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1.
Eur Heart J ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33748830

RESUMO

AIMS: Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1ß can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown. METHODS AND RESULTS: We explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality. CONCLUSION: The NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.

2.
Lancet ; 397(10278): 985-995, 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33714389

RESUMO

BACKGROUND: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). METHODS: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. FINDINGS: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3·7 (IQR 3·0-4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0-15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2-10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25-4·13) and non-culprit lesion-specific MACEs (7·83, 4·12-14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0-10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4-17·6). INTERPRETATION: Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. FUNDING: Abbott Vascular, Infraredx, and The Medicines Company.

3.
Disabil Rehabil ; : 1-9, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33621136

RESUMO

PURPOSE: The study aimed to explore the self-perceived cognitive status and cognitive challenges associated with lifestyle changes in cardiac rehabilitation among elderly myocardial infarction (MI) patients (≥65 years). Further, the study explored coping strategies developed to manage these challenges in the everyday life. METHODS: Nine patients were included in the study. Data were collected by telephone or in person, between 6 and 12 weeks post MI, using semi-structured interviews. Data were analysed inductively, using thematic analysis. RESULTS: Four major themes were identified, highlighting elderly MI patients' experiences of their cognitive status and cardiac rehabilitation management: (1) A change in cognition over time, (2) Situating the MI within a challenging and changing life context, (3) Navigating the hurdles of cardiac rehabilitation, and (4) Being seen within the healthcare system. CONCLUSION: Elderly MI patients are situated in a complex life context, dealing with a transition to retirement, multiple health issues and age-related cognitive decline. In this context, the MI experience is marginalised, and cognitive decline normalized. By adopting individually tailored interventions and improving healthcare provider continuity and accessibility, cognitive challenges associated with cardiac rehabilitation could be easier to overcome.IMPLICATIONS FOR REHABILITATIONSelf-perceived cognitive impairment, in particular regarding memory, seems fairly common among elderly MI patients and should likely be identified prior to hospital discharge in order to optimize the prospects of self-care.There seems to exist an unmet need to implement the practice of individually adapted education and information further, in accordance with current recommendations for elderly cardiac patients.The overall health and cognitive status, social network and the objective living conditions (e.g., distance from service and housing) should be taken into account when planning the patient's cardiac rehabilitation management.Healthcare providers likely need to strengthen the continuity of care and increase its accessibility for elderly MI patients, in particular following the transfer from hospital care to local health centres.

4.
Am Heart J ; 233: 92-101, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33400910

RESUMO

BACKGROUND: In patients with coronary heart disease (CHD), atrial fibrillation (AF) is associated with increased morbidity and mortality. We investigated the associations between clinical risk factors and biomarkers with incident AF in patients with CHD. METHODS AND RESULTS: Around 13,153 patients with optimally treated CHD included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial with plasma samples obtained at randomization. Mean follow-up time was 3.5 years. The association between clinical risk factors and biomarkers with incident AF was estimated with Cox-regression models. Validation was performed in 1,894 patients with non-ST-elevation acute coronary syndrome included in the FRISC-II trial. The median (min-max) age was 64 years (range 26-92) and 2,514 (19.1%) were women. A total of 541 patients, annual incidence rate of 1.2%, developed AF during follow-up. In multivariable models, older age, higher levels of NT-proBNP, higher body mass index (BMI), male sex, geographic regions, low physical activity, and heart failure were independently associated with increased risk of incident AF with hazard ratios ranging from 1.04 to 1.79 (P ≤ .05). NT-proBNP improved the C-index from 0.70 to 0.71. In the validation cohort, age, BMI, and NT-proBNP were associated with increased risk of incident AF with similar hazard ratios. CONCLUSIONS: In patients with optimally treated CHD, the incidence of new AF was 1.2% per year. Age, NT-proBNP as a marker of impaired cardiac function, and BMI were the strongest factors, independently and consistently associated with incident AF. Male sex and low physical activity may also contribute to the risk of AF in patients with CHD.


Assuntos
Fibrilação Atrial/sangue , Doença das Coronárias/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Doença das Coronárias/tratamento farmacológico , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Sedentário , Fatores Sexuais
5.
PLoS Med ; 18(1): e1003513, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33439866

RESUMO

BACKGROUND: Circulating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and/or organ dysfunction. We explored the associations between 157 cardiovascular (CV) and inflammatory biomarkers and CV death using proximity extension assays (PEA) in patients with chronic CHD. METHODS AND FINDINGS: The derivation cohort consisted of 605 cases with CV death and 2,788 randomly selected non-cases during 3-5 years follow-up included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial between 2008 and 2010. The replication cohort consisted of 245 cases and 1,042 non-cases during 12 years follow-up included in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study between 1997 and 2000. Biomarker levels were measured with conventional immunoassays and/or with the OLINK PEA panels CVD I and Inflammation. Associations with CV death were evaluated by Random Survival Forest (RF) and Cox regression analyses. Both cohorts had the same median age (65 years) and 20% smokers, while there were slight differences in male sex (82% and 76%), hypertension (70% and 78%), and diabetes (39% and 30%) in the respective STABILITY and LURIC cohorts. The analyses identified 18 biomarkers with confirmed independent association with CV death by Boruta analyses and statistical significance (all p < 0.0001) by Cox regression when adjusted for clinical characteristics in both cohorts. Most prognostic information was carried by N-terminal prohormone of brain natriuretic peptide (NTproBNP), hazard ratio (HR for 1 standard deviation [SD] increase of the log scale of the distribution of the biomarker in the replication cohort) 2.079 (95% confidence interval [CI] 1.799-2.402), and high-sensitivity troponin T (cTnT-hs) HR 1.715 (95% CI 1.491-1.973). The other proteins with independent associations were growth differentiation factor 15 (GDF-15) HR 1.728 (95% CI 1.527-1.955), transmembrane immunoglobulin and mucin domain protein (TIM-1) HR 1.555 (95% CI 1.362-1.775), renin HR 1.501 (95% CI 1.305-1.727), osteoprotegerin (OPG) HR 1.488 (95% CI 1.297-1.708), soluble suppression of tumorigenesis 2 protein (sST2) HR 1.478 (95% CI 1.307-1.672), cystatin-C (Cys-C) HR 1.370 (95% CI 1.243-1.510), tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) HR 1.205 (95% CI 1.131-1.285), carbohydrate antigen 125 (CA-125) HR 1.347 (95% CI 1.226-1.479), brain natriuretic peptide (BNP) HR 1.399 (95% CI 1.255-1.561), interleukin 6 (IL-6) HR 1.478 (95% CI 1.316-1.659), hepatocyte growth factor (HGF) HR 1.259 (95% CI 1.134-1.396), spondin-1 HR 1.295 (95% CI 1.156-1.450), fibroblast growth factor 23 (FGF-23) HR 1.349 (95% CI 1.237-1.472), chitinase-3 like protein 1 (CHI3L1) HR 1.284 (95% CI 1.129-1.461), tumor necrosis factor receptor 1 (TNF-R1) HR 1.486 (95% CI 1.307-1.689), and adrenomedullin (AM) HR 1.750 (95% CI 1.490-2.056). The study is limited by the differences in design, size, and length of follow-up of the 2 studies and the lack of results from coronary angiograms and follow-up of nonfatal events. CONCLUSIONS: Profiles of levels of multiple plasma proteins might be useful for the identification of different pathophysiological pathways associated with an increased risk of CV death in patients with chronic CHD. TRIAL REGISTRATION: ClinicalTrials.gov NCT00799903.

6.
Circulation ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33186054

RESUMO

Background: Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and kidney events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease. Methods: In the DAPA-CKD trial (Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomized to dapagliflozin 10 mg once daily or placebo. The primary endpoint was a composite of sustained decline in estimated GFR ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The secondary endpoints were a kidney composite outcome (primary endpoint, minus cardiovascular death), the composite of hospitalization for heart failure or cardiovascular death and all-cause death. In a prespecified subgroup analysis, we divided patients into primary and secondary prevention subgroups according to history of cardiovascular disease. Results: Secondary prevention patients (n=1610; 37.4%) were older, more often male, had a higher blood pressure and body-mass index, and were more likely to have diabetes. Mean estimated glomerular filtration rate and median urinary albumin-to-creatinine ratio was similar in the primary and secondary prevention groups. The rates of adverse cardiovascular outcomes were higher in the secondary prevention group, but kidney failure occurred at the same rate in the primary and secondary prevention groups. Dapagliflozin reduced the risk of the primary composite outcome to a similar extent in both the primary (HR, 0.61 [95% CI, 0.48-0.78]) and secondary (0.61, 0.47-0.79) prevention groups (P-interaction=0.90). This was also true for the composite of heart failure hospitalization or cardiovascular death (0.67, 0.40-1.13 versus 0.70, 0.52-0.94, respectively, P-interaction=0.88), and all-cause (0.63, 0.41-0.98 versus 0.70, 0.51-0.95, respectively, P-interaction=0.71). Rates of adverse events were low overall and did not differ between patients with and without cardiovascular disease. Conclusions: Dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalization for heart failure, and prolonged survival, in people with chronic kidney disease, with or without type 2 diabetes, independently of the presence of concomitant cardiovascular disease Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03036150.

7.
J Am Coll Cardiol ; 76(20): 2289-2301, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33069847

RESUMO

BACKGROUND: Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild. OBJECTIVES: This study sought to examine the outcomes of percutaneous coronary intervention (PCI) of non-flow-limiting vulnerable plaques. METHODS: Three-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with myocardial infarction (MI). Patients with an angiographically nonobstructive stenosis not intended for PCI but with IVUS plaque burden of ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) versus GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (nonpowered) safety endpoint was randomized target lesion failure (cardiac death, target vessel-related MI, or clinically driven target lesion revascularization) at 24 months. The secondary (nonpowered) clinical effectiveness endpoint was randomized lesion-related major adverse cardiac events (cardiac death, MI, unstable angina, or progressive angina) at latest follow-up. RESULTS: A total of 182 patients were randomized (93 BVS, 89 GDMT alone) at 15 centers. The median angiographic diameter stenosis of the randomized lesions was 41.6%; by near-infrared spectroscopy-IVUS, the median plaque burden was 73.7%, the median MLA was 2.9 mm2, and the median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and the median clinical follow-up was 4.1 years. The follow-up MLA in BVS-treated lesions was 6.9 ± 2.6 mm2 compared with 3.0 ± 1.0 mm2 in GDMT alone-treated lesions (least square means difference: 3.9 mm2; 95% confidence interval: 3.3 to 4.5; p < 0.0001). Target lesion failure at 24 months occurred in similar rates of BVS-treated and GDMT alone-treated patients (4.3% vs. 4.5%; p = 0.96). Randomized lesion-related major adverse cardiac events occurred in 4.3% of BVS-treated patients versus 10.7% of GDMT alone-treated patients (odds ratio: 0.38; 95% confidence interval: 0.11 to 1.28; p = 0.12). CONCLUSIONS: PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up MLA, and was associated with favorable long-term clinical outcomes, warranting the performance of an adequately powered randomized trial. (PROSPECT ABSORB [Providing Regional Observations to Study Predictors of Events in the Coronary Tree II Combined with a Randomized, Controlled, Intervention Trial]; NCT02171065).

8.
J Med Internet Res ; 22(9): e19066, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32940615

RESUMO

BACKGROUND: The involvement of patient research partners (PRPs) in research aims to safeguard the needs of patient groups and produce new interventions that are developed based on patient input. Myocardial infarction with nonobstructive coronary arteries (MINOCA), unlike acute myocardial infarction (MI) with obstructive coronary arteries, is presented with no significant obstructive coronary artery disease. Patients with this diagnosis are a subset of those diagnosed with traditional MI and often need more psychological support, something that is presently not established in the current treatment scheme in Swedish health care or elsewhere, to our knowledge. An internet-delivered intervention might offer patients with MINOCA the opportunity to access a psychological treatment that is tailored to their specific needs after MINOCA and could therefore supplement the existing medical care in an easily accessible format. OBJECTIVE: This paper aims to describe the development of a therapist-guided, internet-delivered psychological intervention designed specifically for patients with MINOCA. METHODS: The study used a participatory design that involved 7 PRPs diagnosed with MINOCA who collaborated with a team consisting of researchers, cardiologists, and psychologists. Intervention content was developed iteratively and presented to the PRPs across several prototypes, each continually adjusted and redesigned according to the feedback received. The intervention and experience of it were discussed by PRPs in a final meeting and then presented to a panel of 2 clinical psychologists and a cardiologist for further input. RESULTS: The outcome of the collaboration between PRPs and the research group produced a web-based psychological 9-step program focusing on stress, worry, and valued action. The input from PRPs contributed substantially to the therapy content, homework tasks, interactive activities, multimedia, and design presentation. CONCLUSIONS: Working with PRPs to develop an intervention for people with MINOCA produced a web-based intervention that can be further evaluated with the goal of offering a new psychological treatment option to a patient group currently without one. Direct contribution from PRPs enabled us to obtain relevant, insightful, and valuable feedback that was put towards the overall design and content of the intervention.

9.
JAMA Netw Open ; 3(9): e2015943, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936298

RESUMO

Importance: Most patients with atrial fibrillation (AF) and coronary artery disease have indications for preventing stroke with oral anticoagulation therapy and preventing myocardial infarction and stent thrombosis with platelet inhibition. Objective: To evaluate whether the recently developed ABC (age, biomarkers, and clinical history)-bleeding risk score might be useful to identify patients with AF with different risks of bleeding during concomitant aspirin and anticoagulation therapy. Design, Setting, and Participants: The biomarkers in the ABC-bleeding risk score (growth differentiation factor 15, hemoglobin, and troponin) were measured in blood samples collected at randomization between 2006 and 2010 in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial and between 2005 and 2009 in the RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial, both of which were multinational randomized clinical trials. The trials were reported 2011 and 2009, respectively. A total of 24 349 patients with AF (14 980 patients from the ARISTOTLE trial and 9369 patients from the RE-LY trial) were analyzed in the present cohort study. The median (interquartile range) length of follow-up was 1.8 (1.3-2.3) years in the ARISTOTLE cohort and 2.0 (1.6-2.3) years in the RE-LY cohort. Data analysis was performed from February 2018 to June 2019. Exposures: Concomitant aspirin treatment during study follow-up. Main Outcomes and Measures: Time to first occurrence of a major bleeding was determined according to International Society on Thrombosis and Hemostasis definition. Hazard ratios were estimated with Cox models adjusted for ABC-bleeding risk score and randomized treatment. Results: The median (interquartile range) age was 70 (63-76) years in the ARISTOTLE cohort and 72 (67-77) years in the RE-LY cohort (5238 patients [35.6%] in the ARISTOTLE cohort and 3086 patients [36.4%] in the RE-LY cohort were women). The total number of patients with a first major bleeding event was 651 (207 with aspirin and 444 without) in ARISTOTLE and 463 (238 with aspirin and 225 without) in RE-LY. For both cohorts, in those with a low ABC-bleeding risk score, the absolute bleeding rate was low even with concomitant aspirin treatment, whereas in those with a higher ABC-bleeding risk score, the rate of bleeding was higher with concomitant aspirin compared with oral anticoagulation alone (ARISTOTLE, hazard ratio, 1.65; 95% CI, 1.40-1.95; P < .001; RE-LY, hazard ratio, 1.70; 95% CI, 1.42-2.04; P < .001). Thus, a low annual ABC-bleeding risk (eg, 0.5% without aspirin use) would with concomitant aspirin result in an annual rate of 0.8%, and a high estimated ABC-bleeding risk (eg, 3.0%) would result in a substantially higher rate of 5.0%. Conclusions and Relevance: These findings suggest that the ABC-bleeding risk score identifies patients with different risks of bleeding when combining aspirin and oral anticoagulation. The ABC-bleeding risk score may, therefore, be a useful tool for decision support concerning intensity and duration of combination antithrombotic treatment in patients with AF and coronary artery disease.

10.
Circulation ; 142(6): 546-555, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32654539

RESUMO

BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I2=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity. CONCLUSIONS: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.

11.
Am Heart J ; 225: 97-107, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32480059

RESUMO

BACKGROUND: In patients with stable coronary heart disease, it is not known whether achievement of standard of care (SOC) targets in addition to evidence-based medicine (EBM) is associated with lower major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, and stroke. METHODS: EBM use was recommended in the STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY trial. SOC targets were blood pressure (BP) <140/90 mm Hg and low-density lipoprotein-cholesterol (LDL-C) <100 mg/dL and <70 mg/dL. In patients with diabetes, glycosylated hemoglobin A1c (HbA1c) < 7% and BP of <130/80 mm Hg were recommended. Feedback to investigators about rates of EBM and SOC was provided regularly. RESULTS: In 13,623 patients, 1-year landmark analysis assessed the association between EBM, SOC targets, and MACE during follow-up of 2.7 years (median) after adjustment in a Cox proportional hazards model. At 1 year, aspirin was prescribed in 92.5% of patients, statins in 97.2%, ß-blockers in 79.0%, and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers in 76.9%. MACE was lower with LDL-C < 100 mg/dL (70-99 mg/dL) compared with LDL-C ≥ 100 mg/dL (hazard ratio [HR] 0.694, 95% CI 0.594-0.811) and lower with LDL-C < 70 mg/dL compared with LDL-C < 100 mg/dL (70-99 mg/dL) (HR 0.834, 95% CI 0.708-0.983). MACE was lower with HbA1c < 7% compared with HbA1c ≥ 7% (HR 0.705, 95% CI 0.573-0.866). There was no effect of BP targets on MACE. CONCLUSIONS: MACE was lower with LDL-C < 100 mg/dL (70-99 mg/dL) and even lower with LDL-C < 70 mg/dL. MACE in patients with diabetes was lower with HbA1c < 7%. Achievement of targets is associated with improved patient outcomes.


Assuntos
LDL-Colesterol/sangue , Doença das Coronárias/sangue , Hemoglobina A Glicada/análise , Infarto do Miocárdio/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Doença das Coronárias/complicações , Doença das Coronárias/mortalidade , Medicina Baseada em Evidências , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
12.
J Am Heart Assoc ; 9(10): e015258, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32375553

RESUMO

Background Identification of patients with stable coronary heart disease who are at significant residual risk could be helpful for targeted prevention. Our aim was to determine the prognostic value of the recently introduced ceramide- and phospholipid-based risk score, the Cardiovascular Event Risk Test (CERT2), in patients with stable coronary heart disease on optimal medical therapy and to identify biological processes that contribute to the CERT2 score. Methods and Results Plasma samples (n=11 222) obtained from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were analyzed using a tandem liquid chromatography-mass spectrometry method. STABILITY was a trial in patients with stable coronary heart disease randomized to the lipoprotein-associated phospholipase A2 inhibitor darapladib or placebo on optimized medical therapy at baseline, with a median follow-up of 3.7 years. Hazard ratios per SD for the CERT2 risk score were 1.32 (95% CI, 1.25-1.39) for major adverse cardiovascular event, 1.47 (95% CI, 1.35-1.59) for cardiovascular death, 1.32 (95% CI, 1.16-1.49) for stroke, 1.23 (95% CI, 1.14-1.33) for myocardial infarction, and 1.56 (95% CI, 1.39-1.76) for hospitalization due to heart failure, when adjusted for traditional cardiovascular risk factors. CERT2 showed correlation (P<0.001, r>0.2) with inflammatory markers high-sensitivity C-reactive protein, interleukin 6, the heart failure marker N-terminal pro-B-type natriuretic peptide, and low-density lipoprotein cholesterol. After also adjusting for levels of other prognostic biomarkers, the CERT2 score was still independently related to the risk of cardiovascular death but not to nonfatal events. Conclusions The CERT2 risk score can detect residual risk in patients with stable coronary heart disease and is associated with biomarkers indicating inflammation, myocardial necrosis, myocardial dysfunction, renal dysfunction, and dyslipidemia. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT00799903.

13.
JAMA Cardiol ; 5(7): 773-786, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32227128

RESUMO

Importance: While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization. Objective: To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants. Design, Setting, and Participants: This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018. Interventions: CCTA and angina assessment. Main Outcomes and Measures: Sex differences in stress test, CCTA findings, and symptom severity. Results: Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76). Conclusions and Relevance: Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease. Trial Registration: ClinicalTrials.gov Identifier: NCT01471522.

14.
N Engl J Med ; 382(15): 1395-1407, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32227755

RESUMO

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).


Assuntos
Cateterismo Cardíaco , Ponte de Artéria Coronária , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/cirurgia , Revascularização Miocárdica/métodos , Intervenção Coronária Percutânea , Idoso , Angina Instável/epidemiologia , Teorema de Bayes , Doenças Cardiovasculares/mortalidade , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/terapia , Qualidade de Vida
15.
Am Heart J ; 221: 1-8, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31896036

RESUMO

OBJECTIVES: A history of gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) may impact decisions about anticoagulation treatment. We sought to determine whether prior GIB in patients with AF taking anticoagulants was associated with an increased risk of stroke or major hemorrhage. METHODS: We analyzed key efficacy and safety outcomes in patients with prior GIB in ARISTOTLE. Centrally adjudicated outcomes according to GIB history were analyzed using Cox proportional hazards models adjusted for randomized treatment and established risk factors. RESULTS: A total of 784 (4.3%) patients had prior GIB events (321 [41%] lower, 463 [59%] upper); 215 (27%) occurred <1 year before study enrollment. Patients with prior GIB were older, had more comorbidities, and higher CHADS2 and HAS-BLED scores than those with no GIB. Major GIB occurred more frequently in those with prior GIB (lower: aHR 1.72, 95% CI 0.86-3.42; upper: aHR 3.13, 95% CI 1.97-4.96). This association with major GIB was more pronounced in patients with GIB <1 year before randomization versus no recent GIB (recent lower: aHR 2.58, 95% CI 0.95-7.01; recent upper: aHR 5.16, 95% CI 2.66-10.0). There was no association between prior GIB and risk of stroke/systemic embolism or all-cause death. In those with prior GIB, the apixaban versus warfarin relative risks for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding were consistent with the results of the overall trial. CONCLUSIONS: In patients with AF on oral anticoagulants, prior GIB was associated with an increased risk of subsequent major GIB but not stroke, intracranial bleeding, or all-cause mortality. For the key outcomes of stroke, hemorrhagic stroke, death, and major bleeding, we found no evidence that the treatment effect (apixaban vs. warfarin) was modified by a history of GIB.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/epidemiologia , Hemorragias Intracranianas/epidemiologia , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Varfarina/efeitos adversos , Fatores Etários , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Hemorragias Intracranianas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Mortalidade , Modelos de Riscos Proporcionais , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Risco , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Varfarina/uso terapêutico
16.
Eur J Prev Cardiol ; 27(2): 145-154, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514507

RESUMO

BACKGROUND: The Heart School is a standard component of cardiac rehabilitation after myocardial infarction in Sweden. The group-based educational intervention aims to improve modifiable risks, in turn reducing subsequent morbidity and mortality. However, an evaluation with respect to mortality is lacking. AIMS: Using linked population registries, we estimated the association of attending Heart School with both all-cause and cardiovascular mortality, two and five years after admission for first-time myocardial infarction. METHODS: Patients with first-time myocardial infarction (<75 years) were identified as consecutively registered in the nationwide heart registry, SWEDEHEART (2006-2015), with >99% complete follow-up in the Causes of Death registry for outcome events. Of 192,059 myocardial infarction admissions, 47,907 unique patients with first-time myocardial infarction surviving to the first cardiac rehabilitation visit constituted the study population. The exposure was attending Heart School at the first cardiac rehabilitation visit 6-10 weeks post-myocardial infarction. Data on socioeconomic status was acquired from Statistics Sweden. After multiple imputation, propensity score matching was performed. The association of exposure with mortality was estimated with Cox regression and survival curves. RESULTS: After matching, attending Heart School was associated (hazard ratio (95% confidence interval)) with a markedly lower risk of both all-cause (two-year hazard ratio = 0.53 (0.44-0.64); five-year hazard ratio = 0.62 (0.55-0.69)) and cardiovascular (0.50 (0.38-0.65); 0.57 (0.47-0.69)) mortality. The results were robust in several sensitivity analyses. CONCLUSIONS: Attending Heart School during cardiac rehabilitation is associated with almost halved all-cause and cardiovascular mortality after first-time myocardial infarction. The result warrants further investigation through adequately powered randomised trials.

18.
Circulation ; 141(1): 10-20, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31747786

RESUMO

BACKGROUND: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin. METHODS: The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models. RESULTS: Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11-2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16-2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome. CONCLUSIONS: A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anticoagulantes/administração & dosagem , Fibrilação Atrial , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Varfarina/administração & dosagem , Administração Oral , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Taxa de Sobrevida , Varfarina/efeitos adversos
19.
Eur J Prev Cardiol ; 27(1): 18-27, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31349776

RESUMO

BACKGROUND: While patient performance after participating in cardiac rehabilitation programmes after acute myocardial infarction is regularly reported through registry and survey data, information on cardiac rehabilitation programme characteristics is less well described. AIM: The aim of this study was to evaluate Swedish cardiac rehabilitation programme characteristics and adherence to European Guidelines on Cardiovascular Disease Prevention. METHOD: Cardiac rehabilitation programme characteristics at all 78 cardiac rehabilitation centres in Sweden in 2016 were surveyed using a web-based questionnaire (100% response rate). The questions were based on core components of cardiac rehabilitation as recommended by European Guidelines. RESULTS: There was a wide variation in programme duration (2-14 months). All programmes reported offering an individual post-discharge visit with a nurse, and 90% (n = 70) did so within three weeks from discharge. Most programmes offered centre-based exercise training (n = 76, 97%) and group educational sessions (n = 61, 78%). All programmes reported to the national audit, SWEDEHEART, and 60% (n = 47) reported that performance was regularly assessed using audit data, to improve quality of care. Ninety-six per cent (n = 75) had a core team consisting of a cardiologist, a physiotherapist and a nurse and 76% (n = 59) reported having a medical director. Having other allied healthcare professionals included in the cardiac rehabilitation team varied. Forty per cent (n = 31) reported having regular team meetings where nurses, physiotherapists and cardiologist could discuss patient cases. CONCLUSION: The overall quality of cardiac rehabilitation programmes provided in Sweden is high. Still, there are several areas of potential improvement. Monitoring programme characteristics as well as patient outcomes might improve programme quality and patient outcomes both at a local and a national level.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33620439

RESUMO

AIMS: Dose-dependent effects of ß-blockers on survival and cardiovascular outcomes after myocardial infarction (MI) are not well understood. We investigated the long-term risk of cardiovascular events in patients with different doses of ß-blockers after MI. METHODS AND RESULTS: This was a nationwide observational study linking morbidity, mortality, socioeconomic, and medication data from Swedish national registries. Between 2006 and 2015, 97 575 unique patients with first-time MI were included. In total, 33 126 (33.9%) patients were discharged with ≥50% of the target ß-blocker dose and 64 449 (66.1%) patients with <50% of the target ß-blocker dose used in previous randomized trials. The primary composite endpoint was re-infarction or all-cause death within 1 year from discharge. Multivariable adjusted 1-year follow-up estimates using mixed effects Cox regression [HR (95% CI)] showed that patients treated with ≥50% of the target dose had a similar risk of the composite endpoint [1.03 (0.99-1.08)] and a somewhat higher risk when stroke, atrial fibrillation, or heart failure hospitalization were added to the composite endpoint [1.08 (1.04-1.12)], compared with patients on <50% of the target ß-blocker dose. Results remained similar up to 5 years of follow-up and consistent across relevant patient subgroups, including patients who developed heart failure during the index hospitalization. CONCLUSIONS: In contrast to doses of ß-blockers used in previous trials, ≥50% of the target ß-blocker dose was not associated with superior cardiovascular outcomes up to 5 years as compared with <50% of the target dose. Contemporary randomized clinical trials are needed to clarify the optimal dose of ß-blockers after MI.

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