Impact of vascular disease in predicting stroke and death in patients with atrial fibrillation: the Danish Diet,Cancer and Health cohort study

Summary. Background: The presence of vascular disease (peripheral artery disease [PAD] and/or myocardial infarction [MI]) may impact on the risk of stroke and death among patients with incident atrial fibrillation (AF). To test this hypothesis, we analyzed data from a large Danish prospective cohort, the Danish Diet, Cancer and Health (DCH) study, to assess the risk of stroke or death among those who developed AF according to concomitant presence of vascular disease. Methods: A prospective cohort study of 57 053 persons (27 178 men and 29 876 women, respectively), aged between 50 and 64 years. The risk of stroke or death for patients with vascular disease was assessed amongst 3315 patients with incident AF (mean age, 67.1 years; 2130 men, 1185 women) using Cox proportional hazard models, after a median follow‐up of 4.8 years. Results: Of the subjects with AF, 417 (12.6%) had ‘vascular disease’ (PAD and/or prior MI). The risk of the primary endpoint (stroke or death) was significantly higher in patients with vascular disease at 1‐year follow‐up (crude hazard ratio [HR] 2.51 [1.91–3.29]), with corresponding crude HRs for PAD and MI being 3.51 (2.40–5.13), and 1.99 (1.46–2.72), respectively. For the secondary endpoints of death or stroke individually, these risk estimates were similar (crude HR 2.48 [1.89–3.26] and 1.77 [1.18–2.66], respectively). After adjustment for risk factors within the CHADS₂ score, the adjusted HR for the primary endpoint (stroke or death) in patients with vascular disease was 1.91 (1.44–2.54), which was also significant for death (1.97 [1.48–2.62]). Conclusion: Vascular disease (prior MI and PAD) is an independent risk factor for the primary endpoint of ‘stroke or death’ in patients with AF, even after adjustment for the CHADS₂ risk score, although this is driven by the impact on mortality. This reaffirms that patients with vascular disease represent a ‘high‐risk’ population, which necessitates proactive management of all cardiovascular risk factors and effective thromboprophylaxis (i.e. oral anticoagulation), which has been shown to significantly reduce the risk of stroke and death in AF.     

Prevalence and prognostic impact of electrocardiographic abnormalities in outpatients with extracardiac artery disease

Identifying cardiac disease in patients with extracardiac artery disease (ECAD) is essential for clinical decision‐making. Electrocardiography (ECG) is an easily accessible tool to unmask subclinical cardiac disease and to risk stratify patient with or without manifest cardiovascular disease (CV). We aimed to examine the prevalence and prognostic impact of ECG changes in outpatients with ECAD. Outpatients with carotid or lower extremity artery disease (n = 435) and community‐based controls (n = 397) underwent resting ECG. The patients were followed during a median of 4·8 years for CV events (hospitalization or death caused by ischaemic heart disease, cardiac arrest, heart failure, or stroke). ECG abnormalities were classified according to the Minnesota Code. Major (33% versus 15%, P<0·001) but not minor ECG abnormalities (23% versus 26%, P = 0·42) were significantly more common in patients versus controls. During the follow‐up, 141 patients experienced CV events. Both major ECG abnormalities [hazard ratio (HR) 1·58, 95% confidence interval (CI) 1·11–2·25, P = 0·012] and any ECG abnormalities (HR 1·57, 95% CI 1·06–2·33, P = 0·024) were significantly associated with CV events after adjustment for potential risk factors. In conclusion, ECG abnormalities were common in these outpatients with ECAD. Major and any ECG abnormalities were independent predictors of CV events. Addition of easily accessible ECG information might be useful in risk stratification for such patients.     

Statins after recent stroke reduces recurrence and improves survival in an aging Mediterranean population without known coronary heart disease

What is known and Objective: The effect of a statin‐based medical intervention on prevention of fatal and non‐fatal stroke recurrence and the incidence of all‐causes mortality have been explored previously in aging populations within the scope of clinical trials research. However, such evidence needs to be explored under conditions of routine clinical practice. The objective of this study was to determine whether statin therapy in patients with a first stroke episode reduces the incidence of 6‐year recurrent fatal or non‐fatal stroke and all‐cause mortality in an aging Mediterranean population without known coronary heart disease followed in routine medical practice. Methods: A retrospective study was carried out using records on death, hospitalizations owing to stroke and history of statin therapy included in the Badalona Serveis Assistencials (BSA) database. The cohort studied consisted of consecutive patients covered by the BSA health provider plan with a first‐ever acute stroke episode during January 2003 until December 2008, for whom there was available information covering the 6‐year follow‐up period. Recurrence rate (RR) and incidence rate (IR) of fatal/non‐fatal stroke and all‐causes mortality were computed. Association with statin therapy was assessed by means of calculation of relative risk (RR) and hazard ratio (HR) using multivariate logistic regression and Cox proportional hazards models controlling for confounding covariates. Results and Discussion: The cohort comprised a series of 601 consecutive patients [57% men, 75·9 (12·4) years old (88% >60 years)]. Of these, 32% received statins, which were associated with lower fatal/non‐fatal recurrent stroke RR; 7% vs. 18% [adjusted RR = 0·32 (CI: 0·16–0·61), P = 0·001] and lower IR; 16·78 vs. 45·22 events/year‐1000 subjects [adjusted HR = 0·35 (0·19–0·64), P = 0·001]. Similarly, observed all‐causes mortality was lower in the cohort receiving statins; 11% vs. 16% [adjusted RR = 0·29 (CI: 0·08–1·12), P = 0·072], and also mortality rate; 26·09 vs. 36·25 deaths/year‐1000 subjects [adjusted HR = 0·23 (0·08–0·67), P = 0·007]. What is new and Conclusions:  Statin therapy in patients with first‐ever acute stroke lowers the risk of 6‐year stroke recurrence and improves survival in an aging Mediterranean cohort. These results add additional evidence in routine clinical practice to the observed effects of statins in clinical trials.     

Low-grade inflammation can partly explain the association between the metabolic syndrome and either coronary artery disease or severity of peripheral arterial disease: the CODAM study

Background Low‐grade inflammation has been hypothesized to underlie the coronary artery disease (CAD) risk associated with the metabolic syndrome, but the evidence is not conclusive. For peripheral arterial disease (PAD; as measured by the ankle‐arm index), this association has not been studied before. The aim was to study whether the association between the metabolic syndrome and CAD or the severity of PAD can be explained by low‐grade inflammation. Methods The Cohort study Diabetes and Atherosclerosis Maastricht population includes 574 subjects, with an increased risk of type 2 diabetes, of whom 560 were included in the analyses (343 males; age: 59·5 ± 7·0 years). The inflammation markers that were measured were C‐reactive protein, interleukin 6, soluble vascular cell adhesion molecule‐1, soluble intercellular adhesion molecule‐1 and serum amyloid A. All analyses were adjusted for age, sex and smoking. Results Logistic regression showed that the metabolic syndrome was significantly associated with CAD [odds ratio (OR) = 1·86, 95% CI: 1·21; 2·84, P = 0·004]. Further adjustment for inflammatory status, as captured in a combination of the inflammation markers (using an averaged Z‐score), resulted in significant associations of both the metabolic syndrome and inflammatory status with CAD [OR_{metabolic syndrome} (95% CI) = 1·58 (1·01; 2·46), P = 0·044; OR_inflammation (95% CI) = 1·59 (1·14; 2·21), P = 0·007]. Linear regression analysis showed similar results for the ankle‐arm index. Conclusions The association between the metabolic syndrome, on the one hand, and prevalence of CAD or the severity of PAD, on the other, can be partly but not completely, 26% and 29% respectively, explained by low‐grade inflammation.     

Efficacy of aspirin for secondary prevention in patients with peripheral artery disease

Evaluation of: Berger JS, Krantz MJ, Kittelson JM, Hiatt WR. Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials. JAMA 301, 1909–1919 (2009).

Aspirin decreases the risk of cardiovascular events in patients with prior coronary heart or cerebrovascular disease. The American College of Cardiology/American Heart Association guidelines recommend a low-dose aspirin regimen (75–325 mg/day) to reduce the risk of cardiovascular events in patients with peripheral artery disease (PAD). However, the effect of aspirin for secondary prevention in patients with PAD has not been well established. The paper under evaluation performed a meta-analysis of 18 trials to investigate the effect of aspirin on cardiovascular events (nonfatal myocardial infarction, nonfatal stroke and cardiovascular death) in patients with PAD. The results of this meta-analysis in a PAD cohort revealed that treatment with aspirin did not significantly reduce the combined end point of cardiovascular events; however, aspirin resulted in a significant reduction in the incidence of nonfatal stroke. This analysis raises a number of questions regarding the overall efficacy of aspirin in PAD and what should be the optimal antiplatelet therapy in patients with PAD: aspirin, clopidogrel or perhaps a combination of aspirin and clopidogrel.     

Significance of white blood cell count and its subtypes in patients with acute coronary syndrome

Background Inflammation plays a role in the pathogenesis of coronary atherosclerosis. Materials and methods Six hundred twenty‐three patients with acute coronary syndrome (ACS) referred for coronary angiography for the first time in our hospital were enrolled in this study. White blood cell and its subtypes were measured on admission. The study population was divided into three groups based on total white blood cell count and followed up. Clinical end points were major adverse cardiac events (MACEs), including cardiogenic death, stroke, heart failure, non‐fatal myocardial infarction, rehospitalization for angina pectoris. Results The median age was 68 years (range 31–92) and 64·2% of the patients were men. The median white blood cell count was 6·48 × 10⁹ L⁻¹ (range 2·34–27·10 × 10⁹ L⁻¹). The median follow‐up duration was 21 months (range 1–116) and MACEs occurred in 167 patients. The multivariable Cox proportional hazards regression model revealed that neutrophil count [Relative risk = 1·098, 95% Confidence interval (CI): 1·010–1·193, P = 0·029) was a risk factor for MACEs. The logistic regression model revealed that lymphocyte count [Odds ratio (OR) = 1·075, 95% CI: 1·012–1·142, P = 0·018] and monocyte count (OR = 8·578, 95% CI: 2·687–27·381, P < 0·001) were predictive of stenosis ≥ 75%; Neutrophil proportion (OR = 1·060, 95% CI: 1·007–1·115, P = 0·026), monocyte count (OR = 12·370, 95% CI: 1·298–118·761, P = 0·029) were predictive of the presence of multivessel disease. Kaplan–Meier analysis of short‐term and long‐term cumulative survival showed no significant statistical differences among three groups. Conclusions Neutrophil count adds prognostic information to MACEs in ACS. Monocyte count and lymphocyte count are predictive of severity of coronary atherosclerosis.     

Coronary artery calcium score and N‐terminal pro‐B‐type natriuretic peptide as potential gatekeepers for myocardial perfusion imaging

Myocardial perfusion imaging (MPI) holds an important place as non‐invasive risk assessment in patients with intermediate risk of coronary heart disease (CHD). However, as much as 60–70% of MPI scans are normal. This study evaluates the role of coronary artery calcium scoring (CAC score) and NT‐proBNP as potential gatekeepers for MPI. Patients with intermediate risk of CHD referred for standard MPI were included. CAC score and NT‐proBNP were both assessed at the day of the stress study. Sensitivity, specificity and NPV for prediction of abnormal MPI scans were calculated for CAC, NT‐proBNP and the combination hereof. A total of 190 patients were included (mean age 61 ± 12 years, 55% female) of whom 24% had known CHD. In all 30% of the scans were abnormal. CAC score achieved the highest AUC regardless of whether patients with known CHD were included or not [AUC 0·75 95% CI (0·66–0·84) and AUC 0·79 (0·68–0·91)]. As a singular variable, CAC score was the most potent predictor with a sensitivity of 85%, specificity of 39% and NPV 88%. The combination of CAC score<10 and NT‐proBNP>26 reached a sensitivity of 98% and NPV 94%, where 8% of scans tentatively could be avoided. In patients referred for MPI with intermediate risk for CHD, a combination of CAC score and NT‐proBNP could be used to identify a group of patients where MPI could be averted with a high degree of diagnostic safety.     

Anatomical vertebral artery hypoplasia and insufficiency impairs dynamic blood flow regulation

Recent studies have suggested that vertebral artery (VA) hypoplasia is a predisposing factor for posterior cerebral stroke. We examined whether anatomical vertebrobasilar ischemia, i.e., unilateral VA hypoplasia and insufficiency, impairs dynamic blood flow regulation. Twenty‐eight female subjects were divided into three groups by defined criteria: (i) unilateral VA hypoplasia (n = 8), (ii) VA insufficiency (n = 6), and (iii) control (n = 14). Hypoplastic VA criterion was VA blood flow of 40 ml min^?1, whereas VA insufficiency criterion was net (left + right) VA blood flow of 100 ml min^?1 or less. We evaluated left, right, and net VA blood flows by ultrasonography during hypercapnia, normocapnia, and hypocapnia to evaluate VA CO₂ reactivity. The unilateral VA hypoplasia group showed lower CO₂ reactivity at hypoplastic VA than at non‐hypoplastic VA (2·65 ± 0·58 versus 3·00 ± 0·48% per mmHg, P = 0·027) and net VA CO₂ reactivity was preserved (Unilateral VA hypoplasia, 2·95 ± 0·48 versus Control, 2·93 ± 0·42% per mmHg, P = 0·992). However, the VA insufficiency group showed a lower net VA CO₂ reactivity compared to the control (2·29 ± 0·55 versus 2·93 ± 0·42% per mmHg, P = 0·032) and the unilateral VA hypoplasia (P = 0·046). VA hypoplasia reduced CO₂ reactivity, although non‐hypoplastic VA may compensate this regulatory limitation. In subjects with VA insufficiency, lowered CO₂ reactivity at the both VA could not preserve normal net VA CO₂ reactivity. These findings provide a possible physiological mechanism for the increased risk of posterior cerebral stroke in subjects with VA hypoplasia and insufficiency.     

Atherosclerosis measured by whole body magnetic resonance angiography and carotid artery ultrasound is related to arterial compliance,but not to endothelium‐dependent vasodilation – the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

Background: Arterial compliance and endothelium‐dependent vasodilation are two characteristics of the vessel wall. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, we studied the relationships between arterial compliance and endothelium‐dependent vasodilation versus atherosclerosis as measured with two imaging modalities. Methods: In the population‐based PIVUS study (1016 subjects aged 70), arterial compliance was determined by ultrasound in the carotid artery and the stroke volume to pulse pressure ratio by echocardiography, while endothelium‐dependent vasodilation was assessed by the invasive forearm technique with acetylcholine and brachial artery ultrasound. Intima‐media thickness was evaluated by ultrasound in the carotid artery (n = 954). Stenosis in the carotid, aorta, renal, upper and lower leg arteries were determined by magnetic resonance angiography in a random subsample of 306 subjects. Results: After adjustments for gender, Framingham risk score, obesity, myocardial infarction and stroke, distensibility in the carotid artery and the stroke volume to pulse pressure ratio were both significantly related to a weighted index of stenosis in the five arterial territories evaluated by magnetic resonance angiography (p<0·02 for both). Distensibility in the carotid artery (P = 0·021), but not the stroke volume to pulse pressure ratio (P = 0·08), was also significantly related to intima‐media thickness. Conclusion: In the elderly population, atherosclerosis is mainly related to arterial compliance, but not to endothelium‐dependent vasodilation in peripheral conduit or resistance vessels.     

Diagnostic performance of cardiac magnetic resonance imaging in coronary artery disease

Background: Cardiac magnetic resonance imaging (CMR) is a promising method for detecting coronary artery disease (CAD). The first reports of new diagnostic techniques indicated generally unrealistic diagnostic performance relying on retrospectively observed cut‐off values of quantitative parameters. Although visual analysis of CMR is the most applicable method for clinical work, its diagnostic performance is not fully elucidated for study components such as wall motion, perfusion and late enhancement in patients with different severity of CAD. Methods: A total of 30 subjects including 20 patients with CAD and 10 healthy volunteers were selected for the study. Of the patients, ten had stable CAD, five confirmed myocardial infarction (MI) without Q‐waves in electrocardiogram (ECG) and five confirmed MI with Q‐waves in ECG. All patients underwent coronary angiography and CMR for evaluating resting wall motion, rest and stress perfusion and late enhancement. Results: Combining the data from the three CMR techniques, 12 out of 20 patients were correctly identified as having CAD, and all controls were found to be healthy. Sensitivity, specificity, accuracy, positive and negative predictive values were 60·0%, 100·0%, 73·0%, 100·0% and 55·6%, respectively. Of the CMR components, resting wall motion and late enhancement gave the most diagnostic yield. Conclusions: We conclude that evaluation of CAD is feasible in patients with different severity of CAD using visually analysed CMR, especially when available CMR methodologies are combined together.     

N-terminal pro-brain natriuretic peptide used for the prediction of coronary artery stenosis

Background The level of the inactive N‐terminal fragment of pro‐brain (B‐type) natriuretic peptide (NT‐proBNP) is a prognostic marker in patients with acute and chronic coronary artery disease (CAD). It might also be valuable for non‐invasive diagnosis of coronary artery disease. Materials and methods The NT‐proBNP was measured in 781 consecutive patients with normal left ventricular function referred for coronary angiography owing to symptoms or signs of CAD. The diagnostic value of NT‐proBNP was assessed for predicting CAD at angiography. Results Elevated NT‐proBNP levels were associated with the extent of CAD and with the female sex (P < 0·001). The ability of NT‐proBNP to predict significant coronary disease at angiography was assessed separately for men using a cut‐off point of 85 pg mL⁻¹, positive likelihood ratio 2·2 (95% CI, 1·7–3·0), negative likelihood ratio 0·53 (95% CI 0·45–0·63) and area under the receiver‐operating‐characteristic (ROC) curve 0·72: for women, it was assessed using a cut‐off point of 165 pg mL⁻¹, positive likelihood ratio 2·4 (95% CI, 1·7–3·4), negative likelihood ratio 0·55 (95% CI, 0·44–0·70) and area under ROC curve 0·71. In multiple logistic‐regression analysis, NT‐proBNP added significant independent predictive power to other clinical variables in models predicting CAD (odds ratio 2·76, 95% CI, 1·76–4·32, P < 0·001). Conclusions The NT‐proBNP is a marker of non‐obstructive CAD and of significant coronary stenosis. In conjunction with other clinical information, measurement of NT‐proBNP with the use of sex‐specific reference ranges may improve the non‐invasive prediction of CAD.     

高机械指数灰阶谐波超声造影评价肾动脉狭窄的初步研究

目的 评价高机械指数实时灰阶谐波超声造影诊断肾动脉狭窄的临床价值.方法 怀疑肾动脉狭窄者21例,包括3例肾移植术后患者,行常规彩色多普勒超声和谐波造影检查.使用SonoVue造影剂,机械指数设置在1.0左右.超声检查结果与X线血管造影、CT血管成像、磁共振血管成像检查结果相对照.结果 常规超声诊断肾动脉狭窄的敏感性、特异性、阳性预测值、阴性预测值及准确性分别为85.7%,57.1%,80.0%,66.7%及76.2%;结合谐波造影可分别提高到100%,66.7%,88.2%,100%及90.5%.结论 高机械指数谐波超声造影能够明显提高肾动脉与周围组织的回声对比,直观显示肾动脉的流道变化,有助于对肾动脉狭窄的诊断.     

Safety and efficacy of protease‐activated receptor‐1 antagonists in patients with coronary artery disease: a meta‐analysis of randomized clinical trials

Summary. Background: Thrombin receptor antagonists blocking protease‐activated receptor‐1 (PAR‐1) on platelets represent a new class of oral antiplatelet agents for patients with atherothrombotic disease manifestations. Objectives: We investigated the safety and efficacy of PAR‐1 antagonists in patients with coronary artery disease (CAD). Patients/Methods: Randomized, placebo‐controlled trials of the PAR‐1 antagonists atopaxar or vorapaxar in CAD patients were identified. The primary safety endpoint was the composite of Thrombolysis In Myocardial Infarction (TIMI) clinically significant bleeding. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke. Results: A total of 41 647 patients from eight trials were included. PAR‐1 antagonists were associated with higher risks of TIMI clinically significant (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.39–1.57, P < 0.001), major (OR 1.46, 95% CI 1.28–1.67, P < 0.001) and minor (OR 1.67, 95% CI 1.40–2.00, P < 0.001) bleeding than placebo in the fixed‐effects model. PAR‐1 antagonists reduced the composite of death, MI or stroke as compared with placebo (OR 0.87, 95% CI 0.81–0.92, P < 0.001), driven by a lower risk of MI (OR 0.85, 95% CI 0.78–0.92, P < 0.001). Conversely, PAR‐1 antagonists and placebo did not differ in terms of risk of death (OR 0.99, 95% CI 0.90–1.09, P = 0.81) or stroke (OR 0.96, 95% CI 0.84–1.10, P = 0.59). Conclusions: PAR‐1 antagonists decrease ischemic events in patients with CAD as compared with placebo, mainly driven by a reduction in MI, at the cost of an increased risk of clinically significant bleeding.     

Resource use and costs in high-risk symptomatic peripheral artery disease patients with diabetes and prior acute coronary syndrome: a retrospective analysis

Objectives: As the prevalence of peripheral artery disease (PAD) increases there is growing concern about the associated healthcare burden. This burden has not been well-characterized in high-risk patients with concurrent diabetes and/or acute coronary syndrome (ACS). The objective of this analysis was to assess comorbidities, medication use, outcomes, services and costs for 3 high-risk symptomatic PAD groups.

Methods: This retrospective longitudinal analysis used the MarketScan Commercial Claims and Encounters Database (2005-2013). The 3 high-risk symptomatic PAD groups were (1) symptomatic PAD with/without diabetes, (2) symptomatic PAD with/without prior ACS, and (3) symptomatic PAD with/without diabetes and prior ACS. The study time frame was a period of 1-year before the earliest date of a symptomatic PAD record and 3 years post.

Results: In all, 16,663 symptomatic PAD patients were identified across the three risk groups. Mean age ranged from 66.4-67.4 years; the majority (55.0%-63.3%) were men. At 3 years post index, patients with symptomatic PAD and a risk factor had significantly higher use of beta-blockers, ACE inhibitors and statins (P<0.0007), and higher rates of all-cause and symptomatic PAD-related medical services, diagnoses and procedures (P<0.05). Clopidogrel and statins were used by ≤41.2% and ≤66.7% of symptomatic PAD patients without risk, respectively, and ≤68.9% and ≤80.2% of patients with risks. All cause and symptomatic PAD-related treatment costs (P<0.0001) were higher for symptomatic PAD patients with risks versus patients without risks where annualized all-cause cost differences ranged from $7,482 to $13,504 and annualized PAD-related cost differences ranged from $605 to $1,997.

Conclusions: Symptomatic PAD patients with diabetes and/or prior ACS have significantly higher medical resource use and costs compared to symptomatic PAD patients without these risk factors. The utilization rate of secondary prevention therapies is suboptimal; therefore, greater effort must be made to increase utilization and optimize treatment to minimize the impact of symptomatic PAD.     

High-density lipoprotein cholesterol, C-reactive protein, and prevalence and severity of coronary artery disease in 5641 consecutive patients undergoing coronary angiography

Background Although high‐density lipoprotein cholesterol (HDL‐C) and C‐reactive protein (CRP) are well‐established predictors for future cardiovascular events, little information is available regarding their correlation with the prevalence and severity of angiographically evaluated coronary artery disease (CAD). Material and methods Five thousand six hundred forty‐one consecutive patients undergoing coronary angiography for the evaluation of CAD were analysed. Cardiovascular risk factors were assessed by routine blood chemistry and questionnaire. CAD severity was graded by visual estimation of lumen diameter stenosis with significant stenoses defined as lumen diameter reduction of ≥ 70%. Coronary angiograms were graded as one‐, two‐ or three‐vessel disease, as nonsignificant CAD (lumen irregularities < 70%) or non‐CAD. Results HDL‐C (60·3 ± 18·5 vs. 51·9 ± 15·3 mg dL^?1; P < 0·001) was higher and CRP was lower (0·65 ± 1·68 vs. 1·02 ± 2·38 mg dL^?1; P < 0·001) in non‐CAD (n = 1517) compared to overall CAD patients (n = 4124). CAD patients were older (65·2 ± 10·5 years vs. 59·9 ± 11·4 years), more often diabetics (19·2% vs. 10·6%) and hypertensives (79·2% vs. 66·0%) and included more smokers (18·8% vs. 16·5%) (all P < 0·005). Low‐density lipoprotein cholesterol (124·5 ± 38·3 vs. 126·0 ± 36·3 mg dL^?1; P = NS) was similar in overall CAD and non‐CAD patients with more statin users (43·4% vs. 27·9%; P < 0·001) among CAD patients. Comparing non‐CAD with different CAD severities using analysis of variance, results did not change substantially. In a multivariate analysis, HDL‐C and CRP remained independently associated with the prevalence of CAD. In addition, HDL‐C is also a potent predictor for the severity of CAD. Conclusions In this large consecutive patient cohort, HDL‐C and CRP are independently associated with the prevalence of CAD. In this analysis, HDL‐C is an even stronger predictor for CAD than some other major classical risk factors.     

Dabigatran and rivaroxaban for prevention of venous thromboembolism--systematic review and adjusted indirect comparison

What is known and objective: Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta‐analysis, and adjusted indirect comparison. Methods: We searched PubMed, EMBASE, trial registries and regulatory documents through May 2009 for randomized controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10 mg daily) compared with enoxaparin (40–60 mg daily) in elective orthopaedic surgery. We used random effects meta‐analysis to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous thromboembolism, VTE (deep venous thrombosis, non‐fatal pulmonary embolism and all‐cause mortality), and haemorrhagic adverse events (major and clinically relevant non‐major bleeds). Adjusted indirect comparison was used for the pooled RRs of dabigatran and rivaroxaban with enoxaparin as the common control. Results: Rivaroxaban was superior to enoxaparin for the prevention of venous thromoboembolism (RR 0·56, 95% CI 0·43–0·73, P < 0·0001), with a trend for increased haemorrhage (RR 1·26, 95% CI 0·94–1·69, P = 0·13). Dabigatran was not superior to enoxaparin for prevention of VTE (RR 1·12, 95% 0·97–1·29, P = 0·12), and did not reduce haemorrhage risk (RR 1·10, 95% 0·90–1·35, P = 0·32). Adjusted indirect comparison showed that rivaroxaban was superior to dabigatran in preventing VTE, RR 0·50 (95% CI 0·37–0·68), but with a slight trend towards increased haemorrhage RR 1·14 (95% CI 0·80–1·64). What is new and conclusion: Rivaroxaban may be more effective than dabigatran for prevention of VTE after elective orthopaedic surgery but might also slightly increase the risk of haemorrhage.     

The effect of pre‐hospital statins therapy on incidence of in‐hospital death and total MACCE in patients with PCI

Objective: To investigate the influence of preoperative statin therapy on rate of major adverse cardiac and cerebrovascular events (MACCE) during hospital stay after successful percutaneous coronary intervention (PCI). Methods: Review of patients who underwent PCI between June 2003 and September 2005 (n = 3893) at Beijing Anzhen Hospital of Capital University of Medical Science. (Group I, on statins, n = 3361; group II, not on statins, n = 532). To investigate if preoperative statin therapy was independently associated with the reduction in the risk of adverse postoperative outcomes after PCI. Prognostic factors were assessed using Cox multivariate regression analysis to determine if preoperative statin therapy was independently associated with a reduction in the risk of adverse postoperative outcomes. Results: Our study demonstrated that preoperative statin therapy was not associated with a reduction in risk of mortality and overall MACCE during the hospital stay (0·3% vs. 0·4%; 1·4% vs. 1·2%P > 0·05, respectively).Compared with patients not receiving statins therapy, the hazard ratio for mortality in hospital was 0·738 (95% CI, 0·499–1·211, P = 0·229). Conclusions: Preoperative statin therapy did not reduce the risk of mortality and the rates of MACCE during the hospital stay after successful PCI. Cox multivariate regression analysis showed that independent prognostic parameters for mortality were Age, LVEF<50%, Triple vessel CAD, and DM (diabetes mellitus).     

Myeloperoxidase level in patients with stable coronary artery disease and acute coronary syndromes

Background No studies have measured plasma myeloperoxidase (MPO) across the entire spectrum of patients with coronary artery disease (CAD). The aim of the study was to compare MPO level across the entire spectrum of CAD, to assess the accuracy of MPO in predicting acute coronary syndromes and to define independent correlates of MPO level. Design This case–control study included 874 patients with angiographically proven CAD. Cases included 680 patients with CAD (382 patients with stable CAD, 107 patients with non-ST-segment elevation acute coronary syndromes and 191 patients with ST-segment elevation acute myocardial infarction). Controls included 194 subjects with normal coronary angiograms. MPO was measured using an enzyme immunoassay before angiography and heparin administration. Results MPO level [median (25th–75th percentiles)] was 74·5 (52·5–135·3) µg L⁻¹ in cases vs. 61·2 (44·6–80·9), µg L⁻¹ in controls (P < 0·001). MPO level was 61·2 (47·5–85·8), µg L⁻¹ in patients with stable CAD, 99·2 (62·2–154·9), µg L⁻¹ in patients with non-ST-segment elevation acute coronary syndromes and 129·5 (72·2–216·0) µg L⁻¹ in patients with acute myocardial infarction (P < 0·001). Elevated MPO level was associated with acute coronary syndromes with an area under receiver operating characteristic (ROC) curve of 0·731 (95% confidence interval 0·692–0·770; P < 0·001). Independent correlates of MPO level were acute coronary syndrome (P < 0·001), high-sensitivity C-reactive protein (P = 0·007), creatinine (P = 0·026), left ventricular ejection fraction (P = 0·027, negative association) and smoking (P = 0·028). Conclusions MPO level is elevated in patients with CAD and higher levels of MPO were found with progression of CAD from stable CAD to non-ST-segment elevation acute coronary syndromes and to acute myocardial infarction.     

Risk factor profile, management and prognosis of patients with peripheral arterial disease with or without coronary artery disease: results of the prospective German REACH registry cohort

Aims  Peripheral arterial disease (PAD) and coronary artery disease (CAD) are manifestations of the same underlying condition, atherothrombosis. We compared patients with PAD only with those having PAD and concomitant documented CAD in terms of characteristics, risk factors, treatment and prognosis. Methods and results  This is a subgroup analysis of the German cohort of the Reduction of Atherothrombosis for Continued Health (REACH) Registry. It includes 483 patients with PAD only, and 479 patients with PAD plus CAD. Patients with concomitant cerebrovascular disease were excluded. Symptomatic PAD was defined as intermittent claudication (IC), confirmed by ankle brachial index <0.9, or PAD-related intervention. Patients in the total cohort were predominantly elderly (mean age 67.3 ± 8.9 years), males (72.3%), current or previous smokers (80.18%), and had often abdominal obesity (49.6%). Atherosclerotic risk factors and comorbidities were highly prevalent. Patients with PAD + CAD compared to those with PAD only were significantly more intensively treated with regards to antihrombotic agents (97.1% vs. 88.8%), statins (80.2% vs. 51.6%), or ACE inhibitors/ARB (75.6% vs. 61.1%). After two-year follow-up, no significant differences between subgroups were noted for total mortality (4.6% vs. 5.5%), cardiovascular mortality (3.7% vs. 3.9%), non-fatal myocardial infarction (1.9% vs. 2.7%) but for non-fatal stroke (4.4% vs. 2.0%, P < 0.05). Conclusion  Peripheral arterial disease patients carry a high burden of risk factors and co-morbidities, and are at high risk of death and cardiovascular events. If documented CAD is absent, PAD patients are undertreated. Thus, in PAD patients, secondary cardiovascular prevention with stringent treatment of risk factors to the same extent as in CAD patients is mandatory, in line with current guidelines.