Cardiometabolic Profile Research Articles

Interleukin-17-targeted treatment in patients with spondyloarthritis and associated cardiometabolic risk profile.

Spondyloarthritis is a group of immune-mediated rheumatic disorders that significantly impact patients' physical function and quality of life. Patients with spondyloarthritis experience a greater prevalence of cardiometabolic disorders, such as obesity, hypertension, dyslipidemia and diabetes mellitus, and these comorbidities are associated with increased spondyloarthritis disease activity and risk of cardiovascular events. This narrative review summarizes the evidence for a physiological link between inflammatory status and cardiometabolic comorbidities in spondyloarthritis, as well as the impact of interleukin (IL)-17 blockade versus other molecular mechanisms in patients with cardiometabolic conditions. The IL-23/IL-17 axis plays a pivotal role in the pathophysiology of spondyloarthritis by promoting inflammation and tissue remodeling at the affected joints and entheses. The importance of the IL-23/IL-17 signaling cascade in underlying sub-clinical inflammation in common cardiometabolic disorders suggests the existence of shared pathways between these processes and spondyloarthritis pathophysiology. Thus, a bidirectional relationship exists between the effects of biologic drugs and patients' cardiometabolic profile, which must be considered during treatment decision making. Biologic therapy may induce changes in patients' cardiometabolic status and cardiometabolic conditions may conversely impact the clinical response to biologic therapy. Available evidence regarding the impact of IL-17 blockade with secukinumab on cardiometabolic parameters suggests this drug does not interfere with traditional cardiovascular risk markers and could be associated with a decreased risk of cardiovascular events. Additionally, the efficacy and retention rates of secukinumab do not appear to be negatively affected by obesity, with somestudies reporting a positive impact on clinical outcomes, contrary to that described with other approaches, such as tumor necrosis factor blockade. Inthisarticle, we also review evidence for this bidirectional association with othertreatments for spondyloarthritis. Current evidence suggests that IL-17-targeted therapy with secukinumab is highly effective in spondyloarthritis patients with cardiometabolic comorbidities and may provide additional cardiometabolic benefits.

Socioeconomic Disparities and Mediators for Recurrent Atherosclerotic Cardiovascular Disease Events After a First Myocardial Infarction.

Low socioeconomic status is associated with worse secondary prevention use and prognosis after myocardial infarction (MI). Actions for health equity improvements warrant identification of risk mediators. Therefore, we assessed mediators of the association between socioeconomic status and first recurrent atherosclerotic cardiovascular disease event (rASCVD) after MI. In this cohort study on 1-year survivors of first-ever MI with Swedish universal health coverage ages 18 to 76 years, individual-level data from SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and linked national registries was collected from 2006 through 2020. Exposure was socioeconomic status by disposable income quintile (principal proxy), educational level, and marital status. The primary outcome was rASCVD and secondary outcomes were cardiovascular and all-cause mortality. We initially assessed the incremental attenuation of hazard ratios with 95% CIs in sequential multivariable models adding groups of potential mediators (ie, previous risk factors, acute presentation and infarct severity, initial therapies, and secondary prevention). Thereafter, the proportion of excess rASCVD associated with a low income mediated through nonparticipation in cardiac rehabilitation, suboptimal statin management, a cardiometabolic risk profile, persistent smoking, and blood pressure above target after MI were calculated using causal mediation analysis. Among 68 775 participants (73.8% men), 7064 rASCVD occurred during a mean 5.7-year follow-up. Income, adjusted for age, sex, and calendar year, was associated with rASCVD (hazard ratio, 1.63 [95% CI, 1.51-1.76] in the lowest versus highest income quintile). Risk attenuated most by adjustment for previous risk factors and by adding secondary prevention variables for a final model (hazard ratio, 1.38 [95% CI, 1.26-1.51]) in the lowest versus highest income quintile. The proportions of the excess 15-year rASCVD risk in the lowest income quintile mediated through nonparticipation in cardiac rehabilitation, cardiometabolic risk profile, persistent smoking, and poor blood pressure control were 3.3% (95% CI 2.1-4.8), 3.9% (95% CI, 2.9-5.5), 15.2% (95% 9.1-25.7), and 1.0% (95% CI 0.6-1.5), respectively. Risk mediation through optimal statin management was negligible. Nonparticipation in cardiac rehabilitation, a cardiometabolic risk profile, and persistent smoking mediate income-dependent prognosis after MI. In the absence of randomized trials, this causal inference approach may guide decisions to improve health equity.

Effect of Obesity on Clinical Characteristics of Primary Aldosteronism Patients at Diagnosis and Postsurgical Response.

Patients with obesity have an overactivated renin-angiotensin-aldosterone system (RAAS) that is associated with essential hypertension. However, the influence of obesity in primary aldosteronism (PA) is unknown. We analyzed the effect of obesity on the characteristics of PA, and the association between obesity and RAAS components. A retrospective study was conducted of the Spanish PA Registry (SPAIN-ALDO Registry), which included patients with PA seen at 20 tertiary centers between 2018 and 2022. Differences between patients with and without obesity were analyzed. A total of 415 patients were included; 189 (45.5%) with obesity. Median age was 55 years (range, 47.3-65.2 years) and 240 (58.4%) were male. Compared to those without obesity, patients with obesity had higher rates of diabetes mellitus, chronic kidney disease, obstructive apnea syndrome, left ventricular hypertrophy, prior cardiovascular events, higher means of systolic blood pressure, and required more antihypertensive drugs. Patients with PA and obesity also had higher values of serum glucose, glycated hemoglobin A1c, creatinine, uric acid, and triglycerides, and lower levels of high-density lipoprotein cholesterol. Levels of blood aldosterone (PAC) and renin were similar between patients with and without obesity. Body mass index was not correlated with PAC nor renin. The rates of adrenal lesions on imaging studies, as well as the rates of unilateral disease assessed by adrenal vein sampling or I-6β-iodomethyl-19-norcholesterol scintigraphy, were similar between groups. Obesity in PA patients involves a worse cardiometabolic profile, and need for more antihypertensive drugs but similar PAC and renin levels, and rates of adrenal lesions and lateral disease than patients without obesity. However, obesity implicates a lower rate of hypertension cure after adrenalectomy.

Exploring New Tools for Risk Classification among Adults with Several Degrees of Obesity.

The epidemic of obesity worldwide has been recognized as a very important challenge. Within its complexity, the identification of higher-risk patients is essential, as it is unsustainable to offer access to treatment to all people with obesity. Several new approaches have recently been presented as important tools for risk stratification. In this research, we applied several of these tools in a cross-sectional study involving adults with obesity classes I, II, III, and super-obesity. The participants had their cardiometabolic risk profiles assessed. The study included adults with obesity aged 18 to 50 years (n = 404), who were evaluated using anthropometric, body composition, hemodynamic, physical fitness, and biochemical assessments. These variables were used to identify the prevalence of risk factors for cardiometabolic diseases according to the classes of obesity by gender and age group. The results showed high prevalence of risk factors, especially among the upper classes of obesity (BMI > 35 kg/m2) using single parameters as the waist circumference, with almost 90% above the cut-off point. For smaller numbers such as Glycated Hemoglobin, however, the prevalence was around 30%. Indexes such as the atherogenic index of plasma (AIP) had the highest prevalence, with 100% of the male participants identified as being at increased risk for cardiovascular disease.

The impact of high intensity interval training in a diverse group of cancer survivors: CAPABLE, a pilot study

PurposeGiven the well-documented benefits of regular exercise to cancer survivors, current American Cancer Society guidelines recommend that patients engage in a minimum of 150 min per week of moderate-to-vigorous physical activity with a minimum of two days of strength training. However, few survivors meet this goal, particularly among minorities. MethodsThe CAPABLE study is a single-arm, pilot exercise intervention that introduced 48 cancer survivors to a high intensity interval and strength training program three days a week for 12 weeks. We evaluated the impact of this unique training method on bodyweight, % body fat, serum markers correlated with an adverse cardiometabolic profile and health-related quality of life (HRQoL). Measures were summarized at baseline and program exit. Paired t-tests were used to assess change in each of these measures over time. ResultsWe observed losses in weight, body mass index, and % body fat, and glycosylated hemoglobin (HbA1c) levels over 12-weeks. There were also clinically meaningful improvements in reported overall HRQoL (FACTG total change +9.5 (95% CI, 4.6, 14.4)) and in each one of the individual domains (physical, social, emotional, and functional well-being). ConclusionsWe observed meaningful improvements in body composition, HbA1c and quality of life over 12 weeks among cancer survivors participating in a high-intensity interval training program. Future work will include a control arm for comparison and address barriers to participation and adherence which will be important in using this intervention and others like it to improve outcomes and reduce cancer health disparities.

1361-P: Patients with Severe Nonalcoholic Steatohepatitis (NASH) Have Profound Insulin Resistance and Lipotoxicity

NASH is the more severe form of nonalcoholic fatty liver disease (NAFLD), prone to advanced fibrosis/cirrhosis. However, the metabolic profile of such patients is not well characterized. The aim of this study was to assess the cardiometabolic features of patients with NASH matched for major variables (age, gender, BMI, A1c), to people with less severe disease activity and without NAFLD. To this end, we recruited 46 patients (age: 57±1.5 years; BMI: 36.2±0.8 kg/m2; A1c: 6.8±0.2%; T2DM: 70%), from our outpatient endocrine and PCP clinics and measured liver disease activity/severity by magnetic resonance (MR) iron corrected T1 imaging (cT1). Patients were grouped based on disease activity (cT1) into those without NAFLD (non-NAFLD; n = 8; cT1 <800 ms), mild-to-moderate NASH (mNASH; n = 16; cT1 ≥800 to ≤875 ms), and severe/high-risk steatohepatitis (sNASH; n = 22; cT1 >875 ms). Insulin resistance increased with the severity of NASH (HOMA-IR: non-NAFLD: 3.6±0.9 vs. mNASH: 4.3±0.7 vs. sNASH: 5.5±0.7), and so did adipose tissue IR (adipo-IR [fasting FFA x insulin]: 3.5±0.5 vs. 5.5±1.0 vs. 8.2±1.0; respectively, p=0.03). Dysfunctional adipose tissue/lipotoxicity was also evident from lower adiponectin levels (non-NAFLD: 7.4±2.4 vs. mNASH: 3.9±0.7 vs. sNASH: 3.7±0.3 µg/mL; p=0.04) and a 2-fold increase in ectopic fat/liver steatosis by MR-PDFF (mNASH: 11.2±0.9 vs. sNASH: 20.3±1.6; p<0.001). Plasma CK-18, a marker of hepatocyte apoptosis, increased with NASH severity (105±13 vs. 220±44 vs. 361±57 U/L; respectively p=0.02) and correlated with the severity of NASH by cT1 (r=0.46; p<0.01). Liver steatosis (r=0.73; p<0.01) and adipo-IR (r=0.32; p=0.1) were also associated with cT1. Conclusion: Increased hepatic disease activity (cT1) in patients with NASH is a strong indicator of insulin resistance and an unfavorable cardiometabolic profile. Its use in the clinic may identify patients with a greater risk of adverse liver and cardiovascular outcomes. Disclosure S.A.Marangi: None. S.Shrestha: None. L.Mansour: None. S.S.Shetty: None. M.M.Calvet: None. R.Lomonaco: None. D.Barb: None. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. S.Kalavalapalli: None. E.Godinez leiva: None. H.B.Thomaides-brears: Employee; Perspectum Ltd., Stock/Shareholder; Perspectum Ltd. C.Diamond: Employee; Perspectum Ltd. Y.Mohseni: None. M.A.Gonzalez: None. A.Ortiz rocha: None. E.Valdez saenz: None. Funding National Institutes of Health (R01120331-01A1)

1349-P: People with Type 2 Diabetes Have a High Prevalence of Nonalcoholic Steatohepatitis with Significant Fibrosis When Screened by NIS4 or Elastography

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Diagnosis remains challenging as a liver biopsy is usually not feasible. NIS4 is a novel plasma diagnostic test combining the measurement of A1c and 3 biomarkers (miR-34a-5p, A2M, YKL-40) linked to NASH disease activity and higher cirrhosis risk. The aim of this study was to assess the prevalence of high-risk NASH (NASH with significant fibrosis [≥F2]) as estimated by NIS4 or elastography in the outpatient setting. A total 400 participants (age: 55±11 years; BMI: 31.6±6.6 kg/m2; T2DM: 32%; obese without T2DM [OB]: 33%), unaware of having NAFLD, were recruited from PCP and endocrine clinics and screened by: a) Elastography (Fibroscan®) for steatosis (controlled attenuation parameter or CAP ≥274 dB/m) and for fibrosis (liver stiffness measurement or LSM ≥7.0 kPa); and b) NIS4 for high-risk NASH (defined as a NIS4 >0.63; low-risk: <0.36). Among patients with T2DM or OB, 68% had steatosis compared to 35% without obesity or T2DM (CON) (p<0.01), while fibrosis (LSM≥7.0 kPa) was present in 14% of patients with T2DM (CON = 1%; p=0.02). High-risk NASH by NIS4 occurred frequently among patients with T2DM, either with (30%) or without (26%) obesity, and rare in those without T2DM (3%; p<0.001). NIS-4 correlated with steatosis (CAP) (r = 0.35) and fibrosis (LSM) (r = 0.32; both p<0.001). Patients with high-risk NASH by NIS4 compared to those with low-risk NASH, more often had steatosis (82% vs 46%), fibrosis (16% vs 4%), AST≥30 IU/L (41% vs. 8%) and ALT≥30 IU/L (36% vs. 15%), hepatic (HOMA-IR: 68% vs. 25%) and adipose tissue (adipo-IR: 80% vs 56%) insulin resistance (all p<0.01). NIS4 correlated with having metabolic syndrome (r=0.41; p<0.01) and was more often increased in people from endocrine vs. PCP clinics (34% vs. 9%; p<0.05). Conclusion: NASH with significant fibrosis is common in T2DM. Patients with elevated NIS4 often have NAFLD with fibrosis and an unfavorable cardiometabolic profile. Disclosure S.Kalavalapalli: None. T.R.Prezant: None. M.A.Connelly: Employee; LabCorp, Stock/Shareholder; LabCorp. D.Barb: None. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. E.Godinez leiva: None. R.Lomonaco: None. S.A.Marangi: None. E.Valdez saenz: None. A.Ortiz rocha: None. J.T.Budd: None. Y.Mohseni: None. K.Y.Chun: None. Funding National Institutes of Health (R01120331-01A1)

1338-P: Characteristics of Patients with Type 2 Diabetes without Nonalcoholic Fatty Liver Disease (NAFLD)

About 70% of patients with type 2 diabetes mellitus (T2DM) have NAFLD which is a risk factor for cirrhosis and hepatocellular carcinoma. Many factors may be associated with more severe disease (i.e., insulin resistance, obesity). However, the metabolic profile of T2DM patients spared from having NAFLD and liver fibrosis is unclear. To this end, we recruited 266 patients with a history of T2DM without a known history of NAFLD (age: 59 ± 10 years; female 58.3 %; BMI: 33.0 ± 6.3 kg/m2, A1c: 7.0 ± 1.4 %) attending the outpatient university clinics. We performed a medical history, physical exam and measured routine/metabolic laboratories, liver fat (by CAP score ≥ 274 dB/m) and fibrosis (by liver stiffness measurement or LSM ≥7.0 kPa or F≥1) by elastography. A total of 32% patients did not have NAFLD, but when compared to NAFLD patients there were no differences in terms of age, gender, or race. Those without NAFLD had a lower mean BMI ± SD (29.6 ± 5.2 vs. 34.6 ± 6.2 kg/m2) and better glycemic control (mean A1c: 6.7 ± 1.3% vs. 7.2 ± 1.4%, both p<0.05). Patients without NAFLD had lower plasma ALT levels (mean 21 ± 12 vs. 28 ± 19 U/L; p<0.05). Patients with NAFLD had more severe (hepatic) insulin resistance (IR) (HOMA-IR: 3.0 ± 2.3 vs. 4.9 ± 3.2, p<0.05), with more people having a HOMA-IR ≥3.0 (35% vs. 72%, p<0.05). In multiple regression analysis, with a 95% CI, obesity (OR 4.0, 2.3-7.1), HOMA-IR (OR 3.1, 1.0-5.7), and worse glycemic control (A1c) (OR 1.7, 1.1-2.9) accounted for most of the difference between subjects with vs. without NAFLD. In NAFLD patients, comparing those with vs. without fibrosis, obesity (OR 2.8, 1.6-4.9) and elevated aminotransferases (OR 2.1, 1.3-3.2) accounted for most of the difference among patient. Conclusion: Patients with type 2 diabetes mellitus without NAFLD are usually more insulin sensitive and have a more favorable cardiometabolic profile than those with NAFLD. This highlights the role of insulin resistance and lipotoxicity in the development of NAFLD in this population. Disclosure E.Valdez saenz: None. D.Barb: None. M.J.Gurka: None. A.Sharma: None. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. E.Godinez leiva: None. R.Lomonaco: None. S.A.Marangi: None. S.Kalavalapalli: None. M.A.Gonzalez: None. X.Chi: None. A.Ortiz rocha: None. Y.Mohseni: None. Funding National Institutes of Health (R01120331-01A1)

1374-P: Ultra-processed Food Consumption and Cardiometabolic Risk in Individuals With and Without Type 1 Diabetes Mellitus

Background: Ultra-processed foods (UPFs) contribute to almost 60% of energy intake in the American diet. The longitudinal association between UPF consumption and cardiometabolic risk is less known, especially in people with type 1 diabetes mellites (T1DM) who are at a higher risk of developing cardiometabolic diseases than people without diabetes (non-DM). Methods: We performed a longitudinal analysis of data from the Coronary Artery Calcification in Type 1 Diabetes study (T1DM: n=652; non-DM: n=764) collected at baseline and years 3, 6, and 14. Baseline age was 37.8±9.3 years. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire, and cardiometabolic biomarkers (BMI, waist circumference, triglycerides, HDL-C, LDL-C, and systolic and diastolic blood pressure) were measured at all four time points. NOVA food classification was used to compute UPF consumption (servings/d). Linear mixed-effects models were used to estimate longitudinal associations of UPF consumption with cardiometabolic risk, adjusting for potential confounders (race, age, sex, education, physical activity, smoking, energy intake, antihypertensive and lipid-lowering drugs, and diabetes duration for T1DM). Results: People with T1DM consumed more UPFs, including processed meat, soft drinks, salty snacks, and margarine, than non-DM at baseline (8.7±7.8 vs. 7.3±6.7 servings/d, P<0.01). Higher UPF consumption was associated with higher anthropometric measures (BMI: β=0.01±0.01, waist circumference: β=0.03±0.01), worse lipid levels (triglycerides: β=0.21±0.09, HDL-C: β=-0.04±0.02), and higher systolic blood pressure (β=0.05±0.02) when adjusted for diabetes status and other covariates (all P<0.05). Conclusion: UPF consumption significantly worsened the cardiometabolic profile over time in people with and without T1DM. Decreasing UPF intake may reduce the risk of developing cardiometabolic diseases across the lifespan. Disclosure T.Pang: None. A.C.Alman: None. H.L.Gray: None. G.Dagne: None. A.Basu: None. A.W.Buro: None. J.K.Snell-bergeon: None. Funding American Diabetes Association (7-13-CD-10 to J.K.S-B.), (7-13-CE-02 to A.C.A.); National Heart, Lung, and Blood Institute (R01HL079611, R01HL113029); Diabetes Endocrinology Research Center (P30DK57516, P30DK1116073)

Cardiac Structure and Function in Young Adults With Various Cardiometabolic Profiles.

Background Cardiovascular diseases are a leading cause of mortality worldwide. Cardiometabolic abnormalities result in alterations in the myocardial structure and function. Limited data are available on these changes in young adults with various cardiometabolic risk profiles. The goal was to study the relationship between cardiometabolic risk and echocardiographic changes in young patients of both sexes in a Russian population, using a risk-based cardiometabolic disease staging (CMDS) system. Methods A total of 191 patients were included. The patients were classified into five groups based on the CMDS system. We gathered patient history and performed a physical exam, biochemical blood analysis, and echocardiography. Statistical analyses were performed using IBMSPSSStatistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York, United States). Results The median age of the participants was 35 (30.0-39.0) years. Elevated systolic and diastolic blood pressure and hypertriglyceridemia were more frequent (p < 0.05) in males than in females. An increase in the end-diastolic volume (EDV) and end-systolic volume (ESV) and a decrease in the ejection fraction were noted from CMDS 0 to 3. The EDV and ESV were associated with most cardiometabolic risk factors and strongly correlated with the visceral fat level, waist circumference, and body mass index. We identified a new subgroup as CMDS 3-overly high in patients with CMDS 3 and an excess level of visceral fat. Conclusion When designing strategies for cardiovascular disease prevention in young adults apart from CMDS parameters, bioimpedance analysis should be considered to assess the level of visceral fat, especially in individuals with CMDS 3 because they are at a higher risk of cardiac chamber enlargements. These results can be used to identify new dominants or phenotypes of heart failure with preserved ejection fraction.

Birth History and Cardiovascular Disease Risk Among Youth With Significant Obesity.

Children born prematurely have greater lifetime risk for hypertension. We aimed to determine (1) the association between prematurity and cardiovascular disease (CVD) risk factors among 90 children with obesity and elevated blood pressure and (2) if dietary sodium intake modified these associations. Multivariable regression analysis explored for associations between prematurity (<37 weeks gestation; early gestational age) and low birth weight (<2.5 kg) with hypertension, left ventricular mass index (LVMI), and left ventricular hypertrophy (LVH). Effect modification by dietary sodium intake was also explored. Patients were predominately male (60%), black (78%), adolescents (13.3 years), and with substantial obesity (body mass index: 36.5 kg/m2). Early gestational age/low birth weight was not an independent predictor for hypertension, LVMI, or LVH. There was no effect modification by sodium load. Our results suggest the increased CVD risk conferred by prematurity is less significant at certain cardiometabolic profiles. Promoting heart-healthy lifestyles to prevent pediatric obesity remains of utmost importance to foster cardiovascular health.

Are (poly)phenols contained in 100% fruit juices mediating their effects on cardiometabolic risk factors? A meta-regression analysis.

The consumption of 100% fruit juices has not been associated with substantial detrimental outcomes in population studies and may even contribute to improving the cardiometabolic profile if included in a healthy balanced diet. The main contributors to such potential beneficial effects include vitamins, minerals, and likely the (poly)phenol content. This study aimed to investigate whether the (poly)phenols contained in 100% fruit juices may mediate their effects on cardiometabolic risk factors based on published randomized controlled trials (RCT). A systematic search in PubMed/MEDLINE and Embase, updated till the end of October 2022, was carried out to identify RCT providing quantitative data on (poly)phenol content in 100% fruit juices and used as an intervention to improve cardiometabolic parameters such as blood lipids, glucose, and blood pressure. Meta-regression analysis was performed to calculate the effect of the intervention [expressed as standardized mean difference and 95% confidence intervals (CI)] using the (poly)phenol content as moderator. A total of 39 articles on RCT investigating the effects of 100% fruit juices on cardiometabolic risk factors reporting data on total (poly)phenol and anthocyanin content were included in the analysis. Total (poly)phenol content was substantially unrelated to any outcome investigated. In contrast, each 100 mg per day increase in anthocyanins was related to 1.53 mg/dL decrease in total cholesterol (95% CI, -2.83, -0.22, p = 0.022) and 1.94 mg/dL decrease in LDL cholesterol (95% CI, -3.46, -0.42, p = 0.012). No other potential mediating effects of anthocyanins on blood triglycerides, glucose, systolic and diastolic pressure were found, while a lowering effect on HDL cholesterol after excluding one outlier study was observed. In conclusion, the present study showed that anthocyanins may mediate the potential beneficial effects of some 100% fruit juices on some blood lipids. Increasing the content of anthocyanins through specific fruit varieties or plant breeding could enhance the health benefits of 100% fruit juices.

Associations between serum vitamin D status and the cardiometabolic profile of patients with obstructive sleep apnea

PurposeObstructive sleep apnea (OSA) and the metabolic syndrome (MetS) frequently coexist. Low serum vitamin D has been positively associated with OSA presence and severity; however, data on its link to cardiometabolic features in patients with OSA remain scarce. We aimed to assess serum 25-hydroxyvitamin D [25(OH)D] and explore its association with cardiometabolic parameters in OSA.MethodsThis was a cross-sectional study among 262 patients (49 ± 9 years old, 73% men) with polysomnography-diagnosed OSA. Participants were evaluated in terms of anthropometric indices, lifestyle habits, blood pressure, biochemical, plasma inflammatory and urinary oxidative stress markers, and the presence of MetS. Serum 25(OH)D was assessed by chemiluminescence, and vitamin D deficiency (VDD) was defined as 25(OH)D < 20 ng/mL.ResultsMedian (1st, 3rd quartile) serum 25(OH)D levels were 17.7 (13.4, 22.9) ng/mL and 63% of participants had VDD. Serum 25(OH)D correlated negatively with body mass index (BMI), homeostasis model of assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), and urinary oxidized guanine species (oxG), and positively with high-density lipoprotein cholesterol (all P < 0.050). In logistic regression analysis, serum 25(OH)D was associated with lower odds of MetS [odds ratio (95% confidence interval): 0.94 (0.90–0.98)], after adjustment for age, sex, season of blood sampling, Mediterranean diet score, physical activity, smoking, apnea–hypopnea index, HOMA-IR, hsCRP, and oxG. In the same multivariate model, VDD was associated with ~ twofold greater odds of MetS [2.39 (1.15, 4.97)].ConclusionVDD is highly prevalent and is associated with a detrimental cardiometabolic profile among patients with OSA.

Prevalence of selected cardiometabolic risk factors in the global ART-naïve HIV infected population: A protocol for a systematic review and meta-analysis.

People living with HIV/AIDS (PLHIV) are at increased risk of cardiometabolic diseases attributable to the effects of the virus, antiretroviral therapy (ART) and traditional risk factors. Most studies have focused on assessing the effect of ART on cardiometabolic diseases in PLHIV with fewer studies assessing the cardiometabolic risk profile prior to exposure to ART. Therefore, this protocol is for a systematic review and meta-analysis to estimate the global prevalence of selected cardiometabolic risk factors in ART-naïve PLHIV and their association with HIV specific factors. We shall conduct a systematic search of observational studies on the prevalence of obesity, hypertension, diabetes, and dyslipidaemia in ART-naïve PLHIV and their association with HIV specific characteristics. We will search PubMed-MEDLINE, CINAHL, SCOPUS, Academic Search Premier, Africa-Wide Information and Africa Journals Online databases to identify relevant studies published before June 2022. Two authors will independently screen, select studies, extract data, and conduct risk of bias assessments. Disagreements between the two authors will be resolved by consensus or consulting a third reviewer. Data consistently reported across studies will be pooled using random-effects meta-analysis. Heterogeneity will be evaluated using Cochrane's Q statistic and quantified using I2 statistics. The Preferred Reporting Items for Systematic reviews and Meta-Analysis protocols (PRISMA-P) 2015 guidelines are used for the reporting of this protocol. This review will help determine the burden of selected cardiometabolic diseases in ART-naïve HIV-infected populations and the contribution of HIV infection, independent of ART, to cardiometabolic diseases in PLHIV. It will provide new information that can help orientate future research and potentially guide healthcare policy making. This is part of a thesis that will be submitted to the Faculty of Health Sciences, University of Cape Town, for the award of a PhD in Medicine with protocol ethical clearance number (UCT HREC 350/2021). PROSPERO: CRD42021226001. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226001.

Associations of insulin-like growth factor binding protein-2 with metabolic profile and hepatic fat deposition in asymptomatic men and women.

Low circulating levels of insulin-like growth-factor binding protein-2 (IGFBP-2) have been associated with increased adiposity and metabolic alterations such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease in individuals with obesity. However, whether IGFBP-2 affects energy metabolism in the early stages of these disorders remains unclear. Herein, we hypothesized that plasma IGFBP-2 concentrations are inversely associated with early liver fat accumulation and alterations in lipid and glucose homeostasis in apparently healthy and asymptomatic men and women. Three hundred thirty-three middle-aged Caucasian men and women apparently healthy and without cardiovascular symptoms were enrolled for a cross-sectional cardiometabolic imaging study. Individuals with BMI ≥ 40 kg/m2, cardiovascular disease, dyslipidemia, hypertension, and diabetes were excluded. Fasting glucose and lipid profiles were measured and an oral glucose tolerance test was performed. Liver fat content was assessed by magnetic resonance spectroscopy. Volume of visceral adipose tissue (VAT) was evaluated by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants with low IGFBP-2 levels were characterized by a higher body fat mass (P < 0.0001), insulin resistance (P < 0.0001), higher plasma triglyceride (TG) (P < 0.0001), and lower HDL-cholesterol levels (P < 0.0001) in a sex-independent manner. IGFBP-2 levels were inversely correlated with hepatic fat fraction in both men (r = -0.36, P < 0.0001) and women (r = -0.40, P < 0.0001). IGFBP-2 concentrations were negatively associated with hepatic fat fraction independently of age and VAT in both men (R2 = 0.23, P = 0.012) and women (R2 = 0.27, P = 0.028). In conclusion, our findings show that even in asymptomatic, apparently healthy individuals, low IGFBP-2 levels are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content in a VAT-independent manner. However, IGFBP-2 does not appear to influence the established sexual dimorphism observed for metabolic variables and hepatic fat fraction. Additional studies are required to better understand the relationships between IGFBP-2 and liver fat content.NEW & NOTEWORTHY Faced with a paucity of reliable clinical etiologic markers for fatty liver, this research article demonstrates, for the first time, that low blood levels of the protein IGFBP-2 are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content independently of visceral fat volume and sex, even in asymptomatic, apparently healthy individuals.

WED-527 - Evaluating the hepatic efficacy and cardiometabolic profile of PNPLA3, TM6SF2, and other therapeutic targets for NALFD: a drug-target Mendelian randomization analysis

WED-527 - Evaluating the hepatic efficacy and cardiometabolic profile of PNPLA3, TM6SF2, and other therapeutic targets for NALFD: a drug-target Mendelian randomization analysis

HIGH BLOOD PRESSURE IN THE NEWLY DIAGNOSED TYPE 2 DIABETES PATIENTS

Objective: Type 2 diabetes mellitus and hypertension often coexisted in type 2 diabetes patients. Hypertension is often present at the time of diagnosis of type 2 diabetes. Our study aim to evaluate the prevalence of arterial hypertension in newly diagnosed type 2 diabetics and to evaluate the comorbidities associated with hypertension at the time of diagnosis of diabetes. Design and method: Is a prospective study based on 126 newly diagnosed type 2 diabetics, 66 men, and 60 women, aged 45 to 70, hospitalized in Internal Medicine. Blood pressure is taken in consultation according to the recommendations of the ESH, based at least in two consecutive consultations. All patients underwent the assessment of the impact on the target organs, as well as a systematic evaluation for micro and macro-vascular complications. Results: At the time of diagnosis of type 2 diabetes mellitus, the prevalence of arterial hypertension is 56.2%. The patients were already followed for arterial hypertension in 24% of the cases, among them, only 11% considered for therapeutic objectives, and 3% presented with ketosis. Hypertensive diabetics are on average 61.2 years old and have metabolic syndrome in 81.1%. Women are more obese and have a significantly higher waist circumference. Men have higher blood sugar, lower HDL, higher coronary risk, and more frequently present with albuminuria. The level of blood pressure, both systolic and diastolic, rises significantly with the number of metabolic syndrome criteria, and the number of cardiovascular risk factors. We find microangiopathy in 59.1% of cases, and cardiovascular disease in 65.2% of cases. The association of microangiopathy with cardiovascular disease is significantly more frequent in hypertensive diabetics than in non-hypertensives (58% vs 31%, p = 0.005). Conclusions: High blood pressure is very prevalent in newly diagnosed diabetics. The hypertensive diabetic has a higher degree of morbidity, and presents a cardiometabolic profile with a very high cardiovascular risk compared to the non-hypertensive diabetic at the time of diagnosis of diabetes mellitus.

Evaluation of the effectiveness and safety of anti-obesity drugs - an update on the current state of knowledge on available and investigational drugs

Introduction and purpose of the work: Disturbing epidemiological data indicate that obesity has become a global problem and has reached the size of a worldwide epidemic. The search for effective methods of combating obesity seems to be an important step in preventing cardiovascular diseases and numerous metabolic complications. The aim of the study is to assess the effectiveness and safety of available drugs used in the treatment of obesity in accordance with the current state of knowledge and to present new pharmacological options.&#x0D; State of knowledge: Pharmacotherapy provides overweight and obese adults with the opportunity to support weight reduction in the event of failure of lifestyle modifications. Currently registered drugs for the treatment of obesity are orlistat, lorcaserin, liraglutide and combination preparations: phentermine/topiramate and naltrexone SR/bupropion SR. &#x0D; Summary: Among the currently available drugs for obesity, the most effective are phentermine/topiramate and liraglutide. Research is also underway on the use of new substances that promote weight loss. The latest data on semaglutide and tirzepatide have better efficacy results compared to currently available drugs with a similar safety profile. The latest data on semaglutide and tirzepatide improve the efficacy results of current drugs while maintaining a similar safety profile. It seems that the best way to lose excessive body weight should be an individualized approach to the treatment of obesity among patients, taking into account i.a. degree of obesity, comorbidities, contraindications, patient preferences, cost and availability of treatment. In clinical practice, when choosing a drug, we should pay attention to side effects and find a balance between effectiveness and safety. In addition to weight loss, the use of anti-obesity drugs has many additional benefits, including improvement of the cardiometabolic profile, reduction of glucose, insulin and lipids in the blood.

Sex modifies the effect of genetic risk scores for polycystic ovary syndrome on metabolic phenotypes.

Females with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women, have an increased risk of developing cardiometabolic disorders such as insulin resistance, obesity, and type 2 diabetes (T2D). While only diagnosable in females, males with a family history of PCOS can also exhibit a poor cardiometabolic profile. Therefore, we aimed to elucidate the role of sex in the cardiometabolic comorbidities observed in PCOS by conducting bidirectional genetic risk score analyses in both sexes. We first conducted a phenome-wide association study (PheWAS) using PCOS polygenic risk scores (PCOSPRS) to identify potential pleiotropic effects of PCOSPRS across 1,380 medical conditions recorded in the Vanderbilt University Medical Center electronic health record (EHR) database, in females and males. After adjusting for age and genetic ancestry, we found that European (EUR)-ancestry males with higher PCOSPRS were significantly more likely to develop hypertensive diseases than females at the same level of genetic risk. We performed the same analysis in an African (AFR)-ancestry population, but observed no significant associations, likely due to poor trans-ancestry performance of the PRS. Based on observed significant associations in the EUR-ancestry population, we then tested whether the PRS for comorbid conditions (e.g., T2D, body mass index (BMI), hypertension, etc.) also increased the odds of a PCOS diagnosis. Only BMIPRS and T2DPRS were significantly associated with a PCOS diagnosis in EUR-ancestry females. We then further adjusted the T2DPRS for measured BMI and BMIresidual (regressed on the BMIPRS and enriched for the environmental contribution to BMI). Results demonstrated that genetically regulated BMI primarily accounted for the relationship between T2DPRS and PCOS. Overall, our findings show that the genetic architecture of PCOS has distinct sex differences in associations with genetically correlated cardiometabolic traits. It is possible that the cardiometabolic comorbidities observed in PCOS are primarily explained by their shared genetic risk factors, which can be further influenced by biological variables including sex and BMI.

The impact of excessive epicardial adipose tissue accumulation on cardiorespiratory fitness in adults without cardiac disease: a cross-sectional magnetic resonance imaging study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research. Background/Introduction Excessive epicardial adipose tissue (EAT) is associated with worse exercise capacity and is thought to play a role in the pathophysiology of heart failure with preserved ejection fraction. Few studies have explored the relationship between EAT, cardiorespiratory fitness in men and women without cardiovascular disease. Purpose To investigate the association between EAT, cardiorespiratory fitness, and physical activity levels in asymptomatic men and women of variable degree of adiposity. Methods A total of 239 participants (43% women) free from cardiovascular disease who underwent concurrent quantification of EAT volume assessed by cardiac magnetic resonance and a cardiopulmonary exercise testing (CPET) (VO2peak [ml/kg/min]) were studied. Physical activity levels/intensity were measured by questionnaire and using pedometer. Participants were categorized into low-EAT, moderate-EAT, and high-EAT groups on the basis of EAT volume. Results Mean age of participants was 49.8 ± 8.3 years, BMI 26.0 ± 3.7 kg/m2 (15% with obesity), waist circumference 89 ± 11 cm, visceral adipose tissue volume 91.3 ± 51.3 cm3, and EAT volume 9.8 ± 3.1 cm3. EAT volume decreased with increment in cardiorespiratory fitness in men and women of variable adiposity (p&amp;lt;0.05). Men and women with high-EAT had worse cardiometabolic profile (visceral adiposity, insulin resistance, high blood pressure, dysglycemia, atherogenic dyslipidemia), and lower cardiorespiratory fitness (VO2peak) than those with low-EAT (all p&amp;lt;0.05). Physical activity levels were comparable across EAT tertiles (p=NS). The association between EAT and cardiorespiratory fitness was no longer significant after controlling for visceral adiposity. Conclusions In men and women of variable degree of adiposity, excessive EAT accumulation is associated with visceral adiposity and worse cardiorespiratory fitness. Further longitudinal studies are needed to understand the interplay between EAT and cardiorespiratory fitness, and the development of obesity-related heart failure features.