International Journal of Cardiology 188 (2015) 10–12
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Plasma mid-regional pro-atrial natriuretic peptide and N-terminal pro-brain natriuretic peptide improve discrimination of lone atrial fibrillation☆ Ian C.Y. Chang a,1, Lin Y. Chen a,⁎,1,2, Jenny P.C. Chong b, Erin Austin c, Chwee N. Quay b, Lingli Gong b, A. Mark Richards b,d,e, Lieng H. Ling b,e,2 a
Cardiovascular Division, Department of Medicine, University of Minnesota, 420 Delaware Street SE, MMC 508, Minneapolis, MN, USA Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore c Division of Biostatistics, School of Public Health, University of Minnesota, 420 Delaware Street SE, MMC 303, Minneapolis, MN, USA d Christchurch Heart Institute, University of Otago, 2 Riccarton Avenue, Dunedin, New Zealand e Cardiac Department, 5 Lower Kent Ridge Road, National University Heart Centre, Singapore b
a r t i c l e
i n f o
Article history: Received 27 March 2015 Accepted 28 March 2015 Available online 31 March 2015 Keywords: Atrial fibrillation Biomarkers Case–control study Mid-regional pro-atrial natriuretic peptide N-terminal pro-brain natriuretic peptide
Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population and is associated with substantial morbidity and mortality. Lone AF is a subtype of AF that occurs in young patients b60 years of age without known established risk factors for AF such as hypertension, diabetes and structural heart disease [1,2]. The pathophysiology underlying lone AF is not well understood. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are cardiac natriuretic circulating hormones with bioactivity promoting pressure and volume homeostasis. Having been derived from common precursors of BNP and ANP, respectively, N-terminal pro-BNP (NTproBNP) and Nterminal pro-ANP (NTproANP) are co-secreted with longer half-lives [3,4]. An immunoassay has been developed to the mid-regional sequence of NTproANP (MRproANP) and plasma levels are reported to perform similarly to BNP and NTproBNP as a heart failure biomarker ☆ This work was supported by the National Medical Research Council of Singapore, Singapore [NMRC/1141/2007 to L.Y.C.]. ⁎ Corresponding author at: Cardiac Arrhythmia Center, Cardiovascular Division, University of Minnesota Medical School, 420 Delaware Street SE, MMC 508, Minneapolis, MN 55455, USA. E-mail address: [email protected] (L.Y. Chen). 1 Both authors contributed equally to the paper. 2 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
http://dx.doi.org/10.1016/j.ijcard.2015.03.415 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
[4]. Both NTproBNP and MRproANP have been found to be elevated in common AF (AF associated with aging and risk factors such as hypertension) [5,6], but thus far, there has been no study describing MRproANP levels in patients with lone AF. In this well-characterized retrospective case–control study of patients with lone AF, we hypothesized that [1] similar to common AF, MRproANP is also associated with lone AF, and [2] MRproANP and NTproBNP will improve our ability to discriminate between the presence and absence of lone AF, and between paroxysmal and persistent lone AF. This study was conducted at the National University Hospital and Tan Tock Seng Hospital in Singapore. Lone AF was defined as onset of AF in patients b60 years of age without established risk factors for AF [1,2]. Between July 2007 and June 2010, consecutive Han Chinese patients referred to the general cardiology clinics with lone paroxysmal or persistent AF were invited to participate. During the same period, consecutive Han Chinese patients b60 years of age evaluated at the general cardiology clinics at both hospitals without AF, other arrhythmias, hypertension, diabetes, CHD, previous myocardial infarction, chronic heart failure, cardiomyopathy, or valvular heart disease were invited to participate as controls. Informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee. All patients were screened by a review of medical records and systematic measurement of risk factors. Detailed 2-dimensional and Doppler transthoracic echocardiographic studies were performed. Blood samples were drawn while in sinus rhythm. The measurement of NTproBNP and MRproANP was performed with commercially available electrochemiluminescence immunoassays. MRproANP and NTproBNP were analyzed as continuous variables, where the natural log (ln) of the biomarkers was used. Odds ratios (ORs) for the natural log transformed biomarkers are given in units of SD. We adjusted for age, sex, systolic and diastolic blood pressure, BMI, LA volume index (LAVI) and LV mass index. To assess the ability of the biomarkers to discriminate between the presence and absence of lone AF, we estimated the area under the receiver operating characteristic curve (AUC) for MRproANP and NTproBNP. We used stepwise logistic regression to fit
I.C.Y. Chang et al. / International Journal of Cardiology 188 (2015) 10–12
the most parsimonious clinico-echocardiographic model for lone AF: candidate variables for this model included age, sex, systolic and diastolic blood pressure, BMI, LAVI, and LV mass index. Table 1 shows the baseline characteristics of both groups. After adjusting for clinico-echocardiographic covariates, we found that higher MRproANP and NTproBNP were associated with higher odds of lone AF. The OR (95% CI) of lone AF per one SD increase of ln (MRproANP) was 3.37 (1.88–6.04), P b 0.001; the OR per one SD increase of ln (NTproBNP) was 3.28 (1.80–5.96), P b 0.001. Using a stepwise logistic regression process, the most parsimonious clinico-echocardiographic model for discriminating lone AF from controls comprised age, systolic and diastolic blood pressure, and LAVI. When added to this model, both MRproANP and NTproBNP significantly improved the ability in discriminating patients with lone AF from controls (Table 2). The ability of using MRproANP or NTproBNP to discriminate paroxysmal from persistent lone AF was compared. The AUC for MRproANP was 0.82 (95% CI: 0.72–0.92), P b 0.001, the AUC for NTproBNP was 0.76 (95% CI: 0.65– 0.88), P b 0.001; and the AUC for using both MRproANP and NTproBNP was 0.85 (95% CI: 0.75–0.94), P b 0.001. MRproANP was marginally better than NTproBNP in discriminating between paroxysmal from persistent lone AF, P = 0.06. To the best of our knowledge, our study is the first to evaluate the association between MRproANP in a group of patients with onset of AF b60 years of age without known established risk factors for AF. In a prior study, Ellinor et al. did not find a significant difference in proANP levels between patients with AF and controls [7]. That study, however, included patients with onset N60 years of age [7] and evaluated proANP rather than MRproANP. We extend current literature by showing that higher MRproANP is not only associated with higher odds of lone AF, but has also good discriminative capacity for the presence or absence of lone AF and paroxysmal versus persistent lone AF. In patients with lone AF, Ellinor et al. and Lee et al. found elevated NTproBNP and BNP, respectively, compared to controls [7,8]. Similar to previous studies, we found that increased NTproBNP was independently associated with higher odds of lone AF. In addition, we extend current literature by showing that NTproBNP has good discriminative capacity for paroxysmal versus persistent lone AF. Research from the Belgrade Atrial Fibrillation Study and Realise-AF has shown that progression of AF from paroxysmal to persistent or permanent AF confers adverse outcomes [9,10], underscoring the need to identify predictors for AF progression. The findings of our study suggest
11
Table 2 Area under the ROC curves for a clinico-echocardiographic model, MRproANP, and NTproBNP in discriminating lone AF and controls. Model
AUC (95% CI)
P
Clinico-echocardiographic model (Model A) Model A + MRproANP Model A + NTproBNP Model A + MRproANP + NTproBNP
0.73 (0.65–0.81) 0.81 (0.75–0.88) 0.79 (0.72–0.86) 0.82 (0.76–0.89)
b0.001⁎ b0.001⁎ b0.001⁎ b0.001⁎
Comparison
Difference in AUC (95% CI)
P
Model A + MRproANP versus Model A alone Model A + NTproBNP versus Model A alone Model A + MRproANP + NTproBNP versus Model A alone Model A + MRproANP versus Model A + NTproBNP Model A + MRproANP + NTproBNP versus Model A + MRproANP Model A + MRproANP + NTproBNP versus Model A + NTproBNP
0.09 (0.02–0.15) 0.06 (0.01–0.12) 0.09 (0.03–0.16)
0.01 0.03 0.01
0.02 (−0.02 to 0.07)
0.30
0.01 (−0.01–0.02)
0.25
0.03 (−0.004–0.07)
0.08
Model A = clinico-echocardiographic model comprised age, systolic and diastolic blood pressure, and LA volume index (LAVI). AF = atrial fibrillation; AUC = area under the ROC curve; CI = confidence interval; MRproANP = mid-regional pro-atrial natriuretic peptide; NTproBNP = N-terminal pro-brain natriuretic peptide; ROC = receiver operating characteristic. ⁎ P-value of model versus random classification.
that MRproANP and NTproBNP may be helpful in discriminating between paroxysmal and persistent lone AF. Further prospective studies are warranted to test the predictive value of these biomarkers for AF progression. In conclusion, our study indicates that higher plasma MRproANP and NTproBNP are associated with higher odds of lone AF. Both biomarkers have good discriminative ability for the presence or absence of lone AF and also paroxysmal versus persistent lone AF.
Conflict of interest The contents of this manuscript are not associated with any financial interest or industry that could lead to a conflict of interest.
Table 1 Baseline characteristics of lone atrial fibrillation cases and controls. Characteristic
Combined AF cases (n = 81)
Paroxysmal AF cases (n = 68)
Persistent AF cases (n = 13)
Controls (n = 81)
P**
Age at enrollment (years) Male sex Brachial pulse pressure (mm Hg) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Heart rate (beats/min) Body mass index (kg/m2) Septal E/e′ LA volume index (ml/m2) LV mass index (g/m2) LV ejection fraction (%) MRproANP (pmol/L) Quartile 1 [17.3–34.6] Quartile 2 [34.7–47.4] Quartile 3 [47.5–76.8] Quartile 4 [76.9–241.8] NTproBNP (pmol/L) Quartile 1 [5.0–19.5] Quartile 2 [19.6–37.0] Quartile 3 [37.1–82.0] Quartile 4 [82.1–1503.0]
49 [37–54] 72 (89) 51.2 ± 11.5 128.9 ± 13.9 77.7 ± 8.7 67.2 ± 10.5* 25.1 ± 3.7 7.7 [6.4–9.1]† 26.0 [18.6–32.3]† 79.5 [71–90]† 65 [60–66]† 71.4 [40.3–114.6] 16 (20) 10 (12) 17 (21) 38 (47) 55 [28–209]‡ 14 (18) 11 (14) 19 (24) 35 (44)
48 [37–54] 60 (88) 52.2 ± 11.3 129.7 ± 14.0 77.5 ± 8.4 67.4 ± 10.6§ 25.0 ± 3.8 7.6 [6.4–9.3]|| 24.5 [18.3–28.8]|| 79 [70–89]|| 65 [62–68]|| 56.6 [35.8–100.0] 21 (31) 19 (28) 15 (22) 13 (19) 48 [23–151]¶ 20 (30) 18 (27) 16 (24) 12 (18)
50 [40–54] 12 (92) 46.0 ± 11.6 125.0 ± 13.4 79.0 ± 10.2 65.7 ± 10.3 26.0 ± 3.6 8.0 [7.6–8.7] 33.3 [30.4–39.4] 86 [79–99] 60 [60–65] 121.5 [101.8–154.5] 0 (0) 1 (8) 5 (38) 7 (54) 292 [98–503] 0 (0) 2 (15) 4 (31) 7 (54)
48 [39–54] 72 (89) 54.2 ± 8.7 129.3 ± 12.5 75.1 ± 8.4 69.1 ± 11.6 24.9 ± 4.3 8.0 [6.5–9.4]* 21.1 [17.0–24.7]* 72.5 [62–80]* 65 [63–68]* 42.4 [31.1–50.7] 25 (31) 30 (37) 24 (30) 2 (2) 26 [16–44]# 25 (32) 28 (36) 20 (26) 4 (5)
0.95 1.00 0.07 0.84 0.06 0.27 0.65 0.57 0.0002 0.0009 0.44 b0.0001
b0.0001
*N = 80, †n = 78, ‡n = 79, §n = 67, ||n = 65, ¶n = 66, #n = 77, **between combined AF cases and controls. Continuous variables are presented as mean ± standard deviation or median [interquartile range] as appropriate; categorical variables are presented as number (%). Combined AF cases include paroxysmal and persistent AF. AF = atrial fibrillation; LA = left atrium; LV = left ventricle; MRproANP = mid-regional pro-atrial natriuretic peptide; NTproBNP = N-terminal pro-brain natriuretic peptide.
12
I.C.Y. Chang et al. / International Journal of Cardiology 188 (2015) 10–12
References [1] T.S. Potpara, G.Y. Lip, Lone atrial fibrillation — an overview, Int. J. Clin. Pract. 68 (2014) 418–433. [2] V. Fuster, L.E. Ryden, D.S. Cannom, et al., ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation), J. Am. Coll. Cardiol. 48 (2006) 854–906. [3] L.B. Daniels, A.S. Maisel, Natriuretic peptides, J. Am. Coll. Cardiol. 50 (2007) 2357–2368. [4] N.G. Morgenthaler, J. Struck, B. Thomas, A. Bergmann, Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma, Clin. Chem. 50 (2004) 234–236. [5] K.K. Patton, S.R. Heckbert, A. Alonso, et al., N-terminal pro-B-type natriuretic peptide as a predictor of incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis: the effects of age, sex and ethnicity, Heart 99 (2013) 1832–1836.
[6] C. Meune, A. Vermillet, K. Wahbi, et al., Mid-regional pro atrial natriuretic peptide allows the accurate identification of patients with atrial fibrillation of short time of onset: a pilot study, Clin. Biochem. 44 (2011) 1315–1319. [7] P.T. Ellinor, A.F. Low, K.K. Patton, M.A. Shea, C.A. Macrae, Discordant atrial natriuretic peptide and brain natriuretic peptide levels in lone atrial fibrillation, J. Am. Coll. Cardiol. 45 (2005) 82–86. [8] S.H. Lee, J.H. Jung, S.H. Choi, et al., Determinants of brain natriuretic peptide levels in patients with lone atrial fibrillation, Circ. J. Off. J. Jpn. Circ. Soc. 70 (2006) 100–104. [9] T.S. Potpara, G.R. Stankovic, B.D. Beleslin, et al., A 12-year follow-up study of patients with newly diagnosed lone atrial fibrillation: implications of arrhythmia progression on prognosis: the Belgrade Atrial Fibrillation study, Chest 141 (2012) 339–347. [10] C.E. Chiang, L. Naditch-Brule, J. Murin, et al., Distribution and risk profile of paroxysmal, persistent, and permanent atrial fibrillation in routine clinical practice: insight from the real-life global survey evaluating patients with atrial fibrillation international registry, Circ. Arrhythm. Electrophysiol. 5 (2012) 632–639.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Plasma mid-regional pro-atrial natriuretic peptide and N-terminal pro-brain natriuretic peptide improve discrimination of lone atrial fibrillation☆ Ian C.Y. Chang a,1, Lin Y. Chen a,⁎,1,2, Jenny P.C. Chong b, Erin Austin c, Chwee N. Quay b, Lingli Gong b, A. Mark Richards b,d,e, Lieng H. Ling b,e,2 a
Cardiovascular Division, Department of Medicine, University of Minnesota, 420 Delaware Street SE, MMC 508, Minneapolis, MN, USA Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore c Division of Biostatistics, School of Public Health, University of Minnesota, 420 Delaware Street SE, MMC 303, Minneapolis, MN, USA d Christchurch Heart Institute, University of Otago, 2 Riccarton Avenue, Dunedin, New Zealand e Cardiac Department, 5 Lower Kent Ridge Road, National University Heart Centre, Singapore b
a r t i c l e
i n f o
Article history: Received 27 March 2015 Accepted 28 March 2015 Available online 31 March 2015 Keywords: Atrial fibrillation Biomarkers Case–control study Mid-regional pro-atrial natriuretic peptide N-terminal pro-brain natriuretic peptide
Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population and is associated with substantial morbidity and mortality. Lone AF is a subtype of AF that occurs in young patients b60 years of age without known established risk factors for AF such as hypertension, diabetes and structural heart disease [1,2]. The pathophysiology underlying lone AF is not well understood. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are cardiac natriuretic circulating hormones with bioactivity promoting pressure and volume homeostasis. Having been derived from common precursors of BNP and ANP, respectively, N-terminal pro-BNP (NTproBNP) and Nterminal pro-ANP (NTproANP) are co-secreted with longer half-lives [3,4]. An immunoassay has been developed to the mid-regional sequence of NTproANP (MRproANP) and plasma levels are reported to perform similarly to BNP and NTproBNP as a heart failure biomarker ☆ This work was supported by the National Medical Research Council of Singapore, Singapore [NMRC/1141/2007 to L.Y.C.]. ⁎ Corresponding author at: Cardiac Arrhythmia Center, Cardiovascular Division, University of Minnesota Medical School, 420 Delaware Street SE, MMC 508, Minneapolis, MN 55455, USA. E-mail address: [email protected] (L.Y. Chen). 1 Both authors contributed equally to the paper. 2 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
http://dx.doi.org/10.1016/j.ijcard.2015.03.415 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
[4]. Both NTproBNP and MRproANP have been found to be elevated in common AF (AF associated with aging and risk factors such as hypertension) [5,6], but thus far, there has been no study describing MRproANP levels in patients with lone AF. In this well-characterized retrospective case–control study of patients with lone AF, we hypothesized that [1] similar to common AF, MRproANP is also associated with lone AF, and [2] MRproANP and NTproBNP will improve our ability to discriminate between the presence and absence of lone AF, and between paroxysmal and persistent lone AF. This study was conducted at the National University Hospital and Tan Tock Seng Hospital in Singapore. Lone AF was defined as onset of AF in patients b60 years of age without established risk factors for AF [1,2]. Between July 2007 and June 2010, consecutive Han Chinese patients referred to the general cardiology clinics with lone paroxysmal or persistent AF were invited to participate. During the same period, consecutive Han Chinese patients b60 years of age evaluated at the general cardiology clinics at both hospitals without AF, other arrhythmias, hypertension, diabetes, CHD, previous myocardial infarction, chronic heart failure, cardiomyopathy, or valvular heart disease were invited to participate as controls. Informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee. All patients were screened by a review of medical records and systematic measurement of risk factors. Detailed 2-dimensional and Doppler transthoracic echocardiographic studies were performed. Blood samples were drawn while in sinus rhythm. The measurement of NTproBNP and MRproANP was performed with commercially available electrochemiluminescence immunoassays. MRproANP and NTproBNP were analyzed as continuous variables, where the natural log (ln) of the biomarkers was used. Odds ratios (ORs) for the natural log transformed biomarkers are given in units of SD. We adjusted for age, sex, systolic and diastolic blood pressure, BMI, LA volume index (LAVI) and LV mass index. To assess the ability of the biomarkers to discriminate between the presence and absence of lone AF, we estimated the area under the receiver operating characteristic curve (AUC) for MRproANP and NTproBNP. We used stepwise logistic regression to fit
I.C.Y. Chang et al. / International Journal of Cardiology 188 (2015) 10–12
the most parsimonious clinico-echocardiographic model for lone AF: candidate variables for this model included age, sex, systolic and diastolic blood pressure, BMI, LAVI, and LV mass index. Table 1 shows the baseline characteristics of both groups. After adjusting for clinico-echocardiographic covariates, we found that higher MRproANP and NTproBNP were associated with higher odds of lone AF. The OR (95% CI) of lone AF per one SD increase of ln (MRproANP) was 3.37 (1.88–6.04), P b 0.001; the OR per one SD increase of ln (NTproBNP) was 3.28 (1.80–5.96), P b 0.001. Using a stepwise logistic regression process, the most parsimonious clinico-echocardiographic model for discriminating lone AF from controls comprised age, systolic and diastolic blood pressure, and LAVI. When added to this model, both MRproANP and NTproBNP significantly improved the ability in discriminating patients with lone AF from controls (Table 2). The ability of using MRproANP or NTproBNP to discriminate paroxysmal from persistent lone AF was compared. The AUC for MRproANP was 0.82 (95% CI: 0.72–0.92), P b 0.001, the AUC for NTproBNP was 0.76 (95% CI: 0.65– 0.88), P b 0.001; and the AUC for using both MRproANP and NTproBNP was 0.85 (95% CI: 0.75–0.94), P b 0.001. MRproANP was marginally better than NTproBNP in discriminating between paroxysmal from persistent lone AF, P = 0.06. To the best of our knowledge, our study is the first to evaluate the association between MRproANP in a group of patients with onset of AF b60 years of age without known established risk factors for AF. In a prior study, Ellinor et al. did not find a significant difference in proANP levels between patients with AF and controls [7]. That study, however, included patients with onset N60 years of age [7] and evaluated proANP rather than MRproANP. We extend current literature by showing that higher MRproANP is not only associated with higher odds of lone AF, but has also good discriminative capacity for the presence or absence of lone AF and paroxysmal versus persistent lone AF. In patients with lone AF, Ellinor et al. and Lee et al. found elevated NTproBNP and BNP, respectively, compared to controls [7,8]. Similar to previous studies, we found that increased NTproBNP was independently associated with higher odds of lone AF. In addition, we extend current literature by showing that NTproBNP has good discriminative capacity for paroxysmal versus persistent lone AF. Research from the Belgrade Atrial Fibrillation Study and Realise-AF has shown that progression of AF from paroxysmal to persistent or permanent AF confers adverse outcomes [9,10], underscoring the need to identify predictors for AF progression. The findings of our study suggest
11
Table 2 Area under the ROC curves for a clinico-echocardiographic model, MRproANP, and NTproBNP in discriminating lone AF and controls. Model
AUC (95% CI)
P
Clinico-echocardiographic model (Model A) Model A + MRproANP Model A + NTproBNP Model A + MRproANP + NTproBNP
0.73 (0.65–0.81) 0.81 (0.75–0.88) 0.79 (0.72–0.86) 0.82 (0.76–0.89)
b0.001⁎ b0.001⁎ b0.001⁎ b0.001⁎
Comparison
Difference in AUC (95% CI)
P
Model A + MRproANP versus Model A alone Model A + NTproBNP versus Model A alone Model A + MRproANP + NTproBNP versus Model A alone Model A + MRproANP versus Model A + NTproBNP Model A + MRproANP + NTproBNP versus Model A + MRproANP Model A + MRproANP + NTproBNP versus Model A + NTproBNP
0.09 (0.02–0.15) 0.06 (0.01–0.12) 0.09 (0.03–0.16)
0.01 0.03 0.01
0.02 (−0.02 to 0.07)
0.30
0.01 (−0.01–0.02)
0.25
0.03 (−0.004–0.07)
0.08
Model A = clinico-echocardiographic model comprised age, systolic and diastolic blood pressure, and LA volume index (LAVI). AF = atrial fibrillation; AUC = area under the ROC curve; CI = confidence interval; MRproANP = mid-regional pro-atrial natriuretic peptide; NTproBNP = N-terminal pro-brain natriuretic peptide; ROC = receiver operating characteristic. ⁎ P-value of model versus random classification.
that MRproANP and NTproBNP may be helpful in discriminating between paroxysmal and persistent lone AF. Further prospective studies are warranted to test the predictive value of these biomarkers for AF progression. In conclusion, our study indicates that higher plasma MRproANP and NTproBNP are associated with higher odds of lone AF. Both biomarkers have good discriminative ability for the presence or absence of lone AF and also paroxysmal versus persistent lone AF.
Conflict of interest The contents of this manuscript are not associated with any financial interest or industry that could lead to a conflict of interest.
Table 1 Baseline characteristics of lone atrial fibrillation cases and controls. Characteristic
Combined AF cases (n = 81)
Paroxysmal AF cases (n = 68)
Persistent AF cases (n = 13)
Controls (n = 81)
P**
Age at enrollment (years) Male sex Brachial pulse pressure (mm Hg) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Heart rate (beats/min) Body mass index (kg/m2) Septal E/e′ LA volume index (ml/m2) LV mass index (g/m2) LV ejection fraction (%) MRproANP (pmol/L) Quartile 1 [17.3–34.6] Quartile 2 [34.7–47.4] Quartile 3 [47.5–76.8] Quartile 4 [76.9–241.8] NTproBNP (pmol/L) Quartile 1 [5.0–19.5] Quartile 2 [19.6–37.0] Quartile 3 [37.1–82.0] Quartile 4 [82.1–1503.0]
49 [37–54] 72 (89) 51.2 ± 11.5 128.9 ± 13.9 77.7 ± 8.7 67.2 ± 10.5* 25.1 ± 3.7 7.7 [6.4–9.1]† 26.0 [18.6–32.3]† 79.5 [71–90]† 65 [60–66]† 71.4 [40.3–114.6] 16 (20) 10 (12) 17 (21) 38 (47) 55 [28–209]‡ 14 (18) 11 (14) 19 (24) 35 (44)
48 [37–54] 60 (88) 52.2 ± 11.3 129.7 ± 14.0 77.5 ± 8.4 67.4 ± 10.6§ 25.0 ± 3.8 7.6 [6.4–9.3]|| 24.5 [18.3–28.8]|| 79 [70–89]|| 65 [62–68]|| 56.6 [35.8–100.0] 21 (31) 19 (28) 15 (22) 13 (19) 48 [23–151]¶ 20 (30) 18 (27) 16 (24) 12 (18)
50 [40–54] 12 (92) 46.0 ± 11.6 125.0 ± 13.4 79.0 ± 10.2 65.7 ± 10.3 26.0 ± 3.6 8.0 [7.6–8.7] 33.3 [30.4–39.4] 86 [79–99] 60 [60–65] 121.5 [101.8–154.5] 0 (0) 1 (8) 5 (38) 7 (54) 292 [98–503] 0 (0) 2 (15) 4 (31) 7 (54)
48 [39–54] 72 (89) 54.2 ± 8.7 129.3 ± 12.5 75.1 ± 8.4 69.1 ± 11.6 24.9 ± 4.3 8.0 [6.5–9.4]* 21.1 [17.0–24.7]* 72.5 [62–80]* 65 [63–68]* 42.4 [31.1–50.7] 25 (31) 30 (37) 24 (30) 2 (2) 26 [16–44]# 25 (32) 28 (36) 20 (26) 4 (5)
0.95 1.00 0.07 0.84 0.06 0.27 0.65 0.57 0.0002 0.0009 0.44 b0.0001
b0.0001
*N = 80, †n = 78, ‡n = 79, §n = 67, ||n = 65, ¶n = 66, #n = 77, **between combined AF cases and controls. Continuous variables are presented as mean ± standard deviation or median [interquartile range] as appropriate; categorical variables are presented as number (%). Combined AF cases include paroxysmal and persistent AF. AF = atrial fibrillation; LA = left atrium; LV = left ventricle; MRproANP = mid-regional pro-atrial natriuretic peptide; NTproBNP = N-terminal pro-brain natriuretic peptide.
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