03170nas a2200481 4500008004100000022001400041245008500055210006900140260001600209300001200225490000800237520177400245653002202019653000902041653002402050653004002074653001102114653003402125653001102159653000902170653001602179653001702195100002302212700001902235700002302254700002202277700002202299700002202321700001802343700002402361700001702385700002202402700001502424700002202439700002302461700002402484700002002508700002402528700002402552700002302576710005302599856003602652 2010 eng d a1524-453900aEuropean ancestry as a risk factor for atrial fibrillation in African Americans.0 aEuropean ancestry as a risk factor for atrial fibrillation in Af c2010 Nov 16 a2009-150 v1223 a
BACKGROUND: Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown whether the higher risk is due to genetic or environmental factors. Because African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF.
METHODS AND RESULTS: We studied whites (n=4543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10 902) and African Americans (n=3517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3517). Percent European ancestry in African Americans was estimated with 1747 ancestry informative markers from the Illumina custom ITMAT-Broad-CARe array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3517 ARIC participants developed incident AF. A meta-analysis from the 2 studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (hazard ratio, 1.13; 95% confidence interval, 1.03 to 1.23; P=0.007). After adjustment for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% confidence interval, 1.07 to 1.29; P=0.001). A second analysis using 3192 ancestry informative markers from a genome-wide Affymetrix 6.0 array in ARIC African Americans yielded similar results.
CONCLUSIONS: European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative.
10aAfrican Americans10aAged10aAtrial Fibrillation10aEuropean Continental Ancestry Group10aFemale10aGenome-Wide Association Study10aHumans10aMale10aMiddle Aged10aRisk Factors1 aMarcus, Gregory, M1 aAlonso, Alvaro1 aPeralta, Carmen, A1 aLettre, Guillaume1 aVittinghoff, Eric1 aLubitz, Steven, A1 aFox, Ervin, R1 aLevitzky, Yamini, S1 aMehra, Reena1 aKerr, Kathleen, F1 aDeo, Rajat1 aSotoodehnia, Nona1 aAkylbekova, Meggie1 aEllinor, Patrick, T1 aPaltoo, Dina, N1 aSoliman, Elsayed, Z1 aBenjamin, Emelia, J1 aHeckbert, Susan, R1 aCandidate-Gene Association Resource (CARe) Study uhttps://chs-nhlbi.org/node/124804127nas a2200745 4500008004100000022001400041245023700055210006900292260001300361300001100374490000600385520175300391653002202144653000902166653001202175653002402187653003102211653001902242653004002261653001102301653001102312653000902323653001602332653005302348653003602401653002902437653001702466653001102483653001802494100002402512700002202536700002202558700002602580700002302606700002202629700002202651700002002673700001502693700002702708700002402735700001702759700001702776700001802793700001902811700002202830700003002852700002102882700002202903700002002925700002302945700002202968700002402990700002203014700002103036700002703057700002203084700002903106700001903135700002403154700001903178700002403197700002303221710010103244856003603345 2011 eng d a1942-326800aLarge-scale candidate gene analysis in whites and African Americans identifies IL6R polymorphism in relation to atrial fibrillation: the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe) project.0 aLargescale candidate gene analysis in whites and African America c2011 Oct a557-640 v43 aBACKGROUND: The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.
METHODS AND RESULTS: We examined a panel of approximately 50,000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18,524; 2260 cases) or African American descent (n=3662; 263 cases) in the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n=19,602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk [RR] C allele, 0.90; 95% confidence interval [CI], 0.85-0.95; P=0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95% CI, 0.72-1.03; P=0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95% CI, 0.57-0.89; P=0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95% CI, 1.16-1.69; P=0.0005).
CONCLUSIONS: In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans.
10aAfrican Americans10aAged10aAlleles10aAtrial Fibrillation10aChromosomes, Human, Pair 410aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aHumans10aMale10aMiddle Aged10aNational Heart, Lung, and Blood Institute (U.S.)10aPolymorphism, Single Nucleotide10aReceptors, Interleukin-610aRisk Factors10aStroke10aUnited States1 aSchnabel, Renate, B1 aKerr, Kathleen, F1 aLubitz, Steven, A1 aAlkylbekova, Ermeg, L1 aMarcus, Gregory, M1 aSinner, Moritz, F1 aMagnani, Jared, W1 aWolf, Philip, A1 aDeo, Rajat1 aLloyd-Jones, Donald, M1 aLunetta, Kathryn, L1 aMehra, Reena1 aLevy, Daniel1 aFox, Ervin, R1 aArking, Dan, E1 aMosley, Thomas, H1 aMüller-Nurasyid, Martina1 aYoung, Taylor, R1 aWichmann, H-Erich1 aSeshadri, Sudha1 aFarlow, Deborah, N1 aRotter, Jerome, I1 aSoliman, Elsayed, Z1 aGlazer, Nicole, L1 aWilson, James, G1 aBreteler, Monique, M B1 aSotoodehnia, Nona1 aNewton-Cheh, Christopher1 aKääb, Stefan1 aEllinor, Patrick, T1 aAlonso, Alvaro1 aBenjamin, Emelia, J1 aHeckbert, Susan, R1 aCandidate Gene Association Resource (CARe) Atrial Fibrillation/Electrocardiography Working Group uhttps://chs-nhlbi.org/node/131603298nas a2200397 4500008004100000022001400041245008200055210006900137260001600206300001000222490000800232520217800240653000902418653002402427653002002451653001902471653002402490653001102514653001102525653000902536653002402545653002702569653002402596653002002620100002302640700002202663700002102685700002302706700002402729700002202753700002002775700002202795700002402817700002302841856003602864 2013 eng d a1539-370400aAtrial ectopy as a predictor of incident atrial fibrillation: a cohort study.0 aAtrial ectopy as a predictor of incident atrial fibrillation a c c2013 Dec 03 a721-80 v1593 aBACKGROUND: Atrial fibrillation (AF) prediction models have unclear clinical utility given the absence of AF prevention therapies and the immutability of many risk factors. Premature atrial contractions (PACs) play a critical role in AF pathogenesis and may be modifiable.
OBJECTIVE: To investigate whether PAC count improves model performance for AF risk.
DESIGN: Prospective cohort study.
SETTING: 4 U.S. communities.
PATIENTS: A random subset of 1260 adults without prevalent AF enrolled in the Cardiovascular Health Study between 1989 and 1990.
MEASUREMENTS: The PAC count was quantified by 24-hour electrocardiography. Participants were followed for the diagnosis of incident AF or death. The Framingham AF risk algorithm was used as the comparator prediction model.
RESULTS: In adjusted analyses, doubling the hourly PAC count was associated with a significant increase in AF risk (hazard ratio, 1.17 [95% CI, 1.13 to 1.22]; P < 0.001) and overall mortality (hazard ratio, 1.06 [CI, 1.03 to 1.09]; P < 0.001). Compared with the Framingham model, PAC count alone resulted in similar AF risk discrimination at 5 and 10 years of follow-up and superior risk discrimination at 15 years. The addition of PAC count to the Framingham model resulted in significant 10-year AF risk discrimination improvement (c-statistic, 0.65 vs. 0.72; P < 0.001), net reclassification improvement (23.2% [CI, 12.8% to 33.6%]; P < 0.001), and integrated discrimination improvement (5.6% [CI, 4.2% to 7.0%]; P < 0.001). The specificity for predicting AF at 15 years exceeded 90% for PAC counts more than 32 beats/h.
LIMITATION: This study does not establish a causal link between PACs and AF.
CONCLUSION: The addition of PAC count to a validated AF risk algorithm provides superior AF risk discrimination and significantly improves risk reclassification. Further study is needed to determine whether PAC modification can prospectively reduce AF risk.
PRIMARY FUNDING SOURCE: American Heart Association, Joseph Drown Foundation, and National Institutes of Health.
10aAged10aAtrial Fibrillation10aAtrial Function10aCause of Death10aElectrocardiography10aFemale10aHumans10aMale10aModels, Statistical10aMyocardial Contraction10aProspective Studies10aRisk Assessment1 aDewland, Thomas, A1 aVittinghoff, Eric1 aMandyam, Mala, C1 aHeckbert, Susan, R1 aSiscovick, David, S1 aStein, Phyllis, K1 aPsaty, Bruce, M1 aSotoodehnia, Nona1 aGottdiener, John, S1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/616601004nas a2200349 4500008004100000022001400041245010500055210006900160260001600229300001100245490000800256653000900264653002400273653001500297653002400312653001900336653002400355653002800379653001100407653001800418653001100436653002600447653000900473653001400482653000900496100002100505700002400526700002300550700002200573700002300595856003600618 2013 eng d a1538-359800aLong-term outcomes of left anterior fascicular block in the absence of overt cardiovascular disease.0 aLongterm outcomes of left anterior fascicular block in the absen c2013 Apr 17 a1587-80 v30910aAged10aAtrial Fibrillation10aBiomarkers10aBundle-Branch Block10aCohort Studies10aElectrocardiography10aEndomyocardial Fibrosis10aFemale10aHeart Failure10aHumans10aKaplan-Meier Estimate10aMale10aPrognosis10aRisk1 aMandyam, Mala, C1 aSoliman, Elsayed, Z1 aHeckbert, Susan, R1 aVittinghoff, Eric1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/607703017nas a2200493 4500008004100000022001400041245006200055210005700117260001300174300001100187490000700198520168900205653000901894653002401903653001901927653002401946653001101970653001101981653001401992653002102006653000902027653001602036653001702052100002102069700002402090700001902114700002302133700002302156700002202179700002402201700002402225700002502249700001802274700002602292700001902318700001802337700002002355700002202375700002202397700002502419700002002444700002302464856003602487 2013 eng d a1556-387100aThe QT interval and risk of incident atrial fibrillation.0 aQT interval and risk of incident atrial fibrillation c2013 Oct a1562-80 v103 aBACKGROUND: Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine.
OBJECTIVE: To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF.
METHODS: We examined a prolonged QT interval corrected by using the Framingham formula (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas.
RESULTS: Among 14,538 ARIC study participants, a prolonged QT(Fram) predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.42-2.96; P < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QT(Fram) was associated with an increased unadjusted (HR 1.14; 95% CI 1.10-1.17; P < .001) and adjusted (HR 1.11; 95% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts.
CONCLUSIONS: A prolonged QT interval is associated with an increased risk of incident AF.
10aAged10aAtrial Fibrillation10aCohort Studies10aElectrocardiography10aFemale10aHumans10aIncidence10aLong QT Syndrome10aMale10aMiddle Aged10aRisk Factors1 aMandyam, Mala, C1 aSoliman, Elsayed, Z1 aAlonso, Alvaro1 aDewland, Thomas, A1 aHeckbert, Susan, R1 aVittinghoff, Eric1 aCummings, Steven, R1 aEllinor, Patrick, T1 aChaitman, Bernard, R1 aStocke, Karen1 aApplegate, William, B1 aArking, Dan, E1 aButler, Javed1 aLoehr, Laura, R1 aMagnani, Jared, W1 aMurphy, Rachel, A1 aSatterfield, Suzanne1 aNewman, Anne, B1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/599803628nas a2200529 4500008004100000022001400041245010700055210006900162260001300231300001100244490000700255520202700262653001002289653002202299653000902321653002202330653002402352653002502376653001902401653002702420653001102447653002202458653001102480653000902491653001602500653004002516653002402556653001702580653002402597100002302621700001902644700002402663700001902687700001702706700001702723700002802740700002202768700002202790700002302812700002402835700001802859700002402877700002502901700002202926710011402948856003603062 2014 eng d a1540-816700aA common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans.0 acommon SCN5A variant is associated with PR interval and atrial f c2014 Nov a1150-70 v253 aOBJECTIVE: We examined the association of rs7626962 (S1103Y) or rs7629265, a variant in high linkage disequilibrium with S1103Y (r(2) = 0.87 - 1), with sudden cardiac death (SCD) and atrial fibrillation (AF) among African Americans.
BACKGROUND: The SCN5A missense variant S1103Y has been associated with SCD among African Americans in small case-control studies, but larger population-based studies are needed to validate these findings. The association of this variant with AF has not been fully explored.
METHODS: Using genotyping data on over 7,000 African Americans from 5 cohorts (Atherosclerosis Risk in Communities [ARIC], Cleveland Family Study [CFS], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], Cardiovascular Health Study [CHS]), we examined the association of rs7629265 with electrocardiographic PR, QRS, and QT intervals, and with incident AF and SCD. We examined association of S1103Y (rs7626962) with SCD using a population-based case-control study of SCD Cardiac Arrest Blood Study (CABS).
RESULTS: Meta-analyses across 5 cohorts demonstrated that rs7629265 was significantly associated with PR duration (β = -4.1 milliseconds; P = 2.2×10(-6) ), but not significantly associated with QRS or QT intervals. In meta-analyses of prospectively followed ARIC and CHS participants (n = 3,656), rs7629265 was associated with increased AF risk (n = 299 AF cases; HR = 1.74, P = 1.9 × 10(-4) ). By contrast, rs7629265 was not significantly associated with SCD risk in ARIC (n = 83 SCD cases; P = 0.30) or CHS (n = 54 SCD cases; P = 0.47). Similarly, S1103Y was not significantly associated with SCD risk in CABS (n = 225 SCD cases; P = 0.29).
CONCLUSION: The common SCN5A variant, rs7629265, is associated with increased AF risk and shorter PR interval among African Americans. In contrast to prior reports, we found no evidence of association of rs7629265 or rs7626962 (S1103Y) with SCD risk in the general population.
10aAdult10aAfrican Americans10aAged10aAged, 80 and over10aAtrial Fibrillation10aCase-Control Studies10aCohort Studies10aDeath, Sudden, Cardiac10aFemale10aGenetic Variation10aHumans10aMale10aMiddle Aged10aNAV1.5 Voltage-Gated Sodium Channel10aProspective Studies10aRisk Factors10aSingle-Blind Method1 aIlkhanoff, Leonard1 aArking, Dan, E1 aLemaitre, Rozenn, N1 aAlonso, Alvaro1 aChen, Lin, Y1 aDurda, Peter1 aHesselson, Stephanie, E1 aKerr, Kathleen, F1 aMagnani, Jared, W1 aMarcus, Gregory, M1 aSchnabel, Renate, B1 aSmith, Gustav1 aSoliman, Elsayed, Z1 aReiner, Alexander, P1 aSotoodehnia, Nona1 aCandidate-Gene Association Resource (CARE) Consortium and the Cardiac Arrest Blood Study (CABS) Investigators uhttps://chs-nhlbi.org/node/657003375nas a2200565 4500008004100000022001400041245012200055210006900177260001300246300001200259490000600271520178500277653001602062653000902078653001002087653002402097653001502121653003202136653002402168653002802192653001102220653003802231653001102269653001402280653001502294653000902309653001402318653003602332653002402368653002002392653001702412653001502429653001302444653001702457100002202474700002302496700002002519700002802539700001402567700001602581700001302597700002202610700002002632700002502652700002802677700002202705700002302727700002302750856003602773 2014 eng d a1941-308400aTelomere length and the risk of atrial fibrillation: insights into the role of biological versus chronological aging.0 aTelomere length and the risk of atrial fibrillation insights int c2014 Dec a1026-320 v73 aBACKGROUND: Advanced age is the most important risk factor for atrial fibrillation (AF); however, the mechanism remains unknown. Telomeres, regions of DNA that shorten with cell division, are considered reliable markers of biological aging. We sought to examine the association between leukocyte telomere length (LTL) and incident AF in a large population-based cohort using direct LTL measurements and genetic data. To further explore our findings, we compared atrial cell telomere length and LTL in cardiac surgery patients.
METHODS AND RESULTS: Mean LTL and the TERT rs2736100 single nucleotide polymorphism were assessed as predictors of incident AF in the Cardiovascular Health Study (CHS). Among the surgical patients, within subject comparison of atrial cell telomere length versus LTL was assessed. Among 1639 CHS participants, we observed no relationship between mean LTL and incident AF before and after adjustment for potential confounders (adjusted hazard ratio, 1.09; 95% confidence interval: 0.92-1.29; P=0.299); chronologic age remained strongly associated with AF in the same model. No association was observed between the TERT rs2736100 single nucleotide polymorphism and incident AF (adjusted hazard ratio: 0.95; 95% confidence interval: 0.88-1.04; P=0.265). In 35 cardiac surgery patients (26 with AF), atrial cell telomere length was longer than LTL (1.19 ± 0.20 versus 1.02 ± 0.25 [T/S ratio], P<0.001), a finding that remained consistent within the AF subgroup.
CONCLUSIONS: Our study revealed no evidence of an association between LTL and incident AF and no evidence of relative atrial cell telomere shortening in AF. Chronological aging independent of biological markers of aging is the primary risk factor for AF.
10aAge Factors10aAged10aAging10aAtrial Fibrillation10aCalifornia10aCardiac Surgical Procedures10aCellular Senescence10aCross-Sectional Studies10aFemale10aGenetic Predisposition to Disease10aHumans10aIncidence10aLeukocytes10aMale10aPhenotype10aPolymorphism, Single Nucleotide10aProspective Studies10aRisk Assessment10aRisk Factors10aTelomerase10aTelomere10aTime Factors1 aRoberts, Jason, D1 aDewland, Thomas, A1 aLongoria, James1 aFitzpatrick, Annette, L1 aZiv, Elad1 aHu, Donglei1 aLin, Jue1 aGlidden, David, V1 aPsaty, Bruce, M1 aBurchard, Esteban, G1 aBlackburn, Elizabeth, H1 aOlgin, Jeffrey, E1 aHeckbert, Susan, R1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/659403175nas a2200409 4500008004100000022001400041245006600055210006500121260001600186300001000202490000700212520203900219653000902258653002202267653002102289653003602310653001102346653001602357653001802373653001102391653000902402653001702411653001802428653003602446100002302482700002302505700002202528700002102550700002302571700002402594700002202618700002002640700002202660700002402682700002302706856003602729 2015 eng d a1558-359700aVentricular Ectopy as a Predictor of Heart Failure and Death.0 aVentricular Ectopy as a Predictor of Heart Failure and Death c2015 Jul 14 a101-90 v663 aBACKGROUND: Studies of patients presenting for catheter ablation suggest that premature ventricular contractions (PVCs) are a modifiable risk factor for congestive heart failure (CHF). The relationship among PVC frequency, incident CHF, and mortality in the general population remains unknown.
OBJECTIVES: The goal of this study was to determine whether PVC frequency ascertained using a 24-h Holter monitor is a predictor of a decrease in the left ventricular ejection fraction (LVEF), incident CHF, and death in a population-based cohort.
METHODS: We studied 1,139 Cardiovascular Health Study (CHS) participants who were randomly assigned to 24-h ambulatory electrocardiography (Holter) monitoring and who had a normal LVEF and no history of CHF. PVC frequency was quantified using Holter studies, and LVEF was measured from baseline and 5-year echocardiograms. Participants were followed for incident CHF and death.
RESULTS: Those in the upper quartile versus the lowest quartile of PVC frequency had a multivariable-adjusted, 3-fold greater odds of a 5-year decrease in LVEF (odds ratio [OR]: 3.10; 95% confidence interval [CI]: 1.42 to 6.77; p = 0.005), a 48% increased risk of incident CHF (HR: 1.48; 95% CI: 1.08 to 2.04; p = 0.02), and a 31% increased risk of death (HR: 1.31; 95% CI: 1.06 to 1.63; p = 0.01) during a median follow-up of >13 years. Similar statistically significant results were observed for PVCs analyzed as a continuous variable. The specificity for the 15-year risk of CHF exceeded 90% when PVCs included at least 0.7% of ventricular beats. The population-level risk for incident CHF attributed to PVCs was 8.1% (95% CI: 1.2% to 14.9%).
CONCLUSIONS: In a population-based sample, a higher frequency of PVCs was associated with a decrease in LVEF, an increase in incident CHF, and increased mortality. Because of the capacity to prevent PVCs through medical or ablation therapy, PVCs may represent a modifiable risk factor for CHF and death.
10aAged10aCatheter Ablation10aEchocardiography10aElectrocardiography, Ambulatory10aFemale10aForecasting10aHeart Failure10aHumans10aMale10aRisk Factors10aStroke Volume10aVentricular Premature Complexes1 aDukes, Jonathan, W1 aDewland, Thomas, A1 aVittinghoff, Eric1 aMandyam, Mala, C1 aHeckbert, Susan, R1 aSiscovick, David, S1 aStein, Phyllis, K1 aPsaty, Bruce, M1 aSotoodehnia, Nona1 aGottdiener, John, S1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/676702377nas a2200205 4500008004100000022001400041245006000055210005900115260001300174490000600187520178700193100001901980700002201999700002302021700002302044700002202067700002302089700002302112856003602135 2016 eng d a2047-998000aConsumption of Caffeinated Products and Cardiac Ectopy.0 aConsumption of Caffeinated Products and Cardiac Ectopy c2016 Jan0 v53 aBACKGROUND: Premature cardiac contractions are associated with increased morbidity and mortality. Though experts associate premature atrial contractions (PACs) and premature ventricular contractions (PVCs) with caffeine, there are no data to support this relationship in the general population. As certain caffeinated products may have cardiovascular benefits, recommendations against them may be detrimental.
METHODS AND RESULTS: We studied Cardiovascular Health Study participants with a baseline food frequency assessment, 24-hour ambulatory electrocardiography (Holter) monitoring, and without persistent atrial fibrillation. Frequencies of habitual coffee, tea, and chocolate consumption were assessed using a picture-sort food frequency survey. The main outcomes were PACs/h and PVCs/hour. Among 1388 participants (46% male, mean age 72 years), 840 (61%) consumed ≥1 caffeinated product per day. The median numbers of PACs and PVCs/h and interquartile ranges were 3 (1-12) and 1 (0-7), respectively. There were no differences in the number of PACs or PVCs/h across levels of coffee, tea, and chocolate consumption. After adjustment for potential confounders, more frequent consumption of these products was not associated with ectopy. In examining combined dietary intake of coffee, tea, and chocolate as a continuous measure, no relationships were observed after multivariable adjustment: 0.48% fewer PACs/h (95% CI -4.60 to 3.64) and 2.87% fewer PVCs/h (95% CI -8.18 to 2.43) per 1-serving/week increase in consumption.
CONCLUSIONS: In the largest study to evaluate dietary patterns and quantify cardiac ectopy using 24-hour Holter monitoring, we found no relationship between chronic consumption of caffeinated products and ectopy.
1 aDixit, Shalini1 aStein, Phyllis, K1 aDewland, Thomas, A1 aDukes, Jonathan, W1 aVittinghoff, Eric1 aHeckbert, Susan, R1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/699202330nas a2200229 4500008004100000022001400041245006900055210006800124260001500192300001000207490000800217520165900225100002201884700002201906700002301928700002101951700002201972700002401994700002302018700002302041856003602064 2016 eng d a1879-191300aElectrocardiographic Predictors of Incident Atrial Fibrillation.0 aElectrocardiographic Predictors of Incident Atrial Fibrillation c2016 Sep 1 a714-90 v1183 aAtrial fibrillation (AF) is likely secondary to multiple different pathophysiological mechanisms that are increasingly but incompletely understood. Motivated by the hypothesis that 3 previously described electrocardiographic predictors of AF identify distinct AF mechanisms, we sought to determine if these electrocardiographic findings independently predict incident disease. Among Cardiovascular Health Study participants without prevalent AF, we determined whether left anterior fascicular block (LAFB), a prolonged QTC, and atrial premature complexes (APCs) each predicted AF after adjusting for each other. We then calculated the attributable risk in the exposed for each electrocardiographic marker. LAFB and QTC intervals were assessed on baseline 12-lead electrocardiogram (n = 4,696). APC count was determined using 24-hour Holter recordings obtained in a random subsample (n = 1,234). After adjusting for potential confounders and each electrocardiographic marker, LAFB (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.1 to 3.9, p = 0.023), a prolonged QTC (HR 2.5, 95% CI 1.4 to 4.3, p = 0.002), and every doubling of APC count (HR 1.2, 95% CI 1.1 to 1.3, p <0.001) each remained independently predictive of incident AF. The attributable risk of AF in the exposed was 35% (95% CI 13% to 52%) for LAFB, 25% (95% CI 0.6% to 44%) for a prolonged QTC, and 34% (95% CI 26% to 42%) for APCs. In conclusion, in a community-based cohort, 3 previously established electrocardiogram-derived AF predictors were each independently associated with incident AF, suggesting that they may represent distinct mechanisms underlying the disease.
1 aNguyen, Kaylin, T1 aVittinghoff, Eric1 aDewland, Thomas, A1 aMandyam, Mala, C1 aStein, Phyllis, K1 aSoliman, Elsayed, Z1 aHeckbert, Susan, R1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/712903570nas a2200349 4500008004100000022001400041245011100055210006900166260001500235300001100250490000600261520253900267100002202806700001602828700002302844700001902867700002302886700002202909700001702931700002002948700002202968700002202990700002003012700002503032700001903057700002903076700002203105700002003127700001403147700002303161856003603184 2016 eng d a2380-659100aGenetic Investigation Into the Differential Risk of Atrial Fibrillation Among Black and White Individuals.0 aGenetic Investigation Into the Differential Risk of Atrial Fibri c2016 Jul 1 a442-500 v13 aIMPORTANCE: White persons have a higher risk of atrial fibrillation (AF) compared with black individuals despite a lower prevalence of risk factors. This difference may be due, at least in part, to genetic factors.
OBJECTIVES: To determine whether 9 single-nucleotide polymorphisms (SNPs) associated with AF account for this paradoxical differential racial risk for AF and to use admixture mapping to search genome-wide for loci that may account for this phenomenon.
DESIGN, SETTING, AND PARTICIPANTS: Genome-wide admixture analysis and candidate SNP study involving 3 population-based cohort studies that were initiated between 1987 and 1997, including the Cardiovascular Health Study (CHS) (n = 4173), the Atherosclerosis Risk in Communities (ARIC) (n = 12 341) study, and the Health, Aging, and Body Composition (Health ABC) (n = 1015) study. In all 3 studies, race was self-identified. Cox proportional hazards regression models and the proportion of treatment effect method were used to determine the impact of 9 AF-risk SNPs among participants from CHS and the ARIC study. The present study began July 1, 2012, and was completed in 2015.
MAIN OUTCOMES AND MEASURES: Incident AF systematically ascertained using clinic visit electrocardiograms, hospital discharge diagnosis codes, death certificates, and Medicare claims data.
RESULTS: A single SNP, rs10824026 (chromosome 10: position 73661450), was found to significantly mediate the higher risk for AF in white participants compared with black participants in CHS (11.4%; 95% CI, 2.9%-29.9%) and ARIC (31.7%; 95% CI, 16.0%-53.0%). Admixture mapping was performed in a meta-analysis of black participants within CHS (n = 811), ARIC (n = 3112), and Health ABC (n = 1015). No loci that reached the prespecified statistical threshold for genome-wide significance were identified.
CONCLUSIONS AND RELEVANCE: The rs10824026 SNP on chromosome 10q22 mediates a modest proportion of the increased risk of AF among white individuals compared with black individuals, potentially through an effect on gene expression levels of MYOZ1. No additional genetic variants accounting for a significant portion of the differential racial risk of AF were identified with genome-wide admixture mapping, suggesting that additional genetic or environmental influences beyond single SNPs in isolation may account for the paradoxical racial risk of AF among white individuals and black individuals.
1 aRoberts, Jason, D1 aHu, Donglei1 aHeckbert, Susan, R1 aAlonso, Alvaro1 aDewland, Thomas, A1 aVittinghoff, Eric1 aLiu, Yongmei1 aPsaty, Bruce, M1 aOlgin, Jeffrey, E1 aMagnani, Jared, W1 aHuntsman, Scott1 aBurchard, Esteban, G1 aArking, Dan, E1 aBibbins-Domingo, Kirsten1 aHarris, Tamara, B1 aPerez, Marco, V1 aZiv, Elad1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/716502724nas a2200265 4500008004100000022001400041245013800055210006900193260001300262300000900275490000800284520189600292100002202188700002302210700002202233700002402255700001902279700001702298700002002315700002202335700001902357700002302376700002302399856003602422 2016 eng d a1097-674400aImpact of genetic variants on the upstream efficacy of renin-angiotensin system inhibitors for the prevention of atrial fibrillation.0 aImpact of genetic variants on the upstream efficacy of reninangi c2016 May a9-170 v1753 aBACKGROUND: Renin-angiotensin system (RAS) inhibition via angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may reduce the risk of developing atrial fibrillation (AF) in certain populations, but the evidence is conflicting. Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with AF, potentially identifying clinically relevant subtypes of the disease. We sought to investigate the impact of carrier status of 9 AF-associated SNPs on the efficacy of RAS inhibition for the primary prevention of AF.
METHODS: We performed SNP-RAS inhibitor interaction testing with unadjusted and adjusted Cox proportional hazards models using a discovery (Cardiovascular Health Study) and a replication (Atherosclerosis Risk in Communities) cohort. Additive genetic models were used for the SNP analyses, and 2-tailed P values <.05 were considered statistically significant.
RESULTS: Among 2,796 Cardiovascular Health Study participants, none of the 9 a priori identified candidate SNPs exhibited a significant SNP-drug interaction. Two of the 9 SNPs, rs2106261 (16q22) and rs6666258 (1q21), revealed interaction relationships that neared statistical significance (with point estimates in the same direction for angiotensin-converting enzyme inhibitor only and angiotensin II receptor blocker only analyses), but neither association could be replicated among 8,604 participants in Atherosclerosis Risk in Communities.
CONCLUSIONS: Our study failed to identify AF-associated SNP genetic subtypes of AF that derive increased benefit from upstream RAS inhibition for AF prevention. Future studies should continue to investigate the impact of genotype on the response to AF treatment strategies in an effort to develop personalized approaches to therapy and prevention.
1 aRoberts, Jason, D1 aDewland, Thomas, A1 aGlidden, David, V1 aHoffmann, Thomas, J1 aArking, Dan, E1 aChen, Lin, Y1 aPsaty, Bruce, M1 aOlgin, Jeffrey, E1 aAlonso, Alvaro1 aHeckbert, Susan, R1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/716602588nas a2200253 4500008004100000022001400041245008900055210006900144260001300213300001400226490000700240520182000247100002802067700002202095700002202117700002402139700002402163700002302187700002202210700002002232700002302252700002302275856003602298 2017 eng d a1556-387100aAtrial ectopy as a mediator of the association between race and atrial fibrillation.0 aAtrial ectopy as a mediator of the association between race and c2017 Dec a1856-18610 v143 aBACKGROUND: Blacks have a lower risk of atrial fibrillation (AF) despite having more AF risk factors, but the mechanism remains unknown. Premature atrial contraction (PAC) burden is a recently identified risk factor for AF.
OBJECTIVE: The purpose of this study was to determine whether the burden of PACs explains racial differences in AF risk.
METHODS: PAC burden (number per hour) was assessed by 24-hour ambulatory electrocardiographic (ECG) monitoring in a randomly selected subset of patients in the Cardiovascular Health Study. Participants were followed prospectively for the development of AF, diagnosed by study ECG and hospital admission records.
RESULTS: Among 938 participants (median age 73 years; 34% black; 58% female), 206 (22%) developed AF over a median follow-up of 11.0 years (interquartile range 6.1-13.4). After adjusting for age, sex, body mass index, coronary disease, congestive heart failure, diabetes, hypertension, alcohol consumption, smoking status, and study site, black race was associated with a 42% lower risk of AF (hazard ratio 0.58, 95% confidence interval [CI] 0.40-0.85; P = .005). The baseline PAC burden was 2.10 times (95% CI 1.57-2.83; P <.001) higher in whites than blacks. There was no detectable difference in premature ventricular contraction (PVC) burden by race. PAC burden mediated 19.5% (95% CI 6.3-52.5) of the adjusted association between race and AF.
CONCLUSION: On average, whites exhibited more PACs than blacks, and this difference statistically explains a modest proportion of the differential risk of AF by race. The differential PAC burden, without differences in PVCs, by race suggests that identifiable common exposures or genetic influences might be important to atrial pathophysiology.
1 aChristensen, Matthew, A1 aNguyen, Kaylin, T1 aStein, Phyllis, K1 aFohtung, Raymond, B1 aSoliman, Elsayed, Z1 aDewland, Thomas, A1 aVittinghoff, Eric1 aPsaty, Bruce, M1 aHeckbert, Susan, R1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/755502652nas a2200265 4500008004100000022001400041245009100055210006900146260001600215490000600231520185100237100002202088700002202110700002302132700002302155700002402178700002202202700002402224700001902248700001702267700002002284700002302304700002302327856003602350 2017 eng d a2047-998000aEctopy on a Single 12-Lead ECG, Incident Cardiac Myopathy, and Death in the Community.0 aEctopy on a Single 12Lead ECG Incident Cardiac Myopathy and Deat c2017 Aug 030 v63 aBACKGROUND: Atrial fibrillation and heart failure are 2 of the most common diseases, yet ready means to identify individuals at risk are lacking. The 12-lead ECG is one of the most accessible tests in medicine. Our objective was to determine whether a premature atrial contraction observed on a standard 12-lead ECG would predict atrial fibrillation and mortality and whether a premature ventricular contraction would predict heart failure and mortality.
METHODS AND RESULTS: We utilized the CHS (Cardiovascular Health) Study, which followed 5577 participants for a median of 12 years, as the primary cohort. The ARIC (Atherosclerosis Risk in Communities Study), the replication cohort, captured data from 15 792 participants over a median of 22 years. In the CHS, multivariable analyses revealed that a baseline 12-lead ECG premature atrial contraction predicted a 60% increased risk of atrial fibrillation (hazard ratio, 1.6; 95% CI, 1.3-2.0; P<0.001) and a premature ventricular contraction predicted a 30% increased risk of heart failure (hazard ratio, 1.3; 95% CI, 1.0-1.6; P=0.021). In the negative control analyses, neither predicted incident myocardial infarction. A premature atrial contraction was associated with a 30% increased risk of death (hazard ratio, 1.3; 95% CI, 1.1-1.5; P=0.008) and a premature ventricular contraction was associated with a 20% increased risk of death (hazard ratio, 1.2; 95% CI, 1.0-1.3; P=0.044). Similarly statistically significant results for each analysis were also observed in ARIC.
CONCLUSIONS: Based on a single standard ECG, a premature atrial contraction predicted incident atrial fibrillation and death and a premature ventricular contraction predicted incident heart failure and death, suggesting that this commonly used test may predict future disease.
1 aNguyen, Kaylin, T1 aVittinghoff, Eric1 aDewland, Thomas, A1 aDukes, Jonathan, W1 aSoliman, Elsayed, Z1 aStein, Phyllis, K1 aGottdiener, John, S1 aAlonso, Alvaro1 aChen, Lin, Y1 aPsaty, Bruce, M1 aHeckbert, Susan, R1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/748902234nas a2200205 4500008004100000022001400041245006600055210006500121260001600186300001200202490000600214520164000220100001901860700002301879700002201902700002301924700002201947700002301969856003601992 2018 eng d a2047-998000aModifiable Predictors of Ventricular Ectopy in the Community.0 aModifiable Predictors of Ventricular Ectopy in the Community c2018 Nov 20 ae0100780 v73 aBackground Premature ventricular contractions (PVCs) predict heart failure and death. Data regarding modifiable risk factors for PVCs are scarce. Methods and Results We studied 1424 Cardiovascular Health Study participants randomly assigned to 24-hour Holter monitoring. Demographics, comorbidities, habits, and echocardiographic measurements were examined as predictors of PVC frequency and, among 845 participants, change in PVC frequency 5 years later. Participants exhibited a median of 0.6 (interquartile range, 0.1-7.1) PVCs per hour. Of the more directly modifiable characteristics and after multivariable adjustment, every SD increase in systolic blood pressure was associated with 9% more PVCs (95% confidence interval [CI], 2%-17%; P=0.01), regularly performing no or low-intensity exercise compared with more physical activity was associated with ≈15% more PVCs (95% CI, 3-25%; P=0.02), and those with a history of smoking exhibited an average of 18% more PVCs (95% CI, 3-36%; P=0.02) than did never smokers. After 5 years, PVC frequency increased from a median of 0.5 (IQR, 0.1-4.7) to 1.2 (IQR, 0.1-13.8) per hour ( P<0.0001). Directly modifiable predictors of 5-year increase in PVCs, described as the odds per each quintile increase in PVCs, included increased diastolic blood pressure (odds ratio per SD increase, 1.16; 95% CI, 1.02-1.31; P=0.02) and a history of smoking (OR, 1.31; 95% CI, 1.02-1.68; P=0.04). Conclusions Enhancing physical activity, smoking cessation, and aggressive control of blood pressure may represent fruitful strategies to mitigate PVC frequency and PVC-associated adverse outcomes.
1 aKerola, Tuomas1 aDewland, Thomas, A1 aVittinghoff, Eric1 aHeckbert, Susan, R1 aStein, Phyllis, K1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/791708664nas a2202749 4500008004100000022001400041245007200055210006900127260001300196300001400209490000700223520107000230100002201300700002101322700001801343700002601361700002001387700002501407700001901432700001901451700002901470700002301499700001901522700001801541700002001559700002401579700002501603700001901628700002201647700002101669700002401690700002301714700001801737700002101755700002301776700002001799700002301819700001701842700002201859700001901881700002201900700003001922700001901952700001801971700001701989700001602006700002102022700002302043700002302066700002202089700001902111700002202130700002102152700002102173700001802194700002102212700002202233700001402255700001602269700001902285700001802304700002202322700001402344700002102358700002302379700002002402700002402422700001702446700001902463700002302482700002102505700002002526700002202546700002202568700002302590700002302613700002202636700001902658700002802677700001502705700001902720700002202739700002002761700002202781700001502803700002502818700001902843700001902862700001902881700002002900700002302920700001802943700002002961700002202981700002803003700002003031700002203051700002303073700002103096700002203117700001903139700002103158700001903179700002203198700001903220700002203239700002403261700002403285700001203309700001903321700001803340700001903358700001503377700002503392700002303417700001803440700002003458700001803478700001803496700002803514700002503542700002503567700002003592700001803612700002303630700002303653700002103676700002603697700002003723700002203743700001903765700002503784700002303809700002303832700002203855700003003877700001903907700002003926700002203946700002903968700002603997700001704023700001904040700002104059700001904080700002204099700002504121700002504146700001704171700002104188700002304209700001704232700002304249700002004272700002004292700001904312700002404331700002104355700002004376700002004396700002004416700002204436700001804458700001804476700002104494700002604515700001804541700002204559700001604581700002504597700002404622700002304646700002404669700002204693700002104715700002104736700002304757700001604780700002104796700001704817700002404834700002304858700001904881700002204900700002204922700002104944700002004965700001804985700002305003700002305026700002405049700002205073700002305095700001605118700001305134700002405147700002205171700002505193700002005218700002405238700002205262700002705284700002005311700002205331700001905353700002805372700001505400700002805415700002605443700001805469700002705487700001705514700001505531700002005546700001505566700001605581700001805597700002005615700002205635700001905657700001605676700002505692700001905717700001305736700002305749700001805772700001805790700002205808700002405830700002405854856003605878 2018 eng d a1546-171800aMulti-ethnic genome-wide association study for atrial fibrillation.0 aMultiethnic genomewide association study for atrial fibrillation c2018 Sep a1225-12330 v503 aAtrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
1 aRoselli, Carolina1 aChaffin, Mark, D1 aWeng, Lu-Chen1 aAeschbacher, Stefanie1 aAhlberg, Gustav1 aAlbert, Christine, M1 aAlmgren, Peter1 aAlonso, Alvaro1 aAnderson, Christopher, D1 aAragam, Krishna, G1 aArking, Dan, E1 aBarnard, John1 aBartz, Traci, M1 aBenjamin, Emelia, J1 aBihlmeyer, Nathan, A1 aBis, Joshua, C1 aBloom, Heather, L1 aBoerwinkle, Eric1 aBottinger, Erwin, B1 aBrody, Jennifer, A1 aCalkins, Hugh1 aCampbell, Archie1 aCappola, Thomas, P1 aCarlquist, John1 aChasman, Daniel, I1 aChen, Lin, Y1 aChen, Yii-Der Ida1 aChoi, Eue-Keun1 aChoi, Seung, Hoan1 aChristophersen, Ingrid, E1 aChung, Mina, K1 aCole, John, W1 aConen, David1 aCook, James1 aCrijns, Harry, J1 aCutler, Michael, J1 aDamrauer, Scott, M1 aDaniels, Brian, R1 aDarbar, Dawood1 aDelgado, Graciela1 aDenny, Joshua, C1 aDichgans, Martin1 aDörr, Marcus1 aDudink, Elton, A1 aDudley, Samuel, C1 aEsa, Nada1 aEsko, Tõnu1 aEskola, Markku1 aFatkin, Diane1 aFelix, Stephan, B1 aFord, Ian1 aFranco, Oscar, H1 aGeelhoed, Bastiaan1 aGrewal, Raji, P1 aGudnason, Vilmundur1 aGuo, Xiuqing1 aGupta, Namrata1 aGustafsson, Stefan1 aGutmann, Rebecca1 aHamsten, Anders1 aHarris, Tamara, B1 aHayward, Caroline1 aHeckbert, Susan, R1 aHernesniemi, Jussi1 aHocking, Lynne, J1 aHofman, Albert1 aHorimoto, Andrea, R V R1 aHuang, Jie1 aHuang, Paul, L1 aHuffman, Jennifer1 aIngelsson, Erik1 aIpek, Esra, Gucuk1 aIto, Kaoru1 aJimenez-Conde, Jordi1 aJohnson, Renee1 aJukema, Wouter1 aKääb, Stefan1 aKähönen, Mika1 aKamatani, Yoichiro1 aKane, John, P1 aKastrati, Adnan1 aKathiresan, Sekar1 aKatschnig-Winter, Petra1 aKavousi, Maryam1 aKessler, Thorsten1 aKietselaer, Bas, L1 aKirchhof, Paulus1 aKleber, Marcus, E1 aKnight, Stacey1 aKrieger, Jose, E1 aKubo, Michiaki1 aLauner, Lenore, J1 aLaurikka, Jari1 aLehtimäki, Terho1 aLeineweber, Kirsten1 aLemaitre, Rozenn, N1 aLi, Man1 aLim, Hong, Euy1 aLin, Henry, J1 aLin, Honghuang1 aLind, Lars1 aLindgren, Cecilia, M1 aLokki, Marja-Liisa1 aLondon, Barry1 aLoos, Ruth, J F1 aLow, Siew-Kee1 aLu, Yingchang1 aLyytikäinen, Leo-Pekka1 aMacfarlane, Peter, W1 aMagnusson, Patrik, K1 aMahajan, Anubha1 aMalik, Rainer1 aMansur, Alfredo, J1 aMarcus, Gregory, M1 aMargolin, Lauren1 aMargulies, Kenneth, B1 aMärz, Winfried1 aMcManus, David, D1 aMelander, Olle1 aMohanty, Sanghamitra1 aMontgomery, Jay, A1 aMorley, Michael, P1 aMorris, Andrew, P1 aMüller-Nurasyid, Martina1 aNatale, Andrea1 aNazarian, Saman1 aNeumann, Benjamin1 aNewton-Cheh, Christopher1 aNiemeijer, Maartje, N1 aNikus, Kjell1 aNilsson, Peter1 aNoordam, Raymond1 aOellers, Heidi1 aOlesen, Morten, S1 aOrho-Melander, Marju1 aPadmanabhan, Sandosh1 aPak, Hui-Nam1 aParé, Guillaume1 aPedersen, Nancy, L1 aPera, Joanna1 aPereira, Alexandre1 aPorteous, David1 aPsaty, Bruce, M1 aPulit, Sara, L1 aPullinger, Clive, R1 aRader, Daniel, J1 aRefsgaard, Lena1 aRibasés, Marta1 aRidker, Paul, M1 aRienstra, Michiel1 aRisch, Lorenz1 aRoden, Dan, M1 aRosand, Jonathan1 aRosenberg, Michael, A1 aRost, Natalia1 aRotter, Jerome, I1 aSaba, Samir1 aSandhu, Roopinder, K1 aSchnabel, Renate, B1 aSchramm, Katharina1 aSchunkert, Heribert1 aSchurman, Claudia1 aScott, Stuart, A1 aSeppälä, Ilkka1 aShaffer, Christian1 aShah, Svati1 aShalaby, Alaa, A1 aShim, Jaemin1 aShoemaker, Benjamin1 aSiland, Joylene, E1 aSinisalo, Juha1 aSinner, Moritz, F1 aSlowik, Agnieszka1 aSmith, Albert, V1 aSmith, Blair, H1 aSmith, Gustav1 aSmith, Jonathan, D1 aSmith, Nicholas, L1 aSoliman, Elsayed, Z1 aSotoodehnia, Nona1 aStricker, Bruno, H1 aSun, Albert1 aSun, Han1 aSvendsen, Jesper, H1 aTanaka, Toshihiro1 aTanriverdi, Kahraman1 aTaylor, Kent, D1 aTeder-Laving, Maris1 aTeumer, Alexander1 aThériault, Sébastien1 aTrompet, Stella1 aTucker, Nathan, R1 aTveit, Arnljot1 aUitterlinden, André, G1 aHarst, Pim1 aVan Gelder, Isabelle, C1 aVan Wagoner, David, R1 aVerweij, Niek1 aVlachopoulou, Efthymia1 aVölker, Uwe1 aWang, Biqi1 aWeeke, Peter, E1 aWeijs, Bob1 aWeiss, Raul1 aWeiss, Stefan1 aWells, Quinn, S1 aWiggins, Kerri, L1 aWong, Jorge, A1 aWoo, Daniel1 aWorrall, Bradford, B1 aYang, Pil-Sung1 aYao, Jie1 aYoneda, Zachary, T1 aZeller, Tanja1 aZeng, Lingyao1 aLubitz, Steven, A1 aLunetta, Kathryn, L1 aEllinor, Patrick, T uhttps://chs-nhlbi.org/node/781102716nas a2200337 4500008004100000022001400041245006000055210005900115260001300174300001400187490000700201520176600208100002801974700001902002700002302021700002202044700001702066700002202083700002402105700001902129700002102148700002002169700002102189700002202210700002002232700002202252700002202274700002302296700002302319856003602342 2018 eng d a1556-387100aSleep characteristics that predict atrial fibrillation.0 aSleep characteristics that predict atrial fibrillation c2018 Sep a1289-12950 v153 aBACKGROUND: The relationship between sleep disruption, independent of obstructive sleep apnea (OSA), and atrial fibrillation (AF) is unknown.
OBJECTIVE: The purpose of this study was to determine whether poor sleep itself is a risk factor for AF.
METHODS: We first performed an analysis of participants in the Health eHeart Study and validated those findings in the longitudinal Cardiovascular Health Study, including a subset of patients undergoing polysomnography. To determine whether the observed relationships readily translated to medical practice, we examined 2005-2009 data from the California Healthcare Cost and Utilization Project.
RESULTS: Among 4553 Health eHeart participants, the 526 with AF exhibited more frequent nighttime awakening (odd ratio [OR] 1.47; 95% confidence interval [CI] 1.14-1.89; P = .003). In 5703 Cardiovascular Health Study participants followed for a median 11.6 years, frequent nighttime awakening predicted a 33% greater risk of AF (hazard ratio [HR] 1.33; 95% CI 1.17-1.51; P <.001). In patients with polysomnography (N = 1127), every standard deviation percentage decrease in rapid eye movement (REM) sleep was associated with a 18% higher risk of developing AF (HR 1.18; 95% CI 1.00-1.38; P = .047). Among 14,330,651 California residents followed for a median 3.9 years, an insomnia diagnosis predicted a 36% increased risk of new AF (HR 1.36; 95% CI 1.30-1.42; P <.001).
CONCLUSION: Sleep disruption consistently predicted AF before and after adjustment for OSA and other potential confounders across several different populations. Sleep quality itself may be important in the pathogenesis of AF, potentially representing a novel target for prevention.
1 aChristensen, Matthew, A1 aDixit, Shalini1 aDewland, Thomas, A1 aWhitman, Isaac, R1 aNah, Gregory1 aVittinghoff, Eric1 aMukamal, Kenneth, J1 aRedline, Susan1 aRobbins, John, A1 aNewman, Anne, B1 aPatel, Sanjay, R1 aMagnani, Jared, W1 aPsaty, Bruce, M1 aOlgin, Jeffrey, E1 aPletcher, Mark, J1 aHeckbert, Susan, R1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/778701867nas a2200253 4500008004100000022001400041245005500055210005400110260001600164300000900180490000600189520117000195100001901365700002101384700002201405700002201427700002301449700002801472700001301500700001701513700002401530700002301554856003601577 2019 eng d a2045-232200aAlcohol consumption and leukocyte telomere length.0 aAlcohol consumption and leukocyte telomere length c2019 Feb 05 a14040 v93 aThe relationship between alcohol consumption and mortality generally exhibits a U-shaped curve. The longevity observed with moderate alcohol consumption may be explained by other confounding factors, and, if such a relationship is present, the mechanism is not well understood. Indeed, the optimal amount of alcohol consumption for health has yet to be determined. Leukocyte telomere length is an emerging quantifiable marker of biological age and health, and a shorter telomere length is a predictor of increased mortality. Because leukocyte telomere length is a quantifiable and objectively measurable biomarker of aging, we sought to identify the amount of alcohol consumption associated with the longest telomere length and least telomere length attrition. Among over 2,000 participants from two distinct cohort studies, we found no pattern of alcohol consumption that was associated with longer telomere length or less telomere length attrition over time. Binge drinking may reduce telomere length. Using telomere length as a marker of age and health, these data fail to demonstrate any benefits of alcohol consumption, even when consumed in moderation.
1 aDixit, Shalini1 aWhooley, Mary, A1 aVittinghoff, Eric1 aRoberts, Jason, D1 aHeckbert, Susan, R1 aFitzpatrick, Annette, L1 aLin, Jue1 aLeung, Cindy1 aMukamal, Kenneth, J1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/797102786nas a2200289 4500008004100000022001400041245010600055210006900161260001600230300001200246490000600258520191000264100002202174700002202196700003002218700002402248700001902272700002002291700002302311700002202334700001902356700002202375700001702397700002302414700002302437856003602460 2019 eng d a2047-998000aNT -pro BNP as a Mediator of the Racial Difference in Incident Atrial Fibrillation and Heart Failure.0 aNT pro BNP as a Mediator of the Racial Difference in Incident At c2019 Apr 02 ae0108680 v83 aBackground Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation ( AF ). Conversely, whites may have a lower risk of heart failure ( CHF ). N-terminal pro-B-type natriuretic peptide ( NT -pro BNP) levels are higher in whites, predict incident AF , and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NT -pro BNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT -pro BNP . The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12 418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT -pro BNP ( CHS : 40% higher than blacks; 95% CI , 29-53; ARIC : 39% higher; 95% CI , 33-46) and had a greater risk of incident AF compared with blacks ( CHS : adjusted hazard ratio, 1.60; 95% CI , 1.31-1.93; ARIC : hazard ratio, 1.93; 95% CI , 1.57-2.27). NT -pro BNP levels explained a significant proportion of the racial difference in AF risk ( CHS : 36.2%; 95% CI , 23.2-69.2%; ARIC : 24.6%; 95% CI , 14.8-39.6%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95% CI , 1.05-1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95% CI , 0.94-1.23), CHF -related mediation analyses were not performed. Conclusions A substantial portion of the relationship between race and AF was statistically explained by baseline NT -pro BNP levels. No consistent relationship between race and CHF was observed.
1 aWhitman, Isaac, R1 aVittinghoff, Eric1 adeFilippi, Christopher, R1 aGottdiener, John, S1 aAlonso, Alvaro1 aPsaty, Bruce, M1 aHeckbert, Susan, R1 aHoogeveen, Ron, C1 aArking, Dan, E1 aSelvin, Elizabeth1 aChen, Lin, Y1 aDewland, Thomas, A1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/800802287nas a2200181 4500008004100000022001400041245008400055210006900139260001600208520171300224100001901937700002301956700002201979700002302001700002202024700002302046856003602069 2019 eng d a1532-209200aPredictors of atrial ectopy and their relationship to atrial fibrillation risk.0 aPredictors of atrial ectopy and their relationship to atrial fib c2019 Mar 063 aAIMS: Premature atrial contractions (PACs) are known to trigger and predict atrial fibrillation (AF). We sought to identify the determinants of PACs and the degree to which PACs mediate the effects of established risk factors for AF.
METHODS AND RESULTS: Predictors of baseline PAC frequency were examined using a Holter Study among 1392 participants in the Cardiovascular Health Study, a community-based cohort of individuals aged ≥65 years. Participants were then followed for their first diagnosis of AF. Independent predictors of PACs were identified, and the extent to which PACs might mediate the relationship between those predictors and AF was determined. The median hourly frequency of PACs was 2.7 (interquartile range 0.8-12.1). After multivariable adjustment, increasing age, increasing height, decreasing body mass index, and a history of myocardial infarction were each associated with more PACs. Regarding modifiable predictors, participants using beta-blockers had 21% less [95% confidence interval (95% CI) 9-30%, P = 0.001] and those performing at least moderate intensity exercise vs. lower intensity exercisers had 10% less (95% CI 1-18%, P = 0.03) PACs. Higher PAC frequency explained 34% (95% CI 22-57%, P < 0.0001) of the relationship between increasing age and AF risk and 27% (95% CI 10-75%, P = 0.004) of the relationship between taller height and AF risk.
CONCLUSION: Enhancing physical activity and use of beta-blockers may represent fruitful strategies to mitigate PAC frequency. A substantial proportion of the excess risk of AF due to increasing age and taller height may be explained by an increase in PAC frequency.
1 aKerola, Tuomas1 aDewland, Thomas, A1 aVittinghoff, Eric1 aHeckbert, Susan, R1 aStein, Phyllis, K1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/800603329nas a2200277 4500008004100000022001400041245012700055210006900182260001600251490000600267520248500273100001902758700002302777700001102800700001902811700002002830700002102850700002002871700002302891700002302914700001502937700002302952700002002975700002002995856003603015 2020 eng d a2379-370800aCharacterization of cardiac mechanics and incident atrial fibrillation in participants of the Cardiovascular Health Study.0 aCharacterization of cardiac mechanics and incident atrial fibril c2020 Oct 020 v53 aBACKGROUND: 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.
1 aPatel, Ravi, B1 aDelaney, Joseph, A1 aHu, Mo1 aPatel, Harnish1 aCheng, Jeanette1 aGottdiener, John1 aKizer, Jorge, R1 aMarcus, Gregory, M1 aTurakhia, Mintu, P1 aDeo, Rajat1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aShah, Sanjiv, J uhttps://chs-nhlbi.org/node/848604417nas a2200649 4500008004100000022001400041245006500055210006400120260001500184300001400199490000800213520264800221653000902869653001002878653002402888653002002912653002402932653001602956653001102972653002202983653001103005653001403016653000903030653003703039653001603076653002703092653002003119100002203139700002203161700001503183700001903198700001503217700002403232700003203256700002003288700001903308700002303327700001903350700001903369700002303388700001803411700002103429700002103450700002003471700002003491700002003511700002203531700002403553700002403577700002103601700002103622700002203643700002403665700001903689700002303708856003603731 2021 eng d a1524-453900aEpigenetic Age and the Risk of Incident Atrial Fibrillation.0 aEpigenetic Age and the Risk of Incident Atrial Fibrillation c2021 12 14 a1899-19110 v1443 aBACKGROUND: The most prominent risk factor for atrial fibrillation (AF) is chronological age; however, underlying mechanisms are unexplained. Algorithms using epigenetic modifications to the human genome effectively predict chronological age. Chronological and epigenetic predicted ages may diverge in a phenomenon referred to as epigenetic age acceleration (EAA), which may reflect accelerated biological aging. We sought to evaluate for associations between epigenetic age measures and incident AF.
METHODS: Measures for 4 epigenetic clocks (Horvath, Hannum, DNA methylation [DNAm] PhenoAge, and DNAm GrimAge) and an epigenetic predictor of PAI-1 (plasminogen activator inhibitor-1) levels (ie, DNAm PAI-1) were determined for study participants from 3 population-based cohort studies. Cox models evaluated for associations with incident AF and results were combined via random-effects meta-analyses. Two-sample summary-level Mendelian randomization analyses evaluated for associations between genetic instruments of the EAA measures and AF.
RESULTS: Among 5600 participants (mean age, 65.5 years; female, 60.1%; Black, 50.7%), there were 905 incident AF cases during a mean follow-up of 12.9 years. Unadjusted analyses revealed all 4 epigenetic clocks and the DNAm PAI-1 predictor were associated with statistically significant higher hazards of incident AF, though the magnitudes of their point estimates were smaller relative to the associations observed for chronological age. The pooled EAA estimates for each epigenetic measure, with the exception of Horvath EAA, were associated with incident AF in models adjusted for chronological age, race, sex, and smoking variables. After multivariable adjustment for additional known AF risk factors that could also potentially function as mediators, pooled EAA measures for 2 clocks remained statistically significant. Five-year increases in EAA measures for DNAm GrimAge and DNAm PhenoAge were associated with 19% (adjusted hazard ratio [HR], 1.19 [95% CI, 1.09-1.31]; <0.01) and 15% (adjusted HR, 1.15 [95% CI, 1.05-1.25]; <0.01) higher hazards of incident AF, respectively. Mendelian randomization analyses for the 5 EAA measures did not reveal statistically significant associations with AF.
CONCLUSIONS: Our study identified adjusted associations between EAA measures and incident AF, suggesting that biological aging plays an important role independent of chronological age, though a potential underlying causal relationship remains unclear. These aging processes may be modifiable and not constrained by the immutable factor of time.
10aAged10aAging10aAtrial Fibrillation10aDNA Methylation10aEpigenesis, Genetic10aEpigenomics10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aMendelian Randomization Analysis10aMiddle Aged10aModels, Cardiovascular10aModels, Genetic1 aRoberts, Jason, D1 aVittinghoff, Eric1 aLu, Ake, T1 aAlonso, Alvaro1 aWang, Biqi1 aSitlani, Colleen, M1 aMohammadi-Shemirani, Pedrum1 aFornage, Myriam1 aKornej, Jelena1 aBrody, Jennifer, A1 aArking, Dan, E1 aLin, Honghuang1 aHeckbert, Susan, R1 aProkic, Ivana1 aGhanbari, Mohsen1 aSkanes, Allan, C1 aBartz, Traci, M1 aPerez, Marco, V1 aTaylor, Kent, D1 aLubitz, Steven, A1 aEllinor, Patrick, T1 aLunetta, Kathryn, L1 aPankow, James, S1 aParé, Guillaume1 aSotoodehnia, Nona1 aBenjamin, Emelia, J1 aHorvath, Steve1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/900102672nas a2200289 4500008004100000022001400041245010200055210006900157260001600226520178900242100002702031700002302058700002202081700002102103700001702124700002002141700002402161700002002185700002202205700002002227700002202247700002102269700001302290700002002303700002302323856003602346 2021 eng d a1468-201X00aPremature ventricular complexes and development of heart failure in a community-based population.0 aPremature ventricular complexes and development of heart failure c2021 Sep 073 aOBJECTIVE: A higher premature ventricular complex (PVC) frequency is associated with incident congestive heart failure (CHF) and death. While certain PVC characteristics may contribute to that risk, the current literature stems from patients in medical settings and is therefore prone to referral bias. This study aims to identify PVC characteristics associated with incident CHF in a community-based setting.
METHODS: The Cardiovascular Health Study is a cohort of community-dwelling individuals who underwent prospective evaluation and follow-up. We analysed 24-hour Holter data to assess PVC characteristics and used multivariable logistic and Cox proportional hazards models to identify predictors of a left ventricular ejection fraction (LVEF) decline and incident CHF, respectively.
RESULTS: Of 871 analysed participants, 316 participants exhibited at least 10 PVCs during the 24-hour recording. For participants with PVCs, the average age was 72±5 years, 41% were women and 93% were white. Over a median follow-up of 11 years, 34% developed CHF. After adjusting for demographics, cardiovascular comorbidities, antiarrhythmic drug use and PVC frequency, a greater heterogeneity of the PVC coupling interval was associated with an increased risk of LVEF decline and incident CHF. Of note, neither PVC duration nor coupling interval duration exhibited a statistically significant relationship with either outcome.
CONCLUSIONS: In this first community-based study to identify Holter-based features of PVCs that are associated with LVEF reduction and incident CHF, the fact that coupling interval heterogeneity was an independent risk factor suggests that the mechanism of PVC generation may influence the risk of heart failure.
1 aLimpitikul, Worawan, B1 aDewland, Thomas, A1 aVittinghoff, Eric1 aSoliman, Elsayed1 aNah, Gregory1 aFang, Christina1 aSiscovick, David, S1 aPsaty, Bruce, M1 aSotoodehnia, Nona1 aHeckbert, Susan1 aStein, Phyllis, K1 aGottdiener, John1 aHu, Xiao1 aHempfling, Ralf1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/892306073nas a2201597 4500008004100000022001400041245008800055210006900143260001300212300001200225490000800237520158400245653001201829653001201841653002501853653003401878653001801912653002901930653001101959653000901970653001301979653003001992100002502022700002802047700002902075700002202104700001902126700001902145700001702164700001802181700001702199700001302216700002202229700001902251700002602270700002602296700002302322700001902345700002002364700001702384700002202401700003102423700001902454700002302473700002602496700002102522700002102543700002402564700002002588700002102608700002002629700002002649700001602669700002702685700001902712700001902731700002002750700001902770700002302789700002402812700001802836700001602854700002602870700002302896700002202919700002002941700001902961700002702980700001903007700002103026700002403047700002403071700001403095700002203109700001503131700001903146700002303165700002303188700002203211700002103233700002503254700001903279700002303298700001903321700002203340700001903362700002303381700001303404700002303417700002203440700002103462700002203483700002303505700002103528700002303549700001803572700001903590700002203609700002103631700002803652700002203680700001903702700002203721700002003743700001703763700001403780700001603794700002203810700001803832700002303850700001803873700002403891700002403915700001903939700001803958700002203976700002403998700001504022700002104037700001804058700002304076700002304099700002504122700002504147700002104172700001804193700002504211700002304236700002204259700002104281700002504302700002304327700002404350710006504374856003604439 2023 eng d a1476-468700aAberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.0 aAberrant activation of TCL1A promotes stem cell expansion in clo c2023 Apr a755-7630 v6163 aMutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis. These lesions are precursors for blood cancers, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, but this effect was not seen in clones with driver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimental knockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
10aAlleles10aAnimals10aClonal Hematopoiesis10aGenome-Wide Association Study10aHematopoiesis10aHematopoietic Stem Cells10aHumans10aMice10aMutation10aPromoter Regions, Genetic1 aWeinstock, Joshua, S1 aGopakumar, Jayakrishnan1 aBurugula, Bala, Bharathi1 aUddin, Md, Mesbah1 aJahn, Nikolaus1 aBelk, Julia, A1 aBouzid, Hind1 aDaniel, Bence1 aMiao, Zhuang1 aLy, Nghi1 aMack, Taralynn, M1 aLuna, Sofia, E1 aProthro, Katherine, P1 aMitchell, Shaneice, R1 aLaurie, Cecelia, A1 aBroome, Jai, G1 aTaylor, Kent, D1 aGuo, Xiuqing1 aSinner, Moritz, F1 avon Falkenhausen, Aenne, S1 aKääb, Stefan1 aShuldiner, Alan, R1 aO'Connell, Jeffrey, R1 aLewis, Joshua, P1 aBoerwinkle, Eric1 aBarnes, Kathleen, C1 aChami, Nathalie1 aKenny, Eimear, E1 aLoos, Ruth, J F1 aFornage, Myriam1 aHou, Lifang1 aLloyd-Jones, Donald, M1 aRedline, Susan1 aCade, Brian, E1 aPsaty, Bruce, M1 aBis, Joshua, C1 aBrody, Jennifer, A1 aSilverman, Edwin, K1 aYun, Jeong, H1 aQiao, Dandi1 aPalmer, Nicholette, D1 aFreedman, Barry, I1 aBowden, Donald, W1 aCho, Michael, H1 aDeMeo, Dawn, L1 aVasan, Ramachandran, S1 aYanek, Lisa, R1 aBecker, Lewis, C1 aKardia, Sharon, L R1 aPeyser, Patricia, A1 aHe, Jiang1 aRienstra, Michiel1 aHarst, Pim1 aKaplan, Robert1 aHeckbert, Susan, R1 aSmith, Nicholas, L1 aWiggins, Kerri, L1 aArnett, Donna, K1 aIrvin, Marguerite, R1 aTiwari, Hemant1 aCutler, Michael, J1 aKnight, Stacey1 aMuhlestein, Brent1 aCorrea, Adolfo1 aRaffield, Laura, M1 aGao, Yan1 ade Andrade, Mariza1 aRotter, Jerome, I1 aRich, Stephen, S1 aTracy, Russell, P1 aKonkle, Barbara, A1 aJohnsen, Jill, M1 aWheeler, Marsha, M1 aSmith, Gustav1 aMelander, Olle1 aNilsson, Peter, M1 aCuster, Brian, S1 aDuggirala, Ravindranath1 aCurran, Joanne, E1 aBlangero, John1 aMcGarvey, Stephen1 aWilliams, Keoki1 aXiao, Shujie1 aYang, Mao1 aGu, Charles1 aChen, Yii-Der Ida1 aLee, Wen-Jane1 aMarcus, Gregory, M1 aKane, John, P1 aPullinger, Clive, R1 aShoemaker, Benjamin1 aDarbar, Dawood1 aRoden, Dan, M1 aAlbert, Christine1 aKooperberg, Charles1 aZhou, Ying1 aManson, JoAnn, E1 aDesai, Pinkal1 aJohnson, Andrew, D1 aMathias, Rasika, A1 aBlackwell, Thomas, W1 aAbecasis, Goncalo, R1 aSmith, Albert, V1 aKang, Hyun, M1 aSatpathy, Ansuman, T1 aNatarajan, Pradeep1 aKitzman, Jacob, O1 aWhitsel, Eric, A1 aReiner, Alexander, P1 aBick, Alexander, G1 aJaiswal, Siddhartha1 aNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium uhttps://chs-nhlbi.org/node/938700800nas a2200277 4500008004100000022001400041245005000055210004900105260001600154300001200170490000700182653003800189653002400227653001600251653001100267653001700278100003100295700002400326700002400350700002000374700002200394700002000416700002700436700002300463856003600486 2023 eng d a2047-998000aInflammation and Incident Conduction Disease.0 aInflammation and Incident Conduction Disease c2023 Jan 03 ae0272470 v1210aCardiac Conduction System Disease10aElectrocardiography10aHeart Block10aHumans10aInflammation1 aFrimodt-Møller, Emilie, K1 aGottdiener, John, S1 aSoliman, Elsayed, Z1 aKizer, Jorge, R1 aVittinghoff, Eric1 aPsaty, Bruce, M1 aBiering-Sørensen, Tor1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/923702451nas a2200205 4500008004100000022001400041245006500055210006400120260001600184520181800200100003102018700002402049700002002073700002202093700002002115700002702135700002402162700002302186856003602209 2023 eng d a1522-964500aLifestyle habits associated with cardiac conduction disease.0 aLifestyle habits associated with cardiac conduction disease c2023 Jan 203 aAIMS: Cardiac conduction disease can lead to syncope, heart failure, and death. The only available therapy is pacemaker implantation, with no established prevention strategies. Research to identify modifiable risk factors has been scant.
METHODS AND RESULTS: Data from the Cardiovascular Health Study, a population-based cohort study of adults ≥ 65 years with annual 12-lead electrocardiograms obtained over 10 years, were utilized to examine relationships between baseline characteristics, including lifestyle habits, and conduction disease. Of 5050 participants (mean age 73 ± 6 years; 52% women), prevalent conduction disease included 257 with first-degree atrioventricular block, 99 with left anterior fascicular block, 9 with left posterior fascicular block, 193 with right bundle branch block (BBB), 76 with left BBB, and 102 with intraventricular block at baseline. After multivariable adjustment, older age, male sex, a larger body mass index, hypertension, and coronary heart disease were associated with a higher prevalence of conduction disease, whereas White race and more physical activity were associated with a lower prevalence. Over a median follow-up on 7 (interquartile range 1-9) years, 1036 developed incident conduction disease. Older age, male sex, a larger BMI, and diabetes were each associated with incident conduction disease. Of lifestyle habits, more physical activity (hazard ratio 0.91, 95% confidence interval 0.84-0.98, P = 0.017) was associated with a reduced risk, while smoking and alcohol did not exhibit a significant association.
CONCLUSION: While some difficult to control comorbidities were associated with conduction disease as expected, a readily modifiable lifestyle factor, physical activity, was associated with a lower risk.
1 aFrimodt-Møller, Emilie, K1 aSoliman, Elsayed, Z1 aKizer, Jorge, R1 aVittinghoff, Eric1 aPsaty, Bruce, M1 aBiering-Sørensen, Tor1 aGottdiener, John, S1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/9288