Lower Myocardial Infarction Research Articles

Fractional flow reserve versus angiography guided percutaneous coronary intervention: An updated systematic review.

To compare outcomes of fractional flow reserve (FFR) to angiography (ANGIO) guided percutaneous coronary intervention (PCI). The results of a recent randomized controlled trial reported unfavorable effects of routine measurement of FFR, thereby questioning its validity in improving clinical outcomes. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were queried from January, 2000 through December, 2016 and studies comparing FFR and ANGIO guided PCI were included. Clinical endpoints assessed during hospitalization and at follow-up (>9 months) included: myocardial infarction (MI), major adverse cardiovascular events (MACE), target lesion revascularization (TLR), and all-cause mortality. Additional endpoints included number of PCIs performed, procedure cost, procedure time, contrast volume, and fluoroscopy time. A total of 51,350 patients (age 65 years, 73% male) were included from 11 studies. The use of FFR was associated with significantly lower likelihood of MI during hospitalization (OR 0.54, 95% CI: 0.39 to 0.75, P = 0.0003) and at follow-up (OR 0.53, 95% CI: 0.40 to 0.70, P = 0.00001). Similarly, FFR-PCI was associated with lower in-hospital MACE (OR 0.51, 95% CI: 0.37 to 0.70, P = 0.0001) and follow-up MACE (OR 0.63, 95% CI: 0.47 to 0.86, P = 0.004). In-hospital TLR was lower in the FFR-PCI group (OR 0.62, 95% CI: 0.40 to 0.97, P = 0.04), but not at follow-up (OR 0.83, 95% CI: 0.50 to 1.37, P = 0.46). There was no difference of in-hospital (OR 0.58, 95% CI: 0.31 to 1.09, P = 0.09) or follow-up all-cause mortality (OR 0.84, 95%CI: 0.59 to 1.20, P = 0.34). FFR-PCI was associated with significantly less PCI (OR 0.04, 95% CI: 0.01 to 0.15, P = 0.00001) with lower procedure cost (Mean Difference -4.27, 95% CI: -6.61 to -1.92, P = 0.0004). However, no difference in procedure time (Mean Difference 0.79, 95% CI: -2.41 to 3.99, P = 0.63), contrast use (Mean Difference -8.28, 95% CI: -24.25 to 7.68, P = 0.31) or fluoroscopy time (Mean Difference 0.38, 95% CI: -2.54 to 3.31, P = 0.80) was observed. FFR-PCI as compared to ANGIO-PCI is associated with lower in-hospital and follow-up MI and MACE rates. Although, in-hospital TLR was lower in the FFR-PCI group, this benefit was not present after 9 months. FFR-PCI group was also associated with less PCI and lower procedure costs with no effect on procedure time, contrast volume or fluoroscopy time.

Developing a data-driven spatial approach to assessment of neighbourhood influences on the spatial distribution of myocardial infarction

BackgroundThere is a growing understanding of the role played by ‘neighbourhood’ in influencing health status. Various neighbourhood characteristics—such as socioeconomic environment, availability of amenities, and social cohesion, may be combined—and this could contribute to rising health inequalities. This study aims to combine a data-driven approach with clustering analysis techniques, to investigate neighbourhood characteristics that may explain the geographical distribution of the onset of myocardial infarction (MI) risk.MethodsAll MI events in patients aged 35–74 years occurring in the Strasbourg metropolitan area (SMA), from January 1, 2000 to December 31, 2007 were obtained from the Bas-Rhin coronary heart disease register. All cases were geocoded to the census block for the residential address. Each areal unit, characterized by contextual neighbourhood profile, included socioeconomic environment, availability of amenities (including leisure centres, libraries and parks, and transport) and psychosocial environment as well as specific annual rates standardized (per 100,000 inhabitants). A spatial scan statistic implemented in SaTScan was then used to identify statistically significant spatial clusters of high and low risk of MI.ResultMI incidence was non-randomly spatially distributed, with a cluster of high risk of MI in the northern part of the SMA [relative risk (RR) = 1.70, p = 0.001] and a cluster of low risk of MI located in the first and second periphery of SMA (RR 0.04, p value = 0.001). Our findings suggest that the location of low MI risk is characterized by a high socioeconomic level and a low level of access to various amenities; conversely, the location of high MI risk is characterized by a high level of socioeconomic deprivation—despite the fact that inhabitants have good access to the local recreational and leisure infrastructure.ConclusionOur data-driven approach highlights how the different contextual dimensions were inter-combined in the SMA. Our spatial approach allowed us to identify the neighbourhood characteristics of inhabitants living within a cluster of high versus low MI risk. Therefore, spatial data-driven analyses of routinely-collected data georeferenced by various sources may serve to guide policymakers in defining and promoting targeted actions at fine spatial level.

Adherence to a healthy Nordic food index and risk of myocardial infarction in middle-aged Danes: the diet, cancer and health cohort study.

For decades, the Mediterranean diet has been in focus regarding healthy eating as it has been associated with reduced risk of non-communicable diseases. Less interest has been given to health benefits of other regional diets. The aim of the present study was to assess whether adherence to a healthy Nordic food index was associated with lower risk of myocardial infarction (MI) among middle-aged Danes. Data were obtained from the Danish Diet, Cancer and Health cohort study of 57 053 men and women aged 50-64 years recruited between 1993 and 1997. The healthy Nordic food index comprised healthy Nordic food items selected a priori (fish, cabbage, rye bread, oatmeal, apple and pears and root vegetables). Information on incident MI was ascertained through linkage with national registries. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated from sex-specific Cox proportional hazard models. In total, 1669 men and 653 women developed MI during follow-up (13.6 median years). In adjusted models, those with an index score of 5-6 points (highest scores) had significantly lower MI risk (men: HR=0.77, 95% CI=0.62, 0.97; women: HR=0.55, 95% CI=0.37, 0.82) relative to those scoring 0 points in the index (lowest score). A significantly lower MI risk was found per 1-point increment in the index in both men (HR=0.95, 95% CI=0.92, 0.99) and women (HR=0.93, 95% CI=0.88, 0.98). A healthy Nordic diet is associated with lower MI risk among middle-aged Danes, suggesting that Nordic diets should be considered in recommendations for dietary changes in the promotion of coronary health.

Stenting versus non-stenting treatment of intermediate stenosis culprit lesion in acute ST-segment elevation myocardial infarction: a multicenter randomized clinical trial.

BackgroundThe benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction (STEMI) patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject of the present study.Methods and resultsIt was a prospective, multicenter, randomized controlled trial. Between April 2012 and July 2015, 399 acute STEMI patients with single vessel disease and intermediate (40%–70%) stenosis of the culprit lesion before or after aspiration thrombectomy and/or intracoronary tirofiban (15 µg/kg) were enrolled and were randomly assigned (1: 1) to stenting group (n = 201) and non-stenting group (n = 198). In stenting group, patients received pharmacologic therapy plus standard percutaneous coronary intervention (PCI) with stent implantation. In non-stenting group, patients received pharmacologic therapy and PCI (thrombectomy), but without dilatation or stenting. Primary endpoint was 12-month rate of major adverse cardiac and cerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction (MI), repeat revascularization and stroke. Secondary endpoints were 12-month rates of all cause death, ischemia driven admission and bleeding complication. Median follow-up time was 12.4 ± 3.1 months. At 12 months, MACCE occurred in 8.0% of the patients in stenting group, as compared with 15.2% in the non-stenting group (adjusted HR: 0.42, 95% CI: 0.19–0.89, P = 0.02). The stenting group had lower non-fatal MI rate than non-stenting group, (1.5% vs. 5.5%, P = 0.03). The two groups shared similar cardiac death, repeat revascularization, stroke, all cause death, ischemia driven readmission and bleeding rates at 12 months.ConclusionsStent implantation had better efficacy and safety in reducing MACCE risks among acute STEMI patients with single vessel intermediate stenosis culprit lesions.

Fish consumption in relation to myocardial infarction, stroke and mortality among women and men with type 2 diabetes: A prospective cohort study

SummaryBackground & aimsThe accumulated evidence supports an inverse association of fish consumption with cardiovascular disease and mortality, but data among patients with type 2 diabetes are sparse. We aimed to assess fish consumption in relation to myocardial infarction (MI), stroke and mortality among individuals with type 2 diabetes.MethodsWomen and men with diagnosed type 2 diabetes (n = 2225; aged 45–84 years) within two population-based cohorts (the Swedish Mammography Cohort and the Cohort of Swedish Men) were followed from 1998 through 2012. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsWe identified 333 incident MI events, 321 incident stroke events and 771 deaths (154 with coronary heart disease [CHD] as underlying cause) during follow-up of up to 15 years. The multivariable HRs comparing >3 servings/week with ≤3 servings/month were 0.60 (95% CI, 0.39–0.92) for MI and 1.04 (95% CI, 0.66–1.64) for stroke. HRs for total mortality were lowest for moderate fish consumption of 1–<2 servings/week (0.82; 95% CI, 0.64–1.04) and 2–3 servings/week (0.79; 95% CI, 0.61–1.01) compared with ≤3 servings/month. The corresponding HRs for CHD-related mortality were 0.53; 95% CI, 0.32–0.90 and 0.75; 95% CI, 0.45–1.27.ConclusionsFish consumption was associated with lower MI incidence among individuals with type 2 diabetes, whereas no association was observed with stroke. Our data further indicated an association with lower mortality, particularly for CHD-related deaths. These findings support the current general advice on regular fish consumption also in the high risk group of type 2 diabetes patients.

ACUTE LOWER MYOCARDIAL INFARCTION: CLINICAL AND DIAGNOSTIC FEATURES

The paper displays the need for an extended electrocardiographic diagnosis including right breast leads for all patients with lower myocardial infarction at early stages of medical care. The diagnosis method presented here will allow to evaluate the localization of myocardial damage and to identify patients with signs of right ventricular damage that require clinical evaluation to identify signs of right ventricular failure and special methods for its correction.

The outcomes of intravascular ultrasound-guided drug-eluting stent implantation among patients with complex coronary lesions: a comprehensive meta-analysis of 15 clinical trials and 8,084 patients.

Objective:The effects of intravascular ultrasound (IVUS)-guided drug-eluting stent (DES) implantation in patients with complex coronary artery lesions remains to be controversial. This study sought to evaluate the outcomes of IVUS guidance in these patients.Methods:The EMBASE, Medline, and other internet sources were searched for relevant articles. The primary endpoint was major adverse cardiac events (MACE), including all-cause mortality, myocardial infarction (MI), and target-vessel revascularization (TVR). The incidence of definite/probable stent thrombosis (ST) was analyzed as the safety endpoint.Results:Fifteen clinical trials involving 8.084 patients were analyzed. MACE risk was significantly decreased following IVUS-guided DES implantation compared with coronary angiography (CAG) guidance (odds ratio [OR] 0.63, 95% confidence intervals [CI]: 0.53–0.73, p<0.001), which might mainly result from the lower all-cause mortality risk (OR 0.52, 95% CI: 0.40–0.67, p<0.001), MI (OR 0.70, 95% CI: 0.56–0.86, p=0.001), and TVR (OR 0.53, 95% CI: 0.40–0.70, p<0.001). The subgroup analyses indicated better outcomes of IVUS guidance in DES implantation for these patients with left main disease or bifurcation lesions.Conclusion:IVUS guidance in DES implantation is associated with a significant reduction in MACE risk in patients with complex lesions, particularly those with left main disease or bifurcation lesions. More large and powerful randomized trials are still warranted to guide stenting decision making. (Anatol J Cardiol 2017; 17: 258-68)

Assessing and Refining Myocardial Infarction Risk Estimation Among Patients With Human Immunodeficiency Virus

Persons with human immunodeficiency virus (HIV) that is treated with antiretroviral therapy have improved longevity but face an elevated risk of myocardial infarction (MI) due to common MI risk factors and HIV-specific factors. Despite these elevated MI rates, optimal methods to predict MI risks for HIV-infected persons remain unclear. To determine the extent to which existing and de novo estimation tools predict MI in a multicenter HIV cohort with rigorous MI adjudication. We evaluated the performance of standard of care and 2 new data-derived MI risk estimation models in 5 Centers for AIDS Research Network of Integrated Clinical Systems sites across the United States where a multicenter clinical prospective cohort of 19 829 HIV-infected adults received care in inpatient and outpatient settings since 1995. The new risk estimation models were validated in a separate cohort from the derivation cohort. Traditional cardiovascular risk factors, HIV viral load, CD4 lymphocyte count, statin use, antihypertensive use, and antiretroviral medication use were used to calculate predicted event rates. We observed MI rates over the course of follow-up that were scaled to 10 years using the Greenwood-Nam-D'Agostino Kaplan-Meier approach to account for dropout and loss to follow-up before 10 years. Of the 11 288 patients with complete baseline data, 6904 were white and 9250 were men. Myocardial infarction rates were higher among black men (6.9 per 1000 person-years) and black women (7.2 per 1000 person-years) than white men (4.4 per 1000 person-years) and white women (3.3 per 1000 person-years), older participants (7.5 vs 2.2 MI per 1000 person-years for adults 40 years and older vs < 40 years old at study entry, respectively), and participants who were not virally suppressed (6.3 vs 4.7 per 1000 person-years for participants with and without detectable viral load, respectively). The 2013 Pooled Cohort Equations, which predict composite rates of MI and stroke, adequately discriminated MI risk (Harrell C statistic = 0.75; 95% CI, 0.71-0.78). Two data-derived models incorporating HIV-specific covariates exhibited weak calibration in a validation sample and did not discriminate risk any better (Harrell C statistic = 0.72; 95% CI, 0.67-0.78 and 0.73; 95% CI, 0.68-0.79) than the Pooled Cohort Equations. The Pooled Cohort Equations were moderately calibrated in the Centers for AIDS Research Network of Clinical Systems but predicted consistently lower MI rates. The Pooled Cohort Equations discriminated MI risk and were moderately calibrated in this multicenter HIV cohort. Adding HIV-specific factors did not improve model performance. As HIV-infected cohorts capture and assess MI and stroke outcomes, researchers should revisit the performance of risk estimation tools.

The association of calcium supplementation and incident cardiovascular events in the Multi-ethnic Study of Atherosclerosis (MESA)

Background and aimsMany US adults use calcium supplements to address inadequate dietary intake and improve bone health. However, recent reports have suggested that use of calcium supplements may elevate cardiovascular disease (CVD) risk. In this study, we examined associations between baseline calcium supplement use and incident myocardial infarction (MI) (n = 208 events) and CVD events (n = 641 events) over 10.3 years in men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 6236), with dietary calcium intake at baseline also examined as a supplementary objective. Methods and resultsUsing Cox proportional hazards models, no compelling associations between calcium intake from supplements or diet and incident CVD events were observed upon multivariate adjustment for potential confounders. An association with lower MI risk was observed comparing those with low levels of calcium supplement use (1–499 mg) to those using no calcium supplements (hazard ratio 0.69, 95% CI 0.48, 0.98, p = 0.039). Relationships were homogeneous by gender, race/ethnicity, or chronic kidney disease. Results were also similar when the analysis was limited to postmenopausal women only. ConclusionAnalysis of incident MI and CVD events in the MESA cohort does not support a substantial association of calcium supplement use with negative cardiovascular outcomes.

Clinical Outcomes of Revascularization Strategies for Patients With MVD/LMCA Disease: A Systematic Review and Network Meta-Analysis.

Hybrid coronary revascularization (HCR), a new minimally invasive procedure for patients requiring revascularization for multivessel coronary lesions, combines coronary artery bypass grafting (CABG) for left anterior descending (LAD) lesions and percutaneous coronary intervention (PCI) for non-LAD coronary lesions. However, available data related to outcomes comparing the 3 revascularization therapies is limited to small studies.We conducted a search in MEDLINE, EMBASE, and the Cochrane Library of Controlled Trials up to December 31, 2014, without language restriction. A total of 16 randomized trials (n=4858 patients) comparing HCR versus PCI or off-pump CABG (OPCAB) were included in this meta-analysis. The primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), all-cause death, myocardial infarction (MI), cerebrovascular events (CVE), and target vessel revascularization (TVR). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using random-effect and fixed-effect models. Ranking probabilities were used to calculate a summary numerical value: the surface under the cumulative ranking (SUCRA) curve.No significant differences were seen between the HCR and PCI in short term (in hospital and 30 days) with regard to MACCE (odds ratio [OR] = 0.51, 95% confidence interval [CI] 0.00–2.35), all-cause death (OR = 2.09, 95% CI 0.34–7.66), MI (OR = 1.02, 95% CI 0.19–2.95), CVE (OR = 4.45, 95% CI 0.39–19.16), and TVR (OR = 6.99, 95% CI 0.17–39.39). However, OPCAB had lower MACCE than HCR (OR = 0.19, 95% CI 0.00–0.95). In midterm (1 year and 3 year), in comparison with HCR, PCI had higher all-cause death (OR = 5.66, 95% CI 0.00–13.88) and CVE (OR = 4.40, 95% CI 0.01–5.68), and lower MI (OR = 0.51, 95% CI 0.00–2.86), TVR (OR = 0.53, 95% CI 0.05–2.26), and thus the MACCE (OR = 0.51, 95% CI 0.00–2.35). Off-pump CABG presented a better outcome than HCR with significant lower MACCE (OR = 0.17, 95% CI 0.01–0.68). Surface under the cumulative ranking probabilities showed that HCR may be the superior strategy for MVD and LMCA disease when regarded to MACCE (SUCRA = 0.84), MI (SUCRA = 0.76) in short term, and regarded to MACCE (SUCRA = 0.99), MI (SUCRA = 0.94), and CVE (SUCRA = 0.92) in midterm.Hybrid coronary revascularization seemed to be a feasible and acceptable option for treatment of LMCA disease and MVD. More powerful evidences are required to precisely evaluate risks and benefits of the 3 therapies for patients who have different clinical characteristics.

Short- and Long-Term Patient Outcomes From Combined Coronary Endarterectomy and Coronary Artery Bypass Grafting: A Meta-Analysis of 63,730 Patients (PRISMA).

This meta-analysis aimed to compare the short- and long-term outcomes in patients undergoing combined coronary endarterectomy and coronary artery bypass grafting (CE + CABG) versus isolated CABG, and particularly to examine subgroup patients with high-risk profile and patients with diffuse disease in the left anterior descending artery (LAD).Studies published between January 1, 1970 and May 31, 2015 were searched in the literature databases, including Ovid Medline, Embase, PubMed, and ISI Web of Science.A total of 30 eligible studies including 63,730 patients were analyzed.Five authors extracted data from the included studies independently.Meta-analysis on the total patients revealed that CE + CABG was associated with significantly increased 30-day postoperative all-cause mortality compared with isolated CABG (OR = 1.86, 95% CI: 1.66–2.08, z = 10.99, P < 0.0001). Subgroup analysis on patients with high-risk profile and patients with diffuse disease in the LAD showed that 30-day mortality after CE + CABG was 2.6 folds (OR = 2.60, 95% CI: 1.39–4.86, z = 2.99, P = 0.003) and 3.93 folds (OR = 3.93, 95% CI: 1.40–11.0, z = 2.60, P = 0.009) of that after isolated CABG in the respective subgroup. In contrast, the mortality was comparable in CE + off-pump CABG and CE + on-pump CABG groups (OR = 0.53, 95% CI: 0.18–1.55, z = 1.16, P = 0.248). In addition, the incidences of perioperative myocardial infarction (MI) and 30-day postoperative complications, including low output syndrome (LOS), MI, ventricular tachycardia (VT), and renal dysfunction after CE + CABG were significantly higher than those after isolated CABG (all P < 0.05). In high-risk patient subgroup, CE + CABG significantly increased the incidences of postoperative LOS, MI, and renal function compared with isolated CABG (all P < 0.05). The incidence of perioperative myocardial after CE + CABG was 2.86 and 2.92 times of that after isolated CABG in high-risk patients and patients with diffuse disease in LAD, respectively. Analysis on the recent reports (published later than 2000) showed consistent results as the analysis including all the eligible reports. Long-term survival was comparable in CE + CABG and isolated CABG groups (hazardous ratio = 1.16, 95% CI: 0.32–4.22, z = 0.23, P = 0.819).CE + CABG appears to be associated with poor short-term outcomes, particularly in high-risk patients and patients with diffuse disease in the LAD.

Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in Treated Hypertensive Patients: LIFE Study.

In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment. Myocardial oxygen demand was assessed indirectly by the left ventricular mass×wall stress×heart rate (triple product) in 905 LIFE participants. The triple product was included as time-varying covariate in Cox models assessing predictors of the LIFE primary composite end point (cardiovascular death, MI, or stroke), its individual components, and all-cause mortality. At baseline, the triple product in both treatment groups was, compared with normal adults, elevated in 70% of patients. During randomized treatment, the triple product was reduced more by atenolol, with prevalences of elevated triple product of 39% versus 51% on losartan (both P≤0.001). In Cox regression analyses adjusting for age, smoking, diabetes mellitus, and prior stroke, MI, and heart failure, 1 SD lower triple product was associated with 23% (95% confidence interval 13%-32%) fewer composite end points, 31% (18%-41%) less cardiovascular mortality, 30% (15%-41%) lower MI, and 22% (11%-33%) lower all-cause mortality (all P≤0.001), without association with stroke (P=0.34). Although losartan-based therapy reduced ventricular mass more, greater heart rate reduction with atenolol resulted in larger reduction of the triple product. Lower triple product during antihypertensive treatment was strongly, independently associated with lower rates of the LIFE primary composite end point, cardiovascular death, and MI, but not stroke.

Zotarolimus-Eluting Versus Bare-Metal Stents in Uncertain Drug-Eluting Stent Candidates

BackgroundThe use of drug-eluting stents (DES) in patients at high risk of bleeding or thrombosis has not been prospectively studied; limited data are available in patients who have a low restenosis risk. ObjectivesThis study sought to compare a hydrophilic polymer-based, second-generation zotarolimus-eluting stent (ZES) with a unique drug fast-release profile versus bare-metal stents (BMS) under similar durations of dual-antiplatelet therapy (DAPT). MethodsWe randomly assigned 1,606 patients with stable or unstable symptoms, and who on the basis of thrombotic bleeding or restenosis risk criteria, qualified as uncertain candidates for DES, to receive ZES or BMS. DAPT duration was on the basis of patient characteristics, rather than stent characteristics, and allowed for a personalized 1-month dual antiplatelet regimen. The primary endpoint was the risk of 1-year major adverse cardiovascular events (MACE), which included death, myocardial infarction (MI), or target vessel revascularization (TVR). ResultsMedian DAPT duration was 32 days (interquartile range [IQR]: 30 to 180 days) and did not differ between the groups. In the ZES group, 140 patients (17.5%) reached the primary endpoint, compared with 178 patients (22.1%) in the BMS group (hazard ratio: 0.76; 95% confidence interval: 0.61 to 0.95; p = 0.011) as a result of lower MI (2.9% vs. 8.1%; p < 0.001) and TVR rates (5.9% vs.10.7%; p = 0.001) in the ZES group. Definite or probable stent thrombosis was also significantly reduced in ZES recipients (2.0% vs. 4.1%; p = 0.019). ConclusionsCompared with BMS, DES implantation using a stent with a biocompatible polymer and fast drug-eluting characteristics, combined with an abbreviated, tailored DAPT regimen, resulted in a lower risk of 1-year MACE in uncertain candidates for DES implantation. (Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS] Study; NCT01385319)

Why Does Exercise "Trigger" Adaptive Protective Responses in the Heart?

Numerous epidemiological studies suggest that individuals who exercise have decreased cardiac morbidity and mortality. Pre-clinical studies in animal models also find clear cardioprotective phenotypes in animals that exercise, specifically characterized by lower myocardial infarction and arrhythmia. Despite the clear benefits, the underlying cellular and molecular mechanisms that are responsible for exercise preconditioning are not fully understood. In particular, the adaptive signaling events that occur during exercise to “trigger” cardioprotection represent emerging paradigms. In this review, we discuss recent studies that have identified several different factors that appear to initiate exercise preconditioning. We summarize the evidence for and against specific cellular factors in triggering exercise adaptations and identify areas for future study.

Dose–response association of physical activity with acute myocardial infarction: Do amount and intensity matter?

ObjectiveThe aims of this study were to analyze the dose–response association between leisure time physical activity (PA) practice and myocardial infarction (MI), considering not only the total amount but also the amount of PA at different levels of intensity, and to determine whether these associations were modified by age. MethodIn a population-based age- and sex-matched case–control study, all first acute MI patients aged 25 to 74years were prospectively registered in four Spanish hospitals between 2002 and 2004. Controls were randomly selected from population-based samples recruited during the same period of time. The Minnesota PA questionnaire was administered to assess total energy expenditure in PA and in light-, moderate-, and high-intensity PA. ResultsFinally, 1339 cases and 1339 controls were included. The association between PA and MI likelihood was non-linear, with significantly lower MI odds at low practice levels (≥500MET·min/week), lowest odds around 1500MET·min/week, and a plateau thereafter. Light- (in subjects older than 64years), moderate-, and high-intensity PA produced similar benefits. ConclusionMost of the population could reduce their likelihood of MI by engaging in PA at a moderate level of intensity or, in individuals older than 64years, at a light level of intensity.

Association Between ALT Level and the Rate of Cardio/Cerebrovascular Events in HIV-Positive Individuals

An inverse association between serum alanine aminotransferase (ALT) levels and the risk of myocardial infarction (MI) has been reported in the general population. We investigated associations between ALT levels and the risk of various cardiovascular and cerebrovascular outcomes in a large cohort study of HIV-positive individuals. Using Poisson regression, we investigated associations between the latest ALT level and MI, coronary heart disease (CHD), and stroke, after adjusting for known confounders and cumulative/recent exposure to antiretroviral drugs. Analyses were also performed for the end points of all-cause/liver-related mortality and new-onset diabetes mellitus. By February 2011, participants had experienced 541 MIs, 804 CHD, and 258 stroke events. The MI rate decreased from 3.1/1000 person-years among those with ALT ≤18 U/L to 2.1/1000 person-years among those with ALT >60 U/L. After adjustment for confounders, each 2-fold increment in ALT was associated with a 19% drop in the MI rate {relative rate, 0.81 [95% confidence interval (CI): 0.74 to 0.89], P = 0.0001}. A weaker inverse association was seen for CHD with no indication of a linear association between ALT levels and stroke (P = 0.72). Adjusted relative rates were 0.88 (95% CI: 0.81 to 0.97) and 0.70 (95% CI: 0.54 to 0.92) in those who were hepatitis C virus negative and hepatitis C virus positive, respectively, and 0.72 (95% CI: 0.58 to 0.89) and 0.84 (0.77 to 0.93) in injection drug users and non-injection drug users, respectively. Liver-related mortality and diabetes both demonstrated a positive association with ALT levels, whereas all-cause mortality showed a U-shaped relationship. Higher ALT levels are associated with lower MI risk in HIV-positive individuals, but with higher risks of liver-related mortality and diabetes mellitus.

Do TNF Inhibitors Reduce the Risk of Myocardial Infarction in Psoriasis Patients?

To assess whether patients with psoriasis treated with tumor necrosis factor (TNF) inhibitors have a decreased risk of myocardial infarction (MI) compared with those not treated with TNF inhibitors. Retrospective cohort study. Kaiser Permanente Southern California health plan. Patients with at least 3 International Classification of Diseases, Ninth Revision, Clinical Modification, codes for psoriasis (696.1) or psoriatic arthritis (696.0) (without antecedent MI) between January 1, 2004, and November 30, 2010. Incident MI. Of 8845 patients included, 1673 received a TNF inhibitor for at least 2 months (TNF inhibitor cohort), 2097 were TNF inhibitor naive and received other systemic agents or phototherapy (oral/phototherapy cohort), and 5075 were not treated with TNF inhibitors, other systemic therapies, or phototherapy (topical cohort). The median duration of follow-up was 4.3 years (interquartile range, 2.9, 5.5 years), and the median duration of TNF inhibitor therapy was 685 days (interquartile range, 215, 1312 days). After adjusting for MI risk factors, the TNF inhibitor cohort had a significantly lower hazard of MI compared with the topical cohort (adjusted hazard ratio, 0.50; 95% CI, 0.32-0.79). The incidence of MI in the TNF inhibitor, oral/phototherapy, and topical cohorts were 3.05, 3.85, and 6.73 per 1000 patient-years, respectively. Use of TNF inhibitors for psoriasis was associated with a significant reduction in MI risk and incident rate compared with treatment with topical agents. Use of TNF inhibitors for psoriasis was associated with a non-statistically significant lower MI incident rate compared with treatment with oral agents/phototherapy.

Abstract 203: Outcomes Comparison of Low Risk Medical and Surgical Patients Treated with Unfractionated Heparin vs. Enoxaparin

Objectives: We sought to compare the relative risks for adverse arterial vascular events in patients considered to be low risk for venous thromboembolism (VTE) events who were treated with enoxaparin compared to unfractionated heparin (UFH) for VTE prophylaxis, while comparing clinical efficacy for VTE and overall inpatient costs. Methods: We retrospectively identified patients admitted to the medical and general surgical services who received VTE prophylaxis with either UFH or enoxaparin and compared outcomes before and after implementation of a evidenced based anticoagulation protocol during a twelve month period. Exclusions were: (1) high risk surgical patients, specifically patients undergoing orthopedic, cardiovascular, and bariatric surgery; (2) high risk medical patients, specifically patients admitted with, or having a history of, pulmonary embolism (PE), deep venous thrombosis, atrial fibrillation, or valve replacement; and (3) patients with a therapeutic INR (&gt;2.0) on admission. Using Logistic regression analysis, the following outcomes were compared between the UFH and enoxaparin treated groups: deep venous thrombosis, PE, myocardial infarction (MI), stroke, transient ischemic attack (TIA), heparin induced thrombocytopenia (HIT) and mortality among both groups. Length of hospital stay (LOS) and length of intensive care unit (ICU) LOS were compared using multiple regression analysis. Total costs between the two treatment groups were also compared using a t-test. Results: From the study group, a total of 6,390 patients received UFH prophylaxis and 1,565 received enoxaparin. The enoxaparin patients’ average age was younger than the UFH treated patients’ age by 2.4 years (59.1 and 61.5 years old, respectively, p&lt;0.0001). The incidence of deep venous thrombosis, PE and HIT was similar in both groups. The enoxaparin group had a 52% higher odds for TIA (3.64 vs. 2.49 per 100 patients, OR=1.52, CI 1.113,2.078, p= 0.0024), 61% higher odds for stroke (9.3 vs. 6.6 per 100 patients, OR=1.589, CI 1.298, 1.945, p= 0.0009), while having a 54% lower odds for MI (2.1 vs. 4.7 per 100 patients, OR=0.46,CI 0.32, 0.66, p&lt;0.0001) and lower mortality rate (0 vs. 1.3 per 100 patients). The hospital LOS in the enoxaparin group was 0.73 days lower than in the heparin group (4.41 days vs. 5.13 days, p&lt;0.0001) and the ICU LOS was also shorter by 0.6 days (0.095 vs. 0.69 days, p&lt;0.0001). The total cost (20, 690 vs. 25,946 dollars) was lower in the enoxaparin group. Conclusions: In low-risk medical and general surgical patients, UFH was as effective as enoxaparin in the prevention of thromboembolic events, with no difference in the incidence of HIT. When compared to UFH, enoxaparin was associated with lower MI and mortality rates, and shorter LOS and ICU LOS, at the expense of higher rates of stroke and TIA. Enoxaparin was associated with lower total inpatient costs than UFH.

Chronic aspirin via dose-dependent and selective inhibition of cardiac proteasome possibly contributed a potential risk to the ischemic heart

Impaired cardiac proteasome has been reported in ischemic heart and heart failure. Recent data highlighted aspirin as an inhibitor of the ubiquitin-proteasome system, however, it's unclear whether it affects cardiac proteasome functions. Myocardial infarction (MI), sham or normal male SD rats were injected intraperitoneally with high (300mg/kg), low (5mg/kg) aspirin or saline (control) once a day for seven weeks. Parallel experiments were performed in the hypoxia/reoxygenated human ventricular myocytes. Dose-related increases in heart and ventricular weight, and impaired cardiac functions, were found more exacerbated in the aspirin-treated MI rat hearts than the saline-treated MI counterparts. The activity of 26S, 20S and 19S declined by about 30%, or the 20S proteasome subunits β5, β2 and β1 decreased by 40%, 20% and 30%, respectively, in the MI rats compared with the non-MI rats (P<0.05). Compared with the saline-treated MI rats, 26S and 20S in high or low dose aspirin-treated MI rats further decreased by 30% and 20%, β5 by 30% and 12%, and β1 by 40% and 30%, respectively, and the lost activity was correlated with the compromised cardiac functions or the decreased cell viability. The dose-related and selective inhibition of 26S and 20S proteasome, or the 20S proteasome subunits β5 and β1 by aspirin was comparable to their protein expressions in the MI rats and in the cultured cells. The impaired cardiac proteasome, enhanced by chronic aspirin treatment, attenuated the removal of oxidative and ubiquitinated proteins, and chronic aspirin treatment via selective and dose-dependent inhibition of cardiac proteasome possibly constituted a potential risk to ischemic heart.

253: The effect of statins on the risk of first non-fatal myocardial infarction: A population-based observational study using the PGRx information system

Despite demonstrated positive effects in a number of clinical trials, the evidence is lacking as to the impact of statins on the risk of first myocardial infarction (MI) in real life settings. To assess the impact of real life statin utilization on the risk of first non-fatal MI Case-control methodology using the pharmacoepidemiological information system PGRx. Data on comorbidities, risk factors and medications were obtained from medical records and patient telephone interviews. General practices (n=371) and cardiology centres (n=60) across France were employed in the study. Cases were patients with the first MI ≤ 1 month before the date of recruitment (n=2238). Controls were patients seen by a general practitioner (GP) with no restriction as to the reasons of consultation (n=2238), matched to MI cases on gender, age, frequency of visits to a doctor, date of recruitment and personal history of non-cardiovascular chronic disease. Statin exposure was defined as any utilisation in the two-year prior to date of MI in cases or recruitment date in controls. Adjusted odds ratios (OR) of the risk of first MI was estimated by multiple conditional logistic regression models. Comparative effectiveness and propensity to use of individual statin molecules were assessed. The use of statins was associated with a lower MI risk (adjusted OR 0.67 [95% CI 0.56 - 0.79] for current use (within 2 months before the index date) and 0.73 [0.62 0.86] for any use within 24 months). Among individual statins, rosuvastatin was associated with the lowest MI risk (adjusted OR 0.49 [0.35 - 0.68] for any use in 24 months preceding the index date) followed by simvastatin (0.62 [0.46 - 0.84]). In this first major population-based observational study we reproduced the results observed in recent meta-analyses accounting for real life compliance and population variability. The results could be of interest and applicable to other industrialised countries as the observed risk reduction was constant across MI risk levels.