Frequency of Visit-to-Visit Variability of Resting Heart Rate and the Risk of New-Onset Atrial Fibrillation in the General Population

Resting heart rate (RHR) has been an established predictor for atrial fibrillation (AF). However, the association of visit-to-visit variability (VVHRV) with new-onset AF risk over long term remains unclear. Our study investigates relation VVHRV to in general population prospective Kailuan cohort. A total 46,126 individuals without arrhythmia were included. They underwent 3 health examinations from 2006 2010 and performed follow up. was measured by coefficient variation (CV), independent mean (VIM), standard deviation (SD). Participants separately divided into 5 categories quintiles RHR-CV, RHR-VIM RHR-SD. Multivariate Cox regression restricted cubic spline models establish between AF. 241 occurred during a median follow-up 7.54 years. The incidence group lowest (Q1) highest (Q5) RHR-CV higher than that other groups. HRs 2.07 (95% CI, 1.34–3.21, p < 0.01), quintile group(Q5) compared Q2, 1.89(95% 1.20–2.97, 0.01) group(Q1) Q2. showed similar trend using (p RHR-SD 0.05) parameters. Further sensitivity analyses indicated consistent results subjects prior cardiovascular disease taking beta blockers or CCB. To match covariates, also propensity score matching, prominent trends found RHR-VIM. In conclusion, lower associated increasing AF, which supporting U-shaped curve existence. Atrial (AF) is one leading causes morbidity mortality.1Vitolo M Lip GYH Understanding global burden regional variations: we need improvement.Cardiovasc Res. 2021; 117: 1420-1422Crossref PubMed Scopus (6) Google Scholar, 2Chugh SS Havmoeller R Narayanan K Singh D Rienstra Benjamin EJ Gillum RF Kim YH McAnulty Jr, JH Zheng ZJ Forouzanfar MH Naghavi Mensah GA Ezzati Murray CJ Worldwide epidemiology fibrillation: Global Burden Disease Study.Circulation. 2014; 129: 837-847Crossref (2428) 3Chen LY Chung MK Allen LA Ezekowitz Furie KL McCabe P Noseworthy PA Perez MV Turakhia MP American Heart Association Council on Clinical CardiologyCouncil Cardiovascular Stroke NursingCouncil Quality Care Outcomes Research; CouncilAtrial burden: moving beyond as binary entity: scientific statement Association.Circulation. 2018; 137: 623-644Google Scholar 2017, nearly 37.6 million people suffered flutter globally, 2.86 new cases each year.4Wang L Ze F Li J Mi Han B Niu H Zhao N Trends fibrillation/flutter 2017.Heart. 107: 881-887Crossref (4) Recent community-based survey shown weighted prevalence rises 1.8% China.5Du X Guo Xia S Du Anderson C Arima Huffman Yuan Y Wu Guang Zhou Lin Cheng Dong Ma C. prevalence, awareness management nationwide adults China.Heart. 535-541Crossref (12) As marker autonomic nervous system (ANS), resting short-term RHR are incident AF,6Grundvold I Skretteberg PT Liestøl Erikssen G Engeseth Gjesdal Kjeldsen SE Arnesen Bodegard J. Low rates predict healthy middle-aged men.Circ Arrhythm Electrophysiol. 2013; 6: 726-731Crossref (44) 7Wang W Alonso Soliman EZ O'Neal WT Calkins Chen Diener-West Szklo Relation (From ARIC [Atherosclerosis Risk Communities] Study).Am Cardiol. 121: 1169-1176Abstract Full Text PDF (8) 8Skov MW Bachmann TN Rasmussen PV Olesen MS Pietersen Graff Lind Struijk JJ Køber Haunsø Svendsen Gerds TA Holst AG Nielsen JB. at rest (from Copenhagen Electrocardiographic 2016; 118: 708-713Abstract (11) 9Agarwal SK Norby FL Whitsel EA Loehr LR Fuster V Heiss Coresh A. Cardiac dysfunction 20 years follow-up.J Am Coll 2017; 69: 291-299Crossref (61) play important role pathological mechanism AF.10Chen PS LS Fishbein MC SF Nattel S. Role pathophysiology therapy.Circ 114: 1500-1515Crossref (379) Scholar,11Linz Elliott AD Hohl Malik Schotten U Dobrev Böhm Floras Lau DH Sanders P. fibrillation.Int 2019; 287: 181-188Abstract (47) our knowledge, effect outcomes such failure all-cause mortality well known.12Böhm Robertson Borer Ford Komajda Mahfoud Ewen Swedberg Tavazzi L. Effect systolic blood pressure chronic failure: treatment if inhibitor ivabradine trial (SHIFT) trial.J Assoc. 5e002160Crossref (16) 13Wang Yang Xing Wang Hidru TH Y. Elevated increased Northern China.Sci Rep. 7: 8043Crossref (5) 14Floyd JS Sitlani CM Wiggins Wallace E Suchy-Dicey Abbasi SA Carnethon MR Siscovick DS Sotoodehnia Heckbert SR McKnight Rice KM Psaty BM. Variation 4 risks myocardial infarction death among older adults.Heart. 2015; 101: 132-138Crossref (19) 15Yang Zhang Liu YL. Link elevated long-term pulse mortality.J 2020; 9e014122Crossref (1) unknown. Therefore, purpose investigate prospectively cohort (ChiCTR-TNC11001489) conducted community Tangshan, China (KCS, clinical no. ChiCTR-TNRC-11001489). Prior research described design methods detail.16Zhang Q Gao Bian Jia X. Ideal metrics ischemic intracerebral hemorrhagic stroke.Stroke. 44: 2451-2456Crossref (122) 101510 participants (81110 men 20400 women) aged 18-98 included first examination June October 2007. Then another 2 biennial check-up 2008/2009, 2010/2011, followed until 30, 2018. make sure changed status characteristics, characteristics assessed 3rd (2010–2011). 57927 received three consecutive (Figure 1). 8930 complete electrocardiography (ECG) recordings 2871 based ECG reading self-reported excluded. Finally, 46126 enrolled analytic sample. protocol approved Ethics Committee General Hospital compliance Declaration Helsinki. All signed informed consent. During examination, standardized questionnaires collect information demographic variables, history, medications history (including calcium channel (CCB) β blockers), lifestyle factors smoking drinking status). Measurements height, weight, (BP) biochemical parameters previously.13Wang Scholar,17Yang link SBP Hypertens. 37: 84-91Crossref (9) Biochemical involved triglycerides (TG), cholesterol (TC), high-density lipoprotein (HDL-C), low-density (LDL-C), fasting glucose (FBG). Body mass index (BMI) calculated weight height squared (kg/ m2). Smoking defined least cigarette per day past year. Drinking average daily wine (i.e., alcohol content 50%) intake approximately 100 mL Physical exercise regarded aerobic >3 sessions week, >30 minutes session. Histories ascertained physician diagnosis. Hypertension BP ≥140/90 mmHg, use antihypertensive medication. Diabetes mellitus FPG ≥7.0 mmol/L random plasma ≥11.1 mmol/L, diabetes, and/or antidiabetic drugs. After had supine min quiet room, trained technicians obtained 10-second 12-lead electrocardiograms (ECG9130P, NIHON KOHDEN CORP, Japan) procedures. undertaken state 6:00 AM 9:00 negate dietary influences recordings. intraindividual visits (in 2006, 2008, 2010). We following formulae calculate (SD):CV=(SDRHR¯)×100%,SD=∑(RHRi−RHR¯)2n−1, where RHRi participant andRHR¯is examinations. Because can still be correlated RHR, further used index. Variability (VIM) VIM=k×SDmean∧β, coefficient, natural logarithm SD population. grouped according RHR-SD, separately. date 2018, endpoint event (new-onset AF). diagnosis method previously.18Li Cui Gurol ME Bhatt DL Fonarow GC Cohort repeated measurements serum urate fibrillation.J 8e012020Crossref According European Society Cardiology guideline, follows: “absolutely” irregular RR intervals surface ECG; (2) no distinct waves regular electrical activity some leads, most often lead V1; (3) cycle length, interval activations, usually <200ms (>300 beats/min).19Camm AJ Kirchhof GY Savelieva Ernst Van Gelder IC Al-Attar Hindricks Prendergast Heidbuchel Alfieri O Angelini Atar Colonna De Caterina Sutter Goette Gorenek Heldal Hohloser SH Kolh Le Heuzey JY Ponikowski Rutten FH Rhythm Association; Cardio-Thoracic SurgeryGuidelines task force european society cardiology (ESC).Eur 2010; 31: 2369-2429Crossref (4022) confirm diagnosis, two experienced cardiologists independently read all ECGs team conduct reviews patient's medical records annually. signs occurrence identified Municipal Social Insurance Institution Discharge Register, cover participants. Continuous variables ± analysis variance (ANOVA). Categorical percentages Pearson's chi-square test X2 test. multivariable adjusted model age, gender, LDL, HDL, physical activity, drinking, smoking, BMI, pressure(SBP), hypertension. Repeated examine consistency results. several excluding (CVD), those who β-blockers assess robustness findings, matching (PSM) five RHR-CV. covariates good balance except sex, SBP. These unbalanced multivariate model. Furthermore, when modeling VIM SD. statistical SAS 9.3 (SAS Institute; Cray, NC). P-values 2-sided. P-value less 0.05 considered statistically significant. patients (35981 [78.01%] 10145 women [21.99%]) this sample sizes 9232 Q1, 9218 9222 Q3, 9230 Q4, 9224 Q5. reported Table 1. Compared low quintile, seem have SBP,DBP,RHR, more likely smoke 0.0001).Table 1Baseline rateVariableQuartiles ratepQ1 n = 9232Q2 9218Q3 9222Q4 9230Q5 9224Coefficient (mean SD)2.75 1.135.57 0.697.91 0.7010.79 1.0216.64 3.69–Age (years, SD)48.37 11.4448.41 11.3348.49 11.6048.78 11.6349.34 11.89<0.0001Men6952 (75.30%)7126 (77.31%)7115 (77.15%)7286 (78.94%)7502 (81.33%)<0.05Systolic (mmHg, SD)128.78 16.43129.07 16.53129.50 16.52130.28 17.06131.84 17.52<0.0001Diastolic SD)83.29 8.9983.60 9.1683.61 9.0683.93 9.2084.65 9.44<0.0001Resting (beats/min, SD)72.79 7.0973.3 7.3073.30 7.5773.89 7.9275.46 9.01<0.0001Triglycerides (mmol/L, SD)1.68 1.391.72 1.441.70 1.371.69 1.381.70 1.38>0.05(mg/dL, SD)148.8 123.2152.4 127.6150.6 121.4149.7 122.3150.6 122.3>0.05Total SD)4.92 1.154.95 1.144.93 1.134.95 1.114.96 1.15<0.05(mg/dL, SD)190.2 44.5191.4 44.1190.6 43.7191.4 42.9191.8 44.5<0.05High-density SD)1.55 0.881.54 0.401.55 0.401.56 0.401.58 0.41<0.0001(mg/dL, SD)59.9 34.059.5 15.559.9 15.560.3 15.561.0 15.9<0.0001Low-density SD)2.30 0.912.31 0.892.33 0.922.34 0.912.35 0.95<0.01(mg/dL, SD)88.9 35.289.3 34.490.1 35.690.5 35.290.9 36.7<0.01Body (kg/m2, SD)25.16 3.4225.07 3.4425.13 3.4325.08 3.4624.96 3.51<0.01Fasting SD)5.37 1.505.44 1.595.37 1.485.41 1.485.47 1.68<0.0001Hypertension4109 (44.51%)4175 (45.29%)4160 (45.11%)4245 (45.99%)4442 (48.16%)<0.0001Diabetes mellitus947 (10.26%)1024 (11.11%)911 (9.88%)994 (10.77%)1082 (11.73%)<0.01Drink3830 (42.60%)3773 (42.12%)3812 (42.34%)3856 (42.81%)3775 (41.87%)>0.05Smoke3500 (38.94%)3602 (40.2%)3638 (40.42%)3694 (41.03%)3729 (41.40%)<0.01Physical exercise1270 (14.17%)1185 (13.25%)1257 (13.99%)1267 (14.10%)1326 (14.74%)>0.05Data numbers, unless otherwise indicated; deviation. Open table tab Data period years, occurred. presents cumulative hazard ratios confidence interval) adjustment confounders, respectively Prominent multivariable-adjusted presented significant relationship 2, left panel), middle panel) right panel). reference points set 8 bpm, 6 bpm bpm.Table 2Cumulative quartile (SD) rateVariableQ1Q2Q3Q4Q5Atrial Fibrillation56 (0.61%)39 (0.42%)30 (0.33%)48 (0.52%)68 (0.74%)Coefficient Variation1.89 (1.20,2.97)⁎⁎p 0.01.1 (reference)1.29 (0.79,2.10)1.51 (0.95,2.41)2.07 (1.34,3.21)**p 0.01.Variability Independent Mean1.88 (1.18,3.01)**p (reference)1.55 (0.95,2.52)1.54 (0.95,2.49)2.30 (1.47,3.58)**p 0.01.Standard Deviation1.54 (1.01,2.35)*p 0.05.1.08 (0.68,1.71)1 (reference)1.01 (0.64,1.60)1.63 (1.08,2.47)*p 0.05.Adjusted lipoprotein, body index, pressure, diabetes mellitus, 0.05. 0.01. Adjusted avoid possible influence excluded prevalent CVD CCB (Table 3). robust after potential factors. Analyses PSM generated findings primary 4). groups 0.01). Similar not significantly AF.Table 3Hazard rateQuintileCoefficient variationVariability meanStandard deviationPatients diseaseQ11.98 (1.22,3.22)⁎⁎p 0.01.2.21 (1.32,3.71)*p 0.05.1.79 (1.12,2.85)⁎⁎p 0.01.Q21.38 (0.82,2.33)1.81 (1.06,3.10)*p 0.05.1.26 (0.76,2.10)Q31 (reference)1 (reference)Q41.43 (0.86,2.38)1.76 (1.03,2.99)*p 0.05.1.21 (0.73,2.00)Q51.97 (1.22,3.18)⁎⁎p 0.01.2.30 (1.39,3.81)*p 0.05.1.68 (1.04,2.71)⁎⁎p 0.01.Patients blockersQ11.96 (1.24,3.09)⁎⁎p 0.01.1,88 (1.17,3.00)⁎⁎p 0.01.1.58 (1.03,2.42)⁎⁎p 0.01.Q21.26 (0.76,2.07)1.47 (0.90,2.41)1.01 (0.63,1.63)Q31 (reference)Q41.53 (0.95,2.46)1.47 (0.90,2.39)1.03 (0.65,1.64)Q52.05 (1.31,3.20)⁎⁎p 0.01.2.20 (1.41,3.45)⁎⁎p (1.03,2.43)⁎⁎p CCBQ11.84 (1.16,2.92)⁎⁎p 0.01.1.88 (1.16,3.04)⁎⁎p 0.01.1.55 (1.00,2.40)*p 0.05.Q21.25 (0.76,2.05)1.50 (0.91,2.48)1 (reference)Q31 (reference)1.02 (0.63,1.65)Q41.50 (0.93,2.42)1.58 (0.97,2.57)1.07 (0.67,1.71)Q52.00 (1.28,3.14)⁎⁎p (0.97,2.57)⁎⁎p (1.02,2.45)*p 4Hazard analysisVariableQ1Q2Q3Q4Q5Coefficient Variation1.92 (1.22,3.00)⁎⁎p 0.01.1.26 (0.77,2.05)1 (reference)1.53 (0.95,2.45)1.89 (1.19,3.00)⁎⁎p Mean1.70 (1.07,2.72)*p 0.05.1.47 (0.91,2.38)1 (reference)1.50 (0.93,2.43)2.28 (1.46,3.57)⁎⁎p Deviation1.45 (0.94,2.24)1.13 (0.72,1.79)1 (reference)1.17 (0.74,1.87)1.42 (0.89,2.27)Adjusted RHR-CV.Adjusted RHR-VIM.Adjusted rate, present confirmed Chinese curve. Previous studies related events failure, infarction, mortality). Findings Study 1.43 times versus quintile.17Yang Besides, it demonstrated great changes (>25 bpm) mid-adulthood 7 (age 36–43) threefold (HR, 95% CI: 3.26, 1.54-6.90).20Ó Hartaigh Gill TM Shah Hughes Deanfield JE Kuh Hardy R. across life course mortality: longitudinal Medical Research (MRC) National Survey Health Development (NSHD).J Epidemiol Community Health. 68: 883-889Crossref Similarly, Atherosclerosis Communities (ARIC) time-updated change preceding visit linked HF, stroke, mortality.21Vazir Claggett Skali Agulair Ballantyne Vardeny Solomon temporal atherosclerosis communities study.JAMA 3: 200-206Crossref (25) these did involve Consistent 52% increase AF.22Böhm Schumacher Linz Reil JC Ukena Lonn Teo Sliwa Schmieder RE Sleight Yusuf vascular disease: ONTARGET/TRANSCEND studies.J Intern Med. 278: 303-312Crossref Of note, high diseases, fibrillation. investigated people. addition, (HRV) “U” shaped curve.9Agarwal Scholar,23Habibi Chahal Greenland Guallar Lima JAC Nazarian Multi-Ethnic (MESA)).Am 124: 1684-1689Abstract 24Perkiömäki Ukkola Kiviniemi Tulppo Ylitalo Kesäniemi YA Huikuri H. population.J Cardiovasc 25: 719-724Crossref (29) 25Khan AA Shantsila sympathetic parasympathetic system.Eur Clin Invest. 49: e13174Crossref (26) 26Heart variability: standards measurement, physiological interpretation use. north pacing electrophysiology.Circulation. 1996; 93: 1043-1065Crossref (MESA) both beat-to-beat HRV diseases.23Habibi visit-to-visit, may additional prognostic value. mechanisms ambiguous. widely indicator AF,22Böhm Scholar,27Persson AP Fedorowski Hedblad Persson Juul-Möller Engström Johnson LSB. premature contractions 24hECG population-based study.Heart. 106: 287-291Crossref Scholar,28Liu Zhu Hong K. dose-response studies.Int 60: 805-811Crossref assessing vagal components ANS. ANS.25Khan evaluate different HRV, geometric methods, time frequency domain analysis. Up now, few focused Growing revealed reflects complex interplay withdrawal activation. sign activation period. Moreover, indicating ANS pathogenesis suggest contribute level VVHRV, eventually incidence. strengths. With large cohort, proposed existed wide range age (18–98 old) up separate twice ECGs, rigorous quality estimation RHR. And variability. ascertainment recorded updated annually limitations should considered. Firstly, study, mostly male coal miner workers. contained males female. Secondly, there exist confounders ignored analysis, although taken main variety consideration. Thirdly, measure accurately, extended indeed. factor curve, novel authors declare they known competing financial interests personal relationships could appeared work paper. Thanks members teams Group their contribution.