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.

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.

Elevated serum PTH is independently associated with poor outcomes in older patients with hip fracture and vitamin D inadequacy.

To determine whether serum 25(OH)D and/or PTH levels in older patients with hip fracture (HF) could predict short-term clinical outcomes, we conducted a prospective observational study of 287 consecutive HF patients (mean age 81.9 + or - 7.5 [SD] years, 72% females). The prevalence of vitamin D inadequacy (25[OH]D < 80 nmol/l) was 97.1%, that of vitamin D deficiency (25[OH]D < 50 nmol/l) was 79.8%, and that of elevated PTH level (>6.8 pmol/l) was 35.5%. After adjustment for age and sex, PTH was significantly associated with in-hospital mortality (OR = 1.12, 95% CI 10.5-1.20, P < 0.001), myocardial injury (OR = 1.05, 95% CI 1.03-1.15, P = 0.002), prolonged length of stay (LOS > or = 20 days; OR = 1.05, 95% CI 1.01-1.06, P = 0.044), and being discharged to institutional care (OR = 1.07, 95% CI 1.01-1.18, P = 0.48). Secondary hyperparathyroidism (SHPT), but not vitamin D deficiency, was associated with older age, a higher prevalence of trochanteric fracture, coronary artery disease, hypertension, previous stroke, renal impairment, increased levels of serum osteocalcin, bone-specific alkaline phosphatase, and adiponectin as well as a significantly higher in-hospital mortality (11.8 vs. 0.54%, P = 0.001), perioperative myocardial injury (32.7 vs. 22.5%, P = 0.043), LOS > or = 20 days (40.2 vs. 26.9%, P = 0.017), and being discharged to institutional care (29.5 vs. 14.6%, P = 0.019). In multivariate regression analyses, SHPT was strongly associated with in-hospital mortality and LOS > or = 20 days. We conclude that elevated PTH (but not vitamin D deficiency per se) is a strong independent predictor of poor outcomes in older patients.

Elevated serum cardiac troponin I in older patients with hip fracture: incidence and prognostic significance.

INTRODUCTION: Cardiovascular complications are the main causes of morbidity and mortality in patients with osteoporotic hip fracture (HF). The aim of this prospective study was to evaluate the incidence and prognostic significance of elevated cardiac troponin I (cTnI) in the early peri-operative period in older patients with HF. MATERIALS AND METHODS: A blind evaluation of myocardial injury as detected by cTnI elevation in 238 consecutive older patients with low-trauma HF (mean age 81.9 +/- 7.8 (SD) years; 72% females). Data on demographic and clinical characteristics, in-hospital mortality, hospital length of stay and discharge destination were collected prospectively. Serum cTnI level was analysed from blood collected routinely in the first 72 h of hospital admission. RESULTS: Sixty-nine (29%) patients had elevated cTnI (>0.06 microg/l) but myocardial injury was clinically recognised in only 23 (33%) and only 24 (34.8%) had a history of coronary artery disease (CAD). Patients with elevated cTnI were significantly older, more often had American Society of Anaesthesiologist status score >or=3, a history of CAD or stroke and more often were current smokers than the patients without cTnI elevation. In multivariate regression analysis only age was an independent predictor of cTnI elevation. Patients with cTnI release were twice as likely to have a length of stay >or=20 days (P = 0.047) and 2.7 times more likely to be discharged to a long-term residential care facility (RCF) (P = 0.013). cTnI level >or=1 microg/l was a strong independent predictor of all-cause mortality with 98.3% specificity and 89.1% negative predictive value. CONCLUSION: Peri-operative myocardial injury is common in older HF patients but is frequently unrecognised clinically. Elevated blood cTnI level is an independent predictor of prolonged length of hospital stay (>or=20 days), need for long-term RCF and mortality (if cTnI >or=1 microg/l).

An application of linear output error modelling for studying lymphocyte migration in peripheral lymphoid tissues.

Lymphocyte recirculation between lymphatic and blood vessels and migration through tissues are essential mechanisms underlying immunological surveillance. However, the kinetics of lymphocyte migration through lymphoid tissues remains poorly understood. The present study of lymphocyte migration, based on a sheep model and entailing the long term cannulation of blood vessels and lymphatic vessels efferent from lymph nodes, represents the first attempt to apply control engineering based models to overcome some of the experimental impediments to understanding the complex phenomena involved in lymphocyte migration. An output error model order (1,2,nk) was systematically selected under given criteria from four classes of Linear Time-Invariant Single-Input Single-Output, (LTI-SISO) systems to represent the peripheral lymph node system. The unit impulse responses were simulated under noise free conditions and their features were extracted to describe the dynamics of the system. The findings from this study revealed novel information about several aspects of the dynamics of lymphocyte migration.

Modelling of peripheral lymphocyte migration: system identification approach.

This is the first application of the prediction error method (PEM) of system identification to modelling lymphocyte migration through peripheral lymphoid tissue. The PEM was applied to the emergence of labelled lymphocytes from the efferent lymphatic of a lymph node following their intravenous administration. Advantages of PEM included the capacity to calculate the response to a unit impulse stimulus, unavailable to direct observation, and to allow for the return to the node of labelled cells that had already recirculated once. Calculation of the system delay (time between introduction of cells into the blood and their first appearance in lymph) indicated 4.67 +/- 1.05 h for the total lymphocyte population. The peak in efferent lymph occurred at 11.91 +/- 4.68 h, much earlier than previous reports, which were affected by cells that had already recirculated. While 75% of labelled cells had emerged in efferent lymph by 20.77 +/- 5.62 h, 86.38 +/- 29.44 h was required for 100% emergence. The considerable heterogeneity in migratory behaviour is likely to reflect frequency and duration of binding of lymphocytes by dendritic cells in paracortical cord corridors. It is proposed that differences in the speed with which lymphocytes pass along corridors depend on their functional status, in particular whether they are naïve or memory cells.

Model of lymphocyte migration in Merino ewes under physiological conditions.

The paper presents an example of a new type of a structured model containing time delays in parallel branches. This model was selected as optimal to describe mathematically the lymphocyte migration between the venous blood and prescapular lymph in Merino ewes under physiological conditions. The model allowed to identify and quantify several lymphocyte fractions exhibiting different migration dynamics.