The impact of patient-reported frailty on cardiovascular outcomes in elderly patients after non-ST-acute coronary syndrome.

BACKGROUND: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. RESULTS: The total study population consisted of 2192 NSTE-ACS patients, aged ≥70 years. The GFI-score was available in 1320 patients (79 ± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01-2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65-2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. CONCLUSIONS: In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.

Effectiveness of out-patient based acute heart failure care: a pilot randomised controlled trial.

OBJECTIVES: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). METHODS: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. RESULTS: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient. CONCLUSIONS: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.

Ethnic differences in the prevalence and aetiology of left ventricular systolic dysfunction in the community: the Harrow heart failure watch.

OBJECTIVE: To assess ethnic differences in the prevalence and aetiology of left ventricular systolic dysfunction (LVSD) in the community. DESIGN: Community cohort study. All patients underwent echocardiography and those found to have LVSD underwent myocardial perfusion imaging with or without coronary angiography to diagnose underlying coronary artery disease (CAD). SETTING: Seven representative general practices in Harrow, UK, a community hospital, and a local district general hospital. PATIENTS: 1392 patients >or= 45 years old randomly selected from the computer records of seven general practices. MAIN OUTCOME MEASURES: The prevalence and aetiology of LVSD in the community, assessing differences between white and non-white populations, and the proportion of patients with LVSD with undiagnosed CAD. RESULTS: 734 patients (53%) attended, 518 (71%) white and 216 (29%) non-white, the majority South Asian. Thirty nine patients (5.5%) had probable LVSD and 25 (3.5%) definite LVSD. No significant differences in prevalence were seen with ethnicity. CAD underlay most cases of LVSD. Non-white patients had a higher prevalence of CAD as the underlying aetiology of significant LVSD than white patients (100% v 56%, p = 0.04) and a trend towards less alcoholic cardiomyopathy. 8% of patients with LVSD had undiagnosed CAD. CONCLUSIONS: LVSD is common. White and non-white patients have a similar overall prevalence of LVSD. Non-white patients, the majority South Asians in this study, have a higher prevalence of CAD as the underlying cause for LVSD than white patients. CAD underlies most cases of LVSD in the community, although it may be undiagnosed unless formally assessed.

Evaluation of N-terminal pro-B type natriuretic peptide analysis on the Elecsys 1010 and 2010 analysers.

BACKGROUND: N-terminal pro-B type natriuretic peptide (NTpBNP) is a potential marker of cardiac failure. METHODS: The Roche Elecsys(trade mark) 1010 and 2010 assays for NTpBNP were evaluated for precision, sample stability, and correlation between sample types and with other natriuretic peptides. Samples from 290 individuals aged 45-89 years with no cardiovascular risk factors, renal failure, electrocardiogram changes, evidence of structural abnormalities, or wall motion abnormalities on echocardiography and with an ejection fraction >50% were used to provide reference NTpBNP ranges. RESULTS: The intra-assay imprecision was <10% across the analytical range and >3% at all concentrations analysed <30 ng/L. Inter-assay imprecision was 5.3-6.7% on the Elecsys 1010 and 4.4-5.0% on the Elecsys 2010, in the range 380-13000 ng/L. There was no statistically significant change in NTpBNP following storage in whole-blood samples at room temperature for 24 h before centrifugation; serum samples at room temperature for 7 days, at 4 degrees C for up to 11 days on clot-activation gel or 22 days separated from the gel. NTpBNP concentrations were stable throughout five freeze-thaw cycles. There was a close correlation between NTpBNP concentrations in matched serum, EDTA plasma and lithium-heparin plasma samples. NTpBNP and BNP were more closely associated than were N-terminal proatrial natriuretic peptide and NTpBNP. This association was stronger at lower concentrations. NTpBNP concentrations increased with age, with values higher in women than men. CONCLUSIONS: NTpBNP is a stable molecule that can be measured easily and precisely using the Roche Elecsys 1010 or 2010 immunoassay analysers.

Is echocardiography a valid tool to screen for left ventricular systolic dysfunction in chronic survivors of acute myocardial infarction? A comparison with radionuclide ventriculography.

OBJECTIVE: To assess the accuracy of echocardiography with Simpson's apical biplane method in screening for left ventricular systolic dysfunction (LVSD) in patients six months after acute myocardial infarction (AMI) as compared with radionuclide ventriculography by assessing the proportion of clinically significant errors that occur with echocardiography. DESIGN: Comparison of results of echocardiography and radionuclide ventriculography in assessing left ventricular ejection fraction among patients six months after AMI. SETTING: District general hospital. PATIENTS: 86 patients thrombolysed for AMI at six month follow up. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Correlation coefficients, mean differences, 95% limits of agreement, and differences of clinical significance between left ventricular ejection fraction on echocardiography and on radionuclide ventriculography. RESULTS: The correlation coefficient between techniques was 0.90, mean difference 1% (p = 0.04), and 95% limits of agreement -13.0% to 10.3%. Only one patient (1.2%, 0.0% to 6.3%) was classified as having normal systolic function on one imaging modality but significant LVSD on the other. Overall accuracy between the two techniques was 86%, kappa value of agreement 0.78. CONCLUSION: Echocardiography is a valid tool to screen for LVSD in patients six months after AMI, accurately differentiating normal from abnormal systolic function and showing excellent agreement with radionuclide ventriculography. This study supports the use of echocardiography in screening for LVSD in chronic stable patients after AMI or alternative high risk patients, with few differences of major clinical significance likely to occur.

Analytical performance of the N terminal pro B type natriuretic peptide (NT-proBNP) assay on the Elecsys 1010 and 2010 analysers.

The Elecsys NT-proBNP assay is based on two polyclonal antibodies directed at residues 1-21 and 39-50 of the NT-proBNP molecule. Analytical performance was assessed using NCCLS protocol EP-5A using three serum pools in a preliminary study then as part of a multicentre evaluation (16 instruments in 8 hospitals). Using pools of 350 pg/l, 8700 pg/l and 13000 pg/l single site within run %CV was 0.7-1.6 (1010) and 1.2-1.5 (2010) and between run CV 5.3-6.7 (1010) and 4.4-5.0 (2010). In the multicentre evaluation within run CV was 1.0-2.5% with total imprecision 1.5-2.5% and between labs imprecision 3.8-4.0%. Functional sensitivity of <50 pg/l and measuring range to 35000 pg/l. There was excellent agreement between instrument platforms, y=0.97x+2.6; r=1.00 (n=215) for Elecsys 2010 (x) vs. Elecsys 1010 (y) and y=1.02x-0.3; r=1.00 (n=99) for Elecsys 2010 (x) vs. E 170 (y). Serum and heparin plasma samples showed good agreement but lower values were seen in EDTA plasma. Samples were stable for 7 days at room temperature; 21 days at 4 degrees C and for 5 freeze thaw cycles. Samples were obtained from a population of 1205 (671 male, 534 female) apparently healthy individuals screened by echocardiography and symptom questionnaire. There was poor correlation with NT-proANP (ELISA) (rs 0.33) and modest correlation with BNP (rs 0.89) with NT-proBNP values approximately 5 times greater than BNP (Biosite Triage). In a subset of 320 with normal ejection fraction (>50%) and no risk factors, NT-proBNP values increased with age and were higher in women than men.

Portable echocardiography: an innovative tool in screening for cardiac abnormalities in the community.

AIMS: Heart failure is placing an increasing burden on society. This has led to calls for echocardiographic-based programmes to screen for left ventricular systolic dysfunction and other cardiac abnormalities. Echocardiography using new fully portable echocardiography devices would allow community-based cost-effective screening programmes once validated. This study was undertaken to evaluate this further in both high and low-risk subjects. METHODS AND RESULTS: 562 consecutive subjects attending a community-based heart failure screening programme, some at high-risk and some at low-risk of cardiac abnormalities, underwent echocardiography by both portable and traditional echocardiography machines. An 'eyeball' estimate of left ventricular ejection fraction was made on the portable device and compared to a quantitative measure of ejection fraction on the traditional machine. Qualitative measures of valvular regurgitation and quantitative measures of left ventricular hypertrophy were also compared. An estimate of ejection fraction was possible in 97% of cases using portable echocardiography. It gave a sensitivity, specificity and negative predictive value in diagnosing left ventricular systolic dysfunction of 96%, 98% and 99.6%, respectively. Inter-observer variability gave a mean difference in ejection fraction of 2%, and 95% limits of agreement of -8% to +12%. All cases of moderate or severe valvular regurgitation and 29 of 31 cases of significant left ventricular hypertrophy were correctly identified as abnormal on the portable device. CONCLUSIONS: Thus, echocardiography performed by experienced sonographers using these new fully portable devices is an accurate and reproducible technique for detecting left ventricular systolic dysfunction, left ventricular hypertrophy and valvular regurgitation in both high-risk and low-risk members of the community. Its very high negative predictive values would allow their use in future community-based screening programmes.

A prospective comparison of echocardiographic wall motion score index and radionuclide ejection fraction in predicting outcome following acute myocardial infarction.

OBJECTIVE: To characterise echocardiographic wall motion score index (WMSI) as a surrogate measure of left ventricular ejection fraction (EF) following acute myocardial infarction (AMI) and to compare its prognostic value with that of EF measured by radionuclide ventriculography (RNV). DESIGN: A prospective study to compare baseline echocardiographic WMSI with RNV EF in consecutive patients thrombolysed for AMI, both performed on the same day before discharge, and their relative prognostic values in predicting cardiac events. SETTING: District general hospital coronary care unit and cardiology department. PATIENTS: 120 consecutive patients free of exclusion criteria thrombolysed for AMI and followed up for a mean (SD) of 13 (10) months. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Correlation coefficients and receiver operating characteristic curve analyses plus cardiac event rates at follow up between RNV EF and echocardiographic WMSI. RESULTS: WMSI correlated well with RNV EF. The best corresponding WMSIs for EFs 45%, 40%, and 35% were 0.6, 0.8, and 1.1, respectively. There were 42 cardiac events during follow up. Although both RNV EF and WMSI were strong univariate predictors of cardiac events, only WMSI independently predicted outcome in a multivariate model. All three WMSI cut offs significantly predicted events, while an RNV EF cut off of 45% failed to reach significance. CONCLUSIONS: Although both RNV and echocardiographic WMSI strongly predicted cardiac outcome, WMSI, a cheaper and more readily available technique, is more discriminatory, especially in cases of mild left ventricular dysfunction following AMI.

Cocaine, a risk factor for myocardial infarction.

Cocaine usage goes back thousands of years, to the times of the Incas. Over the past 20 years, its use has increased dramatically, especially in America, and adverse cardiovascular reactions to the drug have begun to be reported. The first report of myocardial infarction temporally related to the recreational use of cocaine appeared in 1982. Since then, myocardial infarction has become recognized as the drug's most common cardiovascular consequence, with over 250 cases now documented in the literature. This review discusses the history of cocaine use, its pharmacology, the possible pathological mechanisms underlying the pathogenesis of myocardial ischaemia and infarction, and current ideas on the management of cocaine-induced myocardial infarction.

Medical students in general practice: how do patients feel?

BACKGROUND: The General Medical Council has recommended that medical students should gain more experience in general practice. AIM: The study set out to determine patients' reactions to the presence of medical students in general practice consultations. METHOD: Patients attending a random sample of general practice surgeries completed a questionnaire following consultation with and without a medical student present in six general practices in the Oxford area. RESULTS: The questionnaires were completed by 278 patients. Only eight (3%) of all respondents had negative responses to the presence of a medical student. Of those completing questionnaires following a teaching consultation, 107 (56%) felt positively about the presence of students, compared with 36 (41%) who had attended a nonteaching surgery. Only three patients (1%) felt the quality of the consultation to be impaired by the presence of a student, while 48 patients (17%) felt there to be some improvement. The majority felt that the sex of the student was unimportant, but significantly more female than male patients (17% versus 5%) felt that it made a difference. CONCLUSION: Only a small proportion of patients object to the presence of a medical student in general practice consultations. A significant minority said that the presence of a student improves the consultation.

Circulating factors and insulin resistance. II. The action of the novel myo-inositol cyclic 1,2-inositol phosphate phosphoglycan insulin antagonist from human plasma in regulating pyruvate dehydrogenase phosphatase.

A novel low mol wt inositol phosphoglycan antagonist of insulin action of oxidative glucose metabolism in isolated rat adipocytes was partially purified from normal human plasma and shown to be increased in type II diabetic plasma. It was characterized chemically as a myo-inositol phosphoglycan containing a cyclic 1,2-phosphate. This antagonist, termed fraction V3, is now shown to inhibit the action of an inositol glycan insulin pH 2.0 mediator that stimulates pyruvate dehydrogenase phosphatase in a similar manner to insulin. In addition, fraction V3 inhibits stimulation of the pyruvate dehydrogenase (PDH) phosphatase by Mg2+, the enzyme's required metal, and by spermine, a polyamine. Fraction V3 does not inhibit active PDH itself. The inhibitory effect is dose dependent and apparently noncompetitive or nonsurmountable for the insulin inositol glycan pH 2.0 mediator, thus comparing kinetically with its insulin antagonistic action on intact adipocytes. Its inhibitory action on PDH phosphatase is dose dependent and competitive for Mg2+ stimulation of the phosphatase. Additionally, fraction V3 is shown to inhibit stimulation by Mg2+ of cloned recombinant PDH phosphatase catalytic subunit. Inhibition by fraction V3 of Mg(2+)-stimulated PDH phosphatase and its cloned catalytic subunit helps explain its mechanism of action to inhibit insulin-stimulated oxidative glucose metabolism in adipocytes and its potential clinical significance in insulin resistance.

Circulating factors and insulin resistance. I. A novel myoinositol 1,2-cyclic phosphate phosphoglycan insulin antagonist from human plasma is elevated in noninsulin-dependent diabetes mellitus.

A novel low mol wt inositol phosphoglycan inhibitor (M tau 1200-1500) of insulin action in rat adipocytes has been partially purified from normal human plasma. This inhibitor, termed fraction V after the first purification step and fraction V3 after the second, is different from other reported serum insulin antagonists. It contains myoinositol, galactosamine, and mannose in approximate molar ratios of 1:1:3.3. The myoinositol has a 1,2-cyclic phosphate substituent, which is essential for the inhibitory activity. Its inhibitory activity is significantly elevated (161%, P < 0.05 for fraction V; 278%, P < 0.05 for fraction V3) in plasma of humans with noninsulin-dependent diabetes mellitus as compared with plasma of nondiabetic controls. These findings represent the first report of a naturally occurring mammalian inositol 1,2-cyclic phosphate containing phosphoglycan related to insulin action.

chiro-inositol deficiency and insulin resistance: a comparison of the chiro-inositol- and the myo-inositol-containing insulin mediators isolated from urine, hemodialysate, and muscle of control and type II diabetic subjects.

chiro- and myo-Inositols are major components of the two inositol phosphoglycan mediators of insulin action. Previous work in this laboratory has shown hypo-chiro-inositoluria in type II diabetic subjects and decreased chiro-inositol in mediator prepared from skeletal-muscle biopsies of Pima Indian diabetic subjects together with increased myo-inositol concentrations. Because mediator bioactivity was not previously examined, we decided to isolate the two types of insulin mediator from hemodialysate, urine, and autopsy muscle to investigate their bioactivity in control and type II diabetic subjects. Human mediator fractions were isolated at pH 2.0 and pH 1.3 from hemodialysate, urine, and autopsy muscle of type II diabetic subjects and nondiabetic control subjects. Mediators were assayed for bioactivity, and the relative chiro-inositol/myo-inositol concentration ratio was determined for the mediator pH 2.0 samples by using HPLC or GC/MS. Regardless of source, the chiro-inositol-containing mediator pH 2.0 fractions from type II diabetic subjects were markedly less active than those from controls (50% or less) (P < 0.05). In addition, the chiro-inositol/myo-inositol ratio in samples from type II subjects was significantly reduced (1/3-1/9) compared with controls (P < 0.05 for hemodialysate and P < 0.01 for muscle samples). In contrast, no difference in bioactivity was seen in myo-inositol-containing mediator pH 1.3 samples isolated from the same type II diabetic and control subjects. In type II diabetes there is a generalized deficiency of chiro-inositol mediator in the body in terms of both decreased chiro-inositol mediator (pH 2.0) bioactivity and chiro-inositol content.

The caffeine contents of non-alcoholic beverages.

The caffeine content of a number of non-alcoholic beverages was determined using HPLC. It was found that Diet Coke had a greater caffeine content than Coke (4.15 compared with 3.13 mg/fl oz), Tab is virtually caffeine free, and Lucozade, sold as a tonic, contains more caffeine than any of the other carbonated beverages tested (5.17 mg/fl oz). The pure instant coffee tested contained much more caffeine than the coffee/chicory mixtures (12.61 compared with 3.18 mg/fl oz). The caffeine content of Ceylon tea blends increases with the time the tea is allowed to draw (from about 8 mg/fl oz after 1 min to about 12 mg/fl oz after 20 min). Tea that has been allowed to draw for 20 min has a caffeine content similar to that of pure coffee.

Solubility changes on mixing short- and long-acting insulin preparations.

The loss of solubility of short-acting insulins when mixed in a ratio of 1:1 with intermediate-acting insulins in vitro was determined using high-performance liquid chromatography. Insulin preparations (porcine and human) from three different manufacturers were tested and various times of mixing (0-24 h) were investigated. The loss of solubility with mixtures of human insulins and with mixtures of porcine Velosulin (Nordisk) and Insulatard (Nordisk) was small at all the times used. A mixture of porcine Actrapid MC (Novo) and Monotard MC (Novo) led to a 60-95% loss of the soluble component, depending on the duration of mixing. The greater the time the greater the loss. These in vitro data indicate that short-acting insulins may lose solubility when mixed with long- or intermediate-acting ones. This phenomenon could be clinically relevant when patients are changed from mixtures of monocomponent to human insulins.

A proteolytic mechanism for the action of insulin via oligopeptide mediator formation.

Evidence is presented that the chemical mediator of insulin action is a peptide(s) and most likely glycopeptide(s). The mediator is formed proteolytically because 1) protease inhibitors inhibit insulin action and 2) trypsin mimicks insulin action via mediator formation. Trypsin mediator does not faithfully reproduce the action of insulin mediator, which indicates that the sites of proteolytic cleavage by insulin and trypsin differ. A coordinated multivalent proteolytic mechanism by which insulin acts to trigger an external membrane-bound protease to cleave mediator from a membrane glycoprotein precursor is presented.