Yi-Bang Cheng

Diurnal Blood Pressure Rhythmicity in Relation to Environmental and Genetic Cues in Untreated Referred Patients

No previous study has addressed the relative contributions of environmental and genetic cues to the diurnal blood pressure rhythmicity. From 24-hour ambulatory recordings of systolic blood pressure obtained in untreated patients (51% women; mean age, 51 years), we computed the night-to-day ratio in 897 and morning surge in 637. Environmental cues included season, mean daily outdoor temperature, atmospheric pressure, humidity and weekday, and the genetic cues 14 single nucleotide polymorphisms in 10 clock genes. Systolic blood pressure averaged (±SD) 126.7±11.9 mm Hg, night-to-day ratio 0.86±0.07, and morning surge 24.8±10.7 mm Hg. In adjusted analyses, night-to-day ratio was 2.4% higher in summer and 1.8% lower in winter (P<0.001) compared with the annual average with a small effect of temperature (P=0.079); morning surge was 1.7 mm Hg lower in summer and 1.1 mm Hg higher in winter (P<0.001). The other environmental cues did not add to the night-to-day ratio or morning surge variance (P≥0.37). Among the 14 genetic variations, only CLOCK rs180260 was significantly associated with morning surge after adjustment for season, temperature, and other host factors and after Bonferroni correction (P=0.044). In CLOCK rs1801260 C allele carriers (n=83), morning surge was 3.7 mm Hg higher than in TT homozygotes (n=554). Of the night-to-day ratio and morning surge variance, season and temperature explained ≈8% and ≈3%, while for genetic cues, these proportions were ≈1% or less. In conclusion, environmental compared with genetic cues are substantially stronger drivers of the diurnal blood pressure rhythmicity.

Quantification of the Interrelationship between Brachial-Ankle and Carotid-Femoral Pulse Wave Velocity in a Workplace Population.

Background: Brachial-ankle pulse wave velocity (PWV) is increasingly used for the measurement of arterial stiffness. In the present study, we quantified the interrelationship between brachial-ankle and carotid-femoral PWV in a workplace population, and investigated the associations with cardiovascular risk factors and carotid intima-media thickness (IMT). Methods: Brachial-ankle and carotid-femoral PWV were measured using the Omron-Colin VP1000 and SphygmoCor devices, respectively. We investigated the interrelationship by the Pearsons correlation analysis and Bland-Altman plot, and performed sensitivity and specificity analyses. Results: The 954 participants (mean ± standard deviation age 42.6 ± 14.2 years) included 630 (66.0%) men and 203 (21.3%) hypertensive patients. Brachial-ankle (13.4 ± 2.7 m/s) and carotid-femoral PWV (7.3 ± 1.6 m/s) were significantly correlated in all subjects (r = 0.75) as well as in men (r = 0.72) and women (r = 0.80) separately. For arterial stiffness defined as a carotid-femoral PWV of 10 m/s or higher, the sensitivity and specificity of brachial-ankle PWV of 16.7 m/s or higher were 72 and 94%, respectively. The area under the receiver operating characteristic curve was 0.953. In multiple stepwise regression, brachial-ankle and carotid-femoral PWV were significantly (p < 0.001) associated with age (partial r = 0.33 and 0.34, respectively) and systolic blood pressure (partial r = 0.71 and 0.66, respectively). In addition, brachial-ankle and carotid-femoral PWV were significantly (p < 0.001) associated with carotid IMT (r = 0.57 and 0.55, respectively) in unadjusted analysis, but not in analysis adjusted for cardiovascular risk factors (p ≥ 0.08). Conclusions: Brachial-ankle and carotid-femoral PWV were closely correlated, and had similar determinants. Brachial-ankle PWV can behave as an ease-of-use alternative measure of arterial stiffness for assessing cardiovascular risk.

Association of Anthropometric and Bioelectrical Impedance Analysis Measures of Adiposity with High Molecular Weight Adiponectin Concentration.

Objective To investigate the relationship between adiposity measures and plasma concentration of high molecular weight (HMW) adiponectin. Methods In a Chinese sample (n = 1081), we performed measurements of anthropometry and bioelectrical impedance analysis (BIA). We defined overweight and obesity as a body mass index between 24 and 27.4 kg/m² and ≥ 27.5 kg/m², respectively, and central obesity as a waist circumference ≥ 90 cm in men and ≥ 80 cm in women. Plasma HMW adiponectin concentration was measured by the ELISA method. Results Plasma HMW adiponectin concentration was significantly (P < 0.0001) higher in women (n = 677, 2.47 μg/mL) than men (n = 404, 1.58 μg/mL) and correlated with advancing age in men (r = 0.28) and women (r = 0.29). In adjusted analyses, it was lower in the presence of overweight (n = 159, 1.26 μg/mL in men and n = 227, 2.15μg/mL in women) and obesity (n = 60, 1.31 μg/mL and n = 82, 2.10 μg/mL, respectively) than normal weight subjects (n = 185, 2.07μg/mL and n = 368, 2.94 μg/mL, respectively) and in the presence of central obesity (n = 106, 1.28 μg/mL and n = 331, 2.12 μg/mL, respectively) than subjects with a normal waist circumference (n = 298, 1.74 μg/mL and n = 346, 2.74 μg/mL, respectively). In multiple regression analyses stratified for gender, adjusted for confounders and considered separately each of the adiposity measures, all adiposity measures were significantly (r -0.18 to -0.31, P < 0.001) associated with plasma HMW adiponectin concentration. However, in further stratified and adjusted regression analyses considered stepwise all adiposity measures, only waist-to-hip ratio was significantly (P < 0.05) associated with plasma HMW adiponectin concentration in men (r = -0.10) and women (r = -0.15). Conclusions Anthropometric measures of obesity, such as waist-to-hip ratio, but not BIA measures, are independently associated with plasma adiponectin concentration.

A Comparative Study on Skin and Plasma Advanced Glycation End Products and Their Associations with Arterial Stiffness

Background: We compared skin and plasma measurements of advanced glycation end products (AGEs), with particular focus on their levels in the presence of hypertension or diabetes and prediabetes and their associations with arterial stiffness in outpatients with suspected or diagnosed hypertension. Methods: Skin AGE accumulation was measured as autofluorescence on the left forearm using the skin autofluorescence Reader and expressed in arbitrary units in the range from 0 to 25. Plasma AGE concentration was measured by the enzyme-linked immunosorbent assay method and logarithmically transformed for statistical analysis. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV) using the SphygmoCor system (Sydney, Australia). Results: The 218 participants (96 [44.0%] men, mean age 51.9 years) had a mean skin autofluorescence of 1.89 arbitrary units, plasma AGE concentration of 4.47 μg/ml, and cfPWV of 8.0 m/s. Skin autofluorescence was significantly correlated with plasma AGEs in diabetic or prediabetic patients (n = 31, r = 0.37, p = 0.04) but not in subjects with normoglycemia (n = 187, r = -0.05, p = 0.48). Nonetheless, both measurements were significantly (p ≤ 0.001) higher in men (2.00 arbitrary units and 6.73 μg/ml, respectively) than women (1.81 arbitrary units and 3.60 μg/ml, respectively) and in diabetic or prediabetic (2.03 arbitrary units and 6.61 μg/ml, respectively) than normoglycemia subjects (1.87 arbitrary units and 4.17 μg/ml, respectively), but similar in hypertensive (n = 105) and normotensive subjects (n = 113, p ≥ 0.35). In adjusted multiple regression analyses, plasma AGE concentration, but not skin autofluorescence (p ≥ 0.37), was significantly associated with cfPWV in all subjects (β 0.44 m/s for each 10-fold increase; p = 0.04) and in subgroups of men and diabetes and prediabetes (β 0.12-0.55 m/s for each 10-fold increase; p ≤ 0.02). Conclusions: Although skin and plasma AGEs were similarly associated with gender and diabetes or prediabetes, they might measure something different and have different clinical relevance, such as for arterial stiffness.

Persistence of Masked Hypertension in Chinese Patients

BACKGROUND Masked hypertension (MH) has 10-15% prevalence and carries risk similar to that of sustained hypertension, but its short-term persistence remains uncertain. METHODS Forty-five patients with MH (mean age 52.2 years; 37.8% women) were enrolled in the placebo arm of a randomized clinical trial of Chinese medicine (NCT02156024) and followed up for 4 weeks. MH was office normotension (<140/90mm Hg) and daytime (8:00-18:00) hypertension (≥135/85mm Hg). RESULTS At enrolment, office and daytime systolic/diastolic blood pressure (BP) averaged 129.0/80.6mm Hg and 132.9/88.9mm Hg, respectively. Daytime BP thresholds for MH were met in 5 patients (11.1%) for systolic BP, in 25 (55.6%) for diastolic BP and in 15 (33.3%) for both. At follow-up, systolic and diastolic BP had not changed compared with baseline (P ≥ 0.12), except for a 2.1mm Hg decrease in office systolic BP (P = 0.049). MH remained present in 28 patients (62.2%; 95% CI, 48.1-76.3%), whereas 13 (28.9%; 15.7-42.1%) and 4 (8.9%; 0.6-17.2%) converted to normotension (daytime BP <135/85mm Hg) or sustained hypertension (office BP ≥140/90mm Hg), respectively. Substituting daytime by 24-hour BP, using 130/80mm Hg as threshold, produced consistent results. Systolic office BP at baseline independently predicted persistence of MH or progression to sustained hypertension at 4 weeks (odds ratio per 1 - SD increase, 3.49; 95% CI, 1.06-11.2; P = 0.04). CONCLUSIONS The information that MH persists over 4 weeks in over two-thirds of this sample of patients should inform future clinical trials and guidelines.

Validation of a Piezoelectric Sensor Array-Based Device for Measurement of Carotid-Femoral Pulse Wave Velocity: The Philips Prototype

Background: Multiple piezoelectric pressure mechanotransducers topologized into an array might improve efficiency and accuracy in collecting arterial pressure waveforms for measurement of pulse wave velocity (PWV). Objective: In the present study, we validated a piezoelectric sensor array-based prototype (Philips) against the validated and clinically widely used Complior device (Alam Medical). Methods: We recruited 33 subjects with a wide distribution of PWV. For the validation, PWV was measured sequentially with the Complior device (four times) and the Philips prototype (three times). With the 99 paired PWV values, we investigated the agreement between the Philips prototype and the Complior device using Pearson correlation analysis and Bland-Altman plot. We also performed analysis on the determinants and reproducibility of PWV measured with both devices. Results: The correlation coefficient for PWV measured with the two devices was 0.92 (p < 0.0001). Compared with the Complior device, the Philips prototype slightly overestimated PWV by 0.24 (± 2 standard deviations, ± 1.91) m/s, especially when PWV was high. The correlation coefficient between the difference and the average of the Philips and Complior measurements was 0.21 (p = 0.035). Nonetheless, they had similar determinants. Age, mean arterial pressure, and sex altogether explained 81.6 and 83.9% of the variance of PWV values measured with the Philips prototype and Complior device, respectively. When the two extremes of the three PWV values measured with the Philips prototype and the Complior device were investigated, the coefficients of variation were 8.26 and 3.26%, respectively. Conclusions: Compared with the Complior device, the Philips prototype had similar accuracy, determinants, and reproducibility in measuring PWV.

Independent effects of blood pressure and parathyroid hormone on aortic pulse wave velocity in untreated Chinese patients

Objective: Whether or not calcium-regulating hormones stiffen arteries independent of blood pressure (BP) is uncertain. We investigated the independent associations of carotid–femoral pulse wave velocity (PWV) with 25-hydroxy-vitamin D [25(OH)D], parathyroid hormone (PTH) and 24-h ambulatory BP in untreated Chinese patients. Methods: Consecutive untreated patients referred for ambulatory BP monitoring were recruited. PWV was measured with a high-fidelity micromanometer and the SphygmoCor software (AtCor Medical, West Ryde, New South Wales, Australia). Serum 25(OH)D and PTH were determined by electrochemiluminescence immunoassay. Analysis of variance, single and multiple regressions were applied for analyses. Results: In 1052 untreated patients (50.7% women; mean age, 51 years), PWV averaged 7.8 m/s, 24-h SBP/DBP 126.5/81.7 mmHg, serum 25(OH)D and PTH 36.0 nmol/l and 61.6 pg/ml, respectively. In multivariable-adjusted analyses, BP (P < 0.001) and PTH (P = 0.012) increased from less than 25th to at least 75th percentile of the PWV distribution. In continuous analyses, PWV independently increased by 0.40/0.23 m/s per 1-SD increment in SBP/DBP (P < 0.001) and by 0.14 m/s for a doubling of serum PTH (P = 0.029). Associations of PWV with BP were tighter than with PTH (P < 0.001). In pathway analysis, the effect of PTH on PWV did not run via serum or urinary calcium (P = 0.65), but PTH had both a direct (P = 0.026) and a BP-mediated indirect effect (P = 0.043) on PWV. In none of our analyses were PWV associated with serum 25(OH)D. Conclusion: Arterial stiffness, as assessed by PWV, independently increased both with BP and with PTH, but BP remains the main driver of arterial stiffening.

OS 09-02 PREVALENCE AND DETERMINANTS OF EXAGGERATED MORNING SURGE AND MORNING HYPERTENSION IN CHINESE: THE CHINA AMBULATORY AND HOME BLOOD PRESSURE REGISTRY (ABPR).

Objective: Prognosis of exaggerated morning surge (MS) of blood pressure (BP) remains controversial, possibly due to the ethnic difference in the size of MS. Compared to MS, evidence on morning hypertension (MH) is more consistent. With the use of a national BP registry database, we studied the size of MS and the prevalence and determinants of exaggerated MS and MH in Chinese. Design and Method: In the 3547 patients (mean age, 56.8 years; women, 49.1%; hypertension, 79.0%) enrolled in the China Ambulatory and Home BP Registry (ABPR), we performed both 24-h ambulatory and 7-day self-measured home BP monitoring. Exaggerated MS was a sleep-trough MS ≥ 35 mmHg as recommended by the Chinese guidelines. Morning hypertension was a mean BP of at least 135/85 mmHg either self-measured at home in the morning or recorded by ambulatory monitors during 6:00–10:00 (8:00–12:00 for patients from Xinjiang Province). Results: In all registered patients, sleep-trough systolic MS averaged (SD) 20.5 (13.5) mmHg, and 457 (12.9%) had an exaggerated MS. Multivariate regression analysis showed that the size of MS was greater in women (&bgr; = 1.26 mmHg; P = 0.02), increased with age (0.04 mmHg, P = 0.03), body-mass index (0.16 mmHg, P = 0.03) and 24-h systolic BP (0.05 mmHg, P = 0.006). Totally, 1796 (50.6%) and 1873 (52.8%) patients had MH on home and ambulatory BP monitoring, respectively. In treated hypertensive patients with office BP < 140/90 mmHg (n = 1230), the corresponding values were 32.6% and 37.5%, respectively. Overall, MH was significantly (P ⩽ 0.01) associated with male sex (standardized OR [95% CI], 1.17 [1.04–1.28]), older age (1.27 [1.18–1.37]), body mass index (1.20 [1.12–1.28]), alcohol intake (1.42 [1.16–1.73]), and home heart rate (1.19 [1.11–1.28]). Conclusions: The size of the sleep-trough MS in Chinese is modest, but similar to that reported in Europeans. However, MH is prevalent in Chinese patients, especially in those with cardiovascular risk factors.

OS 13-05 PREVALENCE OF CENTRAL HYPERTENSION AND ITS ASSOCIATION WITH TARGET ORGAN DAMAGE IN UNTREATED CHINESE PATIENTS.

Objective: Central blood pressure (BP) is suggested to be more closely correlated to target organ damage and cardiovascular events than brachial BP. Outcome-based thresholds for the diagnosis of central hypertension has been recently proposed. However, little is known about central hypertension. In an untreated patient cohort, we therefore investigated the prevalence of central hypertension and its association with target organ damage. Design and Method: Consecutive untreated patients referred for ambulatory BP monitoring to our Hypertension Clinic were recruited. Office brachial and central BP were measured using the Omron 7051 (Omron, Japan) and SphygmoCor (AtCor, Australia) devices, respectively. Patients were cross-classified according to the presence of brachial and central hypertension defined as a brachial and central systolic BP of at least 140 mmHg and 130 mmHg, respectively. Measures of target organ damage, including left ventricular mass index by echocardiography (GE, E9), carotid-femoral pulse wave velocity (cfPWV) and urinary albumin-to-creatinine ratio (ACR), were determined. Results: The 1928 participants (mean age, 51 years; women, 52%) included 1036 (54%) patients with brachial and central consistent normotension, 662 (34%) brachial and central combined hypertension, 74 (4%) isolated central hypertension, and 156 (8%) isolated brachial hypertension. Compared to patients with isolated brachial hypertension, patients with brachial and central combined hypertension had significant greater urinary ACR (0.96 vs. 0.68 mg/mmol, P < 0.001) and more patients with microalbuminuria (5% vs 0.7%, P = 0.017), faster cfPWV (8.50 vs. 8.17 m/s, P = 0.003), but similar left ventricular mass index (85.7 vs. 86.6 g/m2, P = 0.60) after multivariate adjustment. Patients with isolated central hypertension also had faster cfPWV (7.83 vs. 7.51 m/s, P = 0.03) than those with consistent normotension. Conclusions: Central hypertension was prevalent (about 38%) in this untreated patient cohort, 90% combined with brachial hypertension. Brachial and central combined hypertension was associated with worse target organ measures and might be a subtype we shall pay attention to.

THE ASSOCIATION OF INTRACRANIAL ARTERIAL STENOSIS WITH HOME BLOOD PRESSURE LEVEL AND VARIABILITY

Objective: Intracranial arterial stenosis (ICAS) is a major cause of ischemic stroke. However, the associations of ICAS with home blood pressure (BP) and variability remains unclear. Design and method: Outpatients not on antihypertensive medications were recruited from 2009 to 2013. ICAS was defined if the peak systolic flow velocities measured with transcranial Doppler sonography were respectively of at least 140 cm/s, 120 cm/s, or 100 cm/s at middle, anterior, or posterior and vertical cerebaral arteries. Home BP was self-measured by Omron HEM-7051 device for seven days. BP variability was assessed as variability independent of the mean, standard deviation, maximum–minimum difference, and average real variability. Results: The prevalence of ICAS in the 801 participants (average age 51 years, 50% males) was 7.9% (63 cases). Patients with ICAS compared to those without had significantly higher clinic (135.8 vs 131.9 mmHg, P = 0.01) and home systolic BPs (134.8 vs 128.6 mmHg, P < 0.001). In multivariate-adjusted regression model, home systolic BPs, irrespective of at morning or evening, were associated with ICAS independently of other risk factors including any BP variability indices (OR, 1.47 to 1.82; P < 0.005). However, after similar adjustment including home systolic BP, ICAS was only associated with seven-day morning systolic BP variability (OR, 1.35 to 1.47; P < 0.02), neither with evening BP variability (P > 0.47), nor any day-to-day BP variability indices (P > 0.07). Conclusions: Asymptomatic ICAS was moderately prevalent in Chinese untreated patients. Both home morning and evening systolic BPs were important determinants of ICAS, and BP variability in the morning was also associated with ICAS.