Study participants
Following a cross-sectional study design, since 2006–2007 (hereafter “2006”), 11 hospitals affiliated with Kailuan Hospital have conducted physical examinations on their current, dismissed, and retired staff members, collecting body measurements and biochemical indexes. All the staff came from China. They were included in the study subjects if they had met the following criteria: aged 18 years or older; with complete data on height and weight; with no history of CVEs. The same medical staff who conducted the first health examination continued to examine the same group of people at the same sites every 2 years in the same chronological order, making up the second (2008–2009), third (2010–2011), fourth (2012–2013), and fifth (2014–2015) waves of data collection (referred to in this article as “2008,” “2010,” “2012,” and “2014,” respectively). The investigation content, anthropometric measurements, and biochemical index tests were identical at each wave. Those who had missed any systolic blood pressure (SBP) test across the five study waves and incidence of CVEs between first and fifth physical examinations were excluded. In accordance with the Helsinki Declaration, this study has been approved by the Ethics Committee of Kailuan General Hospital, and written informed consent was obtained from all individuals in the observation group.
Data collection
Details of the epidemiological investigation and anthropometry index have been described elsewhere [12]. Smoking was operationalized as smoking at least one cigarette per day on average in the last year. Drinking was operationalized as consuming more than 300 ml of liquor (alcohol concentration > 50% volume per volume) per day for at least 1 year. Physical exercise was defined as exercising more than three times per week, with each time lasting more than 30 min. CVEs included stroke (namely, hemorrhagic stroke or ischemic stroke) and myocardial infarction.Trained medical staff members checked all of the inpatient diagnoses for individuals in the study group at the hospitals in the Kailuan Group and at the hospitals that were municipally listed for medical insurance every year. These staff members also recorded final events. All of these diagnoses were confirmed by professional doctors in line with inpatient records.
For the measurement of BP, subjects were required to refrain from smoking or drinking tea or coffee for 30 min before the measurement and to sit upright for 15 min quietly. The measurement was taken with the subject sitting with his/her bare right upper arm slightly stretched out, with the elbow lying at the same level as the heart. A suitable cuff was selected for the subject’s upper arm circumference and was then wound with moderate tension, close to the skin of the upper arm, with the cuff’s upper edge approximately 2.5 cm above the chelidon and centered over the brachial artery. The first four physical examinations used an adjusted mercury sphygmomanometer to test the BP of the right brachial artery. The SBP reading used Korotkoff sounds phase one, and the DBP reading used the fifth phase. For the fifth physical examination, an Omron electronic sphygmomanometer (HEM-8102A, Omron Co., Ltd. Daling China) was used to measure the BP of the right brachial artery. During each physical examination, BP was tested three times, with an interval of 1 min between tests, and the average of these three readings was recorded as the final BP of each subject.
To measure height and weight, trained medical staff members use an adjusted scale (model RGZ-120) to measure the subject’s height and weight from 7:30 a.m. to 9:00 a.m. For these measurements, the subjects were barefoot, had nothing on their heads, wore light clothing, and stood upright. Height was measured to the nearest 0.1 cm, and weight was measured to the nearest 0.1 kg.
Biochemical measurements
Blood samples taken from the antecubital vein were collected in EDTA tubes from the participants fasting overnight. By centrifugating at 3000 g for 10 min (centrifuge radius of 17 cm) at room temperature, plasma was then isolated. The measurement of supernatant serum was carried out in 4 h. Hexokinase/glucose-6-phosphate dehydrogenase method was adopted to measure fasting blood glucose. Total cholesterol (TC) was measured enzymatically (Mind Bioengineering Co. Ltd., Shanghai, China). All biochemical variables were measured by an automatic biochemical analyzer (Hitachi 747; Hitachi, Tokyo, Japan).
Relevant definitions
Hypertension and diabetes
Hypertension was defined as having a history of hypertension, SBP ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg, or SBP < 140 mmHg and/or DBP < 90 mmHg but taking antihypertensive drugs. Criteria for diabetes was a fasting glucose level of 126 mg/dL (7.0 mmol/L) or greater, or use of medications used to treat hyperglycemia.
BMI
BMI was calculated as weight/height2 (unit: kg/m2).
Long-term blood pressure variability
Measures of long-term BPV [13] include the standard deviation of BP, the coefficient of variation, the variability uncorrelated with mean BP, and the average real variability (ARV). ARV requires that the order of the BP readings be in line with the formula. This measurement can better predict damage to the target organ [14,15,16]. For this reason, ARV was adopted in the present study to estimate long-term BPV. The average real variability of systolic blood pressure (ARVSBP) was calculated using the following formula: ARVSBP = (|sbp2 − sbp1| + |sbp3 − sbp2| + |sbp4 − sbp3| + |sbp5 − sbp4|)/4, where sbp1, sbp2, sbp3, sbp4, and sbp5 represent the subject’s SBP at the first through the fifth physical examinations.
Statistical methods
All of the information from the physical examinations was recorded by unifying trained professional staff members and gathered by Kailuan General Hospital. SPSS 13.0 (SPSS, Chicago, IL, USA) was used for the data analysis. Averages ± standard deviations (x̅ ± s) were calculated for continuous variables. Single-factor analysis of variance was used for group comparisons, comparing averages using the least significant difference test in cases of variance homogeneity or Dunnett’s T3 test in cases of variance non-homogeneity For categorical variables, n (%) was reported, and the χ2 test was used for group comparisons. Stepwise multiple linear regression models were used to analyze the impact of BMI on ARVSBP, and logistic regression models were used to estimate the risk of an increase in ARVSBP associated with BMI. For the latter analysis, the subjects were divided into two groups according to ARVSBP (less than vs. equal to or greater than the average ARVSBP [12.64]). Differences were considered statistically significant if P < 0.05 (two-sided test).
Including patients with hypertension and those taking antihypertensive drugs, and using different methods of measuring BP may affect our assessment of long-term BPV. Therefore, patients with hypertension, those taking antihypertensive drugs, and the fifth physical examination (which used a electronic sphygmomanometer to measure BP) were sequentially excluded in a sensitivity analysis, where we calculated the effect of BMI using partial regression coefficients, odds ratios (OR), and 95% confidence intervals (95% CI) of ARVSBP. Here, differences were considered statistically significant if P < 0.05 (two-side test).