Qian-Hui Guo

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.

Extreme rejuvenation and softening in a bulk metallic glass

Rejuvenation of metallic glasses, bringing them to higher-energy states, is of interest in improving their plasticity. The mechanisms of rejuvenation are poorly understood, and its limits remain unexplored. We use constrained loading in compression to impose substantial plastic flow on a zirconium-based bulk metallic glass. The maximum measured effects are that the hardness of the glass decreases by 36%, and its excess enthalpy (above the relaxed state) increases to 41% of the enthalpy of melting. Comparably high degrees of rejuvenation have been reported only on microscopic scales at the centre of shear bands confined to low volume fractions. This extreme rejuvenation of a bulk glass gives a state equivalent to that obtainable by quenching the liquid at ~1010 K s–1, many orders of magnitude faster than is possible for bulk specimens. The contrast with earlier results showing relaxation in similar tests under tension emphasizes the importance of hydrostatic stress.Deforming metallic glasses can rejuvenate them to higher energy states, but only in the shear bands where deformation is usually concentrated. Here, the authors use a notched setup to suppress shear banding and promote significant bulk softening of a zirconium-based metallic glass.

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.

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.

GLOMERULAR HYPERFILTRATION AS AN EARLY MARKER OF RENAL DYSFUNCTION IN MASKED HYPERTENSION

Objective: Glomerular hyperfiltration, an early marker of renal dysfunction, is prevalent in the early stage of hypertension but had not been investigated in masked hypertension. The aim of the present study is to investigate the association of hyperfiltration with masked hypertension. Design and method: We recruited consecutive untreated outpatients who were referred for 24-h ambulatory blood pressure monitoring to the Hypertension Clinic. Masked hypertension was defined as an elevated 24-hour ambulatory blood pressure (> = 130/80 mm Hg) with a normal office blood pressure (<140/90 mm Hg). Glomerular hyperfiltration was defined as estimated glomerular filtration rate (eGFR) above the sex-and age- specific 95th percentile of normotensive subjects. Results: Among the 1768 participants (mean age, 50.9 years; 52.9% women), 646 (36.5%) had masked hypertension, 88 (5.0%) had microalbuminuria, and 176 (10.0%) had glomerular hyperfiltration. In multivariate analyses, glomerular hyperfiltration was independently associated with younger age, female sex, increased body mass index, 24-h systolic blood pressure and heart rate, and the presence of diabetes mellitus. The prevalence of glomerular hyperfiltration was significantly higher in masked hypertension compared with that in normotensives (12.2% vs.5.1%, P < 0.001), with an adjusted odds ratio of 2.42 (95% CI: 1.20–4.89, P = 0.01). The corresponding difference in prevalence (12.4% vs. 5.2%, P < 0.001) and the adjusted odds ratio (2.33, 95%CI, 1.44–3.76, P = 0.005) remained significant after excluding 88 patients with microalbuminuria. Conclusions: In conclusion, glomerular hyperfiltration was prevalent in masked hypertension as an early marker of renal damage.

Ambulatory blood pressure in relation to oxygen desaturation index as simultaneously assessed by nighttime finger pulse oximetry at home

We investigated the relationship between ambulatory blood pressure (BP) and oxygen desaturation index (ODI), while accounting for pulse rate and age. ODI was assessed by overnight finger pulse oximetry in 2342 participants on the day of ambulatory BP monitoring, and calculated as the number of desaturation episodes per sleeping hour. Both BP and pulse rate increased significantly (P ≤ .006) from normal (< 5 events/h) to mildly (5‐14), moderately (15‐30), and severely (≥ 30 events/h) elevated ODI. The association for BP was substantially attenuated by accounting for pulse rate (partial r² from .003‐.012 to .002‐.006). In adjusted analysis, the associations of 24‐hour diastolic BP and 24‐hour pulse rate with ODI were dependent on age (P ≤ .0001) and only significant in younger subjects (< 60 years, P ≤ .0001). In conclusion, the association between ambulatory BP and ODI was partially mediated by pulse rate, a measure of sympathetic activity, and was more prominent in younger subjects.

Association of pulse wave velocity with single nucleotide polymorphisms related to parathyroid hormone

Abstract Objective: Carotid-femoral pulse wave velocity (cfPWV) was associated with serum parathyroid hormone (PTH) in untreated Chinese. We investigated in the same cohort whether cfPWV, brachial-ankle (baPWV) and heart-brachial (hbPWV) pulse wave velocity (PWV) were associated with rs6127099 (CYP24A1) and rs4074995 (RGS14). A previously published genome-wide association study demonstrated that each additional copy of the T (rs6127099) or G (rs4074995) allele was associated with a 7% or 3% higher serum PTH, respectively. Methods: In 1601 untreated Chinese patients (mean age, 51.0 years; 51.9% women), we measured cfPWV by tonometry (SphygmoCor) and baPWV and hbPWV by combined oscillometry and plethysmography (VP-2000 PWV/ABI analyser), serum PTH by an immunoassay, and genotypes by the SNapShot method. Results: cfPWV, baPWV and hbPWV averaged 7.9, 14.6 and 5.5 m/s and serum PTH 65.7 pg/mL. Genotype frequencies were in Hardy-Weinberg equilibrium, amounting to 41.7% (AA), 44.9% (AT) and 13.4% (TT) for rs6127099 and to 70.7% (GG), 26.9% (GA) and 2.3% (AA) for rs4074995. With adjustments applied for sex, age, body mass index, heart rate and season, hbPWV was 0.05 m/s (p = .042) lower with each additional copy of the minor allele (T) of rs6127099. In similarly adjusted analyses of 157 normotensive participants younger than 50 years, cfPWV was 0.32 m/s (p = .004) higher per additional copy of the T allele. Sensitivity analyses additionally accounting for the total-to-HDL serum cholesterol ratio, plasma glucose, glomerular filtration rate and 24 h systolic blood pressure were consistent. No other association of PWV with the genetic variants reached significance. Conclusions: With an increasing number of rs6127099 T alleles, arterial stiffness, as exemplified by PWV, was lower in all participants in a muscular artery (hbPWV), but higher in young normotensive participants in an elastic artery (cfPWV).