator epoxyeicosatrienoic acids (EETs) and the vasoconstrictor 20-HETE, are important in regulating blood pressure, vascular tone, and cardiac and renal function. This study examined plasma 20-HETE and EETs in relation to blood pressure and vascular stiffness in a cohort of 1054 community-dwelling young adults from the Raine Study at 27 years. Plasma 20-HETE, EETs, and their hydroxylated products were measured by liquid chromatography-tandem mass spectrometry. Pulse wave velocity and aortic distensibility were measured to assess vascular stiffness. Sex differences were assessed using univariate analysis. Multiple regression models assessed the relationship between 20-HETE and systolic blood pressure (SBP) and measures of vascular stiffness. The regression model for SBP showed a positive relationship with plasma 20-HETE (β, 0.092; P<0.0001), after adjusting for sex (P<0.0001), body mass index (P<0.0001), (ln)triglycerides (P<0.0001), and (ln)HOMA-IR (P=0.015), and accounted for 29% of the variance in SBP. 20-HETE was positively related to pulse wave velocity (β, 0.059; P=0.021); after adjusting for sex (P<0.0001), SBP (P<0.0001), (ln)triglycerides (P=0.014), (ln)HOMA-IR (P=0.0001), (ln)high-sensitivity C-reactive protein (P=0.005), and age (P=0.002), the model accounted for 34% of the variance in pulse wave velocity. 20-HETE was inversely associated with aortic distensibility (β, -0.051; P=0.029), independent of sex (P<0.0001), SBP (P<0.0001), and (ln)HOMA-IR (P<0.0001); the model accounted for 25% of the variance in aortic distensibility. Plasma EETs were not significant predictors of SBP or vascular stiffness. In young adults, 20-HETE may play a fundamental role in regulating blood pressure and vascular stiffness independent of numerous cardiometabolic risk factors and cytochrome 450-derived EETs. URL: https://www.anzctr.org.au; Unique identifier: CTRN12617001599369.

Effect of 5β-dihydrotestosterone on vasodilator function and on cell proliferation.

Aging is one of the main factors associated with cardiovascular diseases. Androgens exert beneficial effects on the cardiovascular system and testosterone (TES) replacement therapy improves cardiometabolic risk factors. However, TES is contraindicated in patients with prostate cancer due to its proliferative effects on prostatic tumor cells. Additionally, TES and its reduced metabolites 5α- and 5β-dihydrotestosterone (5α-DHT and 5β-DHT) exert vasodilatory effects. Since androgen levels decrease during aging and 5β-DHT lacks genomic effects, this study is focused on analyzing its effect on vasodilator function and the proliferation rate of prostatic tumor and vascular smooth muscle cells. To study the vascular function, mesenteric arteries from aged-orchidectomized Sprague-Dawley rats were used. Mesenteric segments were divided into one control (without treatment) and three groups with the androgens (10 nM, 30 min) to analyze: acetylcholine- and sodium nitroprusside-induced responses and nitric oxide and superoxide anion production. To analyze cell proliferation, the effect of androgens on cell viability was determined. The results showed that 5β-DHT improves vasodilator function in arteries from aged-orchidectomized rats and induces antioxidant action, while the proliferation rate of the androgen-dependent prostatic tumor cells remains unaltered. These results make 5β-DHT a promising therapeutic agent for the treatment of cardiovascular pathologies.

Effects of Whole-Body Electromyostimulation on Metabolic Syndrome in Adults at Moderate-to-High Cardiometabolic Risk-A Systematic Review and Meta-Analysis.

In the present work, we aimed to determine the effect of whole-body electromyostimulation (WB-EMS) on metabolic syndrome (MetS) as a cluster of cardiometabolic risk factors in people at moderate-to-high cardiometabolic risk. The present meta-analysis is based on a systematic literature search of a recent evidence map, which searched five electronic databases, two registers, and Google Scholar, according to PRISMA, until 31 March 2023. Controlled trials comprising adult cohorts with central obesity that compared the effect of WB-EMS versus controls using a continuous score representing MetS were included. We applied a random-effects meta-analysis and used the inverse heterogeneity model to analyze the data of the five eligible trials identified by our search. Outcome measures were standardized mean differences (SMDs) with 95% confidence intervals (95%-CIs). The risk of bias was determined using the PEDro-Score. In summary, we identified five eligible articles containing 117 participants in the WB-EMS group and 117 participants in the control group. We observed a small effect (SMD: -0.30; 95%-CI: -0.04 to -0.56) in favor of the WB-EMS intervention. The heterogeneity between the trials was very low (I2: 0%); further evidence for risks of small study/publication bias was minimal. The methodologic quality of these studies can be classified as moderate to high. In summary, the present work provides evidence of the favorable effect of WB-EMS on cardiometabolic risk in adults at moderate-high cardiometabolic risk. Considering the time effectiveness of WB-EMS, along with its safety and attractiveness, as indicated by the five studies, WB-EMS can be regarded as a feasible training option for people at cardiometabolic risk.

Effects of multicomponent exercise intervention on cardiometabolic risk factors in children and young adults with cerebral palsy: a multiple-baseline trial.

Adults with cerebral palsy (CP) have a high risk of cardiometabolic diseases. It is unknown whether this risk is elevated in young people with CP and whether exercise can reduce this risk. Therefore, we investigated the effects of the EXErcise for Cerebral Palsy (EXECP) intervention on cardiometabolic risk in children and young adults with CP and compared this risk to typically developing children and young adults (TDs). Ambulatory male and female participants with spastic CP, aged 9-24 years, and age- and sex-matched TDs without musculoskeletal disorders were recruited. Participants with CP were measured at baseline, after a three-month control period manifesting normal development, and after the three-month strength, gait, and flexibility training intervention. TDs were measured at baseline and after the control period. They did not attend the intervention. Cardiometabolic risk factors included body weight, body fat percentage, and skeletal muscle mass index assessed with bioimpedance; resting systolic and diastolic blood pressure and aortic pulse wave velocity assessed with a non-invasive oscillometric device; fasting plasma high-density and low-density lipoprotein cholesterol, triglyceride, and glucose levels. Data were analyzed with independent samples t-tests and linear mixed-effects models adjusted for sex and age. The study involved 18 participants with CP (13 males, 9-22year, mean 14.2 ± 4.4) and 17 TDs (12 males, 9-22year, mean 14.6 ± 4.3). At baseline, participants with CP had a 1.0 (95% confidence interval (CI) [-2.0, -0.0]) kg/m2 lower skeletal muscle mass index than TDs. During the control period, no statistically significant between-group differences were observed in the change of any outcome. In the CP group, body weight (β = 1.87, 95% CI [1.04, 2.70]), fat percentage (β = 1.22 [0.07, 2.37], and blood glucose (β = 0.19, 95% CI [0.01, 0.37]) increased, while diastolic blood pressure (β=-2.31, 95% CI [-4.55, -0.06]) and pulse wave velocity (β=-0.44, 95% CI [-0.73, -0.16]) decreased. In the TD group, only body weight increased (β = 0.85, 95% CI [0.01, 1.68]) statistically significantly. In the CP group, no changes were observed during the intervention. Young people with and without CP do not exhibit significant differences in most cardiometabolic risk factors. EXECP intervention may attenuate some adverse development trajectories occurring without the intervention but greater volume and intensity of aerobic exercise may be needed to reduce cardiometabolic risk. ISRCTN69044459; Registration date 21/04/2017.

Metabolic Dysfunction-Associated Steatotic Liver Disease Increases the Risk of Severe Infection: A Population-Based Cohort Study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to various intrahepatic and extrahepatic diseases, but its association with severe infectious disease remains to be investigated. We analysed data from the Shanghai Suburban Adult Cohort and Biobank, encompassing participants enrolled in 2016 and 2017 with available abdominal ultrasonography data, and followed them up until December 2022 (median follow-up = 5.71 years). We categorised the participants into the MASLD group and those without steatotic liver disease (non-SLD). Multivariable-adjusted Cox regression was used to estimate hazard ratios (HR) for severe infections in patients with MASLD compared to the non-SLD group. Cumulative incidences were calculated while accounting for competing risks (non-infection-related deaths). Mediation analyses were performed to explore the roles of cardiometabolic risk factors in the association between MASLD and severe infections. Among the 33 072 eligible participants (mean age 56.37 years; 38.20% male), 11 908 (36.01%) were diagnosed with MASLD at baseline. Severe infections occurred in 912 (7.66%) MASLD patients and 1258 (5.94%) non-SLD. The rate of severe infections per 1000 person-years was higher in MASLD patients (13.58) than in comparators (10.48) (fully adjusted HR 1.18, 95% CI 1.07-1.30). The most frequent infections in MASLD were respiratory (7.25/1000 person-years) and urinary tract infections (2.61/1000 person-years). The 5-year cumulative incidence of severe infections was 6.79% (95% CI 6.36-7.26) in MASLD and 5.08% (95% CI 4.79-5.38) in comparators. Cardiometabolic risk factors, including waist circumference, triglycerides and HbA1C, partially mediate the association between MASLD and severe infections. Patients with MASLD were at significantly higher risk of incident severe infections compared to the non-SLD group. Future studies are needed to elucidate the mechanisms linking MASLD to severe infections.

Impact of the COVID-19 pandemic on the incidence of cardiometabolic risk factors among workers: results from the Japan Epidemiology Collaboration on Occupational Health study

BackgroundThe COVID-19 pandemic and associated restrictions on human activities have greatly changed lifestyles, which might have deteriorated the cardiometabolic profile.ObjectiveThis study aimed to examine the effect of the COVID-19 pandemic...

The interrelation of cardiometabolic risk factors and metabolic dysfunction-associated steatotic liver disease subtypes

Introduction. Metabolic dysfunction-associated steatotic liver disease is one of the leading causes of cirrhosis, liver cancer and extrahepatic complications. The number and various combinations of cardiometabolic risk factors, as well as the severity of liver steatosis, can affect the aggressiveness and prognosis of the disease. The article presents the results of own studies aimed at determining the prognostic significance of risk factors (individual and in different combinations) and steatometry.Objective. To determine the influence of individual cardiometabolic factors, their number and various combinations on the aggressiveness and prognosis of metabolic dysfunction-associated steatotic liver disease; to assess the prognostic value of steatometry for the disease.Material and methods. The examination results (steatometry, blood biochemistry tests, abdominal ultrasound) of patients diagnosed with metabolic dysfunction-associated steatotic liver disease were retrospectively analyzed. Statistical analysis: Student's t-test, Pearson's χ2-test, odds ratio, relative risk, Fisher's φ-test, ROC-analysis.Results. 146 patients were included. Cohort characteristics: average age 49.3 years, 84 men (57.5%). Aggressive forms (steatohepatitis, advanced steatosis) were associated with arterial hypertension, carbohydrate metabolism disorders (the most significant is insulin resistance), dyslipidemia, hyperuricemia. The severity of liver steatosis was less in patients who received therapy for lipid metabolism disorders comparing with those who didn’t. The presence of three or more cardiometabolic risk factors in a patient increased the risk of steatohepatitis and advanced steatosis. The combination of arterial hypertension and hyperuricemia significantly increased the risk of steatohepatitis. Advanced hepatic steatosis (≥310 dB/m2 by steatometry) was reliably associated with steatohepatitis.Conclusion. Individual risk factors, their number and combinations, contribute differently to the development of aggressive forms of the disease. Hyperuricemia should be considered as an additional cardiometabolic risk factor. Steatometry is capable of identifying advanced hepatic steatosis, being a risk factor for the development of steatohepatitis, which allows us to recommend it for the early diagnosis of metabolic dysfunction-associated steatotic liver disease.

Study of the relationships of polymorphisms of the folate cycle genes with the levels of homocysteine and folic acid as risk factors of cardiovascular disorders in the post-covid period

Enzymes of the folate cycle participate in the process of remethylation of homocysteine (HC) to methionine, where folates are coenzymes for methyl transfer. The aim of the work was to identify the interrelationships of gene polymorphisms of associations between folate cycle enzyme gene polymorphisms and cardiometabolic risk factors such as increased serum homocysteine levels and folic acid deficiency in patients in the post-covid period. In 51 patients who suffered from COVID-19, a general clinical and laboratory examination, and assessment of serum homocysteine and folic acid concentrations by immunoenzymatic method was carried out. Polymorphisms of the genes: methylenetetrahydrofolate reductase (677C&gt;T and 1298A&gt;C), methionine synthase-reductase (66A&gt;G) and methionine synthase (2756A&gt;G) were determined by real time polymerase chain reaction. For each of the named polymorphisms, the examined patients were divided into 3 groups according to the nucleotide alleles in the corresponding position: 1) homozygous dominant, 2) heterozygous and 3) homozygous recessive. For the methylenetetrahydro­folatereductase gene at position 677, serum levels of homocysteine and folate did not differ between the groups 1 and 2 with genotypes 677 C/C (n=26) and 677C/T (n=21), (p&gt;0.05); in group 3, the recessive genotype 677 T/T was found in only 4 people (8%), that did not allow comparison of indices. The distribution of patients into 3 groups according to the genotype of the same gene at position 1298 revealed that the recessive 1298 C/C mutation in group 3 (n=9) associated with an increased homocysteine level (19.56±1.89 μmol/l), versus 10.68±0.76 (p=0.012) and 11.63±1.25 μmol/l (p=0.013) in groups 1 and 2, with no difference in folate levels between groups. Group 3 differed by a higher degree of obesity, a higher frequency of hypertension disease and chronic heart failure (in 85% of patients in group 3, against 41 and 50% in groups 1 and 2), a higher number of platelets, a longer duration of hospitalization due to COVID-19, a higher level of D-dimer. The study of groups of patients, divided depending on the genotype of methioninesynthase reductase at position 66, showed that carriers of the recessive homozygous 66 G/G mutation (group 3, n=15) had increased serum homocysteine level (16.56±1.64 μmol/l) in comparison with individuals of group 1 (n=17) 66 A/A (10.28±1.17 μmol/l; p=0.004) and group 2 (n=19) 66 A/G (11.32±1.17 μmol/l, p=0.013). In group 3, a longer duration of hospitalization due to COVID-19 was noted (17.15±1.65 vs. 11.88±0.97 days, p=0.008), higher frequency of hypertension (67% vs. 35%) and heart failure (67% against 29%) compared to group 1. The use of a molecular genetic approach made it possible to establish that the presence of recessive mutations of the folate cycle genes is associated with a potential predisposition to hyperhomocysteinemia, thrombophilia, severe forms of cardiometabolic complications and coronavirus disease.