Adjustment For BMI Research Articles

Screening for Circulating Inflammatory Proteins Does Not Reveal Plasma Biomarkers of Constant Tinnitus

Background and ObjectiveTinnitus would benefit from an objective biomarker. The goal of this study is to identify plasma biomarkers of constant and chronic tinnitus among selected circulating inflammatory proteins.MethodsA case–control retrospective study on 548 cases with constant tinnitus and 548 matched controls from the Swedish Tinnitus Outreach Project (STOP), whose plasma samples were examined using Olink’s Inflammatory panel. Replication and meta-analysis were performed using the same method on samples from the TwinsUK cohort. Participants from LifeGene, whose blood was collected in Stockholm and Umeå, were recruited to STOP for a tinnitus subtyping study. An age and sex matching was performed at the individual level. TwinsUK participants (n = 928) were selected based on self-reported tinnitus status over 2 to 10 years. Primary outcomes include normalized levels for 96 circulating proteins, which were used as an index test. No reference standard was available in this study.ResultsAfter adjustment for age, sex, BMI, smoking, hearing loss, and laboratory site, the top proteins identified were FGF-21, MCP4, GDNF, CXCL9, and MCP-1; however, these were no longer statistically significant after correction for multiple testing. Stratification by sex did not yield any significant associations. Similarly, associations with hearing loss or other tinnitus-related comorbidities such as stress, anxiety, depression, hyperacusis, temporomandibular joint disorders, and headache did not yield any significant associations. Analysis in the TwinsUK failed in replicating the top candidates. Meta-analysis of STOP and TwinsUK did not reveal any significant association. Using elastic net regularization, models exhibited poor predictive capacity tinnitus based on inflammatory markers [sensitivity = 0.52 (95% CI 0.47–0.57), specificity = 0.53 (0.48–0.58), positive predictive value = 0.52 (0.47–0.56), negative predictive values = 0.53 (0.49–0.58), and AUC = 0.53 (0.49–0.56)].DiscussionOur results did not identify significant associations of the selected inflammatory proteins with constant tinnitus. Future studies examining longitudinal relations among those with more severe tinnitus and using more recent expanded proteomics platforms and sampling of cerebrospinal fluid could increase the likelihood of identifying relevant molecular biomarkers.

Incidence and risk of dementia in people with Anxiety over 50 years old – an electronic health records study

AbstractBackgroundDepression is a well‐established risk factor for dementia, but we know far less about the links between Anxiety and future dementia risk in older people. The aim was therefore to investigate the incidence of dementia in people with and without Anxiety above the age of 50 years over a 10‐year period.MethodThe Health Improvement Network (THIN) was used, a large UK primary care dataset, that includes approximately 15.6 million patients, which is representative of the UK population. All people between 1st January 2008 and 31 December 2018 who had new onset Anxiety over the age of 50 years were identified. At the time of the first record of Anxiety, each person was individually matched to 4 unexposed persons based on their sex and age and Exposure Density Sampling was used, creating a dynamic cohort. Weibull survival regression models were fitted and hazard ratios (HR) were estimated for modelling time‐to‐dementia in those with and without Anxiety; and when determining the risk of developing dementia in those with Anxiety. Hazard ratio estimates were adjusted for sociodemographic and lifestyle factors, and relevant physical and mental health conditions.ResultIn this cohort study, there were 37,824 men and 68,761 women diagnosed with a first episode of Anxiety. Of those who had Anxiety, 2,792 people developed dementia during the follow up period, compared to 19,000 people in the non‐Anxiety group. The incidence of dementia in those with and without Anxiety was 7.21 (95% CI 6.94‐7.48) and 3.22 (95% CI 3.18‐3.28) respectively per 1,000 person‐years. The risk of dementia was increased 2.47‐fold [HR 2.47 (CI 2.37‐ 2.57)] in the Anxiety group when compared to the non‐Anxiety group after adjustment for age, sex, social deprivation, alcohol, smoking, BMI, diabetes mellitus, cardiovascular diseases, learning disabilities, HIV, multiple sclerosis, brain injury and hearing impairment.ConclusionThe incidence of dementia was greater in those with Anxiety and the risk of developing dementia was more than doubled in people with Anxiety compared to those without. This provides further evidence that Anxiety is a potential risk factor for dementia.

Association between Anemia and Dementia in Korea older adults: A national cohort study

AbstractBackgroundAs the global elderly population increases, the prevalence of dementia is also increasing. Korea is one of the rapidly aging countries in the world, and 10.33% of elderly people aged 65 and older are receiving treatment for dementia as reported in 2021. Since disease modifying drugs have not yet been developed for dementia, the importance of modifiable risk factors that can lower the risk of dementia is being emphasized, and one of them is anemia in the elderly. We analyze national cohort data of approximately 20 years to disclose the relationship between anemia and dementia in Korean elderly, and suggest that anemia is a modifiable risk factor for dementia needed active intervention.MethodWe analyzed a large population‐based cohort study of aged ³65 years who participated in the national health screening program including blood tests and cognitive function tests from 2007 to 2008 in Korean National Health Insurance Service database 2006‐2020. The risk of AD according to the presence and severity of anemia was evaluated using a multivariable Cox regression model, after adjustments for sex, BMI, HTN, DM, LDL, TG, SCr, GFR and past medical history (depression, HTN, DM, cardiovascular disease, cerebrovascular disease).ResultAs a result of the analysis, dementia occurred in 27.9% of the total subjects (316,881 persons) during the follow‐up period until 2020. Also, dementia occurred in 27.5% of the normal group, but 30.1% of the anemia group. As a result of survival analysis, even after adjusting for sex, there was a statistically significant difference between the presence of anemia and the prevalence of dementia (HR 1.07, 95% CI 1.05‐1.09). In addition, even after adjusting for sex, BMI, HTN, DM, LDL, SCr, GFR, and past medical history, there was a statistically significant association between anemia and dementia (HR 1.05, 95% CI 1.03‐1.07).ConclusionWe reported that the presence of anemia statue and the severity of anemia in the elderly were related to the occurrence of dementia through a national date of Korea. We suggest that anemia is a modifiable risk factor for dementia and requires intensive intervention in the elderly.

Ultra-processed Food Intake and Risk of Type 2 Diabetes in Korean Adults

BackgroundSeveral studies from the United States and European countries reported a positive association between ultra-processed food intake and diabetes risk. However, little is known about the association in Asian populations. It is also unknown about the individual ultra-processed food items that are most unfavorably associated with diabetes risk. ObjectiveWe examined the associations of ultra-processed food intake (combined, as well as individual ultra-processed food items) with the risk of type 2 diabetes. MethodsThis prospective analysis included 7438 participants aged 40–69 y from the Korean Genome and Epidemiology Study Ansan–Ansung cohort. Dietary intake was assessed at baseline using a 103-item semiquantitative food-frequency questionnaire. Ultra-processed foods were classified using the Nova definition. Incident type 2 diabetes cases were identified via follow-up interviews and health examination. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential confounders. ResultsDuring the follow-up (2001–2019; median: 15 y), a total of 1187 type 2 diabetes cases were identified. Compared with the lowest quartile of ultra-processed food intake, the highest quartile was positively associated with diabetes risk [HR (95% CI) = 1.34 (1.13, 1.59), P-trend = 0.002]. The association did not change after additional adjustment for diet quality or BMI. Among individual ultra-processed food items, a higher consumption of ham/sausage [per 1% increase in the weight ratio: HR (95% CI) = 1.40 (1.05, 1.86)], instant noodles [1.07 (1.02, 1.11)], ice cream [1.08 (1.03, 1.13)], and carbonated beverages [1.02 (1.00, 1.04)] were associated with an increased risk of type 2 diabetes, whereas a higher intake of candy/chocolate was associated with a decreased risk [0.78 (0.62, 0.99)]. ConclusionsOur data suggest that the high intake of ultra-processed foods, particularly ham/sausage, instant noodles, ice cream, and carbonated beverages, is associated with an increased risk of type 2 diabetes in Korean adults.

Increased Plasma Branched Short-Chain Fatty Acids and Improved Glucose Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Short chain fatty acids (SCFA) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched short chain fatty acids (BSCFA), isobutyrate, isovalerate, and methylbutyrate, is largely unknown. In a cohort of 219 non-Hispanic Whites and 126 African Americans, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, lipid traits, and other SCFA. We observed a bimodal distribution of BSCFA, with 25 individuals having high levels (HBSCFA group) and 320 individuals having lower levels (L-BSCFA group). The prevalence of dysglycemia was lower in the H-BSCFA group compared to the L-BSCFA group (16% versus 49%, P=0.0014). This association remained significant after adjustment for age, sex, race, BMI, and levels of other SCFA. Consistent with the lower rate of dysglycemia, fasting and postprandial glucose were lower and disposition index was higher in the H-BSCFA group. Additional findings in H-BSCFA versus L-BSCFA included lower fasting and postprandial Cpeptide levels and lower insulin clearance without differences in insulin levels, insulin sensitivity, insulin secretion, or other variables examined, including diet and physical activity. As one of the first human studies associating higher BSCFA levels with lower odds of dysglycemia and improved glucose homeostasis, this study sets the stage for further investigation of BSCFA as a novel target for prevention or treatment of diabetes.

Physiological and haemodynamic differences between peak exercise blood pressure and blood pressure-power output slope in healthy women

Abstract Background A hypertensive response to exercise (HRE) is considered indicative of increased arterial stiffness (1). However, HRE is common in individuals with high cardiorespiratory fitness (CRF) (2), which we hypothesize is due to increased stroke volume (SV) and cardiac output (Qc). Purpose This study compared differences in CRF and peak-exercise SV (SVpeak) and Qc (Qcpeak) according to absolute and workload-indexed definitions of exercise hypertension in women. Methods Women free of overt CVD (n=142; 52±8years, BMI: 26.3±4.5kg/m2) underwent exercise cardiac magnetic resonance to quantify SVpeak and Qcpeak, and cardiopulmonary exercise testing to quantify peak VO2, power output (PO) and systolic blood pressure (SBP) responses. SBP-PO slope was determined using linear regression of SBP and PO values obtained every 2-minutes throughout exercise. HRE was defined as peak SBP ≥190mmHg (3), and elevated SBP-PO slope was defined as a slope >90th percentile for sex and age based on previously published values (4). Results 51% and 23% of the cohort met criteria for HRE and elevated SBP-PO slope, respectively, with 16% meeting both criteria. HRE was associated with higher VO2peak (2.03±0.53 vs 1.83±0.44 L/min, P=0.015), peak PO (191±66 vs 167±51 Watts, P=0.014), SVpeak (109±27 vs 98±19 mLs, P=0.008), and Qcpeak (15.1±3.3 vs 13.9±2.8 L/min, P=0.023). In contrast, elevated SBP-PO slope was associated with lower VO2peak (1.57±0.36 vs 2.04±0.48 L/min), peak PO (135±34 vs 192±60Watts) SVpeak (88±13 vs 108±24 mLs) and Qcpeak (12.5±1.8 vs 15.1±3.1 L/min; P<0.001 for all). Overall, the group with HRE and elevated SBP-PO slope had the lowest physical capacity, VO2peak and haemodynamic response to exercise (Figure 1A-D), whilst the opposite trend was seen for those with a HRE and a normal SBP-PO slope. All results remained significant (P<0.05) after adjustment for age, BMI, resting SBP and menopausal status (pre vs peri/post-menopausal). Conclusion Contextualising exercise SBP responses against measures of PO better accounts for confounding from increased Qcpeak, and may improve identification of women with increased arterial stiffness.Figure 1A-D

Increased inflammatory proteins in patients with severe obesity is associated with persistent myocardial dysfunction one year after bariatric surgery. The FatWest study

Abstract Background Over half of patients with severe obesity have subclinical cardiac dysfunction and about 40% maintain impaired left ventricular (LV) mechanics one year after bariatric surgery despite impressive weight reduction. Purpose To investigate whether measurement of serum markers of chronic inflammation before bariatric surgery can help identify patients with persistent postoperative cardiac dysfunction. Methods In the prospective FatWest (Bariatric Surgery on the West Coast of Norway) study 75 patients with severe obesity (44±9 years, 72% women, body mass index [BMI] 41.5±4.7 kg/m², 56% with hypertension) underwent echocardiography before and 1 year after Roux-en-Y gastric bypass surgery. We assessed LV mechanics in the radial and longitudinal direction by the midwall shortening (MWS) and global longitudinal strain (GLS). Myocardial oxygen (O2) demand was derived from the LV mass-wall stress-heart rate product. Inflammation was assessed by high-sensitive C-reactive protein, serum amyloid A and calprotectin in biobank samples. Results Preoperatively, patients with low MWS (45% of the group) had increased high-sensitive C-reactive protein, total calprotectin, and several amyloid A isoforms, and patients with high myocardial O2 demand (20%) had high total calprotectin (all p<0.05). In the whole study population, bariatric surgery induced a significant improvement in both BMI (12.6±3.7 kg/m²), GLS (4.74±5.20%), myocardial O2 demand and inflammatory proteins (Figure A, all p<0.001). However, there were no significant improvement in MWS, and 33% of patients still had low MWS at the 1-year control. In logistic regression analyses, after adjustment for sex, BMI and hypertension, increased preoperative serum total calprotectin was independently associated with high myocardial O2 demand both pre- and postoperatively (Nagelkerke R² 0.47 and 0.51, p<0.05). In similar analyses, higher preoperative serum total amyloid A was related to low MWS and high myocardial O2 demand 1 year after surgery (Nagelkerke R² 0.55 and 0.51, p<0.05). A simple preoperative risk score based on sex, hypertension, biplane ejection fraction, and serum total amyloid A above 4.0 mg/ml predicted low 1-year MWS with 79% sensitivity and 75% specificity at a value of 1.75 in Receiver Operating Characteristic (ROC) analysis (AUC 0.80, p<0.001) (Figure B). Low GLS was not predicted by inflammatory biomarkers at any timepoint. Conclusion Increased serum concentration of inflammatory proteins in patients with severe obesity is linked to persistently elevated myocardial O2 demand and impaired LV midwall mechanics 1 year after bariatric surgery.Figure AFigure B

Effectiveness of Chinese herbal medicine compared with angiotensin II receptor blockers in patients with diabetic kidney disease: A hospital-based matched cohort study

Angiotensin II receptor blockers (ARBs) are one of the standard treatments for diabetic kidney disease (DKD). Some patients may opt for Chinese herbal medicine (CHM) of their own free will. However, there is no real-world evidence regarding the effectiveness and safety of CHM. We aimed to explore the effectiveness of CHM for DKD in comparison to ARBs. We enrolled 732 DKD patients (72 used only CHM and 661 used ARBs) from 2007 to 2016, and all patients were followed until December 2016 at China Medical University Hospital in Taiwan. A total of 355 ARB users and 71 CHM users were analyzed after propensity score matching. The estimated glomerular filtration rate (eGFR) after treatment was 84.9 ± 28.1 ml/min/1.73 m2 in CHM users, which was higher than that (67.8 ± 35.4 ml/min/1.73 m2) in ARB users (p < 0.001). The change in the eGFR was −6.0 ± 21.4 ml/min/1.73 m2 in CHM users and −12.9 ± 24.8 ml/min/1.73 m2 in ARB users (p = 0.029). The blood urea nitrogen (BUN) and creatinine levels of patients taking CHM were 22 ± 16 mg/dl and 0.9 ± 0.4 mg/dl, respectively, and were lower than those (30 ± 28 mg/dl and 1.7 ± 2.0 mg/dl) of patients taking ARBs (p = 0.025 and p = 0.003). Using linear regression with adjustments for age, sex, BMI, baseline eGFR, and HbA1c levels, we found that the declines in the eGFR/baseline eGFR and changes in the urine albumin–creatinine ratio (ACR) were comparable between the two groups (p = 0.86 and 0.73). This study suggests that CHM may have comparable effectiveness to ARBs, which provides insights for further investigations.

Association of Perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposures and the risk of systemic lupus erythematosus: a case–control study in China

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) may have a role in impaired health. However, the data on the association between PFASs and Systemic lupus erythematosus (SLE) have been limited. We designed a population-based case–control study in China and evaluated the association. 100 normal persons (Control) and 100 SLE patients (Case) were obtained from 113 controls and 125 cases according to matching conditions. Serum samples were collected by venipuncture for UHPLC-MRM-MS Analysis to obtain the concentration of five PFASs in participants. Demographic characterization description was performed for the two groups of participants, the PFASs concentration distribution of the two groups was described and compared, then divided into three tiers (< 50th, 50th ~ 75th, > 75th) for subsequent analysis. Conditional logistic regression models were utilized to calculate the odds ratios (ORs) and 95% CIs for SLE. Relationship between changes in the concentration of PFASs and the risk of SLE assessed by restricted cubic spline. As the highest serum levels of the five PFASs tested in this study population, the highest perfluoroundecanoic acid (PFUnA) quartile had a 2.78-fold (95%CI: 1.270, 6.10) compared with the lowest quartile of PFUnA exposure, other types of PFASs also showed high association with SLE as well as PFASs mixture. Additionally, the exposure of PFASs exist a dose–response relationship (ptrend < 0.05). This risk association remained be found after adjusting the covariates in model 1 (adjustment of BMI) and in model 2(adjustment of BMI, smoking, drinking, hypertension and leukocyte). The restricted cubic spline illustrated a gradual increase in the possible risk of SLE with the increasing exposure of PFASs components levels. Our study firstly revealed that PFASs are risk factors for SLE and PFASs exposures are associated with SLE risk in a dose − response manner. Evidence from larger and more adequately powered cohort studies is needed to confirm our results.

Abstract 14024: Proteomic Predictors of Transitioning From Metabolically Healthy to Unhealthy Status in Middle-Aged Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Metabolic health status predicts adverse cardiovascular outcomes. Among persons with similar weight, some metabolically healthy individuals stay metabolically healthy, whereas others develop metabolic syndrome (MetS) over time. Hypothesis: Plasma proteins can identify biological correlates of transitioning from metabolically healthy to unhealthy status. Methods: We quantified 4,955 plasma proteins using SomaLogic v4.0 in stored samples of ARIC Visit 2 participants. We assessed metabolic health at Visits 2 (1990-92) and 4 (1996-98). We split the sample into 2/3 discovery and 1/3 validation subsamples and used Bonferroni-corrected p-values. Among metabolically healthy individuals (no MetS) at Visit 2, we evaluated the associations of baseline plasma protein concentrations with the odds of developing metabolic unhealthy status by Visit 4 using logistic regression. We performed gene product enrichment analysis to assess biological pathways associated with transitioning to metabolically unhealthy status. Results: We included 4,539 participants (mean age: 56±6 years, 58% women, 17% Black adults, mean BMI 25 kg/m 2 ). Adjusting for confounders, 306 proteins were significantly associated with transitioning from metabolically healthy to unhealthy status. After further adjustment for BMI, 121 proteins had significant associations (p&lt;10 -5 ). Of these, 49 proteins were validated (p&lt;0.05/121). We identified proteins with known associations (growth hormone receptor, adiponectin, plasminogen activator inhibitor) with metabolically unhealthy status and ~20 novel proteins (MXRA8, VOPP1, CRYZL1). Biological pathways overrepresented by these proteins included tyrosine kinase signaling, complement and coagulation cascades, and calcium signaling pathways. Conclusions: Plasma proteins are linked to developing metabolic unhealthy status over 6 years. These proteins could be useful in identifying and preventing poor metabolic health.

Abstract 15927: Polyunsaturated Fatty Acid Levels and Their Relationship With Peak Exercise Measures in HFpEF

Background: Polyunsaturated fatty acids (PUFAs) regulate the inflammatory cascade and have been implicated in potential pathologic and therapeutic roles in heart failure with preserved LVEF (HFpEF). The purpose of this study was to explore the relationship between plasma levels of omega-3 (ω-3) fatty acids and invasive hemodynamic profiles characteristic of early HFpEF. Methods: In a single-center referral cohort undergoing evaluation for exertional dyspnea and suspected HFpEF, we assayed ω-3 concentrations in plasma by liquid chromatography. We derived an ω-3 score by summing Z-scores of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Linear regression was used to relate plasma ω -3 levels to simultaneously collected physiologic data from cardiopulmonary exercise testing (CPET) with invasive catheterization. Results: 588 patients (52% female, age 62 ± 12 years, BMI 30 ± 6 kg/m 2 , peak oxygen uptake (VO 2 ) 15.5 ± 5.1 mL/min/kg [76 ± 20% predicted], NTproBNP 118 [33 - 405] pg/mL) were studied. Median ω -3 concentrations were 72 [46 - 107] pg/mL for EPA and 315 [225 - 457] pg/mL for DHA. Female sex and increased age were associated with higher levels of ω-3 fatty acids ( Table , p=0.03). After adjustment for age, sex, and BMI, a higher ω-3 score was associated with greater exercise capacity measured by peak VO 2 (p&lt;0.001) and peak workload (p&lt;0.001) along with an increase in peak exercise peripheral O 2 extraction (CavO 2 ; p &lt; 0.001). Notably, increased ω-3 score was associated with lower supine pulmonary capillary wedge pressure (PCWP; p=0.03), PCWP to cardiac output (CO) slope during exercise (p = 0.009), and NTproBNP (p &lt; 0.001). Conclusion: These data demonstrate that circulating ω-3 fatty acid levels are associated with exercise capacity and both central cardiac and peripheral function in HFpEF. Further studies are needed to unravel the relationship between modulation of plasma PUFAs and rest and exercise hemodynamic profiles of HFpEF.

Abstract 14300: Biomarkers of Myocardial Injury, but Not Systemic Inflammation, Predict the Risk of Incident Ventricular Arrhythmia

Background: Cardiac troponins and biomarkers of inflammation are elevated in heart failure (HF) and predict cardiovascular risk. Whether these biomarkers associate with risk of ventricular arrhythmias (VA) is unclear. Purpose: To assess whether cardiac Troponin T (cTnT), growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations are associated with incident VA. Methods: In a prospective, observational study of patients treated with implantable cardioverter defibrillator (ICD), cTnT, GDF-15, IL-6, and CRP were measured at baseline and after 1.4±0.5y, and associated with ICD-detected incident VA, HF hospitalizations and mortality. Results: We included 489 patients, aged 66±12y and 83% were men. Median (quartile 1-3) concentrations of cTnT were 15 (9-25) ng/L at inclusion, and higher concentrations were associated with higher age, male sex, diabetes mellitus, coronary artery disease (CAD), and HF. During 3.1±0.7y follow-up, 137 (28%) patients had ≥1 VA. cTnT concentrations were associated with an increased VA risk (HR 1.63 [95% CI 1.31-2.01] per log-unit, p&lt;0.001), also after adjustment for age, sex, BMI, CAD, HF, renal function, and LVEF (p&lt;0.001). GDF-15, IL-6, and CRP concentrations were not associated with incident VA, but all (including cTnT) were associated with HF hospitalization and mortality. Changes in cTnT, GDF-15, IL-6, and CRP from baseline to 1.4y were not associated with subsequent VA. Conclusions: Higher concentrations of cTnT, GDF-15, IL-6, and CRP associate with HF hospitalization and death, but only cTnT predicts incident VA. These findings suggest that myocardial injury rather than inflammation may play a pathophysiological role in VA and sudden cardiac death.

Abstract 12593: Associations of Serum Uric Acid and Cardiovascular Events in a Clinical Trial of IL-1β Blockade

Background: Serum uric acid (SUA) associates with CV events, mortality, and gout. We assessed whether SUA predicts CV risk in a trial of IL-1β inhibition with canakinumab, a therapy known to reduce both CV events and gout. Aims: To validate associations between SUA and CV risk in a large cohort with chronic CAD and determine whether these associations were altered by IL-1β blockade or baseline renal function. Methods: The Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) randomized 10,061 patients with prior MI and hsCRP ≥ 2 mg/L to canakinumab 50 mg, 150 mg, 300 mg, or placebo subcutaneously every four weeks. SUA levels were obtained at baseline. Cox proportional hazards models compared the outcomes of major adverse cardiovascular events (MACE), CV death (CVD), and all-cause mortality (ACM) among those with baseline SUA ≤ 6.8 mg/dL, 6.8- 9.0 mg/dL, and ≥ 9.0 mg/dL (format: HR (95% CI); p). This analysis was repeated separately within canakinumab, placebo, eGFR ≥ 60 mL/min, and eGFR &lt; 60 mL/min sub-groups. Results: High SUA associated with MACE (1.66 (1.38-1.99); p&lt;0.0001), CVD (2.52 (1.98-3.21); p&lt;0.0001), and ACM (2.43 (2.01-2.94); p&lt;0.0001) compared to low SUA. These associations were minimally attenuated after adjustment for age, sex, BMI, smoking, hypertension, diabetes, LDL-C, and hsCRP. After further adjusting for eGFR and diuretic use, high SUA independently predicted CVD and ACM. In the IL-1β blockade arm, high SUA associated with MACE (1.82 (1.46-2.26); p&lt;0.0001), CVD (2.80 (2.10-3.73); p&lt;0.0001), and ACM (2.72 (2.17-3.40); p&lt;0.0001). In participants with normal eGFR, high SUA associated with CVD and ACM, but not MACE. Conclusions: These data from a large cohort of patients with chronic CAD confirm that individuals with elevated SUA have increased CV risk despite aggressive medical therapies. IL-1β blockade did not modify these associations. Future trials may consider inclusion of patients with high SUA and CKD as a method to increase absolute risk.

DNA methylation of insulin signaling pathways is associated with HOMA2-IR in primary myoblasts from older adults

BackgroundWhile ageing is associated with increased insulin resistance (IR), the molecular mechanisms underlying increased IR in the muscle, the primary organ for glucose clearance, have yet to be elucidated in older individuals. As epigenetic processes are suggested to contribute to the development of ageing-associated diseases, we investigated whether differential DNA methylation was associated with IR in human primary muscle stem cells (myoblasts) from community-dwelling older individuals.MethodsWe measured DNA methylation (Infinium HumanMethylationEPIC BeadChip) in myoblast cultures from vastus lateralis biopsies (119 males/females, mean age 78.24 years) from the Hertfordshire Sarcopenia Study extension (HSSe) and examined differentially methylated cytosine phosphate guanine (CpG) sites (dmCpG), regions (DMRs) and gene pathways associated with HOMA2-IR, an index for the assessment of insulin resistance, and levels of glycated hemoglobin HbA1c.ResultsThirty-eight dmCpGs (false discovery rate (FDR) < 0.05) were associated with HOMA2-IR, with dmCpGs enriched in genes linked with JNK, AMPK and insulin signaling. The methylation signal associated with HOMA2-IR was attenuated after the addition of either BMI (6 dmCpGs), appendicular lean mass index (ALMi) (7 dmCpGs), grip strength (15 dmCpGs) or gait speed (23 dmCpGs) as covariates in the model. There were 8 DMRs (Stouffer < 0.05) associated with HOMA2-IR, including DMRs within T-box transcription factor (TBX1) and nuclear receptor subfamily-2 group F member-2 (NR2F2); the DMRs within TBX1 and NR2F2 remained associated with HOMA2-IR after adjustment for BMI, ALMi, grip strength or gait speed. Forty-nine dmCpGs and 21 DMRs were associated with HbA1c, with cg13451048, located within exoribonuclease family member 3 (ERI3) associated with both HOMA2-IR and HbA1c. HOMA2-IR and HbA1c were not associated with accelerated epigenetic ageing.ConclusionsThese findings suggest that insulin resistance is associated with differential DNA methylation in human primary myoblasts with both muscle mass and body composition making a significant contribution to the methylation changes associated with IR.

The relationships between the plasma metabolome and orthostatic blood pressure responses

Whereas autonomic dysfunction and the metabolic syndrome are clinically associated, the relationships with the plasma metabolome is unknown. We explored the association between orthostatic blood pressure responses and 818 plasma metabolites in middle-aged subjects from the general population. We included 3803 out of 6251 subjects (mean age, 57 years; 52% women) from the Malmö sub-cohort of The Swedish CardioPulmonary bioImage Study with information on smoking habits, diabetes, antihypertensive drug treatment, anthropometrics, hemodynamic measurements and 818 plasma metabolites (mass-spectrometry). The associations between each metabolite and orthostatic systolic blood pressure responses were determined using multivariable linear regression analysis and p values were corrected using the Bonferroni method. Six amino acids, five vitamins, co-factors and carbohydrates, nine lipids and two xenobiotics were associated with orthostatic blood pressure after adjusting for age, gender and systolic blood pressure. After additional adjustments for BMI, diabetes, smoking and antihypertensive treatment, the association remained significant for six lipids, four amino acids and one xenobiotic. Twenty-two out of 818 plasma metabolites were associated with orthostatic blood pressure responses. Eleven metabolites, including lipids in the dihydrosphingomyelin and sphingosine pathways, were independently associated with orthostatic systolic blood pressure responses after additional adjustment for markers of cardio-metabolic disease.

Myocardial Fibrosis and Steatosis in Patients with Aortic Stenosis: Roles of Myostatin and Ceramides.

Aortic stenosis (AS) involves progressive valve obstruction and a remodeling response of the left ventriculum (LV) with systolic and diastolic dysfunction. The roles of interstitial fibrosis and myocardial steatosis in LV dysfunction in AS have not been completely characterized. We enrolled 31 patients (19 women and 12 men) with severe AS undergoing elective aortic valve replacement. The subjects were clinically evaluated, and transthoracic echocardiography was performed pre-surgery. LV septal biopsies were obtained to assess fibrosis and apoptosis and fat deposition in myocytes (perilipin 5 (PLIN5)), or in the form of adipocytes within the heart (perilipin 1 (PLIN1)), the presence of ceramides and myostatin were assessed via immunohistochemistry. After BMI adjustment, we found a positive association between fibrosis and apoptotic cardiomyocytes, as well as fibrosis and the area covered by PLIN5. Apoptosis and PLIN5 were also significantly interrelated. LV fibrosis increased with a higher medium gradient (MG) and peak gradient (PG). Ceramides and myostatin levels were higher in patients within the higher MG and PG tertiles. In the linear regression analysis, increased fibrosis correlated with increased apoptosis and myostatin, independent from confounding factors. After adjustment for age and BMI, we found a positive relationship between PLIN5 and E/A and a negative correlation between septal S', global longitudinal strain (GLS), and fibrosis. Myostatin was inversely correlated with GLS and ejection fraction. Fibrosis and myocardial steatosis altogether contribute to ventricular dysfunction in severe AS. The association of myostatin and fibrosis with systolic dysfunction, as well as between myocardial steatosis and diastolic dysfunction, highlights potential therapeutic targets.

Association between sleep duration and high blood pressure in Lithuanian adolescents

Abstract Background Sufficient sleep duration in children plays an essential role in physical, mental, and emotional development. High blood pressure (HBP) is growing public health problem in youth. The aim of this study was to evaluate the association between short sleep duration (SSD) and HBP in Lithuanian adolescents aged 11-18 years. Methods The cross-sectional study was conducted from 2019 to 2020 in Kaunas district, Lithuania. HBP was defined according to the 2017 AAP guidelines. Sleep duration was calculated from the time of going to bed to the time of waking up. SSD was defined as sleeping &amp;lt;8 h/day. Multivariate logistic regression was used to calculate aORs and 95% CI. Results The present analysis included 1368 subjects (723 boys and 645 girls) with a mean age of 13.96±1.76 years. Overall, the prevalence of HBP was 43.6% (51.3% for boys and 34.9% for girls). Overall, 21.7% of the subjects reported sleep duration of 7- &amp;lt; 8 h/day, and 11.3% - &amp;lt;7 h/day. In the total sample, after adjustment for sex, BMI, breakfast consumption, and parental smoking, significant associations were found between SSDs and HBP (7-&amp;lt;8 h/day: aOR=1.47; 95% CI, 1.12-1.95; P = 0.006, and &amp;lt;7 h/day: aOR=1.52; 95% CI, 1.05-2.20; P = 0.025), compared to subjects who were sleeping ≥8 h/day. In boys, after adjustment for potential confounders, SSDs were associated with higher odds of HBP (7-&amp;lt;8 h/day: aOR=1.94; 95% CI, 1.30-2.89; P = 0.001, and &amp;lt;7 h/day: aOR=2.35; 95% CI, 1.35-4.12; P = 0.003). There was no significant association between SSD and HBP among girls. Conclusions Our study showed that SSD was significantly associated with increased odds of HBP in Lithuanian adolescents, especially in boys. Public health strategies should focus more on prevention of modifiable cardiovascular disease risk factors. Key messages • Sufficient sleep duration is important for adolescents’ health and may contribute to reduce the risk of cardiovascular disease. • Future prospective studies are needed to confirm these findings.

The association between diet quality and chronic obstructive pulmonary disease: a case-control study

BackgroundPrevious investigations have primarily examined the relationship between various dietary patterns and the risk of chronic obstructive pulmonary disease (COPD); however, there have been limited studies that have evaluated the association between diet quality presented by Healthy Eating Index 2010 (HEI-2010) and COPD. The aim of this study was to investigate this association in Iranian population.MethodsThis case-control study recruited 84 cases and 252 healthy controls who were randomly selected. Diet, smoking, and physical activity were assessed using validated questionnaires. The HEI-2010 score ranged from zero to hundred twenty, with zero indicating an unhealthy diet and hundred twenty indicating a healthy diet. Logistic regression models were utilized to analyze the association between HEI-2010 and the odds of COPD.ResultsResults from logistic regression showed that individuals with higher HEI scores had a significantly lower odds of COPD (OR: 0.34; 95% CI: 0.16–0.72). After adjusting for confounders, individuals with the highest HEI score were 82% less likely to have COPD (OR: 0.18; 95% CI: 0.03–0.96). This association remained significant after adjusting for smoking and physical activity (OR: 0.08; 95% CI: 0.01–0.93) and with additional adjustment for BMI (OR: 0.08; 95% CI: 0.01–0.92).ConclusionsThis study found a significant association between a higher HEI-2010 score and a lower odd of COPD in the Iranian population. These results suggest that a healthy diet may play a crucial role in reducing the odds of COPD and in improving the function of the lungs. However, further prospective studies are warranted to elucidate this relationship.

Significance of fatty liver index to detect prevalent ischemic heart disease: evidence from national health and nutrition examination survey 1999-2016.

Non-alcoholic fatty liver disease (NAFLD) contributes to the development of ischemic heart disease via multiple mechanisms. Fatty liver index (FLI) has been proposed as an accurate, convenient, and economic surrogate of the severity of NAFLD. Our present study aims to assess the association between FLI and the prevalent IHD and to evaluate the potential value of FLI to refine the detection of prevalent IHD in the general population. Our work recruited 32,938 subjects from the National Health and Nutrition Examination Survey 1999-2016. IHD was diagnosed according to the subjects' self-report. FLI was determined based on triglycerides, BMI, γ-glutamyltransferase, and waist circumference. 2,370 (7.20%) subjects were diagnosed with IHD. After adjustment of age, sex, race, current smoking, current drinking, PIR, BMI, WC, TC, TG, GGT, Scr, FPG, SBP, anti-hypertensive therapy, anti-diabetic therapy, and lipid-lowering therapy, one standard deviation increase of FLI resulted in a 27.0% increment of the risk of prevalent IHD. In the quartile analysis, we observed a 1.684 times risk of prevalent IHD when comparing the fourth quartile with the first quartile, and there was a trend towards higher risk across the quartiles. The smooth curve fitting displayed a linear relationship between FLI and the presence of IHD without any threshold or saturation effect. Subgroup analysis revealed a robust association in conventional cardiovascular subpopulations, and the association could be more prominent in female subjects and diabetes patients. ROC analysis demonstrated an incremental value of FLI for detecting prevalent IHD after introducing it to conventional cardiovascular risk factors (AUC: 0.823 vs. 0.859, P for comparison <0.001). Also, results from reclassification analysis implicated that more IHD patients could be correctly identified by introducing FLI into conventional cardiovascular risk factors (continuous net reclassification index: 0.633, P < 0.001; integrated discrimination index: 0.034, P < 0.001). The current analysis revealed a positive and linear relationship between FLI and the prevalent IHD. Furthermore, our findings suggest the incremental value of FLI to refine the detection of prevalent IHD in the general population.

Alteration of Plasma Indoles in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive-aged women. The occurrence of PCOS was reported to be associated with the alteration of gut microbiota. Microbiota-derived indoles may possibly play a key role in glycemic control. The purpose of this work is to reveal the alteration of plasma indoles in PCOS patients and to investigate the correlation between indoles levels and glucose metabolism. Sixty-five patients with PCOS and twenty-eight age-matched women were enrolled in this work. The concentrations of plasma indoles, including indoxyl sulfate (IS), indole-3-acetic acid (IAA), indole-3-propionate (IPA), indole (IND), and 3-methylindole (3-MI), were measured by HPLC with the fluorescence detection. The plasma levels of IS, IAA, and IND were significantly elevated in patients with PCOS compared to those in the control group (p < 0.05). Furthermore, the plasma levels of IS, IAA, and IND were positively correlated with fasting glucose, fasting insulin, and the homeostatic model of insulin resistance index (HOMA-IR) (p < 0.05). Besides, the 3-MI level in the plasma was positively correlated with the fasting glucose level, whereas plasma levels of IS, IAA, IND, and 3-MI were negatively correlated with glucagon-like peptide 1 (p < 0.05). Moreover, IS and IND were considered to be risk factors for PCOS after age, BMI, T, LH, and HOMA-IR adjustment. The area under the receiver-operating characteristic curve of the combined index of five indoles was 0.867 for PCOS diagnosis. Additionally, plasma indoles altered in PCOS, which was closely associated with the glucose metabolism.