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Articles by H. D White
Total Records ( 7 ) for H. D White
  H. D White , A. A Joshi , A. M Ahmad , B. H Durham , J. P Vora and W. D. Fraser

Difficulties associated with measuring ionized calcium in clinical practice have led to the use of total calcium, with or without adjustment for albumin concentration, as an estimate of calcium metabolism. We examined the correlation between ionized and total/adjusted calcium over a 24-h period in patients with adult growth hormone deficiency (AGHD), a group of patients with previously reported alterations in calcium metabolism.


Four patients with AGHD were consented to the study. They were hospitalized for 24 h where half-hourly blood samples were collected for ionized calcium, total calcium, albumin and creatinine, before and one month after the commencement of growth hormone replacement. Total calcium concentration was adjusted for serum albumin.


Strong correlations were found between ionized calcium and adjusted calcium (r2 = 0.840 and 0.766 for visits 1 and 2, respectively, P < 0.001), and between ionized calcium and total calcium (r2 = 0.828 and 0.731 for visits 1 and 2, respectively, P < 0.001). Correlations remained significant during the day (ionized versus adjusted calcium: r2 = 0.847 and 0.780 for visits 1 and 2, respectively; ionized versus total calcium: r2 = 0.860 and 0.792 for visits 1 and 2, respectively, all P < 0.001) and at night (ionized versus adjusted calcium: r2 = 0.831 and 0.802 for visits 1 and 2, respectively; ionized versus total calcium: r2 = 0.767 and 0.722 for visits 1 and 2, respectively, all P < 0.001).


The results of our study suggest that total calcium and serum-adjusted calcium can be used in place of ionized calcium as a reliable indicator of calcium metabolism over a 24-h period in patients with AGHD.

  S. J Pocock , R Mehran , T. C Clayton , E Nikolsky , H Parise , M Fahy , A. J Lansky , M. E Bertrand , A. M Lincoff , J. W Moses , E. M Ohman , H. D White and G. W. Stone

Background— Both ischemic and hemorrhagic complications increase mortality rate in acute coronary syndromes. Their frequency and relative importance vary according to individual patient risk profiles. We sought to develop prognostic models for the risk of myocardial infarction (MI) and major bleeding to assess their impact on risk of death and to examine the manner in which alternative antithrombotic regimens affect these risks in individual patients.

Methods and Results— The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial randomized 13 819 patients with acute coronary syndrome to heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. By logistic regression, there were 5 independent predictors of MI within 30 days (n=705; 5.1%) and 8 independent predictors of major bleeding (n=645; 4.7%), only 2 of which were common to both event types. In a covariate-adjusted, time-updated Cox regression model, both MI and major bleeding significantly affected subsequent mortality rate (hazard ratios, 2.7 and 2.9, respectively; both P<0.001). Treatment with bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor was associated with a nonsignificant 8% increase in MI and a highly significant 50% decrease in major bleeding. Given the individual patient risk profiles and the fact that bivalirudin prevented 6 major bleeds for each MI that might occur from its use, the estimated reduction in bleeding was greater than the estimated increase in MI by bivalirudin alone rather than heparin plus a glycoprotein IIb/IIIa inhibitor for nearly all patients.

Conclusions— Consideration of the individual patient risk profile for MI and major bleeding and the relative treatment effects of alternative pharmacotherapies permits personalized decision making to optimize therapy of patients with acute coronary syndrome.

Clinical Trial Registration— Identifier: NCT00093158.

  A. J Lansky , K Goto , E Cristea , M Fahy , H Parise , F Feit , E. M Ohman , H. D White , K. P Alexander , M. E Bertrand , W Desmet , M Hamon , R Mehran , J Moses , M Leon and G. W. Stone

Contemporary adjunctive pharmacology and revascularization strategies have improved the prognosis of patients with acute coronary syndromes (ACSs). We sought to identify the clinical and angiographic predictors of cardiac ischemic events in patients with ACSs treated with an early invasive strategy.

Methods and Results—

Multivariable logistic regression was used to analyze the relation between baseline characteristics and 30-day and 1-year composite ischemia (death, myocardial infarction, or unplanned revascularization) among the 6921 ACS patients included in the prespecified angiographic substudy of the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial. Of the 6921 patients, 3826 (55.3%) were treated with percutaneous coronary intervention, 755 (10.9%) with coronary artery bypass grafting, and 2340 (33.8%) with medical therapy. Composite ischemia occurred in 595 (8.6%) patients at 30 days and in 1153 (17.4%) at 1 year. Renal insufficiency, biomarker elevation, ST-segment deviation, nonuse of aspirin or thienopyridine, insulin-treated diabetes, older age, baseline lower hemoglobin value, history of percutaneous coronary intervention, and current smoking were independently associated with 30-day or 1-year ischemic events. Angiographic characteristics predicting ischemic events included number of diseased vessels, moderate/severe calcification, worst percent diameter stenosis, jeopardy score, lower left ventricular ejection fraction, lesion eccentricity, and thrombus. With use of receiver operating characteristic methodology, the c statistic improved for the predictive model by adding angiographic to clinical parameters for the 30-day composite ischemia (from 0.62 to 0.68) and myocardial infarction (from 0.64 to 0.71) and 1-year composite ischemia (from 0.61 to 0.65) and myocardial infarction (from 0.63 to 0.69) end points.


Among ACS patients managed with an early invasive strategy, baseline angiographic markers of disease burden, calcification, lesion severity, lower left ventricular ejection fraction, and morphological characteristics provided important added independent predictive value for 30-day and 1-year ischemic outcomes, beyond the well-recognized clinical risk factors. These findings emphasize the prognostic importance of the diagnostic angiogram in the risk stratification of patients presenting with ACSs.

Clinical Trial Registration—

URL: Unique identifier: NCT00093158.

  A Stebbins , R. H Mehta , P. W Armstrong , K. L Lee , C Hamm , F Van de Werf , S James , T Toftegaard Nielsen , R Seabra Gomes , H. D White , C. B Granger and for the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI Investigators)

Accurate models to predict mortality are needed for risk stratification in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Methods and Results—

We examined 5745 patients with STEMI undergoing primary PCI in the Assessment of Pexelizumab in Acute Myocardial Infarction Trial within 6 hours of symptom onset. A Cox proportional hazards model incorporating regression splines to accommodate nonlinearity in the log hazard ratio (HR) scale was used to determine baseline independent predictors of 90-day mortality. At 90 days, 271 (4.7%) of 5745 patients died. Independent correlates of 90-day mortality were (in descending order of statistical significance) age (HR, 2.03/10-y increments; 95% CI, 1.80 to 2.29), systolic blood pressure (HR, 0.86/10-mm Hg increments; 95% CI, 0.82 to 0.90), Killip class (class 3 or 4 versus 1 or 2) (HR, 4.24; 95% CI, 2.97 to 6.08), heart rate (>70 beats per minute) (HR, 1.45/10-beat increments; 95% CI, 1.31 to 1.59), creatinine (HR, 1.23/10-µmol/L increments >90 µmol/L; 95% CI, 1.13 to 1.34), sum of ST-segment deviations (HR, 1.25/10-mm increments; 95% CI, 1.11 to 1.40), and anterior STEMI location (HR, 1.47; 95% CI, 1.12 to 1.93) (c-index, 0.82). Internal validation with bootstrapping confirmed minimal overoptimism (c-index, 0.81).


Our study provides a practical method to assess intermediate-term prognosis of patients with STEMI undergoing primary PCI, using baseline clinical and ECG variables. This model identifies key factors affecting prognosis and enables quantitative risk stratification that may be helpful in guiding clinical care and for risk adjustment for observational analyses.

  C Berry , K. S Pieper , H. D White , S. D Solomon , F Van de Werf , E. J Velazquez , A. P Maggioni , R. M Califf , M. A Pfeffer and J. J.V. McMurray

The number of patients presenting with an acute myocardial infarction (MI) and prior coronary artery bypass grafting (CABG) is increasing. We compared the baseline characteristics, treatment, and clinical outcomes of patients with and without prior CABG in the VALIANT trial.

Methods and results

Of the 14 703 patients with heart failure (HF), left ventricular systolic dysfunction, or both enrolled in VALIANT, 1026 (7%) had prior CABG. Prior CABG patients were older [mean age (SD): 67 (10) vs. 65 (12) years; P < 0.0001], had more comorbidity, and more frequent non-Q wave MI (66 vs. 30%; P < 0.0001). At hospital presentation, prior CABG patients received less aspirin (82 vs. 90%; P < 0.0001) and thrombolysis (21 vs. 36%; P < 0.0001), but had a similar rate of primary percutaneous coronary intervention (14 vs. 15%; P = 0.2). Prior CABG patients were more likely to experience the composite outcome of cardiovascular death, MI, HF, resuscitated cardiac arrest, or stroke; 3 year Kaplan–Meier rate, 64 vs. 39% (adjusted hazard ratio 1.29, 95% confidence interval 1.17–1.43; P < 0.0001).


Patients with prior CABG had a worse clinical profile and experienced more fatal and non-fatal outcomes. Greater recognition is necessary for these high-risk patients including optimization of evidence-based secondary preventive therapy.

  R Mehran , S. J Pocock , G. W Stone , T. C Clayton , G. D Dangas , F Feit , S. V Manoukian , E Nikolsky , A. J Lansky , A Kirtane , H. D White , A Colombo , J. H Ware , J. W Moses and E. M. Ohman

To evaluate the associations of myocardial infarction (MI) and major bleeding with 1-year mortality. Both MI and major bleeding predict 1-year mortality in patients presenting with acute coronary syndrome (ACS). However, the risk of each of these events on the magnitude and timing of mortality has not been well studied.

Methods and Results

A multivariable Cox regression model was developed relating 13 independent baseline predictors to 1-year mortality for 13 819 patients with moderate and high-risk ACS enrolled in the Acute Catheterization and Urgent Intervention Triage strategy trial. After adjustment for baseline predictors, Cox models with major bleeding and recurrent MI as time-updated covariates estimated the effect of these events on mortality hazard over time. Within 30 days of randomization, 705 patients (5.1%) had an MI, 645 (4.7%) had a major bleed; 524 (3.8%) died within a year. The occurrence of an MI was associated with a hazard ratio of 3.1 compared with patients not yet having an MI, after adjustment for baseline predictors. However, MI within 30 days markedly increased the mortality risk for the first 2 days after the event (adjusted hazard ratio of 17.6), but this risk declined rapidly post-infarct (hazard ratio of 1.4 beyond 1 month after the MI event). In contrast, major bleeding had a prolonged association with mortality risk (hazard ratio of 3.5) which remained fairly steady over time throughout 1 year.


After accounting for baseline predictors of mortality, major bleeds and MI have similar overall strength of association with mortality in the first year after ACS. MI is correlated with a dramatic increase in short-term risk, whereas major bleeding correlates with a more prolonged mortality risk.

  H. D White , J Blair , J Pinkney , D. J Cuthbertson , R Day , A Weber and I. A. MacFarlane

Background: Multiple endocrine neoplasia type 1 (MEN1) is associated with significant morbidity and mortality. Timely detection of MEN1 kindred, together with treatment of associated tumours, results in an improved outcome. We describe how the development of a dedicated multidisciplinary MEN clinic has improved the diagnosis and treatment of MEN1-associated endocrinopathies.

Design and patients: A dedicated MEN clinic was developed at Aintree University Hospital, Liverpool in 2002 for patients living in Merseyside, Cheshire and North Wales. The multidisciplinary approach adopted, aimed to improve communication and continuity of care. Patients see all clinicians involved in their care (Consultant Endocrinologist, Paediatrician, Clinical Geneticist and Endocrine Surgeon) simultaneously, allowing for a unified, clear approach and a reduction in unnecessary attendances. The clinicians adopt a proactive approach to tracing the relatives of patients, with the aim of identifying kindred with previously asymptomatic disease.

Results: In 2002, 16 patients from 5 families were diagnosed clinically with MEN1. Twenty MEN1-associated endocrinopathies had been diagnosed and 21 surgical procedures had been performed. By the end of 2008, 45 patients from 15 families had been identified, with 83 endocrinopathies diagnosed and 50 surgical procedures performed. Ninety-four known relatives are awaiting screening for MEN1.

Conclusion: The successful identification of patients with MEN1 has resulted in an exponential increase in the number of patients attending the clinic. As relatives undergo screening, the diagnosis of MEN is likely to increase. The ever increasing numbers of patients requiring screening, surveillance and treatment has implications in the planning of future service provision.

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