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1.
PLoS One ; 15(11): e0242062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33196677

RESUMO

OBJECTIVE: To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time. METHODS: Data from the population-based Cardiovascular Health Study (n = 5,888, aged ≥65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function. RESULTS: After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99-1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87-1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 ß = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 ß = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 ß = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 ß = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment. INTERPRETATION: The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses.

2.
J Am Soc Nephrol ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239392

RESUMO

BACKGROUND: Although proximal tubular secretion is the primary mechanism of kidney drug elimination, current kidney drug dosing strategies are on the basis of eGFR. METHODS: In a dedicated pharmacokinetic study to compare GFR with tubular secretory clearance for predicting kidney drug elimination, we evaluated stable outpatients with eGFRs ranging from 21 to 140 ml/min per 1.73 m2. After administering single doses of furosemide and famciclovir (metabolized to penciclovir), we calculated their kidney clearances on the basis of sequential plasma and timed urine measurements. Concomitantly, we quantified eight endogenous secretory solutes in plasma and urine using liquid chromatography-tandem mass spectrometry and measured GFR by iohexol clearance (iGFR). We computed a summary secretion score as the scaled average of the secretory solute clearances. RESULTS: Median iGFR of the 54 participants was 73 ml/min per 1.73 m2. The kidney furosemide clearance correlated with iGFR (r=0.84) and the summary secretion score (r=0.86). The mean proportionate error (MPE) between iGFR-predicted and measured furosemide clearance was 30.0%. The lowest MPE was observed for the summary secretion score (24.1%); MPEs for individual secretory solutes ranged from 27.3% to 48.0%. These predictive errors were statistically indistinguishable. Penciclovir kidney clearance was correlated with iGFR (r=0.83) and with the summary secretion score (r=0.91), with similar predictive accuracy of iGFR and secretory clearances. Combining iGFR with the summary secretion score yielded only modest improvements in the prediction of the kidney clearance of furosemide and penciclovir. CONCLUSIONS: Secretory solute clearance measurements can predict kidney drug clearances. However, tight linkage between GFR and proximal tubular secretory clearance in stable outpatients provides some reassurance that GFR, even when estimated, is a useful surrogate for predicting secretory drug clearances in such patients.

3.
BMC Med ; 18(1): 246, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32933497

RESUMO

BACKGROUND: Mechanistic studies suggest that mitochondria DNA (mtDNA) dysfunction may be associated with increased risk of atrial fibrillation (AF). The association between mtDNA copy number (mtDNA-CN) and incident AF in the general population, however, remains unknown. METHODS: We conducted prospective analyses of 19,709 participants from the Atherosclerosis Risk in Communities Study (ARIC), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Cardiovascular Health Study (CHS). mtDNA-CN from the peripheral blood was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array 6.0 in ARIC and MESA and from multiplexed real-time quantitative polymerase chain reaction (qPCR) in CHS. Incident AF cases were identified through electrocardiograms, review of hospital discharge codes, Medicare claims, and death certificates. RESULTS: The median follow-up time was 21.4 years in ARIC, 12.9 years in MESA, and 11.0 years in CHS, during which 4021 participants developed incident atrial fibrillation (1761 in ARIC, 790 in MESA, and 1470 in CHS). In fully adjusted models, participants with the lowest quintile of mitochondria DNA copy number had an overall 13% increased risk (95% CI 1 to 27%) of incident atrial fibrillation compared to those with the highest quintile. Dose-response spline analysis also showed an inverse association between mitochondria DNA copy number and hazard for atrial fibrillation for all three cohorts. These associations were consistent across subgroups. CONCLUSIONS: Mitochondria DNA copy number was inversely associated with the risk of AF independent of traditional cardiovascular risk factors. These findings implicate mitochondria DNA copy number as a novel risk factor for atrial fibrillation. Further research is warranted to understand the underlying mechanisms and to evaluate the role of mitochondria DNA copy number in the management of atrial fibrillation risk.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32986961

RESUMO

Heart rate fragmentation (HRF), a marker of abnormal sinoatrial dynamics, was shown to be associated with incident cardiovascular events in the Multi-Ethnic Study of Atherosclerosis (MESA). Here, we test the hypothesis that HRF is also associated with incident atrial fibrillation (AF) in the MESA cohort of participants who underwent in-home polysomnography (PSG) and in two high-risk subgroups: those ≥70 years taking antihypertensive medication and those with serum concentrations of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) >125 pg/ml (top quartile). Heart rate time series (n=1,865) derived from the ECG channel of the PSG were analyzed using newly developed HRF metrics, traditional heart rate variability (HRV) indices and two widely used nonlinear measures. Eighty-three participants developed AF over a median follow-up period of 3.83 ± 0.87 years. A one-SD increase in HRF was associated with a 35% (95% CI: 7%-70%) increase in risk of incident AF, in Cox models adjusted for age, height, NT-proBNP and frequent premature supraventricular complexes. Furthermore, HRF added value to the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF model. Traditional HRV and nonlinear indices were not significantly associated with incident AF. In the two high-risk subgroups defined above, HRF was also significantly associated with incident AF in unadjusted and adjusted models. These findings support the translational utility of HRF metrics for short-term (approximately four-year) prediction of AF. In addition, they support broadening the concept of atrial remodeling to include electrodynamical remodeling, a term used to refer to pathophysiologic alterations in sinus interbeat interval dynamics.

5.
JCI Insight ; 5(19)2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-32910807

RESUMO

BACKGROUND: Left atrial (LA) and left ventricular (LV) remodeling are associated with atrial fibrillation (AF). The prospective associations of impairment in cardiac mechanical function, as assessed by speckle-tracking echocardiography, with incident AF are less clear. METHODS: In the Cardiovascular Health Study, a community-based cohort of older adults, participants free of AF with echocardiograms of adequate quality for speckle tracking were included. We evaluated the associations of indices of cardiac mechanics (LA reservoir strain, LV longitudinal strain, and LV early diastolic strain rate) with incident AF. RESULTS: Of 4341 participants with strain imaging, participants with lower LA reservoir strain were older, had more cardiometabolic risk factors, and had lower renal function at baseline. Over a median follow-up of 10 years, 497 (11.4%) participants developed AF. Compared with the highest quartile of LA reservoir strain, the lowest quartile of LA reservoir strain was associated with higher risk of AF after covariate adjustment, including LA volume and LV longitudinal strain (heart rate [HR], 1.80; 95% CI, 1.31-2.45; P < 0.001). The association of LA reservoir strain and AF was stronger in subgroups with higher blood pressure, NT-proBNP, and LA volumes. There were no associations of LV longitudinal strain and LV early diastolic strain rate with incident AF after adjustment for LA reservoir strain. CONCLUSION: Lower LA reservoir strain was associated with incident AF, independent of LV mechanics, and with stronger associations in high-risk subgroups. These findings suggest that LA mechanical dysfunction precedes the development of AF. Therapies targeting LA mechanical dysfunction may prevent progression to AF. FUNDING: This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grants KL2TR001424, R01HL107577, U01HL080295, and U01HL130114 from the NIH's National Center for Advancing Translational Sciences, and National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org.

6.
Arterioscler Thromb Vasc Biol ; 40(11): 2756-2763, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32878478

RESUMO

OBJECTIVE: Venous thromboembolism (VTE) is a common disease that has a genetic basis. Lifestyle factors contribute to risk, but it is unknown whether healthy lifestyle can mitigate the genetic risk. We studied whether greater adherence to the American Heart Association's cardiovascular health metric, Life's Simple 7 (LS7), is associated with lower incidence of VTE in individuals across categories of a genetic risk score (GRS) for VTE. Approach AND RESULTS: We followed 9026 White participants from the ARIC (Atherosclerosis Risk in Communities) Study, a prospective cohort enrolled in 1987 to 1989 until 2015. We tested the joint associations with VTE of a validated VTE GRS comprising 5 well-known gene variants and baseline LS7 categories. There were 466 incident VTE events over 22.8 years. Participants with an optimal LS7 score had a lower incidence of VTE (3.9%) than those with inadequate LS7 (5.7%). Compared with the high GRS and inadequate LS7 group (hazard ratio=1), those with high GRS and optimal LS7 indeed had a reduced hazard ratio of VTE: 0.65 (95% CI, 0.48-0.89). The group with low GRS and optimal LS7 had the lowest hazard ratio of VTE (0.39 [95% CI, 0.25-0.61]). Of the LS7 components, in all GRS groups, the factor most strongly protective for VTE was normal weight. CONCLUSIONS: Among people at low or high genetic risk for VTE, healthier lifestyle factors, particularly normal weight, were associated with a lower incidence of VTE. Further studies should determine the impact of lifestyle changes among patients at high genetic risk of VTE, such as in thrombophilic families.

7.
Circ Genom Precis Med ; 13(5): 387-395, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32822252

RESUMO

BACKGROUND: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. METHODS: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. RESULTS: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk. CONCLUSIONS: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.

8.
J Rheumatol ; 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611668

RESUMO

OBJECTIVE: Cardiovascular (CV) morbidity and mortality are increased in axial spondyloarthritis (axSpA). We conducted a cross-sectional study evaluating the 10-year atherosclerotic cardiovascular disease (ASCVD) risk in axSpA compared to the general US population. METHODS: We included 211 adults 40-75 years old with ankylosing spondylitis (AS) or non-radiographic axSpA from two sites, who had available data on comorbidities, medication use, blood pressure measures, and laboratory cholesterol values. We matched 4:1 to general population comparators from the 2009-2014 National Health and Examination Survey (NHANES) cycles on age, sex, and race. We estimated the prevalence ratio for a 10-year ASCVD risk score ≥7.5% comparing axSpA and matched NHANES comparators using conditional Poisson regression. RESULTS: Overall, subjects were 53.9 ± 11.2 years old, 69% were male, and 74% were white. The mean 10-year ASCVD risk score was 6.7 ± 6.9% for those with axSpA and 9.0 ± 10.5% for NHANES comparators. Compared to those with axSpA, the prevalence of current smoking and diabetes was higher among NHANES comparators. The estimated prevalence ratio for a 10-year ASCVD risk score ≥7.5% comparing those with axSpA and their age-, sex-, and race-matched comparators was 0.96 (95% CI, 0.74-1.24). CONCLUSION: The prevalence of a 10-year ASCVD risk score ≥7.5% was not significantly different comparing axSpA patients and those drawn from the general population, who were similar in terms of age, sex, and race. Future studies should focus on improved CV risk prediction in axSpA, as underestimation by a general population risk score may potentially explain these results.

9.
Circ Genom Precis Med ; 13(4): e002680, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32602732

RESUMO

BACKGROUND: We examined how expanding electrocardiographic trait genome-wide association studies to include ancestrally diverse populations, prioritize more precise phenotypic measures, and evaluate evidence for shared genetic effects enabled the detection and characterization of loci. METHODS: We decomposed 10 seconds, 12-lead electrocardiograms from 34 668 multi-ethnic participants (15% Black; 30% Hispanic/Latino) into 6 contiguous, physiologically distinct (P wave, PR segment, QRS interval, ST segment, T wave, and TP segment) and 2 composite, conventional (PR interval and QT interval) interval scale traits and conducted multivariable-adjusted, trait-specific univariate genome-wide association studies using 1000-G imputed single-nucleotide polymorphisms. Evidence of shared genetic effects was evaluated by aggregating meta-analyzed univariate results across the 6 continuous electrocardiographic traits using the combined phenotype adaptive sum of powered scores test. RESULTS: We identified 6 novels (CD36, PITX2, EMB, ZNF592, YPEL2, and BC043580) and 87 known loci (adaptive sum of powered score test P<5×10-9). Lead single-nucleotide polymorphism rs3211938 at CD36 was common in Blacks (minor allele frequency=10%), near monomorphic in European Americans, and had effects on the QT interval and TP segment that ranked among the largest reported to date for common variants. The other 5 novel loci were observed when evaluating the contiguous but not the composite electrocardiographic traits. Combined phenotype testing did not identify novel electrocardiographic loci unapparent using traditional univariate approaches, although this approach did assist with the characterization of known loci. CONCLUSIONS: Despite including one-third as many participants as published electrocardiographic trait genome-wide association studies, our study identified 6 novel loci, emphasizing the importance of ancestral diversity and phenotype resolution in this era of ever-growing genome-wide association studies.

10.
Ophthalmol Retina ; 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32565383

RESUMO

PURPOSE: Microvascular diseases may contribute to the occurrence of atrial fibrillation (AF). Retinal microvascular signs that are similar to other microvasculature in the body and can be visualized directly via ophthalmoscopy may provide insights into such a relationship. DESIGN: Prospective, longitudinal, multiethnic study. PARTICIPANTS: We examined the association between retinal microvascular signs and incident AF in 4994 participants 47 to 86 years of age and free of prior AF who underwent fundus photography from 2002 through 2004 and were followed up through 2015 in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: Retinal microvascular signs evaluated include central retinal arteriolar equivalent and central retinal venular equivalent (CRVE) and presence of any retinopathy signs (e.g., retinal microaneurysms or hemorrhages). A multivariate Cox regression analysis was used to determine the relationship while adjusting for traditional risk factors, alcohol intake, body mass index, diabetes status, chronic kidney disease status, hemoglobin A1c level, C-reactive protein level, medications, and prevalent cardiovascular diseases or heart failure. MAIN OUTCOME AND MEASURES: Incident AF events were identified using 12-lead electrocardiographic findings, hospital discharge records, and Medicare claims data. RESULTS: During a median follow-up of 14.1 years, 643 AF events were identified. No association was found between any retinal microvascular signs and incident AF except for retinal focal arteriolar narrowing (hazard ratio, 1.75; 95% confidence interval, 1.06-2.87) in the overall population. However, in the subgroup analyses by gender, wider CRVE was associated with a higher risk of incident AF in women, but not in men (hazard ratio for every 10-µm increase in CRVE, 1.08 [95% confidence interval, 1.01-1.15] and 0.97 [95% confidence interval, 0.92-1.03], respectively; P = 0.041 for interaction). CONCLUSIONS: No consistent pattern of association was found between retinal microvascular signs and incident AF. We observed an association in women, but not in men, of wider retinal venular calibers with incidence of AF. The reasons for a possible interaction are incompletely understood.

11.
Pharmacoepidemiol Drug Saf ; 29(9): 1175-1182, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32558036

RESUMO

PURPOSE: Opioids, gabapentinoids, and nonsteroidal anti-inflammatory drugs (NSAIDs) may have adverse cardiovascular effects. We evaluated whether these medications were associated with incident clinically detected atrial fibrillation (AF) or monitor-detected supraventricular ectopy (SVE), including premature atrial contractions (PACs) and supraventricular tachycardia (SVT). METHODS: We used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study that enrolled 6814 Americans without clinically detected cardiovascular disease in 2000 to 2002. At the 2016 to 2018 examination, 1557 individuals received ambulatory electrocardiographic (ECG) monitoring. Longitudinal analyses investigated time-varying medication exposures at the first five exams (through 2011) in relation to incident clinically detected AF through 2015 using Cox proportional hazards regression models. Cross-sectional analyses investigated medication exposures at 2016 to 2018 examination and the risk of monitor-detected SVE using linear regression models. RESULTS: The longitudinal cohort included 6652 participants. During 12.4 years of mean follow-up, 982 participants (14.7%) experienced incident clinically detected AF. Use of opioids, gabapentinoids, and NSAIDs were not associated with incident AF. The cross-sectional analysis included 1435 participants with ECG monitoring. Gabapentinoid use was associated with an 84% greater average frequency of PACs/hour (95% CI, 25%-171%) and a 44% greater average number of runs of SVT/day (95% CI, 3%-100%). No associations were found with use of opioids or NSAIDs in cross-sectional analyses. CONCLUSIONS: In this study, gabapentinoid use was associated with SVE. Given the rapid increase in gabapentinoid use, additional studies are needed to clarify whether these medications cause cardiovascular complications.

12.
J Pain Symptom Manage ; 60(4): 765-773, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32389606

RESUMO

CONTEXT: Goal-concordant care is an important indicator of high-quality care in serious illness. OBJECTIVES: To estimate the prevalence of patient-reported receipt of goal-concordant care among seriously ill outpatients and identify factors associated with the absence of patient-reported goal concordance. METHODS: Analysis of enrollment surveys from a multicenter cluster-randomized trial of outpatients with serious illness. Patients reported their prioritized health care goal and the focus of their current medical care; these items were matched to define receipt of goal-concordant care. RESULTS: Of 405 patients with a prioritized health care goal, 58% reported receipt of goal-concordant care, 17% goal-discordant care, and 25% were uncertain of the focus of their care. Patient-reported receipt of goal concordance differed by patient goal. For patients who prioritized extending life, 86% reported goal-concordant care, 2% goal-discordant care, and 12% were uncertain of the focus of their care. For patients who prioritized relief of pain and discomfort, 51% reported goal-concordant care, 21% goal-discordant care, and 28% were uncertain of the focus of their care. Patients who prioritized a goal of relief of pain and discomfort were more likely to report goal-discordant care than patients who prioritized a goal of extending life (relative risk ratio 22.20; 95% CI 4.59, 107.38). CONCLUSION: Seriously ill outpatients who prioritize a goal of relief of pain and discomfort are less likely to report receipt of goal-concordant care than patients who prioritize extending life. Future interventions designed to improve receipt of goal-concordant care should focus on identifying patients who prioritize relief of pain and discomfort and promoting care aligned with that goal.

13.
J Cardiovasc Magn Reson ; 22(1): 36, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32434529

RESUMO

BACKGROUND: While studies of the left atrium (LA) have demonstrated associations between volumes and emptying fraction with atrial fibrillation (AF), the contribution of right atrial (RA) abnormalities to incident AF remains poorly understood. OBJECTIVES: Assess the association between RA structure and function with incident AF using feature-tracking cardiovascular magnetic resonance (CMR). METHODS: This is a prospective cohort study of all participants in the Multi-Ethnic Study of Atherosclerosis with baseline CMR, sinus rhythm, and free of clinical cardiovascular disease at study initiation. RA volume, strain, and emptying fraction in participants with incident AF (n = 368) were compared against AF-free (n = 2779). Cox proportional-hazards models assessed association between variables. RESULTS: Participants were aged 60 ± 10 yrs., 55% female, and followed an average 11.2 years. Individuals developing AF had higher baseline RA maximum volume index (mean ± standard deviation [SD]: 24 ± 9 vs 22 ± 8 mL/m2, p = 0.002) and minimum volume index (13 ± 7 vs 12 ± 6 mL/m2, p < 0.001), and lower baseline RA emptying fraction (45 ± 15% vs 47 ± 15%, p = 0.02), peak global strain (34 ± 17% vs 36 ± 19%, p < 0.001), and peak free-wall strain (40 ± 23% vs 42 ± 26%, p = 0.049) compared with the AF-free population. After adjusting for traditional cardiovascular risk factors and LA volume and function, we found RA maximum volume index (hazards ratio [HR]: 1.13 per SD, p = 0.041) and minimum volume index (HR: 1.12 per SD, p = 0.037) were independently associated with incident AF. CONCLUSIONS: In a large multiethnic population, higher RA volume indices were independently associated with incident AF after adjustment for conventional cardiovascular risk factors and LA parameters. It is unclear if this predictive value persists when additional adjustment is made for ventricular parameters.


Assuntos
Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/etnologia , Função do Átrio Direito , Remodelamento Atrial , Átrios do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/fisiopatologia , Feminino , Átrios do Coração/fisiopatologia , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
14.
Acad Radiol ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32279912

RESUMO

RATIONALE AND OBJECTIVES: Left Atrial (LA) adverse remodeling is an important predictor of morbidity and mortality in several cardiovascular (CV) diseases. Our goals were to quantify and provide reference ranges for LA structure and function using feature tracking cine cardiac magnetic resonance. MATERIALS AND METHODS: 2526 participants of the Multiethnic Study of Atherosclerosis study who had feature tracking cine cardiac magnetic resonance derived LA data and were free of atrial fibrillation/flutter and prior CV events at year five follow-up examination (2010-2012) were included in this study. LA phasic indexed volumes: maximum (LAVi max), minimum (LAVi min), and preatrial contraction (LAVi preA); LA empty fractions: total, passive, and active (LAtEF, LApEF, and LAaEF); LA longitudinal strain: maximum and preatrial contraction (S max and S preA); and LA longitudinal strain rate: systolic (SR max) and early/late diastolic (SR e and SR a) were measured. Age, gender, and race/ethnicity-specific reference ranges were identified. Also, reference values in a select subgroup of healthy participants free of traditional CV risk factors at the time of exam date were reported. RESULTS: The mean ± SD for LAVi max, LAVi min, LAVi preA, S max, SR e, and SR a were in the 45-65-year-old participants: (33.8 ± 10 mL/m2), (14.5 ± 6.4 mL/m2), (24.8 ± 8.2 mL/m2), (34.6 ± 13.8 %), (-1.4 ± 0.7 s-1), (-2.1 ± 1 s-1) and in the ≥ 65-year-old participants: (35 ± 11.5 mL/m2), (16.6 ± 8.3 mL/m2), (27.6 ± 9.9 mL/m2), (31.2 ± 14.3 %), (-1 ± 0.6 s-1), (-2.1 ± 1 s-1) respectively. Younger individuals had Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation smaller LA volumes and better LA function compared to their older counterparts. Similar findings were observed in Chinese-Americans as compared to Whites. CONCLUSION: This study provides reference values of LA structure and function parameters from a healthy multiethnic community-based population aged 53-94 years evaluated by FTMRI.

16.
BMJ Open ; 10(3): e031487, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32198297

RESUMO

OBJECTIVE: Anaemia is common among people living with HIV (PLWH) and has been associated with certain, often older, antiretroviral medications. Information on current antiretroviral therapy (ART) and anaemia is limited. The objective was to compare the associations between anaemia incidence or haemoglobin change with core ART classes in the current ART era. DESIGN: Retrospective cohort study. SETTING: USA-based prospective clinical cohort of PLWH aged 18 and above receiving care at eight sites between January 2010 and March 2018. PARTICIPANTS: 16 505 PLWH were included in this study. MAIN OUTCOME MEASURES: Anaemia risk and haemoglobin change were estimated among PLWH for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI)-based regimen, relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based reference. We also examined PLWH on regimens containing multiple core classes. Cox proportional hazards regression analyses were conducted to measure the associations between time-updated ART classes and incident anaemia or severe anaemia. Linear mixed effects models were used to examine the relationships between ART classes and haemoglobin change. RESULTS: During a median of 4.9 years of follow-up, 1040 developed anaemia and 488 developed severe anaemia. Compared with NNRTI use, INSTI-based regimens were associated with an increased risk of anaemia (adjusted HR (aHR) 1.26, 95% CI 1.00 to 1.58) and severe anaemia (aHR 1.51, 95% CI 1.07 to 2.11) and a decrease in haemoglobin level. Time on multiple core classes was also associated with increased anaemia risk (aHR 1.39, 95% CI 1.13 to 1.70), while no associations were found for PI use. CONCLUSION: These findings suggest INSTI use may increase the risk of anaemia. If confirmed, screening for anaemia development in users of INSTIs may be beneficial. Further research into the underlying mechanisms is warranted.

17.
J Am Heart Assoc ; 9(4): e012853, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32019406

RESUMO

Background Ceramides exhibit multiple biological activities that may influence the pathophysiological characteristics of atrial fibrillation (AF). Whether the length of the saturated fatty acid carried by the ceramide or their sphingomyelin precursors are associated with AF risk is not known. Methods and Results Among 4206 CHS (Cardiovascular Health Study) participants (mean age, 76 years; 40% men) who were free of prevalent AF at baseline, we identified 1198 incident AF cases over a median 8.7 years of follow-up. We examined 8 sphingolipid species: ceramide and sphingomyelin species with palmitic acid and species with very-long-chain saturated fatty acids: arachidic; behenic; and lignoceric. In adjusted Cox regression analyses, ceramides and sphingomyelins with very-long-chain saturated fatty acids were associated with reduced AF risk (ie, per 2-fold higher ceramide with behenic acid hazard ratio, 0.71; 95% CI, 0.59-0.86; sphingomyelin with behenic acid hazard ratio, 0.60; 95% CI, 0.46-0.77). In contrast, ceramides and sphingomyelins with palmitic acid were associated with increased AF risk (ceramide with palmitic acid hazard ratio, 1.31; 95% CI, 1.03-1.66; sphingomyelin with palmitic acid hazard ratio, 1.73; 95% CI, 1.18-2.55). Associations were attenuated with adjustment for NT-proBNP (N-terminal pro-B-type natriuretic peptide), but did not differ significantly by age, sex, race, body mass index, or history of coronary heart disease. Conclusions Our findings suggest that several ceramide and sphingomyelin species are associated with incident AF, and that these associations differ on the basis of the fatty acid. Ceramides and sphingomyelins with palmitic acid were associated with increased AF risk, whereas ceramides and sphingomyelins with very-long-chain saturated fatty acids were associated with reduced AF risk.

18.
Circ Arrhythm Electrophysiol ; 13(2): e007685, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32013555

RESUMO

BACKGROUND: Asthma and atrial fibrillation (AF) share an underlying inflammatory pathophysiology. We hypothesized that persistent asthmatics are at higher risk for developing AF and that this association would be attenuated by adjustment for baseline markers of systemic inflammation. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective longitudinal study of adults free of cardiovascular disease at baseline. Presence of asthma was determined at exam 1. Persistent asthma was defined as asthma requiring use of controller medications. Intermittent asthma was defined as asthma without use of controller medications. Participants were followed for a median of 12.9 (interquartile range, 10-13.6) years for incident AF. Multivariable Cox regression models were used to assess associations of asthma subtype and AF. RESULTS: The 6615 participants were a mean (SD) 62.0 (10.2) years old (47% male, 27% black, 12% Chinese, and 22% Hispanic). AF incidence rates were 0.11 (95% CI, 0.01-0.12) events/10 person-years for nonasthmatics, 0.11 (95% CI, 0.08-0.14) events/10 person-years for intermittent asthmatics, and 0.19 (95% CI, 0.120.49) events/10 person-years for persistent asthmatics (log-rank P=0.008). In risk-factor adjusted models, persistent asthmatics had a greater risk of incident AF (hazard ratio, 1.49 [95% CI, 1.03-2.14], P=0.03). IL (Interleukin)-6 (hazard ratio, 1.26 [95% CI, 1.13-1.42]), TNF (tumor necrosis factor)-α receptor 1 (hazard ratio, 1.09 [95% CI, 1.08-1.11]) and D-dimer (hazard ratio, 1.10 [95% CI, 1.02-1.20]) predicted incident AF, but the relationship between asthma and incident AF was not attenuated by adjustment for any inflammation marker (IL-6, CRP [C-reactive protein], TNF-α R1, D-dimer, and fibrinogen). CONCLUSIONS: In a large multiethnic cohort with nearly 13 years follow-up, persistent asthma was associated with increased risk for incident AF. This association was not attenuated by adjustment for baseline inflammatory biomarkers.


Assuntos
Asma/complicações , Fibrilação Atrial/etiologia , Asma/etnologia , Asma/fisiopatologia , Fibrilação Atrial/etnologia , Fibrilação Atrial/fisiopatologia , Biomarcadores/sangue , Eletrocardiografia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estados Unidos
19.
Circ Arrhythm Electrophysiol ; 13(1): e007698, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31934795

RESUMO

BACKGROUND: African Americans are consistently found to have a lower prevalence of clinically detected atrial fibrillation (AF) than whites, despite a higher prevalence of major AF risk factors and higher risk of ischemic stroke. Long-term ambulatory ECG monitors provide the opportunity for unbiased AF detection. We determined differences by race/ethnicity in the prevalence of clinically detected AF and in the proportion with monitor-detected AF. METHODS: We conducted a cross-sectional analysis in the MESA (Multi-Ethnic Study of Atherosclerosis), a community-based cohort study that enrolled 6814 Americans free of clinically recognized cardiovascular disease in 2000 to 2002. At the 2016 to 2018 examination, 1556 individuals participated in an ancillary study involving ambulatory ECG monitoring and had follow-up for clinically detected AF since cohort entry. RESULTS: Among 1556 participants, 41% were white, 25% African American, 21% Hispanic, and 14% Chinese; 51% were women; and the mean age was 74 years. The prevalence of clinically detected AF after 14.4 years' follow-up was 11.3% in whites, 6.6% in African Americans, 7.8% in Hispanics, and 9.9% in Chinese and was significantly lower in African Americans than in whites, in both unadjusted and risk factor-adjusted analyses (adjusted rate difference, -6.6% [95% CI, -10.1% to -3.1%]; P<0.001). By contrast, in the same individuals, the proportion with monitor-detected AF using a 14-day ambulatory ECG monitor was similar in the 4 race/ethnic groups: 7.1%, 6.4%, 6.9%, and 5.2%, respectively (compared with whites, all P>0.5). CONCLUSIONS: The prevalence of clinically detected AF was substantially lower in African American than in white participants, without or with adjustment for AF risk factors. However, unbiased AF detection by ambulatory monitoring in the same individuals revealed little difference in the proportion with AF by race/ethnicity. These findings provide support for the hypothesis of differential detection by race/ethnicity in the clinical recognition of AF, which may have important implications for stroke prevention.


Assuntos
Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/etnologia , Grupos de Populações Continentais/etnologia , Eletrocardiografia/métodos , Grupos Étnicos , Afro-Americanos/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Americanos Asiáticos/estatística & dados numéricos , Intervalos de Confiança , Estudos Transversais , Eletrocardiografia Ambulatorial/métodos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Estados Unidos/epidemiologia
20.
J Thromb Haemost ; 18(2): 445-453, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31680443

RESUMO

BACKGROUND: Rare coding mutations underlying deficiencies of antithrombin and proteins C and S contribute to familial venous thromboembolism (VTE). It is uncertain whether rare variants play a role in the etiology of VTE in the general population. OBJECTIVES: We conducted a deep whole-exome sequencing (WES) study to investigate the associations between rare coding variants and the risk of VTE in two population-based prospective cohorts. PATIENTS/METHODS: Whole-exome sequencing was performed in the Longitudinal Investigation of Thromboembolism Etiology (LITE), which combines the Atherosclerosis Risk in Communities (ARIC) study (316 incident VTE events among 3159 African Americans [AAs] and 458 incident VTEs among 7772 European Americans [EAs]) and the Cardiovascular Healthy Study (CHS; 60 incident VTEs among 1751 EAs). We performed gene-based tests of rare variants (allele frequency < 1%, exome-wide significance P < 1.47 × 10-6 ) separately in each study and ancestry group, and meta-analyzed the results for the EAs in ARIC and CHS. RESULTS: In the meta-analysis of EAs, we identified one gene, PROC, in which the burden of rare, coding variants was significantly associated with increased risk of VTE (HR = 5.42 [3.11, 9.42] for carriers versus non-carriers, P = 2.27 × 10-9 ). In ARIC EAs, carriers of the PROC rare variants had on average 0.75 standard deviation (SD) lower concentrations of plasma protein C and 0.28 SD higher D-dimer (P < .05) than non-carriers. Adjustment for low protein C status did not eliminate the association of PROC burden with VTE. In AAs, rare coding PROC variants were not associated with VTE. CONCLUSIONS: Rare coding variants in PROC contribute to increased VTE risk in EAs in this general population sample.

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