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Biomedical subjects

Norman Sharpe

Publications and source records attributed to Norman Sharpe.

At least 19 recordsLinked to original sources
PubMed2006

How low can it go? Projecting ischaemic heart disease mortality in New Zealand to 2015.

AIMS: This study aims to identify how ischaemic heart disease (IHD) mortality rates in New Zealand have varied between successive cohorts and time periods. This information is then used to project IHD mortality rates and counts (burdens) out to year 2011-15. METHODS: Age/period/cohort models were constructed (5-year periods and 5-year age groups, generating 10-year overlapping cohorts) using both frequentist and Bayesian methods. Data were available from 1956 for the total population and from 1981 for Maori. The projection period was 2001-5 to 2011-15. Uncertainty was quantified as the Bayesian 90% credible interval. RESULTS: IHD mortality rates for all age by gender groups increased from 1956-60 to peak in 1966-70, then declined by more than 60% to current (1996-2000) levels. However, the decline has been much shallower for Maori. This decline has resulted from increasingly favourable period effects since 1971-75 (less marked for Maori). However, no substantive cohort effects have been seen, at least from the 1891 to the 1951 cohort. Our model suggests that, for the first time, a substantive and unfavourable cohort effect may be emerging among recent birth cohorts. CONCLUSIONS: IHD mortality rates are projected to continue to fall from 2001-05 to 2011-15, albeit more slowly than in the past as the increasing (favourable) period effect is partly offset by an emerging (unfavourable) cohort effect. The result is a relatively small projected decline in absolute IHD mortality burden overall, but an actual increase among Maori.

Adult↗
PubMed2005

Comparison of B-type natriuretic peptides for assessment of cardiac function and prognosis in stable ischemic heart disease.

UNLABELLED: In 1,049 patients with stable ischemic heart disease (IHD), brain natriuretic peptide (BNP) and amino terminal pro-brain natriuretic peptide (NTproBNP) correlated closely (r = 0.09, p < 0.001) and were similarly related to left ventricular ejection fraction (LVEF) (r = -0.50 and -0.46, respectively), age (0.44 and 0.47), and creatinine clearance (-0.51 and -0.51). Receiver-operating characteristic curves for detection of LVEF <30% were similar (area under the curves = 0.83 and 0.80, both p < 0.001), and both peptides had strong negative predictive value (95% and 94%). Both independently predicted all-cause mortality and/or heart failure with closely overlapping event-free survival curves; BNP and NTproBNP display strong, near-identical test performance in ruling about severely reduced LVEF and in prediction of all-cause mortality or heart failure in stable IHD. OBJECTIVES: The aim of this work was to test B-type natriuretic peptides for assessment of function and prognosis in stable ischemic heart disease (IHD) and to compare brain natriuretic peptide (BNP) with amino terminal pro-brain natriuretic peptide (NTproBNP), including the relative effects of age and renal function on test performance. BACKGROUND: Brain natriuretic peptide and NTproBNP are emerging diagnostic and prognostic markers in heart failure and acute coronary syndromes. Their performance in assessing function and prognosis in stable IHD is unknown. Whether one marker is superior and the relative effects of age and renal function on test performance are uncertain. METHODS: In 1,049 patients with stable IHD, left ventricular ejection fraction (LVEF) was measured by radionuclide scanning and creatinine clearance estimated by the Cockroft-Gault equation. Age, gender, and body mass index were recorded. Twelve-month all-cause mortality or admission with heart failure was prospectively recorded; BNP and NTproBNP were measured by radioimmunoassay. RESULTS: Brain natriuretic peptide and NTproBNP correlated closely (r = 0.90, p < 0.001) and had similar relationships to LVEF (r = -0.50 and -0.46, respectively, both p < 0.001), age (0.44 and 0.47, both p < 0.001), and creatinine clearance (-0.51 and -0.51, both p < 0.001). Areas under receiver-operating characteristic curves for detection of LVEF <30% were similar (0.83 and 0.80, both p < 0.001) with strong negative predictive values for both (95% and 94%). Both markers independently predicted the clinical end point with closely overlapping event-free survival curves. CONCLUSIONS: In stable IHD, BNP and NTproBNP display strong and near-identical test performance in ruling out severely reduced LVEF and in prediction of all-cause mortality or heart failure despite significant effects of age, gender, and renal function on levels of both markers.

Aged↗
PubMed2005

The HOPE TIPS: the HOPE study translated into practices.

The HOPE TIPS study assessed the practicality and tolerability of ramipril titration to a target dose of 10 mg (as achieved in definitive efficacy studies) in a clinical practice setting. 3881 patients at high cardiovascular risk (HOPE study criteria) were recruited in primary and specialist care settings in 9 countries by 439 investigators. Dose titration of ramipril from 2.5 mg to 10 mg daily took place over 9-12 weeks. The mean age of the patients was 64 years, 60% were male and 79% Asian. The target dosage of 10 mg daily was reached in 73% of patients with 96% of patients achieving 5 mg or 10 mg daily. During the study period uncontrolled hypertension (> 160/90) was recorded in 15% of patients, myocardial infarction or unstable angina 1.6%, heart failure 0.4%, new diabetes 0.6%. Only 9.8% of patients discontinued treatment with 5.9% attributed to treatment side-effects and 4% related to cough. The large majority of patients in a wide range of clinical practice settings with high cardiovascular risk can be treated with ramipril titrated to 10 mg daily with good tolerability.

Aged↗
PubMed2005

Quantitative evaluation of regional endocardial visualisation with second harmonic imaging and contrast left ventricular opacification in heart failure patients.

AIMS: Wall motion score index (WMSI) is an important prognostic indicator in heart failure (HF) patients but requires endocardial visualisation. This study evaluated the role tissue harmonic imaging (THI) and contrast opacification (LVO) for improving endocardial visualisation and the determination of WMSI in HF patients. METHODS AND RESULTS: Thirty-one HF patients and 30 controls underwent apical echocardiography with fundamental imaging (FUND), THI and THI with contrast agent (Levovist). Visualisation and motion were graded in the six segments from each of the apical two and four chamber views. Both THI and LVO reduced the percentage of non-visualised segments (FUND 13.6%, THI 5.6%, LVO 2.8%, p=0.01) in the controls, but in HF patients, only THI improved visualisation (% segments not visualised FUND 9.7%, THI 3.5%, LVO 4.8%, p=0.06). The anterior and lateral walls were the least well visualised with FUND, but improved with LVO (anterior p=0.0026, lateral p=0.0003). No improvement was seen in the inferior wall (p=0.30) or septum (p=0.2). WMSI was similar by all methods and negatively correlated with ejection fraction (FUND r=-0.69, THI r=-0.74, LVO r=-0.77, all p<0.001). CONCLUSION: THI improved endocardial visualisation in all subjects and LVO offered additional benefit in the controls, but not in HF patients. Regional endocardial visualisation was inconsistent. Thus, both patient factors and wall segment site need to be considered when using contrast agents for endocardial visualisation.

Case-Control Studies↗
PubMed2004

Cardiac remodeling in coronary artery disease.

Cardiac remodeling is a central mechanism of heart failure progression in patients with coronary artery disease (CAD). The remodeling effect of beta-blockade with carvedilol has been studied in patients with left ventricular dysfunction after myocardial infarction and in patients with chronic heart failure of ischemic etiology. Carvedilol has been found to prevent progressive adverse ventricular remodeling in both conditions. This effect is concordant with the improvement in long-term clinical outcomes established for carvedilol in such patients. Thus, ventricular remodeling appears to be an important treatment target in patients with CAD and is likely to mediate at least part of the clinical improvement achieved with carvedilol.

Adrenergic beta-Antagonists↗
PubMed2004

Effects of carvedilol on left ventricular remodeling after acute myocardial infarction: the CAPRICORN Echo Substudy.

BACKGROUND: The CAPRICORN trial has shown that carvedilol improved outcome in patients with left ventricular dysfunction after acute myocardial infarction treated with ACE inhibitors. The aim of this substudy was to determine the effects of carvedilol on left ventricular remodeling in this patient group. METHODS AND RESULTS: Patients entering the CAPRICORN trial from 13 centers in New Zealand, Australia, and Spain were recruited for this echocardiographic substudy. In 127 patients, quantitative 2D echocardiography was performed according to a standard protocol before randomization and repeated after 1, 3, and 6 months of treatment with carvedilol or placebo. Left ventricular volumes, ejection fraction (Simpson's method), and wall motion score index were determined in a blinded analysis at the Core Echo Laboratory. At 6 months, left ventricular end systolic volume was 9.2 mL less in the carvedilol group than in the placebo group (P=0.023), and left ventricular ejection fraction was 3.9% higher (P=0.015). Left ventricular end diastolic volume and wall motion score index were not statistically different between the 2 groups at 6 months. CONCLUSIONS: In patients with left ventricular dysfunction after acute myocardial infarction treated with ACE inhibitors, carvedilol had a beneficial effect on ventricular remodeling, which may, in part, mediate the substantial clinical beneficial effects of carvedilol in this patient population.

Adrenergic beta-Antagonists↗
PubMed2004

Effect of tissue harmonic imaging and contrast upon between observer and test-retest reproducibility of left ventricular ejection fraction measurement in patients with heart failure.

AIMS: To investigate the effects of tissue harmonic imaging (THI) and contrast chamber opacification (LVO) upon measurement variability and reproducibility of echocardiographic left ventricular (LV) volume and ejection fraction (EF) measurements in patients with heart failure (HF). BACKGROUND: Echocardiography is often used in HF patients to determine LV volumes and EF. However, current echo methods are variable and may not be applicable for repeat testing in individual patients. THI and LVO have both been shown to improve endocardial visualisation, but it remains to be determined whether this results in better measurement reproducibility. METHODS: Thirty-one HF patients and 30 control subjects underwent echocardiography on two separate days. LV volumes were measured under four different imaging conditions: fundamental, THI, LVO and LVO with ECG-triggered Power Doppler. Chamber opacification, pulmonary transit time (PTT), endocardial enhancement, reproducibility and bias were assessed. RESULTS: Chamber opacification was inferior and the PTT longer in the HF patients. PTT was related to LV volumes, EF, jugular venous pressure and mitral filling pattern. THI improved endocardial visualisation, and although LVO improved endocardial visualisation in the controls, it offered no benefit over THI in the HF patients. LV volumes and EF were different for each method and THI was the least variable method for repeat measurements. CONCLUSIONS: THI improved endocardial visualisation and was the least variable of the techniques. LVO offered no further advantage in patients with HF and thus cannot be routinely advocated and since LV volumes and EF were different for each, these methods are neither comparable nor interchangeable for follow-up assessments.

Contrast Media↗
PubMed2003

Amino-terminal pro-C-type natriuretic peptide in heart failure.

The levels and pathophysiological role of amino terminal C-type natriuretic peptide in heart failure are unknown. The potential of plasma amino-terminal C-type natriuretic peptide (N-CNP) as a marker of cardiac function was investigated in symptomatic patients. In 305 patients with recent-onset dyspnea and/or peripheral edema, presenting to primary care, assay of plasma amino-terminal C-type natriuretic peptide and other plasma vasoactive hormones was conducted together with echocardiography. Heart failure was diagnosed in 77 (of the 305) patients by rigorous application of predefined criteria. Plasma amino-terminal C-type natriuretic peptide concentrations were elevated in patients with heart failure, and by univariate analysis were related to age, renal function, and other hormones. On multivariate analysis, tertile of plasma N-CNP interacted with tertile of plasma amino-terminal B-type natriuretic peptide to predict heart failure independent of age, gender, renal function, or echocardiographic left ventricular fractional shortening. N-CNP showed significant relations to concurrent plasma CNP, atrial natriuretic peptide (ANP), N-ANP, B-type (or brain) natriuretic peptide (BNP), N-BNP, endothelin-1, and adrenomedullin but not to echocardiographic indicators of left ventricular systolic function. Plasma amino-terminal C-type natriuretic peptide is elevated in heart failure and is related to other plasma hormones in heart failure. These findings suggest a possible compensatory response from the peripheral vasculature to heart failure by an endothelium-based vasodilator peptide and mandate further exploration of the role of C-type natriuretic peptide in this condition.

Adult↗
PubMed2003

Randomised trials in general practice--a New Zealand experience in recruitment.

AIM: To examine general practitioner (GP) and patient recruitment in a randomised clinical trial to determine the usefulness of brain natriuretic peptide (BNP) in the diagnosis of heart failure in the community. METHODS: Different techniques were used to maximise GP recruitment including early consultation with GPs, benefits for participating GPs and patients, and a comprehensive suburb-by-suburb approach to GPs using letters and personal visits. GPs then referred patients. At the conclusion of the study, GPs were given a questionnaire focussing on barriers to referral and reasons for participation. RESULTS: Three hundred and twenty seven GPs from 135 practices were sent an introductory letter; 294 were eligible to participate. Of these, 186 GPs (63% of eligible GPs) agreed to participate. Ninety two GPs (31% of eligible GPs) from 62 practices referred 307 patients to the study (range 1-14 patients). There were no significant differences between referring and non-referring GPs with respect to sociodemographic characteristics. Referring GPs were very supportive of GP participation in research and strongly agreed that GPs should be reimbursed for involvement in trials. CONCLUSIONS: Patient recruitment by GPs may be aided by the use of a range of strategies including financial reimbursement. GPs who agree to participate will not always recruit patients. Closer collaboration and understanding between primary healthcare professionals and researchers may further enhance recruitment to clinical trials.

Attitude of Health Personnel↗
PubMed2003

Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure diagnosis in primary care: a randomized, controlled trial.

OBJECTIVES: The purpose of this study was to determine the effect of amino-terminal pro-brain natriuretic peptide (N-BNP) on the diagnostic accuracy of heart failure (HF) in primary care. BACKGROUND: The accurate diagnosis of patients with suspected HF presenting in primary care is difficult. Amino-terminal pro-brain natriuretic peptide is present in high levels in cardiac dysfunction and may improve the diagnostic accuracy of HF in primary care. METHODS: The Natriuretic Peptides in the Community Study was a prospective, randomized controlled trial of the effect of N-BNP on the accuracy of HF diagnosis. Patients presenting to their general practitioner (GP) with symptoms of dyspnea and/or peripheral edema were included. The GPs formulated an initial diagnosis based on clinical assessment. All patients underwent a full cardiologic assessment that included echocardiography and N-BNP. Each patient was randomized to the BNP group (GP received the N-BNP result) or the control group (GP did not receive the N-BNP result). Patients were then reviewed by their GP, and their diagnosis was reviewed. The primary end point was the accuracy of the GPs' diagnoses compared with the panel standard. RESULTS: A total of 305 patients were included; mean age was 72 years, 65% were female. Seventy-seven patients met the panel criteria for HF. The diagnostic accuracy improved 21% in the BNP group and 8% in the control group (p = 0.002). The main impact of N-BNP measurement on diagnostic accuracy was the GPs' correctly ruling out HF. The number needed to diagnose by N-BNP measurement was seven patients. CONCLUSION: This study demonstrates that N-BNP measurement significantly improves the diagnostic accuracy of HF by GPs over and above customary clinical review.

Adult↗
PubMed2003

Cardiovascular aging and heart failure.

The aging process is a major factor that contributes to changes seen in the cardiovascular system in older people. Stiffening of the arterial tree alters afterload and left ventricular geometry and although resting left ventricular systolic function is maintained, left ventricular diastolic function changes substantially. Cardiovascular function in older people during exercise is also significantly altered but can be modified by exercise training in older adults or genetic modification in animals. Age-related changes in cardiovascular structure and function also lower the threshold at which cardiac diseases become apparent. This review describes the changes in cardiovascular structure and function at rest and during exercise in older people and highlights their consequences.

Aging↗
PubMed2003

Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON).

BACKGROUND: The association between sympathetic activation and mortality in chronic heart failure and the favorable effect of beta blocking drugs has raised the possibility of therapeutic efficacy for central sympathetic inhibition with sustained-release (SR) moxonidine, an imidazoline receptor agonist. METHODS: A randomized double-blind, placebo-controlled trial was initiated in 425 centers in 17 countries with a plan to enter 4533 patients with New York Heart Association class II-IV heart failure and a reduced ejection fraction. Moxonidine SR or matching placebo was titrated to a target dose of 1.5 mg BID. The trial was powered to detect a 20% reduction in mortality, which required a total of 724 deaths. FINDINGS: An early increase in death rate and adverse events in the moxonidine SR group led to premature termination of the trial because of safety concerns after 1934 patients were entered. Final analysis revealed 54 deaths (5.5%) in the moxonidine SR group and 32 deaths (3.4%) in the placebo group during the active treatment phase. Survival curves revealed a significantly (P=0.012) worse outcome in the moxonidine SR group. Hospitalization for heart failure, acute myocardial infarction and adverse events were also more frequent in the moxonidine SR group. Plasma norepinephrine was significantly decreased by moxonidine SR (-18.8% from baseline) vs. placebo (+6.9%). INTERPRETATION: Early termination of the trial limited conclusions regarding the long-term effects of central sympathetic inhibition. Nonetheless, the excess early mortality and morbidity suggest the likelihood of an adverse effect of moxonidine SR and raise concerns regarding the efficacy of generalized sympathetic inhibition in heart failure.

Delayed-Action Preparations↗
PubMed2003

Age-related changes in myocardial relaxation using three-dimensional tagged magnetic resonance imaging.

PURPOSE: Marked changes in left ventricular diastolic filling occur with advancing age, but alterations in myocardial movement accompanying these findings have not been previously documented. We aimed to identify differences in myocardial motion during relaxation and diastole using magnetic resonance imaging (MRI), with tagging, which uniquely allows accurate, noninvasive assessment of myocardial movement in three dimensions. METHODS: Tagged MRI images from two groups of normal individuals were analyzed using dedicated computer software to provide values for group comparison of apical rotation, torsion, and circumferential and longitudinal strain throughout the cardiac cycle. RESULTS: The mean age of the younger group was 22 years, (n = 15) and that of the older group was 69 years, (n = 16). In the older group, peak apical rotation and torsion were increased during systole and significantly more apical rotation, torsion, circumferential, and longitudinal strain persisted during myocardial relaxation and diastole. In addition, peak normalized reversal of apical rotation was reduced (-5.1 +/- 1.2 degrees s-1 vs. -6.7 +/- 1.2 degrees s-1, p = 0.001), and there were slower peak rates of circumferential lengthening (76.2 +/- 28% s-1 vs. 142.5 +/- 17% s-1, p < 0.001) and longitudinal lengthening (62.7 +/- 21% s-1 vs. 122.5 +/- 20% s-1, p < 0.001). CONCLUSIONS: Tagged MRI is a unique, noninvasive imaging method that can identify significant prolongation and reduction of myocardial relaxation in older compared with young normal individuals.

Adult↗
PubMed2003

The effect of an integrated care approach for heart failure on general practice.

BACKGROUND: Recent studies have investigated specific strategies for heart failure management. None has involved collaboration between primary and secondary care. Potential gains for patients may result from collaborative strategies. OBJECTIVE: To assess the effect of an integrated management approach for patients with heart failure on general practice. METHODS: The study design was a cluster randomized controlled trial of integrated primary/ secondary care compared with usual care for heart failure patients. The study took place at Auckland Hospital, New Zealand and involved 197 patients admitted with an episode of heart failure. Patients were randomized to management group or control group (who received "usual" care). Management group patients received early clinical review, education sessions, a personal diary for medications and weight, and regular clinical follow-up alternating between GP and hospital clinic. Follow-up was for 12 months. RESULTS: Patients visited GPs frequently (median 14 visits, range 0-40), with no statistical difference between the two groups. Heart failure was the most common reason for consulting the GP. There was no relationship between GP consultations and patients' attendance at the study clinic, or hospital admissions. Management group GPs and patients expressed a high level of satisfaction. CONCLUSION: GP consultation rates were not affected by the programme. Further research will determine if general practice based programmes result in further gains.

Adult↗