Smoking Cessation in People With and Without Diabetes After Acute Coronary Syndrome.

INTRODUCTION: People with diabetes smoke at similar rates as those without diabetes, with cardiovascular consequences. Smoking cessation rates were compared between people with and without diabetes 1 year after an acute coronary syndrome (ACS). AIMS AND METHODS: People with ACS who smoked and were part of an observational prospective multicenter study in Switzerland were included from 2007 to 2017 and followed for 12 months. Seven-day point prevalence abstinence was assessed at 12 months follow-up. Association between diabetes and smoking cessation was assessed using multivariable-adjusted logistical regression model. RESULTS: 2457 people with ACS who smoked were included, the mean age of 57 years old, 81.9% were men and 13.3% had diabetes. At 1 year, smoking cessation was 35.1% for people with diabetes and 42.6% for people without diabetes (P-value .01). After adjustment for age, sex, and educational level, people with diabetes who smoked were less likely to quit smoking compared with people without diabetes who smoked (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.59-0.98, P-value = .037). The multivariable-adjusted model, with further adjustments for personal history of previous cardiovascular disease and cardiac rehabilitation attendance, attenuated this association (OR 0.85, 95% CI 0.65-1.12, P-value = .255). Among people with diabetes, cardiac rehabilitation attendance was a positive predictor of smoking cessation, and personal history of cardiovascular disease was a negative predictor of smoking cessation. CONCLUSIONS: People with diabetes who smoke are less likely to quit smoking after an ACS and need tailored secondary prevention programs. In this population, cardiac rehabilitation is associated with increased smoking cessation. IMPLICATIONS: This study provides new information on smoking cessation following ACSs comparing people with and without diabetes. After an ACS, people with diabetes who smoked were less likely to quit smoking than people without diabetes. Our findings highlight the importance of tailoring secondary prevention to people with diabetes.

Long-term effects of systematic smoking cessation counselling during acute coronary syndrome, a multicentre before-after study.

TRIAL DESIGN: In the Special Program University Medicine-Acute Coronary Syndromes (SPUM-ACS) observational study (clinical trial registration: NCT01000701), a multicentre before-after clinical trial, we assessed 5-year outcome after acute coronary syndrome, comparing a systematic with an opportunistic smoking cessation counselling phase. METHODS: We studied smokers who were hospitalised for acute coronary syndromes (ACS), and we assessed self-reported smoking cessation, incidence of cardiovascular events and mortality 5 years after hospital discharge. In the observational phase, from August 2009 to October 2010, only smokers who requested smoking cessation counselling received it during hospitalisation. In the interventional phase, from November 2010 to February 2012, hospitalised smokers with ACS were systematically offered intensive smoking cessation counselling including four telephone calls within 2 months of discharge. Because of the before-after design, the care givers were aware of study phase. The objective was to assess whether systematic counselling to every smoker with ACS has an impact on the long-term smoking cessation rate, incidence of cardiovascular events and mortality. Missing data on smoking cessation were analysed with multiple imputation. The study was not powered to assess differences in 5-year smoking cessation rates or cardiovascular outcomes. RESULTS: Overall, 458 smokers with ACS were included at baseline (225 during the intervention phase and 233 during the observation phase). At 5 years, 286 (62.4%) reported their smoking status (140 for the intervention phase and 146 for the observation phase) and 51 (11.1%) had died. There was no statistically significant difference in the abstinence rate between the interventional phase (75/140, 54%), and the observational phase (68/146, 47%), with a risk ratio with multiple imputation adjusted for age, sex, education and ACS type of 1.13 (95% confidence interval [CI] 0.84-1.51, p = 0.4). The 5-year risk of major acute cardiovascular event was similar in the intervention phase as compared with the observational phase. The multivariate adjusted hazard ratio for all-cause mortality was 0.84 (95% CI 0.45-1.60, p = 0.6). CONCLUSIONS: In this controlled long-term interventional study, systematic intensive smoking cessation counselling in all hospitalised smokers with ACS did not increase 5-year smoking cessation rates, nor decrease cardiovascular event recurrence, as compared with opportunistic smoking cessation counselling during hospitalization.

Smoking cessation and depression after acute coronary syndrome.

Smoking and depression are risk factors for acute coronary syndrome (ACS) that often co-exist. We investigated the evolution of depression according to smoking cessation one-year after ACS. Data from 1822 ACS patients of the Swiss multicenter SPUM-ACS cohort study were analyzed over a one-year follow-up. Participants were classified in three groups based on smoking status one-year post-ACS - continuous smokers, smokers who quit within the year, and non-smokers. Depression status at baseline and one-year was assessed with the Center for Epidemiologic Studies Depression scale (CES-D) and antidepressant drug use. A CES-D score ≥ 16 defined depression. A multivariate-adjusted logistic regression model was used to calculate odds ratios (OR) between groups. The study sample mean age was 62.4 years and females represented 20.8%. At baseline, 22.6% were depressed, 40.9% were smokers, and 47.5% of these quit smoking over the year post-ACS. In comparison to depressed continuous smokers, depressed smokers who quit had an adjusted OR 2.59 (95% confidence interval (CI) 1.27-5.25) of going below a CES-D score of 16 or not using antidepressants. New depression at one-year was found in 24.4% of non-depressed smokers who quit, and in 27.1% of non-depressed continuous smokers, with an adjusted OR 0.85 (95% CI 0.55-1.29) of moving to a CES-D score of ≥16 or using antidepressants. In conclusion, smokers with depression at time of ACS who quit smoking improved their depression more frequently compared to continuous smokers. The incidence of new depression among smokers who quit after ACS was similar compared to continuous smokers.

Cysteine-Rich Angiogenic Inducer 61 Improves Prognostic Accuracy of GRACE (Global Registry of Acute Coronary Events) 2.0 Risk Score in Patients With Acute Coronary Syndromes.

Background It remains unclear whether the novel biomarker cysteine-rich angiogenic inducer 61 (CCN1) adds incremental prognostic value to the GRACE 2.0 (Global Registry of Acute Coronary Events) risk score and biomarkers high-sensitivity Troponin T, hsCRP (high-sensitivity C-reactive protein), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in patients with acute coronary syndromes. Methods and Results Patients referred for coronary angiography with a primary diagnosis of acute coronary syndromes were enrolled in the Special Program University Medicine - Acute Coronary Syndromes and Inflammation cohort. The primary/secondary end points were 30-day/1-year all-cause mortality and the composite of all-cause mortality or myocardial infarction as used in the GRACE risk score. Associations between biomarkers and outcome were assessed using log-transformed biomarker values and the GRACE risk score (versions 1.0 and 2.0). The incremental value of CCN1 beyond a reference model was assessed using Harrell's C-statistics calculated from a Cox proportional-hazard model. The P value of the C-statistics was derived from a likelihood ratio test. Among 2168 patients recruited, 1732 could be analyzed. CCN1 was the strongest single predictor of all-cause mortality at 30 days (hazard ratio [HR], 1.77 [1.31, 2.40]) and 1 year (HR, 1.81 [1.47, 2.22]). Adding CCN1 alone to the GRACE 2.0 risk score improved C-statistics for prognostic accuracy of all-cause mortality at 30 days (0.87-0.88) and 1 year (0.81-0.82) and when combined with high-sensitivity Troponin T, hsCRP, NT-proBNP for 30 days (0.87-0.91), and for 1-year follow-up (0.81-0.84). CCN1 also increased the prognostic value for the composite of all-cause mortality or myocardial infarction. Conclusions CCN1 predicts adverse outcomes in patients with acute coronary syndromes adding incremental information to the GRACE risk score, suggesting distinct underlying molecular mechanisms. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01000701.

Improving 1-year mortality prediction in ACS patients using machine learning.

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) score is an established clinical risk stratification tool for patients with acute coronary syndromes (ACS). We developed and internally validated a model for 1-year all-cause mortality prediction in ACS patients. METHODS: Between 2009 and 2012, 2'168 ACS patients were enrolled into the Swiss SPUM-ACS Cohort. Biomarkers were determined in 1'892 patients and follow-up was achieved in 95.8% of patients. 1-year all-cause mortality was 4.3% (n = 80). In our analysis we consider all linear models using combinations of 8 out of 56 variables to predict 1-year all-cause mortality and to derive a variable ranking. RESULTS: 1.3% of 1'420'494'075 models outperformed the GRACE 2.0 Score. The SPUM-ACS Score includes age, plasma glucose, NT-proBNP, left ventricular ejection fraction (LVEF), Killip class, history of peripheral artery disease (PAD), malignancy, and cardio-pulmonary resuscitation. For predicting 1-year mortality after ACS, the SPUM-ACS Score outperformed the GRACE 2.0 Score which achieves a 5-fold cross-validated AUC of 0.81 (95% CI 0.78-0.84). Ranking individual features according to their importance across all multivariate models revealed age, trimethylamine N-oxide, creatinine, history of PAD or malignancy, LVEF, and haemoglobin as the most relevant variables for predicting 1-year mortality. CONCLUSIONS: The variable ranking and the selection for the SPUM-ACS Score highlight the relevance of age, markers of heart failure, and comorbidities for prediction of all-cause death. Before application, this score needs to be externally validated and refined in larger cohorts. CLINICAL TRIAL REGISTRATION: NCT01000701.

Impact of malignancy on clinical outcomes in patients with acute coronary syndromes.

BACKGROUND: The impact of cancer on survival in patients with coronary artery disease has not been well defined. We designed the present study to explore the prevalence and prognostic influence of cancer in patients with acute coronary syndrome (ACS). METHODS: 2'132 patients with ACS were enrolled in the prospective, multicenter Special Program University Medicine ACS (SPUM-ACS) cohort. The primary endpoints of major cardiovascular and cerebrovascular events (MACCE) and death were independently adjudicated at 30-day and at one-year follow-up. RESULTS: Of the 2'132 ACS patients 7.74% (n = 165) had cancer. At 30-day, except for net adverse clinical events (NACE defined as MACCE plus major bleeding), outcomes did not differ significantly between the two groups. At one year, MACCE rate was higher in cancer than in non-cancer patients (21.8 vs. 12.2%, p < 0.001). Even after adjusting for covariates, one-year all-cause mortality was higher in cancer patients than in those without (30.3% vs. 11.9%; p < 0.0001) as was cardiovascular mortality (15.7% vs. 5.9%; p < 0.001) and revascularization (12.7% vs. 5.5%, p < 0.001). Net adverse clinical events were also higher in patients with cancer at one-year follow-up (33.9% vs. 19.8%, p < 0.001). A sub-analysis revealed that those with solid tumors, but not hematological malignancies were more likely to experience MACCE (p = 0.001) as well as a higher cardiovascular and all cause mortality (both p = 0.001) at one-year follow-up. CONCLUSIONS: ACS patients with cancer, specifically those with solid tumors, have a higher MACCE as well as cardiovascular and total mortality rate than non-cancer patients independent of cardiovascular risk factors. Thus, cancer is an independent risk factor for a poor outcome in ACS patients.

Diabetes and baseline glucose are associated with inflammation, left ventricular function and short- and long-term outcome in acute coronary syndromes: role of the novel biomarker Cyr 61.

BACKGROUND: Hyperglycemia in the setting of an acute coronary syndrome (ACS) impacts short term outcomes, but little is known about longer term effects. We therefore designed this study to firstly determine the association between hyperglycemia and short term and longer term outcomes in patients presenting with ACS and secondly evaluate the prognostic role of diabetes, body mass index (BMI) and the novel biomarker Cyr61 on outcomes. METHODS: The prospective Special Program University Medicine-Acute Coronary Syndrome (SPUM-ACS) cohort enrolled 2168 patients with ACS between December 2009 and October 2012, of which 2034 underwent PCI (93.8%). Patients were followed up for 12 months. Events were independently adjudicated by three experienced cardiologists. Participants were recruited from four tertiary hospitals in Switzerland: Zurich, Geneva, Lausanne and Bern. Participants presenting with acute coronary syndromes and who underwent coronary angiography were included in the analysis. Patients were grouped according to history of diabetes (or HbA1c greater than 6%), baseline blood sugar level (BSL; < 6, 6-11.1 and > 11.1 mmol/L) and body mass index (BMI). The primary outcome was major adverse cardiac events (MACE) which was a composite of myocardial infarction, stroke and all-cause death. Secondary outcomes included the individual components of the primary endpoint, revascularisations, bleeding events (BARC classification) and cerebrovascular events (ischaemic or haemorrhagic stroke or TIA). RESULTS: Patients with hyperglycemia, i.e. BSL ≥ 11.1 mmol/L, had higher levels of C-reactive protein (CRP), white blood cell count (WBC), creatinine kinase (CK), higher heart rates and lower left ventricular ejection fraction (LVEF) and increased N-terminal pro-brain natriuretic peptide. At 30 days and 12 months, those with BSL ≥ 11.1 mmol/L had more MACE and death compared to those with BSL < 6.0 mmol/L or 6.0-11.1 mmol/L (HR-ratio 4.78 and 6.6; p < 0.001). The novel biomarker Cyr61 strongly associated with high BSL and STEMI and was independently associated with 1 year outcomes (HR 2.22; 95% CI 1.33-3.72; Tertile 3 vs. Tertile 1). CONCLUSIONS AND RELEVANCE: In this large, prospective, independently adjudicated cohort of in all comers ACS patients undergoing PCI, both a history of diabetes and elevated entry glucose was associated with inflammation and increased risk of MACE both at short and long-term. The mediators might involve increased sympathetic activation, inflammation and ischemia as reflected by elevated Cyr61 levels leading to larger levels of troponin and lower LVEF. Trial registration Clinical Trial Registration Number: NCT01000701. Registered October 23, 2009.

Prognostic value of elevated lipoprotein(a) in patients with acute coronary syndromes.

BACKGROUND: Minimal lipoprotein(a) [Lp(a)] target values are advocated for high-risk cardiovascular patients. We investigated the prognostic value of Lp(a) in the acute setting of patients with acute coronary syndromes (ACS). MATERIALS AND METHODS: Plasma levels of Lp(a) were collected at time of angiography from 1711 patients hospitalized for ACS in a multicentre Swiss prospective cohort. Associations between elevated Lp(a) ≥30 mg/dL (cut-off corresponding to the 75th percentile of the assay) or Lp(a) tertiles at baseline, and major adverse cardiovascular events (MACE) at 1 year, defined as a composite of cardiac death, myocardial infarction or stroke, were assessed using hazard ratios (HR) and 95% confidence intervals (CI) adjusting for traditional cardiovascular risk factors (age, sex, smoking, diabetes, hypertension, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and triglycerides. RESULTS: Lp(a) levels range between 2.5 and 132 mg/dL with a median value of 6 mg/dL and a mean value of 14.2 mg/dL. A total of 276 patients (23.0%) had Lp(a) plasma levels ≥30 mg/dL. Patients with elevated Lp(a) were more likely to be of female gender and to have higher levels of total cholesterol, LDL-C, HDL-C and triglycerides. Higher Lp(a) was associated with failure to reach the LDL-C target <1.8 mmol/L at 1 year (HR 1.71, 95% CI 1.13-2.58, P = 0.01). No association was found between elevated Lp(a) and MACE at 1 year (HR 1.05, 95% CI 0.64-1.73), nor for Lp(a) tertiles (HR 0.82, 95% CI 0.52-1.28, P > 0.20) or standardized continuous variables (0.98, 95% CI 0.82-1.19 for each increase of standard deviation). CONCLUSIONS: Our real-world data suggest high Lp(a) levels at time of angiography are not predictive for cardiovascular outcomes in patients otherwise medically well controlled, but might be useful to identify patients who would not be on LDL-C targets 1 year after ACS.

Inflammation during acute coronary syndromes - Risk of cardiovascular events and bleeding.

BACKGROUND: Many parameters can affect the level of inflammation during acute coronary syndromes (ACS). We aimed to assess the one-year risk of major adverse cardiovascular events (MACE) and bleeding associated with elevated hsCRP levels during ACS, taking into account the severity of myocardial infarction, the timing of blood sampling and established long-term prognostic factors. METHODS: We studied 1864 consecutive patients with ACS enrolled in a contemporary multicenter prospective cohort study in Switzerland. HsCRP levels were determined at hospital admission. One year after discharge MACE and bleeding events were assessed. Multivariable adjusted Cox proportional hazards were computed with age, sex, time from symptom onset to blood draw, body mass index, current smoking, hypertension, diabetes mellitus, pre-existing cardiovascular disease, history of inflammatory disease, LDL-cholesterol levels, type of ACS, left ventricular ejection fraction and GRACE 1.0 risk score. RESULTS: At one-year follow-up, 151 (8.1%) patients suffered MACE. Compared to patients with hsCRP below 2 mg/l, the risk of MACE was higher in patients with hsCRP levels between 2 and 5 mg/l, with a multivariate adjusted hazard ratio (HR) of 1.63 (95% confidence interval (CI) 0.93-2.84), in those with levels between 5 and 10 mg/l, with a HR of 2.80 (95% CI 1.58-4.96), and in those with levels above 10 mg/l, with a HR of 2.23 (95% CI 1.28-3.88). There was no difference in bleeding risk between the four groups. CONCLUSIONS: Systemic inflammation in the acute phase of myocardial infarction is an independent predictor for cardiovascular events, but not for bleeding.

Gender and age differences in outcomes of patients with acute coronary syndromes referred for coronary angiography.

OBJECTIVES: The number of elderly patients undergoing coronary revascularization is steadily increasing, and data on the impact of gender on outcomes are scarce. This study sought to assess gender-related differences in outcomes in elderly patients with acute coronary syndromes (ACS). METHODS: We investigated outcomes in elderly ACS patients referred for coronary angiography and prospectively enrolled in the Swiss ACS Cohort between December 2009 and October 2012. Adjudicated major adverse cardiovascular and cerebrovascular events (MACCE) included all-cause death, non-fatal myocardial infarction, clinically indicated repeat coronary revascularization, definite stent thrombosis, and transient ischemic attack/stroke. RESULTS: Among 2,168 patients recruited, 481 (22%) patients were >75 years of age (37% women). In patients >75 years, 1-year MACCE rates were 15% and 23% in women and men (OR 0.59, 95% CI 0.36-0.97, P = 0.04), respectively, and differences remained significant after adjustments for baseline variables (adjusted OR 0.48, 95% CI 0.26-0.90, P = 0.02). Women >75 years had a lower cardiovascular mortality (6% versus 12%, adjusted OR 0.31, 95% CI 0.12-0.81, P = 0.02). In patients ≤75 years, 1-year MACCE rates did not differ between gender (10% and 8% for women and men, adjusted OR 1.28, 95% CI 0.77-2.14, P = 0.34). Rates of TIMI major bleeding for women and men were 4% and 4% in patients >75 years (P = 0.96), and 5% and 3% in those ≤75 years (P = 0.11). CONCLUSIONS: The low rates of MACCE observed in elderly women in this patient cohort suggest that with current interventional strategies the gender gap in ACS management has been attenuated.

Predictive value of the age, creatinine, and ejection fraction (ACEF) score in patients with acute coronary syndromes.

BACKGROUND: This study sought to investigate the predictive value of the age, creatinine, and ejection fraction (ACEF) score in patients with acute coronary syndromes (ACS). The ACEF score (age/left ventricular ejection fraction +1 [if creatinine > 176 µmol/L]) has been established in patients evaluated for coronary artery bypass surgery. Data on its predictive value in all-comer ACS patients undergoing percutaneous coronary intervention are scarce. METHODS: A total of 1901 patients prospectively enrolled in the Swiss ACS Cohort were included in the analysis. Optimal ACEF score cut-off values were calculated by decision tree analysis, and patients divided into low-risk (≤1.45), intermediate-risk (>1.45 and ≤2.0), and high-risk groups (>2.0). The primary endpoint was all-cause mortality. Major adverse cardiac and cerebrovascular events (MACCE) included all-cause death, non-fatal myocardial infarction, clinically indicated repeat coronary revascularization, definite stent thrombosis, and transient ischemic attack/stroke. RESULTS: One-year rates of all-cause death increased across ACEF score groups (1.6% versus 5.6% versus 23.0%, p < 0.001). In multivariate analysis, the ACEF score was related with an increased risk of all-cause mortality (adjusted HR 3.53, 95% CI 2.90-4.31, p < 0.001), MACCE (adjusted HR 2.23, 95% CI 1.88-2.65, p < 0.001), and transient ischemic attack/stroke (adjusted HR 2.58, 95% CI 1.71-3.89, p < 0.001) at 1 year. Rates of Thrombolysis in Myocardial Infarction (TIMI) major and Global use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe bleeding paralleled the increased ischemic risk across the groups (p < 0.001). CONCLUSIONS: The ACEF score is a simple and useful risk stratification tool in patients with ACS referred for coronary revascularization.

Prognosis of cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome.

OBJECTIVE: To examine the prognosis of patients with cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome compared to patients without prior multimorbidity. METHODS: This multicenter prospective cohort study in Switzerland included 5,635 patients hospitalized with acute coronary syndrome between 2009 and 2014, with a one-year follow-up period. We defined cardiovascular and non-cardiovascular multimorbidity as having at least two prior comorbidities before the index hospitalization. Multivariable adjusted Cox proportional models were built to assess the one-year risk of recurrent cardiovascular events, defined as cardiovascular mortality and non-fatal myocardial infarction or stroke. The final model was adjusted for age, gender, body mass index, tobacco consumption, education, and family history of cardiovascular disease, prescription of high-dose statinsat discharge and use of cardiac rehabilitation after discharge. RESULTS: Overall, 3,664 patients (65%) had no multimorbidity, 1,839 (33%) had cardiovascular multimorbidity, 62 (1%) had non-cardiovascular multimorbidity, and 70 (1%) had both cardiovascular and non-cardiovascular multimorbidity. The multivariate risk of recurrent cardiovascular events was increased among patients with cardiovascular multimorbidity (hazard ratio (HR) 2.05, 95% CI: 1.54-2.73, p<0.001) and patients with non-cardiovascular multimorbidity (HR 2.57, 95% CI: 1.04-6.35, p = 0.04) compared to patients without multimorbidity. Patients with cardiovascular and non-cardiovascular multimorbidity had the highest risk of recurrence with a HR of 5.19, 95% CI: 2.79-9.64, p<0.001, compared to patients without multimorbidity. CONCLUSIONS: Multimorbidity increased by two-fold the risk of cardiovascular events over the year after an acute coronary syndrome. The magnitude of this increased risk was similar for patients with cardiovascular or non-cardiovascular multimorbidity.

Cysteine-rich angiogenic inducer 61 (Cyr61): a novel soluble biomarker of acute myocardial injury improves risk stratification after acute coronary syndromes.

AIMS: We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. METHODS AND RESULTS: Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P < 0.001) comparable to high-sensitivity troponin T (30 days: 0.88 to 0.89, P < 0.001; 1 year: 0.77 to 0.79, P < 0.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n = 362), Cyr61 was not associated with adverse outcome. CONCLUSION: Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients.

Prognosis of Patients With Familial Hypercholesterolemia After Acute Coronary Syndromes.

BACKGROUND: Patients with heterozygous familial hypercholesterolemia (FH) and coronary heart disease have high mortality rates. However, in an era of high-dose statin prescription after acute coronary syndrome (ACS), the risk of recurrent coronary and cardiovascular events associated with FH might be mitigated. We compared coronary event rates between patients with and without FH after ACS. METHODS: We studied 4534 patients with ACS enrolled in a multicenter, prospective cohort study in Switzerland between 2009 and 2013 who were individually screened for FH on the basis of clinical criteria according to 3 definitions: the American Heart Association definition, the Simon Broome definition, and the Dutch Lipid Clinic definition. We used Cox proportional models to assess the 1-year risk of first recurrent coronary events defined as coronary death or myocardial infarction and adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, existing cardiovascular disease, high-dose statin at discharge, attendance at cardiac rehabilitation, and the GRACE (Global Registry of Acute Coronary Events) risk score for severity of ACS. RESULTS: At the 1-year follow-up, 153 patients (3.4%) had died, including 104 (2.3%) of fatal myocardial infarction. A further 113 patients (2.5%) experienced nonfatal myocardial infarction. The prevalence of FH was 2.5% with the American Heart Association definition, 5.5% with the Simon Broome definition, and 1.6% with the Dutch Lipid Clinic definition. Compared with patients without FH, the risk of coronary event recurrence after ACS was similar in patients with FH in unadjusted analyses, although patients with FH were >10 years younger. However, after multivariable adjustment including age, the risk was greater in patients with FH than without, with an adjusted hazard ratio of 2.46 (95% confidence interval, 1.07-5.65; P=0.034) for the American Heart Association definition, 2.73 (95% confidence interval, 1.46-5.11; P=0.002) for the Simon Broome definition, and 3.53 (95% confidence interval, 1.26-9.94; P=0.017) for the Dutch Lipid Clinic definition. Depending on which clinical definition of FH was used, between 94.5% and 99.1% of patients with FH were discharged on statins and between 74.0% and 82.3% on high-dose statins. CONCLUSIONS: Patients with FH and ACS have a >2-fold adjusted risk of coronary event recurrence within the first year after discharge than patients without FH despite the widespread use of high-intensity statins.

Prognostic value of PCSK9 levels in patients with acute coronary syndromes.

AIMS: Proprotein convertase subtilisin kexin 9 (PCSK9) is an emerging target for the treatment of hypercholesterolaemia, but the clinical utility of PCSK9 levels to guide treatment is unknown. We aimed to prospectively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospective cohort. At 1 year, the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events (GRACE) variables, as well as the achievement of LDL cholesterol targets of <1.8 mmol/L. Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia (rate ratio, RR 1.21, 95% confidence interval, CI 1.09-1.53), be treated with lipid-lowering therapy (RR 1.46, 95% CI 1.30-1.63), present with longer time interval of chest pain (RR 1.29, 95% CI 1.09-1.53) and higher C-reactive protein levels (RR 1.22, 95% CI 1.16-1.30). PCSK9 increased 12-24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001). At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI 0.69-1.85) for all-cause death and remained similar after adjustment for the GRACE score. Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets (RR 0.81, 95% CI 0.66-0.99). CONCLUSION: In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year.

Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes.

AIMS: We aimed to assess the prevalence and management of clinical familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). METHODS AND RESULTS: We studied 4778 patients with ACS from a multi-centre cohort study in Switzerland. Based on personal and familial history of premature cardiovascular disease and LDL-cholesterol levels, two validated algorithms for diagnosis of clinical FH were used: the Dutch Lipid Clinic Network algorithm to assess possible (score 3-5 points) or probable/definite FH (>5 points), and the Simon Broome Register algorithm to assess possible FH. At the time of hospitalization for ACS, 1.6% had probable/definite FH [95% confidence interval (CI) 1.3-2.0%, n = 78] and 17.8% possible FH (95% CI 16.8-18.9%, n = 852), respectively, according to the Dutch Lipid Clinic algorithm. The Simon Broome algorithm identified 5.4% (95% CI 4.8-6.1%, n = 259) patients with possible FH. Among 1451 young patients with premature ACS, the Dutch Lipid Clinic algorithm identified 70 (4.8%, 95% CI 3.8-6.1%) patients with probable/definite FH, and 684 (47.1%, 95% CI 44.6-49.7%) patients had possible FH. Excluding patients with secondary causes of dyslipidaemia such as alcohol consumption, acute renal failure, or hyperglycaemia did not change prevalence. One year after ACS, among 69 survivors with probable/definite FH and available follow-up information, 64.7% were using high-dose statins, 69.0% had decreased LDL-cholesterol from at least 50, and 4.6% had LDL-cholesterol ≤1.8 mmol/L. CONCLUSION: A phenotypic diagnosis of possible FH is common in patients hospitalized with ACS, particularly among those with premature ACS. Optimizing long-term lipid treatment of patients with FH after ACS is required.

Safety of Prasugrel Loading Doses in Patients Pre-Loaded With Clopidogrel in the Setting of Primary Percutaneous Coronary Intervention: Results of a Nonrandomized Observational Study.

OBJECTIVES: The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention. BACKGROUND: Prasugrel is one of the preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients. METHODS: Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days. RESULTS: Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36). CONCLUSIONS: This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).

Safety profile of prasugrel and clopidogrel in patients with acute coronary syndromes in Switzerland.

OBJECTIVE: To assess safety up to 1 year of follow-up associated with prasugrel and clopidogrel use in a prospective cohort of patients with acute coronary syndromes (ACS). METHODS: Between 2009 and 2012, 2286 patients invasively managed for ACS were enrolled in the multicentre Swiss ACS Bleeding Cohort, among whom 2148 patients received either prasugrel or clopidogrel according to current guidelines. Patients with ST-elevation myocardial infarction (STEMI) preferentially received prasugrel, while those with non-STEMI, a history of stroke or transient ischaemic attack, age ≥75 years, or weight <60 kg received clopidogrel or reduced dose of prasugrel to comply with the prasugrel label. RESULTS: After adjustment using propensity scores, the primary end point of clinically relevant bleeding events (defined as the composite of Bleeding Academic Research Consortium, BARC, type 3, 4 or 5 bleeding) at 1 year, occurred at a similar rate in both patient groups (prasugrel/clopidogrel: 3.8%/5.5%). Stratified analyses in subgroups including patients with STEMI yielded a similar safety profile. After adjusting for baseline variables, no relevant differences in major adverse cardiovascular and cerebrovascular events were observed at 1 year (prasugrel/clopidogrel: cardiac death 2.6%/4.2%, myocardial infarction 2.7%/3.8%, revascularisation 5.9%/6.7%, stroke 1.0%/1.6%). Of note, this study was not designed to compare efficacy between prasugrel and clopidogrel. CONCLUSIONS: In this large prospective ACS cohort, patients treated with prasugrel according to current guidelines (ie, in patients without cerebrovascular disease, old age or underweight) had a similar safety profile compared with patients treated with clopidogrel. CLINICAL TRIAL REGISTRATION NUMBER: SPUM-ACS: NCT01000701; COMFORTABLE AMI: NCT00962416.