Wichat Srikusalanukul

Influence of Adiposity and Physical Activity on Arterial Stiffness in Healthy Children: The Lifestyle of Our Kids Study

Abstract—Childhood obesity is increasingly prevalent in the community and is related to adverse cardiovascular outcomes during adulthood. In this study of healthy children, we evaluated the influence of adiposity and physical activity on carotid-femoral pulse wave velocity (PWV), an index of arterial stiffness and a marker of cardiovascular risk in adults. In 573 community-based children (mean age: 10.1±0.3 years; 51% boys), we measured body mass index and waist circumference. Percentage body fat was quantitated by dual-energy x-ray absorptiometry. Cardiorespiratory fitness (CRF) and physical activity levels were assessed using a 20-m shuttle run and 7-day pedometer count, respectively. PWV was estimated by applanation tonometry. In univariate analysis, PWV was positively correlated with body mass index (r=0.34), waist circumference (r=0.32), and percentage body fat (r=0.32; P<0.001 for all) and negatively correlated with CRF (r=−0.23; P<0.001) and pedometer count (r=−0.08; P=0.046). In separate multivariable linear regression models, body mass index, waist circumference, and percentage of body fat were independently and positively associated with PWV (P<0.01 for all) after adjusting for age, sex, systolic blood pressure, mean arterial pressure, heart rate, and CRF (P<0.01 for all). The influence of CRF on PWV was attenuated after adjusting for adiposity. In conclusion, increased body mass and adiposity and decreased CRF are associated with arterial stiffening in healthy prepubescent children.

Postprandial Hypotension Predicts All‐Cause Mortality in Older, Low‐Level Care Residents

Objectives: To evaluate which indices of blood pressure (BP) homeostasis are the strongest predictors of mortality in older low‐level‐care residents in long‐term health facilities.

Aortic stiffness for the detection of preclinical left ventricular diastolic dysfunction: pulse wave velocity versus pulse pressure.

Objective An age-dependent relationship between aortic and left ventricular (LV) stiffening has been observed in community-based adults. Our aim was to compare the performances of wave reflection-dependent (pulse pressure) and independent [carotid-femoral pulse wave velocity (PWV)] indexes of aortic stiffness to detect preclinical LV diastolic dysfunction. Methods In this case–control study, a stratified subsample of participants of a population-based echocardiographic survey with LV ejection fraction higher than 45% and without overt heart failure was randomly selected to undergo assessment of brachial blood pressure, LV diastolic function by Doppler echocardiography, and estimation of central aortic pressures and PWV by applanation tonometry. Results Of the 233 subjects (mean age 73 ± 6 years, 54% men), 84 had normal diastolic function, 99 had mild diastolic dysfunction, and 50 had moderate or severe diastolic dysfunction. Brachial pulse pressure, central pulse pressure, and PWV progressively increased according to the severity of diastolic dysfunction, independent of age and sex. The overall performance of PWV was superior to brachial pulse pressure [area under receiver operating characteristic curve (AUC): 0.70 versus 0.59, respectively; P = 0.005] and central pulse pressure (AUC: 0.70 versus 0.56, respectively; P = 0.001) for the detection of any diastolic dysfunction. Conclusion PWV appeared to be superior to central and brachial pulse pressure for the detection of diastolic dysfunction in older adults with ‘preserved’ LV ejection fraction.

Bisphosphonate use and hip fracture epidemiology: ecologic proof from the contrary

Aim: The objective of this article is to evaluate the relationship between the changes in prescriptions of antiosteoporotic drugs (mainly the rapid fall in the use of bisphosphonates [BPs]) and standardized hip fracture (HF) rates over the period 2005–2008 in the Australian Capital Territory (ACT). Methods: Annual sex- and age-specific HF rates (per 100,000 population) were determined and standardized using the Australian 2006 population census. Data on the annual prescriptions of BPs (mainly alendronate and risedronate), strontium ranelate, and hormone replacement therapy were obtained from the Australian Pharmaceutical Benefits Scheme (PBS) and Repatriation Australian Pharmaceutical Benefits Scheme (RPBS) databases. Results: In the ACT, the peak annual number of prescriptions for BPs was observed in 2006. Following reports linking osteonecrosis of the jaw with BP use, the number of BP prescriptions dropped by 14% in 2007–2008 compared with 2005, when the lowest HF rates were recorded. The reduction in BP prescriptions coincided with increased HF rates in females in 2007 (+22.6%) and in 2008 (+25.2%) compared with 2005; in males, HF incidence declined by 6.6% and 16.7%, respectively. The proportion of filled prescriptions for strontium ranelate, risedronate, and alendronate in 2007–2008 was 1:8.4:15.5, indicating that BPs were the dominant antiosteoporotic drugs. There was an inverse statistically significant relationship between the total annual number of BP prescriptions and standardized HF incidence rates for the 10-year period 1999–2008. Conclusion: Although currently there is no clear understanding of factors contributing to changing HF epidemiology, the available evidence suggests that much of the decline in HF rates is due to the use of BPs. The fall in the use of BPs is associated with an increase in HF rates in females, indicating that BPs should still be considered the first-line medications for the prevention and treatment of osteoporosis. Our results need to be confirmed in other populations and countries.

Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

Background Considerable controversy exists regarding the contribution of mineral/bone metabolism abnormalities to the association between cardiovascular diseases (CVDs) and osteoporotic fractures. Aims and methods To determine the relationships between mineral/bone metabolism biomarkers and CVD in 746 older patients with hip fracture, clinical data were recorded and serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D, calcium, phosphate, magnesium, troponin I, parameters of bone turnover, and renal, liver, and thyroid functions were measured. Results CVDs were diagnosed in 472 (63.3%) patients. Vitamin D deficiency was similarly prevalent in patients with (78.0%) and without (82.1%) CVD. The CVD group had significantly higher mean PTH concentrations (7.6 vs 6.0 pmol/L, P < 0.001), a higher prevalence of secondary hyperparathyroidism (SPTH) (PTH > 6.8 pmol/L, 43.0% vs 23.3%, P < 0.001), and excess bone resorption (urinary deoxypyridinoline corrected by creatinine [DPD/Cr] > 7.5 nmol/μmol, 87.9% vs 74.8%, P < 0.001). In multivariate regression analysis, SHPT (odds ratio [OR] 2.6, P = 0.007) and high DPD/Cr (OR 2.8, P = 0.016) were independent indictors of CVD. Compared to those with both PTH and DPD/Cr in the normal range, multivariate-adjusted ORs for the presence of CVD were 17.3 (P = 0.004) in subjects with SHPT and 9.7 (P < 0.001) in patients with high DPD/Cr. CVD was an independent predicator of SHPT (OR 2.8, P = 0.007) and excess DPD/Cr (OR 2.5, P = 0.031). CVD was predictive of postoperative myocardial injury, while SHPT was also an independent predictor of prolonged hospital stay and in-hospital death. Conclusion SHPT and excess bone resorption are independent pathophysiological mediators underlying the bidirectional associations between CVD and hip fracture, and therefore are important diagnostic and therapeutic targets.

Poststroke Hip Fracture: Prevalence, Clinical Characteristics, Mineral-Bone Metabolism, Outcomes, and Gaps in Prevention

Objective. To assess the prevalence, clinical and laboratory characteristics, and short-term outcomes of poststroke hip fracture (HF). Methods. A cross-sectional study of 761 consecutive patients aged ≥60 years (82.3 ± 8.8 years; 75% females) with osteoporotic HF. Results. The prevalence of poststroke HF was 13.1% occurring on average 2.4 years after the stroke. The poststroke group compared to the rest of the cohort had a higher proportion of women, subjects with dementia, history of TIA, hypertension, coronary artery disease, secondary hyperparathyroidism, higher serum vitamin B12 levels (>350 pmol/L), walking aid users, and living in residential care facilities. The majority of poststroke HF patients had vitamin D insufficiency (68%) and excess bone resorption (90%). This group had a 3-fold higher incidence of postoperative myocardial injury and need for institutionalisation. In multivariate analysis, independent indicators of poststroke HF were female sex (OR 3.6), history of TIA (OR 5.2), dementia (OR 4.1), hypertension (OR 3.2), use of walking aid (OR 2.5), and higher vitamin B12 level (OR 2.3). Only 15% of poststroke patients received antiosteoporotic therapy prior to HF. Conclusions. Approximately one in seven HFs occurs in older stroke survivors and are associated with poorer outcomes. Early implementation of fracture prevention strategies is needed.

Clinical profiles and risk factors for outcomes in older patients with cervical and trochanteric hip fracture: similarities and differences

BackgroundData on clinical characteristics and outcomes in regard to hip fracture (HF) type are controversial. This study aimed to evaluate whether clinical and laboratory predictors of poorer outcomes differ by HF type.MethodsProspective evaluation of 761 consecutively admitted patients (mean age 82.3 ± 8.8 years; 74.9% women) with low-trauma non-pathological HF. Clinical characteristics and short-term outcomes were recorded. Haematological, renal, liver and thyroid status, C-reactive protein, cardiac troponin I, serum 25(OH) vitamin D, PTH, leptin, adiponectin and resistin were determined.ResultsThe cervical compared to the tronchanteric HF group was younger, have higher mean haemoglobin, albumin, adiponectin and resistin and lower PTH levels (all P < 0.05). In-hospital mortality, length of hospital stay (LOS), incidence of post-operative myocardial injury and need of institutionalisation were similar in both groups. Multivariate analysis revealed as independent predictors for in-hospital death in patient with cervical HF male sex, hyperparathyroidism and lower leptin levels, while in patients with trochanteric HF only hyperparathyroidism; for post-operative myocardial injury dementia, smoking and renal impairment in the former group and coronary artery disease (CAD), hyperparathyroidism and hypoleptinaemia in the latter; for LOS > 20 days CAD, and age > 75 years and hyperparathyroidism, respectively. Need of institutionalisation was predicted by age > 75 years and dementia in both groups and also by hypovitaminosis D in the cervical and by hyperparathyroidism in the trochanteric HF.ConclusionsClinical characteristics and incidence of poorer short-term outcomes in the two main HF types are rather similar but risk factors for certain outcomes are site-specific reflecting differences in underlying mechanisms.

Serum resistin in older patients with hip fracture: Relationship with comorbidity and biochemical determinants of bone metabolism.

OBJECTIVES To determine the relationship of serum resistin concentrations to biochemical determinants of bone metabolism, comorbidity and outcomes in patients with hip fracture (HF). METHODS In 256 consecutive patients (mean age 81.9±7.8 years; 71.1% women) serum levels of resistin (determined by ELISA), biochemical parameters of bone turnover and mineral metabolism as well as routine haematological and biochemical parameters were measured. Clinical data were recorded prospectively. RESULTS In multivariate analysis cervical HF (OR=1.81; 95% CI 1.05-3.11), diabetes (OR=2.60; 95% CI 1.23-5.51) and history of stroke (OR=2.67; 95% CI 1.17-6.13) were significant independent predictors of higher resistin levels (≥16.26 ng/ml, median value). The independent correlates of serum resistin levels in patients with cervical HF were serum osteocalcin and magnesium (both negatively associated) and in patients with trochanteric HF, serum PTH, calcium and age (all positively associated). Resistin and glomerular filtration rate were the only independent (inverse) predictors of serum osteocalcin. Resistin levels on admission did not predict short-term outcomes. CONCLUSIONS In older patients with HF there is a significant association of higher resistin levels with cervical fracture, type 2 diabetes and history of stroke, which is partly influenced by the reciprocal interaction between resistin and osteocalcin. However, the design of the study does not prove causality and further prospective studies are needed to clarify these relationships.

Interactions between Serum Adipokines and Osteocalcin in Older Patients with Hip Fracture.

Introduction. Experiments on genetically modified animals have discovered a complex cross-regulation between adipokines (leptin, adiponectin) and osteocalcin. The relationships between these molecules in human osteoporosis are still unclear. We evaluated the hypothesis of a bidirectional link between adipokines and osteocalcin. Materials and Methods. In a cross-sectional study of 294 older patients with osteoporotic hip fracture, we estimated serum concentrations of leptin, adiponectin, resistin, osteocalcin, parameters of mineral metabolism, and renal function. Results. After adjustment for multiple potential confounders, serum osteocalcin concentration was inversely associated with resistin and positively with leptin, leptin/resistin ratio, and adiponectin/resistin ratio. In multivariate regression models, osteocalcin was an independent predictor of serum leptin, resistin, leptin/resistin, and adiponectin/resistin ratios. Conclusions. Our data support the bidirectional regulation between osteocalcin and adipokines, but contrary to the genetically modified animal models, in older subjects with osteoporotic hip fracture, serum osteocalcin is positively associated with leptin and inversely with resistin.

Directional Migration of Recirculating Lymphocytes through Lymph Nodes via Random Walks

Naive T lymphocytes exhibit extensive antigen-independent recirculation between blood and lymph nodes, where they may encounter dendritic cells carrying cognate antigen. We examine how long different T cells may spend in an individual lymph node by examining data from long term cannulation of blood and efferent lymphatics of a single lymph node in the sheep. We determine empirically the distribution of transit times of migrating T cells by applying the Least Absolute Shrinkage & Selection Operator () or regularised to fit experimental data describing the proportion of labelled infused cells in blood and efferent lymphatics over time. The optimal inferred solution reveals a distribution with high variance and strong skew. The mode transit time is typically between 10 and 20 hours, but a significant number of cells spend more than 70 hours before exiting. We complement the empirical machine learning based approach by modelling lymphocyte passage through the lymph node . On the basis of previous two photon analysis of lymphocyte movement, we optimised distributions which describe the transit times (first passage times) of discrete one dimensional and continuous (Brownian) three dimensional random walks with drift. The optimal fit is obtained when drift is small, i.e. the ratio of probabilities of migrating forward and backward within the node is close to one. These distributions are qualitatively similar to the inferred empirical distribution, with high variance and strong skew. In contrast, an optimised normal distribution of transit times (symmetrical around mean) fitted the data poorly. The results demonstrate that the rapid recirculation of lymphocytes observed at a macro level is compatible with predominantly randomised movement within lymph nodes, and significant probabilities of long transit times. We discuss how this pattern of migration may contribute to facilitating interactions between low frequency T cells and antigen presenting cells carrying cognate antigen.