Adjustment For Traditional Risk Factors Research Articles

Neutrophil-To-Lymphocyte Ratio and Abdominal Aortic Atherosclerosis among Asymptomatic Individuals.

ResumoFundamento A razão neutrófilo-linfócito (RNL) tem sido proposta como um marcador inflamatório possivelmente associado a aterosclerose coronariana, embora a maioria dos dados atuais seja restrita à fase aguda. Além disso, a associação entre a RNL e a aterosclerose extracoronariana ainda não está clara.Objetivo Analisar a associação entre a RNL e aterosclerose da aorta abdominal (AtAA).Métodos Foram incluídos pacientes assintomáticos submetidos a um programa de rastreamento. A AtAA foi avaliada através de ultrassom. Os números absolutos de leucócitos e linfócitos foram utilizados para calcular a RNL. Foi estabelecido um nível de significância estatística de 0,05.Resultados De 36.985 indivíduos (idade: 42±10 anos, 72% homens), foi identificada a presença de AtAA em 7%. Aqueles com AtAA eram mais velhos e tinham maior propensão a serem homens e diabéticos. A presença de AtAA foi associada a RNL aumentada (odds ratio [OR] 1,17; intervalo de confiança de 95% [IC95%] 1,13-1,21). No entanto, a associação deixou de ser significativa quando a análise foi ajustada para os fatores de risco (OR 1,02; IC95% 0,97-1,06), principalmente devido à inclusão da idade no modelo. Quando os neutrófilos e linfócitos foram analisados separadamente, a associação negativa entre os linfócitos e a RNL foi invertida com a inclusão da idade, o que sugere um forte efeito confundidor da idade na relação entre linfócitos e aterosclerose. Por fim, a associação entre os neutrófilos e a AtAA deixou de ser significativa após o ajuste adicional para os fatores de risco tradicionais, mas não apenas para a idade.Conclusão Embora a RNL tenha se associado a AtAA, foi principalmente devido ao efeito confundidor da idade. No geral, os resultados sugerem um papel limitado da contagem de leucócitos como biomarcador de AtAA.

Coronary Artery Disease Events and Carotid Intima-Media Thickness in Type 1 Diabetes in the DCCT/EDIC Cohort.

BackgroundCarotid artery intima‐media thickness (IMT) is associated with the risk of subsequent cardiovascular events in the general population. This association has not been established in type 1 diabetes.Methods and ResultsWe studied if carotid IMT is associated with the risk of a first coronary artery disease event in participants with type 1 diabetes in the EDIC (Epidemiology of Diabetes Interventions and Complications) study, the long‐term observational follow‐up of the DCCT (Diabetes Control and Complications Trial). Between 1994 and 1996, common carotid artery and internal carotid artery IMT were measured with high‐resolution ultrasound in 1309 study participants with a mean age of 35 years and diabetes duration of 13.8 years; 52% were men. Cox proportional hazards models evaluated the association of standardized common carotid artery IMT and internal carotid artery IMT with subsequent cardiovascular events over the next 17 years. Models were adjusted for age, sex, mean hemoglobin A1c levels, and traditional cardiovascular risk factors. Associations of common carotid artery IMT with subsequent CAD were significant after adjustment for imaging device, sex, and age (hazard ratio [HR], 1.23 per 0.09 mm [95% CI, [1.04–1.45]; P=0.0141), but did not remain significant after further adjustment for traditional risk factors and hemoglobin A1c (HR, 1.14 per 0.09 mm [95% CI, 0.97–1.33]; P=0.1206). No significant associations with subsequent coronary artery disease events were seen for internal carotid artery IMT.ConclusionsIn the DCCT/EDIC cohort with type 1 diabetes, common carotid artery IMT, but not internal carotid artery IMT, is weakly associated with subsequent coronary artery events, an association eliminated after adjusting for coexistent traditional cardiovascular risk factors.RegistrationURL: https://www.clinicaltrials.gov; Unique identifiers: NCT00360815 and NCT00360893.

Serum free sulfhydryl status associates with new-onset chronic kidney disease in the general population

BackgroundSerum sulfhydryl groups (R-SH, free thiols) reliably reflect the systemic redox status in health and disease. As oxidation of R-SH occurs rapidly by reactive oxygen species (ROS), oxidative stress is accompanied by reduced levels of free thiols. Oxidative stress has been implicated in the pathophysiology of chronic kidney disease (CKD), in which redox imbalance may precede the onset of CKD. Therefore, we aimed to investigate associations between serum free thiols and the risk of incident CKD as defined by renal function decline and albuminuria in a population-based cohort study. MethodsSubjects without CKD (n = 4,745) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, a prospective, population-based cohort study in the Netherlands, were included. Baseline protein-adjusted serum free thiols were studied for their associations with the development of CKD, defined as a composite outcome of an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2, urinary 24-h albumin excretion (UAE) > 30 mg/24-h, or both. ResultsMedian level of protein-adjusted serum free thiols at baseline was 5.14 μmol/g of protein (interquartile range [IQR]: 4.50–5.75 μmol/g) and median eGFR was 96 mL/min/1.73 m2 [IQR: 85–106]. Protein-adjusted serum free thiols were significantly associated with incident CKD (hazard ratio [HR] per doubling 0.42 [95% confidence interval [CI]: 0.36–0.52, P < 0.001), even after adjustment for traditional risk factors (HR 0.67 [95% CI: 0.47–0.94], P=0.022). In secondary analyses, the highest tertile of protein-adjusted serum free thiols was inversely associated with incident UAE >30 mg/24-h after full adjustment for confounding factors (HR per doubling 0.70 [95% CI: 0.51–0.96], P=0.028). ConclusionHigher levels of serum R-SH, reflecting less oxidative stress, are associated with a decreased risk of developing CKD in subjects from the general population. This association is primarily driven by incident CKD as defined by UAE.

Metabolomic Profiles Associated With Incident Ischemic Stroke.

Women have higher lifetime risk of stroke than men, and metabolic factors seem more strongly associated with stroke for women than men. However, few studies in either men or women have evaluated metabolomic profiles and incident stroke. We applied liquid chromatography-tandem mass spectrometry to measure 519 plasma metabolites in a discovery set of women in the Nurses' Health Study (NHS; 454 incident ischemic stroke cases, 454 controls) with validation in 2 independent, prospective cohorts: Prevención con Dieta Mediterránea (PREDIMED; 118 stroke cases, 791 controls) and Nurses' Health Study 2 (NHS2; 49 ischemic stroke cases, 49 controls). We applied logistic regression models with stroke as the outcome to adjust for multiple risk factors; the false discovery rate was controlled through the q value method. Twenty-three metabolites were significantly associated with incident stroke in NHS after adjustment for traditional risk factors (q < 0.05). Of these, 14 metabolites were available in PREDIMED and 3 were significantly associated with incident stroke: methionine sulfoxide, N6-acetyllysine, and sucrose (q < 0.05). In NHS2, one of the 23 metabolites (glucuronate) was significantly associated with incident stroke (q < 0.05). For all 4 metabolites, higher levels were associated with increased risk. These 4 metabolites were used to create a stroke metabolite score (SMS) in the NHS and tested in PREDIMED. Per unit of standard deviation of SMS, the odds ratio for incident stroke was 4.12 (95% confidence interval [CI] 2.26-7.51) in PREDIMED, after adjustment for risk factors. In PREDIMED, the area under the receiver operating characteristic curve (AUC) for the model including SMS and traditional risk factors was 0.70 (95% CI 0.75-0.79) vs the AUC for the model including the traditional risk factors only of 0.65 (95% CI 0.70-0.75), corresponding to a 5% improvement in risk prediction with SMS (p < 0.005). Metabolites associated with stroke included 2 amino acids, a carboxylic acid, and sucrose. A composite SMS including these metabolites was associated with ischemic stroke and showed improvement in risk prediction beyond traditional risk factors. This study provides Class II evidence that a SMS accurately predicts incident ischemic stroke risk.

Abstract 10442: Temporal Changes in Plasma Lipidome in Patients with St-Segment Elevation Myocardial Infarction: Impact of Reperfusion

Aim: We aim to investigate the temporal changes in plasma lipidome before and after reperfusion in ST-segment elevation myocardial infarction (STEMI) patients and their association with myocardial injury. Methods: Venous blood samples were drawn from STEMI patients (N=80) serially before percutaneous coronary intervention (PCI) and at 2 h, 24 h, 48 h, and 30 days after PCI. Plasma lipid profiling (322 lipids) was performed on STEMI patients and age and gender-matched control subjects (N=50) using an LC/MS platform. Results: Overall, 56.01% of the identified lipid species were significantly altered (corrected p&lt;0.05 ) in the first 24 h following reperfusion in STEMI patients. During early reperfusion, except oxidized phospholipids, the majority of lipid classes/subclasses (14 out of 25) were significantly lower (corrected p&lt;0.05 ) at 2 h post-reperfusion compared to the ischemic state. Of all the lipid classes/subclasses, fatty acids showed the most remarkable change (74.5% lower) in the first 24 h after reperfusion. Multivariable linear regression analyses following adjustment of traditional risk factors identified 33 lipid species that significantly associate (p&lt;0.05) with change in troponin concentration (delta troponin) at different time intervals. Five of these lipid species, namely, acylcarnitine 18:2, TG 51:0, PE (O-38:5), LPC 17:1, and LPC 18:0, could stratify patients in the highest tertile of delta troponin from those in the lowest tertiles. These lipids also were correlated with in-hospital cardiovascular events. Acylcarnitine 18:2, LPC 17:1, and LPC 18:0 as well as their respective whole class amount, were significantly higher (p&lt;0.05) in the STEMI population than the control subjects. Conclusions: Our analyses elucidated a detailed characterization of the temporal alterations in plasma lipidome that occur during human myocardial reperfusion injury.

Abstract 12024: Galectin 4 Is Associated With Incident Stroke - The Malmö Preventive Project Study

Introduction: Galectin-4 (Gal-4) is a small protein in the gastrointestinal tract. It has been implicated in diabetes mellitus, incident coronary events, incident heart failure as well as all-cause and cardiovascular mortality. However, possible associations of Gal-4 with stroke have not yet been examined. Hypothesis: We explored if Gal-4 is associated with prevalent and incident stroke in a large population cohort. Methods: Gal-4 was analyzed by the proximity extension assay technique in 1737 participants from a subsample of the population-based Malmö Preventive Project (mean age 67 years, 29% women). Stroke was defined as all strokes (ischemic, hemorrhagic and undefined). Multivariable logistic regression models were applied for prevalent stroke (n=72). Prior to analyses of incident stroke, cases of prevalent stroke were excluded. Multivariate Cox regression models were applied for incident stroke. Results: Gal-4 levels were significantly higher in subjects with prevalent stroke (p=0.003) than in subjects free from prevalent stroke. Gal-4 (per doubling of concentration) was significantly associated with prevalent stroke in age and sex adjusted models (odds ratio 1.49; 95% confidence interval (1.04-2.14); p=0.032), but the associations was no longer significant upon further adjustment for traditional risk factors for stroke (OR 1.22 (0.82-1.82), p=0.339). Further, each doubling in Gal-4 concentration was associated with higher risk of incident stroke (n=1604; 327 events; median follow up time 12.6 (interquartile range 10.0-13.6) years; hazard ratio 1.24 (1.02-1.49); p=0.027) in a model adjusted for BMI, systolic blood pressure, triglycerides, HDL-cholesterol, smoking, diabetes, prevalent coronary events and anti-hypertensive treatment. Conclusions: In a large population cohort, Gal-4 was associated with incident stroke during a follow-up of 12 years, further implicating a role of Gal-4 in both cardiovascular and metabolic disease.

Abstract 9434: Cigarette Smoking and Incident Heart Failure With Preserved Ejection Fraction in African Americans: The Jackson Heart Study

Background: Cigarette smoking has been associated with incident heart failure (HF), however the relationships with HF phenotypes have not been adequately investigated, particularly in African Americans. Methods and Results: Among 4129 African Americans participants in the Jackson Heart Study without a history of HF or coronary heart disease (CHD) at baseline, we investigated the relationships between baseline smoking status, smoking intensity (number of cigarettes/day) among current smokers, and smoking burden (pack years) among ever smokers and incident HF hospitalization. HF phenotypes were categorized either as HF with reduced ejection fraction (HFrEF: EF&lt;50%) or HF with preserved EF (HFpEF: EF≥50%). There were 2884 (70%) never smokers, 503 (12%) current smokers, and 742 (18%) former smokers. Over a median of 11.0 years follow-up (interquartile range: 10.4-11.0), there were 215 incident HF hospitalizations (95 incident HFrEF, 120 incident HFpEF). After adjustment for traditional risk factors of age, sex, body mass index, systolic blood pressure, anti-hypertensive medication, diabetes, estimated glomerular filtration rate, and incident CHD, current smoking was associated with incident HFpEF (hazard ratio, 3.21; 95% confidence interval, 1.80-5.71), but not with incident HFrEF in comparison with never smokers. Smoking intensity among current smokers (hazard ratio, 1.06 per 1 cigarette/day; 95% confidence interval, 1.02-1.09), and smoking burden among ever smokers (hazard ratio, 1.08 per 10 pack-years; 95% confidence interval, 1.01-1.16) were also significantly associated with incident HFpEF but not with incident HFrEF (Table). Conclusion: In this large community-based African American cohort, cigarette smoking (smoking status, smoking intensity, and smoking burden) was significantly associated with incident HFpEF, but not with HFrEF. Smoking cessation in African Americans who smoke may reduce risk for HFpEF in this high-risk population.

Association of inflammatory markers and lipoprotein particle subclasses with progression of coronary artery calcium: The multi-ethnic study of atherosclerosis

Background and aimsAtherosclerosis is a complex phenomenon manifesting several features typical of chronic inflammation and disorders of lipid metabolism. We assessed association of nuclear magnetic resonance (NMR) lipid variables and inflammatory markers with incident coronary artery calcium (CAC) and CAC progression among participants with baseline CAC ≥0. MethodsMESA is a longitudinal cohort study of 6,814 participants (aged 45–85). 3,115 had CAC = 0 and 2,896 had CAC>0 at baseline. Repeat CAC measurements were obtained (mean duration of follow up, 6.5 years). ResultsIL-6 (log pg/mL) and fibrinogen (50 mg/dL) were associated with a higher relative risk (RR) of incident CAC (HU) (RR = 1.09, p=0.010 & RR 1.05, p=0.004, respectively). Small LDL (100 nmol/L) (RR = 1.03, p<0.001) and log large VLDL (log nmol/L) (RR = 1.06, p=0.001) were associated with higher risks, whereas large HDL (μmol/L) was associated with an inverse risk of incident CAC (RR = 0.97, p< 0.001) in a model adjusted for follow up time, age, gender and race. Among participants with baseline CAC>0, progression of CAC was positively associated with hsCRP (log mg/L) (β = 1.99), IL-6 (log pg/mL) (β = 2.9), fibrinogen (50 mg/dL) (β = 1.0), large VLDL (log nmol/L) (β = 2.2), and small LDL (100 nmol/L) (β = 0.36) (all p values < 0.05) in a model adjusted for scanner type, age, gender and race. Relationships with inflammatory markers and NMR lipoprotein particles lost significance after adjustment for traditional risk factors and statin use. Traditional risk factors were strongly associated with both CAC incidence and progression with the exception of cholesterol parameters not associated with CAC progression in adjusted model. ConclusionsInflammatory markers and lipoprotein particles were associated with CAC incidence and progression in minimally adjusted models, but not after adjustment for traditional risk factors.

Associations of Sex Hormone-binding Globulin with Bone Mineral Density Among US Adults, NHANES 2013-2016.

BackgroundBone metabolism can be influenced by sex steroid hormones. However, the relationship between sex steroid hormones and bone mineral density (BMD) remains inconsistent. Our study explored existing evidence of the association between sex hormones, blood glucose and BMD.MethodsWe conducted a cross-sectional study of 6434 participants aged 18–80 years in the National Health and Nutrition Examination Survey (NHANES) 2013–2016 to assess the association between SHBG and BMD. The multivariable linear regression models were performed to evaluate the associations between testosterone, estrogen, sex hormone-binding globulin (SHBG) and BMD.ResultsOn adjustment for traditional risk factors (age, BMI, ALB, ALK, ASP, calcium, cholesterol, potassium, sodium, total protein, uric acid), SHBG could be regarded as an independent predictor for BMD, while fasting blood glucose did not. SHBG levels were significant associated with BMD in the multivariate model; however, it will be a different effect between the genders. On comparative analysis, high level SHBG was predictive of lumbar BMD irrespective of other two sex steroid hormones.ConclusionThis study indicated that SHBG may improve the predictive value for bone loss in adults.

Differential prognostic value of resistin for cardiac death in patients with coronary artery disease according to the presence of metabolic syndrome.

Resistin is associated with atherosclerosis progression by affecting inflammation and insulin resistance. There are controversial data regarding the prognostic value of resistin in stable coronary artery disease (CAD) patients. We prospectively investigated the long-term prognostic value of resistin in patients with stable CAD. A total 741 consecutive patients with stable CAD were followed for a median of 5.5years. Serum resistin, lipids, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels were measured at baseline. Primary endpoints were cardiac death and secondary hospitalizations for acute coronary syndrome, arrhythmic event or ischemic stroke. Follow-up data were obtained from 703 patients of whom 79 had a cardiac death (11.2%) and 205 (29.2%) met the secondary endpoints. Resistin was positively correlated with hsCRP (r = 0.159, p < 0.001) and IL-6 (r = 0.165, p = 0.002), and negatively with high-density lipoprotein-cholesterol (r = -0.176, p < 0.001). Resistin levels could not predict cardiac death [HR 1.044; 95% CI 0.994-1.096; p = 0.087] neither secondary endpoints [HR 1.025; 95% CI 0.983-1.068; p = 0.250). Among 298 patients (42.4%) with metabolic syndrome (MS) resistin levels were independently associated with cardiac death after adjustment for conventional risk factors [HR 1.121; 95% CI 1.045-1.204; p = 0.002). Further adjustment for ejection fraction of left ventricle(LVEF) did not change the association (HR 1.145; 95% CI 1.057-1.240; p = 0.001). Patients with resistin values ≥ 7.6ng/mL (median level) had 2.8 times higher risk of cardiac death compared to those with resistin levels < 7.6ng/mL after adjustment for traditional risk factors and LVEF (HR 2.882; 95% CI 1.311-6.336; p = 0.008). Resistin is independently associated with cardiac death in patients with stable CAD and MS.

Prevalence and Prognostic Significance of Malnutrition Risk in Patients With Acute Ischemic Stroke: Results From the Third China National Stroke Registry.

To investigate the prevalence of malnutrition risk in patients with acute ischemic stroke (AIS) at admission, the association between malnutrition risk and long-term outcomes, and whether the predictive ability would be improved after adding to previous prognostic models for poor outcomes. Based on the Third China National Stroke Registry data from August 2015 to March 2018, we evaluated malnutrition risk using objective scores, including the controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index. The primary outcome was death or major disability (modified Rankin Scale score ≥3) at 1 year after stroke onset. We calculated the crude prevalence of malnutrition risk and investigated the association between malnutrition risk and clinical outcomes. Prognostic performance of 3 objective malnutrition scores for poor outcomes was assessed. Moderate to severe malnutrition risk was identified in 5.89%, 5.30%, and 1.95% of the Third China National Stroke Registry AIS patients according to the controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index, respectively. At 1-year follow-up, 1143 participants (13.5%) experienced death or major disability. After adjustment for traditional risk factors, moderate to severe malnutrition risk was associated with high risk of composite events (odds ratio, 2.25 [95% CI, 1.75-2.90], for controlling nutritional status score; odds ratio, 2.10 [95% CI, 1.63-2.69], for geriatric nutritional risk index; odds ratio, 3.36 [95% CI, 2.33-4.84], for prognostic nutritional index; all P<0.01). Addition of the 3 malnutrition scores to different predicted scales (iScore and Acute Stroke Registry and Analysis of Lausanne) improved predictive ability for long-term poor outcomes validated by the integrated discrimination index (all P<0.05). The prevalence of moderate or severe malnutrition risk in Chinese patients with AIS ranged from 1.95% to 5.89%. Malnutrition risk in patients with AIS was associated with increased risk of long-term death and major disability. Our study provides evidence supporting the prognostic significance of objective malnutrition scores after AIS.

Association between malnutrition status and incident heart failure in community population

Abstract Background Malnutrition is commonly prevalent in patients with heart failure (HF) and associated with poor prognosis. However, few studies have explored the association between malnutrition status and incident HF in community population. Method 379,759 participants (46.3% women) without HF at baseline from the UK Biobank were included. Nutritional status was evaluated using the Controlling Nutritional Status (CONUT) score, with higher scores reflecting worse nutritional status. Association between CONUT score and incident HF were investigated using Cox proportional hazard regression models, with adjustment for traditional risk factors. Results During a median follow-up of 8.1 years, 5,520 cases (1.5%) of HF occurred. The hazard ratio for incident HF with 1-point increase of CONUT scores was 1.16 (95% CI, 1.12–1.20, P&amp;lt;0.001), after adjustment for traditional HF risk factors. Compared with good nutritional status, malnutrition was associated with significantly increased risk for incident HF [adjust hazard ratio were 1.25 (95% CI 1.17–1.34, P&amp;lt;0.001) for mild malnutrition and 2.06 (95% CI 1.36–3.12, P=0.001) for moderate or severe malnutrition]. Conclusion Malnutrition status were associated with increased risk of incident HF. Further studies are needed to confirm these findings and evaluate the use of CONUT in community monitoring. Funding Acknowledgement Type of funding sources: None.

Serum uric acid is associated with the progression of left ventricular diastolic dysfunction in apparently healthy subjects

Abstract Background Left ventricular (LV) diastolic dysfunction (LVDD) which is one of major characteristics of diastolic heart failure (HF) is also prevalent in the community. Patients with LVDD are predisposed to poor cardiovascular outcomes. Serum uric acid (SUA), an important component of metabolic disorders, has been shown to have close relationship with cardiovascular events including LVDD. In the present study, we sought to investigate whether SUA is a potential predictor of LVDD progression in relatively healthy subjects. Methods From November 2018 to December 2019 in our Hospital, subjects who had physical examination were consecutively enrolled and followed up for ∼12 months. LVDD was graded by tissue doppler imaging (TDI). At baseline, only individuals with normal LV diastolic function or mild LVDD were finally enrolled and underwent repeated echocardiography and TDI assessment after follow-up. The incidence of LVDD progression, defined as LVDD grade 0–1 escalated to grade 2–3, and its relationship with SUA levels were analyzed. Multivariate regression models were constructed to test the predictive value of SUA for LVDD progression. Results A total of 1082 subjects were included in the final analysis. During a mean follow-up of 12.6 (IQR 12.0–13.8) months, the incidence of LVDD progression was 37.6% and mean change in E/e' ratio was 1.18±1.85 cm/s, which was positively correlated with baseline SUV level (Spearman's r=0.140, P&amp;lt;0.001). In multivariate analysis, SUA was independently associated with LVDD progression after adjustment for traditional risk factors. The highest quartile of SUA corresponded to a 1.851-fold [95% CI 1.215–2.828] increased risk for progression of LVDD as compared to the lowest quartile. A 100 μmol/L increase in SUA conferred a 1.351-fold [95% CI 1.125–1.625] higher risk of LVDD progression when treated as continuous variable. Principal component analysis revealed SUA accounted for 14.7% of the variance in patients with LVDD progression, following insulin resistance and cholesterol factor which accounted for 27.9% and 19.0%, respectively. Conclusions This study suggests that SUA is an independent predictor of LVDD progression in apparently healthy subjects. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China, Shanghai Municipal Commission of Health and Family Planning

Association between atrial fibrillation and coronary slow flow

Abstract Background The relationship between arrhythmia and coronary slow flow (CSF) is unclear. We aimed to explore the association between atrial fibrillation (AF) and CSF. Method In this cross-sectional study, we included 2,060 participants patients from PCI-registry (NCT 02498470) who underwent coronary angiography with clinical chest pain and without significant coronary stenosis. According to coronary blood flow rate measured by the thrombolysis in myocardial infarction frame count (TFC) method, CSF was defined as TFC&amp;gt;27. AF was identified by ECG performed during hospitalization. We used logistic regression to assess the association between AF and CSF. Results Among 2,060 participants, 132 participants were diagnosed with AF. CSF rates were higher in AF group than in the control group (22.0% vs 13.9%, P=0.011). Logistic regression showed that AF was independently associated with CSF after adjustment for traditional risk factors (OR=2.06; 95%, 1.28–3.34; P=0.003). Conclusion Our study demonstrated that AF was association with increased risk of CSF. Further studies are needed to confirm this finding and explore the potential mechanism. Funding Acknowledgement Type of funding sources: None.

Differential prognostic value of resistin for cardiovascular death in patients with stable coronary artery disease according to the presence of metabolic syndrome

Abstract Background Resistin is associated with atherosclerosis progression by affecting inflammation and insulin resistance. There are controversial data regarding the prognostic value of resistin in patients with coronary artery disease (CAD). Purpose We prospectively investigated the long-term prognostic value of resistin in patients with stable CAD. Methods A total 741 consecutive patients with stable CAD were followed for a median of 5.5 years. Serum resistin, lipids, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels were measured at baseline. Primary endpoints were cardiac death (CD) and secondary hospitalizations for acute coronary syndrome, arrhythmic event or stroke. Results Follow-up data were obtained from 703 patients of whom 79 had a CD (11.2%) and 205 (29.2%) met the secondary endpoints. Resistin was positively correlated with hsCRP (r=0.159, p&amp;lt;0.001) and IL-6 (r=0.165, p=0.002), and negatively with HDL-cholesterol (r=−0.176, p&amp;lt;0.001). Resistin levels could not predict CD [HR: 1.044; 95% CI: 0.994 to 1.096; p=0.087] neither secondary endpoints [HR: 1.025; 95% CI: 0.983 to 1.068; p=0.250). Among 298 patients (42.4%) with metabolic syndrome (MS) resistin levels were independent predictors of CD after adjustment for conventional risk factors and left ventricular ejection fraction (LVEF) [HR: 1.145; 95% CI: 1.057 to 1.240; p=0.001]. Patients with resistin values ≥7.6 ng/mL (median level) had 2.8 times higher risk of CD compared to those with resistin levels &amp;lt;7.6 ng/mL after adjustment for traditional risk factors and LVEF (HR: 2.882; 95% CI: 1.311 to 6.336; p=0.008). Conclusions Resistin is an independent long-term predictor of CD in patients with stable CAD and MS. Funding Acknowledgement Type of funding sources: None. Figure 1

Serum cholesterol efflux capacity is associated with coronary plaque progression in patients with coronary heart disease

Abstract Background Coronary plaque progression is a major risk factor of adverse cardiac events in patients with coronary heart disease (CHD). Emerging evidence showed that attenuated high-density lipoprotein (HDL) function measured by cholesterol efflux capacity (CEC) was associated with development of atherosclerosis independent of HDL cholesterol level. In this study, we sought to investigate whether CEC is a predictor for coronary plaque progression in CHD patients. Methods We consecutively enrolled CHD patients from January 2017 to August 2019 in our Hospital who underwent elective percutaneous coronary intervention and had at least one non-target coronary lesion. Follow-up coronary angiography were performed at around 12 months. Fluorescence-labeled cholesterol and J774 macrophages were used to measure the CEC of ApoB-depleted serum sample from all patients. Quantitative coronary angiography (QCA) was performed both at baseline and follow-up to analyze the plaque progression. Results A total of 430 CHD patients with 586 non-target coronary lesions were included in the final analysis. During a mean follow-up time of 381.04±59.52 days, patients with decreased CEC presented more severe plaque progression (net luminal loss in highest to lowest CEC quartile: 0.22±0.42mm vs 0.20±0.41mm vs 0.13±0.36mm vs 0.11±0.34mm, p=0.035). In multivariate analysis, baseline CEC was independently associated with coronary plaque progression after adjustment for traditional risk factors including HDL cholesterol and ApoA-I, no matter treated as categorical variable (OR: 0.382 [95% CI 0.180–0.781] for highest to lowest quartile) or continuous variable (OR: 0.522 [95% CI 0.373–0.714] for per SD increase]. Furthermore, CEC demonstrated a better power in predicting coronary plaque progression compared with HDL cholesterol concentration (AUC=0.644 vs 0.514). Conclusions This study suggests that HDL function reflected by serum CEC is an independent predictor for coronary plaque progression in CHD patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China, Shanghai Municipal Commission of Health and Family Planning

Nonalcoholic Fatty Liver Disease and the Kidney: A Review

Nonalcoholic fatty liver disease (NAFLD) is associated with several extrahepatic manifestations such as cardiovascular disease and sleep apnea. Furthermore, NAFLD is reported to be associated with an increased risk of incident chronic kidney disease (CKD). Inflammation and oxidative stress are suggested to be the key factors involved in the inflammatory mechanisms and pathways linking NAFLD to CKD and are responsible for both the pathogenesis and the progression of CKD in NAFLD patients. This review aims to provide a more comprehensive overview of the association between CKD and NAFLD, also considering the effect of increasing severity of NAFLD. A PubMed search was conducted using the terms “non-alcoholic fatty liver disease AND kidney”. In total, 537 articles were retrieved in the last five years and 12 articles were included in the qualitative analysis. Our results showed that CKD developed more frequently in NAFLD patients compared to those without NAFLD. This association persisted after adjustment for traditional risk factors and according to the severity of NAFLD. Therefore, patients with NAFLD should be considered at high risk of CKD. Intensive multidisciplinary surveillance over time is needed, where hepatologists and nephrologists must act together for better and earlier treatment of NAFLD patients.

Atherothrombotic factors and atherosclerotic cardiovascular events: the multi-ethnic study of atherosclerosis.

Traditional atherosclerotic cardiovascular disease (ASCVD) risk factors fail to address the full spectrum of the complex interplay of atherosclerotic and atherothrombotic factors integral to ASCVD events. This study sought to examine the association between atherothrombotic biomarkers and ASCVD events. The association between atherothrombotic biomarkers and 877 ASCVD events with and without adjustment for traditional risk factors was evaluated via Cox proportional hazards models and factor analysis in 5789 Multi-Ethnic Study of Atherosclerosis participants over a median follow-up of 14.7 years. Factor analysis accounted for multidimensional relationship and shared variance among study biomarkers, which identified two new variables: a thrombotic factor (Factor 1), principally defined by shared variance in fibrinogen, plasmin-antiplasmin complex, factor VIII, D-dimer, and lipoprotein(a), and a fibrinolytic factor (Factor 2), principally defined by shared variance of plasminogen and oxidized phospholipids on plasminogen. In a model including both factors, the thrombotic factor was associated with the higher risk of ASCVD events [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.45, 1.70], while the fibrinolytic factor was associated with the lower risk of ASCVD events (HR 0.76, 95% CI 0.70, 0.82), with estimated ASCVD free survival highest for low atherothrombotic Factor 1 and high atherothrombotic Factor 2. Two atherothrombotic factors, one representative of thrombotic propensity and the other representative of fibrinolytic propensity, were significantly and complementarily associated with incident ASCVD events, remained significantly associated with incident ASCVD after controlling for traditional risk factors, and have promise for identifying patients at high ASCVD event risk specifically due to their atherothrombotic profile.

Prognostic value of subclinical myocardial necrosis using high-sensitivity cardiac troponin T in patients with prediabetes

BackgroundRisk stratification of patients with prediabetes is an unmet clinical need. Here, we examine the utility of subclinical myocardial necrosis assessed by high-sensitivity cardiac troponin T (hs-cTnT) in predicting health outcomes in stable subjects with prediabetes.Methodshs-cTnT was analyzed by a high-sensitivity assay (Roche 5th generation) in 2631 stable subjects with prediabetes (HbA1c 5.7–6.4% or fasting glucose 100–125 mg/dL without previous diagnosis of diabetes or glucose-lowering therapy) who underwent elective coronary angiography for cardiac evaluation, and followed for major adverse cardiac events (MACE; death, myocardial infarction, stroke) over 3 years and all-cause mortality over 5 years.ResultsIn our study cohort, hs-cTnT was highly prevalent with a median level of 13 ng/L (interquartile range 8.2–21.6 ng/L). Hs-cTnT was independently associated with incident MACE at 3 years (Q4 vs. Q1 adjusted hazard ratio (HR) 2.42 [95% CI 1.69–3.46], P < 0.001) and 5-year mortality (adjusted HR 3.8 [95% CI 2.55–5.67], P < 0.001). This association remained significant in all subsets after adjustment for traditional risk factors and multiple factors known to increase hs-cTnT levels. Moreover, hs-cTnT independently predicted event risk in primary prevention subjects (n = 557, HR 5.46 [95% CI 1.50–19.89), p < 0.01) for MACE; HR 9.53 [95% CI 2.08–43.73] for all-cause mortality) and secondary prevention subjects (n = 2074, HR 1.86 [95% CI 1.31–2.66], P < 0.001 for MACE; and 2.7 [95% CI 1.79–4.08), P < 0.001 for all-cause mortality).ConclusionsIn stable prediabetic subjects, the presence of subclinical myocardial necrosis as detected by hs-cTnT portends heightened long-term adverse cardiovascular event risk. Hs-cTnT levels may help to stratify risk and improve clinical decision making in patients with prediabetes.Trial registration ClinicalTrials.gov Identifier: NCT00590200.

A metabolomic index based on lipoprotein subfractions and branched chain amino acids is associated with incident hypertension

ObjectiveThe present study aims to evaluate the performance of the Diabetes Risk Index (DRI), a metabolomic index based on lipoprotein particles and branched chain amino acids, on the incidence of newly developed hypertension in a large community dwelling cohort. MethodsThe DRI was calculated by combining 6 lipoprotein parameters [sizes of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), concentrations of large VLDL, small LDL, and large HDL particles], and the concentrations of valine and leucine. DRI scores were estimated in 4169 participants from the PREVEND prospective cohort. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident hypertension. ResultsDuring a median follow-up of 8.6 years, 924 new hypertension cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI and incident hypertension with a hazard ratio (HR) per 1 SD increase of 1.45 (95% CI 1.36,1.54; p < 0.001). After additional adjustment for traditional risk factors, the HR remained significant (HRadj 1.21, 95% CI 1.10, 1.33, p <0.001). Likewise, subjects in the top quartile of DRI presented with a higher risk of hypertension (HRadj 1.64, 95% CI 1.28, 2.10, p <0.001). Furthermore, the net reclassification improvement assessment improved after the addition of DRI to a traditional risk model (p <0.001), allowing proper reclassification of 34% of the participants. ConclusionHigher DRI scores were associated with an increased risk of incident hypertension. Such association was independent of traditional clinical risk factors for hypertension.