SD Increment Research Articles

Polygenic risk score in comparison with C-reactive protein for predicting incident coronary heart disease

Background and aimsDespite interest in the use of polygenic risk scores (PRS) for predicting coronary heart disease (CHD) risk, the clinical utility of PRS compared to conventional risk factors has not been demonstrated. We compared the performance of PRS with that of high-sensitivity C-reactive protein (hsCRP) in two well-established cohorts. MethodsThe study population included individuals of European ancestry free of baseline CHD from ARIC (N = 13,113) and the Framingham Offspring Study (FHS) (N = 2,696). The primary predictors included a validated PRS consisting of >6.6 million single nucleotide polymorphisms and hsCRP. The outcome was incident CHD, defined as non-fatal or fatal myocardial infarction. We compared the performance of both predictors after adjusting for the Pooled Cohort Equations in multivariable-adjusted Cox regression models. We assessed discrimination and reclassification using c-statistics and net reclassification improvement. ResultsIncident CHD occurred in 565 ARIC and 153 FHS participants. In multivariable-adjusted models, both PRS and hsCRP were associated with incident CHD (p < 0.05 in both cohorts). In models incorporating both predictors, strengths of association were similar. For instance, in ARIC, the hazard ratio per SD increment was 1.38 (95% CI, 1.27–1.50, p = 2.94 × 10−14) for PRS and 1.41 (1.30–1.55, p = 3.10 × 10−15) for hsCRP. Neither predictor significantly increased model discrimination or net reclassification when compared with models containing the Pooled Cohort Equations alone. ConclusionsIn two independent cohorts, PRS performed similarly to hsCRP for the prediction of CHD risk. These findings suggest PRS does not have unique clinical utility beyond this widely-available, inexpensive measure of risk in unselected middle-aged populations.

Association between lipoprotein(a) and ischemic stroke: Fibrinogen as a mediator

BackgroundPrevious studies have reported lipoprotein(a) was related to increased risk of ischemic stroke. However, the role of fibrinogen in their associations was not fully elucidated. AimWe aimed to investigate the mediating role of fibrinogen in the association between lipoprotein(a) and risk of ischemic stroke. MethodsA total of 516 patients with ischemic stroke were matched 1:1 to patients without ischemic stroke for age and gender. Serum lipoprotein(a) and plasma fibrinogen levels were collected on the basis of the results of biochemical tests. Multivariate conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for lipoprotein(a) levels and ischemic stroke risk. Mediation analysis were further conducted to evaluate the potential mediating role of fibrinogen in the association between lipoprotein(a) and ischemic stroke risk. ResultsThe lipoprotein(a) level of subjects with ischemic stroke was significantly higher than that of subjects without ischemic stroke (P < 0.001). Each SD increment of lipoprotein(a) was associated with 27% higher odds (OR 1.27, 95%CI: 1.11, 1.45) increment in ORs of ischemic stroke. Furthermore, mediation analyses indicated that fibrinogen mediated 10.15% of the associations between lipoprotein(a) and ischemic stroke. ConclusionsHigher level of lipoprotein(a) was independently associated with increased risk of ischemic stroke and fibrinogen partially mediated the associations of lipoprotein(a) and ischemic stroke risk.

Various ambient air pollutants, residential green spaces, fibrosis 4 scores, genetic susceptibility, and risk of severe liver disease

BackgroundThe relationship of air pollutants and residential exposure to greenspace with severe liver disease remains inconclusive. ObjectiveOur objective was to assess the relationship of joint exposure to air pollutants, residential exposure to greenspaces with new-onset severe liver disease. MethodsWe included 427,697 participants without prior liver diseases from UK Biobank. A weighted air pollution score was calculated based on PM2.5, PM10, PM2.5–10, NO2, and NOX. The percentage of land coverage by residential greenspaces was estimated using land use data. The primary outcome was new-onset severe liver disease, defined as a composite outcome including hospitalization or death due to compensated or decompensated liver cirrhosis, liver failure, and hepatocellular carcinoma. ResultsDuring a median follow-up of 12.0 years, 4572 participants developed severe liver disease. A higher air pollution score was significantly associated with an increased risk of new-onset severe liver disease (per SD increment; adjusted hazard ratio [HR],1.07; 95% confidence interval [CI],1.04–1.10). Moreover, residential greenspace coverage was inversely associated with new-onset severe liver disease (per SD increment; adjusted HR, 0.95; 95% CI,0.92–0.98). Genetic risks of liver cirrhosis did not significantly modify the associations (both P-interactions >0.05). However, we observed a stronger positive association between air pollution scores and new-onset severe liver disease in individuals with higher fibrosis-4 (FIB-4) scores, lower residential greenspaces, hypertension, and smokers (all P-interactions <0.05). Similarly, a more pronounced inverse association between residential exposure to greenspaces and new-onset severe liver disease was found in smokers and individuals with higher FIB-4 scores (both P-interactions<0.05). ConclusionsOur findings suggest a positive association between air pollution scores and the risk of new-onset severe liver disease, while residential greenspaces show an inverse association. These results underscore the importance of maintaining high exposure to green space and reducing air pollution to prevent serious liver disease.

Both LDL and HDL particle concentrations associate positively with an increased risk of developing microvascular complications in patients with type 2 diabetes: lost protection by HDL (Zodiac-63)

BackgroundTriglyceride-rich lipoproteins (TRL) and low-density lipoproteins (LDL) are associated positively whereas high-density lipoproteins (HDL) are associated inversely with the development of new-onset type 2 diabetes (T2D). Here we studied potential associations between these lipoprotein particle concentrations and the risk of developing microvascular complications in patients with established T2D.MethodsLipoprotein particle concentrations (TRLP, LDLP, and HDLP) were determined in 278 patients with T2D participating in a primary care-based longitudinal cohort study (Zwolle Outpatient Diabetes project Integrating Available Care [ZODIAC] study) leveraging the Vantera nuclear magnetic resonance (NMR) platform using the LP4 algorithm. Associations between lipoprotein particles and incident microvascular complications (nephropathy, neuropathy, and retinopathy) were assessed using Cox proportional hazards regression models.ResultsIn total, 136 patients had microvascular complications at baseline. During a median follow-up of 3.2 years, 49 (34.5%) of 142 patients without microvascular complications at baseline developed new-onset microvascular complications. In multivariable Cox proportional hazards regression analyses, both total LDLP and HDLP concentrations, but not total TRLP concentrations, were positively associated with an increased risk of developing any microvascular complications after adjustment for potential confounding factors, including age, sex, disease duration, HbA1c levels, history of macrovascular complications, and statin use (adjusted hazard ratio [HR] per 1 SD increment: 1.70 [95% CI 1.24–2.34], P < 0.001 and 1.63 [95% CI 1.19–2.23], P = 0.002, respectively). When analyzing each microvascular complication individually, total LDLP concentrations were positively associated with retinopathy (adjusted HR 3.35, 95% CI 1.35–8.30, P = 0.009) and nephropathy (adjusted HR 2.13, 95% CI 1.27–3.35, P = 0.004), and total HDLP concentrations with neuropathy (adjusted HR 1.77, 95% CI 1.15–2.70, P = 0.009). No significant associations were observed for lipoprotein particle subfractions.ConclusionsTotal lipoprotein particle concentrations of both LDL and HDL associate positively with an increased risk of developing microvascular complications in T2D. We propose that the protective role of HDL on the development of microvascular complications may be lost in established T2D.

1314-P: Adherence to Life’s Essential 8 and Incident Chronic Kidney Disease—A Prospective Study of 142,567 UK Biobank Participants

Background: The American Heart Association (AHA) recently updated an improved method for evaluating cardiovascular health (CVH): Life’s essential 8 (LE8). We aimed to investigate the association between levels of CVH and the risk of CKD in UK biobank. Methods: A total of 142,567 participants free of CKD and CVD were included. LE8 score at baseline was created including DASH diet, physical activity, smoking, sleep, BMI, non-HDL cholesterol, HbA1c, and BP. CVH levels were categorized as low, moderate, and high. Cox proportional hazard model was used to investigate the association between LE8 and CKD. Results: During a median follow-up of 11.8 years, 4,914 CKD cases were documented. We observed a linear dose-response relationship. Compared to participants with a low CVH, those with a moderate CVH were associated with a 35% lower risk of developing CKD (HR=0.65, 95% CI: 0.59, 0.73). Participants with a high CVH had a 48% lower risk of CKD incidence (HR=0.52, 95% CI: 0.45, 0.60) after adjustment for covariates. Additionally, the HR (95% CI) for each SD increment in behavior subscale score was 0.46 (0.39, 0.53) for CKD, and the HR (95% CI) for each SD increment in biological subscale score was 0.86 (0.76, 0.98) for CKD. Conclusion: Participants with high CVH, defined by LE8, were significantly associated with a lower risk of CKD. The burden of CKD may be reduced by promoting adherence to optimal CVH levels. Disclosure R.Tang: None. X.Wang: None. X.Li: None. H.Ma: None. Y.Heianza: None. L.Qi: None.

Risk factors for raised left ventricular filling pressure by cardiovascular magnetic resonance: prognostic insights from UK Biobank

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute for Health and Care Research British Cardiovascular Society. Background Cardiovascular magnetic resonance imaging (CMR) can estimate left ventricular filling pressure (LVFP). The relationship between LVFP, determined by CMR measurements, and established risk factors for cardiovascular disease is unknown. This study quantifies these associations and investigates the prognostic value of CMR-derived LVFP compared to known risk factors for cardiovascular disease. Methods Using data from the UK Biobank prospective observational cohort study, CMR-derived LVFP was calculated using a model incorporating left atrial volume and left ventricular mass. Logistic regression was used to explore the relationships between raised LVFP (≥15mmHg) and typical cardiovascular risk factors. The non-linear relationship between LVFP and age was analysed using ordinary least squares regression and a restricted cubic spline of age with nine knots. Cox proportional hazards regression was used to analyse the relationships between typical cardiovascular risk factors and CMR-derived LVFP, and outcomes of incident heart failure and major adverse cardiovascular events. Results In this prospective population-based cohort study, 39,163 UK Biobank participants had CMR with adequate image quality. In a multivariable logistic regression model, male sex (OR 4.55, 95% CI 3.85–5.42, p&amp;lt;0.001), age (OR 1.89, 95% CI 1.72 - 2.09, per decade increment, p&amp;lt;0.001), BMI (OR 1.57, 95% CI 1.48–1.67, per SD increment, p&amp;lt;0.001), and hypertension (OR 1.46, 95% CI 1.26–1.68, p&amp;lt;0.001) were associated with increased odds of raised LVFP (Figure 1a). A non-linear regression model of the relationship between age and LVFP, adjusted for all covariables studied, showed little correlation between CMR-derived LVFP and age until 70 years, after which LVFP increased rapidly with age (Figure 2). In multivariable Cox regression models, elevated CMR-derived LVFP was associated with increased hazard of incident heart failure (HR 3.31, 95% CI 1.99–5.49, p&amp;lt;0.001) but not MACE (HR 1.33, 95% CI 0.86–2.07, p = 0.20) (Figure 1b). Conclusions Raised LVFP, as determined using CMR, is independently associated with male sex, age, BMI and hypertension. CMR-derived LVFP is independently associated with incident heart failure. These findings may have implications for clinical risk stratification, targeted population screening strategies and public health measures to reduce the risk of heart failure development.

Association of choline and betaine with the risk of cardiovascular disease and all-cause mortality: Meta-analysis.

This study aimed to systematically evaluate the role of circulating levels of choline and betaine in the risk of cardiovascular disease (CVD) and all-cause mortality by comprehensively reviewing observational studies. This study was conducted according to PRISMA 2020 statement. Six electronic databases, including PubMed, Embase and China National Knowledge Infrastructure (CNKI), were searched for cohort studies and derivative research design types (nested case-control and case-cohort studies) from the date of inception to March 2022. We pooled relative risk (RR) and 95% confidence interval (CI) of the highest versus lowest category and per SD of circulating choline and betaine concentrations in relation to the risk of CVD and all-cause mortality. In the meta-analysis, 17 studies with a total of 33,009 participants were included. Random-effects model results showed that highest versus lowest quantile of circulating choline concentrations were associated with the risk of CVD (RR = 1.29, 95% CI: 1.04-1.61) and all-cause mortality (RR = 1.62, 95% CI: 1.12-2.36). We also observed the risk of CVD were increased 13% (5%-22%) with per SD increment. Furthermore, highest versus lowest quantile of circulating betaine concentrations were not associated with the risk of CVD (RR = 1.07, 95% CI: 0.92-1.24) and all-cause mortality (RR = 1.39, 95% CI: 0.96-2.01). However, the risk of CVD was increased 14% (5%-23%) with per SD increment. Higher levels of circulating choline were associated with a higher risk of CVD and all-cause mortality.

#5619 THE ASSOCIATION BETWEEN THE LEVELS OF URIC ACID AND RENAL OUTCOMES IN EARLY CKD PATIENTS: A MULTI-CENTER REAL-WORLD DATA ANALYSIS

Abstract Background and Aims It is well known that serum uric acid (SUA) plays an important role both in patients with and without chronic kidney disease (CKD). However, the effect of SUA on renal outcomes of CKD patients, especially with asymptomatic hyperuricemia, remains controversial. Therefore, our study explores the relationship between SUA and adverse events in early CKD (stage 1-3) patients in a real-world setting. Method This multi-center real-world study analyzed the data from Chinese Renal Data System (CRDS). Eligible CKD patients (eGFR) (estimated glomerular filtration rate≥30 mL/min/1.73 m2) were enrolled. The primary endpoint is the decline of renal function defined as at least 40% decrease in eGFR. The secondary endpoints include onset of composite cardiovascular events and all-cause mortality. A multivariable cox regression model were used and the associations between levels of mean SUA and all endpoints were evaluated on a continuous scale with restricted cubic spline (RCS) curves based on Cox proportional hazards models. Kaplan-Meier survival curves were used to illustrate the ability of SUA to predict the end points. Results 25,202 adults (mean [SD] age, 52.59 [17.90] years, 8,212 male [46.1%], 9,604 female [53.9%]) were included in this study. During a median follow-up period of 2.61 years, 3,451 (15.9%) at least 40% decreased in eGFR. After adjustment for confounders, higher uric acid concentrations were independently associated with the higher risk for the decline of renal function [Per SD increment adjusted hazard ratio [aHR]: 1.41, 95%CI 1.36-1.47]; composite cardiovascular events [Per SD increment [aHR]: 1.04, 95%CI 1.01-1.07], all-cause mortality [Per SD increment [aHR]:1.32, 95%CI 1.14-1.54]. RCS curves showed that HRs for renal function progression, all-cause mortality and composite cardiovascular events increased significantly with the increase of SUA concentration in CKD patients. Results were consistent in stratified analyses. The KM curves suggested that patients with asymptomatic hyperuricemia had a substantially worse survival rate for renal function. Conclusion SUA is an independent risk factor for the decline of renal function, cardiovascular events and all-cause mortality in early CKD patients (stage 1-3). Treatment of asymptomatic hyperuricemia may be a potential avenue to improve outcomes in CKD patients.

ASSOCIATION OF HANDGRIP STRENGTH WITH CARDIOMETABOLIC MULTIMORBIDITY: FINDINGS FROM FOUR LONGITUDINAL COHORT STUDIES

Objective: Cardiometabolic multimorbidity is an increasing public health burden and clinical concern. However, predictors for the development of cardiometabolic multimorbidity are poorly understood. We aimed to investigate the association between handgrip strength and the risk of cardiometabolic multimorbidity among adults aged 50 years or above from high-income and low- and middle-income countries. Design and method: In this multicohort study, we extracted individual-level data from four longitudinal cohort studies that included nationally representative samples across 20+ countries, including the Health and Retirement Study (HRS), the English Longitudinal Study of Aging (ELSA), the Survey of Health, Ageing and Retirement in Europe (SHARE), and the China Health and Retirement Longitudinal Study (CHARLS). Handgrip strength was measured following a homogeneous procedure, in which the maximum measurements of dominant hand were used and expressed in absolute units (kg) for subsequent analysis. Cardiometabolic multimorbidity was defined as the simultaneous occurrence of two or more of the following conditions: type 2 diabetes, stroke, and heart diseases. Cox proportional hazards models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: We included 50,118 participants recruited between 2011 and 2019 with a median follow-up of 7.6 years. The incident rates of cardiometabolic multimorbidity in participants from HRS, ELSA, SHARE, and CHARLS were 9.1%, 4.0%, 3.1%, and 2.7%, respectively. After adjusting for sociodemographic characteristics, lifestyle factors, and vascular risk factors, the HRs (95% CIs) of per SD increment in handgrip strength for cardiometabolic multimorbidity were 0.80 (0.73-0.87) in HRS, 0.62 (0.55-0.71) in ELSA, 0.69 (0.64-0.75) in SHARE, and 0.85 (0.75-0.96) in CHARLS. Those associations remained statistically significant for separate outcomes including diabetes, heart diseases, and stroke in all four cohorts. Conclusions: Higher grip strength was associated with a range of cardiometabolic outcomes as well as cardiometabolic multimorbidity regardless of whether they live in high-income or low- and middle-income countries. Further work on the use of grip strength in risk scores or risk screening is needed to establish its potential clinical utility.

Peripheral immunity is associated with the risk of incident dementia

AbstractBackgroundCentral immunity components especially microglia in dementia have been well studied and corresponding immunotherapy gradually caught the attention. However, few studies focused on peripheral immunity and dementia.MethodTo address the issue, we examined the longitudinal association between incident dementia and peripheral immunity markers encompassing immune cell counts, and their derived ratios including neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), systemic immune‐inflammation index (SII) and lymphocyte‐to‐monocyte ratio (LMR), utilizing data of 361653 participants from the UK Biobank (UKB).ResultDuring a median follow‐up of 8.99 years, 4239 participants developed dementia. The results revealed that increased innate immunity markers were associated with higher dementia risk (per SD increment hazard ratio [HR]; 95% confidence interval [CI] 1.14; 1.09‐1.19 for neutrophils, 1.16; 1.11‐1.20 for NLR and 1.11; 1.07‐1.16 for SII), while increased adaptive immunity markers were associated with lower dementia risk (0.93; 0.90‐0.97 for lymphocytes and 0.94; 0.90‐0.98 for LMR).ConclusionOur study pinpoints the differential role of innate and adaptive immunity in dementia incidence, which may provide some new perspectives in etiology and therapy of dementia.

Low-density lipoprotein electronegativity and risk of death after acute coronary syndromes: A case-cohort analysis

Background and aimsLow-density lipoprotein (LDL)-cholesterol (LDL-C) promotes atherosclerotic cardiovascular disease (ASCVD), with changes in LDL electronegativity modulating its pro-atherogenic/pro-thrombotic effects. Whether such alterations associate with adverse outcomes in patients with acute coronary syndromes (ACS), a patient population at particularly high cardiovascular risk, remains unknown. MethodsThis is a case-cohort study using data from a subset of 2619 ACS patients prospectively recruited at four university hospitals in Switzerland. Isolated LDL was chromatographically separated into LDL particles with increasing electronegativity (L1-L5), with the L1-L5 ratio serving as a proxy of overall LDL electronegativity. Untargeted lipidomics revealed lipid species enriched in L1 (least) vs. L5 (most electronegative subfraction). Patients were followed at 30 days and 1 year. The mortality endpoint was reviewed by an independent clinical endpoint adjudication committee. Multivariable-adjusted hazard ratios (aHR) were calculated using weighted Cox regression models. ResultsChanges in LDL electronegativity were associated with all-cause mortality at 30 days (aHR, 2.13, 95% CI, 1.07–4.23 per 1 SD increment in L1/L5; p=.03) and 1 year (1.84, 1.03–3.29; p=.04), with a notable association with cardiovascular mortality (2.29; 1.21–4.35; p=.01; and 1.88; 1.08–3.28; p=.03). LDL electronegativity superseded several risk factors for the prediction of 1-year death, including LDL-C, and conferred improved discrimination when added to the updated GRACE score (area under the receiver operating characteristic curve 0.74 vs. 0.79, p=.03). Top 10 lipid species enriched in L1 vs. L5 were: cholesterol ester (CE) (18:2), CE (20:4), free fatty acid (FA) (20:4), phosphatidyl-choline (PC) (36:3), PC (34:2), PC (38:5), PC (36:4), PC (34:1), triacylglycerol (TG) (54:3), and PC (38:6) (all p < .001), with CE (18:2), CE (20:4), PC (36:3), PC (34:2), PC (38:5), PC (36:4), TG (54:3), and PC (38:6) independently associating with fatal events during 1-year of follow-up (all p < .05). ConclusionsReductions in LDL electronegativity are linked to alterations of the LDL lipidome, associate with all-cause and cardiovascular mortality beyond established risk factors, and represent a novel risk factor for adverse outcomes in patients with ACS. These associations warrant further validation in independent cohorts.

Autoantibodies of inflammatory cytokines as serum biomarkers in OSA patients

As many as 90% of patients with obstructive sleep apnea (OSA) may be undiagnosed. It is necessary to explore the potential value of autoantibodies against CRP, IL-6, IL-8 and TNF-α in the diagnosis of OSA. ELISA was performed to detect the level of autoantibodies against CRP, IL-6, IL-8 and TNF-α in sera from 264 OSA patients and 231 normal controls (NCs). The expression level of autoantibodies against CRP, IL-6 and IL-8 in OSA were significantly higher than that in NC while the level of anti-TNF-α was lower in OSA than that in NC. The per SD increment of anti-CRP, anti-IL-6 and anti-IL-8 autoantibodies were significantly associated with a 430%, 100% and 31% higher risk for OSA, respectively. The AUC of anti-CRP was 0.808 (95% CI: 0.771–0.845) when comparing OSA with NC, while the AUC increased to 0.876 (95% CI: 0.846–0.906) combining four autoantibodies. For discrimination of severe OSA versus NC and non-severe OSA versus NC, the AUC for four autoantibodies combination was 0.885 (95% CI: 0.851–0.918) and 0.876 (95% CI: 0.842–0.913). This study revealed the association between autoantibodies against inflammatory factors and OSA, and the combination of autoantibodies against CRP, IL-6, IL-8 and TNF-α may function as novel biomarker for monitoring the presence of OSA.

Cardiovascular Interactions of Renin-Angiotensin-Aldosterone System Assessed by Cardiac Magnetic Resonance: The Multi-Ethnic Study of Atherosclerosis.

The effects of the renin-angiotensin-aldosterone system in cardiovascular system have been described based on small studies. The aim of this study was to evaluate the relationship between aldosterone and plasma renin activity (PRA) and cardiovascular structure and function. We studied a random sample of Multi-Ethnic Study of Atherosclerosis participants who had aldosterone and PRA blood assays at 2003-2005 and underwent cardiac magnetic resonance at 2010. Participants taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were excluded. The aldosterone group was composed by 615 participants, mean age 61.6 ± 8.9 years, while the renin group was 580 participants, mean age 61.5 ± 8.8 years and both groups had roughly 50% females. In multivariable analysis, 1 SD increment of log-transformed aldosterone level was associated with 0.07 g/m2 higher left ventricle (LV) mass index (P = 0.04) and 0.11 ml/m2 higher left atrium (LA) minimal volume index (P < 0.01). Additionally, higher log-transformed aldosterone was associated with lower LA maximum strain and LA emptying fraction (P < 0.01). Aldosterone levels were not significantly associated with aortic measures. Log-transformed PRA was associated with lower LV end diastolic volume index (β standardized = 0.08, P = 0.05). PRA levels were not significantly associated with LA and aortic structural or functional differences. Higher levels of aldosterone and PRA are associated with concentric LV remodeling changes. Moreover, aldosterone was related to deleterious LA remodeling changes.

Cardiovascular interactions of renin angiotensin aldosterone system assessed by cardiac magnetic resonance: The Multi-Ethnic Study of Atherosclerosis.

The effects of the Renin Angiotensin Aldosterone System in cardiovascular system has been described based on small studies. The aim of this study was to evaluate the relationship between aldosterone and plasma renin activity and cardiovascular structure and function. We studied a random sample of Multi-Ethnic Study of Atherosclerosis participants who had aldosterone and plasma renin activity blood assays at 2003-2005 and underwent cardiac magnetic resonance at 2010. Participants taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were excluded. The aldosterone group was composed by 615 participants, mean age 61.6 ± 8.9 years, while the renin group was 580 participants, mean age 61.5 ± 8.8 years and both groups had roughly 50% females. In multivariable analysis, 1 SD increment of log-transformed aldosterone level was associated with 0.07g/m 2 higher left ventricle mass index (p=0.04) and 0.11ml/m 2 higher left atrium minimal volume index (p < 0.01). Additionally, higher log-transformed aldosterone was associated with lower left atrium maximum strain and left atrium emptying fraction (βstandardized = -0.12, p < 0.01 and - 0.15, p < 0.01, respectively). Aldosterone levels were not significantly associated with aortic measures. Log-transformed plasma renin activity was associated with lower left ventricle end diastolic volume index (βstandardized = 0.08, p=0.05). Plasma renin activity levels were not significantly associated with left atrium and aortic structural or functional differences. Higher levels of aldosterone and plasma renin activity are associated with concentric left ventricle remodeling changes. Moreover, aldosterone was related to deleterious left atrium remodeling changes.

Relationship between clinic and ambulatory blood pressure and mortality: an observational cohort study in 59 124 patients

Ambulatory blood pressure provides a more comprehensive assessment than clinic blood pressure, and has been reported to better predict health outcomes than clinic or home pressure. We aimed to examine associations of clinic and 24-h ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of primary care patients referred for assessment of hypertension. We did an observational cohort study using clinic and ambulatory blood pressure data obtained from March 1, 2004, to Dec 31, 2014, from the Spanish Ambulatory Blood Pressure Registry. This registry included patients from 223 primary care centres from the Spanish National Health System in all 17 regions of Spain. Mortality data (date and cause) were ascertained by a computerised search of the vital registry of the Spanish National Institute of Statistics. Complete data were available for age, sex, all blood pressure measures, and BMI. For each study participant, follow-up was from the date of their recruitment to the date of death or Dec 31, 2019, whichever occurred first. Cox models were used to estimate associations between usual clinic or ambulatory blood pressure and mortality, adjusted for confounders and additionally for alternative measures of blood pressure. For each measure of blood pressure, we created five groups (ie, fifths) defined by quintiles of that measure among those who subsequently died. During a median follow-up of 9·7 years, 7174 (12·1%) of 59 124 patients died, including 2361 (4·0%) from cardiovascular causes. J-shaped associations were observed for several blood pressure measures. Among the top four baseline-defined fifths, 24-h systolic blood pressure was more strongly associated with all-cause death (hazard ratio [HR] 1·41 per 1 - SD increment [95% CI 1·36-1·47]) than clinic systolic blood pressure (1·18 [1·13-1·23]). After adjustment for clinic blood pressure, 24-h blood pressure remained strongly associated with all-cause deaths (HR 1·43 [95% CI 1·37-1·49]), but the association between clinic blood pressure and all-cause death was attenuated when adjusted for 24-h blood pressure (1·04 [1·00-1·09]). Compared with the informativeness of clinic systolic blood pressure (100%), night-time systolic blood pressure was most informative about risk of all-cause death (591%) and cardiovascular death (604%). Relative to blood pressure within the normal range, elevated all-cause mortality risks were observed for masked hypertension (HR 1·24 [95% CI 1·12-1·37]) and sustained hypertension (1·24 [1·15-1·32]), but not white-coat hypertension, and elevated cardiovascular mortality risks were observed for masked hypertension (1·37 [1·15-1·63]) and sustained hypertension (1·38 [1·22-1·55]), but not white-coat hypertension. Ambulatory blood pressure, particularly night-time blood pressure, was more informative about the risk of all-cause death and cardiovascular death than clinic blood pressure. Spanish Society of Hypertension, Lacer Laboratories, UK Medical Research Council, Health Data Research UK, National Institute for Health and Care Research Biomedical Research Centres (Oxford and University College London Hospitals), and British Heart Foundation Centre for Research Excellence.

Abstract #1405106: The Associations of Total Testosterone with Nonalcoholic Fatty Liver Disease Inflammatory and Fibrotic Progression in Men with Type 2 Diabetes: A Cross-Sectional Study

Men with type 2 diabetes mellitus (T2DM) are predisposed to hypogonadism. Testosterone has an impact on metabolic disorders and it may play different roles in the progression of nonalcoholic fatty liver disease (NAFLD). We aim to investigate whether total testosterone is associated with NAFLD progression in men with T2DM. It is a cross-sectional study. A total of 1782 male participants with T2DM were enrolled from seven communities in Shanghai. Probable nonalcoholic steatohepatitis (NASH) was defined by the concurrence of NAFLD and metabolic syndrome (MetS). NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. Multinomial logistic regression and ordinal logistic regression was used to measure the association of total testosterone (independent variable) and the progression category of NAFLD (dependent variable). In male, TT quartiles were negatively associated with probable NASH (Q1 vs. Q4 OR 2.07 95%CI, 1.31-3.28, P for trend=0.001) and inflammatory progression of NAFLD with OR of 1 SD increment of ln (TT) 0.81 (95% CI 0.72-0.92, P for trend<0.001), but positively with fibrotic progression (Q1 vs. Q4 OR 0.45, 95% CI 0.29-0.72, P for trend=0.001) with OR of 1 SD increment of ln(TT) 1.24 (95% CI 1.07-1.45). According to stratified analyses, for inflammatory progression, the interactions of age strata, duration of diabetes strata and dyslipidemia status with 1 SD increment of ln (TT) were significant (P for interaction 0.007,0.003 and 0.012 respectively); as for fibrotic progression, we found no interactoins (all P for interaction ≥0.05). In this population-based study including 1782 male patients with T2DM, we found that TT of male patients was negatively associated with probable NASH and NAFLD inflammatory progression but positively with fibrotic progression. Our results indicate that in male patients with T2DM, testosterone may play significant but opposite roles in inflammatory and fibrotic progression of NAFLD. Hence, understanding androgen hormone changes during T2DM and differentiating the stages of NAFLD may help clinicians personalize treatment strategy for male NAFLD patients with T2DM.

Associations of dietary patterns with risk of incident atrial fibrillation in the REasons for Geographic And Racial Differences in Stroke (REGARDS)

BackgroundWe examined whether the risk of incident atrial fibrillation (AF) in a large, biracial, prospective cohort is lower in participants who adhere to heart-healthy dietary patterns and higher in participants who adhere to less heart-healthy diets.MethodsBetween 2003 and 2007, the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study enrolled 30,239 Black and White Americans aged 45 years or older. Dietary patterns (convenience, plant-based, sweets, Southern, and alcohol and salads) and the Mediterranean diet score (MDS) were derived based on food frequency questionnaire data. The primary outcome was incident AF at the follow-up visit 2013–2016, defined by either electrocardiogram or self-reported medical history of a physician diagnosis.ResultsThis study included 8977 participants (mean age 63 ± 8.3 years; 56% women; 30% Black) free of AF at baseline who completed the follow-up exam an average of 9.4 years later. A total of 782 incident AF cases were detected. In multivariable logistic regression analyses, neither the MDS score (odds ratio (OR) per SD increment = 1.03; 95% confidence interval (CI) 0.95–1.11) or the plant-based dietary pattern (OR per SD increment = 1.03; 95% CI 0.94–1.12) were associated with AF risk. Additionally, an increased AF risk was not associated with any of the less-healthy dietary patterns.ConclusionsWhile specific dietary patterns have been associated with AF risk factors, our findings fail to show an association between diet patterns and AF development.

Sleep Patterns, Plasma Metabolome, and Risk of Incident Type 2 Diabetes Mellitus.

A healthy sleep pattern has been related to a lower risk of type 2 diabetes mellitus (T2DM). We aimed to identify the metabolomic signature for the healthy sleep pattern and assess its potential causality with T2DM. This study included 78 659 participants with complete phenotypic data (sleep information and metabolomic measurements) from the UK Biobank study. Elastic net regularized regression was applied to calculate a metabolomic signature reflecting overall sleep patterns. We also performed genome-wide association analysis of the metabolomic signature and one-sample mendelian randomization (MR) with T2DM risk. During a median of 8.8 years of follow-up, we documented 1489 incident T2DM cases. Compared with individuals who had an unhealthy sleep pattern, those with a healthy sleep pattern had a 49% lower risk of T2DM (multivariable-adjusted hazard ratio [HR], 0.51; 95% CI, 0.40-0.63). We further constructed a metabolomic signature using elastic net regularized regressions that comprised 153 metabolites, and robustly correlated with sleep pattern (r = 0.19; P = 3×10-325). In multivariable Cox regressions, the metabolomic signature showed a statistically significant inverse association with T2DM risk (HR per SD increment in the signature, 0.56; 95% CI, 0.52-0.60). Additionally, MR analyses indicated a significant causal relation between the genetically predicted metabolomic signature and incident T2DM (P for trend < .001). In this large prospective study, we identified a metabolomic signature for the healthy sleep pattern, and such a signature showed a potential causality with T2DM risk independent of traditional risk factors.

Liver biomarkers, lipid metabolites, and risk of gestational diabetes mellitus in a prospective study among Chinese pregnant women

BackgroundLiver plays an important role in maintaining glucose homeostasis. We aimed to examine the associations of liver enzymes and hepatic steatosis index (HSI, a reliable biomarker for non-alcoholic fatty liver disease) in early pregnancy with subsequent GDM risk, as well as the potential mediation effects of lipid metabolites on the association between HSI and GDM.MethodsIn a birth cohort, liver enzymes were measured in early pregnancy (6-15 gestational weeks, mean 10) among 6,860 Chinese women. Multivariable logistic regression was performed to examine the association between liver biomarkers and risk of GDM. Pearson partial correlation and least absolute shrinkage and selection operator (LASSO) regression were conducted to identify lipid metabolites that were significantly associated with HSI in a subset of 948 women. Mediation analyses were performed to estimate the mediating roles of lipid metabolites on the association of HSI with GDM.ResultsLiver enzymes and HSI were associated with higher risks of GDM after adjustment for potential confounders, with ORs ranging from 1.42 to 2.24 for extreme-quartile comparisons (false discovery rate-adjusted P-trend ≤0.005). On the natural log scale, each SD increment of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and HSI was associated with a 1.15-fold (95% CI: 1.05, 1.26), 1.10-fold (1.01, 1.20), 1.21-fold (1.10, 1.32), 1.15-fold (1.04, 1.27), and 1.33-fold (1.18, 1.51) increased risk of GDM, respectively. Pearson partial correlation and LASSO regression identified 15 specific lipid metabolites in relation to HSI. Up to 52.6% of the association between HSI and GDM risk was attributed to the indirect effect of the HSI-related lipid score composed of lipid metabolites predominantly from phospholipids (e.g., lysophosphatidylcholine and ceramides) and triacylglycerol.ConclusionsElevated liver enzymes and HSI in early pregnancy, even within a normal range, were associated with higher risks of GDM among Chinese pregnant women. The association of HSI with GDM was largely mediated by altered lipid metabolism.

Association of a novel nutritional index with stroke in Chinese population with hypertension: Insight from the China H-type hypertension registry study.

The abbreviated TCB index (TCBI) is a novel indicator of nutritional status, calculated by multiplying the serum values of triglycerides (TG), total serum cholesterol (TC), and body weight. The research on the relationship between this index and stroke is limited. We aimed to investigate the association between TCBI and stroke in Chinese hypertensive patients. A total of 13,358 adults with hypertension from the China H-type Hypertension Registry Study were enrolled. The TCBI was calculated as TG (mg/dL) * TC (mg/dL) * body weight (kg)/1,000. The primary outcome was an incidence of stroke. Multivariable adjusted models revealed an inverse association between TCBI and the prevalence of stroke. In the fully adjusted model, the results showed that the prevalence of stroke decreased by 13% (OR, 0.87; 95% CI, 0.78-0.98, p = 0.018) per SD increment of LgTCBI. When TCBI was assessed as a categorical variable, compared with those in group Q4 (TCBI ≥ 2,399), the participants in group Q3 (TCBI ≥ 1,476 and <2,399), group Q2 (TCBI ≥ 920 and <1,476), and group Q1 (TCBI < 920) had increases in stroke prevalence of 42% (OR, 1.42; 95% CI, 1.13-1.80; p-value = 0.003), 38% (OR, 1.38; 95% CI, 1.07-1.80; p-value = 0.014), and 68% (OR, 1.68; 95% CI, 1.24-2.27; p-value = 0.001), respectively. Subgroup analysis showed an interaction between age and TCBI and stroke (age < 60 years OR, 0.69; 95% CI, 0.58-0.83; vs. age ≥ 60 years OR, 0.95; 95% CI, 0.84-1.07; P for interaction = 0.001). We found an independent negative association between TCBI and the prevalence of stroke, especially in hypertensive patients aged < 60 years.