scholarly journals Longitudinal Plasma Lipidome and Risk of Type 2 Diabetes in a Large Sample of American Indians With Normal Fasting Glucose: The Strong Heart Family Study

2021 ◽  
Author(s):  
Guanhong Miao ◽  
Ying Zhang ◽  
Zhiguang Huo ◽  
Wenjie Zeng ◽  
Jianhui Zhu ◽  
...  
Keyword(s):  
Risk Factors ◽  
American Indians ◽  
Baseline Level ◽  
Longitudinal Change ◽  
Mixed Effect ◽  
Lipid Species ◽  
Increased Risk ◽  
Traditional Risk Factors ◽  
Continuous Measures

<strong>OBJECTIVE:</strong> Comprehensive assessment of alterations in lipid species preceding T2D is largely unknown. We aimed to identify plasma molecular lipids associated with risk of T2D in American Indians. <p><strong>RESEARCH DESIGN AND METHODS</strong>: Using an untargeted LC-MS, we repeatedly measured 3,907 fasting plasma samples from 1,958 participants who attended two exams (~5.5 year apart) and were followed up to 16 years in the Strong Heart Study. Mixed-effect logistic regression was used to identify lipids associated with risk of T2D adjusting for traditional risk factors. Repeated measurement analysis was performed to examine the association between change in lipidome and change in continuous measures of T2D adjusting for baseline lipids. Multiple testing was controlled by false discovery rate at 0.05.</p> <p><strong>RESULTS:</strong> Higher baseline level of 33 lipid species, including TAGs, DAGs, PEs, and PCs, was significantly associated with increased risk of T2D (odds ratio [OR] per SD increase in log2-transformed baseline lipids: 1.50-2.85) at 5-year follow-up. Of these, 21 lipids were also associated with risk of T2D at 16-year follow-up. Aberrant lipid profiles were also observed in prediabetes (OR per SD increase in log2-transformed baseline lipids: 1.30-2.19 for risk lipids; 0.70-0.78 for protective lipids). Longitudinal changes in 568 lipids were significantly associated with changes in continuous measures of T2D. Multivariate analysis identified distinct lipidomic signatures differentiating high from low risk groups. </p> <p><strong>CONCLUSIONS:</strong> Lipid dysregulation occurs many years preceding T2D, and novel molecular lipids (both baseline level and longitudinal change over time) are significantly associated with risk of T2D beyond traditional risk factors. Our findings shed light on the mechanisms linking dyslipidemia to T2D and may yield novel therapeutic targets for early intervention tailored to American Indians.</p>

scholarly journals Longitudinal Plasma Lipidome and Risk of Type 2 Diabetes in a Large Sample of American Indians With Normal Fasting Glucose: The Strong Heart Family Study

2021 ◽  
Author(s):  
Guanhong Miao ◽  
Ying Zhang ◽  
Zhiguang Huo ◽  
Wenjie Zeng ◽  
Jianhui Zhu ◽  
...  
Keyword(s):  
Risk Factors ◽  
American Indians ◽  
Baseline Level ◽  
Longitudinal Change ◽  
Mixed Effect ◽  
Lipid Species ◽  
Increased Risk ◽  
Traditional Risk Factors ◽  
Continuous Measures

<strong>OBJECTIVE:</strong> Comprehensive assessment of alterations in lipid species preceding T2D is largely unknown. We aimed to identify plasma molecular lipids associated with risk of T2D in American Indians. <p><strong>RESEARCH DESIGN AND METHODS</strong>: Using an untargeted LC-MS, we repeatedly measured 3,907 fasting plasma samples from 1,958 participants who attended two exams (~5.5 year apart) and were followed up to 16 years in the Strong Heart Study. Mixed-effect logistic regression was used to identify lipids associated with risk of T2D adjusting for traditional risk factors. Repeated measurement analysis was performed to examine the association between change in lipidome and change in continuous measures of T2D adjusting for baseline lipids. Multiple testing was controlled by false discovery rate at 0.05.</p> <p><strong>RESULTS:</strong> Higher baseline level of 33 lipid species, including TAGs, DAGs, PEs, and PCs, was significantly associated with increased risk of T2D (odds ratio [OR] per SD increase in log2-transformed baseline lipids: 1.50-2.85) at 5-year follow-up. Of these, 21 lipids were also associated with risk of T2D at 16-year follow-up. Aberrant lipid profiles were also observed in prediabetes (OR per SD increase in log2-transformed baseline lipids: 1.30-2.19 for risk lipids; 0.70-0.78 for protective lipids). Longitudinal changes in 568 lipids were significantly associated with changes in continuous measures of T2D. Multivariate analysis identified distinct lipidomic signatures differentiating high from low risk groups. </p> <p><strong>CONCLUSIONS:</strong> Lipid dysregulation occurs many years preceding T2D, and novel molecular lipids (both baseline level and longitudinal change over time) are significantly associated with risk of T2D beyond traditional risk factors. Our findings shed light on the mechanisms linking dyslipidemia to T2D and may yield novel therapeutic targets for early intervention tailored to American Indians.</p>

scholarly journals The correlation between traditional risk factors and the severity of acute coronary syndrome and long-term prognosis

2015 ◽  
Vol 6 (4) ◽  
pp. 6-10
Author(s):  
I. S Skopets ◽  
N. N Vezikova ◽  
I. M Marusenko ◽  
O. Yu Barysheva
Keyword(s):  
Risk Factors ◽  
Acute Coronary Syndrome ◽  
Family History ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Life Threatening ◽  
Traditional Risk Factors ◽  
Long Term Prognosis

A number of studies demonstrate that patients with traditional risk factors (TRF) have not only increases primary risk of atherothrombotic events, but are also associated with many complicates and poor prognosis.Purpose: assessment of TRF effect on the incidence of complications and outcomes in patients with acute coronary syndrome (ACS).Materials and methods: in 255 patients hospitalized with ACS were retrospective determined the TRF prevalence, frequency of the complications and correlation between the presence of TRF and the risk of complications and long-term prognosis (follow-up 1 year).Results: patients had TRF very often, 80% patients had more than 3 TRFs. The presence of some TRFs (smoking, abdominal obesity, family history) was associated with a significantly increased risk of complications in patients with ACS, including life-threatening. Effect of TRF on long-term prognosis was not determined.Conclusion: the findings suggest the need to evaluation TRF not only in primary preventive and also to improve the effectiveness of risk stratification in patients with ACS.

Abstract 22: Novel Plasma Lipids Predict Risk of Diabetes: A Longitudinal Lipidomics Study in American Indians

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Yun Zhu ◽  
Ying Zhang ◽  
Jianhui Zhu ◽  
Jason G Umans ◽  
Shelley Cole ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Risk Prediction ◽  
American Indians ◽  
Plasma Lipids ◽  
Network Connectivity ◽  
Diabetes Risk ◽  
Fasting Plasma ◽  
Traditional Risk Factors

Background: American Indians (AIs) suffer disproportionately high rate of type 2 diabetes (T2D). Traditional biomarkers have limited value in predicting and tracking early onset and progression of T2D. There is an urgent need for early biomarkers in this high-risk but understudied minority population. Objective: To identify novel lipids predictive of T2D onset among American Indians, independent of standard risk factors. Methods: We studied 2,000 American Indians attending two clinical exams (2001-2003, 2006-2009, average 5-yr apart) in the Strong Heart Family Study (SHFS). Fasting plasma lipids were repeatedly measured by untargeted lipidomics using LC-MS/MS. All participants were free of overt CVD at baseline (2001-2003) and followed through 2017 (average 16-yr follow-up). Cox regression with frailty model was used to identify lipids predictive of T2D onset, adjusting for traditional risk factors including age, sex, smoking, BMI, triglyceride, HDL, insulin resistance, eGFR and dietary intake of protein. Longitudinal analysis was conducted by regressing changes in lipids on changes in T2D-related traits (e.g., fasting glucose, HbA1c, or insulin resistance) between baseline and 5-yr follow-up, adjusting for changes in BMI, triglyceride, HDL, and eGFR. Incremental prognostic value of lipids in diabetes risk prediction above traditional risk factors was estimated using area under the curve (AUC). Network analysis was conducted to examine the dynamic changes in lipid networks between baseline and 5-yr follow-up. Multiple testing was controlled by FDR. Results: Of 1,628 non-diabetic participants at baseline (mean age 39.8, 62% women), 189 and 359 individuals developed incident T2D after 5-yr and 16-yr follow-up, respectively. Our high-resolution lipidomics detected 1,826 lipids, of which 1,119 lipids (460 known, 659 unknown) passed stringent quality control. Seven lipids with known structures significantly predict over 30% increased (FA(18:1), FA(20:2), FA(22:2), SM(d34:0) ) or 19% decreased (PC(37:4), PC(37:5), PC(38:4)) risk of T2D onset at both follow-ups. Nine unknown lipids also predicted T2D onset. Longitudinal changes in CE(20:2), CE(22:6), PC(32:0) and two unknowns explain about 6.4% changes in fasting plasma glucose. These newly identified lipids significantly improve the performance of risk prediction over traditional risk factors (AUC increased from 0.787 to 0.803, P=0.002). Network topology analysis revealed that the network connectivity among lipids was much stronger in participants who developed new T2D compared to those who didn’t (degree of network connectivity, 4.2 vs 2.5, P<0.001). Conclusion: We identified several novel plasma lipids significantly predictive of incident T2D, independent of traditional risk factors. These findings highlight the importance of identifying novel lipid markers in early diabetes risk prediction.

scholarly journals Comprehensive Metabolomics Identified the Prominent Role of Glycerophospholipid Metabolism in Coronary Artery Disease Progression

2021 ◽  
Vol 8 ◽  
Author(s):  
Hui Chen ◽  
Zixian Wang ◽  
Min Qin ◽  
Bin Zhang ◽  
Lu Lin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Adverse Outcomes ◽  
Combined Model ◽  
C Statistic ◽  
Lipid Species ◽  
Increased Risk ◽  
Traditional Risk Factors ◽  
Artery Disease

Background: Coronary stenosis severity determines ischemic symptoms and adverse outcomes. The metabolomic analysis of human fluids can provide an insight into the pathogenesis of complex disease. Thus, this study aims to investigate the metabolomic and lipidomic biomarkers of coronary artery disease (CAD) severity and to develop diagnostic models for distinguishing individuals at an increased risk of atherosclerotic burden and plaque instability.Methods: Widely targeted metabolomic and lipidomic analyses of plasma in 1,435 CAD patients from three independent centers were performed. These patients were classified as stable coronary artery disease (SCAD), unstable angina (UA), and myocardial infarction (MI). Associations between CAD stages and metabolic conditions were assessed by multivariable-adjusted logistic regression. Furthermore, the least absolute shrinkage and selection operator logistic-based classifiers were used to identify biomarkers and to develop prediagnostic models for discriminating the diverse CAD stages.Results: On the basis of weighted correlation network analysis, 10 co-clustering metabolite modules significantly (p &lt; 0.05) changed at different CAD stages and showed apparent correlation with CAD severity indicators. Moreover, cross-comparisons within CAD patients characterized that a total of 72 and 88 metabolites/lipid species significantly associated with UA (vs. SCAD) and MI (vs. UA), respectively. The disturbed pathways included glycerophospholipid metabolism, and cysteine and methionine metabolism. Furthermore, models incorporating metabolic and lipidomic profiles with traditional risk factors were constructed. The combined model that incorporated 11 metabolites/lipid species and four traditional risk factors represented better discrimination of UA and MI (C-statistic = 0.823, 95% CI, 0.783–0.863) compared with the model involving risk factors alone (C-statistic = 0.758, 95% CI, 0.712–0.810). The combined model was successfully used in discriminating UA and MI patients (p &lt; 0.001) in a three-center validation cohort.Conclusion: Differences in metabolic profiles of diverse CAD subtypes provided a new approach for the risk stratification of unstable plaque and the pathogenesis decipherment of CAD progression.

Abstract P388: Novel Metabolic Markers for the Risk of Carotid Plaque Progression in American Indians

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Yun Zhu ◽  
An Qiang ◽  
Lyle G Best ◽  
Elisa T Lee ◽  
Barbara V Howard ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Prediction ◽  
American Indians ◽  
Carotid Plaque ◽  
Plasma Metabolites ◽  
Plaque Progression ◽  
Cross Sectional ◽  
Metabolic Markers ◽  
Traditional Risk Factors

Background: Carotid atherosclerotic plaque and its progression significantly predict cardiovascular events. Traditional clinical factors have limited value in early risk prediction. Metabolomics is an emerging technology that can accurately quantify hundreds to thousands of small metabolites in biofluids, thus providing a powerful tool for early biomarker discovery. Previous studies were largely cross-sectional with a focus on the European population, results of which may not be generalized to other ethnic groups. In addition, causality cannot be resolved in cross-sectional analysis. Objective: To prospectively identify novel metabolic markers predictive of carotid plaque onset and progression in American Indians in the Strong Heart Study (SHS). Methods: This study includes 396 apparently healthy American Indians attending both clinical exams in 2001-2003 and 2006-2009 (average 5.5 years of follow-up). All participants had normal fasting glucose and were free of overt CVD at baseline. Plaque progression was defined as having a higher plaque score at the end of follow-up compared to baseline. Fasting plasma metabolites were detected using untargeted LC-MS. A total of 1,364 matching metabolites that passed stringent QC were included in the current analysis. The prospective association of plaque progression with each metabolite was examined using Cox proportional hazards model, adjusting for sex, site, age, BMI, eGFR, lipids, blood pressure, smoking and alcohol drinking at baseline. The combined metabolic effect was examined using a weighted multi-marker metabolites score comprising of all significant metabolites. Incremental value of novel metabolites over traditional risk factors for risk prediction was tested using the net reclassification improvement index (NRI). Multiple testing was corrected using the q-value method (q< 0.05 was considered statistical significance). Results: Of all 396 participants, 100 developed new plaque or progressed to a high order of atherosclerosis during follow-up. Five metabolites including PC (6:2/14:2) (HR 1.56[1.23-1.96]), proscillaridin A (HR 1.68 [1.27-2.21]), 8e-heptadecenedioic acid (HR 1.56 [1.22-1.98]), flavone (HR 1.69 [1.27-2.26]), and n-palmitoyl methionine (HR 1.72 [1.28-2.32]), significantly increase, whereas one metabolite, PC (18:0/18:1) (HR 0.62 [0.52-0.73]), significantly decreases the risk of plaque progression. A multi-marker score comprising of all six metabolites significantly improves risk prediction beyond traditional risk factors (NRI=0.22, P=1.23x10-5). Conclusions: Altered levels of fasting plasma metabolites significantly predict the risk of plaque onset and progression over and above conventional risk factors. The newly detected metabolites may unravel novel metabolic pathways underlying CVD pathogenesis and could be used as new markers for risk prediction and stratification.

P0278CARDIOVASCULAR RISK FACTORS AND THE LONG TERM OUTCOME OF LUPUS NEPHRITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marwa Omrane ◽  
Raja Aoudia ◽  
Mondher Ounissi ◽  
Soumaya Chargui ◽  
Mouna Jerbi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Renal Failure ◽  
Cardiovascular Risk ◽  
Lupus Nephritis ◽  
Cardiovascular Risk Factors ◽  
Increased Risk ◽  
Traditional Risk Factors

Abstract Background and Aims Systemic Lupus Erythematosus (SLE) is associated with an increased risk of cardiovascular morbidity and cardiovascular mortality. The risk of cardiovascular events is 1.3–2.7 times higher in SLE patients than in the general population, and even higher in patients with lupus nephritis (LN). Traditional risk factors as well as SLE-specific and treatment-related factors all contribute to the increased risk of cardiovascular disease. The primary aim of the present study was to evaluate cardiovascular risk factors, morbidity and mortality in patients with LN. Method This is a retrospective study of patients over the age of 16, with LN proved by kidney biopsy and followed up in our department over a period of 17 years. The diagnosis of lupus was made according to criteria of The American College of Rheumatology revised in 1997. Demographic, clinical and para-clinical data were collected from medical observations. Results We collected 155 women and 19 men with a sex ratio F / H of 8.2. The mean age at the time of the discovery of LN was 32.6 years [15-45 years]. Overall median follow-up time was 81.2 months. Renal symptomatology was dominated by proteinuria noted in all patients with an average proteinuria at 3.3 g / 24h, associated to a nephrotic syndrome in 68% of patients, hematuria was present in 69% of patients and renal failure was present in half of cases with an average serum creatinine of 110 µmol / l. At the time of diagnosis of LN, hypertension was noted in 48.9% of cases, diabetes in 2.8% of cases and obesity in 57.4% of cases with an index average body mass of 28.5 Kg / m2. Smoking was reported in 17.2% of the cases. The average cholesterol level was 5,5±2,1 mmol/l, the average triglycerid level was 2,5±1,1 mmol/. Antiphospholipid syndrome was found in 14.9% of cases. We performed 243 renal biopsies with 174 initial and 69 iterative biopsies. The histological lesions were polymorphic dominated by LN class IV (54.3%), arteriolosclerosis was observed in 47.7% and lesions of thrombotic microangiopathy in 29.8%. Corticosteroid therapy was prescribed in all patients combined with immunosuppressive therapy in 54.6% of cases. The overall survival of the patients at 10 years was 85%. During follow-up, cardiovascular complications found in our series were mainly strokes (6.3%) and coronary insufficiency (5.2%) and transient ischemic attack (6.9%). After a univariate analysis, the additional cardiovascular risk factors identified in our study were antiphospholipid syndrome (p = 0.01), renal failure (p = 0.01), long-term corticosteroid therapy (p = 0.009), the chronicity of the disease (evolution of lupus&gt; 10 years) (p = 0.014), proliferative forms (p=0.001), arteriolosclerosis (p=0.0002) and lesions of thrombotic microangiopathy (p=0.018). Survival in patients without cardiovascular risk factors was better (96% vs 88%). Conclusion In conclusion, in addition to traditional risk factors SLE patients have several disease related risk factors that explain increase cardiovascular disease. A careful control for this risk factors is essential to continuously improve survival in SLE.

scholarly journals Nasal symptoms increase the risk of snoring and snoring increases the risk of nasal symptoms. A longitudinal population study

2021 ◽  
Author(s):  
Maria Värendh ◽  
Christer Janson ◽  
Caroline Bengtsson ◽  
Johan Hellgren ◽  
Mathias Holm ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Health ◽  
Smoking Status ◽  
Northern Europe ◽  
Nasal Breathing ◽  
Nasal Symptoms ◽  
Increased Risk ◽  
Study Population ◽  
Independent Risk Factors

Abstract Purpose Humans have a preference for nasal breathing during sleep. This 10-year prospective study aimed to determine if nasal symptoms can predict snoring and also if snoring can predict development of nasal symptoms. The hypothesis proposed is that nasal symptoms affect the risk of snoring 10 years later, whereas snoring does not increase the risk of developing nasal symptoms. Methods In the cohort study, Respiratory Health in Northern Europe (RHINE), a random population from Denmark, Estonia, Iceland, Norway, and Sweden, born between 1945 and 1973, was investigated by postal questionnaires in 1999–2001 (RHINE II, baseline) and in 2010–2012 (RHINE III, follow-up). The study population consisted of the participants who had answered questions on nasal symptoms such as nasal obstruction, discharge, and sneezing, and also snoring both at baseline and at follow-up (n = 10,112). Results Nasal symptoms were frequent, reported by 48% of the entire population at baseline, with snoring reported by 24%. Nasal symptoms at baseline increased the risk of snoring at follow-up (adj. OR 1.38; 95% CI 1.22–1.58) after adjusting for age, sex, BMI change between baseline and follow-up, and smoking status. Snoring at baseline was associated with an increased risk of developing nasal symptoms at follow-up (adj. OR 1.22; 95% CI 1.02–1.47). Conclusion Nasal symptoms are independent risk factors for development of snoring 10 years later, and surprisingly, snoring is a risk factor for the development of nasal symptoms.

scholarly journals Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Radiation Induced ◽  
Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

Abstract P122: Racial/Ethnic Variation in Incidence and Progression of Coronary Artery Calcification: Implications for Understanding the Hispanic Paradox

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Sandra S Albrecht ◽  
Pamela L Lutsey ◽  
Matthew Allison ◽  
Teresa Seeman ◽  
Martha L Daviglus ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery ◽  
Future Research ◽  
Foreign Born ◽  
Hispanic Health ◽  
Current Cigarette Smoking ◽  
Current Cigarette ◽  
Traditional Risk Factors ◽  
Adjusted Incidence

Background: Previous studies show that Hispanic persons have similar or lower levels of coronary artery calcium (CAC) and slower progression than non-Hispanic whites (NHW), even after adjustment for traditional risk factors. We examined whether this health advantage in CAC incidence and progression among Hispanic adults extends across all levels of risk factor (RF) burden, and whether associations vary by nativity (foreign-born, US-born) and by heritage group (Mexican, non-Mexican). Methods: We analyzed data on Hispanic and NHW participants aged 45-84 years from the Multi-Ethnic Study of Atherosclerosis (MESA). Follow-up CAC measurements and complete covariate data were available for 3694 participants with an average of 6.6 years between the follow-up and baseline scans (2000-2002). Baseline measures of the following traditional RFs were considered: current cigarette smoking, high total cholesterol, hypertension, diabetes, and obesity, with RF burden scores ranging from 0-5. Outcomes were incident CAC (any follow-up CAC >0 Agatston units) among individuals without detectable CAC at baseline, and CAC progression (any positive increase in CAC) among all participants estimated using relative risk regression. All models were adjusted for age, sex, RF burden, race/ethnicity, education, income, and time between scans Results: Although a higher proportion of Hispanics had RF burden scores ≥3 compared to NHW (14.6% vs 8.9%, p<0.0001), Hispanics had a lower adjusted incidence (risk ratio (RR) = 0.83, 95% CI: 0.72-0.96) and less progression of CAC (RR=0.90, 95% CI: 0.86-0.95) than NHW. However, there was evidence of heterogeneity in this pattern. For example, among individuals with no detectable baseline CAC, a Hispanic health advantage was only seen among individuals with RF burden scores of 0 (RR=0.66, 95% CI: 0.48-0.91 for Hispanics vs. NHW at RF=0), with race/ethnic differences getting progressively smaller with increasing RF burden (for RF ≥3: RR=1.01, 95% CI: 0.69-1.48). Compared to NHW, lower adjusted incidence and progression of CAC was evident to an even greater extent among foreign-born Hispanics, but a health advantage was still present for US-born Hispanics, and for both Hispanic heritage groups. However, these patterns also only remained among individuals with lower RF burden scores. Conclusions: The Hispanic health advantage in CAC incidence and progression was primarily evident among individuals with fewer traditional risk factors for CVD, but was present among different Hispanics groups. Future research is necessary to identify the factors underlying this advantage, and the dynamics that erode it as RF burden increases.

Abstract 14760: Myocardial Scarring by Magnetic Resonance Predicts Sudden Cardiac Death in Pediatric Patients With Hypertrophic Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Lars Grosse-Wortmann ◽  
Laurine van der Wal ◽  
Aswathy Vaikom House ◽  
Lee Benson ◽  
Raymond Chan
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Hypertrophic Cardiomyopathy ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Pediatric Patients ◽  
Risk Markers ◽  
C Statistic ◽  
Increased Risk ◽  
Traditional Risk Factors

Introduction: Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) has been shown to be an independent predictor of sudden cardiac death (SCD) in adults with hypertrophic cardiomyopathy (HCM). The clinical significance of LGE in pediatric HCM patients is unknown. Hypothesis: LGE improves the SCD risk prediction in children with HCM. Methods: We retrospectively analyzed the CMR images and reviewed the outcomes pediatric HCM patients. Results: Amongst the 720 patients from 30 centers, 73% were male, with a mean age of 14.2±4.8 years. During a mean follow up of 2.6±2.7 years (range 0-14.8 years), 34 experienced an episode of SCD or equivalent. LGE (Figure 1A) was present in 34%, with a mean burden of 14±21g, or 2.5±8.2g/m2 (6.2±7.7% of LV myocardium). The presence of ≥1 adult traditional risk factor (family history of SCD, syncope, LV thickness >30mm, non-sustained ventricular tachycardia on Holter) was associated with an increased risk of SCD (HR=4.6, p<0.0001). The HCM Risk-Kids score predicted SCD (p=0.002). The presence of LGE was strongly associated with an increased risk (HR=3.8, p=0.0003), even after adjusting for traditional risk factors (HR adj =3.2, p=0.003) or the HCM Risk-Kids score (HR adj =3.5, p=0.003). Furthermore, the burden of LGE was associated with increased risk (HR=2.1/10% LGE, p<0.0001). LGE burden remained independently associated with an increased risk for SCD after adjusting for traditional risk factors (HRadj=1.5/10% LGE, p=0.04) or HCM Risk-Kids (HRadj=1.9/10% LGE, p=0.0018, Figure 1B). The addition of LGE burden improved the predictive model using traditional risk markers (C statistic 0.67 vs 0.77, p=0.003) and HCM Risk-Kids (C statistic 0.68 vs 0.74, p=0.045). Conclusions: Quantitative LGE is an independent risk factor for SCD in pediatric patients with HCM and improves the performance of traditional risk markers and the HCM Risk-Kids Score for SCD risk stratification in this population.

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