Dataset Information

Association of Lipoprotein(a) With Risk of Recurrent Ischemic Events Following Acute Coronary Syndrome: Analysis of the dal-Outcomes Randomized Clinical Trial.

ABSTRACT: Importance:It is uncertain whether lipoprotein(a) [Lp(a)], which is associated with incident cardiovascular disease, is an independent risk factor for recurrent cardiovascular events after acute coronary syndrome (ACS). Objective:To determine the association of Lp(a) concentration measured after ACS with the subsequent risk of ischemic cardiovascular events. Design, Setting, and Participants:This nested case-cohort analysis was performed as an ad hoc analysis of the dal-Outcomes randomized clinical trial. This trial compared dalcetrapib, the cholesteryl ester transfer protein inhibitor, with placebo in patients with recent ACS and was performed between April 2008 and September 2012 at 935 sites in 27 countries. There were 969 case patients who experienced a primary cardiovascular outcome, and there were 3170 control patients who were event free at the time of a case event and had the same type of index ACS (unstable angina or myocardial infarction) as that of the respective case patients. Concentration of Lp(a) was measured by immunoturbidimetric assay. Data analysis for this present study was conducted from June 8, 2016, to April 21, 2017. Interventions:Patients were randomly assigned to receive treatment with dalcetrapib, 600 mg daily, or matching placebo, beginning 4 to 12 weeks after ACS. Main Outcomes and Measures:Death due to coronary heart disease, a major nonfatal coronary event (myocardial infarction, hospitalization for unstable angina, or resuscitated cardiac arrest), or fatal or nonfatal ischemic stroke. Results:The mean (SD) age was 63 (10) years for the 969 case patients and 60 (9) years for the 3170 control patients, and both cohorts were composed of predominantly male (770 case patients [79%] and 2558 control patients [81%]; P?=?.40) and white patients (858 case patients [89%] and 2825 control patients [89%]; P?=?.62). At baseline, the median (interquartile range) Lp(a) level was 12.3 (4.7-50.9) mg/dL. There was broad application of evidence-based secondary prevention strategies after ACS, including use of statins in 4030 patients (97%). The cumulative distribution of baseline Lp(a) levels did not differ between cases and controls at P?=?.16. Case-cohort regression analysis showed no association of baseline Lp(a) level with risk of cardiovascular events. For a doubling of Lp(a) concentration, the hazard ratio (case to control) was 1.01 (95% CI, 0.96-1.06; P?=?.66) after adjustment for 16 baseline variables, including assigned study treatment. Conclusions and Relevance:For patients with recent ACS who are treated with statins, Lp(a) concentration was not associated with adverse cardiovascular outcomes. These findings call into question whether treatment specifically targeted to reduce Lp(a) levels would thereby lower the risk for ischemic cardiovascular events after ACS. Trial Registration:clinicaltrials.gov Identifier: NCT00658515.

SUBMITTER: Schwartz GG

PROVIDER: S-EPMC5838593 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Association of Lipoprotein(a) With Risk of Recurrent Ischemic Events Following Acute Coronary Syndrome: Analysis of the dal-Outcomes Randomized Clinical Trial.

Schwartz Gregory G GG Ballantyne Christie M CM Barter Philip J PJ Kallend David D Leiter Lawrence A LA Leitersdorf Eran E McMurray John J V JJV Nicholls Stephen J SJ Olsson Anders G AG Shah Prediman K PK Tardif Jean-Claude JC Kittelson John J

JAMA cardiology 20180201 2

<h4>Importance</h4>It is uncertain whether lipoprotein(a) [Lp(a)], which is associated with incident cardiovascular disease, is an independent risk factor for recurrent cardiovascular events after acute coronary syndrome (ACS).<h4>Objective</h4>To determine the association of Lp(a) concentration measured after ACS with the subsequent risk of ischemic cardiovascular events.<h4>Design, setting, and participants</h4>This nested case-cohort analysis was performed as an ad hoc analysis of the dal-Out ...[more]

PMID: 29071331

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Project description:Estimates of the risk of recurrent cardiovascular events (residual risk) among patients with acute coronary syndromes have largely been based on clinical trial populations. Our objective was to estimate the residual risk associated with common comorbidities in a large, unselected, population-based cohort of acute coronary syndrome patients. 31,056 ACS patients (49.5%-non-ST segment elevation myocardial infarction [NSTEMI], 34.0%-ST segment elevation myocardial infarction [STEMI] and 16.5%-unstable angina [UA]) hospitalised in Alberta between April 2010 and March 2016 were included. The primary composite outcome was major adverse cardiovascular events (MACE) including: death, stroke or recurrent myocardial infarction. The secondary outcome was death from any cause. Cox-proportional hazard models were used to identify the impact of ACS type and commonly observed comorbidities (heart failure, hypertension, peripheral vascular disease, renal disease, cerebrovascular disease and diabetes). At 3.0 +/- 3.7 years, rates of MACE were highest in the NSTEMI population followed by STEMI and UA (3.58, 2.41 and 1.68 per 10,000 person years respectively). Mortality was also highest in the NSTEMI population followed by STEMI and UA (2.23, 1.38 and 0.95 per 10,000 person years respectively). Increased burden of comorbidities was associated with an increased risk of MACE, most prominently seen with heart failure (adjusted HR 1.83; 95% CI 1.73-1.93), renal disease (adjusted HR 1.52; 95% CI 1.40-1.65) and diabetes (adjusted HR 1.51; 95% CI 1.44-1.59). The cumulative presence of each of examined comorbidities was associated with an incremental increase in the rate of MACE ranging from 1.7 to 9.98 per 10,000 person years. Rates of secondary prevention medications at discharge were high including: statin (89.5%), angiotensin converting enzyme inhibitor/angiotensin receptor blocker (84.1%) and beta-blockers (85.9%). Residual cardiovascular risk following an acute coronary syndrome remains high despite advances in secondary prevention. A higher burden of comorbidities is associated with increased residual risk that may benefit from aggressive or novel therapies.

Project description:Background Patients who have had an acute coronary syndrome ( ACS ) are at increased risk of recurrent cardiovascular events; however, paradoxically, high-risk patients who may derive the greatest benefit from guideline-recommended therapies are often undertreated. The aim of our study was to examine the management, clinical outcomes, and temporal trends of patients after ACS stratified by the Thrombolysis in Myocardial Infarction (TIMI) risk score for secondary prevention, a recently validated clinical tool that incorporates 9 clinical risk factors. Methods and Results Included were patients with ACS enrolled in the biennial Acute Coronary Syndrome Israeli Surveys ( ACSIS ) between 2008 and 2016. Patients were stratified by the TIMI risk score for secondary prevention to low (score 0-1), intermediate (2), or high (≥3) risk. Clinical outcomes included 30-day major adverse cardiac events (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1-year mortality. Of 6827 ACS patients enrolled, 35% were low risk, 27% were intermediate risk, and 38% were high risk. Compared with the other risk groups, high-risk patients were older, were more commonly female, and had more renal dysfunction and heart failure ( P<0.001 for each). High-risk patients were treated less commonly with guideline-recommended therapies during hospitalization (percutaneous coronary intervention) and at discharge (statins, dual-antiplatelet therapy, cardiac rehabilitation). Overall, high-risk patients had higher rates of 30-day major adverse cardiac events (7.2% low, 8.2% intermediate, and 15.1% high risk; P<0.001) and 1-year mortality (1.9%, 4.6%, and 15.8%, respectively; P<0.001). Over the past decade, utilization of guideline-recommended therapies has increased among all risk groups; however, the rate of 30-day major adverse cardiac events has significantly decreased among patients at high risk but not among patients at low and intermediate risk. Similarly, the 1-year mortality rate has decreased numerically only among high-risk patients. Conclusions Despite an improvement in the management of high-risk ACS patients, they are still undertreated with guideline-recommended therapies. Nevertheless, the outcome of high-risk patients after ACS has significantly improved in the past decade, thus they should not be denied these therapies.

Project description:IntroductionObstructive sleep apnea (OSA) severity is based on the apnea-hypopnea index (AHI). The AHI is a simplistic measure that is inadequate for capturing disease severity and its consequences in cardiovascular diseases (CVDs). Deleterious effects of OSA have been suggested to influence the prognosis of specific endotypes of patients with acute coronary syndrome (ACS). We aim to identify respiratory polygraphy (RP) patterns that contribute to identifying the risk of recurrent cardiovascular events in patients with ACS.MethodsPost hoc analysis of the ISAACC study, including 723 patients admitted for a first ACS (NCT01335087) in which RP was performed. To identify specific RP patterns, a principal component analysis (PCA) was performed using six RP parameters: AHI, oxygen desaturation index, mean and minimum oxygen saturation (SaO2), average duration of events and percentage of time with SaO2 < 90%. An independent HypnoLaus population-based cohort was used to validate the RP components.ResultsFrom the ISAACC study, PCA showed that two RP components accounted for 70% of the variance in the RP data. These components were validated in the HypnoLaus cohort, with two similar RP components that explained 71.3% of the variance in the RP data. The first component (component 1) was mainly characterized by low mean SaO2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO2 and long-duration obstructive respiratory events without severe desaturation. In the ISAACC cohort, component 2 was associated with an increased risk of recurrent cardiovascular events in the third tertile with an adjusted hazard ratio (95% CI) of 2.44 (1.07 to 5.56; p-value = 0.03) compared to first tertile. For component 1, no significant association was found for the risk of recurrent cardiovascular events.ConclusionA RP component, mainly characterized by intermittent hypoxemia, is associated with a high risk of recurrent cardiovascular events in patients without previous CVD who have suffered a first ACS.

Project description:BackgroundResidual risk remained significant despite effective low density lipoprotein cholesterol (LDL-C) lowering treatment. Small dense low density lipoprotein cholesterol (sdLDL-C) as part of LDL-C has been found to be predictor of coronary heart disease (CHD) and cardiovascular (CV) events in patients with stable CHD independently of LDL-C. However, to date, few studies have explored the role of sdLDL-C in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Accordingly, this study aimed to evaluate the association of sdLDL-C with CV events in patients with ACS undergoing PCI.MethodsPatients hospitalized with ACS undergoing PCI were enrolled and followed up for 18 months. The risk of sdLDL-C for CV events was compared according to sdLDL-C quartiles. The primary outcome was major cardiovascular and cerebrovascular adverse events (MACCE), which was the composite of all cause of death, nonfatal myocardial infarction (MI), nonfatal stroke or unplanned repeat revascularization. A Cox proportional hazards regression model was performed to estimate the risk of CV events. Subgroup analysis according to diabetes status and LDL-C were performed separately for MACCE.ResultsA total of 6092 patients were included in the analysis (age: 60.2 ± 10.13 years, male: 75.3%, BMI: 25.9 ± 3.33 kg/m2, dyslipidemia: 74.1% and diabetes: 44.5%). During 18 months of follow-up, 320 (5.2%) incident CV events occurred. Compared to the lowest sdLDL-C quartile group, patients in the highest quartile had a greater risk of CV events after multivariable adjustment (HR 1.92; 95% CI 1.37-2.70). In addition, it was mainly due to the increase of unplanned repeat revascularization. In the subgroup analyses, significant association was observed regardless of level of LDL-C and diabetes status.ConclusionsPatients with elevated sdLDL-C have a higher risk of CV events in Chinese patients with ACS undergoing PCI, providing additional value for better risk assessment.

Project description:TIA and minor stroke have a high risk of recurrent stroke. Abnormalities on CT/CTA and MRI predict recurrent events in TIA and minor stroke. However there are many other imaging abnormalities that could potentially predict outcome that have not been assessed in this population. Also the definition of recurrent events used includes deterioration due to stroke progression or recurrent stroke and whether imaging is either of these is not known.To improve upon the clinical, CT/CTA and MRI parameters that predict recurrent events after TIA and minor stroke by assessing further imaging parameters. Secondary aim was to explore predictors of stroke progression versus recurrent stroke.510 consecutive TIA and minor stroke patients had CT/CTA and most had MRI. Primary outcome was recurrent events (stroke progression or recurrent stroke) within 90 days. Further imaging parameters were assessed for prediction of recurrent events (combined outcome of stroke progression and recurrent stroke). We also explored predictors of symptom progression versus recurrence individually.36 recurrent events (36/510, 7.1% (95% CI: 5.0-9.6)) including 19 progression and 17 recurrent strokes. On CT/CTA: white matter disease, prior stroke, aortic arch focal plaque?4 mm, or intraluminal thrombus did not predict recurrent events (progression or recurrent stroke). On MRI: white matter disease, prior stroke, and microbleeds did not predict recurrent events. Parameters predicting the individual outcome of symptom progression included: ongoing symptoms at initial assessment, symptom fluctuation, intracranial occlusion, intracranial occlusion or stenosis, and the CT/CTA metric. No parameter was strongly predictive of a distinct recurrent stroke.There was no imaging parameter that could improve upon our original CT/CTA or MRI metrics to predict the combined outcome of stroke progression or a recurrent stroke after TIA and minor stroke. We are better at using imaging to predict stroke progression rather than recurrent stroke.

Dataset Information

Association of Lipoprotein(a) With Risk of Recurrent Ischemic Events Following Acute Coronary Syndrome: Analysis of the dal-Outcomes Randomized Clinical Trial.

Publications

Association of Lipoprotein(a) With Risk of Recurrent Ischemic Events Following Acute Coronary Syndrome: Analysis of the dal-Outcomes Randomized Clinical Trial.

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