European Heart Journal

ObjectivateTo assess demographic characteristics and investigate the correlation between cardiovascular diseases and long COVID-19 patients. MethodsComprehensive details, encompassing the first authors name, publication year, sample inclusion criteria, sample size, and demographic characteristics, including age and gender of participants, were systematically extracted from all incorporated studies. Meanwhile, the analysis encompassed the assessment of the risk associated with nineteen cardiovascular outcomes. ResultsA total of 3, 201 potentially eligible studies were initially identified for consideration. Following rigorous literature screening and quality control measures, eighteen studies, encompassing 46, 083, 975 patients, met the specified criteria. In comparison to the control cohort, our investigation unveiled a heightened risk of 19 cardiovascular outcomes associated with long COVID-19. Our meta-analysis revealed a pooled OR of 1.68 (95% CI 1.55-1.81) (I2 = 69.1%, p= 0.000) for the overall risk of cardiovascular outcomes, indicating an elevated risk of cardiovascular diseases in individuals affected by long COVID-19. While the heterogeneity was relatively high, it is essential to acknowledge that all studies inherently carry an unavoidable risk of bias, irrespective of their quality rating. Moreover, there appears to be no significant publication bias based on the funnel plot, Beggs, and Eggers tests. Sensitivity analysis did not reveal substantial alterations in the overall stability of the results. ConclusionsOur meta-analysis substantiates that individuals afflicted with long COVID-19 face an elevated risk of developing cardiovascular diseases. Routine assessment of cardiac function is deemed essential for a long COVID-19 high-risk cardiovascular disease population. Timely interventions have the potential to mitigate the risk of cardiovascular diseases and associated mortality in this population. TRIAL REGISTRATION PROSPERO IdentifierCRD42023455701

ObjectiveTo evaluate the strength and certainty of the evidence underlying an association between increased adiposity, as assessed by body-mass index (BMI), waist circumference (WC), or waist-to-hip ratio (WHR) and identify the risk of incident cardiovascular disease (CVD) events or mortality DesignUmbrella review of systematic reviews and meta-analyses. Data sourcesGoogle Scholar, PubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references Eligibility criteriaSystematic reviews or meta-analyses of observational studies and Mendelian randomisation (MR) studies that evaluated the association between various obesity-related indices and the risk of developing CVD and/or mortality due to CVD Data synthesisEleven systematic reviews and 53 meta-analyses that investigated associations between obesity and cardiovascular outcomes were included. Results from recently published cohort studies were also incorporated into the existing meta-analyses to update them with more recent data. Thus, the present study compiled all the relevant evidence accumulated to date, encompassing a total of 488 cohorts and over 30 million participants. MR studies were collected to identify any causal relationship between obesity and various CVD outcomes, and to avoid reverse causality. The degree of obesity was measured with BMI, WC, and WHR. The evidence levels of pooled results were graded into high, moderate, low, and very low according to the Grading of Recommendations Assessment, Development and Evaluation framework. ResultsAn increase in BMI was associated with a higher risk of developing coronary heart disease, heart failure, atrial fibrillation, stroke, hypertension, aortic valve stenosis, pulmonary embolism, and venous thromboembolism; the study results corroborate the casual effect of obesity on the incidence of CVD, except stroke, based on MR studies. The increase in the risk of developing CVD for every 5 kg/m2 increase in BMI ranged from 7% (relative risk [RR], 1.07; 95% confidence interval [CI], 1.03 to 1.11) for stroke to 49% (RR, 1.49; 95% CI, 1.41 to 1.58) for hypertension. The risk of all-cause mortality and CVD-specific mortality increased with adiposity, which was supported by a high grade of evidence from observational analyses; however, the causal effect of obesity on mortality outcomes was not significant in MR studies. ConclusionsOnly 15 out of the 53 associations (28%) reported for obesity and CVD outcomes were supported with high evidence levels from observational analyses. Although other reported associations might be valid, various degrees of uncertainty remain. The causal effect of obesity on 9 of the 14 CVD-related outcomes was corroborated by MR studies. As obesity is progressively increasing around the globe and because CVD remains a constant threat to public health, it is necessary to understand the gradient of evidence underlying the association between these two clinical entities. Any weak links in the association and causality discovered in this review should be reinforced with further scientific research, while high-certainty associations with established causality should be reflected in clinical practices and health policies. Systematic review registrationPROSPERO CRD42020179469. Summary BoxO_ST_ABSSection 1C_ST_ABSWhat is already known on this topic - Obesity is progressively increasing worldwide and cardiovascular disease (CVD) remains a continued threat to public health. - Although obesity as a risk factor for various cardiovascular outcomes has been studied for decades, the results from previous studies are heterogeneous, making it difficult for clinicians and policy makers to determine genuine and reliable associations. - The level of evidence underlying the associations between obesity and CVD remains unknown. Section 2: What this study adds- Only 15 of the 53 reported associations (28%) between obesity and CVD outcomes are supported with a high level of evidence. While other associations may be genuine, various degrees of uncertainty remain. - An increase in body-mass index was associated with a higher risk of developing coronary heart disease, heart failure, atrial fibrillation, stroke, hypertension, aortic valve stenosis, pulmonary embolism, and venous thromboembolism; the casual effect of obesity on the incidence of CVD was corroborated by Mendelian randomisation (MR) studies, with the exception of stroke. - The increase in the risk of all-cause mortality and CVD-specific mortality with adiposity was supported by a high grade of evidence in observational analyses, but the causal effect of obesity on mortality outcomes was not significant in MR studies.

BackgroundThe Non-HDL-C/HDL-C ratio (NHHR) is an emerging lipid marker, but its role in Cardiovascular-Kidney-Metabolic (CKM) syndrome remains unclear. ObjectiveThis study investigated NHHRs association with CKM stages in a U.S. cohort. MethodsA total of 14638 participants were included out of 51,199 from the NHANES 2005-2018 survey. Analyzed using a survey weighting approach to ensure a nationally representative sample. The connection of NHHR with CKM syndrome was assessed via multivariate logistic regression, restricted cubic splines (RCS), and subgroup analyses. The predictive performance of NHHR across different CKM stages was assessed via the Receiver operating characteristic (ROC) curve. ResultsThe NHHR level in patients with CKM syndrome was higher than in patients without (2.87{+/-}1.14 vs 2.35{+/-}0.93 mg/dL, P<0.001). The multivariate logistic regression analysis suggested a positive connection between NHHR and CKM syndrome. The RCS analysis revealed a nonlinear association between the NHHR and CKM syndrome (nonlinear p < 0.001). ROC curve analysis demonstrated that NHHR had the best discriminatory ability for CKM stage 2 (area under the curve 0.673). Subgroup analyses revealed that age, race, and education significantly influenced the connection between NHHR and CKM syndrome. ConclusionThis research confirmed that NHHR was positively correlated with CKM syndrome and had the best predictive ability for CKM stage 2, suggesting that NHHR may assist in the early diagnosis and intervention of CKM syndrome.

BackgroundCardiac involvement in coronavirus disease 2019 (COVID-19) is associated with poor outcomes. Transthoracic echocardiography (TTE) can be used to assess cardiac structure and function non-invasively, and has been shown to influence management in COVID-19. ObjectivesWe aim to investigate the prognostic value of TTE findings in hospitalized adults with confirmed COVID-19. MethodsAll consecutive hospitalized adult patients with confirmed COVID-19 who underwent TTE assessment between 3rd April 2020 - 6th April 2021 were included. Comprehensive clinical data including TTE findings were collected from electronic medical records. Patients with mild-moderate and severe-critical COVID-19 were compared. Within the severe-critical group, patients who survived hospitalization and died were compared. Further analyses were conducted after matching for age >60 years, obesity, and diabetes. ResultsA total of 488 COVID-19 patients were included in this study; 202 with mild-moderate and 286 severe-critical disease. All mild-moderate patients and 152 severe-critical patients survived hospitalization. In the matched cohorts, TTE findings associated with severe-critical COVID-19 included left ventricular (LV) hypertrophy (OR: 1.91; CI: 1.21 - 3.02), LV diastolic dysfunction (OR: 1.55; CI: 1.00 - 2.38), right ventricular (RV) dysfunction (OR: 3.86; CI: 1.06 - 14.08), wall motion abnormalities (WMAs) (OR: 2.76; CI: 1.28 - 5.96), and any TTE abnormalities (OR: 2.99; CI: 1.73 - 5.17). TTE findings associated with mortality included RV dysfunction (OR: 3.53; CI: 1.12 - 11.19) and WMAs (OR: 2.63; CI: 1.26 - 5.49). ConclusionTTE is a non-invasive modality that can potentially be used for risk-stratification of hospitalized COVID-19 patients. These findings must be confirmed in larger prospective studies.

ImportanceCoronavirus disease 2019 (COVID-19) has been reported to cause worse outcomes in patients with underlying cardiovascular disease, especially in patients with acute cardiac injury, which is determined by elevated levels of high-sensitivity troponin. There is paucity of data on the impact of congestive heart failure (CHF) on outcomes in COVID-19 patients. ObjectiveTo evaluate the occurrence of acute cardiac injury and arrhythmias and to assess the impact of pre-existing CHF and hypertension (HTN) in COVID-19 patients. Data SourcesWe conducted a literature search of PubMed/Medline, EMBASE, and Google Scholar databases from 11/1/2019 till 06/07/2020. databases using following search terms or keywords: "(COVID) AND (Clinical); ((heart) OR (myocard*)) AND (COVID); (COVID) AND (Troponin); (Coronavirus) AND (Heart)." Study SelectionWe identified all relevant studies reporting cardiovascular comorbidities, cardiac biomarkers, disease severity, and survival in COVID-19 patients. Data Extraction and SynthesisWe followed preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for abstracting data. Pooled data was meta-analyzed using random-effects model and between-study heterogeneity was calculated with Higgins I2 statistic. Main outcome and measuresTo assess the impact of HTN and CHF and to evaluate different cardiac biomarkers in COVID-19 patients based on their disease severity. ResultsWe collected pooled data on 5,967 COVID-19 patients from 20 individual studies. We found that both non-survivors and those with severe disease had an increased risk of acute cardiac injury and cardiac arrhythmias, our pooled relative risk (RR) was -- 8.52 (95% CI 3.63- 19.98) (p<0.001); and 3.61 (95% CI 2.03-6.43) (p=0.001), respectively. Mean difference in the levels of Troponin-I, CK-MB, and NT-proBNP was higher in deceased and severely infected patients. The RR of in-hospital mortality was 2.35 (95% CI 1.18-4.70) (p=0.022) and 1.52 (95% CI 1.12-2.05) (p=0.008) among patients who had pre-existing CHF and hypertension, respectively. Conclusion and RelevanceCardiac involvement in COVID-19 infection appears to significantly adversely impact patient prognosis and survival. Pre-existence of CHF, and high cardiac biomarkers like NT-pro BNP and CK-MB levels in COVID-19 patients correlates with worse outcomes.

BackgroundAcute myocarditis is a disease with variable prognosis, ranging from complete recovery to end-stage heart failure (HF) and death. The aim of this study was to examine the risk of mortality and HF in patients with suspected acute myocarditis (AM) in comparison to patients hospitalized for unexplained acute chest pain (ACP). MethodsWe used the SWEDEHEART-registry to identify patients >16 years admitted to hospital between 1 January 1998 and 31 December 2018 with either AM or ACP. Risks of all-cause mortality and development of HF were calculated and compared by use of adjusted Cox regression analyses. ResultsA total of 3,792 patients with AM and 109,934 patients with ACP were included. Median follow-up time was 7.8 years (Q1, Q3; 3.4, 12.3). AM patients were younger compared to ACP patients, median age 37 years (Q1, Q3; 26, 52) vs 59 years (Q1, Q3; 49, 69), and more likely to be men (79.9% vs 51.4%, p <0.001). Comorbidity burden was lower within the AM cohort. Chest pain was the most common presenting symptom in both groups. Mortality rate at 30 days (OR 3.75, 95% CI 1.9-7.3, p<0,001) as well as long term (OR 2.0, 95% CI 1.69-2.39, p <0.001) were significantly higher among AM patients and AM patients were more likely to develop HF during follow-up (OR 2.3, 95% CI 1.81-2.93, p<0,001). ConclusionsAM patients had a worse short -and long-term outcome compared with ACP. The risk for development of HF was higher for AM patients even after the first year.

IntroductionVisceral adiposity is emerging as a key driver of cardio-metabolic risk factors and cardiovascular disease (CVD), but its relationship with cardiac structure and function is not well characterized across sexes. Using the Canadian Alliance for Healthy Heart and Minds (CAHHM), a large population-based cohort study, we sought to determine the association of visceral adipose tissue (VAT) on subclinical left ventricular (LV) remodeling in males and females. MethodsAs part of the CAHHM study, 6522 participants free of clinical CVD (mean age: 57.4 [8.8 SD] years; 3,671 females, 56%) underwent magnetic resonance imaging (MRI) in which LV parameters and VAT volume were measured. Information about demographic factors, CV risk factors, and anthropometric measurements were obtained. Subclinical cardiac remodelling was defined as altered LV concentricity, represented by increased LV mass-to-volume ratio (LVMV). ResultsMales had a higher VAT volume (80.8 mL; 95% CI: 74.6 t 86.9) compared to females (64.7 mL; 95% CI: 58.5 to 70.8), adjusted for age and height. Among both males and females, VAT was significantly associated with subclinical cardiac remodeling (increased LVMV), independent of other CV risk factors. In multiple regression models adjusted for cardiovascular risk factors, age, and height, every 1 sex-specific standard deviation increase in VAT corresponded to an increase of 0.037 g/mL in LVMV (95% CI: 0.032 to 0.041; p<0.001), which was consistent across both sexes. Notably, a 1 standard deviation increase in VAT is associated with a LVMV that is 20 times higher than what is observed with natural aging alone (0.0020 g/mL rise in LVMV (95% CI 0.0016 to 0.0025), and 1.5 times higher than the impact of an integrated measure of CV risk factors (0.024 g/mL; 95% CI: 0.020 to 0.028). ConclusionVAT significantly influences subclinical cardiac remodeling in both males and females, independent of other cardiovascular risk factors and age. Further research to understand the pathways by which VAT contributes to accelerated cardiac aging is needed.

BackgroundHypothalamic gliosis is mechanistically linked to obesity and insulin resistance in rodent models. We tested cross-sectional associations between radiologic measures of hypothalamic gliosis in humans and clinically relevant cardiovascular disease risk factors, as well as prevalent coronary heart disease. MethodsUsing brain MRI images from Framingham Heart Study participants (N=867; mean age, 55 years; 55% females), T2 signal intensities were extracted bilaterally from the region of interest in the mediobasal hypothalamus (MBH) and reference regions in the amygdala (AMY) and putamen (PUT). T2 signal ratios were created in which greater relative T2 signal intensity suggests gliosis. The primary measure compared MBH to AMY (MBH/AMY); a positive control ratio (MBH/PUT) also assessed MBH whereas a negative control (PUT/AMY) did not. Outcomes were BMI, HDL-C, LDL-C, fasting triglycerides, and the presence of hypertension (n=449), diabetes mellitus (n=66), metabolic syndrome (n=254), or coronary heart disease (n=25). Dietary risk factors for gliosis were assessed in a prospective analysis. Statistical testing was performed using linear or logistic regression. ResultsGreater MBH/AMY T2 signal ratios were associated with higher BMI ({beta} = 21.5 [95% CI, 15.4- 27.6]; P<0.001), higher fasting triglycerides ({beta} = 1.1 [95% CI, 0.6-1.7]; P<0.001), lower HDL-C ({beta} = -20.8 [95% CI, -40.0 to -1.6]; P=0.034), and presence of hypertension (odds ratio, 1.2 [95% CI, 1.1-1.4]; P=0.0088), and the latter two were independent of BMI. Findings for diabetes mellitus were mixed and attenuated by adjusting for BMI. Metabolic syndrome was associated with MBH/AMY T2 signal ratios (odds ratio, 1.3 [95% CI, 1.1-1.6]; P<0.001). Model results were almost uniformly confirmed by the positive control ratios, whereas negative control ratios that did not test the MBH were unrelated to any outcomes (all P[&ge;]0.05). T2 signal ratios were not associated with prevalent coronary heart disease (all P>0.05), but confidence intervals were wide. Self-reported percentages of macronutrient intake were not consistently related to future T2 signal ratios. ConclusionsUsing a well-established study of cardiovascular disease development, we found evidence linking hypothalamic gliosis to multiple cardiovascular disease risk factors, even independent of adiposity. Our results highlight the need to consider neurologic mechanisms to understand and improve cardiometabolic health.

ObjectiveTo characterize trends in prevalence of ASCVD, risk-factor control and medication use among adults with atherosclerotic cardiovascular disease (ASCVD), with frequent update of relevant guidelines. Patients and MethodsWe conducted a cross-sectional analysis of data from 55,081 adults in the National Health and Nutrition Examination Surveys (NHANES) 1999-2018. ResultsThe age-standardized prevalence of ASCVD did not change significantly from 1999-2002 (7.9%, CI 7.1%-8.7%) to 2015-2018 (7.5%, CI 6.8%-8.3%) (P for trend =0.18). Over 60.0% ASCVD participants had very-high risk. The percentage with blood-pressure control (<130/80 mmHg) increased from 51.2% (CI, 41.0%-61.3%) in 1999-2002 to 57.2% (CI, 48.4%-65.6%) in 2011-2014, but then declined to 52.8% (CI, 44.4%-81.3%) in 2015-2018. From 1999-2002 to 2015-2018, the percentage with lipid control (non-high-density lipoprotein cholesterol <100 mg/dL) increased from 7.0% (CI, 3.5%-12.3%) to 26.4% (CI, 16.2%-38.9%), and with glycemic control (HbA1c <7.0%) decreased from 95.0% (CI, 90.2%-97.9%) to 84.0% (CI, 75.9%-90.3%). The percentage who achieved all 3 targets was 18.6% (CI, 8.2%-33.8%) in 2015-2018. After 2014, the percentages with blood-pressure, lipid, and glycemic control decreased in very-high-risk ASCVD, but increased in not-very-high-risk ASCVD. The percentage of ASCVD participants who used statins increased from 1999-2002 to 2011-2014, but then leveled off. The percentage who used blood-pressure-lowering drugs remained largely constant, and who used glucose-lowering drugs increased. ConclusionsThe prevalence of ASCVD generally remained stable, with over 60.0% had very-high risk. Blood-pressure, lipid, and glycemic control decreased in very-high-risk ASCVD but increased in not-very-high-risk ASCVD after 2014.

BACKGROUNDSarcoidosis is a multi-systemic granulomatous inflammatory disorder. In the setting of cardiac involvement, clinical manifestations include ventricular arrhythmias, high-grade atrioventricular block (AVB) and heart failure (HF). The impact of HF in patients with sarcoidosis has not been established from real-world data. METHODSPatients admitted with sarcoidosis from 2010-2019 were identified from the Nationwide Readmissions Database. Those with ischemic heart disease were excluded. Sarcoidosis patients without HF were propensity matched for age, gender and Charlson comorbidity index and compared to patients with HF. Clinical characteristics, length of stay (LOS), adjusted healthcare-associated costs (HAC), 90-day readmission and 90-day mortality was observed. RESULTSDuring the 10-year study period, 97,961 patients (median age 63 [54-71] years, 37.9% male) with a diagnosis of sarcoidosis were hospitalized (35.9% with HF and 64.1% without HF). On index admission, HF patients had a higher prevalence of AVB (3.3% vs 1.4%, p<0.0001), ventricular tachycardia (6.5% vs 1.3%, p<0.0001), ventricular fibrillation (0.4% vs 0.1%, p<0.0001) and atrial fibrillation (22.1% vs 7.5%, p<0.0001). The median LOS (4 [3-7] vs. 4[2-6] days, p<0.0001) was similar but median HAC (US$ 9,954.5 [5,934.7-18,128.8] vs. 8,828.3 [5,303.1-15,384.9], p<0.0001) during the index admission were higher in HF patients. The LOS and HAC were greater in HF patients on 90-day readmission. HF patients were significantly more likely to be re-admitted within 90 days [adjusted all-cause readmissions (HR [95% CI: 1.28 [1.25 - 1.31], p<0.0001), atrial fibrillation (HR 1.35 [1.05-1.75], p=0.02), acute HF (HR 10.77 [9.45 - 12.16], p<0.0001) and ventricular tachycardia/ventricular fibrillation (HR 2.55 [1.69 - 3.85], p<0.0001)]. Adjusted inpatient mortality at readmission was also higher in HF patients (5.1% vs. 3.8%, p<0.0001). CONCLUSIONThe presence of HF in hospitalized sarcoidosis patients is associated with an increased prevalence of conduction disorders, ventricular arrhythmias and atrial fibrillation. HF patients had greater costs, readmissions and mortality at 90-days. What is known?1) Cardiac involvement in sarcoidosis is associated with ventricular arrhythmias, high-grade atrioventricular block and heart failure 2) Retrospective small, single-center studies have reported relatively poor long-term survival outcomes for symptomatic cardiac sarcoidosis patients with reduced left ventricular ejection fraction What the study adds?1) Using a large real-world database, this study has demonstrated that heart failure in hospitalized sarcoidosis patients is associated with increased prevalence of arrythmia, conduction disorders, cardiac implanted electronic devices, catheter ablations and cardiac transplantation. 2) Heart failure in hospitalized sarcoidosis patients leads to a significantly higher length of stay, healthcare-adjusted costs, 90-days readmissions and mortality following readmission.

BackgroundLeft atrium (LA) may be labeled as a "forgotten" chamber in echocardiographic evaluation of pediatric myocarditis. Recently, LA stiffness has gained attention in identifying both diastolic dysfunction and myocardial injury in children. MethodsWe retrospectively analyzed 51 pediatric patients with acute myocarditis diagnosed by cardiac MRI based on updated Lake-Louise-Criteria, along with 40 age-matched healthy controls. Only patients with preserved LVEF (>55%) were included, given their increased risk of adverse outcomes due to diastolic impairment. Follow-up imaging was available for 41 of the 51 patients. LV systolic and diastolic function, and LA strain were evaluated by conventional 2D and speckle-tracking echocardiography. LA stiffness was calculated as the ratio of E/e to peak LA strain as depicted in following equation: O_FD O_INLINEFIG[Formula]C_INLINEFIGC_FD ResultsLA stiffness was significantly increased in myocarditis patients (0.27 {+/-} 0.09 vs. 0.15 {+/-} 0.04 %-1, p<0.001) and remained impaired at early follow-up. LA stiffness showed the best correlation with peak BNP (r = 0.66, p<0.001). Moreover, LA stiffness had the highest diagnostic performance among all echocardiographic indices, with an AUC of 0.94, and remained an independent diagnostic power in multivariable regression model (OR 1.58 [95% CI: 1.32 - 1.89], p<0.001). When it was incorporated into a composite score with LV peak longitudinal strain, the AUC yielded the highest with 98% sensitivity. ConclusionAn optimal LA stiffness cutoff of 0.2%-1 may provide incremental value as a new diagnostic marker for the diagnosis of acute myocarditis with preserved LVEF in children, when this value is exceeded. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIWe evaluated the diagnostic utility of left atrial (LA) stiffness in pediatric patients with acute myocarditis and preserved left ventricular ejection fraction (LVEF), using both conventional and two-dimensional speckle-tracking echocardiography. C_LIO_LILA stiffness was significantly elevated alongside reduced peak LA strain in pediatric myocarditis patients confirmed by cardiac magnetic resonance imaging (CMR), even during early follow-up, reflecting persistent left ventricular diastolic dysfunction. C_LIO_LILA stiffness demonstrated the highest diagnostic accuracy in distinguishing patients with acute myocarditis from normal control, with an AUC of 0.94 (cutoff of 0.2%-1), and incorporating it with LV longitudinal strain enhanced the diagnostic performance. C_LI What Are The Clinical Implications?O_LILA strain analysis may play a pivotal role in helping clinicians identify diastolic dysfunction and detect pediatric patients with CMR-proven acute myocarditis, even with preserved LVEF, facilitating early diagnosis and support tailored management during follow-up. C_LI

ObjectiveLow-grade inflammation in the young may contribute to the early development of adverse cardiometabolic risk profiles. We assessed whether measures of glycoprotein acetylation (GlycA) were better able to detect the development of these changes compared to the more commonly used biomarker high-sensitivity C-reactive protein (CRP), and investigated whether these relationships differed in an adolescent compared to young adult cohort. Research Design and MethodsA total of 3306 adolescents (Avon Longitudinal Study of Parents and Children - ALSPAC; mean age 15.4{+/-}0.3; n=1750) and young adults (Cardiovascular Risk in Young Finns Study - YFS; mean age 32.1{+/-}5.0; n=1556) were included. Inflammatory biomarkers (GlycA/CRP), body composition (BMI / waist circumference) and cardiometabolic risk factors (blood pressure, triglycerides, HDL-c, glucose, insulin, and homeostasis model of insulin resistance [HOMA_IR]), were measured at baseline and again in 9-10 year follow-up. Metabolic Syndrome (MetS) was defined using adolescent-specific National Cholesterol Education Programme (NCEP) guidelines in ALSPAC and standard NCEP guidelines in YFS. ResultsGlycA levels showed greater within-subject correlation over the 9-10 year duration of follow-up in both cohorts when compared to CRP, particularly in the younger adolescent group. In adjusted models, only GlycA was found to increase in line with cardiometabolic risk factor burden at baseline, and to predict adverse changes in several cardiometabolic risk factors in follow-up. In both cohorts, GlycA predicted future risk of MetS (OR [95%CI] for Q4 vs. Q1 = 1.95 [1.08,3.53] and 2.74 [1.30,5.73] for ALSPAC and YFS, respectively), whereas CRP showed a neutral or even negative relationship in fully-adjusted models (OR [95%CI] = 0.50 [0.29,0.86] and 0.93 [0.53,1.64]). ConclusionsChronic inflammation is associated with adverse cardiometabolic risk profiles from as early as adolescence and predicts risk of future cardiometabolic risk and MetS in up to 10 year follow-up. GlycA may be a more sensitive inflammatory biomarker to CRP for detecting early cardiometabolic and cardiovascular risk in the young.

BackgroundAlbuminuria is associated with cardiovascular events among adults with underlying cardiovascular disease and diabetes, even at low levels of urinary albumin excretion. We hypothesized that low levels of albuminuria in the normal range (urinary albumin-to-creatine ratio (UACR) <30 mg/g) are associated with cardiovascular death among apparently healthy adults. MethodsWe studied adults who participated in the 1999-2014 National Health and Nutrition Examination Survey. We excluded participants with baseline cardiovascular disease, hypertension, diabetes, estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2, those who were currently pregnant, and those who had received dialysis in the last year. After excluding these conditions, only 5.0% of the remaining population had UACR [&ge;]30 mg/g (N=873) and were excluded. The final sample size was 16,247. We assessed the relationship between UACR and cardiovascular and all-cause mortality using multivariable-adjusted Cox proportional hazards models. Models were adjusted for age, sex, race or ethnicity, smoking status, systolic blood pressure, hemoglobin A1c, total cholesterol, health insurance, food insecurity, serum albumin, body mass index, use of statins, and eGFR. ResultsMean age was 38.9 years (SD 13.6) and 53.7% were women. The median length of follow-up was 12.2 years. In multivariable-adjusted models, each doubling of UACR (within the <30 mg/g range) was associated with a 36% higher risk of cardiovascular death [HR 1.36 (95% confidence interval (CI) 1.11-1.65)] and a 28% higher risk of all-cause mortality [HR 1.28 (95%CI 1.17-1.41)]. The highest tertile of UACR (7.1-29.9 mg/g) was associated with an 87% higher risk of cardiovascular death [HR 1.87 (95%CI 1.20-2.92)] and 59% higher risk of all-cause mortality [HR 1.59 (95%CI 1.28-1.96)], compared with the lowest tertile (< 4.3 mg/g). ConclusionsIn a nationally representative sample of relatively healthy community-dwelling adults, higher levels of albuminuria in the conventionally "normal" range <30 mg/g in healthy individuals are associated with greater mortality. Overall, our findings contribute to the growing body of evidence on the existence of a risk gradient across all levels of albuminuria, even in the so-called normal range.

Background & AimsObesity is associated with an increased risk of atherosclerosis, though recent evidence shows conflicting results. This study aimed to evaluate whether obesity or its associated metabolic abnormalities play a more significant role in atherosclerosis development in a primary care population. MethodsA cross-sectional study using data from the Cardiometabolic Risk Factor Registry (CARFARE) at Hospital Universitario Austral included adults undergoing their first healthcare visit for primary cardiovascular prevention. Participants were classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO), according to the BioShare-EU criteria and body mass index. Metabolic abnormalities (MAs) were defined by the same criteria. Atherosclerosis prevalence was analyzed using univariate analysis and multivariable logistic regression models. ResultsAmong 6,735 participants, 23.3% were MHNO, 3.13% MHO, 45.6% MUNO, and 25.9% MUO. MHO subjects were 10.1% of the obese population. In univariate analysis, atherosclerosis prevalence was higher in obese than non-obese individuals (57.1% vs. 52.0%, p=0.001), but lower in MHNO and MHO compared to MUNO and MUO groups (33.1% and 34.4% vs. 60.4% and 59.5%, p<0.0001). In multivariate regressions, these latter groups presented an increased adjusted odds ratio (aOR) of atherosclerosis compared to MHNO, while atherosclerosis prevalence was no different between the MHO and MHNO groups [aOR: 0.79 (95% CI 0.55-1.11)]. Moreover, in a second logistic regression model, MAs were independently associated with atherosclerosis [aOR: 1.84 (95% CI: 1.60-2.11)], while obesity was not [aOR: 0.91 (95% CI: 0.79-1.04)]. ConclusionIn this primary care population, the MHO phenotype was not associated with increased atherosclerosis. MAs, rather than obesity alone, were independently associated with atherosclerosis. These findings highlight the need for further longitudinal studies to clarify the interactions between obesity and metabolic health in atherosclerosis development.

BACKGROUNDIncreasing attention has been paid to cardiac involvement in patients with coronavirus disease 2019 (COVID-19). Yet, scarce information is available regarding the morphological and functional features of cardiac impairments in these patients. METHODSWe conducted a prospective and serial echocardiographic study to investigate the structural and functional cardiac changes among COVID-19 patients admitted to the intensive care unit (ICU). From January 21 to April 8, 2020, a total of 51 ICU patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were monitored by serial transthoracic echocardiography examinations. Outcomes were followed up until April 8, 2020. RESULTSOf 51 ICU patients, 33 (64.7%) had cardiovascular comorbidities. Elevations of levels of cardiac biomarkers including high-sensitivity cardiac troponin-I (hs-cTnI) and brain natriuretic peptide were observed in 62.7% and 86.3% of patients, respectively. Forty-two (82.3%) had at least one left-heart and/or right-heart echocardiographic abnormality. The overall median left ventricular ejection fraction (LVEF) was 65.0% (IQR 58.0-69.0%), with most (44/86.3%) having preserved LVEF. Sixteen patients (31.4%) had increased pulmonary artery systolic pressure, and 14 (27.5%) had right-ventricle (RV) enlargement. During the study period, 12 (23.5%) patients died. LVEF was comparable between survivors and non-survivors, while non-survivors had more often pulmonary hypertension (58.3% vs. 23.1%; P=0.028) and RV enlargement (58.3% vs. 17.9%, P=0.011). Kaplan-Meier analysis demonstrated similar survival curves between patients with vs. without echocardiographic left-heart abnormalities (P=0.450 by log-rank test), while right-heart abnormalities had adverse impact on mortality (P=0.012 by log-rank test). CONCLUSIONSTypical cardiac abnormality in ICU patients with COVID-19 was right-heart dysfunction with preserved LVEF. Echocardiographic right-heart dysfunction was associated with disease severity and increased mortality in patients affected by COVID-19. CLINICAL TRIAL REGISTRATIONUnique identifier: NCT04352842.

BackgroundMetabolic Syndrome is a cluster of cardiometabolic risk factors including abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Its prevalence in Nepal has been reported inconsistently, with figures ranging from very low to extremely high. Reliable evidence is needed to inform policy and prevention strategies. MethodsWe conducted a systematic review and meta-analysis of observational studies reporting the prevalence of Metabolic Syndrome among Nepalese adults. Databases searched included PubMed, Embase, Scopus, and Nepalese journals up to May 2025. Eligible studies used recognized diagnostic criteria, enrolled [&ge;]100 participants, and were assessed for quality using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. The primary analysis employed a binomial generalized linear mixed model (GLMM). Heterogeneity was quantified using I^2 and {tau}^2, and 95% prediction intervals were emphasized. Subgroup, sensitivity, and leave-one-out analyses were performed. Certainty of evidence was evaluated using GRADE. ResultsEight studies comprising 21,708 participants were included. The pooled prevalence of MetS was 21.3% (95% CI: 11.6-35.9%), but heterogeneity was extreme (I^2 = 99.4%). The 95% PI indicated that true prevalence in new populations could range from 2.0% to 78.6%. Subgroup analysis by setting (urban vs. mixed) did not explain the variability. Component analysis revealed high prevalence of low HDL (64.5%), abdominal obesity (59.5%), and hypertriglyceridemia (47.0%). GRADE certainty was very low for overall prevalence, but low to moderate for individual components. ConclusionsMetabolic syndrome represents a significant but unevenly distributed burden in Nepal. The extreme heterogeneity underscores that national averages are misleading. Public health strategies should prioritize local data and address widespread dyslipidemia and obesity while future research must clarify the determinants of disparity.

ObjectivesTo conduct a systematic review and meta-analysis to assess the evidence of cardiovascular magnetic resonance imaging (CMR) in patients with suspected myocardial infarction and nonobstructive coronary arteries (MINOCA), and how time to CMR influences diagnosis. BackgroundCMR is indicated in patients with suspected MINCOA but it is unclear when is best to perform the CMR and how this timing can influence diagnosis. MethodsWe systematically conducted a comprehensive literature search to identify relevant studies. These studies were assessed to determine the study quality and analysis was performed using a Random-effects model. ResultsThere were 23 eligible studies, including 4,231 patients. The mean quality score was 9.35 out of 10. For MINOCA patients assessed by CMR, the average median time from presentation to CMR was 12.50 days (SD: 14 days, range 0-365 days). The pooled frequencies of the most common diagnoses were: myocarditis (29%), myocardial infarction (22%), Takotsubo syndrome (10%), cardiomyopathy (7%), and 22% had no cardiac diagnosis (normal CMR findings). In pooled analysis, the prevalence of normal CMR findings increased by three percentage points for each extra day of waiting between presentation and CMR scanning over the studied range of 0-14 days (Slope: 3.1 %-points/day; r=0.67, p=0.003). ConclusionsIn patients with suspected MINOCA, the longer it takes a patient to have a CMR scan, the more likely the results will be normal and no diagnosis made by CMR. CMR should be performed as early as possible in suspected MINOCA. HighlightsO_LIIn patients with suspected MINOCA, the pooled frequency of diagnoses made by CMR include myocarditis (29%), myocardial infarction (22%), Takotsubo syndrome (10%), cardiomyopathy (7%), and no diagnosis/normal study (22%). C_LIO_LIThe longer it takes to have a CMR scan the more likely the patient will have a normal scan. C_LIO_LIIn patients with suspected MINOCA, CMR scanning should be performed as soon as possible. C_LI

BackgroundCardiovascular-Kidney-Metabolic (CKM) syndrome, as defined by the American Heart Ass ociation (AHA) in 2023, encompasses pathophysiological interconnections among the cardiovascular, rena l, and metabolic systems, which collectively lead to multi-organ dysfunction. The Inflammatory Burden In dex (IBI), a newly developed inflammatory marker, has an unclarified association with mortality in the con text of CKM syndrome. Our study aimed to explore the relationships between IBI and mortality in this pop ulation, with the goal of facilitating early clinical intervention. Methods6,091 NHANES (1999-2018) participants with CKM syndrome were analyzed. Weighted Cox models and Restricted cubic spline (RCS) analysis assessed IBIs association with all-cause and cardiovasc ular mortality. We tested proportional hazards (Schoenfeld residuals), model performance (ROC curves), a nd confounding (subgroup/stratified analyses). ResultsIBI independently predicted mortality after full adjustment: All-cause mortality: HR=1.13, 95% C I:1.05-1.21, *p*=0.002;Cardiovascular mortality: HR=1.35, 95% CI:1.21-1.51, *p*<0.001.The fully ad justed model (AUC>0.8) showed optimal predictive performance. IBI exhibited non-linear ("U-shaped" all-cause, "J-shaped" cardiovascular) mortality relationships. The highest IBI quartile (Q4) robustly predicted cardiovascular death (HR=1.77, 95% CI:1.18-2.67).Subgroup and stratified analyses revealed that male s ex, advanced age, smoking, and high-risk chronic kidney disease (CKD) were synergistic factors exacerbating the association between IBI and all-cause mortality risk, while female sex, smoking, diabetes, and meta bolic abnormalities were synergistic factors exacerbating the association with cardiovascular mortality risk. ConclusionOur study is the first to demonstrate that IBI exhibits significant non-linear associations with both all-cause and cardiovascular mortality in patients with CKM syndrome and serves as a risk factor for t hese patients. Monitoring the Inflammatory Burden Index holds important clinical significance for assessin g mortality risk in individuals with CKM syndrome.

BackgroundConflicting results have been reported as to the relative importance of apoA-1 versus HDL-C as markers of ASCVD risk. MethodsResidual discordance analysis with Cox proportional hazard models comparing apoA-1 and HDL-C as markers of ASCVD risk was applied to a sample of 291,995 UK Biobank, followed for a median of 11 years. Interaction test for the two markers and estimation of the effects of partitioning HDL-C into apoA-I, log-triglyceride and the remaining residual were also performed. ResultsApoA-1 and HDL-C had similar associations with ASCVD risk (HRs of 0.85, p-value < 0.001 for both). The residual of HDL-C added significantly to the risk associated with apoA-1 as did the residual of apoA-1 to HDL-C. There was a statistically significant interaction between apoA-I and HDL-C (HR=1.05, 95% CI: (1.04, 1.06); p < 0.001). Decomposing HDL-C into the 3 components, apoA-I accounted for the largest portion of the effect with a HR of 0.85 95%CI: (0.83, 0.86) with smaller effects for lnTG: 1.04 (1.02, 1.06) and residual of HDL-C: 0.98 95%CI: (0.96, 0.995). ConclusionsHDL-C and apoA-1 have associations of equivalent strength with ASCVD risk with significant interaction modifying the effect of one by the other. Upon decomposition, ApoA-I retained more of the effect of HDL-C as compared to log-triglycerides. While only observational, the results are consistent with the relation of HDL to risk not being determined by the concurrent level of triglyceride. Clinical PerspectiveThe plasma levels of HDL-C and apoA-I are potent predictors of cardiovascular risk. However, there are few data comparing the relative precision of HDL-C and apoA-I for this purpose. Moreover, the risk of low HDL-C has been attributed to concurrent hypertriglyceridemia, consequently downgrading the potential importance of HDL in predicting or explaining risk. Novel FindingsBased on residual discordance analysis, HDL-C and apoA-I have similar predictive precision for ASCVD risk. However, each adds significantly to the other and. Moreover, triglycerides account for only a small portion of the risk attributable to HDL with apoA-I accounting for the principal portion. Clinical SignificanceHDL, whether measured as HDL-C or apoA-I, is a potent predictor of ASCVD risk. It remains essential to search for the biological basis or bases for these relationships.

BackgroundSystemic chronic inflammation plays a role in the pathophysiology of both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated fatty liver disease (MAFLD). AimThis study aimed to investigate whether serum high-sensitivity C-reactive protein (hs-CRP) levels were associated with the future risk of heart failure (HF) hospitalization in patients with MAFLD and a normal left ventricular ejection fraction (LVEF). MethodsThe study enrolled consecutive individuals with MAFLD and normal LVEF who underwent coronary angiography for suspected coronary heart disease. The study population was subdivided into non-HF, pre-HFpEF, and HFpEF groups at baseline. The study outcome was the first hospitalization for HF. ResultsIn 10,019 middle-aged individuals (mean age 63.3{+/-}10.6 years; 38.5% female), the prevalence rates of HFpEF and pre-HFpEF were 34.2% and 34.5%, with a median serum hs-CRP level of 4.5 mg/L (IQR: 1.9-10 mg/L) and 5.0 mg/L (IQR: 2.1-10.1 mg/L), respectively. Serum hs-CRP levels were significantly higher in the pre-HFpEF and HFpEF groups than in the non-HF group. HF hospitalizations occurred in 1942 (19.4%) patients over a median of 3.2 years, with rates of 3.7% in non-HF, 20.8% in pre-HFpEF, and 32.1% in HFpEF, respectively. Cox regression analyses showed that patients in the highest hs-CRP level quartile had a [~]4.5-fold increased risk of being hospitalized for HF compared to those in the lowest hs-CRP level quartile (adjusted-Hazard Ratio 4.42, 95% CI 3.72-5.25). ConclusionsThere was a high prevalence of baseline pre-HFpEF and HFpEF in subjects with MAFLD. There was an increased risk of HF hospitalization in those with elevated hs-CRP levels.