Smoking abstinence 1 year after acute coronary syndrome: follow-up from a randomized controlled trial of varenicline in patients admitted to hospital.

BACKGROUND: Patients who continue to smoke after acute coronary syndrome are at increased risk of reinfarction and death. We previously found use of varenicline to increase abstinence 24 weeks after acute coronary syndrome; here we report results through 52 weeks. METHODS: The EVITA trial was a multicentre, double-blind, randomized, placebo-controlled trial of varenicline for smoking cessation in patients admitted to hospital with acute coronary syndrome. Participants were randomly assigned (1:1) to receive varenicline or placebo for 12 weeks, in conjunction with low-intensity counselling. Smoking abstinence was assessed via 7-day recall, with biochemical validation using exhaled carbon monoxide. Participants lost to follow-up or withdrawn were assumed to have returned to smoking. RESULTS: Among the 302 participants, abstinence declined over the course of the trial, with 34.4% abstinent 52 weeks after acute coronary syndrome. Compared with placebo, point estimates suggest use of varenicline increased point-prevalence abstinence (39.9% v. 29.1%, difference 10.7%, 95% confidence interval [CI] 0.01% to 21.44%; number needed to treat 10), continuous abstinence (31.1% v. 21.2%, difference 9.9%, 95% CI -0.01% to 19.8%) and reduction in daily cigarette smoking by 50% or greater (57.8% v. 49.7%, difference 8.1%, 95% CI -3.1% to 19.4%). Varenicline and placebo groups had similar occurrence of serious adverse events (24.5% v. 21.9%, risk difference 2.7%, 95% CI -7.3% to 12.6%) and major adverse cardiovascular events (8.6% v. 9.3%, risk difference -0.7%, 95% CI -7.8% to 6.5%). INTERPRETATION: Varenicline was efficacious for smoking cessation in this high-risk patient population. However, 60% of patients who received treatment with varenicline still returned to smoking. Trial registration: ClinicalTrials.gov, no. NCT00794573.

Computed Tomography Perfusion Aids in the Prognostication of Comatose Postcardiac Arrest Patients.

Early assessment of the potential for neurologic recovery in comatose cardiac arrest patients (CCAP) has been a challenge despite significant evolution in management and imaging techniques. The purpose of study was to determine if the use of computed tomography perfusion (CTP) in CCAPs is feasible and if this technique can predict the likelihood that CCAPs will have a devastating outcome at hospital discharge. We prospectively enrolled 10 newly admitted comatose adults who had an out-of-hospital cardiac arrest and were treated with standard therapeutic hypothermia protocols. Patients underwent CTP of the head within 6 hours after finishing therapeutic hypothermia treatment. The imaging findings were compared with the results of a clinical assessment, as well as the modified Rankin Scale (mRS) score at hospital discharge. Sensitivity, specificity, and positive and negative predictive values for CTP were calculated to predict clinical outcome. Eight patients had an mRS score of ≥5, and 2 patients had an mRS score of ≤2 at hospital discharge. CTP predicted a good clinical outcome in both patients with an mRS score of ≤2. The area under the curve (AUC) for plain computed tomography of the head, computerized tomography angiogram 4-point scale, computerized tomography angiogram 7-point scale, CTP of the whole brain, and CTP of the brainstem for predicting the results of the immediate clinical assessment were 0.76, 0.83, 0.67, 0.83, and 1.0, respectively. The AUCs for predicting outcome at discharge were 0.69, 0.63, 0.56, 0.63, 0.63, and 0.69, respectively. In conclusion, our pilot study showed that CTP is feasible and had a very high AUC for predicting the results of immediate clinical assessment in CCAP.

Smokers and Postcessation Weight Gain After Acute Coronary Syndrome.

BACKGROUND: Smoking cessation and weight management are recommended after acute coronary syndrome (ACS); however, little is known about the effects of smoking cessation on weight change after ACS. We aimed to assess the effect of smoking cessation after ACS on weight over a 12-month follow-up period. METHODS AND RESULTS: Data were prospectively collected from the EVITA (Evaluation of Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome) trial. Weight change was compared among 3 groups of patients: those who were completely abstinent (n=70), those who smoked intermittently (n=68), and those who smoked persistently (n=34). Patients' mean baseline weight was 83.9 kg (SD 17.7) with a mean body mass index of 28.5 (SD 5.4). Patients smoked a mean of 37.7 years (SD 17.7) and a mean of 21.0 cigarettes (SD 9.0) per day prior to their ACS. Weight change varied across groups, with abstainers gaining a mean of 4.8 kg (SD 8.6), intermittent smokers gaining a mean of 2.0 kg (SD 8.9) and persistent smokers losing a mean of 0.7 kg (SD 7.4). At 52 weeks, abstainers were more likely to gain weight than persistent smokers (difference in means 5.5 kg; 95% CI 2.3-8.8). This weight gain was not associated with an increase in the use of antihypertensive or antidiabetic medications. CONCLUSIONS: Following an ACS, significant weight is gained by patients who quit smoking. Weight-management interventions among smokers who quit after ACS should be a focus of investigation in future research so that the cardiovascular benefits achieved by smoking cessation are not offset by weight gain in this high-risk population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794573.

Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome.

BACKGROUND: Less than one-third of smokers hospitalized with an acute coronary syndrome (ACS) remain abstinent following discharge. We assessed whether varenicline, begun in-hospital, is efficacious for smoking cessation following ACS. METHODS AND RESULTS: We conducted a multi-center, double-blind, randomized, placebo-controlled trial in which smokers hospitalized with an ACS were randomized to varenicline or placebo for 12 weeks. All patients received low-intensity counseling. The primary end point was point-prevalence smoking abstinence assessed at 24 weeks by 7-day recall and biochemical validation using expired carbon monoxide. A total of 302 patients were randomized (mean age 55±9 years; 75% male; 56% ST-segment elevation myocardial infarction; 38% non-ST-segment elevation myocardial infarction; 6% unstable angina). Patients smoked a mean of 21±11 cigarettes/d at the time of hospitalization and had been smoking for a mean of 36±12 years. At 24 weeks, patients randomized to varenicline had significantly higher rates of smoking abstinence and reduction than patients randomized to placebo. Point-prevalence abstinence rates were 47.3% in the varenicline group and 32.5% in the placebo group (P=0.012; number needed to treat=6.8). Continuous abstinence rates were 35.8% and 25.8%, respectively (P=0.081; number needed to treat=10.0), and rates of reduction ≥50% in daily cigarette consumption were 67.4% and 55.6%, respectively (P=0.05; number needed to treat=8.5). Adverse event rates within 30 days of study drug discontinuation were similar between groups (serious adverse events: varenicline 11.9%, placebo 11.3%; major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%). CONCLUSIONS: Varenicline, initiated in-hospital following ACS, is efficacious for smoking cessation. Future studies are needed to establish safety in these patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794573.

A randomized controlled trial of the efficacy and safety of varenicline for smoking cessation after acute coronary syndrome: design and methods of the Evaluation of Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome trial.

UNLABELLED: Patients who continue to smoke after an acute coronary syndrome (ACS) have a significantly increased risk of reinfarction and death compared with those who quit. Varenicline is a first-line smoking cessation therapy with proven efficacy in the general population. However, its efficacy and safety immediately after an ACS are unknown. METHODS: The EVITA trial is a multicenter, double-blind, randomized, placebo-controlled trial (NCT00794573). The primary objective is to evaluate the efficacy of varenicline after ACS in achieving biochemically validated smoking abstinence at 24 weeks. The secondary objectives are to examine the efficacy of varenicline for smoking abstinence and reduction in daily cigarette consumption at 52 weeks and to describe the occurrence of adverse events. Three hundred and two patients motivated to quit smoking were enrolled in the United States and Canada from November 2009 to December 2014 while hospitalized with an ACS. These participants were randomized (1:1) to either varenicline (1.0 mg twice daily) or placebo for 12 weeks. The trial includes follow-ups by telephone at weeks 1, 2, and 8 and clinic visits at weeks 4, 12, 24, and 52. Data collected include demographic and clinical characteristics, self-reported smoking, exhaled carbon monoxide (an indicator of current smoking), and adverse events. CONCLUSION: The EVITA trial will provide novel information concerning the efficacy and safety of varenicline immediately after ACS. If varenicline is efficacious in this population, it will have a major impact on secondary prevention of recurrent clinical events in patients post-ACS.

Therapeutic hypothermia for out-of-hospital cardiac arrest: An analysis comparing cooled and not cooled groups at a Canadian center.

BACKGROUND: Out of hospital cardiac arrest is a devastating event and is associated with poor outcomes; however, therapeutic hypothermia (TH) is a novel treatment which may improve neurological outcome and decrease mortality. Despite this, TH is not uniformly implemented across Coronary Care and Intensive Care Units in Canada. OBJECTIVE: The purpose of this study was to compare cerebral recovery and mortality rates between patients in our Coronary Care Unit who received TH with a historical control group. MATERIALS AND METHODS: A retrospective chart review was performed of patients admitted to a tertiary care center with out-of-hospital cardiac arrest. Twenty patients who were admitted and cooled after December 2006 were compared with 29 noncooled patients admitted in the 5 years prior as a historical control group. The primary outcomes of interest were in-hospital mortality and neurological outcome. RESULTS: Eleven of 20 (11/20, 55%) patients who were cooled as per protocol survived to hospital discharge, all having a good neurological outcome. Eleven of 29 (11/29, 38%) noncooled patients survived to hospital discharge (Odds Ratio: 0.50, 95% CI: 0.16- 1.60, P=0.26). Eleven of 20 patients who were cooled had a good neurological outcome (CPS I-II, 11/20, 55%), versus 7 of 29 (7/29, 24%) of noncooled patients (Odds ratio: 3.84, 95% CI: 1.13- 13.1, P=0.03). One hundred percent (11/11) of survivors in the cooled group had a good neurological outcome. CONCLUSION: In our center, the use of TH in out-of-hospital cardiac arrest survivors was associated with improved neurological outcome.

Time from first medical contact to reperfusion in ST elevation myocardial infarction: a Which Early ST Elevation Myocardial Infarction Therapy (WEST) substudy.

BACKGROUND: Recent research and contemporary ST elevation myocardial infarction guidelines emphasize the importance of prompt reperfusion and have redefined the traditional time to treatment metric to include prehospital paramedical staff as the point of first medical contact. However, an important knowledge gap exists relating to data systematically addressing the impact of arrival at the hospital by ambulance and the delays inherent in transfer from a community hospital to tertiary centres for percutaneous coronary intervention (PCI). METHODS: The Which Early ST Elevation Myocardial Infarction Therapy (WEST) study initiated treatment at the point of first medical contact, including prehospital contact. Patients were randomly assigned to receive fibrinolysis with usual care or coupled with mechanical cointervention, or primary PCI. To assess the impact of this strategy on time to treatment, the following randomly assigned patient groups were compared: prehospital versus in-hospital; those arriving at the hospital by ambulance versus ambulatory self transport; and those whose initial hospital care was a community versus PCI centre. RESULTS: Of the 328 patients enrolled in the study, 221 received fibrinolysis and 107 received primary PCI. Compared with the in-hospital group, patients who underwent prehospital random assignment (44%, n=145) experienced a 48 min reduction in median (interquartile range) time from symptom onset to first study medication (87 min [65 min to 147 min] versus 135 min [95 min to 186 min]; P<0.001) and a 56 min reduction in time to first balloon inflation (148 min [117 min to 214 min] versus 204 min [166 min to 290 min]; P<0.001). Arrival by ambulance without prehospital random assignment (n=90) incurred a substantial delay from first medical contact to reperfusion (fibrinolysis 76 min [63 min to 105 min] and PCI 160 min [141 min to 212 min]) compared with prehospital random assignment (n=145; fibrinolysis 43 min [33 min to 54 min] and PCI 105 min [90 min to 127 min]) or ambulatory patients (n=93; fibrinolysis 47 min [32 min to 68 min] and PCI 108 min [85 min to 150 min]). Community (n=165) versus PCI hospital (n=163) random assignment was associated with a longer delay from first medical contact to reperfusion: fibrinolysis, 56 min versus 47 min (P=0.008) and primary PCI, 139 min versus 105 min (P=0.001). DISCUSSION: Prehospital diagnosis, random assignment and treatment substantially reduced treatment delay with both pharmacological and mechanical reperfusion. Those activating the prehospital medical response system without receiving prehospital random assignment experienced the longest delay from first medical contact to reperfusion, indicating a lost opportunity to enhance ST elevation myocardial infarction patient outcomes.

Impact of ramipril on the incidence of atrial fibrillation: results of the Heart Outcomes Prevention Evaluation study.

OBJECTIVES: We evaluated the effect of angiotensin-converting enzyme (ACE) inhibitor ramipril on the incidence of atrial fibrillation (AF) in patients enrolled in the Heart Outcomes Prevention Evaluation trial. BACKGROUND: Atrial fibrillation is the most common arrhythmia affecting the general population and is associated with increased morbidity and mortality. Retrospective secondary analyses of some of the large trials of ACE inhibitors have suggested that ACE inhibitors may prevent AF. METHODS: We evaluated the occurrence of AF by reviewing the electrocardiogram tracings at entry, at 2 years, and at the end of the study, as well as hospitalizations among 8335 high-risk participants from the Heart Outcomes Prevention Evaluation study, > or = 55 years, without known heart failure or left ventricular (LV) systolic dysfunction and followed for a median period of 4.5 years. We compared the impact of ramipril and matched placebo on occurrence of AF. The results were compared to similar trials. RESULTS: Over the 4.5 years follow-up, the incidence of new AF was low (2.1%, 177/8335), and ramipril did not significantly reduce the rate of new AF compared with placebo (86/4291 [2.0%] vs 91/4044 [2.2%]) with an odds ratio of 0.92 (95% confidence interval, 0.68-1.24; P = .57). These results added to the previous ACE inhibitor trials (excluding trials in patients with LV dysfunction) showed no significant reduction in new AF among patients treated with these agents (1088/20,930 [5.0%] vs 1343/22,878 [5.9%]; relative risk, 0.92; 95% confidence interval, 0.80-1.05). CONCLUSION: Although the incidence of AF was low, treatment with ramipril in this population without known LV systolic dysfunction did not significantly reduce this dysrhythmia.

Insights into the change in brain natriuretic peptide after ST-elevation myocardial infarction (STEMI): why should it be better than baseline?

While baseline N-terminal brain natriuretic peptide (NT-proBNP) is useful in the prognosis of acute ST-elevation myocardial infarction (STEMI), it is unclear whether a relationship exists between serial NT-proBNP, reperfusion success, and prognosis. We prospectively defined a NT-proBNP analysis in the WEST (Which Early ST-elevation myocardial infarction Therapy) trial that enrolled 304 acute STEMI patients. NT-proBNP (pg/mL) was measured at baseline prior to treatment (n=258) and 72 to 96 h (n=247) and 30 days (n=221) after treatment (Delta NT-proBNP=72 h value - the baseline NT-proBNP). Reperfusion success was measured by ST-segment resolution at 180 min, infarct size by peak creatine kinase (CK) during the first 24 h, and QRS score at discharge (QRSd). The primary endpoint was a 30 day clinical composite. The ability of either baseline NT-proBNP or Delta NT-proBNP to predict the primary endpoint was compared using single-variable logistic regression and the c-statistic. Median (interquartile range) NT-proBNP in pg/mL was 87 (39-316) at baseline, 864 (338-1857) at 72 h, and 585 (264-1212) at 30 days. ST resolution was inversely correlated with Delta NT-proBNP (r=-0.23, p=0.002) and 30 day NT-proBNP (30 day NT-proBNP 1016, 828, and 397 for <30%, 30%-70%, >or=70% STR, respectively, p<0.001). Infarct size was correlated with Delta NT-proBNP by CK (r=0.41, p<0.001) and QRSd (r=0.31, p<0.001); the 30 day NT-proBNP relationship was similar for CK (r=0.48, p<0.001) and QRSd (p=0.003). The baseline NT-proBNP was associated with an increased 30-day composite endpoint (Q1, 19%; Q2, 20%; Q3, 15%; Q4, 38%; p=0.03 for trend) as was Delta NT-proBNP (Q1, 16%; Q2, 18%; Q3, 19%; Q4, 37%; p=0.009 for trend). The c-statistic for baseline, 72 to 96 h, and Delta NT-proBNP was 0.59, 0.61, and 0.62 for the 30-day composite and 0.64, 0.62, and 0.62 for the 90-day composite, respectively. Delta NT-proBNP clearly predicts short-term adverse cardiac events and is superior to baseline NT-proBNP, but similar to the 72 to 96 h NT-proBNP in predicting clinical events after STEMI. This likely reflects the variability in NT-proBNP at presentation and the ability to integrate subsequent important physiologic sequelae of STEMI such as reperfusion and infarct size.

Trends in event rate and case fatality of patients hospitalized with myocardial infarction between 1984 and 2001.

Between 1984 and 1993, prevalence and case fatality of hospitalized acute myocardial infarction (AMI) had declined in the population of Halifax County. We aimed to determine whether these trends continued into the 21st century by investigating patient characteristics, treatment methods, and fatality for hospital admissions of residents of Halifax County, aged 25-74, during 1984-1989 (period 1), 1990-1993 (period 2), and 1998-2001 (period 3) and diagnosed as AMI that were extracted from databases for the Halifax County MONICA and ICONS (Improving Cardiovascular Outcomes in Nova Scotia) Studies. Trends in patient characteristics and treatment methods were assessed by chi2 statistics. Their association with 28-day fatality was determined by logistic regression. Event rate declined during 1984-1993 but not into 1998-2001 (p = 0.206). Compared with 1990-1993, fewer AMI patients during 1998-2001 were > or = 55 years (73.3% vs. 69.9%), cigarette smokers (49.8% vs. 42.9%), had a history of myocardial infarction (28.9% vs. 24.9%), and had an admission heart rate >100 (34.8% vs. 17.4%). Additionally, more patients had a history of diabetes (22.5% vs. 28.1%). Case fatality declined progressively over the 3 study time periods (16.6%, 13.1%, and 9.4%, respectively). Changes also occurred in prevalence of Killip class 4 status during admission (20.2%, 10.3%, and 13.3%, respectively), use of thrombolysis (9.0%, 30.9, and 32.6%, respectively), and percutaneous coronary intervention (PCI) (4.3%, 11.2%, and 22.4%, respectively) in the different periods. Significant associations were found between case fatality and patient history of diabetes, history of MI, age, elevated admission heart rate, Killip class 4 impairment, thrombolysis, and PCI. The ICONS registry of hospitalized acute myocardial infarctions was used to compare case fatality during 1998-2001 with that reported by the Halifax County MONICA Project for 1984-1993. Whereas the population rate of myocardial infarctions had declined between 1984-1993 but not subsequently, case fatality declined significantly throughout the study period. The continued decline in case fatality is likely explained by changes in patient profile on presentation and medical therapies, including the increased use of thrombolysis and PCI.

Trends in five-year survival of patients discharged after acute myocardial infarction.

BACKGROUND: It has previously been shown that the increased use of therapeutic intervention may not reduce patient fatality if there is a simultaneous increase in case severity. The present study was designed to extend the relationship between case severity and therapeutic interventions to long-term survival in the same study population. OBJECTIVE: To compare five-year survival of patients discharged after acute myocardial infarction from 1984 to 1988 and from 1989 to 1993, and to evaluate possible reasons for survival differences. METHODS: The present study was population-based. Survival time was determined by record linkage into the Canadian Mortality Database. Association of five-year survival with patient characteristics, in-hospital treatment and discharge medications was assessed by logistical regression analysis. Case severity was calculated as the probability of death within five years, given the patient profile and excluding any interventions. RESULTS: Between the two study periods, most patient characteristics and treatment intensity changed, but case severity for the study population remained constant. Five-year survival improved from 74.8% to 79.2% (P(chi2)=0.001). The improvement was adequately described by the combination of changes in patient profile and treatment without residual period effect (P(goodness-of-fit)=0.752). The treatments significantly associated with five-year survival were coronary artery bypass graft surgery (OR 2.74; 95% CI 1.86 to 4.05), percutaneous coronary intervention (OR 2.63; 95% CI 1.67 to 4.14) and thrombolysis (OR 1.98; 95% CI 1.50 to 2.62) during admission, as well as acetylsalicylic acid (OR 1.39; 95% CI 1.15 to 1.68) or beta-blocker (OR 1.60; 95% CI 1.34 to 1.92) prescription at discharge. CONCLUSIONS: Changes in patient profile did not affect long-term prognosis; instead, treatment modalities accounted for the observed improvement in five-year survival.

Improved prediction of early-onset coronary artery disease using APOE epsilon4, BChE-K, PPARgamma2 Pro12 and ENOS T-786C in a polygenic model.

OBJECTIVES: Coronary artery disease (CAD) is often polygenic due to multiple mutations that contribute small effects to susceptibility. Since most prior studies only evaluated the contribution of single candidate genes, we therefore looked at a combination of genes in predicting early-onset CAD [apolipoprotein E (APOE) epsilon4, butyrylcholinesterase (BChE) K, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala and endothelial nitric oxide synthase (ENOS) T-786C]. DESIGN AND METHODS: We examined the frequencies, individually and in combination, of all four alleles among patients with early-onset CAD (n = 150; <50 years), late-onset CAD (n = 150; >65 years) and healthy controls (n = 150, age range 47-93 years). Differences in the proportion of subjects in each group with the given gene combination were assessed and likelihood ratios (LR) were calculated using logistic regression to combine the results of multiple genes. RESULTS: Early-onset CAD patients had increased, but non-significant, frequencies of PPARgamma2 Pro12/Pro12 (P = 0.39) and ENOS T-786C (P = 0.72), while BChE-K was only significantly higher in early-onset CAD patients compared to controls (P = 0.03). There were significantly more APOE epsilon4 alleles alone (P = 0.02) or in combination with BChE-K (P = 0.02) among early-onset CAD patients compared to late-onset CAD ones or controls. When combined, there was a higher prevalence of all four alleles in early-onset CAD (early-onset CAD patients: 10.7%, late-onset CAD patients: 3.3% and controls: 2.7%, P = 0.01). LR for early-onset CAD for a single allele was relatively small (1.08 for PPARgamma2 to 1.70 for APOE epsilon4). This increased to 2.78 (1.44-5.37) when combining all four alleles, therefore increasing the pre-test probability of CAD from 5% to a post-test probability of 12.7%. CONCLUSIONS: While any single mutation causes only a mildly increased LR (none > 1.7), in combination, the likelihood of early-onset CAD increased to 2.78 with four mutations. The genetics of early-onset CAD appear to be multifactorial, requiring polygenic models to elucidate risk.

Relation between butyrylcholinesterase K variant, paraoxonase 1 (PON1) Q and R and apolipoprotein E epsilon 4 genes in early-onset coronary artery disease.

OBJECTIVES: The common K variant of butyrylcholinesterase (BChE-K), an enzyme which metabolizes acetylcholine and organophosphates, has been associated with Alzheimer's disease, especially in the presence of the apolipoprotein E epsilon 4 allele (APOE-epsilon 4). Although APOE-epsilon 4 has been associated with the development of coronary artery disease (CAD), an association between the BChE-K variant and CAD has not been explored. Paraoxonase 1 (PON1), located within HDL, is an enzyme which also metabolizes organophosphates and may be antiatherogenic. The R192 variant of PON1 (PON1-R) has been associated with CAD. DESIGN AND METHODS: To determine whether BChE-K is also associated with premature CAD, we examined the frequency of BChE-K among patients with early-onset CAD (n = 150; < 50 yr) vs. late-onset CAD (n = 150; > 65 yr) by molecular analysis. We also examined the frequency of the PON1-R allele in both groups, and explored whether there was synergism between BChE-K and APOE-epsilon 4, BChE-K and PON1-R or PON1-R and APOE-epsilon 4. RESULTS: The frequency of the BChE-K allele tended to be greater among early-onset CAD patients compared to late-onset CAD patients (41.3% vs. 31.3%; p = 0.07), but without any significant difference between males and females. There was no difference in the prevalence of the PON1-R allele between those with early- or late-onset CAD (46.0% vs. 52.7%; p = 0.25). Twenty-two patients with early-onset CAD had both the BChE-K plus APOE-epsilon 4 alleles (14.7%) compared to 11 late-onset CAD patients (7.3%) (p = 0.04). There was no such association between BChE-K and PON1-R, nor PON1-R and APOE-epsilon 4. CONCLUSIONS: Our study suggests that there is a minor association between BChE-K and early-onset CAD, especially in the presence of the APOE-epsilon 4 allele.