Study population

Between January 2013 and August 2013, a representative sample of men and women from Liaoning province of China were evaluated for cardiovascular risk factors (primarily hypertension) using a multi-stage, random, stratified, cluster-sampling scheme, referred to as the Northeast China Rural Cardiovascular Health Study. The current study intentionally enrolled a representative sample aged ≥35 years, due to its purpose of evaluating hypertension and related cardiovascular risk factors. Within the Liaoning province, three counties (Dawa, Zhangwu and Liaoyang) were selected from the eastern, southern and northern regions, where the greater majority of residents are agricultural labourers. One township near a city in each county was randomly selected, totaling 3 townships and 5–8 villages from each township were randomly selected, with a total of 18 rural villages finally selected. Those who were pregnant, suffering from cancers or mental disorders were excluded from the current study.

All eligible permanent residents ≥35 years of age from each village (n=14 016) were initially recruited, and a total of 11 956 (85.3%) participants completed the study. Subjects with incomplete data, poor ECG quality, atrial fibrillation (AF)/flutter, paced rhythm, Wolff-Parkinson-White syndrome or congenital heart diseases were excluded from the study, leaving a total of 11 264 participants for the final analyses. All participants signed written consent after they had been informed of the study’s objectives, benefits, medical procedures and confidentiality safeguards for personal information. Also, informed consent was obtained from the proxies of participants who were illiterate.

Data collection and measurements

Data were collected during a single clinic visit by cardiologists and trained nurses using a standard questionnaire with face-to-face interviews. All the potential investigators had received training in relation to the objectives of the study, how to perform the questionnaire, the standard methods of measurement, the importance of standardisation, as well as the finer details of the study procedures. Only those who earned a perfect score on a post-training test were permitted to participate as study investigators. During the process of data collection, the investigators were provided with additional instructions and support. Data on demographic characteristics, medical history and lifestyle risk factors were obtained using the abovementioned interviews with a standardised questionnaire. A central steering committee with a subcommittee for quality control ensured that all data were collected in accordance with the aforementioned standards.

According to the guidelines of the American Heart Association, blood pressure (BP) was measured three times at 2 min intervals, with a resting period of at least 5 min using a standardised automatic electronic sphygmomanometer (HEM-907; Omron, Kyoto, Japan). Independently, two doctors checked the calibration of the Omron device every month using a standard mercury sphygmomanometer in accordance with the British Hypertension Society protocol.17 All participants were directed to avoid caffeinated beverages and exercise at least 30 min prior to evaluation. During BP measurement, the participants were seated with their arms supported at the level of their hearts. The mean value of three BP measurements were calculated and used in all the subsequent analyses. Hypertension was defined by the criteria widely employed and considered to be the worldwide standard in epidemiological research studies: a systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg and/or the use of antihypertensive medications. All participants were classified into the following groups based on mean SBP/DBP values and the most recent 2017 American College of Cardiology/American Heart Association guidelines18: (a) normal: SBP <120 mm Hg and DBP <80 mm Hg, (b) elevated BP: SBP 120–129 mm Hg and DBP <80 mm Hg, (c) stage 1 hypertension: SBP 130–139 mm Hg or DBP 80–89 mm Hg and (d) stage 2 hypertension: SBP ≥140 mm Hg or DBP ≥90 mm Hg. During the course of the study, subjects who were taking anti-hypertensive medication and had a history of hypertension were considered to be at stage 2 hypertension as their BP levels would have exceeded 140/90 mm Hg during their initial hypertension diagnosis in accordance with the previous criteria. Weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively, with all participants given lightweight clothing and evaluated barefoot. The body mass index (BMI) was calculated as weight in kilograms divided by the square of height in metres (kg/m²). As recommended by the Working Group on Obesity in China, overweight was defined as a BMI of 24.0–27.9 kg/m² and obesity as a BMI of 28.0 kg/m² or higher.19

Fasting blood samples were collected in the morning after ≥8 hour of fasting. Blood samples were collected from the antecubital vein using BD Vacutainer tubes containing EDTA (Becton, Dickinson and Co., Franklin Lakes, NJ, USA). Subsequently, serum was isolated from whole blood, with all serum samples subsequently frozen at −20°C for testing at a central, certified laboratory. Fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), low-density lipid cholesterol (LDL-C), serum uric acid (SUA) and other routine blood biochemical indices were analysed enzymatically using an auto-analyzer (Olympus AU640 Auto-Analyzer; Olympus Corp., Kobe, Japan). According to the criteria issued by WHO, diabetes mellitus was defined as a FBG ≥7.0 mmol/L and/or patients currently being treated for diabetes.20

In addition, 12-lead resting, 10-s ECGs were performed on all participants by well-trained cardiologists using an electrocardiography machine (MAC 5500; GE Healthcare, Little Chalfont, Buckinghamshire, UK). The results were automatically analysed by the MUSE Cardiology Information System (V.7.0.0; GE Healthcare). The P wave in each lead was defined as the initial upward point or downward deflection from the isoelectric line to the point of the initial baseline. For the calculation of the P wave duration, onsets were defined as the earliest deflection in any lead and offsets were defined as the latest deflection in any lead. Employing the most recent consensus guidelines,1 IAB was defined as a prolonged P wave duration ≥120 ms on a 12-lead ECG in the current study.

Echocardiograms were obtained using a commercially available Doppler echocardiograph (Vivid; GE Healthcare) with a 3.0-MHz transducer. Echocardiogram analyses and readings were performed by three separate doctors, all of whom were specialised in echocardiography, while two other specialists were called in case of any questions or uncertainties. LAD in the current study was defined as the left atrial anteroposterior measurement in the parasternal long-axis view according to the recommendations of the American Society of Echocardiography.21 The reported LAD values in our study were not indexed by body surface area. Left ventricular mass index (LVMI) was calculated based on body surface area, while left ventricular hypertrophy (LVH) was defined as a LVMI >115 g/m² in men and >95 g/m² in women.

Statistical analysis

All statistical analyses were performed using SPSS V.17.0 statistical software (SPSS, Inc, Chicago, IL, USA). Differences between groups were compared using a two-tailed Student’s t-test for continuous variables and a χ2 test for categorical variables. IAB prevalence by BMI category and hypertension were calculated and presented accordingly. Multivariate linear regression analyses were performed to identify the linear correlation among BP, BMI and P wave duration. Multivariate logistic regression analyses were conducted to evaluate the link between hypertension and obesity with IAB. Data were expressed as OR and 95% CI, β, mean ±SD or frequency and percentages; A p value <0.05 was considered to be statistically significant.

Patient and public involvement

No patients were involved in setting the research questions or the outcome measures, nor were they involved in the design or performance of the study. No participants or patients were asked to advise on the interpretation or writing up of results. No plans were set in place to disseminate the results of the research to study participants.

Characteristics of the study population

A total of 11 264 participants were included for final analyses, comprising of 5126 men and 6138 women with a mean age of 53.8 years. The general prevalence of IAB was calculated to be 6.3% (711/11 264) within the total population, which was significantly higher in subjects with left atrial enlargement (LAE) than those without (12.7 vs 5.6%; p<0.001). The subjects with IAB (n=711) were significantly older and exhibited higher BMI, SBP, DBP, FBG, TC, TG, LDL-C, SUA, LAD, LVMI and heart rate values compared with those with normal P wave durations (all ps<0.005) (table 1). Furthermore, the participants with IAB had significantly higher percentages of men, current drinker, anti-arrhythmic medication and anti-hypertensive medication, and higher prevalences of obesity, hypertension, diabetes mellitus, LAE and LVH (all ps<0.05). Notably, HDL-C levels were found to be lower in subjects with IAB than those without IAB (p=0.002). No significant differences were detected regarding smoking status between the two groups (p=0.699). Furthermore, IAB participants were identified with a relatively higher prevalence of myocardial infarction (MI), heart failure (HF) and mitral stenosis/regurgitation, even though no statistical significance was detected (all ps>0.05).

IAB prevalence by hypertension and BMI category

The gender-specific prevalence of IAB categorised according to hypertension and BMI category were shown in figure 1. The prevalence of IAB in hypertensive subjects was found to be higher than the normotensive in both men (9.5 vs 5.9%; p<0.001) and women (6.6 vs 3.6%; p<0.001). In addition, the prevalence of IAB demonstrated a sharp rise with advancing BMI in both men (4.9% , 9.0% and 13.0% in those with BMI<24.0, 24.0–27.9 and ≥28.0 kg/m², respectively; p for trend <0.001) and women (3.5% , 5.9% and 6.9% in those with BMI<24.0, 24.0–27.9 and ≥28.0 kg/m², respectively; p for trend <0.001). The prevalence of IAB for BMI category by hypertension was calculated and presented in figure 2. Our results demonstrated that the prevalence of IAB rose significantly with advancing BMI in both normotensive and hypertensive subjects (ps for trend <0.001). Furthermore, higher prevalence of IAB was detected in the hypertensive subgroup at each BMI category (all ps <0.05).

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Figure 1

Gender-specific prevalence of interatrial block (IAB) by hypertension and body mass index (BMI) category.

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Figure 2

Prevalence of interatrial block (IAB) for body mass index (BMI) category by hypertension.

Linear relationship of BP, BMI with P wave duration

Multivariate linear regression analyses were performed to elucidate the association of BP, BMI and P wave duration, which are presented in table 2. To better understand the complex effects of the numerous clinical factors associated with P wave duration, 4 sets of multivariate models were employed accordingly. In model 1, factors such as BP, BMI, age, gender and race were included, with results demonstrating that SBP, DBP and BMI were all independently associated with P wave duration (β=0.03, 0.11 and 0.44, respectively; all ps <0.001). In model 2, additional variables such as FBG, plasma lipids, SUA, smoking, drinking, education, income, use of anti-arrhythmic medication, use of anti-hypertensive medication, mitral stenosis/regurgitation and history of MI and HF were adjusted accordingly, the results of which revealed that the independent associations were presented with a relatively lower β (all ps <0.001). In model 3, after LAD had been further adjusted, the linear regression coefficients were found to decline to 0.02, 0.09 and 0.25 for SBP, DBP and BMI, respectively (all ps <0.001). Finally, in model 4, while LVMI was added to the multivariate linear regression, SBP, DBP and BMI were still all found to be independently associated with P wave duration (all ps <0.005).

Associations between hypertension, overweight/obesity and IAB

In an attempt to further evaluate the associations of hypertension and overweight/obesity with IAB, we performed a series of multivariate logistic regression analyses, the results of which were shown in table 3. In model 1, factors such as hypertension, BMI categories, age, gender and race were included, with results demonstrating that hypertensive subjects exhibited higher odds of IAB than the normotensive subjects (OR=1.42; 95% CI 1.19 to 1.68). Compared with individuals with a BMI <24.0 kg/m², higher odds of IAB were found in both overweight (OR=1.76; 95% CI 1.46 to 2.11) and obese individuals (OR=2.32; 95% CI 1.88 to 2.87). In model 2, additional variables of diabetes, plasma lipids, SUA, smoking, drinking, education, income, use of anti-arrhythmic medication, use of anti-hypertensive medication, mitral stenosis/regurgitation, history of MI and history of HF were adjusted accordingly, with the subsequent results obtained indicating that the independent associations preserved with relatively lower ORs (all ps <0.05). In model 3, after LAD had been further adjusted, the ORs decreased to 1.29, 1.40 and 1.64 for hypertension, overweight and obesity, respectively (all ps <0.05). Finally, LVMI was added in model 4, and the ORs changed to 1.27, 1.42 and 1.67 (all ps <0.05).