Combined Endpoint Of Myocardial Infarction Research Articles

Compliance in primary prevention with statins and associations with cardiovascular risk and death in a low-risk diabetes population

Abstract Background Contemporary data exploring cardiovascular risk associated with primary prevention statin treatment according to compliance, in a low-risk diabetes population are limited. Purpose To investigate whether primary prevention with statins and high adherence to statins reduce the associated risk of cardiovascular events or death in a low-risk diabetes population. Methods By use of Danish nationwide registers, we included 59,985 patients with newly diagnosed diabetes aged 40–79 years between 1 January 2005 until 31 June 2010 with no atherosclerotic cardiovascular disease, heart failure or chronic kidney failure prior to 18 months following diabetes diagnosis (index). Individuals were considered treated with statins if they were in treatment at diabetes diagnosis or initiated treatment within the first 6 months following diabetes diagnosis. Among individuals who were treated within the first 6 months, we calculated the proportion of the days covered (PDC) of statins within one year prior to index. We standardized 5-year risks of the combined end-point of myocardial infarction, ischemic stroke or all-cause mortality according to age at index, sex, atrial fibrillation, chronic obstructive pulmonary disease, cancer, ethnicity, year at index, highest attained educational level and claimed prescriptions of antidiabetic, antihypertensive, non-statin lipid-lowering drugs and anticoagulant drugs. Reported were standardized 5-year risk differences of the composite outcome between untreated vs. treated, including PDC, by sex and age-group. Results Following 6 months from the diagnosis of diabetes, 38,029 (63%) individuals were treated with statins, and among individuals treated with statins 23,894 (63%) individuals had a PDC-level of ≥80%. Any use of statins was associated with a lower standardized 5-year risk of the composite outcome (not covered: 15.1% 95% confidence intervals [CI] 14.7–16.0; covered 11.0% [CI 10.7–11.4]), corresponding to a risk difference of 4.1% [CI 3.5–4.6]. The standardized 5-year risks differed by sex, but the risk reductions were similar between men (4.3% [CI 3.5–5.0]) and women (3.9% [CI 3.1–4.7]), and the standardized risk reduction increased with advancing age-group (age 40–49 1.1% [0.2–1.9], 50–59 2.4% [1.5–3.3], 60–69 4.2% [3.2–5.2], 70–79 8.3% [6.7–9.9]. A statin PDC-level of <80% was associated with an increased standardized risk difference (reference PDC≥80%; PDC=60–80% 1.6% [CI 0.7–2.5]; PDC=40–60% 2.1% [CI 0.9–3.3], PDC=20–40% 4.1% [CI 2.8–5.5], PDC<20% 3.2% [CI 2.0–4.5]). Conclusions In 18-month surviving low-risk patients with diabetes, use of statins was associated with a lower 5-year risk of cardiovascular events or death, but a high adherence was important to maintain this effect. The reduced risk associated with statins was similar in men and women, and the magnitude of associated risk reduction increased with advancing age. Standardized 5-year risk differences Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Danish Heart Foundation

Long-term prognostic impact of CT-Leaman score in patients with non-obstructive CAD: Results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study

BackgroundNon-obstructive coronary artery disease (CAD) identified by coronary computed tomography angiography (CCTA) demonstrated prognostic value. CT-adapted Leaman score (CT-LeSc) showed to improve the prognostic stratification. Aim of the study was to evaluate the capability of CT-LeSc to assess long-term prognosis of patients with non-obstructive (CAD). MethodsFrom 17 centers, we enrolled 2402 patients without prior CAD history who underwent CCTA that showed non-obstructive CAD and provided complete information on plaque composition. Patients were divided into a group without CAD and a group with non-obstructive CAD (<50% stenosis). Segment-involvement score (SIS) and CT-LeSc were calculated. Outcomes were non-fatal myocardial infarction (MI) and the combined end-point of MI and all-cause mortality. ResultsPatient mean age was 56±12years. At follow-up (mean 59.8±13.9months), 183 events occurred (53 MI, 99 all-cause deaths and 31 late revascularizations). CT-LeSc was the only multivariate predictor of MI (HRs 2.84 and 2.98 in two models with Framingham and risk factors, respectively) and of MI plus all-cause mortality (HR 2.48 and 1.94 in two models with Framingham and risk factors, respectively). This was confirmed by a net reclassification analysis confirming that the CT-LeSc was able to correctly reclassify a significant proportion of patients (cNRI 0.28 and 0.23 for MI and MI plus all-cause mortality, respectively) vs. baseline model, whereas SIS did not. ConclusionCT-LeSc is an independent predictor of major acute cardiac events, improving prognostic stratification of patients with non-obstructive CAD.

Migraine and risk of cardiovascular disease in women: prospective cohort study

Objective To evaluate the association between migraine and incident cardiovascular disease and cardiovascular mortality in women.Design Prospective cohort study among Nurses’ Health Study II participants, with follow-up from 1989 and...

Abstract W P349: Prediction of Major Adverse Cardiovascular Events by Age-Normalized Carotid Intimal Medial Thickness.

Background: Increases in carotid intimal medial thickness (CIMT), as measured by noninvasive ultrasonography, have been associated with increased risk of myocardial infarction and stroke. From 706 patients who had CIMT measured between 1995 and 2003 at the University of Virginia, we created age-specific quartiles of carotid thickness. Over a mean follow-up of 4.8 years, we found that bulb and internal but not common CIMT predicted the combined endpoint of myocardial infarction, stroke, and revascularization (Atherosclerosis 187:186, 2006). We now present the analysis as of 2012 for CIMT to predict major adverse cardiovascular events in a population of patients referred for carotid IMT measurement. Methods: From 1995-2012, 1427 patients had carotid IMT measured at the University of Virginia’s Preventive Cardiology practice. In 2012, we successfully contacted 1259 of these patients to determine clinical outcomes. The 1259 patients were entered into a database and odds ratios were calculated with logistic regression in SAS. Results: Over a mean follow-up period of 7.8 years (range, 1 to 16), 30 patients died and 66 had major adverse cardiovascular events (MACE): 17 patients had CV death/myocardial infarction; 20 required revascularization; and 29 had a stroke or transient ischemic attack. The highest quartile of bulb CIMT demonstrated an odds ratio for MACE of 7.2 (95% confidence interval, 3.0 to 18.6; P&lt;0.001) when compared to the quartile with the lowest thickness (P&lt;0.001 for trend). The highest quartile of internal CIMT demonstrated an odds ratio for MACE of 3.1 (95% confidence interval, 1.2 to 8.3; P=0.02) when compared to the quartile with the lowest thickness (P=0.009 for trend). Common carotid IMT did not significantly predict MACE (p=0.23). The highest quartile of bulb CIMT demonstrated an odds ratio for mortality of 3.4 (95% confidence interval, 1.03 to 11.2; P=0.044) when compared to the quartile with the lowest thickness (not significant for common or internal CIMT). Conclusions: Age-normalized measurement of bulb and internal but not common CIMT appear to predict which individuals would most benefit from aggressive risk-factor modification.

Meta-Analysis of Staged Versus Combined Carotid Endarterectomy and Coronary Artery Bypass Grafting

The multiple options in the management of patients with concomitant carotid and coronary artery disease (CAD) make it difficult to find a clear consensus regarding the ideal surgical strategy. We performed a meta-analysis of studies comparing early outcomes of synchronous and staged approach of carotid endarterectomy and coronary artery bypass grafting. All English language publications were searched using the terms "carotid artery disease," "coronary artery disease," "carotid endarterectomy," and "coronary artery bypass grafting" alone or in combination. The endpoints studied were early mortality, major stroke, and major postoperative morbidity; myocardial infarction (MI) and stroke, and combined early mortality or stroke. Early events were compared using pooled estimates of risk ratios (RR) (random effects model) utilizing the inverse-variance method. Twelve studies were identified with a total of 17,469 and 7,552 patients in the combined and staged group, respectively. The pooled analysis revealed no difference in the early mortality (RR 1.36 [0.78, 2.36]; p = 0.27), post operative stroke (RR 1.14 [0.99, 1.31], p = 0.07), combined early mortality or stroke (RR 1.08 [0.98, 1.20], p = 0.11) and combined endpoint of MI or stroke (RR 0.75 [0.48, 1.17; I(2) = 11%], p = 0.2) between the 2 surgical approaches. Our meta-analysis of observational studies suggests comparable outcomes in combined and staged approach for synchronous carotid and coronary artery disease. Hence, the 2 strategies can be used interchangeable in the clinical practice, with each having specific applications linked to specific clinical conditions. A randomized trial is warranted to answer this question definitively.

Non-steroidal anti-inflammatory drugs and risk of cardiovascular disease in patients with rheumatoid arthritis: a nationwide cohort study

ObjectiveTo examine the risk of major cardiovascular disease associated with non-steroidal anti-inflammatory drugs (NSAIDs) in a large ‘real-world’ contemporary rheumatoid arthritis (RA) cohort.MethodsA longitudinal cohort study was conducted with use...

FRI0115 Non-steroidal anti-inflammatory drug use and the risk of cardiovascular disease in patients with rheumatoid arthritis – is there a risk?

BackgroundSafety data from clinical trials have raised concerns over the cardiovascular (CV) safety of non-steroidal anti-inflammatory drug (NSAID) use in general. Despite the widespread use of NSAIDs in RA patients,...

The thiazolidinediones rosiglitazone and pioglitazone and the risk of coronary heart disease: A retrospective cohort study using a US health insurance database

Background: The thiazolidinediones (TZDs), including rosiglitazone maleate and pioglitazone hydrochloride, are commonly prescribed in patients with type 2 diabetes mellitus. Although recent meta-analyses suggest there is an increased risk of myocardial infarction (MI) among rosiglitazone users, these findings were not supported by data from other studies. Objective: The goal of this research was to compare the risk of MI, coronary revascularization (CR), and sudden death in patients who began rosiglitazone therapy versus those who began pioglitazone therapy. Methods: This was a retrospective cohort study using information from a large health care database (with data available on ~14 million individuals). All initiators of rosiglitazone or pioglitazone from July 1, 2000, through March 31, 2007, for whom the first dispensing followed ≥6 months of health plan membership and the member's 18th birthday were identified. The propensity score method was used to create matched cohorts of patients in 3 treatment groups: TZD monotherapy, dual therapy (a TZD plus another antidiabetic agent), and TZD therapy with concomitant insulin. Follow-up continued to a change in treatment regimen, defined as regimen switch (ie, the addition of any antidiabetic agent to an existing regimen) or regimen stop (ie, the discontinuation of any component of the therapeutic regimen). Three outcomes that represent coronary heart disease were assessed for this analysis: MI, CR, and sudden death. The proportional hazards model, stratified by therapeutic regimen, was used to estimate hazard ratios (HRs) and 95% CIs of coronary heart disease risk associated with use of rosiglitazone relative to pioglitazone. Results: Among 47,501 matched pairs of rosiglitazone and pioglitazone users, 72,104 (75.9%) were receiving TZD monotherapy, 17,822 (18.8%) were receiving dual therapy, and 5076 (5.3%) were receiving TZD therapy with insulin. Mean follow-up was 9.6 months with regimen switch as the censoring event and 8.4 months with regimen stop as the censoring event. For MI, the HR was 1.35 (95% CI, 1.12–1.62) through regimen switch and 1.41 (95% CI, 1.13–1.75) through regimen stop. For the composite outcome of MI, CR, and/or sudden death, the HR was 1.09 (95% CI, 0.97–1.22) through regimen switch and 1.12 (95% CI, 0.98–1.27) through regimen stop. Conclusions: In this retrospective cohort analysis, MI was more common in users of rosiglitazone than in users of pioglitazone. The incidence of a combined end point of MI, CR, and/or sudden death in patients receiving rosiglitazone was not significantly different from that in patients receiving pioglitazone.

The impact of micro troponin leak on long‐term outcomes following elective percutaneous coronary intervention

To evaluate the clinical impact of microleaks of troponin, which are below the reference standard defining troponin elevation, on cardiovascular outcomes in stable coronary patients undergoing elective percutaneous coronary intervention (PCI). Troponin elevation, either pre- or post-PCI, has been shown to predict poor cardiovascular outcomes. However, troponin measurements that are above the limit of detection but below the 99th percentile limit defining elevation ("microleak") have uncertain clinical significance. We assessed subsequent myocardial infarction (MI) and death over a mean follow-up of 4.2 years in 2,272 patients undergoing elective PCI, where baseline troponins were normal and follow-up troponins were obtained 12-24 hr post-PCI. Patients were divided into three groups based on post-PCI troponin levels: Group 1 (n = 1,313) nondetectable; group 2 (n = 587) microleak, and group 3 (n = 372) elevated suggesting myocardial necrosis. The combined endpoint of MI and death was similar in groups 2 and 3 (50.3 vs. 51.9%, respectively, P = NS), which was significantly more than group 1 patients (35.6%, P < 0.01) over the follow-up period. Multivariate analysis of patients in groups 1 and 2 demonstrated that troponin microleak was an independent predictor of MI and death (P = 0.01). Microleak of troponin following elective PCI suggests myocardial injury and predicts an increased risk of subsequent MI and death. Troponins should be routinely assessed following PCI, and preventive therapies are needed to reduce micro and macro troponin elevation in the PCI setting.

PLTP activity is a risk factor for subsequent cardiovascular events in CAD patients under statin therapy: the AtheroGene Study

Phospholipid transferprotein (PLTP) mediates both net transfer and exchange of phospholipids between different lipoproteins. Although many studies have investigated the role of PLTP in atherogenesis, the role of PLTP in atherosclerotic diseases is unclear. We investigated the association of serum PLTP activity with the incidence of a combined endpoint (myocardial infarction and cardiovascular death) and its relation to other markers of atherosclerosis in 1,085 patients with angiographically documented coronary artery disease (CAD). In the median follow-up of 5.1 years, 156 patients had suffered from the combined endpoint of myocardial infarction or cardiovascular death including 47 of 395 patients who were on statins at baseline. In Kaplan-Meyer analyses serum PLTP activity was not associated with the combined endpoint in all patients. However, in the subgroup of patients receiving statins at baseline, PLTP was shown to be a significant predictor of cardiovascular outcome (P = 0.019), and this also remained stable in univariate (P = 0.027) and multivariate cox regression analyses (P = 0.041) including potential confounders (classical risk factors, HDL cholesterol (HDL-C), and others). We showed in our study that, under statin treatment, high plasma PLTP activity was related to fatal and nonfatal cardiovascular events in CAD patients.

Adverse effect of increased left ventricular wall thickness on five year outcomes of patients with negative dobutamine stress.

BackgroundTo determine if patients without dobutamine induced left ventricular wall motion abnormalities (WMA) but an increased LV end-diastolic wall thickness (EDWT) exhibit a favorable cardiac prognosis.ResultsBetween 1999 and 2001, 175 patients underwent a dobutamine stress cardiovascular magnetic resonance (DCMR) procedure utilizing gradient-echo cines. Participants had a LV ejection fraction >55% without evidence of an inducible WMA during peak dobutamine/atropine stress. After an average of 5.5 years, all participants were contacted and medical records were reviewed to determine the post-DCMR occurrence of cardiac death, myocardial infarction (MI), and unstable angina (USA) or congestive heart failure (CHF) warranting hospitalization.In a multivariate analysis, that took into account Framingham and other risk factors associated with cardiac events, a cine gradient-echo derived LV EDWT ≥12 mm was associated independently with an increase in cardiac death and MI (HR 6.0, p = 0.0016), and the combined end point of MI, cardiac death, and USA or CHF warranting hospitalization (HR 3.0, p = 0.0005).ConclusionSimilar to echocardiography, CMR measures of increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prognostic studies of the importance of LV wall thickness and mass measured with steady-state free precession techniques are warranted.

Effects of Antibiotic Therapy on Outcomes of Patients With Coronary Artery Disease

Although Chlamydia pneumoniae infection has been associated with the initiation and progression of atherosclerosis, results of clinical trials investigating antichlamydial antibiotics as adjuncts to standard therapy in patients with coronary artery disease (CAD) have been inconsistent. To conduct a meta-analysis of clinical trials of antichlamydial antibiotic therapy in patients with CAD. The MEDLINE and Cochrane Central Register of Controlled Trials databases were searched from 1966 to April 2005 for English-language trials of antibiotic therapy in patients with CAD. Bibliographies of retrieved articles were searched for further studies. Presentations at major scientific meetings (2003-2004) were also reviewed. Search terms included antibacterial agents, myocardial infarction, unstable angina, and coronary arteriosclerosis. Eligible studies were prospective, randomized, placebo-controlled trials of antichlamydial antibiotic therapy in patients with CAD that reported all-cause mortality, myocardial infarction, or unstable angina. Of the 110 potentially relevant articles identified, 11 reports enrolling 19,217 patients were included. Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points. End points of interest included all-cause mortality, myocardial infarction (MI), and a combined end point of MI and unstable angina. Event rates were combined using a random-effects model. Antibiotic therapy had no impact on all-cause mortality among treated vs untreated patients (4.7% vs 4.6%; odds ratio [OR], 1.02; 95% confidence interval [CI], 0.89-1.16; P = .83), on the rates of MI (5.0% vs 5.4%; OR, 0.92; 95% CI, 0.81-1.04; P = .19), or on the combined end point of MI and unstable angina (9.2% vs 9.6%; OR, 0.91; 95% CI, 0.76-1.07; P = .25). Evidence available to date does not demonstrate an overall benefit of antibiotic therapy in reducing mortality or cardiovascular events in patients with CAD.

Is There Any Reason to Withhold α2Agonists from Patients with Coronary Disease during Surgery?

* Erasmus Medical Center, Rotterdam, The Netherlands. d.poldermans@erasmusmc.nlWe appreciate the interest and valuable comments of Drs. Quintin and Ghignone in our Editorial View published in the January issue of Anesthesiology.1Along with β blockers, α2agonists may offer significant protection against cardiac morbidity and mortality in patients undergoing major noncardiac surgery.2–5α2Agonists have also been proposed as an alternative cardioprotective treatment strategy in high-risk surgical patients who have relative or absolute contraindication to β-blocker use.6To support their view, Drs. Quintin and Ghignone refer to large-scale clinical trials and several meta-analyses performed in recent years. However, the only large-scale study available to date is that of Oliver et al. ,5which showed no overall effect of mivazerol (an intravenous α2agonist) on the prespecified combined endpoint of myocardial infarction and cardiac death in the whole study population of 2,854 patients. Only a post hoc analysis showed that in a subgroup of 904 patients with known coronary artery disease who underwent major vascular surgery, mivazerol was associated with a significantly lower incidence of the combined endpoint. The meta-analyses cited also show similar findings that perioperative benefits may depend largely on the patients at risk and the surgical procedure involved, with the largest benefit observed in patients undergoing major vascular surgery.2–4These findings and Drs. Quintin and Ghignone’s7own experience prompted them to surmise that clinicians could consider α2agonists as first-line drugs. However, the previous meta-analysis that concluded that clonidine reduced perioperative ischemia4was underpowered (358 noncardiac surgical patients in two studies), and effects were only reported on ischemia.3Furthermore, the results of the two more recent meta-analyses2,3are mainly driven by the results of the large-scale mivazerol trial.In summary, we agree with the statement of Drs. Quintin and Ghignone that future studies directly comparing α2agonists and β blockers are needed. Until then, high-risk patients undergoing major noncardiac surgery should be given β blockers that not only reduce perioperative cardiac morbidity but also improve long-term outcome in patients with coronary artery disease, congestive heart failure, and hypertension.8–11In case of contraindication to β blockers, an α2agonist should be considered as a possible alternative to reduce perioperative cardiac complications.12* Erasmus Medical Center, Rotterdam, The Netherlands. d.poldermans@erasmusmc.nl

Surrogate markers for cardiovascular disease: structural markers.

Pignoli et al1 validated the concept that intima-media thickness (IMT), as measured by B-mode ultrasound and applied either in vitro or in situ at the time of autopsy, reflected direct measurements of aortic and/or carotid specimens. Values obtained by ultrasound at autopsy and by direct measurement were similar to those obtained from living subjects. The characteristic double-line pattern was most consistently found in the far wall of postmortem specimens judged to be relatively normal or affected only by fatty streaks. Histologically, these segments showed homogeneous intima with varying amounts of intimal thickening, intimal fibrosis, internal elastic lamina fragmentation, and duplication. In specimens with more advanced atherosclerosis, the double-line pattern was sometimes perturbed and more complex; these samples showed evidence of a fibrous/muscular cap with a lipid and/or necrotic core and, histologically, the intima showed focal areas of fibrotic smooth muscle cell proliferation, microcalcification, and necrosis. Based on this important article, it is clear that carotid IMT is a direct measure of the status of the vascular wall, and abnormalities are not a surrogate but a direct measure of atherosclerotic and arteriosclerotic processes. The issue of surrogacy pertains to whether a measurement in the carotid bed is associated with atherosclerosis in other beds, particularly the coronary bed and, even more important, whether this measurement is predictive of vascular events that result from atherothrombotic disease. ### Methodology Carotid ultrasound is routinely applied for evaluation of ischemic cerebrovascular signs (eg, bruits) and symptoms. In the context of risk stratification, however, the goal is to identify preclinical disease. The degree of carotid disease that appears to be of prognostic value is much subtler, requiring meticulous and detailed measurements of IMT through B-mode ultrasound. These measurements can be made in a reproducible and reliable fashion if sonographers and those making the measurements are trained comprehensively and …

The HOPE Study: practical implications for people with diabetes

Cardiovascular disease is a cause of premature morbidity and mortality in people with diabetes. Methods to reduce the burden of cardiovascular disease in diabetes have included control of glycaemia, reduction of conventional cardiovascular risk factors, and aggressive cardiological treatment for existing cardiovascular disease. ACE inhibitors have been used for control of hypertension, diabetic nephropathy, and for patients with a low ejection fraction. The Heart Outcomes Prevention Evaluation (HOPE) study examined the effects of 10 mg ramipril or placebo in 9297 high risk patients aged 55 or over. Diabetes was a pre-defined subgroup, and 3577 patient with diabetes were recruited who had evidence of vascular disease or had diabetes and one other cardiovascular risk factor (cholesterol>5.2, hypertension, microalbuminuria, smoking). The primary combined endpoint of myocardial infarction, stroke and cardiovascular death was significantly reduced by 25%, with a one third reduction in stroke. This reduction was seen both in patients with and without previous cardiovascular disease, and the benefit was greater than could be attributed to any decrease in blood pressure. The development of overt nephropathy was also reduced. This suggests that treatment with ramipril has vasculoprotective and renoprotective properties in people with diabetes, and should be prescribed or diabetic patients with existing cardiovascular disease or who have a high risk of disease because of the presence of cardiovascular risk factors. Copyright © 2000 John Wiley & Sons, Ltd.

973-110 Successful PTCA for Post-Infarction Ischemia is Associated with Significantly Lower Long-term Mortality

Prognosis after myocardial infarction (MI) is influenced by the occurrence of post-myocardial infarction ischemia and by the presence of an open infarct related artery. Revascularization is performed in patients with postmyocardial infarction ischemia to alleviate symptoms. Due to small numbers of patients in studies observing outcome after PTCA for post-infarction ischemia, it has not been possible to determine outcome for patients with open versus severely narrowed or closed vessels following PTCA. In this study, we compared long-term outcome for reinfarction and death in patients with open versus closed or severely narrowed coronary arteries following PTCA for post-infarction ischemia. 505 consecutive patients undervvent PTCA for post-infarction ischemia at Deaconess Hospital between 1981 and 1989. Follow-up (mean 34 months) after hospital discharge for reinfarction, death, repeat PTCA and coronary bypass grafting was then compared based on the status of the artery at the end of angioplasty (open versus closed or severely narrowed). The 5-year Kaplan-Meier actuarial mortality rate was 4.7% for patients with open vessels and 11.4% for those with severely narrowed or closed vessels. Patients with open vessels had a significantly lower mortality (p = 0.009) and mortality or reinfarction (p = 0.007) as judged by the log-rank statistic. Multivariate Cox proportional hazards analyses controlling for age, gender, type and location of MI and year of PTCA revealed a hazard ratio for death for closed or severely narrowed compared with open arteries of 4.7 (95% CI, 1.49-14.75) and for the combined endpoint of MI or death of 3.2 (95% CI, 1.38-7.39). Patients who undergo successful revascularization with PTCA for post-infarction ischemia have significantly lower death rates than those with severely narrowed or closed arteries following attempted PTCA.