Publications by authors named "Susan R Heckbert"

490 Publications

Left Atrioventricular Coupling Index to Predict Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis.

Front Cardiovasc Med 2021 1;8:704611. Epub 2021 Sep 1.

Division of Cardiology, Johns Hopkins Hospital, Johns Hopkins University, School of Medicine, Baltimore, MD, United States.

Although left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic value as predictors of heart failure (HF), the close physiological relationship between the LA and LV suggest that the assessment of LA/LV coupling could better reflect left atrioventricular dysfunction and be a better predictor of HF. We investigated the prognostic value of a left atrioventricular coupling index (LACI), measured by cardiovascular magnetic resonance (CMR), as well as change in LACI to predict incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA). In the MESA, 2,250 study participants, free of clinically recognized HF and cardiovascular disease (CVD) at baseline, had LACI assessed by CMR imaging at baseline (Exam 1, 2000-2002), and 10 years later (Exam 5, 2010-2012). Left atrioventricular coupling index was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident HF after adjustment for traditional MESA-HF risk factors. The incremental risk prediction was calculated using C-statistic, categorical net reclassification index (NRI) and integrative discrimination index (IDI). Among the 2,250 participants (mean age 59.3 ± 9.3 years and 47.6% male participants), 50 incident HF events occurred over 6.8 ± 1.3 years after the second CMR exam. After adjustment, greater LACI and ΔLACI were independently associated with HF (adjusted HR 1.44, 95% CI [1.25-1.66] and adjusted HR 1.55, 95% CI [1.30-1.85], respectively; both < 0.0001). Adjusted models for LACI showed significant improvement in model discrimination and reclassification compared to currently used HF risk score model for predicting HF incidence (C-statistic: 0.81 vs. 0.77; NRI = 0.411; IDI = 0.043). After adjustment, ΔLACI showed also significant improvement in model discrimination compared to the multivariable model with traditional MESA-HF risk factors for predicting incident HF (C-statistic: 0.82 vs. 0.77; NRI = 0.491; IDI = 0.058). In a multi-ethnic population, atrioventricular coupling (LACI), and coupling change (ΔLACI) are independently associated with incident HF. Both have incremental prognostic value for predicting HF events over traditional HF risk factors.
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http://dx.doi.org/10.3389/fcvm.2021.704611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442844PMC
September 2021

Adhesion pathway proteins and risk of atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis.

BMC Cardiovasc Disord 2021 Sep 14;21(1):436. Epub 2021 Sep 14.

Department of Quantitative Health Sciences, Mayo Clinic, 200 First Street Southwest, Rochester, MN, USA.

Background: The cellular adhesion pathway has been suggested as playing an important role in the pathogenesis of atrial fibrillation (AF). However, prior studies that have investigated the role of adhesion pathway proteins in risk of AF have been limited in the number of proteins that were studied and in the ethnic and racial diversity of the study population. Therefore we aimed to study the associations of fifteen adhesion pathway proteins with incident AF in a large, diverse population.

Methods: Multi-Ethnic Study of Atherosclerosis participants from four races/ethnicities (n = 2504) with protein levels measured were followed for incident AF (n = 253). HGF protein was measured on Exam 1 samples (N = 6669; AF n = 851). Cox proportional hazards regression was used to assess the association of AF with 15 adhesion pathway proteins. Bonferroni correction was applied to account for multiple comparisons.

Results: After adjusting for potential confounding variables (age, sex, race/ethnicity, height, body mass index, systolic blood pressure, antihypertension therapy, diabetes status, current smoker, current alcohol use, and total and HDL cholesterol), and accounting for multiple testing (P < 0.05/15 = 0.0033), circulating levels of the following proteins were positively associated with a higher risk of AF: MMP-2 (HR per standard deviation increment, 1.27; 95% CI 1.11‒1.45), TIMP-2 (HR 1.28; 95% CI 1.12‒1.46), VCAM-1 (HR 1.32; 95% CI 1.16‒1.50), and SLPI (HR 1.22; 95% CI 1.07‒1.38). The association between proteins and AF did not differ by race/ethnicity.

Conclusions: Circulating levels of MMP-2, TIMP-2, VCAM-1, and SLPI were positively associated with an increased risk of incident AF in a diverse population. Our findings suggest that adhesion pathway proteins may be important risk predictors of AF.
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http://dx.doi.org/10.1186/s12872-021-02241-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442417PMC
September 2021

Prediction of Cognitive Decline Using Heart Rate Fragmentation Analysis: The Multi-Ethnic Study of Atherosclerosis.

Front Aging Neurosci 2021 26;13:708130. Epub 2021 Aug 26.

Margret and H. A. Rey Institute for Non-linear Dynamics in Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

Heart rate fragmentation (HRF), a new non-invasive metric quantifying cardiac neuroautonomic function, is associated with increasing age and cardiovascular disease. Since these are risk factors for cognitive decline and dementia, in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated whether disrupted cardiac neuroautonomic function, evidenced by increased HRF, would be associated with worse cognitive function assessed concurrently and at a later examination, and with greater cognitive decline. HRF was derived from the ECG channel of the polysomnographic recordings obtained in an ancillary study ( = 1,897) conducted in conjunction with MESA (2010-2012). Cognitive function was assessed at and 6.4 ± 0.5 years later at (2016-2018) with tests of global cognitive performance (the Cognitive Abilities Screening Instrument, CASI), processing speed (Digit Symbol Coding, DSC) and working memory (Digit Span). Multivariable regression models were used to quantify the associations between HRF indices and cognitive scores. The participants' mean age was 68 ± 9 years (54% female). Higher HRF at baseline was independently associated with lower cognitive scores at both and . Specifically, in cross-sectional analyses, a one-standard deviation (SD) (13.7%) increase in HRF was associated with a 0.51 (95% CI: 0.17-0.86) points reduction in CASI and a 1.12 (0.34-1.90) points reduction in DSC. Quantitatively similar effects were obtained in longitudinal analyses. A one-SD increase in HRF was associated with a 0.44 (0.03-0.86) and a 1.04 (0.28-1.81) points reduction in CASI and DSC from exams 5 to 6, respectively. HRF added predictive value to the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE-APOE-ε4) risk score and to models adjusted for serum concentration of NT-proBNP, an analyte associated with cognitive impairment and dementia. Increased HRF assessed during sleep was independently associated with diminished cognitive performance (concurrent and future) and with greater cognitive decline. These findings lend support to the links between cardiac neuroautonomic regulation and cognitive function. As a non-invasive, repeatable and inexpensive probe, HRF technology may be useful in monitoring cognitive status, predicting risk of dementia and assessing therapeutic interventions.
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http://dx.doi.org/10.3389/fnagi.2021.708130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428192PMC
August 2021

Association Between Testosterone Treatment and Risk of Incident Cardiovascular Events Among US Male Veterans With Low Testosterone Levels and Multiple Medical Comorbidities.

J Am Heart Assoc 2021 Sep 21;10(17):e020562. Epub 2021 Aug 21.

VA Puget Sound Health Care System (VAPSHCS) Seattle WA.

Background Testosterone treatment is common in men, although risks for major cardiovascular events are unclear. Methods and Results A study was conducted in US male veterans, aged ≥40 years, with low serum testosterone and multiple medical comorbidities and without history of myocardial infarction, stroke, venous thromboembolism, prostate cancer, or testosterone treatment in the prior year. For the primary outcome, we examined if testosterone treatment was associated with a composite cardiovascular outcome (incident myocardial infarction, ischemic stroke, or venous thromboembolism). Testosterone use was modeled as intramuscular or transdermal and as current use, former use, and no use. Current testosterone users were compared with former users to reduce confounding by indication. The cohort consisted of 204 857 men with a mean (SD) age of 60.9 (9.9) years and 4.7 (3.5) chronic medical conditions. During follow-up of 4.3 (2.8) years, 12 645 composite cardiovascular events occurred. In adjusted Cox regression analyses, current use of transdermal testosterone was not associated with risk for the composite cardiovascular outcome (hazard ratio [HR], 0.89; 95% CI, 0.76-1.05) in those without prevalent cardiovascular disease, and in those with prevalent cardiovascular disease was associated with lower risk (HR, 0.80; 95% CI, 0.70-0.91). In similar analyses, current use of intramuscular testosterone was not associated with risk for the composite cardiovascular outcome in men without or with prevalent cardiovascular disease (HR, 0.91; 95% CI, 0.80-1.04; HR, 0.98; 95% CI, 0.89-1.09, respectively). Conclusions In a large cohort of men without a history of myocardial infarction, stroke, or venous thromboembolism, testosterone treatment was not associated with increased risk for incident composite cardiovascular events.
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http://dx.doi.org/10.1161/JAHA.120.020562DOI Listing
September 2021

Longitudinal Associations between the Neighborhood Built Environment and Cognition in US Older Adults: The Multi-Ethnic Study of Atherosclerosis.

Int J Environ Res Public Health 2021 07 28;18(15). Epub 2021 Jul 28.

Department of Internal Medicine, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27109, USA.

Few studies have examined associations between neighborhood built environments (BE) and longitudinally measured cognition. We examined whether four BE characteristics were associated with six-year change in global cognition and processing speed. We obtained data on 1816 participants without dementia from the Multi-Ethnic Study of Atherosclerosis. BE measures included social destination density, walking destination density, proportion of land dedicated to retail, and network ratio (street connectivity). Global cognition was measured with the Cognitive Abilities Screening Instrument (CASI) and processing speed with the Digit Symbol Coding test (DSC). Multivariable random intercept logistic models tested associations between neighborhood BE at 2010-2012 and maintained/improved cognition (versus decline) from 2010-2018, and mediation by minutes of physical activity (PA)/week. The sample was an average of 67 years old (standard deviation = 8.2) (first cognitive measurement) and racially/ethnically diverse (29% African American, 11% Chinese, 17% Hispanic, 44% White). Compared to individuals with no walking destinations in the 1-mile surrounding their residence, those with 716 walking destinations (maximum observed) were 1.24 times more likely to have maintain/improved DSC score (Odds ratio: 1.24; 95% confidence interval: 1.03-1.45). No other associations were observed between BE and cognition, and PA minutes/week did not mediate the association between walking destination density and DSC change. This study provides limited evidence for an association between greater neighborhood walking destinations and maintained/improved processing speed in older age and no evidence for associations between the other BE characteristics and cognition. Future studies with finer grained BE and cognitive measures and longer-term follow up may be required.
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http://dx.doi.org/10.3390/ijerph18157973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345405PMC
July 2021

Early Cumulative Fluid Balance and Outcomes in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients With Acute Respiratory Failure: A Multicenter Study.

Front Oncol 2021 20;11:705602. Epub 2021 Jul 20.

Division of Critical Care, Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.

Objectives: To evaluate the associations between early cumulative fluid balance (CFB) and outcomes among critically ill pediatric allogeneic hematopoietic cell transplant (HCT) recipients with acute respiratory failure, and determine if these associations vary by treatment with renal replacement therapy (RRT).

Methods: We performed a secondary analysis of a multicenter retrospective cohort of patients (1mo - 21yrs) post-allogeneic HCT with acute respiratory failure treated with invasive mechanical ventilation (IMV) from 2009 to 2014. Fluid intake and output were measured daily for the first week of IMV (day 0 = day of intubation). The exposure, day 3 CFB (CFB from day 0 through day 3 of IMV), was calculated using the equation [Fluid in - Fluid out] (liters)/[PICU admission weight](kg)*100. We measured the association between day 3 CFB and PICU mortality with logistic regression, and the rate of extubation at 28 and 60 days with competing risk regression (PICU mortality = competing risk).

Results: 198 patients were included in the study. Mean % CFB for the cohort was positive on day 0 of IMV, and increased further on days 1-7 of IMV. For each 1% increase in day 3 CFB, the odds of PICU mortality were 3% higher (adjusted odds ratio (aOR) 1.03, 95% CI 1.00-1.07), and the rate of extubation was 3% lower at 28 days (adjusted subdistribution hazard ratio (aSHR) 0.97, 95% CI 0.95-0.98) and 3% lower at 60 days (aSHR 0.97, 95% CI 0.95-0.98). When day 3 CFB was dichotomized, 161 (81%) had positive and 37 (19%) had negative day 3 CFB. Positive day 3 CFB was associated with higher PICU mortality (aOR 3.42, 95% CI 1.48-7.87) and a lower rate of extubation at 28 days (aSHR 0.30, 95% CI 0.18-0.48) and 60 days (aSHR 0.30, 95% 0.19-0.48). On stratified analysis, the association between positive day 3 CFB and PICU mortality was significantly stronger in those not treated with RRT (no RRT: aOR 9.11, 95% CI 2.29-36.22; RRT: aOR 1.40, 95% CI 0.42-4.74).

Conclusions: Among critically ill pediatric allogeneic HCT recipients with acute respiratory failure, positive and increasing early CFB were independently associated with adverse outcomes.
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http://dx.doi.org/10.3389/fonc.2021.705602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329703PMC
July 2021

Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis.

Circ Genom Precis Med 2021 Aug 28;14(4):e003300. Epub 2021 Jul 28.

Regeneron Genetics Center, Tarrytown, NY. Departments of Medicine, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (S.R.).

Background: Alterations in electrocardiographic (ECG) intervals are well-known markers for arrhythmia and sudden cardiac death (SCD) risk. While the genetics of arrhythmia syndromes have been studied, relations between electrocardiographic intervals and rare genetic variation at a population level are poorly understood.

Methods: Using a discovery sample of 29 000 individuals with whole-genome sequencing from Trans-Omics in Precision Medicine and replication in nearly 100 000 with whole-exome sequencing from the UK Biobank and MyCode, we examined associations between low-frequency and rare coding variants with 5 routinely measured electrocardiographic traits (RR, P-wave, PR, and QRS intervals and corrected QT interval).

Results: We found that rare variants associated with population-based electrocardiographic intervals identify established monogenic SCD genes (, , and ), a controversial monogenic SCD gene (), and novel genes ( and ) involved in cardiac conduction. Loss-of-function and pathogenic variants, carried by 0.1% of individuals, were associated with a nearly 6-fold increased odds of the first-degree atrioventricular block (=8.4×10). Similar variants in and (0.2% of individuals) were associated with a 23-fold increased odds of marked corrected QT interval prolongation (=4×10), a marker of SCD risk. Incomplete penetrance of such deleterious variation was common as over 70% of carriers had normal electrocardiographic intervals.

Conclusions: Our findings indicate that large-scale high-depth sequence data and electrocardiographic analysis identifies monogenic arrhythmia susceptibility genes and rare variants with large effects. Known pathogenic variation in conventional arrhythmia and SCD genes exhibited incomplete penetrance and accounted for only a small fraction of marked electrocardiographic interval prolongation.
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http://dx.doi.org/10.1161/CIRCGEN.120.003300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373440PMC
August 2021

DEEPMIR: a deep neural network for differential detection of cerebral microbleeds and iron deposits in MRI.

Sci Rep 2021 Jul 8;11(1):14124. Epub 2021 Jul 8.

Neuroimage Analytics Laboratory (NAL) and the Biggs Institute Neuroimaging Core (BINC), Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center San Antonio (UTHSCSA), San Antonio, TX, USA.

Lobar cerebral microbleeds (CMBs) and localized non-hemorrhage iron deposits in the basal ganglia have been associated with brain aging, vascular disease and neurodegenerative disorders. Particularly, CMBs are small lesions and require multiple neuroimaging modalities for accurate detection. Quantitative susceptibility mapping (QSM) derived from in vivo magnetic resonance imaging (MRI) is necessary to differentiate between iron content and mineralization. We set out to develop a deep learning-based segmentation method suitable for segmenting both CMBs and iron deposits. We included a convenience sample of 24 participants from the MESA cohort and used T2-weighted images, susceptibility weighted imaging (SWI), and QSM to segment the two types of lesions. We developed a protocol for simultaneous manual annotation of CMBs and non-hemorrhage iron deposits in the basal ganglia. This manual annotation was then used to train a deep convolution neural network (CNN). Specifically, we adapted the U-Net model with a higher number of resolution layers to be able to detect small lesions such as CMBs from standard resolution MRI. We tested different combinations of the three modalities to determine the most informative data sources for the detection tasks. In the detection of CMBs using single class and multiclass models, we achieved an average sensitivity and precision of between 0.84-0.88 and 0.40-0.59, respectively. The same framework detected non-hemorrhage iron deposits with an average sensitivity and precision of about 0.75-0.81 and 0.62-0.75, respectively. Our results showed that deep learning could automate the detection of small vessel disease lesions and including multimodal MR data (particularly QSM) can improve the detection of CMB and non-hemorrhage iron deposits with sensitivity and precision that is compatible with use in large-scale research studies.
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http://dx.doi.org/10.1038/s41598-021-93427-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266884PMC
July 2021

Left Atrioventricular Coupling Index as a Prognostic Marker of Cardiovascular Events: The MESA Study.

Hypertension 2021 Sep 6;78(3):661-671. Epub 2021 Jul 6.

From the Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (T.P., B.A.V., H.D.D.V., Y.K., M.S., E.X., W.S.P., C.O.W., J.A.C.L.).

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363553PMC
September 2021

Association of Vascular Risk Scores and Cognitive Performance in a Diverse Cohort: The Multi-Ethnic Study of Atherosclerosis.

J Gerontol A Biol Sci Med Sci 2021 Jul 3. Epub 2021 Jul 3.

Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine.

Background: Vascular risk scores are associated with incident dementia. Information regarding their association with cognitive performance and decline in racially/ethnically diverse cohorts is lacking.

Methods: In 4392 Multi-Ethnic Study of Atherosclerosis participants (aged 60.1±9.4 years; 53% women; 41% white, 11% Chinese-American, 26% African-American, 21% Hispanic), we compared associations of Exam 1 (2000-02) Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham stroke (FSRP), and atherosclerotic disease pooled cohort equation (ASCVD-PCE) risk scores with Exam 5 (2010-12) Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS) cognitive test performance using multivariable linear regression, and examined racial/ethnic interactions. In 1838 participants with repeat CASI data at Exam 6 (2016-18), we related risk scores to odds of a 1-standard deviation (SD) decline in CASI performance using multivariable logistic regression.

Results: SD increments in each risk score were associated with worse cognitive performance. CAIDE had stronger associations with CASI performance than the FSRP and ASCVD-PCE, but associations of ASCVD-PCE with the DSC and DS were similar to CAIDE (difference in β [95% CI] = -0.57 [-1.48, 0.34] and -0.21 [-0.43, 0.01], respectively). Race/ethnicity modified associations. For example, associations between CAIDE and CASI were greater in African-Americans and Hispanics than whites (difference in β = 0.69 [0.02, 1.36] and 1.67 [0.95, 2.39], respectively). Risk scores were comparably associated with decline in CASI performance.

Conclusions: Antecedent vascular risk scores are associated with cognitive performance and decline in the four most common US racial/ethnic groups, but associations differ among risk scores and by race/ethnicity.
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http://dx.doi.org/10.1093/gerona/glab189DOI Listing
July 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Associations Between Neighborhood Park Access and Longitudinal Change in Cognition in Older Adults: The Multi-Ethnic Study of Atherosclerosis.

J Alzheimers Dis 2021 ;82(1):221-233

Departments of Internal Medicine and Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Background: Preliminary evidence suggests associations between neighborhood park access and better late-life cognition and reduced Alzheimer's disease (AD) risk.

Objective: Examine associations between neighborhood park access and longitudinal change in cognition among U.S. older adults without dementia.

Methods: We used 2000-2018 observational data from the population-based, multi-site Multi-Ethnic Study of Atherosclerosis (n = 1,733). Measures included proportion of neighborhood park space (park access), distance to nearest park, and 6-year dichotomous and continuous change in scores on the Cognitive Abilities Screening Instrument (CASI; global cognition) and Digit Symbol Coding task (processing speed). Multivariable random intercept models tested main associations and mediation by depressive symptoms, physical activity, and PM2.5 exposure. Effect modification by race (African Americans/Blacks versus Whites) was tested using interaction terms.

Results: Greater park access (equivalent to 10%more in 1/2-mile around home) was associated with maintained/improved CASI score over six years independent of several covariates including individual- and neighborhood-level socioeconomic status (Odds ratio: 1.04; 95%confidence interval: 1.00-1.08). No other associations were observed with the dichotomous or continuous measures of cognitive change and no mediators were found. While a borderline association was seen between greater park access and maintained/improved CASI for African Americans/Blacks but not for Whites, effect modification was not confirmed by testing interaction terms.

Conclusion: Neighborhood park access may help maintain/improve late-life global cognition. However, our findings need replication in other population-based studies and regions. Additionally, studies are needed to determine if associations between park access and change in cognition vary by race/ethnicity to inform intervention efforts.
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http://dx.doi.org/10.3233/JAD-210370DOI Listing
September 2021

Longitudinal Measures of Blood Pressure and Subclinical Atrial Arrhythmias: The MESA and the ARIC Study.

J Am Heart Assoc 2021 Jun 20;10(11):e020260. Epub 2021 May 20.

Cardiovascular Division Department of Medicine University of Minnesota Medical School Minneapolis MN.

Background High blood pressure (BP) is a well-known risk factor for atrial fibrillation (AF), but a single BP measurement may provide limited information about AF risk in older adults. Methods and Results This study included 1256 MESA (Multi-Ethnic Study of Atherosclerosis) and 1948 ARIC (Atherosclerosis Risk in Communities) study participants who underwent extended ambulatory electrocardiographic monitoring and who were free of clinically detected cardiovascular disease, including AF. Using BP measurements from 6 examinations (2000-2018 in MESA and 1987-2017 in ARIC study), we calculated individual long-term mean, trend, and detrended visit-to-visit variability in systolic BP and pulse pressure for each participant. Outcomes, assessed at examination 6, included subclinical AF and supraventricular ectopy. Results from each study were combined with inverse variance-weighted meta-analysis. At examination 6, the mean age was 73 years in MESA and 79 years in ARIC study, and 4% had subclinical AF. Higher visit-to-visit detrended variability in systolic BP was associated with a greater prevalence of subclinical AF (odds ratio [OR], 1.20; 95% CI, 1.02-1.38) and with more premature atrial contractions/hour (geometric mean ratio, 1.08; 95% CI, 1.01-1.15). For pulse pressure as well, higher visit-to-visit detrended variability was associated with a greater prevalence of AF (OR, 1.18; 95% CI, 1.00-1.37). In addition, higher long-term mean pulse pressure was associated with a greater prevalence of subclinical AF (OR, 1.36; 95% CI, 1.08-1.70). Conclusions Antecedent visit-to-visit variability in systolic BP and pulse pressure, but not current BP, is associated with a higher prevalence of subclinical atrial arrhythmias. Prior longitudinal BP assessment, rather than current BP, may be more helpful in identifying older adults who are at higher risk of atrial arrhythmias.
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http://dx.doi.org/10.1161/JAHA.120.020260DOI Listing
June 2021

A System for Phenotype Harmonization in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program.

Am J Epidemiol 2021 Apr 16. Epub 2021 Apr 16.

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.

Genotype-phenotype association studies often combine phenotype data from multiple studies to increase power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data set organization. Here we describe a centralized system for phenotype harmonization that includes input from phenotype domain and study experts, quality control, documentation, reproducible results, and data sharing mechanisms. This system was developed for the National Heart, Lung and Blood Institute's Trans-Omics for Precision Medicine program, which is generating genomic and other omics data for >80 studies with extensive phenotype data. To date, 63 phenotypes have been harmonized across thousands of participants from up to 17 studies per phenotype (participants recruited 1948-2012). We discuss challenges in this undertaking and how they were addressed. The harmonized phenotype data and associated documentation have been submitted to National Institutes of Health data repositories for controlled-access by the scientific community. We also provide materials to facilitate future harmonization efforts by the community, which include (1) the code used to generate the 63 harmonized phenotypes, enabling others to reproduce, modify or extend these harmonizations to additional studies; and (2) results of labeling thousands of phenotype variables with controlled vocabulary terms.
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http://dx.doi.org/10.1093/aje/kwab115DOI Listing
April 2021

Incidence of Atrial Fibrillation in Persons with Very High Serum Levels of N-Terminal Pro-B-Type Natriuretic Peptide: The Multi-Ethnic Study of Atherosclerosis.

Clin Epidemiol 2021 7;13:265-272. Epub 2021 Apr 7.

Department of Epidemiology, University of Washington, Seattle, WA, USA.

Objective: While persons in the upper fourth or fifth of the distribution of serum levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) are at a sharply increased risk of developing atrial fibrillation, their absolute risk of this condition (about 20 per 1000 per year) is not clearly high enough to justify prevention or early detection measures. We sought to determine whether the incidence of atrial fibrillation among persons with VERY high levels of NT-proBNP might be sufficiently high to warrant further action.

Design And Setting: Among persons enrolled in the Multi-Ethnic Study of Atherosclerosis, we documented rates of new onset atrial fibrillation in those with increasingly high serum levels of NT-proBNP.

Results: There was a monotonic increase in the incidence of atrial fibrillation with increasing serum level of NT-proBNP, reaching rates of about 50-70 cases per 1000 person-years among those in the upper 3.1% of the distribution (above 422 pg/mL). In this group the incidence tended to be somewhat higher still among persons who were at increased risk of atrial fibrillation for other reasons (eg older age), but in no subgroup did the incidence reach 100 per 1000 person-years.

Conclusion: Serum levels of NT-proBNP have a considerable ability to predict the development of atrial fibrillation. However, the value of screening middle aged and older adults for these levels hinges largely on the ability of interventions in screen-positive people to lead to a reduced incidence of atrial fibrillation and its complications.
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http://dx.doi.org/10.2147/CLEP.S303560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039022PMC
April 2021

The association of novel inflammatory marker GlycA and incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA).

PLoS One 2021 25;16(3):e0248644. Epub 2021 Mar 25.

Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

Background: Emerging evidence has implicated that inflammation contributes to the pathogenesis of atrial fibrillation (AF). GlycA is a novel marker of systemic inflammation with low intra-individual variability and high analytic precision. GlycA has been associated with incident cardiovascular disease (CVD) independent of other inflammatory markers. However, whether GlycA is associated with AF, specifically, has yet to be established. We examined the association between GlycA and AF in a multi-ethnic cohort.

Methods: We studied 6,602 MESA participants aged 45-85, with no clinical CVD at baseline, with data on GlycA and incident AF. We used multivariable-adjusted Cox models to evaluate the association between GlycA and incident AF. We also examined other inflammatory markers [high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6) and fibrinogen] and incident AF for comparison.

Results: The mean (SD) age was 62 (10) years, 53% women. The mean plasma GlycA was 381 (62) μmol/L. Over median follow-up of 12.9 years, 869 participants experienced AF. There was no statistically significant association between GlycA and incident AF after adjusting for sociodemographics, CVD risk factors, and other inflammatory markers [Hazard Ratio (95% CI) per 1 SD increment in GlycA: 0.97 (0.88-1.06)]. Neither hsCRP nor fibrinogen was associated with incident AF in same model. In contrast, IL-6 was independently associated with incident AF [HR 1.12 per 1 SD increment (1.05-1.19)].

Conclusions: Although GlycA has been associated with other CVD types, we found that GlycA was not associated with AF. More research will be required to understand why IL-6 was associated with AF but not GlycA.

Clinical Trial Registration: MESA is not a clinical trial. However, the cohort is registered at: URL: https://clinicaltrials.gov/ct2/show/NCT00005487 Unique identifier: NCT00005487.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248644PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993599PMC
March 2021

Brachial Flow-Mediated Dilation and Risk of Atrial Fibrillation in Older Adults: The Cardiovascular Health Study.

Vasc Health Risk Manag 2021 11;17:95-102. Epub 2021 Mar 11.

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: Endothelial dysfunction is associated with common risk factors for AF and has been implicated in the pathophysiology of atrial fibrillation (AF) through a variety of mechanisms. We determined the prospective association of brachial flow-mediated dilation (FMD) with incident AF among older adults.

Methods: We included 2027 Cardiovascular Health Study participants (mean age=78.3 years, male=39%, Black=17%) who underwent brachial FMD measurement at the 1997 to 1998 clinic visit. Incident AF was ascertained by study electrocardiograms, hospital discharge diagnosis coding and Medicare claims data. Cox regression models were used to examine the association between FMD and incident AF.

Results: We identified 754 incident of AF cases (37%) over a median follow-up of 11.0 years. After adjusting for age, sex, race, height, weight, cardiovascular disease, cigarette smoking, hypertension, diabetes, kidney function, c-reactive protein, physical activity, alcohol consumption, and statins, the risk of AF did not differ according to brachial FMD response (4th vs 1st quartile hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.81, 1.26; per FMD unit increment HR=1.01, 95% CI: 0.97, 1.05).

Conclusion: We found no relationship between brachial FMD and the risk of developing AF in this elderly cohort. Our findings suggest that the utility of brachial FMD as a risk marker for AF in older individuals is minimal.
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http://dx.doi.org/10.2147/VHRM.S297720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961139PMC
March 2021

Cyclic guanosine monophosphate and 10-year change in left ventricular mass: the Multi-Ethnic Study of Atherosclerosis (MESA).

Biomarkers 2021 Jun 9;26(4):309-317. Epub 2021 Mar 9.

Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Cyclic guanosine monophosphate (cGMP) is a second messenger for natriuretic peptide (NP) and nitric oxide pathways; its enhancement a target for heart failure and cardiovascular disease (CVD). We evaluated whether plasma cGMP was associated with change in left ventricular mass (LVM) among individuals free of CVD and if this differed by sex. In 611 men and 612 women aged 45-84 years with plasma cGMP measured at baseline and cardiac MRI performed at baseline and 10 years later, we tested associations of cGMP [log-transformed, per 1 SD increment] with LVM, adjusting for CVD risk factors and N-terminal pro-B-type-NP (NT-proBNP). Participants had mean (SD) age of 63.1(8.5) years and cGMP 4.8(2.6) pmol/mL. Cross-sectionally, higher cGMP was associated with lesser LVM, non-lin- early. In contrast, longitudinally, higher cGMP was associated with increase in LVM [1.70g (0.61, 2.78)] over 10 years. Higher cGMP was associated with greater LVM change in men [2.68g (1.57, 3.79)] but not women [0.24g ((-0.92, 1.39); p-interaction < 0.001]. In conclusion, in a community-based cohort, higher cGMP levels were associated with increase in LVM over 10 years independent of CVD risk factors and NT-proBNP in men, perhaps reflecting compensatory changes. Further studies are needed to understand mechanistic roles of cGMP in LV remodelling and associated sex differences.
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http://dx.doi.org/10.1080/1354750X.2021.1893811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281442PMC
June 2021

Plasma ω-3 and ω-6 PUFA Concentrations and Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis.

J Nutr 2021 Jun;151(6):1479-1486

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.

Background: Current literature examining the prospective relation of circulating omega-3 (n-3) and omega-6 (n-6) PUFAs and atrial fibrillation (AF) is limited to predominantly white populations.

Objectives: We investigated the association of circulating n-3 and n-6 PUFAs with incident AF in participants from the Multi-Ethnic Study of Atherosclerosis.

Methods: A total of 6229 participants (mean age = 62 y; 53% female; 39% white, 27% black, 22% Hispanic, and 12% Chinese) who were free of baseline AF and with plasma phospholipid PUFAs measured at baseline using GC were prospectively followed for the development of AF. Incident AF was ascertained using International Classification of Diseases-9 codes from hospital discharge records and Medicare claims data with follow-up through 2014. Multivariable Cox proportional hazards regression analysis was performed to determine the risk of incident AF.

Results: During a median follow-up of 12.9 y, 813 (13%) participants developed AF. Each higher SD increment in arachidonic acid (AA; 20:4n-6) concentrations was associated with an 11% decreased risk of incident AF (HR: 0.89; 95% CI: 0.82, 0.96). Similarly, higher overall n-6 PUFA concentrations were also associated with a reduced AF risk (HR per SD increment: 0.93; 95% CI: 0.87, 1.00). Although no significant overall associations were observed for any individual n-3 PUFAs, higher circulating concentrations of DHA (22:6n-3) and EPA (20:5n-3) were associated with a decreased AF risk in blacks and Hispanics (DHA only) but not whites or Chinese Americans.

Conclusions: In a multiethnic cohort of individuals free of baseline cardiovascular disease, higher plasma concentrations of n-6 PUFAs, particularly AA, were associated with a reduced risk of incident AF. Important differences in AF risk were also noted across race/ethnicity for the n-3 PUFAs DHA and EPA.
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http://dx.doi.org/10.1093/jn/nxab016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243886PMC
June 2021

Types of Stroke Among People Living With HIV in the United States.

J Acquir Immune Defic Syndr 2021 04;86(5):568-578

Neurology, University of Washington, Seattle, WA.

Background: Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes.

Setting: CNICS, a U.S. multisite clinical cohort of PLWH in care.

Methods: We implemented a centralized adjudication stroke protocol to identify stroke type, subtype, and precipitating conditions identified as direct causes including infection and illicit drug use in a large diverse HIV cohort.

Results: Among 26,514 PLWH, there were 401 strokes, 75% of which were ischemic. Precipitating factors such as sepsis or same-day cocaine use were identified in 40% of ischemic strokes. Those with precipitating factors were younger, had more severe HIV disease, and fewer traditional stroke risk factors such as diabetes and hypertension. Ischemic stroke subtypes included cardioembolic (20%), large vessel atherosclerosis (13%), and small vessel (24%) ischemic strokes. Individuals with small vessel strokes were older, were more likely to have a higher current CD4 cell count than those with cardioembolic strokes and had the highest mean blood pressure of the ischemic stroke subtypes.

Conclusion: Ischemic stroke, particularly small vessel and cardioembolic subtypes, were the most common strokes among PLWH. Traditional and HIV-related risk factors differed by stroke type/subtype. Precipitating factors including infections and drug use were common. These results suggest that there may be different biological phenomena occurring among PLWH and that understanding HIV-related and traditional risk factors and in particular precipitating factors for each type/subtype may be key to understanding, and therefore preventing, strokes among PLWH.
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http://dx.doi.org/10.1097/QAI.0000000000002598DOI Listing
April 2021

HIV Viremia and Risk of Stroke Among People Living with HIV Who Are Using Antiretroviral Therapy.

Epidemiology 2021 05;32(3):457-464

College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.

Background: Rates of stroke are higher in people living with HIV compared with age-matched uninfected individuals. Causes of elevated stroke risk, including the role of viremia, are poorly defined.

Methods: Between 1 January 2006 and 31 December 2014, we identified incident strokes among people living with HIV on antiretroviral therapy at five sites across the United States. We considered three parameterizations of viral load (VL) including (1) baseline (most recent VL before study entry), (2) time-updated, and (3) cumulative VL (copy-days/mL of virus). We used Cox proportional hazards models to estimate hazard ratios (HRs) for stroke risk comparing the 75th percentile ("high VL") to the 25th percentile ("low VL") of baseline and time-updated VL. We used marginal structural Cox models, with most models adjusted for traditional stroke risk factors, to estimate HRs for stroke associated with cumulative VL.

Results: Among 15,974 people living with HIV, 139 experienced a stroke (113 ischemic; 18 hemorrhagic; eight were unknown type) over a median follow-up of 4.2 years. Median baseline VL was 38 copies/mL (interquartile interval: 24, 3,420). High baseline VL was associated with increased risk of both ischemic (HR: 1.3; 95% CI = 0.96-1.7) and hemorrhagic stroke (HR: 3.1; 95% CI = 1.6-5.9). In time-updated models, high VL was also associated with an increased risk of any stroke (HR: 1.8; 95% CI = 1.4-2.3). We observed no association between cumulative VL and stroke risk.

Conclusions: Our findings are consistent with the hypothesis that elevated HIV VL may increase stroke risk, regardless of previous VL levels.
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http://dx.doi.org/10.1097/EDE.0000000000001331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012252PMC
May 2021

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.

Nature 2021 02 10;590(7845):290-299. Epub 2021 Feb 10.

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes). In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.
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http://dx.doi.org/10.1038/s41586-021-03205-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875770PMC
February 2021

Associations of Left Atrial Function and Structure With Supraventricular Ectopy: The Multi-Ethnic Study of Atherosclerosis.

J Am Heart Assoc 2021 02 4;10(4):e018093. Epub 2021 Feb 4.

Department of Medicine, Division of Cardiology Johns Hopkins University Baltimore MD.

Background High levels of supraventricular ectopy are associated with greater risk of atrial fibrillation, stroke, and death. Little information is available about differences by race/ethnicity in the extent of supraventricular ectopy, or about whether high levels of supraventricular ectopy are associated with impaired left atrial (LA) function and LA enlargement. Methods and Results In the MESA (Multi-Ethnic Study of Atherosclerosis), 1148 participants (47% men; mean age, 67 years) had cardiovascular magnetic resonance imaging in 2010 to 2012, followed by 14-day ambulatory electrocardiographic monitoring in 2016 to 2018. We analyzed participant characteristics and cardiovascular magnetic resonance measures of LA function and structure in relation to average count of premature atrial contractions (PACs) per hour and average number of runs per day of supraventricular tachycardia. In adjusted regression analyses, older age, male sex, White race, elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide), and a history of clinically detected atrial fibrillation were associated with more PACs/hour. Chinese and Hispanic participants had on average fewer PACs/hour than White participants (Chinese participants, 31% less [95% CI, 8%-49%]; Hispanic participants, 38% less [95% CI, 19%-52%]). Greater LA total emptying fraction was associated with fewer PACs/hour (per SD, 16% fewer PACs/hour [95% CI, 7%-25% fewer PACs/hour]). Larger LA minimum volume was associated with more PACs/hour (per SD, 7% more PACs/hour [95% CI, 2%-13% more PACs/hour]). Associations of LA volumes with runs of supraventricular tachycardia/day were similar in direction but were weaker. Conclusions Impaired LA function and LA enlargement were associated with more PACs/hour on extended ambulatory electrocardiographic monitoring. Measurement of supraventricular ectopy may provide information about the extent of atrial myopathy.
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http://dx.doi.org/10.1161/JAHA.120.018093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955336PMC
February 2021

The relationship between body mass index, disease activity, and exercise in ankylosing spondylitis.

Arthritis Care Res (Hoboken) 2021 Jan 27. Epub 2021 Jan 27.

University of California, San Francisco, USA.

Background: Ankylosing spondylitis (AS) is associated with elevated cardiovascular (CV) risk and obesity is a common, modifiable risk factor. Our aims were 1) to assess the relationship of BMI with disease activity in AS patients, and 2) to assess the extent to which the effect is mediated through exercise.

Methods: We used data from a prospective AS cohort with a median follow-up of 7 years. To determine the association of BMI (kg/m ) with disease activity as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS), we used generalized estimating equations with inverse probability weighting to account for repeated measures per subject and time-varying confounding. To estimate the direct effect of overweight/obese BMI on disease activity, and the indirect effect through exercise, we performed a mediation analysis.

Results: There were 183 subjects with available BMI and disease activity data (77% male, 70% white, mean age 40.8 ± 13.3 years). Higher BMI was significantly associated with higher disease activity over time; on average, for a 1 kg/m higher BMI, the ASDAS was 0.06 units higher (95% CI 0.04 - 0.08) after adjustment for important confounders. The direct effect of an overweight/obese BMI accounted for most of the total effect on disease activity, with a smaller indirect effect mediated by exercise (7%).

Conclusion: Higher BMI was associated with higher disease activity in a prospective AS cohort. We found that being overweight/obese largely influenced disease activity directly, rather than indirectly through exercise. Other mechanisms such as increased inflammation may better explain the obesity-disease activity association.
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http://dx.doi.org/10.1002/acr.24565DOI Listing
January 2021

Association of Longitudinal Changes in NT-proBNP With Changes in Left Atrial Volume and Function: MESA.

Am J Hypertens 2021 06;34(6):626-635

Department of Cardiology, Johns Hopkins University, Baltimore, Maryland, USA.

Background: The mechanism of left atrial (LA) remodeling is poorly understood. The aim of this longitudinal study was to investigate whether changes in NT-proBNP levels relate to alterations of LA structure and function over time in a multiethnic population.

Methods: From the prospective cohort study, the Multi-Ethnic Study of Atherosclerosis, our analysis included 1,838 participants who underwent cardiac magnetic resonance imaging at the baseline and 10-year examinations, had NT-proBNP levels available at both time points, and did not develop heart failure, myocardial infarction, and/or atrial fibrillation. Multivariable linear regression was used to analyze the association between NT-proBNP level (log-transformed) at the 2 time points and change in LA volumes, LA emptying fractions (total, active, and passive), and LA longitudinal strain. Log NT-proBNP was categorized into Low-Low (N = 681), Low-High (N = 238), High-Low (N = 237), and High-High (N = 682) based on the median value at both time points.

Results: With the Low-Low group as the reference group, the High-High group experienced a greater increase in LA maximum and minimum indexed volumes: 3.1 ml/m2 (95% confidence interval 1.98, 4.20) and 2.7 ml/m2 (1.89, 3.51), respectively. The High-High group also experienced a greater decrease in LA total, passive, active emptying fraction, and longitudinal strain: -3.3% (-4.46, -2.11), -0.9% (-1.80, -0.02), -4.2% (-5.55, -2.76), and -2.3% (-3.80, -0.72), respectively. The Low-High group had similar associations, but the effect sizes were not as high.

Conclusions: Adverse LA remodeling over 10 years of follow-up strongly correlates with prolonged elevated levels of intracardiac stress, as assessed by NT-proBNP levels.
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http://dx.doi.org/10.1093/ajh/hpab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219363PMC
June 2021

Individual non-esterified fatty acids and incident atrial fibrillation late in life.

Heart 2021 Jan 22. Epub 2021 Jan 22.

Medical Service, San Francisco VA Medical Center, San Francisco, California, USA.

Objective: Obesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Expansion of fat depots is associated with increased circulating total non-esterified fatty acids (NEFAs), elevated levels of which are associated with incident AF. We undertook comprehensive serum measurement of individual NEFA to identify specific associations with new-onset AF late in life.

Methods: The present study focused on participants with available serum and free of AF selected from the Cardiovascular Health Study, a community-based longitudinal investigation of older US adults. Thirty-five individual NEFAs were measured by gas chromatography. Cox regression was used to evaluate the association of individual NEFAs with incident AF.

Results: The study sample included 1872 participants (age 77.7±4.4). During median follow-up of 11.3 years, 715 cases of incident AF occurred. After concurrent adjustment of all NEFAs and full adjustment for potential confounders, higher serum concentration of nervonic acid (24:1 n-9), a long-chain monounsaturated fatty acid, was associated with higher risk of AF (HR per SD: 1.18, 95% CI 1.08 to 1.29; p<0.001). Conversely, higher serum concentration of gamma-linolenic acid (GLA) (18:3 n-6), a polyunsaturated n-6 fatty acid, was associated with lower risk of AF (HR per SD: 0.81, 95% CI 0.71 to 0.94; p=0.004). None of the remaining NEFAs was significantly associated with AF.

Conclusions: Among older adults, serum levels of non-esterified nervonic acid were positively associated, while serum levels of non-esterified GLA were inversely associated, with incident AF. If confirmed, these results could offer new strategies for AF prevention and early intervention in this segment of the population at highest risk.
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http://dx.doi.org/10.1136/heartjnl-2020-317929DOI Listing
January 2021

Natural killer cells, gamma delta T cells and classical monocytes are associated with systolic blood pressure in the multi-ethnic study of atherosclerosis (MESA).

BMC Cardiovasc Disord 2021 01 22;21(1):45. Epub 2021 Jan 22.

Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA.

Background: Hypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP).

Methods: We assayed immune cells from cryopreserved samples collected at the baseline examination (2000-2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10 years. The analysis provides estimates of the association with blood pressure level.

Results: The mean age of the MESA participants at baseline was 64 ± 10 years and 53% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40 mmHg [95% confidence interval (CI) 1.34-3.42] higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88 mmHg (95% CI 0.82-2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14CD16) was associated with 2.01 mmHG (95% CI 0.79-3.24) lower average systolic blood pressure. There were no associations of CD4 T helper cell subsets with average systolic blood pressure.

Conclusion: These findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.
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http://dx.doi.org/10.1186/s12872-021-01857-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821496PMC
January 2021
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