Serum tryptase detected during acute coronary syndrome is significantly related to the development of major adverse cardiovascular events after 2?years

Background

One of the greatest challenges in cardiovascular medicine is to define the best tools for performing an accurate risk stratification for the recurrence of ischemic events in acute coronary syndrome (ACS) patients.

Methods

We followed 65 ACS patients enrolled in a previous pilot study for 2 years after being discharged, focusing on the occurrence of major adverse cardiovascular events (MACE).The relationship between serum tryptase levels on admission, SYNergy between percutaneous coronary intervention with the TAXUS drug-eluting stent and the cardiac surgery score (SX-score), cardiovascular complexity and MACE at 2 years follow-up were analyzed.

Results

The ACS population was divided in two groups: patients with MACE (n = 23) and patients without MACE (n = 42).The tryptase measurement at admission (T0) and at discharge (T3) and SX-score were higher in patients who experienced MACE than in those without (p = 0.0001, p < 0.0001 and p = 0.006, respectively). Conversely, we found no significant association between MACE and C-reactive protein (CRP), and between MACE and maximum level of high-sensitivity troponin (hs-Tn) values.Among all patients with MACE, 96% belonged to the group that presented with cardiovascular complexity at the beginning of ACS index admission (p < 0.0001).The predictive accuracy of serum tryptase for MACE at follow up set at the cut-off point of 4.95 ng/ml at T0 and of 5.2 ng/ml at T3. Interestingly, patients with both the above cut-off tryptase values at T0 and at T3 presented a 1320% increase in the odds of developing MACE (p < 0.0001).

Conclusion

In ACS patients, serum tryptase measured during index admission is significantly correlated to the development of MACE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker.

Electronic supplementary material

The online version of this article (doi:10.1186/s12948-015-0013-0) contains supplementary material, which is available to authorized users.     

Comparison of the Efficacy of Rosuvastatin versus Atorvastatin in Preventing Contrast Induced Nephropathy in Patient with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention

Objectives

We prospectively compared the preventive effects of rosuvastatin and atorvastatin on contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI).

Methods

We enrolled 1078 consecutive patients with CKD undergoing elective PCI. Patients in Group 1 (n = 273) received rosuvastatin (10 mg), and those in group 2 (n = 805) received atorvastatin (20 mg). The primary end-point was the development of CIN, defined as an absolute increase in serum creatinine ≥0.5 mg/dL, or an increase ≥25% from baseline within 48–72 h after contrast medium exposure.

Results

CIN was observed in 58 (5.4%) patients. The incidence of CIN was similar in patients pretreated with either rosuvastatin or atorvastatin (5.9% vs. 5.2%, p = 0.684). The same results were also observed when using other definitions of CIN. Clinical and procedural characteristics did not show significant differences between the two groups (p>0.05). Additionally, there were no significant inter-group differences with respect to in-hospital mortality rates (0.4% vs. 1.5%, p = 0.141), or other in-hospital complications. Multivariate logistic regression analysis revealed that rosuvastatin and atorvastatin demonstrated similar efficacies for preventing CIN, after adjusting for potential confounding risk factors (odds ratio = 1.17, 95% confidence interval, 0.62–2.20, p = 0.623). A Kaplan–Meier survival analysis showed that patients taking either rosuvastatin or atorvastatin had similar incidences of all-cause mortality (9.4% vs. 7.1%, respectively; p = 0.290) and major adverse cardiovascular events (29.32% vs. 23.14%, respectively; p = 0.135) during follow-up.

Conclusions

Rosuvastatin and atorvastatin have similar efficacies for preventing CIN in patients with CKD undergoing PCI.     

High-Maintenance-Dose Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Background

Despite routine use of clopidogrel, adverse cardiovascular events recur among some patients undergoing percutaneous coronary intervention (PCI). To optimize antiplatelet therapies, we performed a meta-analysis to quantify the efficacy of high versus standard-maintenance-dose clopidogrel in these patients.

Methods

Randomized controlled trials (RCTs) comparing high (>75 mg) and standard maintenance doses of clopidogrel in patients undergoing PCI were included. The primary efficacy and safety end-points were major adverse cardiovascular/cerebrovascular events (MACE/MACCE) and major bleeding. The secondary end-points were other ischemic and bleeding adverse effects. The pooled odds ratio (OR) for each outcome was estimated.

Results

14 RCTs with 4424 patients were included. Compared with standard-maintenance-dose clopidogrel, high-maintenance-dose clopidogrel significantly reduced the incidence of MACE/MACCE (OR 0.60; 95% CI 0.43 to 0.83), stent thrombosis (OR 0.56; 95% CI 0.32 to 0.99) and target vessel revascularization (OR 0.38; 95% CI 0.20 to 0.74), without significant decrease of the risk of cardiovascular death (OR 0.92; 95% CI 0.74 to 1.13) and myocardial infarction (OR 0.83; 95% CI 0.51 to 1.33). For safety outcomes, it did not significantly increase the risk of major bleeding (OR 0.73; 95% CI 0.41 to 1.32), minor bleeding (OR 1.29; 95% CI 1.00 to 1.66) and any bleeding (OR 1.14; 95% CI 0.91 to 1.43).

Conclusion

High-maintenance-dose clopidogrel reduces the recurrence of most ischemic events in patients post-PCI without increasing the risk of bleeding complications.     

Increased Risk for Developing Major Adverse Cardiovascular Events in Stented Chinese Patients Treated with Dual Antiplatelet Therapy after Concomitant Use of the Proton Pump Inhibitor

Background

Some clinical studies have demonstrated that the proton pump inhibitor (PPI) could decrease clopidogrel platelet response and increase major adverse cardiovascular events (MACE) in white or black subjects. However, that remains to be determined in Chinese patients. In this study, we sought to determine whether there could be an increased risk for developing MACE after concomitant use of dual antiplatelet therapy (DAT) and a PPI in Chinese patients treated with percutaneous coronary intervention (PCI) and stenting.

Methods

This study was a 5-year, single-center, retrospective cohort analysis of eligible patients (n = 6188) who received DAT and a PPI concomitantly (defined as PPI users) before discharge and/or 12-month follow-up after discharge as compared with those who received DAT alone (also defined as non-PPI users, n = 1465). The incidence of recurrent MACE, such as myocardial infarction (MI), definite stent thromboses (ST), or cardiovascular death, was compared between the PPI users and non-users.

Results

PPI users had a significantly higher incidence of the MACE than non-users (13.9% vs. 10.6%; adjusted HR: 1.33; 95% CI: 1.12 – 1.57, P = 0.007). Stratified analysis revealed that concurrent use of DAT and a PPI was associated with a significantly increased risk for developing ST compared with DAT alone (1% vs. 0.4%; adjusted HR: 2.66, 95% CI: 1.16 – 5.87, P = 0.012). However, there were no significant differences in the risk of MI, cardiovascular death and other adverse events, regardless of combination of clopidogrel and a PPI.

Conclusions

The study further suggests that concomitant use of DAT and a PPI may be associated with an increased risk for developing MACE, in particular definite ST, in Chinese PCI patients after discharge as compared with use of DAT alone.     

A comparison of clinical outcomes of Chinese sirolimus-eluting stents versus foreign sirolimus-eluting stents for the treatment of coronary artery disease

Background

Chinese sirolimus-eluting stents (SES) have been widely used in recent years. However, the comparison of clinical outcomes between Chinese and foreign SES remains unknown.

Objectives

To compare the outcomes of Chinese SES (Firebird) with foreign SES (Cypher Select) in the treatment of patients undergoing percutaneous coronary intervention (PCI).

Methods

4000 consecutive patients treated with SESs from January 2008 to December 2009 were included in this study. Based on the differences of the stents, the patients were divided into a Chinese SES group (Firebird; n = 2008) and a foreign SES group (Cypher Select; n = 1992). Outcomes were monitored for 1 year. The primary clinical endpoint was major adverse cardiac events (MACE): a composite of death, non-fatal myocardial infarction (MI) and target-vessel revascularisation (TVR).

Results

No differences were observed in the incidence of MACE (17.8% vs. 18.6%, p = 0.514) and TVR rate (9.0% vs. 8.6%, p = 0.632) during 1-year follow-up.

Conclusions

Chinese SES and foreign SES have similar effects on 1-year clinical outcomes and safety.     

Multivessel revascularisation versus infarct-related artery only revascularisation during the index primary PCI in STEMI patients with multivessel disease: a meta-analysis

Background

There are controversial data regarding infarct-related artery only (IRA-PCI) revascularisation versus multivessel revascularisation (MV-PCI) in ST-elevation myocardial infarction (STEMI) patients with multivessel disease undergoing primary percutaneous coronary intervention (PCI). We performed a meta-analysis comparing outcome in same stage MV-PCI versus IRA-PCI in STEMI patients with multivessel disease.

Methods

Systematic searches of studies comparing MV-PCI with IRA-PCI in the MEDLINE and the Cochrane Database of systematic reviews were conducted. A meta-analysis was performed of all available studies. Primary outcome was all-cause mortality. Secondary endpoints were re-infarction, revascularisation, bleeding and major adverse cardiac events (MACE).

Results

A total of 15 studies were identified with a total number of 35,975 patients. Mortality rate was significantly higher in the MV-PCI group compared with the IRA-PCI group, odds ratio (OR): 1.64 (1.46–1.85). Both the incidence of re-infarction and re-PCI were significantly lower in the MV-PCI group compared with the IRA-PCI group: OR 0.54 (0.34–0.88) and OR 0.67 (0.48–0.93), respectively. Bleeding complications occurred more often in the MV-PCI group as compared with the IRA-PCI group: OR 1.24 (1.08–1.42). Rates of MACE were comparable between the two groups.

Conclusions

MV-PCI during the index of primary PCI in STEMI patients is associated with a higher mortality rate, a higher risk of bleeding complications, but lower risk of re-intervention and re-infarction and comparable rates of MACE.     

Renal Function Interferes with Copeptin in Prediction of Major Adverse Cardiac Events in Patients Undergoing Vascular Surgery

Objective

Precise perioperative risk stratification is important in vascular surgery patients who are at high risk for major adverse cardiovascular events (MACE) peri- and postoperatively. In clinical practice, the patient’s perioperative risk is predicted by various indicators, e.g. revised cardiac index (RCRI) or modifications thereof. Patients suffering from chronic kidney disease (CKD) are stratified into a higher risk category. We hypothesized that Copeptin as a novel biomarker for hemodynamic stress could help to improve the prediction of perioperative cardiovascular events in patients undergoing vascular surgery including patients with chronic kidney disease.

Methods

477 consecutive patients undergoing abdominal aortic, peripheral arterial or carotid surgery from June 2007 to October 2012 were prospectively enrolled. Primary endpoint was 30-day postoperative major adverse cardiovascular events (MACE).

Results

41 patients reached the primary endpoint, including 63.4% aortic, 26.8% carotid, and 9.8% peripheral surgeries. Linear regression analysis showed that RCRI (P< .001), pre- (P< .001), postoperative Copeptin (P< .001) and Copeptin level change (P= .001) were associated with perioperative MACE, but CKD remained independently associated with MACE and Copeptin levels. Multivariate regression showed that increased Copeptin levels added risk predictive information to the RCRI (P= .003). Especially in the intermediate RCRI categories was Copeptin significantly associated with the occurrence of MACE. (P< .05 Kruskal Wallis test). Subdivision of the study cohort into CKD stages revealed that preoperative Copeptin was significantly associated with CKD stages (P< .0001) and preoperative Copeptin measurements could not predict MACE in patients with more severe CKD stages.

Conclusion

Preoperative Copeptin loses its risk predictive potential for perioperative MACE in patients with chronic kidney disease undergoing vascular surgery.     

High-Dose Statin Pretreatment Decreases Periprocedural Myocardial Infarction and Cardiovascular Events in Patients Undergoing Elective Percutaneous Coronary Intervention: A Meta-Analysis of Twenty-Four Randomized Controlled Trials

Background

Evidence suggests that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and major adverse cardiac events (MACE) for certain patients; however, previous analyses have not considered patients with a history of statin maintenance treatment. In this meta-analysis of randomized controlled trials (RCTs), we reevaluated the efficacy of short-term high-dose statin pretreatment to prevent PMI and MACE in an expanded set of patients undergoing elective percutaneous coronary intervention.

Methods

We searched the PubMed/Medline database for RCTs that compared high-dose statin pretreatment with no statin or low-dose statin pretreatment as a prevention of PMI and MACE. We evaluated the incidence of PMI and MACE, including death, spontaneous myocardial infarction, and target vessel revascularization at the longest follow-up for each study for subgroups stratified by disease classification and prior low-dose statin treatment.

Results

Twenty-four RCTs with a total of 5,526 patients were identified. High-dose statin pretreatment was associated with 59% relative reduction in PMI (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.34–0.49; P<0.00001) and 39% relative reduction in MACE (OR: 0.61; 95% CI: 0.45–0.83; P = 0.002). The benefit of high-dose statin pretreatment on MACE was significant for statin-naive patients (OR: 0.69; 95% CI: 0.50–0.95; P = 0.02) and prior low dose statin-treated patients (OR: 0.28; 95% CI: 0.12–0.65; P = 0.003); and for patients with acute coronary syndrome (OR: 0.52; 95% CI: 0.34–0.79; P = 0.003), but not for patients with stable angina (OR: 0.71; 95% CI 0.45–1.10; P = 0.12). Long-term effects on survival were less obvious.

Conclusions

High-dose statin pretreatment can result in a significant reduction in PMI and MACE for patients undergoing elective PCI. The positive effect of high-dose statin pretreatment on PMI and MACE is significant for statin-naïve patients and patients with prior treatment. The positive effect of high-dose statin pretreatment on MACE is significant for patients with acute coronary syndrome.     

Magnesium Modifies the Cardiovascular Mortality Risk Associated with Hyperphosphatemia in Patients Undergoing Hemodialysis: A Cohort Study

Background

In vitro studies have shown inhibitory effects of magnesium (Mg) on phosphate-induced calcification of vascular smooth muscle cells, raising the possibility that maintaining a high Mg level may be useful for reducing cardiovascular risks of patients with hyperphosphatemia. We examined how serum Mg levels affect the association between serum phosphate levels and the risk of cardiovascular mortality in patients undergoing hemodialysis.

Methods

A nationwide register-based cohort study was conducted using database of the Renal Data Registry of the Japanese Society for Dialysis Therapy in 2009. We identified 142,069 patients receiving in-center hemodialysis whose baseline serum Mg and phosphate levels were available. Study outcomes were one-year cardiovascular and all-cause mortality. Serum Mg levels were categorized into three groups (lower, <2.7 mg/dL; intermediate, ≥2.7, <3.1 mg/dL; and higher, ≥3.1 mg/dL).

Results

During follow-up, 11,401 deaths occurred, out of which 4,751 (41.7%) were ascribed to cardiovascular disease. In multivariable analyses, an increase in serum phosphate levels elevated the risk of cardiovascular mortality in the lower- and intermediate-Mg groups, whereas no significant risk increment was observed in the higher-Mg group. Moreover, among patients with serum phosphate levels of ≥6.0 mg/dL, the cardiovascular mortality risk significantly decreased with increasing serum Mg levels (adjusted odds ratios [95% confidence intervals] of the lower-, intermediate-, and higher-Mg groups were 1.00 (reference), 0.81 [0.66–0.99], and 0.74 [0.56–0.97], respectively.). An interaction between Mg and phosphate on the risk of cardiovascular mortality was statistically significant (P = 0.03).

Conclusion

Serum Mg levels significantly modified the mortality risk associated with hyperphosphatemia in patients undergoing hemodialysis.     

Efficacy and Safety of Intracoronary versus Intravenous Administration of Tirofiban during Percutaneous Coronary Intervention for Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials

Background

Percutaneous coronary intervention (PCI) is known as the most effective treatment for acute coronary syndrome (ACS). However, without proper therapy and patient management, stent thrombosis after PCI may lead to another myocardial infarction. In addition to aspirin and clopidogrel, tirofiban is often used as an antiplatelet therapy in patients with ACS. To date, there has been no comprehensive evaluation of the efficacy and safety of intracoronary (IC) tirofiban administration for ACS patients undergoing PCI compared with intravenous (IV) administration. Therefore, this meta-analysis was conducted to investigate the clinical efficiency and safety of IC versus intravenous (IV) tirofiban in ACS patients undergoing PCI.

Methods

We searched PubMed and Medline for randomized controlled trials (RCTs) comparing IC versus IV administration of tirofiban in ACS patients undergoing PCI. We evaluated the effects of tirofiban on thrombolysis in myocardial infarction (TIMI) grade 3 flow after PCI, TIMI myocardial perfusion grade 3 (TMP grade 3), left ventricular ejection fraction (LVEF), major adverse cardiovascular events (MACE), target vessel revascularization (TVR), death, reinfarction and adverse drug effects (specifically bleeding events).

Results

Seven trials involving 1,027 patients were included in this meta-analysis. IC administration of tirofiban significantly increased TIMI grade 3 flow (OR 2.11; 95% CI 1.02 to 4.37; P = 0.04) and TMP grade 3 (OR 2.67; 95% CI 1.09 to 6.49; P = 0.03, I² = 64%) while reducing MACE (OR 0.46, 95% CI: 0.28 to 0.75; P = 0.002) compared with IV administration of tirofiban. No significant differences were observed in the occurrence of TVR, death, reinfarction and the incidence of bleeding events between the two groups.

Conclusions

This meta-analysis supports the use of IC over IV administration of tirofiban in patients with ACS to improve TIMI flow, TMP flow and MACE. However, there was no statistically significant difference in the risk of bleeding complications between the two groups.     

Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis

Background

Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury.

Methods and Results

Medline, EMBASE and Cochrane databases were searched for randomized clinical trials comparing remote ischemic conditioning, regardless of timing, with no conditioning. Two investigators independently selected suitable trials, assessed trial quality and extracted data. 23 studies in patients undergoing cardiac surgery (15 studies), percutaneous coronary intervention (four studies) and vascular surgery (four studies), comprising in total 1878 patients, were included in this review. Compared to no conditioning, remote ischemic conditioning did not reduce mortality (odds ratio 1.22 [95% confidence interval 0.48, 3.07]) or major adverse cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as was peak troponin release (standardized mean difference −0.28 [−0.47, −0.09]).

Conclusion

There is no evidence that remote ischemic conditioning reduces mortality associated with ischemic events; nor does it reduce major adverse cardiovascular events. However, remote ischemic conditioning did reduce the incidence of peri-procedural myocardial infarctions, as well as the release of troponin.     

Relationship between Serum Bilirubin and Left Ventricular Hypertrophy in Patients with Essential Hypertension

Background

Prospective studies have found low bilirubin levels were an important predictive factor of cardiovascular events. However, few have yet investigated possible association between serum bilirubin level and LVH in essential hypertension. The aim of the present study was to evaluate the relationship between serum bilirubin levels with LVH in newly diagnosed hypertension patients.

Methods

The present study evaluated the relationship between serum total bilirubin level and left ventricle hypertrophy (LVH) in newly diagnosed hypertensive patients with a sample size of 344. We divided subjects into LVH group (n=138) and non-LVH group (n=206). Physical examination, laboratory tests and echocardiography were conducted. The multivariate logistic regression model was used to verify the independent association between RDW and LVH.

Results

Our results found that patients with LVH had lower bilirubin levels than non-LVH ones. Stepwise multiple linear regression analysis showed total bilirubin level (B=-0.017, P=0.008) was negatively associated with left ventricle mass index (LVMI) even adjusting for some confounders. The multiples logistic regression found total bilirubin level was independently related with of LVH, as a protective factors (OR=0.91, P=0.010).

Conclusion

As a routine and quick laboratory examination index, serum bilirubin may be treated as novel marker for evaluating LVH risk in hypertensive patients. Cohort study with larger sample size are needed.     

Circulating Progenitor Cell Count for Cardiovascular Risk Stratification: A Pooled Analysis

Background

Circulating progenitor cells (CPC) contribute to the homeostasis of the vessel wall, and a reduced CPC count predicts cardiovascular morbidity and mortality. We tested the hypothesis that CPC count improves cardiovascular risk stratification and that this is modulated by low-grade inflammation.

Methodology/Principal Findings

We pooled data from 4 longitudinal studies, including a total of 1,057 patients having CPC determined and major adverse cardiovascular events (MACE) collected. We recorded cardiovascular risk factors and high-sensitive C-reactive protein (hsCRP) level. Risk estimates were derived from Cox proportional hazard analyses. CPC count and/or hsCRP level were added to a reference model including age, sex, cardiovascular risk factors, prevalent CVD, chronic renal failure (CRF) and medications. The sample was composed of high-risk individuals, as 76.3% had prevalent CVD and 31.6% had CRF. There were 331 (31.3%) incident MACE during an average 1.7±1.1 year follow-up time. CPC count was independently associated with incident MACE even after correction for hsCRP. According to C-statistics, models including CPC yielded a non-significant improvement in accuracy of MACE prediction. However, the integrated discrimination improvement index (IDI) showed better performance of models including CPC compared to the reference model and models including hsCRP in identifying MACE. CPC count also yielded significant net reclassification improvements (NRI) for CV death, non-fatal AMI and other CV events. The effect of CPC was independent of hsCRP, but there was a significant more-than-additive interaction between low CPC count and raised hsCRP level in predicting incident MACE.

Conclusions/Significance

In high risk individuals, a reduced CPC count helps identifying more patients at higher risk of MACE over the short term, especially in combination with a raised hsCRP level.     

Effect of HDL-Raising Drugs on Cardiovascular Outcomes: A Systematic Review and Meta-Regression

Background

Substantial residual cardiovascular risk remains after optimal LDL lowering in patients of established coronary artery disease. A number of therapeutic agents that raise HDL-C have been tested in clinical trials to cover this risk. However, the results of clinical trials are conflicting.

Objectives

To determine whether raising HDL-C with pharmacologic therapies translates into beneficial cardiovascular outcomes and to find out if this change was proportional to the percentage change in HDL levels.

Methods

Electronic and printed sources were searched up to August, 2013 for randomised controlled trials (RCTs) using at least one of the HDL raising therapies for secondary prevention of adverse cardiovascular events over optimal LDL levels. Data from eligible studies were pooled for the following outcomes: all cause mortality, cardiovascular disease mortality, hospitalization for unstable angina, non-fatal myocardial infarction, coronary revascularization and ischemic stroke. Mantel Haensnzel fixed effect model was used preferentially. Meta-regression was done to see the correlation of change in HDL levels and cardiovascular outcomes. Pooled odds ratios with 95% confidence interval (CI) were calculated.

Results

A total of 12 RCTs including 26,858 patients with follow up period ranging from 1 year to 6.2 years were included in the analysis. Pooled analysis showed no significant difference in all-cause mortality between the treatment and control group (Pooled OR 1.07; 95% CI 0.98–1.16, p = 0.15). No significant difference was found between the groups for any of the secondary outcomes. Similarly no correlation was seen between percentage change in HDL and adverse cardiovascular outcomes on meta-regression analysis.

Conclusion

Increasing HDL levels via pharmacological manipulation beyond optimal lipid lowering therapy for secondary prevention is not beneficial.     

Treatment of non-culprit lesions detected during primary PCI: long-term follow-up of a randomised clinical trial

Background

There are conflicting data regarding optimal treatment of non-culprit lesions detected during primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). We aimed to investigate whether ischaemia-driven early invasive treatment improves the long-term outcome and prevents major adverse cardiac events (MACE).

Methods

121 patients with at least one non-culprit lesion were randomised in a 2:1 manner, 80 were randomised to early fractional flow reserve (FFR)-guided PCI (invasive group), and 41 to medical treatment (conservative group). The primary endpoint was MACE at 3 years.

Results

Three-year follow-up was available in 119 patients (98.3 %). There was no significant difference in all-cause mortality between the invasive and conservative strategy, 4 patients (3.4 %) died, all in the invasive group (P = 0.29). Re-infarction occurred in 14 patients (11.8 %) in the invasive group versus none in the conservative group (p = 0.002). Re-PCI was performed in 7 patients (8.9 %) in the invasive group and in 13 patients (32.5 %) in the conservative group (P = 0.001). There was no difference in MACE between these two strategies (35.4 vs 35.0 %, p = 0.96).

Conclusions

In STEMI patients with MVD, early FFR-guided additional revascularisation of the non-culprit lesion did not reduce MACE at three-year follow-up compared with a more conservative strategy. The rate of MACE in the invasive group was predominantly driven by death and re-infarction, whereas in the conservative group the rate of MACE was only driven by repeat interventions.     

Cardiovascular events in patients received combined fibrate/statin treatment versus statin monotherapy: Acute Coronary Syndrome Israeli Surveys data

Background

The effect of combination of fibrate with statin on major adverse cardiovascular events (MACE) following acute coronary syndrome (ACS) hospitalization is unclear. The main aim of this study was to investigate the 30-day rate of MACE in patients who participated in the nationwide ACS Israeli Surveys (ACSIS) and were treated on discharge with a fibrate (mainly bezafibrate) and statin combination vs. statin alone.

Methods

The study population comprised 8,982 patients from the ACSIS 2000, 2002, 2004, 2006, 2008 and 2010 enrollment waves who were alive on discharge and received statin. Of these, 8,545 (95%) received statin alone and 437 (5%) received fibrate/statin combination. MACE was defined as a composite measure of death, recurrent MI, recurrent ischemia, stent thrombosis, ischemic stroke and urgent revascularization.

Results

Patients from the combination group were younger (58.1±11.9 vs. 62.9±12.6 years). However, they had significantly more co-morbidities (hypertension, diabetes), current smokers and unfavorable cardio-metabolic profiles (with respect to glucose, total cholesterol, triglyceride and HDL-cholesterol). Development of MACE was recorded in 513 (6.0%) patients from the statin monotherapy group vs. 13 (3.2%) from the combination group, p = 0.01. 30-day re-hospitalization rate was significantly lower in the combination group: 68 (15.6%) vs. 1691 (19.8%) of patients, respectively; p = 0.03. Multivariable analysis identified the fibrate/statin combination as an independent predictor of reduced risk of MACE with odds ratio of 0.54, 95% confidence interval 0.32–0.94.

Conclusion

A significantly lower risk of 30-day MACE rate was observed in patients receiving combined fibrate/statin treatment following ACS compared with statin monotherapy. However, caution should be exercised in interpreting these findings taking into consideration baseline differences between our observational study groups.     

Dickkopf-1 as a Novel Predictor Is Associated with Risk Stratification by GRACE Risk Scores for Predictive Value in Patients with Acute Coronary Syndrome: A Retrospective Research

Objective

Dickkopf-1 (DKK-1), a major regulator of the Wnt pathway, plays an important role in cardiovascular disease. However, no study has evaluated the association of DKK-1 and acute coronary syndrome (ACS). We investigated this association and whether the Global Registry of Acute Coronary Events (GRACE) hospital-discharge risk score predicting major adverse cardiac events (MACE) can be improved by adding the DKK-1 value.

Methods

We enrolled 291 patients (46 with ST-segment elevation myocardial infarction [STEMI] and 245 with non-ST elevated ACS [NSTE-ACS]) who were divided into groups by tertiles of baseline plasma DKK-1 level measured by ELISA. The GRACE risk score was calculated and predictive value alone and together with DKK-1 and/or high-sensitivity C-reactive protein (hs-CRP) level were assessed, respectively.

Results

Compared with patients with NSTE-ACS, those with STEMI had higher plasma DKK-1 level at baseline (P = 0.006). Plasma DKK-1 level was correlated with hs-CRP level (r = 0.295, P<0.001) and was greater with high than intermediate or low GRACE scores (P = 0.002 and P<0.001, respectively). We found 44 (15.1%) MACEs during a median 2-year follow-up. DKK-1 levels were higher for patients with than without events (P<0.001). The rate of MACE increased with increasing DKK-1 level (P<0.001). The area under the receiver operating characteristic curve for GRACE score with MACE was 0.524 and improved to 0.791 with the addition of hs-CRP level, 0.775 with the addition of DKK-1 level and 0.847 with both values added.

Conclusions

DKK-1 is an independent predictor of long-term MACE of patients with ACS. The long-term predictive ability of post-discharge GRACE score may be enhanced by adding DKK-1 level.     

Genetic variants of diabetes risk and incident cardiovascular events in chronic coronary artery disease

Objective

To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence.

Methods

From the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve.

Results

Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610).

Conclusions

Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease.

Clinical Trial Registration Information

Medicine, Angioplasty, or Surgery Study (MASS II). Unique identifier: ISRCTN66068876 URL.     

Resistant Hypertension,Patient Characteristics,and Risk of Stroke

Background

Little is known about the prognosis of resistant hypertension (RH) in Asian population. This study aimed to evaluate the impacts of RH in Taiwanese patients with hypertension, and to ascertain whether patient characteristics influence the association of RH with adverse outcomes.

Methods and Results

Patients aged ≥45 years with hypertension were identified from the National Health Insurance Research Database. Medical records of 111,986 patients were reviewed in this study, and 16,402 (14.6%) patients were recognized as having RH (continuously concomitant use of ≥3 anti-hypertensive medications, including a diuretic, for ≥2 years). Risk of major adverse cardiovascular events (MACE, a composite of all-cause mortality, acute coronary syndrome, and stroke [included both fatal and nonfatal events]) in patients with RH and non-RH was analyzed. A total of 11,856 patients experienced MACE in the follow-up period (average 7.1±3.0 years). There was a higher proportion of females in the RH group, they were older than the non-RH (63.1 vs. 60.5 years) patients, and had a higher prevalence of cardiovascular co-morbidities. Overall, patients with RH had higher risks of MACE (adjusted HR 1.17; 95%CI 1.09–1.26; p<0.001). Significantly elevated risks of stroke (10,211 events; adjusted HR 1.17; 95%CI 1.08–1.27; p<0.001), especially ischemic stroke (6,235 events; adjusted HR 1.34; 95%CI 1.20–1.48; p<0.001), but not all-cause mortality (4,594 events; adjusted HR 1.06; 95%CI 0.95–1.19; p = 0.312) or acute coronary syndrome (2,145 events; adjusted HR 1.17; 95%CI 0.99–1.39; p = 0.070) were noted in patients with RH compared to those with non-RH. Subgroup analysis showed that RH increased the risks of stroke in female and elderly patients. However, no significant influence was noted in young or male patients.

Conclusions

Patients with RH were associated with higher risks of MACE and stroke, especially ischemic stroke. The risks were greater in female and elderly patients than in male or young patients.     

The Impact of SYNTAX Score of Non-Infarct-Related Artery on Long- Term Outcome among Patients with Acute ST Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Objective

We investigated the impact of the severity of stenosis in a non-infarct-related artery (IRA) on the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Methods

Three hundred one consecutive patients (age: 59.7 ± 13.2 years, 85.5% men) underwent primary PCI during 2009–2012. Receiver operating characteristic curve analysis found the optimal cutoff for non-IRA SYNTAX score (SS) to be 2.5. We divided the patients into two groups according to this cutoff value.

Results

By multivariable analysis, non-IRA SS (≥2.5) was an independent predictor of major adverse cardiac events (hazard ratio [HR]: 2.15, 95% confidence interval [CI]: 1.21–3.79, P  =  0.008) and all-cause mortality (HR: 3.49, 95% CI: 1.13–10.8, P  =  0.03). However, the prediction of cardiovascular mortality had only borderline significance (HR: 3.29, 95% CI: 0.90–12.08, P  =  0.07).

Conclusion

STEMI patients treated with primary PCI and moderate to severe non-IRA stenosis (SS ≥2.5) have more subsequent cardiac events. Those populations should be treated with more aggressive preventive and medical management.