Prognostic value and prevalence of complete right bundle branch block in an elderly population: a community-based 10-year prospective study

Results

Among 5,830 healthy people enrolled in the HALST cohort, 3,745 were aged ≥65; of these, 362 were excluded due to left bundle branch block, old MI, lung diseases, and pacing rate, leaving 3,383 individuals for analysis (Figure 1). Twenty-two of these individuals (0.65%) dropped out or were lost to follow-up during the study period. The mean age of the study cohort was 73.5±5.9 years, and 1,597 (47.21%) were men. Of the 3,383 individuals, 171 (5.05%) had CRBBB (Figure 1). Subjects with CRBBB were significantly older than those without CRBBB (75.4±6.5 vs. 73.4±5.9, P<0.0001; Table 1), and the prevalence of CRBBB was higher in men (n=113; 7.08%) than in women (n=58; 3.25%).

Figure 1. Flowchart of study subject selection.

Table 1. General characteristics and prognosis of individuals with CRBBB and those without in the HALST cohort.

	CRBBB(-) (n = 3212)	CRBBB(+) (n = 171)	P-value
Men, n (%)	1484 (46.20)	113 (66.08)	<0.0001
Age, years	73.4±5.9	75.4±6.5	<0.0001
65-70, n (%)	1090 (33.94)	41 (23.98)	0.0011
70-74, n (%)	1010 (31.44)	48 (28.07)
≥ 75, n (%)	1112 (34.62)	82 (47.95)
Height, cm	157.8±8.4	160.4±8.7	<0.0001
Weight, kg	60.9±10.5	62.1±11.0	0.1447
Hypertension, n (%)	1595 (49.66)	87 (50.88)	0.7599
Diabetes mellitus, n (%)	658 (20.49)	37 (21.64)	0.7164
Dyslipidemia, n (%)	1014 (31.57)	51 (29.82)	0.6322
Stroke, n (%)	200 (6.23)	6 (3.51)	0.1476
ECG parameters
Heart rate (beats/min)	67.5±10.3	67.0±10.8	0.5111
QRS, ms	91.8 (9.51)	143.1 (12.24)	<0.0001
QTc, ms	436.9±22.3	456.1±24.9	<0.0001
QRS axis, degree	25.6±35.5	18.3±51.2	0.0112
T axis, degree	40.9±31.8	21.6±31.0	<0.0001
Abbreviations: HALST, Healthy Aging Longitudinal Study in Taiwan; ECG, electrocardiogram; CRBBB(+), Complete right bundle branch block positive; CRBBB(-), Complete right bundle branch block negative.

Figure 2A illustrates the age distribution among patients with and without CRBBB, showing that the group with CRBBB had a much higher percentage of people over 75. Figure 2B illustrates the prevalence of CRBBB in various age groups, showing that it significantly increased with age (P<0.001). On the other hand, the prevalence of CRBBB in elderly men was higher than that in elderly women regardless of age in this study (Figure 3). In additional subgroup analyses, we found that men older than 70 had significantly more CRBBB than women older than 70, whereas the difference was not significant below age 70 (P=0.0055 in 70-74 group, P=0.0002 in ≥75 group).

Figure 2. (A) The age distribution among patients with and without CRBBB. (B) Prevalence of CRBBB and non-CRBBB in each age group. (Abbreviation: CRBBB, complete right bundle branch block).

Figure 3. Prevalence of complete right bundle branch block by gender and age. *P<0.05, **P<0.005.

There were no significant differences in weight, body mass index, blood pressure, diabetes, dyslipidemia, previous events of stroke, atrial fibrillation, heart rate, and prognosis between those who had CRBBB and those who did not have CRBBB (Table 1). During an average follow-up of 92.6±23.6 months (7.7 years), neither all-cause mortality nor cardiovascular mortality were significantly different between the two groups (log-rank test, P=0.44, 0.52, respectively, Figure 4). After performing a Cox regression analysis controlling for potential confounders including stroke, hypertension, diabetes, dyslipidemia, and chronic kidney disease, CRBBB was still not significantly associated with all-cause mortality and cardiovascular mortality (P=0.48 and 0.56, respectively).

Figure 4. Kaplan-Meier survival analysis of all-cause mortality (A) and cardiovascular mortality (B) in elderly individuals with and without complete right bundle branch block.

We also summarized the prevalence of CRBBB in community-based studies worldwide in Table 2. Because our study cohort is all elderly individuals (≥65 years), as expected, the average age of the individuals (73.5±5.9) in our study was the highest. In addition, the total prevalence of CRBBB (5.05%) in our study was the highest compared to the prevalence of other previously published studies (0.28-2.10%) and the mean worldwide prevalence (1.14%, an average of the values in Table 2). Regarding the gender difference, the prevalence of CRBBB in both men and women in our study (7.08% and 3.25%, respectively) was also the highest among the published community-based studies (0.95-2.10% and 0.42-1.25%, respectively).

Table 2. Summary of prevalence of CRBBB, age distribution, association with clinical outcomes of the published community-based studies worldwide

Study	Year	Country	Screened population N	Gender	Age (years)	Subjects ≥ 65 years old	CRBBB (+)			All-cause mortality	Cardiovascular mortality
							N (%)	M (%)	F (%)
Van Der Ende et al.[6]	2017	Netherlands	149,803	Both	18-93 (mean: 45±13)	10,777	<65 y: 825 (0.59) ≥65 y: 369 (3.42)	817 (1.29)	377 (0.42)	NA	NA
Zhang et al.[7]	2015	USA	15,408	Both	45-64 (mean: 54)	0	228 (1.48)	-	-	NA	NA
Nakamura et al.[9]	2013	Japan	9,090	Both	≥30 (mean: 51)	?	117 (1.29) 64.2±12.4 y	76 (1.91)	41 (0.80)	Not increased	Not increased
Bussink et al.[8]	2013	Denmark	18,441	Both	≥20 (mean: 50±13)	1,015	166 (0.90) M: 64.0±12.3 y F: 61.6±10.2 y	119 (1.40)	47 (0.47)	increased	increased
Zhang et al.[10]	2012	USA	66,450	Only women	Mean: 63	?	832 (1.25) 65-67 y	-	832 (1.25)	Not increased	Not increased
Adesanya et al.[11]	2008	USA	52,582	Both	≥18	?	997 (1.90) 68.9 ±10 y	-	-	NA	NA
Aro et al.[12]	2010	Finland	10,899	Both	Mean: 44±9	0	31 (0.28)	-	-	Not increased	Not increased
Eriksson et al.[13]	2005	Sweden	7,392	Only men	Mean: 52±2	0	70 (0.95) 52.4±2.3 y	70 (0.95)	-	Not increased	Not increased
Taniguchi et. al.[18]	2003	Japan	2,722	Only men	Mean: 43.2±1.2	0	36 (1.32) 44.4±1.0 y	36 (1.32)	-	Not increased	Not increased
Thrainsdottir et al.[2]	1993	Iceland	18,762	Both	33-79	4677	193 (1.03)	126 (1.38)	67 (0.70)	Not increased	Not increased
Fleg et. al.[15]	1983	USA	1,142	Only men	?	?	24 (2.10) 75.4±6.5 y	24 (2.10)	-	Not increased	NA
Yeh et al. present study	2020	Taiwan	3,383	Both	65-104 (mean 73.5±5.9)	3,383	171 (5.05) 75.4±6.5 y	113 (7.08)	58 (3.25)	Not increased	Not increased
Abbreviations: CRBBB, complete right bundle branch block; NA: not available, means no number was provided in the papers.

Patients and methods

Recruitment process and study population

The HALST cohort has been described in our previous work [22]. In brief, the recruitment process was as follows: adults living in the townships located within 2 kilometers of the study hospital in 7 regions across Taiwan were stratified by age, gender, and education level, and respondents were selected from each stratum by the systematic random sampling method. These 7 locations (Figure 5) cover both urban and rural areas, as well as different ethnic groups speaking different dialects, reasonably representing diverse sociodemographic characteristics of the Taiwanese background population. The eligibility criterion was age 65 years or older, and exclusion criteria were a highly contagious infectious disease or severe illness including malignancy undergoing active treatment, inability to ambulate, and institutionalization or hospitalization. Subjects with severe hearing, speech, mental, or cognitive impairments were also excluded because of their inability to answer questions accurately.

Figure 5. Locations of the 7 participating sites across Taiwan in the HALST study. Individuals were recruited from multiple regions across Taiwan, including 2 areas in the northern region, 2 in the central region, 2 in the southern region, and 1 in the eastern region. (Abbreviation: HALST, Healthy Aging Longitudinal Study in Taiwan).

All of the study participants underwent home-visit assessments that included interviewer-administered questionnaires as well as standardized clinical and laboratory examinations in a hospital. The demographic variables explored include age, educational level, marital status, smoking status, alcohol intake, physical activity, and medications including antiarrhythmic drugs. Height, body weight, and blood pressure were recorded. Blood tests included lipid profile (total cholesterol, triglycerides, and HDL cholesterol), fasting glucose, and glycated hemoglobin (HbA1c). Hypertension was defined by self-report, the current use of anti-hypertensive medication, systolic blood pressure ≥130 mm Hg, or diastolic blood pressure ≥85 mm Hg at home. Dyslipidemia was defined by self-report, medication use, or high total cholesterol (≥240 mg/dL) or triglycerides (≥150 mg/dL) or reduced HDL cholesterol (men <40 mg/dL; women <50 mg/dL). Diabetes mellitus was defined by self-report, medication use, or high fasting plasma glucose (≥126 mg/dL) or HbA1c (≥6.5%).

This long-term prospective study was reviewed and approved by the Institutional Review Board of the National Health Research Institutes in Taiwan and their participating hospitals, and all participants provided written informed consent. Recruitment began in December 2008 and ended in March 2013. All enrollees were followed until death, and the cut-off for data collection in the current study was the end of April 2019. Among the 5,830 individuals enrolled in the HALST, we included 3,383 individuals ≥65 years of age who were free of documented heart disease at the time of enrollment (Figure 1). The participants with left bundle branch block, old MI, heart failure, severe valvular heart diseases, and arrhythmia were excluded from this study.

ECG analysis and diagnostic criteria

All study subjects received 3 serial ECG examinations on the same day at enrollment. These 12-lead ECGs were recorded at 1-minute intervals using the standard settings of 10 mm/mV and 25 mm/s; PR, QRS, and corrected QT interval were automatically computed by Bazett’s formula. CRBBB was classified according to the Minnesota Code criteria (7-2-1) by a QRS duration ≥120 ms in a majority of beats in any of leads I, II, III, aVL, or aVF, plus R’ > R in lead V1 or V2; or QRS mainly upright, with an R-peak duration ≥60 ms in V1 or V2; or S duration > R duration in all beats in lead I or II, as in previous studies [9, 10, 23]. All ECGs were analyzed and interpreted by two independent cardiologists who were blinded to the participants’ clinical data. Those with left bundle branch block, old MI, pacing rhythm, lung diseases, or poor image quality on ECG were excluded from this study (Figure 1).

Follow-up and outcomes

An annual follow-up telephone interview was carried out for all study participants. Information on the cause of death, if applicable, was determined by linking the database of death records from the Taiwan Ministry of Health and Welfare. We used International Classification of Diseases version 10 (ICD-10) codes to identify the cause of death and defined cardiovascular death by the ICD codes I01-I02.0, I05-I09, I20-I25, I27, and I30-I52. Survival curves were plotted by the Kaplan–Meier method, and the log-rank test was used for the comparison of the difference in mortality between patients with and without CRBBB.

Statistical and survival analysis

We used either Chi-square or Fisher’s exact tests to compare categorical variables and one-way ANOVA for continuous variables. Inter-observer agreement was determined by the overall proportion of agreement across all ECGs using the Kappa statistic. The log-rank test and a Cox regression model were used for the comparison of the difference in mortality between participants with and without CRBBB. A two-tailed P value <0.05 was considered significant.

Author Contributions

Conceptualization, I.-C. W., C.-C. H., T.-Y. C., W.-T. T., C. A. H., and J.-M. J. J.; Formal Analysis, S. S.-F. Y. and C.-Y. J. C., D.-H. Y., and J.-M. J. J.; Investigation, I.-C. W., C.-C. H., T.-Y. C., W.-T. T., F.-C. T., C.-C. W., C.-C. J., H.-C. C., and H.-M. L.; Data Curation, I.-C. W., C.-C. H., T.-Y. C. W.-T. T., F.-C. T., C.-C. W., C.-C. J., H.-C. C., and H.-M. L.; Writing – Original Draft Preparation, S. S.-F. Y., C.-Y. J. C. and D.-H. Y.; Writing – Review & Editing, S. S.-F. Y., C.-Y. J. C., I.-C. W., C.-C. H., T.-Y. C., W.-T. T., F.-C. T., C.-C. W., C.-C. J., H.-C. C., H.-M. L., D.-H. Y., J.-M. J. J., and C. A. H.; Supervision, C. A. H., and J.-M. J. J; Funding Acquisition, C. A. H. and J.-M. J. J.

Acknowledgments

The authors thank Melissa Stauffer of Scientific Editing Solutions for editing the manuscript. We are grateful to the HALST study's advisory committee (Drs. Luigi Ferrucci, Jack M. Guralnik, Dilip V. Jeste, and Kung-Yee Liang) for the valuable suggestions. We wish to thank the men and women who participated in the study, and all the members of the HALST study group. The members of the HALST study group are as follows: Drs. Chao-Agnes Hsiung, Chih-Cheng Hsu, I-Chien Wu, Hsing-Yi Chang, Chu-Chih Chen, Yen-Feng Chiu, Hui-Ju Tsai, and Ken N. Kuo, of National Heath Research Institutes; Dr. Ching-Yu Chen of National Taiwan University; Dr. Kiang Liu of Northwestern University Medical School; Dr. Marion Lee of University of California at San Francisco; Dr. Ida Chen of Cedars-Sinai Medical Center; Dr. Shu-Han Yu of Chung Shan Medical University; Dr. Kai-Ting Ko of Mackay Memorial Hospital; Dr. Tzuo-Yun Lan of National Yang-Ming University; Dr. Hou-Chang Chiu of Shin Kong Wu Ho-Su Memorial Hospital; Dr. Wen-Jin Liaw of Yee Zen General Hospital; Dr. Yo-Hann Liu of Hope Doctors Hospital; Dr. I-Ching Lin of Changhua Christian Hospital; Dr. Ping-An Wu of Potz General Hospital; Dr. Chon-Chou Juan of Yuan's General Hospital; and Dr. Shi-Chen Shen of Mennonite Christian Hospital. We are also grateful to the staff of the Sixth Core Lab, Department of Medical Research, National Taiwan University Hospital, and the Taiwan Health Foundation for technical support.

Conflicts of Interest

The authors have no conflicts of interest to declare.

Funding

This work was supported by the National Health Research Institutes of Taiwan under Grants PH-101-SP-01, PH-102-SP-01, and PH-103-SP-01; the Ministry of Science and Technology of Taiwan (grant numbers: MOST-104-2314-B-002-193-MY3, MOST 106-2314-B-002-047-MY3, MOST 106-2314-B-002 -134 -MY2, MOST 106-2314-B-002-206, MOST 107-2314-B-002-009, MOST 107-2314-B-002-261-MY3, and MOST 108-2635-B-002-002); and the Taiwan Health Foundation, National Taiwan University Hospital (grant numbers: NTUH 105-S3077, NTUH-105-S2995, NTUH-UN105-012, NTUH 106-S3469, NTUH106-S3458, and NTUH 106-018).

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