Liver Function Parameters in Hip Fracture Patients: Relations to Age,Adipokines, Comorbidities and Outcomes

Aim: To asses liver markers in older patients with hip fracture (HF) in relation to age, comorbidities, metabolic characteristics and short-term outcomes.Methods: In 294 patients with HF (mean age 82.0±7.9 years, 72.1% women) serum alanine aminotransferase (ALT), gammaglutamyltransferase (GGT), alkaline phosphatase (ALP), albumin, bilirubin, 25(OH)vitaminD, PTH, calcium, phosphate, magnesium, adiponectin, leptin, resistin, thyroid function and cardiac troponin I were measured.Results: Elevated ALT, GGT, ALP or bilirubin levels on admission were observed in 1.7% - 9.9% of patients. With age GGT, ALT and leptin decrease, while PTH and adiponectin concentrations increase. Higher GGT (>30U/L, median level) was associated with coronary artery disease (CAD), diabetes mellitus (DM), and alcohol overuse; lower ALT (≤20U/L, median level) with dementia; total bilirubin >20μmol/L with CAD and alcohol overuse; and albumin >33g/L with CAD. Multivariate adjusted regression analyses revealed ALT, ALP, adiponectin, alcohol overuse and DM as independent and significant determinants of GGT (as continuous or categorical variable); GGT for each other liver marker; and PTH for adiponectin. The risk of prolonged hospital stay (>20 days) was about two times higher in patients with GGT>30U/L or adiponectin >17.14 ng/L (median level) and 4.7 times higher if both conditions coexisted. The risk of in-hospital death was 3 times higher if albumin was <33g/L.Conclusions: In older HF patients liver markers even within the normal range are associated with age-related disorders and outcomes. Adiponectin (but not 25(OH)vitaminD, PTH, leptin or resistin) is an independent contributor to higher GGT. Serum GGT and albumin predict prolonged hospital stay and in-hospital death, respectively. A unifying hypothesis of the findings presented.     

The Neutrophil to Lymphocyte Ratio on Admission and Short-Term Outcomes in Orthogeriatric Patients

Aim: To investigate the association of the neutrophil to lymphocyte ratio (NLR) at admission with presence of fracture, comorbid conditions, and its prognostic value for short-term outcomes in orthogeriatric patients.Methods: On 415 consecutive patients (mean age 78.8 ±8.7[SD] years, 281 women, 255 with a non-vertebral bone fracture, including 167 with a hip fracture, HF) admitted to the Department of Orthopaedic Surgery at the Canberra hospital (2010 - 2011) data on clinical and laboratory characteristics were collected prospectively. The validation dataset included 294 consecutive patients (mean age 82.1 ± 8.0 years, 72.1% women) with HF.Results: Multivariate regression revealed four variables, presence of HF, hypoalbuminaemia (<33g/L), anaemia (<120g/L) and hyperparathyroidism (PTH>6.8 pmol/L), as independent determinants of admission NLR≥5.1. There was a dose-graded relationship between presence of fracture, especially HF, postoperative complications and levels of NLR categorized as tertiles. Compared to patients with NLR<5.1(first tertile), patients with NLR 5.1-8.5 (second tertile) had a 1.8-, 3.1-, 2.6-, and 2.5-fold higher risk for presence of any fracture, HF, developing postoperative myocardial injury (troponin I rise) and a high inflammatory response/infection (CRP>100mg/L after the 3rd postoperative day), respectively, while in subjects with NLR>8.5 (third tertile) these risks were 2.6-, 4.9-, 5.9- and 4.5-times higher, respectively; subjects with NLR>8.5 had a 9.7 times higher chance of dying in the hospital compared to patients with NLR 5.1-8.5; the NLR retained its significance on multivariate analyses. The NLR ≥5.1 predicted postoperative myocardial injury with an area under the curve (AUC) of 0.626, CRP>100mg/L with AUC of 0.631 and the NLR >8.5 predicted in-hospital mortality with an AUC of 0.793, showing moderately high sensitivity (86.7%, 80% and 90%, respectively) and negative predictive value (92.9%, 71.2%, 99.6%, respectively), but low specificity. Admission NLR was superior to other, except hypoalbuminaemia, prognostic markers; combined use of both NLR≥5.1 and albumin<33g/L only moderately increased the accuracy of prediction. The validation study confirmed the prognostic value of the admission NLR.Conclusions: In orthogeriatric patients, high NLR on admission is an independent indicator of fracture presence, a significant risk factor and moderate predictor of postoperative myocardial injury, high inflammatory response/infection and in-hospital death.     

Does heart rate predict mortality in older, low-level care residents?

To determine whether abnormalities in heart rate (HR) were associated with long-term mortality in older, low-level care residents, 179 randomly selected persons aged 65 and older (mean, 83.2+/-7.0 [SD] years; 80% women) were prospectively assessed. At baseline, duplicate measurements of HR and blood pressure were recorded in the supine position and after standing. During the 5-year follow-up period, 97 (54%) participants died. Cox survival analysis revealed no association with total mortality when resting HR was analyzed as a continuous or categoric variable (< or = 60, 61-89, and > 90 bpm). However, HR > or = 90 bpm was associated with increased risk of dying in residents who used a walking aid (relative risk, 3.48; 95% confidence interval, 1.07-11.30; p=0.038). Postural HR change was not associated with mortality risk. The authors concluded that resting HR and postural change in HR are not significant predictors of 5-year mortality in older, low-level care residents, except in persons using a walking aid.     

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. DESIGN: Prospective cohort study. SETTING: Eight long-term healthcare facilities in Canberra, Australia. PARTICIPANTS: A total of 179 randomly selected semi-independent residents aged 65 and older (mean age+/-standard deviation 83.2+/-7.0; 80% women). MEASUREMENTS: Baseline BP levels taken while lying, after standing for 1 and 3 minutes, and sitting before and 1 hour after meal intake were recorded, as well as demographic information, chronic medical conditions, medications, and all-cause mortality during follow-up. Postprandial hypotension (PPH) was defined as a fall in systolic BP (SBP) of 20 mmHg or more 1 hour postmeal while sitting. Orthostatic hypotension (OH) was defined as a fall in SBP of 20 mmHg or more or in diastolic BP (DBP) of 10 mmHg or more within 3 minutes of standing from a supine position. Hypertension was defined as BP greater than 160/90 mmHg at commencement of the study. Mean arterial pressure (MAP) and pulse pressure (PP) were calculated. RESULTS: At baseline, 47% of participants had hypertension, 38% PPH, and 23% OH; PP was 70 mmHg or greater in 54%, and DBP was 65 mmHg or lower in 6%. Over 4.7 years, 97 (54%) participants died. Those who died were significantly older and more likely to have PPH (47% vs 28%) and atrial fibrillation (35% vs 17%) and a significantly greater decrease in BP after meal intake. Mortality rates in those with and without PPH were 145.0 and 98.5 per 1,000 person-years, respectively. Using multivariate Cox proportional hazards models after adjustment for age, sex, presence of atrial fibrillation, Parkinson's disease, and use of diuretics, PPH was the only BP parameter that significantly and independently predicted 4.7-year all-cause mortality (relative risk (RR)=1.79; 95% confidence interval (CI)=1.19-2.68; P=.005). Further adjustment for the presence of OH, hypertension, low resting BP, coronary artery disease, cerebrovascular disease, congestive heart failure, history of syncope, cognitive impairment, cancer, diabetes mellitus, chronic obstructive pulmonary disease, and history of smoking did not reveal any new statistically significant associations. There was a dose-response relationship between postprandial fall in SBP and mortality rates. Absolute postprandial SBP of 120 mmHg or less was also significantly associated with total mortality (RR=1.69, 95% CI=1.04-2.78; P=.04). Low DBP was also associated with increased mortality (RR=1.10, 95% CI=1.01-1.13; P=.03), although this association became nonsignificant in multivariate analysis. CONCLUSION: In older low-level-care residents, PPH is an independent predictor of all-cause mortality with no added predictive value explained by other BP indices: OH, hypertension, PP, MAP.     

Six-fold increased risk of hip fracture in older Australians (≥60 years) with dementia

Introduction The objectives were: (1) to estimate the prevalence of dementia in older people with hip fracture (HF) and (2) to evaluate the significance of dementia and residential care as risk factors for HF in the Australian Capital Territory (ACT), Australia. Methods We performed a prospective study of 555 consecutive patients (≥60 years) with HF (mean age 82.6±7.9 (SD) years; 74.2% women) within 162,608 person-years of observation. The main predictor variables of HF were, pre-fracture diagnosed dementia of any type and residential status. ACT population estimates and age- and gender-specific prevalence rates of dementia in the ACT population were used to calculate the relative risk of HF in demented people. Results Of those with HF, 176 (31.7%) were diagnosed with dementia prior to the fracture. Multiple logistic regression analysis revealed that dementia in HF patients was associated with history of stroke (OR=2.2; 95% CI 1.2–4.0; p=0.008), residential care (OR=6.7; 95% CI 4.5–10.2; p=0.001) and older age (OR=1.03; 95% CI 1.0–1.1; p=0.036). The overall relative risk (RR) for HF in persons with dementia was 6.3 (95% CI 5.1–7.1) times higher than in those without pre-fracture dementia, and the RR in the young-old (60–79 years) with dementia was higher than in the old-old (≥85 years). The RR of HF for demented persons living in long-term residential care facilities compared to the non-demented age-matched community-dwelling population was 16.3 (95% CI 14.4–18.2; p=0.001). Conclusions This study demonstrated a high prevalence of demented people among HF patients and a 6.3-fold risk for HF in older persons with dementia. This risk is almost 2.6 times greater in demented people living in residential care. These data may be useful in health policy decisions and strongly support development of targeted HF prevention strategies, planning and allocation of resources and prioritisation of prevention efforts toward those with dementia, especially in residential care.     

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 ± 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 ≥ 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 ≥ 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 ≥ 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.     

Relationships between myocardial injury, all-cause mortality, vitamin D, PTH, and biochemical bone turnover markers in older patients with hip fractures

This study examined the relationships between myocardial injury as indicated by serum cardiac troponin I (cTnI) elevation, 25 hydroxyvitamin D [25(OH)D], and PTH status and biochemical markers of bone metabolism in older patients with hip fracture (HF). In 238 consecutive patients (mean age 81.9 +/- 7.8 yr; 72% women) with low trauma HF, serum concentrations of cTnI, 25(OH)D, PTH, calcium, phosphorus, magnesium, osteocalcin, bone-specific alkaline phosphatase (BAP), and urine excretion of free deoxypyridinoline (DPD) and N-terminal cross-linked teleopeptide of type I collagen (NTx) were measured and clinical data were collected prospectively. Myocardial injury (cTnI >0.06 microg/L) presented in 29%, 25(OH)D deficiency (<50 nmol/L) in 81.6%, elevated PTH (>6.5 pmol/L) in 53%, and excessive bone resorption (increased DPD and/or NTx excretion) in 93.7%. Multivariate logistic regression showed that elevated serum PTH level is a major predictor of peri-operative myocardial injury (OR = 2.13; 95% CI 1.01-4.51; p = 0.049) and in-hospital all-cause mortality (OR = 18.5; 95% CI 2.0-72.3; p = 0.010), independent of age, sex, 25(OH)D status, and comorbidities. The degree of hyperparathyroidism was associated with the risk of cTnI elevation and the mortality rate. In cTnI positive patients, PTH levels correlated with cTnI concentrations (r = 0.28; p = 0.026) and urine DPD exretion (r = 0.37; p = 0.004). These results suggest for the first time that in older patients with HF, elevated PTH level is associated with peri-operative myocardial injury and in-hospital all-cause mortality, and that elevated PTH level contributes to both disturbed bone metabolism and poor outcomes.     

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.     

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 μg/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 ≥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 ≥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 ≥1 μg/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 (≥20 days), need for long-term RCF and mortality (if cTnI ≥1 μg/l).     

Hip fracture type: Important role of parathyroid hormone (PTH) response to hypovitaminosis D

ObjectiveTo investigate whether clinical and laboratory characteristics, including serum 25-hydroxyvitamin D (25(OH) D), PTH and parameters of mineral and bone metabolism, differ by hip fracture (HF) type.Patients and methodsWe studied prospectively 761 consecutively admitted older patients (mean age 82.3 + 8.8(SD) years; 74.9% women) with low trauma non-pathological HF. A detailed clinical examination was performed, haematologic, renal, liver and thyroid function tests, serum 25(OH)D, PTH, calcium, phosphate, magnesium, C-reactive protein (CRP) and cardiac troponin I (cTnI) measured. In a subset of 294 patients' markers of bone formation (serum osteocalcin, OC; bone specific alkaline phosphatase, BAP) and bone resorption (urinary deoxypyridinoline, DPD/Cr; N-terminal cross-linked telopeptide of type 1 collagen, NTx/Cr; both corrected to urinary creatinine, Cr) were also measured.ResultsIn the trochanteric compared to the cervical group, females were older than males and the prevalence of Parkinson's disease, mean haemoglobin and albumin levels were lower. Incidence and degree of myocardial injury (cTnl rise) and inflammatory reaction (CRP elevation) as well as length of hospital stay, need of institutionalisation or in-hospital mortality were similar in both groups. Hypovitaminosis D (25(OH)D < 50 mmol/L) was present in 77.8% of patients with cervical and in 82.1% with trochanteric HF, elevated PTH (> 6.8 pmol/L) in 30.2% and 41.3%, respectively. The associations between 25(OH)D, PTH, and parameters of mineral metabolism and bone turnover were site-specific. In multivariate analyses, PTH (both as a continuous or categorical variable) response to hypovitaminosis D was a strong independent predictor of HF type. Coexistence of vitamin D deficiency (25(OH) D< 25 nmol/L) and elevated PTH predicts trochanteric HF while blunted PTH response predicts cervical HF (OR = 3.5; 95% CI 1.5–80; p = 0.005). PTH response and phosphate status (above or below median level) correctly discriminated HF type in 73.8% of patients with vitamin D deficiency.ConclusionsHF type is significantly associated with PTH response to hypovitaminosis D and impaired phosphate homeostasis. We detected only minor differences between two main HF types with regard to a wide range of clinical and routine laboratory variables as well as short-term outcomes.