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.

Prevention and early treatment of the long-term physical effects of COVID-19 in adults: design of a randomised controlled trial of resistance exercise-CISCO-21.

BACKGROUND: Coronavirus disease-19 (COVID-19) infection causes persistent health problems such as breathlessness, chest pain and fatigue, and therapies for the prevention and early treatment of post-COVID-19 syndromes are needed. Accordingly, we are investigating the effect of a resistance exercise intervention on exercise capacity and health status following COVID-19 infection. METHODS: A two-arm randomised, controlled clinical trial including 220 adults with a diagnosis of COVID-19 in the preceding 6 months. Participants will be classified according to clinical presentation: Group A, not hospitalised due to COVID but persisting symptoms for at least 4 weeks leading to medical review; Group B, discharged after an admission for COVID and with persistent symptoms for at least 4 weeks; or Group C, convalescing in hospital after an admission for COVID. Participants will be randomised to usual care or usual care plus a personalised and pragmatic resistance exercise intervention for 12 weeks. The primary outcome is the incremental shuttle walks test (ISWT) 3 months after randomisation with secondary outcomes including spirometry, grip strength, short performance physical battery (SPPB), frailty status, contacts with healthcare professionals, hospitalisation and questionnaires assessing health-related quality of life, physical activity, fatigue and dyspnoea. DISCUSSION: Ethical approval has been granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (REC) (reference: GN20CA537) and recruitment is ongoing. Trial findings will be disseminated through patient and public forums, scientific conferences and journals. TRIAL REGISTRATION: ClinicialTrials.gov NCT04900961 . Prospectively registered on 25 May 2021.

Tumour biomarkers: association with heart failure outcomes.

BACKGROUND: There is increasing recognition that heart failure (HF) and cancer are conditions with a number of shared characteristics. OBJECTIVES: To explore the association between tumour biomarkers and HF outcomes. METHODS: In 2,079 patients of BIOSTAT-CHF cohort, we measured six established tumour biomarkers: CA125, CA15-3, CA19-9, CEA, CYFRA 21-1 and AFP. RESULTS: During a median follow-up of 21 months, 555 (27%) patients reached the primary end-point of all-cause mortality. CA125, CYFRA 21-1, CEA and CA19-9 levels were positively correlated with NT-proBNP quartiles (all P < 0.001, P for trend < 0.001) and were, respectively, associated with a hazard ratio of 1.17 (95% CI 1.12-1.23; P < 0.0001), 1.45 (95% CI 1.30-1.61; P < 0.0001), 1.19 (95% CI 1.09-1.30; P = 0.006) and 1.10 (95% CI 1.05-1.16; P < 0.001) for all-cause mortality after correction for BIOSTAT risk model (age, BUN, NT-proBNP, haemoglobin and beta blocker). All tumour biomarkers (except AFP) had significant associations with secondary end-points (composite of all-cause mortality and HF hospitalization, HF hospitalization, cardiovascular (CV) mortality and non-CV mortality). ROC curves showed the AUC of CYFRA 21-1 (0.64) had a noninferior AUC compared with NT-proBNP (0.68) for all-cause mortality (P = 0.08). A combination of CYFRA 21-1 and NT-proBNP (AUC = 0.71) improved the predictive value of the model for all-cause mortality (P = 0.0002 compared with NT-proBNP). CONCLUSIONS: Several established tumour biomarkers showed independent associations with indices of severity of HF and independent prognostic value for HF outcomes. This demonstrates that pathophysiological pathways sensed by these tumour biomarkers are also dysregulated in HF.

Novel endotypes in heart failure: effects on guideline-directed medical therapy.

Aims: We sought to determine subtypes of patients with heart failure (HF) with a distinct clinical profile and treatment response, using a wide range of biomarkers from various pathophysiological domains. Methods and results: We performed unsupervised cluster analysis using 92 established cardiovascular biomarkers to identify mutually exclusive subgroups (endotypes) of 1802 patients with HF and reduced ejection fraction (HFrEF) from the BIOSTAT-CHF project. We validated our findings in an independent cohort of 813 patients. Based on their biomarker profile, six endotypes were identified. Patients with endotype 1 were youngest, less symptomatic, had the lowest N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and lowest risk for all-cause mortality or hospitalization for HF. Patients with endotype 4 had more severe symptoms and signs of HF, higher NT-proBNP levels and were at highest risk for all-cause mortality or hospitalization for HF [hazard ratio (HR) 1.4; 95% confidence interval (CI) 1.1-1.8]. Patients with endotypes 2, 3, and 5 were better uptitrated to target doses of beta-blockers (P < 0.02 for all). In contrast to other endotypes, patients with endotype 5 derived no potential survival benefit from uptitration of angiotensin-converting enzyme-inhibitor/angiotensin-II receptor blocker and beta-blockers (Pinteraction <0.001). Patients with endotype 2 (HR 1.29; 95% CI 1.10-1.42) experienced possible harm from uptitration of beta-blockers in contrast to patients with endotype 4 and 6 that experienced benefit (Pinteraction for all <0.001). Results were strikingly similar in the independent validation cohort. Conclusion: Using unsupervised cluster analysis, solely based on biomarker profiles, six distinct endotypes were identified with remarkable differences in characteristics, clinical outcome, and response to uptitration of guideline directed medical therapy.

Sacubitril and valsartan fixed combination to reduce heart failure events in post-acute myocardial infarction patients.

Heart failure is a term used to define a constellation of symptoms and signs that are commonly attributed to the inability of the heart to produce a cardiac output that meets the demands of the body. It remains a deadly disease, affecting between 1-2% of the population, and is more common in the elderly, with around 6-10% of patients over 65 suffering from the condition. Sacubitril/valsartan (LCZ-696) is a combined neprilysin inhibitor and angiotensin AT1 receptor blocker approved in recent years for the treatment of chronic heart failure with reduced ejection fraction. In an area where there have been limited pharmacological advances in the last 10 years, this drug was a game changer and a much welcomed addition to contemporary heart failure therapy. It is currently being studied in patients with heart failure with preserved ejection fraction and for the reduction of heart failure events post-acute myocardial infarction. Results from the ongoing PARADISE-MI study are awaited by the global cardiology community with great interest.

Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study.

INTRODUCTION: Despite clear guidelines recommendations, most patients with heart failure and reduced ejection-fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers. METHODS AND RESULTS: BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching <50% of the recommended ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50-99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43-2.01; for beta-blocker: HR 1.70; 95% CI 1.36-2.05). CONCLUSION: Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%.

Rehabilitation Enablement in Chronic Heart Failure-a facilitated self-care rehabilitation intervention in patients with heart failure with preserved ejection fraction (REACH-HFpEF) and their caregivers: rationale and protocol for a single-centre pilot randomised controlled trial.

INTRODUCTION: The Rehabilitation EnAblement in CHronic Heart Failure in patients with Heart Failure (HF) with preserved ejection fraction (REACH-HFpEF) pilot trial is part of a research programme designed to develop and evaluate a facilitated, home-based, self-help rehabilitation intervention to improve self-care and quality of life (QoL) in heart failure patients and their caregivers. We will assess the feasibility of a definitive trial of the REACH-HF intervention in patients with HFpEF and their caregivers. The impact of the REACH-HF intervention on echocardiographic outcomes and bloodborne biomarkers will also be assessed. METHODS AND ANALYSIS: A single-centre parallel two-group randomised controlled trial (RCT) with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention) or usual care alone (control) in 50 HFpEF patients and their caregivers. The REACH-HF intervention comprises a REACH-HF manual with supplementary tools, delivered by trained facilitators over 12 weeks. A mixed methods approach will be used to assess estimation of recruitment and retention rates; fidelity of REACH-HF manual delivery; identification of barriers to participation and adherence to the intervention and study protocol; feasibility of data collection and outcome burden. We will assess the variance in study outcomes to inform a definitive study sample size and assess methods for the collection of resource use and intervention delivery cost data to develop the cost-effectiveness analyses framework for any future trial. Patient outcomes collected at baseline, 4 and 6 months include QoL, psychological well-being, exercise capacity, physical activity and HF-related hospitalisation. Caregiver outcomes will also be assessed, and a substudy will evaluate impact of the REACH-HF manual on resting global cardiovascular function and bloodborne biomarkers in HFpEF patients. ETHICS AND DISSEMINATION: The study is approved by the East of Scotland Research Ethics Service (Ref: 15/ES/0036). Findings will be disseminated via journals and presentations to clinicians, commissioners and service users. TRIAL REGISTRATION NUMBER: ISRCTN78539530; Pre-results .

Modulation of the renin-angiotensin-aldosterone system in heart failure.

The renin-angiotensin-aldosterone system (RAAS) is well-established and continues to be pursued as a therapeutic target in the treatment of heart failure, predominantly due to the success of agents that block RAAS in clinical trials of systolic heart failure. The optimal treatment of heart failure patients with preserved ejection fraction (HFpEF), however, remains unclear. Early trials of direct renin inhibitors have suggested that these agents may play a role in HFpEF, but recent clinical trial results have not been encouraging. Preliminary trials of angiotensin-receptor/neprilysin inhibitors look promising. Whether results with these or other drugs will alter current recommendations remains to be seen. In this review, we assess the current understanding of the role of RAAS modulation in heart failure.

The impact of age and chronic kidney disease on secondary prevention post-primary percutaneous coronary intervention.

OBJECTIVE: Historical data suggest elderly patients and those with chronic kidney disease (CKD) receive suboptimal secondary prevention following myocardial infarction (MI). We evaluated the impact of age and CKD on secondary prevention following primary percutaneous coronary intervention (PPCI) in a contemporary unselected cohort. DESIGN: We studied 1169 consecutive patients from five UK centres receiving PPCI for ST elevation MI, with use of evidence-based secondary prevention at discharge assessed by age (<60, 60-75 and >75 years) and estimated glomerular filtration rate (eGFR). Follow-up prescribing practice was assessed in 567 patients. RESULTS: One-fifth of patients receiving PPCI were >75 years. This group received fewer secondary prevention drugs at discharge compared to younger patients (P < 0.01 for ß-blockers, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB) and statins). By 6 weeks post-PPCI, there was a small drop-off in evidence-based therapy; ß-blocker and statin use in those >75 years fell from 90% to 86% and 96% to 93%, respectively. CKD (eGFR<60 ml/min/1.73 m(2)) was seen in 17.6%. Declining renal function was associated with age, female sex and lower use of ACE inhibitor/ARB. At discharge 83.5% of patients with eGFR<60 ml/min/1.73 m(2) were receiving ACE inhibitors/ARB, dropping to 77.5% at 6 weeks (compared with 95% and 92%, respectively, in patients with eGFR >60 ml/min/1.73 m(2)). CONCLUSION: The uptake of secondary prevention medication is high following PPCI in the UK, even in the elderly and in those with renal dysfunction. A focus on strategies to improve up-titration and continuation of drugs following discharge is required.

Renin-angiotensin-aldosterone system inhibitors in heart failure.

Heart failure (HF) is a very common condition that, despite advances in treatment, carries significant morbidity and mortality. Although there is good evidence for the treatment of HF with reduced ejection fraction (HFrEF), the treatment for HF with preserved ejection fraction (HFpEF) is not well defined. The renin-angiotensin-aldosterone system (RAAS) has been shown to be an effective target in the treatment of HFrEF using angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockade, although the evidence in HFpEF is less clear. This review aims to look first at the evidence for these drugs, and second at the newer drugs that act on the RAAS, namely, direct renin inhibitors, neutral endopeptidase inhibitors, vasopeptidase inhibitors, and angiotensin receptor blockers.

The prognostic significance of early and late anaemia in acute coronary syndrome.

BACKGROUND AND AIM: Anaemia in acute coronary syndrome (ACS) is a common and strong independent risk factor but it is unknown whether early anaemia is transient or whether it persists over the subsequent weeks. We also sought to evaluate whether late anaemia carries the similar prognostic significance as baseline anaemia. Another unknown is whether haemoglobin improves risk stratification over and above the GRACE score. DESIGN AND METHODS: Haemoglobin levels were prospectively measured in 448 consecutive patients presenting with ACS and at 7-weeks follow-up. Cardiovascular endpoints were defined as death or acute myocardial infarction (AMI) over a median duration of 30 months (range 1-50). RESULTS: The prevalence of anaemia on admission was 20% and this increased to 40% at 7-weeks follow-up. New anaemia occurred in 31% of patients. Baseline anaemia predicted CV endpoints independent of the admission GRACE (Global Registry of Acute Coronary Events) score [adjusted RR 2.54 (95% CI 1.73-3.71)]. Anaemia at 7-weeks follow-up was also a strong predictor of adverse outcomes [adjusted RR 1.67 (95% CI 1.04-2.69)]. Patients with persistent anaemia at 7 weeks were at an increased risk of death or AMI compared to those with persistently normal haemoglobin [unadjusted RR 3.58 (95% CI 2.04-6.29)]. CONCLUSION: In ACS, the prevalence of anaemia doubles from admission to 7-weeks follow-up (40%). Not only did baseline anaemia predict long-term prognosis independent of the admission GRACE score, but haemoglobin at 7-weeks post-ACS was also a simple independent predictor of adverse prognosis.

High sensitivity troponin T provides useful prognostic information in non-acute chest pain.

OBJECTIVE: To evaluate the prognostic value of high-sensitivity troponin T (hs-cTnT) in patients who present to General Practitioners (GPs) with non-acute chest pain. DESIGN, SETTING AND PATIENTS: A total of 625 patients who were referred by their GPs to a regional Rapid Access Chest Pain Clinic in Tayside, Scotland were consented and recruited. Diamond-Forrester pretest probability of coronary artery disease (CAD) was used to select patients with intermediate and high-pretest probability. Hs-cTnT and B-type Natriuretic Peptide (BNP) were measured and final diagnosis recorded. Twelve-month follow-up for cardiac events and hospital admission data was collected. Sensitivity, specificity, positive predictive value and negative predictive value (NPV), for both prognosis and diagnosis, were produced using various pre-specified cut-off values for hs-cTnT and BNP. RESULTS: A total of 579 patients were included in the final analysis. Of these, 477 had intermediate/high-pretest probability of CAD. A total of 431 (90.4%) of patients had a hs-cTnT ≤14 ng/l. In this study, hs-cTnT of 14 ng/l was the best cut-off for ruling out if a patient would have an admission for cardiac chest pain in the following 12 months (specificity 90%, NPV 91.4%). It performed well as a predictor of a subsequent negative diagnosis of cardiac chest pain with a specificity of 92.4% and NPV of 83.5%. CONCLUSIONS: Hs-cTnT, at the same level currently used in clinical practice as a diagnostic cut-off for myocardial infarction and acute coronary syndromes, is also a clinically-meaningful indicator for further 12-month cardiac chest pain hospital admissions in patients with non-acute chest pain referred to chest pain clinics by GPs.

Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study.

SLCO1B1 gene variants are associated with severe statin-induced myopathy. We examined whether these variants are also associated with general statin intolerance in a large population of patients with type 2 diabetes receiving statins as part of routine clinical care. A total of 4,196 individuals were genotyped for rs4149056 (Val174Ala) and rs2306283 (Asp130Asn). Intolerance was defined by serum biochemistry and also by discontinuation, switching, or reduction in dose of the prescribed statin drug. Ala174 was associated with higher intolerance (odds ratio = 2.05, P = 0.043), whereas Asp130 was associated with lower intolerance (odds ratio = 0.71, P = 0.026). Ala174 was associated with a lower low-density lipoprotein cholesterol (LDLc) response to statins (P = 0.01) whereas 130D was associated with a greater LDLc response to statins (P = 0.048), as previously reported; however, this association was no longer present when data for statin-intolerant individuals were removed from the analysis. This study suggests that common genetic variants selected for an extreme phenotype of statin-induced myopathy also predispose to more common milder statin intolerance and may, for this reason, impact lipid-lowering efficacy.

Dysglycaemia and the risk of acute myocardial infarction in multiple ethnic groups: an analysis of 15,780 patients from the INTERHEART study.

AIMS/HYPOTHESIS: Although diabetes is an established risk factor for myocardial infarction (MI), disease control may vary. HbA(1c) is a reliable index of ambient glucose levels and may provide more information on MI risk than diabetes status. METHODS: The relationship between HbA(1c) levels in MI patients and controls who participated in the 52 country INTERHEART study was analysed. RESULTS: In 15,780 participants with a HbA(1c) value (1,993 of whom had diabetes), the mean (SD) levels for HbA(1c) were 6.15% (1.10) in the 6,761 MI patients and 5.85% (0.80) in the control participants. After adjustment for age, sex and nine major MI risk factors (including diabetes), higher HbA(1c) fifths above the lowest fifth (HbA(1c) <5.4%) were associated with progressively higher OR of MI, with OR for the highest HbA(1c) fifth (≥ 6.12%) being 1.55 (95% CI 1.37-1.75). When analysed as a continuous variable after adjustment for the same factors, every 1% higher HbA(1c) value was associated with 19% (95% CI 14-23) higher odds of MI, while every 0.5% higher HbA(1c) was associated with 9% higher odds of MI (95% CI 7-11). Concordant relationships were noted across subgroups, with a higher OR noted in younger people, patients without diabetes or hypertension, and those from some regions and ethnicities. CONCLUSIONS/INTERPRETATION: The HbA(1c) value provides more information on MI odds than self-reported diabetes status or many other established risk factors. Every 1% increment independently predicts a 19% higher odds of MI after accounting for other MI risk factors including diabetes.

Is there a Failure to Optimize theRapy in anGina pEcToris (FORGET) study?

BACKGROUND: In the management of chronic stable angina, percutaneous coronary intervention (PCI) provides symptomatic relief of angina rather than improvement of prognosis. Current guidelines recommend optimization of medical therapy prior to elective PCI. It is not clear if these guidelines are adhered to in clinical practice. AIM: The aim of this multi-centre study was to determine the extent to which these treatment guidelines are being implemented in the UK. DESIGN: This was a multi-centre study involving six hospitals in the UK. METHODS: The medical treatment and extent of risk factor modification was recorded for consecutive patients undergoing elective PCI for chronic stable angina at each site. Data collected included anti-anginal drug therapy, lipid levels and blood pressure (BP). Data on heart rate (HR) control were also collected, since this represents a fundamental part of medical anti-anginal therapy. Target HR is <60 b.p.m. for symptomatic angina. RESULTS: A total of 500 patients [74% male; mean age +/- SD (64.4 +/- 10.1 years)] were included. When considering secondary prevention, 85% were receiving a statin and 76% were on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. In terms of medical anti-ischaemic therapy, 78% were receiving beta-blockers [mean equivalent dose of bisoprolol 3.1 mg (range 1.25-20 mg)], 11% a rate limiting calcium antagonist, 35% a nitrate or nicorandil and one patient was receiving ivabradine. The mean total cholesterol (95% confidence interval) was 4.3 mmol/l (4.2-4.4), mean systolic BP of 130 +/- 24 mmHg and mean diastolic BP of 69 +/- 13 mmHg. Serum cholesterol was <5 mmol/l in 77% and <4 mmol/l in 42% of the patients, 62% of the patients had systolic BP < 140 mmHg and 92% had diastolic BP < 90 mmHg. Considering European Society of Cardiology targets, 50% had systolic BP < 130 mmHg and 76% had diastolic BP < 80 mmHg. A large proportion of patients did not achieve target resting HR; 27% of patients had a resting HR of >or=70 b.p.m., 40% had a resting HR between 60 and 69 b.p.m. and 26% had a resting HR between 50 and 59 b.p.m. The resting HR was not related to the dose of beta-blocker. CONCLUSION: A significant proportion of the patients with chronic stable angina undergoing elective PCI did not achieve therapeutic targets for lipid, BP and HR control. Over 50% of patients did not receive adequate HR lowering anti-anginal therapy to achieve recommended target resting HR.

Loss-of-function CYP2C9 variants improve therapeutic response to sulfonylureas in type 2 diabetes: a Go-DARTS study.

Sulfonylureas are metabolized mainly by the cytochrome p450 2C9 (CYP2C9) enzyme. Two CYP2C9 variants--*2 (Arg144Cys) and *3 (Ile359Leu)--are associated with reduced enzyme activity and impaired substrate metabolism. We identified 1,073 incident users of sulfonylureas in Tayside, Scotland, and assessed the impact of the combined CYP2C9*2 and CYP2C9*3 genotypes on early and sustained sulfonylurea response. We found that patients with two copies of a loss-of-function allele were 3.4 times (P = 0.0009) more likely to achieve a treatment hemoglobin A(1c) (HbA(1c)) level <7% than patients with two wild-type CYP2C9 alleles. This corresponds to a 0.5% (P = 0.003) greater reduction in HbA(1c) concentration. In addition, *2 and *3 allele carriers were less likely to experience treatment failure with sulfonylurea monotherapy (P = 0.04; per-allele hazard ratio 0.79; 95% confidence interval 0.63-0.99). In conclusion, CYP2C9 loss-of-function alleles are associated with greater response to sulfonylureas and decreased failure of therapy consistent with the pharmacokinetic role of CYP2C9.

More than skin deep: atherosclerosis as a systemic manifestation of psoriasis.

There is now growing evidence that psoriasis, like other inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus, is a systemic disorder that is associated with enhanced atherosclerosis and risk of coronary artery disease. Here we summarize the available epidemiological evidence for this association and analyse pathogenic features that are common to psoriasis and atherosclerosis. Further prospective studies are urgently needed to extend knowledge of the risk of cardiovascular morbidity and mortality in patients with psoriasis and to confirm the degree to which treatment of psoriasis reduces this risk. Nevertheless, existing data are sufficient to indicate that severe psoriasis should be more widely recognized as a potential risk factor for cardiovascular disease and should be considered with the established factors when formulating strategies for the management of cardiovascular risk.

A comparison between B-type natriuretic peptide, global registry of acute coronary events (GRACE) score and their combination in ACS risk stratification.

BACKGROUND: In acute coronary syndrome (ACS), both the Global Registry of Acute Coronary Events (GRACE) score and B-type natriuretic peptide (BNP) predict cardiovascular events. However, it is unknown how BNP compares with GRACE and how their combination performs in ACS. METHODS: The authors recruited 449 consecutive ACS patients and measured admission GRACE score and bedside BNP levels. The main outcome measure was all-cause mortality, readmission with ACS or congestive heart failure (defined as a cardiovascular event) at 10 months from presentation. RESULTS: Of the 449 patients, 120 patients presented with ST-elevation myocardial infarction (MI) (27%). There were 90 cardiovascular events at 10 months. Both higher GRACE terciles and higher BNP terciles predicted cardiovascular events. There was a significant but only partial correlation between the GRACE score and log BNP (R = 0.552, p<0.001). On multivariate analyses, after adjusting for the GRACE score itself, increasing BNP terciles independently predicted cardiovascular events (second BNP tercile adjusted RR 2.28 (95% CI 1.15 to 4.51) and third BNP tercile adjusted RR 4.91 (95% CI 2.62 to 9.22)). Patients with high GRACE score-high BNP were more likely to experience cardiovascular events at 10 months (RR 6.00 (95% CI 2.40 to 14.83)) compared to those with high GRACE score-low BNP (RR 2.40 (95% CI 0.76 to 7.56)). CONCLUSION: In ACS, most but not all of our analyses suggest that BNP can predict cardiovascular events over and above the GRACE score. The combined use of both the GRACE score and BNP can identify a subset of ACS patients at particularly high risk. This implies that both the GRACE score and BNP reflect somewhat different risk attributes when predicting adverse prognosis in ACS and their synergistic use can enhance risk stratification in ACS to a small but potentially useful extent.