Background Assessing risk and weighing the potential benefits from evidence-based therapies are essential in the clinical decision making process of optimizing care and outcomes for patients ...presenting with acute coronary syndromes (ACS). Such practices are advocated in international clinical guidelines of ACS care. While the GRACE risk score (GRS) is a guideline advocated, well-validated risk stratification tool, its utility in improving care and outcomes remains unproven, and its application has been limited in routine clinical practice. Objective This study will assess the effectiveness using the GRS tool and treatment recommendations during patient assessment on improving the application of guideline-recommended therapies in ACS care. Design This study employs a PROBE (prospective cluster hospital-level randomized open-label, blinded endpoint) design to evaluate objective measures of hospital performance, with clinical events adjudicated by a blinded event committee. This randomized study is nested within the established CONCORDANCE registry of ACS patients, with existing methods for data collection and monitoring of care and clinical outcomes. The hospital-level intervention is the integration of the GRS into routine ACS patient assessment process. The study will assess the use of early invasive management, prescription of guideline recommended pharmacology and referral to cardiac rehabilitation by hospital discharge; with the key composite clinical endpoint of cardiovascular death, new or recurrent myocardial infarction, in-hospital heart failure or cardiovascular readmission at 12 months. Health economic impacts of risk stratification implementation will also be evaluated. The study will recruit 3000 patients from 30 hospitals. Summary The AGRIS trial will establish the effect of routine objective risk stratification using the GRACE risk score on ACS care and clinical outcomes.
Abstract Background The segment involvement score (SIS) is a semiquantitative measure of the extent of atherosclerosis burden by coronary computed tomography angiography (-CTA). We sought to evaluate ...by meta-analysis the prognostic value of SIS, and to compare it with other CTA measures of coronary artery disease (CAD). Methods Electronic databases from 1946 to January 2016 were searched. Studies reporting SIS, or an equivalent measure by coronary CTA, and clinical outcomes were included. Maximally adjusted hazard ratios (HR), predominantly for clinical variables, were extracted for SIS, obstructive CAD, Agatston coronary artery calcium score, and plaque composition. These were pooled using DerSimonian-Laird random effects models. Results Eleven nonrandomized studies with good methodological quality enrolling 9777 subjects (mean age 61 ± 11 years, 57% male, mean follow up 3.3 years) who had 472 (4.8%) MACE (cardiac or all cause death, non-fatal myocardial infarction or late revascularization), were included. SIS (per segment increase) had pooled HR of 1.25 (95% CI: 1.16,1.35; I2 = 71.4%, p < 0.001) for MACE. HR for MACE was 1.37 (95% CI: 1.32,1.42; I2 = 95.6%, p < 0.001) for number of segments with stenosis (per segment increase), 3.39 (95% CI: 1.65,6.99; I2 = 87.8%, p = 0.001) for obstructive CAD (binary variable) and 1.00 (95% CI: 1.00,1.01; I2 = 75.0%, p = 0.490) for Agatston score (per unit increase). HRs by plaque composition (calcified, non-calcified and mixed; per segment change) were 1.24 (95% CI: 1.10,1.39; I2 = 81.6%, p = 0.001), 1.20 (95% CI: 0.97,1.48; I2 = 92.9%, p = 0.093) and 1.27 (95% CI: 1.03,1.58; I2 = 89.8%, p = 0.029), respectively. Conclusion Despite heterogeneity in endpoints, extent of CAD as quantified by SIS on coronary CTA is a strong, independent predictor of cardiovascular events.
Background The clinical relevance of minor elevations of cardiac troponin (cTn) in the general population remains uncertain. The objective of this systematic review was to examine the literature and ...evaluate the prevalence of raised cTn in asymptomatic, community populations and explore the strength of the relationship between cTn and cardiovascular mortality amongst those studied. Methods Studies were identified by searching Medline, Embase, CINAHL, EBM Reviews, Cochrane Library and using the “related citation” search tool in PubMed from inception through August 2014. Prospective cohort studies of asymptomatic individuals recruited from the community (age ≥ 18 years) that assessed the relationship between cTn levels and mortality or cardiovascular events were included. Results Twenty-one prospective studies involving 64,855 participants were identified. An elevated cTn measurement (>99th percentile) occurred in 5% of individuals and was associated with a tripling of risk of mortality (adjusted RR 3.07, 95% confidence interval CI 2.32-4.06) and cardiovascular mortality (adjusted RR 3.30, 95% CI 1.77-6.12). In studies including high sensitivity assays, cTn was detectable in 58% of individuals. A detectable cardiac troponin T (cTnT) was also associated with an increased risk of cardiovascular mortality (adjusted RR 1.32, 95% CI 1.10 – 1.59). The risk increased with increasing cTnT level. Conclusions Elevated troponin in asymptomatic individuals in the community is associated with a tripling of risk of all-cause and cardiovascular mortality. Cardiac troponin T (cTnT) is generally not measured in this group of patients, but may potentially have utility in predicting risk in this population. Further research is required to assess if this risk is modifiable with usual primary prevention treatments.
Pulmonary Hypertension (PHT) is relatively common, dangerous and under-recognised. Pulmonary hypertension is not a diagnosis in itself; it is caused by a number of differing diseases each with ...different treatments and prognoses. Therefore, timely and accurate recognition of the underlying cause for PHT is essential for appropriate management. This is especially true for patients with Pulmonary Arterial Hypertension (PAH) in the current era of disease-specific drug therapy. Measurement of Pulmonary Vascular Resistance (PVR) helps separate pre-capillary from post-capillary PHT, and is measured with right heart catheterisation (RHC). Echocardiography has been used to derive a number of non-invasive surrogates for PVR, with varying accuracy. Ultimately, the goal of non-invasive assessment of PVR is to separate PHT due to left heart disease from PHT due to increased PVR, to help streamline investigation and subsequent treatment. In this review, we summarise the physiology and pathophysiology of pulmonary blood flow, the various causes of pulmonary hypertension, and non-invasive surrogates for PVR.
Abstract Background There is a perception among Canadian physicians that coronary artery disease (CAD) and adverse cardiac events are more common in those with French Canadian heritage. We sought to ...compare the prevalence of CAD using coronary computed tomography angiography (CCTA) in French Canadians and non-French Caucasian Canadians. Methods Consecutive patients were prospectively enrolled into our institutional CCTA Registry. Of 10,868 CCTA examinations, we analyzed Caucasian patients who identified themselves as French Canadian or non-French Canadian. These 2 groups were compared for baseline characteristics, cardiovascular risk factors and routine markers for CAD on CTCA. Propensity score adjustments were also made to account for differences in demographics. Results We identified 1,683 French Canadians (mean age 58.5±10.7 years, 54.2% male) and 5,077 non-French Caucasian Canadians (mean age 59.4±11.4 years, 57.3% male). French Canadians were more likely to have smoking history (64.1% vs. 56.1%), diabetes (15.6% vs. 13.6%) and family history of premature CAD (53.3% vs. 44.6%) (p <0.05 for all). There was no significant difference in measures of CAD between French Canadians and non-French Caucasian Canadians in obstructive CAD (32.5% vs. 32.2%, p=0.997), total plaque score (4.6±4.3 vs. 4.5±4.4, p=0.616) and Agatston Score (168.1±319.8 vs. 183.6±433.7, p=0.371). After propensity score adjustment, there was still no significant difference between the groups. Conclusions Our study suggests that French Canadians in the Champlain Region have greater prevalence of cardiovascular risk factors compared to Non-French Canadians, however do not appear to have greater prevalence or severity of CAD or coronary atherosclerosis as assessed by CCTA.
Summary Background Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. ...There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. Methods We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill—a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis. Findings Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14–23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen. Interpretation The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability. Funding National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.
Background Familial hypercholesterolemia (FH) is the most common dominantly inherited cause of premature coronary artery disease (CAD). However, the diagnosis of FH in patients who have premature CAD ...in hospital settings is under-recognized, this also represents a missed opportunity for screening their close family members and implementing primary prevention. Objective To investigate the point prevalence of FH in a coronary care unit (CCU) among patients with early-onset CAD. Methods The prevalence of FH, based on modified phenotypic Dutch Lipid Clinic Network Criteria, and the spectrum of associated CAD risk factors, were investigated in a CCU setting. Data were collected on 175 coronary care patients with onset of CAD at age <60 years. Results The prevalence of probable/definite FH was 14.3% (95% confidence interval, 9.0%–19.5%); 46.3% of the patients gave a family history of premature CAD and 20.6% had an untreated low-density lipoprotein cholesterol >5.0 mmol/L. Diabetes, hypertension, obesity, and smoking were common and equally prevalent in patients with and without FH. Conclusions FH is relatively frequent among patients with a history of early-onset CAD in the CCU. Every effort should be made to detect FH in these patients and to initiate cascade testing of available family members to prevent the development of CAD in those who may be unaware that they also have the condition.
Background An elevated preoperative white blood cell count has been associated with a worse outcome after coronary artery bypass grafting (CABG). Leukocyte subtypes, and particularly the ...neutrophil-lymphocyte (N/L) ratio, may however, convey superior prognostic information. We hypothesized that the N/L ratio would predict the outcome of patients undergoing surgical revascularization. Methods Baseline clinical details were obtained prospectively in 1938 patients undergoing CABG. The differential leukocyte was measured before surgery, and patients were followed-up 3.6 years later. The primary end point was all-cause mortality. Results The preoperative N/L ratio was a powerful univariable predictor of mortality (hazard ratio HR 1.13 per unit, P < .001). In a backward conditional model, including all study variables, it remained a strong predictor (HR 1.09 per unit, P = .004). In a further model, including the European system for cardiac operative risk evaluation, the N/L ratio remained an independent predictor (HR 1.08 per unit, P = .008). Likewise, it was an independent predictor of cardiovascular mortality and predicted death in the subgroup of patients with a normal white blood cell count. This excess hazard was concentrated in patients with an N/L ratio in the upper quartile (>3.36). Conclusion An elevated N/L ratio is associated with a poorer survival after CABG. This prognostic utility is independent of other recognized risk factors.
Objective Myocardial ischemia and infarction after surgery remain leading causes of morbidity and mortality in patients undergoing major vascular surgery. B-type natriuretic peptide has been shown to ...predict early postoperative cardiac events in patients undergoing major noncardiac surgery. We aimed to determine if N-terminal pro B-type natriuretic peptide (NT-pro-BNP), with its longer half-life and greater plasma stability, can predict postoperative myocardial injury in vascular patients. Methods Recruited were 136 patients undergoing elective surgery for subcritical limb ischemia or abdominal aortic aneurysm (AAA) repair. Plasma NT-pro-BNP was measured preoperatively, and troponin-I was measured immediately after surgery and on postoperative days 1, 2, 3, and 5. Results Twenty-eight patients (20%) sustained postoperative myocardial injury (troponin-I rise of >0.1 ng/mL). The median NT-pro-BNP level of those with myocardial injury was significantly higher than those who did not (380 pg/mL interquartile range (IQR), 223-967 vs 209 pg/mL 109-363; P = .003). NT-pro-BNP predicted this outcome with an area under the receiver operating characteristic (ROC) curve of 68% (95% confidence interval CI 0.56%-0.78%). In a multivariate analysis, a NT-pro-BNP value of ≥308 pg/mL (the optimal ROC curve–derived cutoff) was associated with an increased incidence of myocardial injury (odds ratio, 3.4; 95% CI, 1.41-9.09, P =.01). Conclusion Elevated preoperative plasma NT-pro-BNP levels independently predict postoperative myocardial injury, which is associated with adverse outcome in the short- and long-term regardless of the presence of symptoms of acute coronary syndrome.
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