Association of frontal QRS-T angle--age risk score on admission electrocardiogram with mortality in patients admitted with an acute coronary syndrome

Risk assessment is central to the management of acute coronary syndromes. Often, however, assessment is not complete until the troponin concentration is available. Using 2 multicenter prospective observational studies (Evaluation of Methods and Management of Acute Coronary Events [EMMACE] 2, test cohort, 1,843 patients; and EMMACE-1, validation cohort, 550 patients) of unselected patients with acute coronary syndromes, a point-of-admission risk stratification tool using frontal QRS-T angle derived from automated measurements and age for the prediction of 30-day and 2-year mortality was evaluated. Two-year mortality was lowest in patients with frontal QRS-T angles <38° and highest in patients with frontal QRS-T angles >104° (44.7% vs 14.8%, p <0.001). Increasing frontal QRS-T angle-age risk (FAAR) scores were associated with increasing 30-day and 2-year mortality (for 2-year mortality, score 0 = 3.7%, score 4 = 57%; p <0.001). The FAAR score was a good discriminator of mortality (C statistics 0.74 [95% confidence interval 0.71 to 0.78] at 30 days and 0.77 [95% confidence interval 0.75 to 0.79] at 2 years), maintained its performance in the EMMACE-1 cohort at 30 days (C statistics 0.76 (95% confidence interval 0.71 to 0.8] at 30 days and 0.79 (95% confidence interval 0.75 to 0.83] at 2 years), in men and women, in ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction, and compared favorably with the Global Registry of Acute Coronary Events (GRACE) score. The integrated discrimination improvement (age to FAAR score at 30 days and at 2 years in EMMACE-1 and EMMACE-2) was p <0.001. In conclusion, the FAAR score is a point-of-admission risk tool that predicts 30-day and 2-year mortality from 2 variables across a spectrum of patients with acute coronary syndromes. It does not require the results of biomarker assays or rely on the subjective interpretation of electrocardiograms.     

Usefulness of standard electrocardiographic parameters for predicting cardiac events after acute myocardial infarction during modern treatment era

Comprehensive information about the independent value of different electrocardiographic (ECG) variables in predicting cardiac events after acute myocardial infarction (AMI) in the era of modern therapy is limited. Patients (n = 1,034) underwent standard electrocardiography from 5 to 7 days after an AMI. Several time intervals and PQRST abnormalities were analyzed from the electrocardiogram. During a mean +/- SD follow-up of 752 +/- 301 days on average, 42 patients (4%) experienced cardiac death, and 259 patients (25%) a cardiac death, nonfatal AMI, or unstable angina. Several ECG variables had a significant association with cardiac events in univariate comparisons. After adjustment for all risk variables in the Cox hazards model, lateral ST-segment depression (hazard ratio [HR] 4.76, 95% confidence interval [CI] 2.40 to 9.44, p <0.0001) and atrial abnormality with a terminal deflection of the P wave > or =0.1 mV deep and > or =40 ms in duration in lead V(1) (HR 2.46, 95% CI 1.25 to 4.82, p = 0.009) were the only ECG variables that independently predicted cardiac death. Lateral ST-segment depression also predicted the combined end point of cardiac death/nonfatal AMI/unstable angina in this model (HR 1.49, 95% CI 1.14 to 1.94, p = 0.003). In conclusion, lateral ST depression and atrial abnormality on the electrocardiogram are independent predictors of cardiac death after AMI. Lateral ST depression is also associated with ischemic cardiac events.     

Biomarkers of inflammation and progression of chronic kidney disease

BACKGROUND: Chronic kidney disease is associated with higher levels of inflammatory biomarkers. Statins have anti-inflammatory properties and may attenuate loss of kidney function. Although inflammation may mediate progressive renal injury, the relation between statin use, markers of inflammation, and the rate of kidney function loss has not been elucidated. We examined the association between pravastatin use, levels of C-reactive protein (CRP), soluble tumor necrosis factor receptor II (sTNFrii), and the rate of kidney function loss. METHODS: We performed a post hoc analysis of data from a randomized placebo controlled trial of pravastatin 40 mg daily in people with previous myocardial infarction. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease Study (MDRD) GFR equation. We studied 687 subjects with chronic kidney disease (GFR < 60 mL/min/1.73 m(2)) who did not experience a cardiovascular event during follow-up. Multivariate linear regression was used to study the relation between baseline CRP and sTNFrii and the rate of kidney function loss in mL/min/1.73 m(2)/year. Cross-product interaction terms were used to determine if these relations varied with pravastatin use. RESULTS: Median baseline GFR was 54.5 mL/min/1.73 m(2) (interquartile range 49.7, 57.8) and median duration of follow-up was 58 months. Higher baseline CRP level was independently associated with more rapid kidney function loss (highest tertile 0.6 mL/min/1.73 m(2) per year faster than lowest tertile) (P= 0.001). A similar independent relation was observed between tertile of sTNFrii and rate of kidney function loss (highest tertile 0.5 mL/min/1.73 m(2) per year faster than lowest tertile) (P= 0.006). Subjects with both CRP and sTNFrii in the highest tertile ("inflamed" status) appeared to derive more renal benefit from pravastatin than those without (P for interaction 0.047). In these 108 subjects, renal function loss in pravastatin recipients was 0.8 mL/min/1.73 m(2)/year slower than placebo (95% CI 0 to 1.5 mL/min/1.73 m(2)/year slower) (P= 0.039). CONCLUSION: Higher CRP and sTNFrii are independently associated with faster rates of kidney function loss in chronic kidney disease. Pravastatin appears to prevent loss of kidney function to a greater extent in individuals with greater evidence of inflammation, although this was of borderline significance. These data suggest that inflammation may mediate the loss of kidney function among subjects with chronic kidney disease and concomitant coronary disease.     

The implications of NICE guidelines on the management of children presenting with head injury

Background: NICE guidelines for the management of head injury were published in June 2003. Their recommendations differ markedly from previous guidelines published by the Royal College of Surgeons (RCS). In place of skull radiography and admission, computed tomography (CT) is advocated. The impact of these guidelines on service provision in the UK is unknown. Methods: Data on all clinical correlates of children presenting with any severity of head injury was collected in three hospitals in the northwest of England. The current skull radiograph (SXR), CT scan, and admission rates were determined. The rates of SXR, CT scan, and admission that should have occurred when following either the RCS or NICE guidelines were then determined. Results: Data from 10 965 patients who attended three hospitals between February 2000 and August 2002 was studied. Twenty five per cent of patients received a SXR, 0.9% a CT scan, and 3.7% were admitted. Strict adherence to the RCS guidelines would have resulted in a 50% SXR rate, a 1.6% CT scan rate, and a 7.1% admission rate. Adherence to NICE guidelines would result in a 0.3% SXR rate, an 8.7% CT scan rate, and a 1.4% admission rate, although the CT rate would drop to 6.3% if vomiting three or more times in the under 12s was used instead of more than one vomit. Conclusions: The new NICE guidelines do not increase the workload caused by patients attending with head injury but they move their management from the observation ward to the radiology department.     

The HORIZON Recurrent Fracture Trial: design of a clinical trial in the prevention of subsequent fractures after low trauma hip fracture repair

OBJECTIVE: To present the novel design of a trial testing the safety and efficacy of a yearly bisphosponate, zoledronic acid, in preventing new clinical fractures in patients with recent low trauma hip fracture repair. Research design and methods: Randomized, placebo-controlled, triple-blind study. One hundred and fifteen clinical centers worldwide are recruiting approximately 1714 subjects aged 50 years and over (no upper age limit, median age of enrolled subjects to date 79 years) who have undergone surgical repair of a low trauma hip fracture in the preceding 90 days. Patients will be assigned at random to an intervention group (5 mg zoledronic acid intravenously yearly) or a control group (placebo infusion yearly). Both groups receive a loading dose of Vitamin D2 or D3 IM or orally, followed by 800-1200 IU Vitamin D and 1000-1500 mg elemental calcium orally on a daily basis. Concomitant therapy with calcitonin, hormone replacement therapy, selective estrogen receptor modulators, tibolone, and external hip protectors are allowed. MAIN OUTCOME MEASURES: The primary endpoint is subsequent skeletal fractures as adjudicated by a clinical endpoints committee blinded to intervention status. Secondary outcomes include delayed hip fracture healing, changes in bone mineral density, and health resource utilization. Subjects will be recruited over a 3-4 year period and will be followed until 211 primary endpoints are accrued and adjudicated. CONCLUSIONS: This randomized clinical trial is novel among osteoporosis therapies as it (1). targets hip fracture patients, a previously understudied group, and (2). uses only clinically evident fractures as the primary outcome. Ethical and practical considerations in studying this frail population are discussed.