Impaired Peripheral Microvascular Function and Risk of Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease.
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ABSTRACT:
SUBMITTER: Young A
PROVIDER: S-EPMC8062308 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
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Impaired Peripheral Microvascular Function and Risk of Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease.
Young An A Garcia Mariana M Sullivan Samaah M SM Liu Chang C Moazzami Kasra K Ko Yi-An YA Shah Amit J AJ Kim Jeong Hwan JH Pearce Brad B Uphoff Irina I Bremner J Douglas JD Raggi Paolo P Quyyumi Arshed A Vaccarino Viola V
Arteriosclerosis, thrombosis, and vascular biology 20210318 5
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Project description:BackgroundCoronary artery bypass grafting using radial artery grafts (RA-CABG) has improved long-term outcomes. However, major adverse cardiovascular events (MACE-4, including all-cause death, myocardial infarction, stroke, and repeat revascularization) after RA-CABG still occur and the predictors remain uncertain. This study aimed to detect independent risk factors of MACE-4 after RA-CABG.MethodsThis is a retrospective case-control study (NCT04935086) conducted among patients who underwent primary isolated RA-CABG between 2009 and 2019 in our center. Baseline characteristics, procedure characteristics, and medication use were compared to identify the independent predictors of MACE-4, all-cause death, and myocardial infarction (MI) with univariate and then multivariate logistic regression.ResultsA total of 370 patients were analyzed using a mean follow-up duration of 48.8 ± 41.0 months. MACE-4, all-cause death, and MI occurred in 102 (27.6%), 27 (7.3%), and 66 patients (17.8%), respectively. Multivariate analysis revealed prior MI (OR = 2.12, 95%CI 1.05-4.25, P = 0.04) and RA to the left anterior descending artery (LAD) (non-left internal mammary artery to LAD) (OR = 4.87, 95%CI 1.41-16.82, P = 0.01) as independent predictors of MACE-4 after surgery. Female (OR = 4.53, 95%CI 1.06-19.41, P = 0.04), left ventricular ejection fraction (LVEF) <40% (OR = 21.00, 95%CI 1.20-368.35, P = 0.04), and RA to LAD (OR = 8.55, 95%CI 1.35-54.10, P = 0.02) were independent predictors of all-cause death. Prior MI (OR = 3.11, 95%CI 1.40-6.94, P = 0.006) emerged as an independent predictor of MI.ConclusionOur data suggested that prior MI and RA to LAD were independent predictors of MACE-4 after RA-CABG. Being female, having an LVEF < 40% and RA to LAD indicated death. Prior MI indicated new MI.
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Project description:Background & aimsHepatic steatosis has been associated with increased risk of major adverse cardiovascular events (MACE) but it is not clear whether steatosis is independently associated with risk of MACE. We investigated whether steatosis is associated with risk of MACE independently of the presence and extent of baseline coronary artery disease, assessed by comprehensive contrast-enhanced computed tomography angiography (CTA).MethodsWe conducted a nested cohort study of 3756 subjects (mean age, 60.6 years; 48.4% men) who underwent coronary CTA at 193 sites in North America, from July 2010 through September 2013, as part of the PROMISE study, which included noninvasive cardiovascular analyses of symptomatic outpatients without coronary artery disease. Independent core laboratory readers measured hepatic and splenic attenuation, using non-contrast computed tomography images to identify steatosis, and evaluated coronary plaques and stenosis in coronary CTA images. We collected data on participants' cardiovascular risk factors, presence of metabolic syndrome, and body mass index. The primary endpoint was an adjudicated composite of MACE (death, myocardial infarction, or unstable angina) during a median follow-up time of 25 months.ResultsAmong the 959 subjects who had steatosis (25.5% of the cohort), 42 had MACE (4.4%), whereas among the 2797 subjects without steatosis, 73 had MACE (2.6%) (hazard ratio [HR] for MACE in subjects with steatosis, 1.69; 95% CI, 1.16-2.48; P = .006 for MACE in subjects with vs without steatosis). This association remained after adjustment for atherosclerotic cardiovascular disease risk scores, significant stenosis, and metabolic syndrome (adjusted HR, 1.72; 95% CI, 1.16-2.54; P = .007) or obesity (adjusted HR, 1.75; 95% CI, 1.19-2.59; P = .005). Steatosis remained independently associated with MACE after adjustment for all CTA measures of plaques and stenosis.ConclusionsHepatic steatosis is associated with MACE independently of other cardiovascular risk factors or extent of coronary artery disease. Strategies to reduce steatosis might reduce risk of MACE. ClinicalTrials.gov no: NCT01174550.
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| S-EPMC10476223 | biostudies-literature
Project description:ObjectiveDespite the advances in the control of traditional risk factors, coronary artery disease (CAD) remains the greatest cause of morbidity and mortality. Our aim was to establish the relation between plasma proteomics analysis and the risk of cardiovascular events in patients with stable CAD.Materials and methodsPatients with stable CAD and documented coronary atherosclerosis were screened for inclusion. Using proximity extension assays, 177 plasma proteins were simultaneously measured. The endpoint consisted of the first major adverse cardiovascular event (MACE) and was the composite of cardiovascular death, acute coronary syndrome, stroke, transient ischemic attack, or acute limb ischemia at 18 months follow-up. Cox proportional-hazards regression with adjustment for multiple comparisons was used to identify biomarkers for the outcomes of interest.ResultsThe cohort consisted of 229 patients. Six mediators were associated with MACE (p < 0.001). For these markers, the risk of MACE was calculated: tumor necrosis factor receptor superfamily member 13B (HR = 1.65; 95% CI: 1.30-2.10), C-C motif chemokine-3 (HR = 1.57; 95% CI: 1.23-1.98), decorin (HR = 1.65; 95% CI: 1.26-2.16), fibroblast growth factor-23 (HR = 1.56; 95% CI: 1.23-1.99), tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) (HR = 1.61; 95% CI: 1.23-2.11), and tumor necrosis factor receptor superfamily member 10A (HR = 1.69; 95% CI: 1.25-2.29). Except for TRAIL-R2, the other proteins were associated with MACE independent of age, sex, diabetes mellitus, or estimated glomerular filtration rate.ConclusionsIn patients with stable CAD, five novel biomarkers were identified as independent risk factors for adverse outcomes. Novel biomarkers could represent pharmacological targets for the prevention of adverse cardiovascular events.
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Project description:BackgroundCoronary artery disease (CAD) and major adverse cardiovascular events (MACE) are the leading causes of death in the general population, but risk stratification remains suboptimal. CAD genetic risk scores (GRSs) predict risk independently from clinical tools, like QRISK3. We assessed the added value of GRSs for a variety of cardiovascular traits (CV GRSs) for predicting CAD and MACE and tested their early-life screening potential by comparing against the CAD GRS only.MethodsWe used data from 379 581 participants in the UK Biobank without known cardiovascular conditions (follow-up, 11.3 years; 3.3% CAD cases and 5.2% MACE cases). In a training subset (50%) we built 3 scores: QRISK3; QRISK3 and an established CAD GRS; and QRISK3, the CAD GRS and the CV GRSs. In an independent subset (50%), we evaluated each score's performance using the concordance index, odds ratio and net reclassification index. We then repeated the analyses without considering QRISK3.ResultsFor CAD, the combination of QRISK3 and the CAD GRS had a better performance than QRISK3 alone (concordance index, 0.766 versus 0.753; odds ratio, 5.47 versus 4.82; net reclassification index, 7.7%). Adding the CV GRSs did not significantly improve risk stratification. When only looking at genetic information, the combination of CV GRSs and the CAD GRS had a better performance than the CAD GRS alone (concordance index, 0.637 versus 0.625; odds ratio, 2.17 versus 2.07; net reclassification index, 3.3%). Similar results were obtained for MACE.ConclusionsIn individuals without known cardiovascular disease, the inclusion of CV GRSs to a clinical tool and an established CAD GRS does not improve CAD or MACE risk stratification. However, their combination only with the CAD GRS increases prediction performance indicating potential use in early-life screening before the advanced development of conventional cardiovascular risk factors.
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Project description:Many susceptibility loci associated with coronary artery disease (CAD) have been identified using genome-wide association studies (GWAS). This study aimed to examine whether a composite of single nucleotide polymorphisms (SNPs) derived from GWAS could identify the risk of major adverse cardiovascular events (MACEs) in patients with established CAD. There were 1059 patients with CAD were included in the analysis. Of the participants, 686 were on statin treatment at the start of follow-up. A weighted genetic risk score (wGRS) was calculated as the sum of risk alleles multiplied by the hazard ratio for a particular SNP. In single variant analyses, rs579459, rs4420638, and rs2107595 were associated with an increased risk of MACE. A wGRS was further constructed to evaluate the cumulative effect of the 3 SNPs on the prognosis of CAD. The risk of MACE among patients with high and intermediate wGRS was 1.968- and 1.838-fold, respectively, higher than those with low wGRS. This effect was more evident in patients using lipid-lowering medication and with hypertension. Furthermore, the interaction analysis revealed that lipid-lowering medication and hypertension interacted with the genetic effect off wGRS on the risk of MACE in patients using lipid-lowering medication or with hypertension (Pinteraction < .001). We further analyzed the follow-up change in low-density lipoprotein cholesterol (LDL-C) level at 6 months after CAD disclosure and evaluated whether that was due to wGRS or statin use. The lowest reduction in LDL-C was observed in patients with high GRS who received statin treatment. Furthermore, LDL-C reduction of patients with intermediate wGRS was less than those with low wGRS in patients treated with statin. Taken together, a wGRS comprised of SNPs significantly predicts MACE in CAD patients receiving statin treatment and hypertension.
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Project description:Background: Coronary artery ectasia (CAE) is found in about 1% of coronary angiography and is associated with poor clinical outcomes. The prognostic value of plasma big Endothelin-1 (ET-1) in CAE remains unknown. Methods: Patients with angiographically confirmed CAE from 2009 to 2015, who had big ET-1 data available were included. The primary outcome was 5-year major adverse cardiovascular events (MACE), defined as a component of cardiovascular death and non-fatal myocardial infarction (MI). Patients were divided into high or low big ET-1 groups using a cut-off value of 0.58 pmol/L, according to the receiver operating characteristic curve. Kaplan-Meier method, propensity score method, and Cox regression were used to assess the clinical outcomes in the 2 groups. Results: A total of 992 patients were included, with 260 in the high big ET-1 group and 732 in the low big ET-1 group. At 5-year follow-up, 57 MACEs were observed. Kaplan-Meier analysis and univariable Cox regression showed that patients with high big ET-1 levels were at increased risk of MACE (9.87 vs. 4.50%; HR 2.23, 95% CI 1.32-3.78, P = 0.003), cardiovascular death (4.01 vs. 1.69%; HR 2.37, 95% CI 1.02-5.48, P = 0.044), and non-fatal MI (6.09 vs. 2.84%; HR 2.17, 95% CI 1.11-4.24, P = 0.023). A higher risk of MACE in the high big ET-1 group was consistent in the propensity score matched cohort and propensity score weighted analysis. In multivariable analysis, a high plasma big ET-1 level was still an independent predictor of MACE (HR 1.82, 95% CI 1.02-3.25, P = 0.043). A combination of high plasma big ET-1 concentrate and diffuse dilation, when used to predict 5-year MACE risk, yielded a C-statistic of 0.67 (95% CI 0.59-0.74). Conclusion: Among patients with CAE, high plasma big ET-1 level was associated with increased risk of MACE, a finding that could improve risk stratification.
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Project description:Background and aimsPeripheral artery disease (PAD) is a systemic manifestation of atherosclerosis that is associated with a high risk of major adverse cardiovascular events (MACE). LDL aggregation contributes to atherosclerotic plaque progression and may contribute to plaque instability. We aimed to determine if LDL aggregation is associated with MACE in patients with PAD undergoing lower extremity revascularization (LER).MethodsTwo hundred thirty-nine patients with PAD undergoing LER had blood collected at baseline and were followed prospectively for MACE (myocardial infarction, stroke, cardiovascular death) for one year. Nineteen age, sex and LDL-C-matched control subjects without cardiovascular disease also had blood drawn. Subject LDL was exposed to sphingomyelinase and LDL aggregate size measured via dynamic light scattering.ResultsMean age was 72.3 ± 10.9 years, 32.6% were female, and LDL-cholesterol was 68 ± 25 mg/dL. LDL aggregation was inversely associated with triglycerides, but not associated with demographics, LDL-cholesterol or other risk factors. Maximal LDL aggregation occurred significantly earlier in subjects with PAD than in control subjects. 15.9% of subjects experienced MACE over one year. The 1st tertile (shortest time to maximal aggregation) exhibited significantly higher MACE (25% vs. 12.5% in tertile 2 and 10.1% in tertile 3, p = 0.012). After multivariable adjustment for demographics and CVD risk factors, the hazard ratio for MACE in the 1st tertile was 4.57 (95% CI 1.60-13.01; p = 0.004) compared to tertile 3. Inclusion of LDL aggregation in the Framingham Heart Study risk calculator for recurrent coronary heart disease events improved the c-index from 0.57 to 0.63 (p = 0.01).ConclusionsWe show that in the setting of very well controlled LDL-cholesterol, patients with PAD with the most rapid LDL aggregation had a significantly elevated MACE risk following LER even after multivariable adjustment. This measure further improved the classification specificity of an established risk prediction tool. Our findings support broader investigation of this assay for risk stratification in patients with atherosclerotic CVD.
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Project description:ObjectivesTo determine whether lesion-specific pericoronary adipose tissue CT attenuation (PCATa) is superior to PCATa around the proximal right coronary artery (PCATa-RCA) and left anterior descending artery (PCATa-LAD) for major adverse cardiovascular events (MACE) prediction in coronary artery disease (CAD).MethodsSix hundred and eight CAD patients who underwent coronary CTA from January 2014 to December 2018 were retrospectively included, with clinical risk factors, plaque features, lesion-specific PCATa, PCATa-RCA, and PCATa-LAD collected. MACE was defined as cardiovascular death, non-fatal myocardial infarction, unplanned revascularization, and hospitalization for unstable angina. Four models were established, encapsulating traditional factors (Model A), traditional factors and PCATa-RCA (Model B), traditional factors and PCATa-LAD (Model C), and traditional factors and lesion-specific PCATa (Model D). Prognostic performance was evaluated with C-statistic, area under receiver operator characteristic curve (AUC), and net reclassification index (NRI).ResultsLesion-specific PCATa was an independent predictor for MACE (adjusted hazard ratio = 1.108, P < .001). The C-statistic increased from 0.750 for model A to 0.762 for model B (P = .078), 0.773 for model C (P = .046), and 0.791 for model D (P = .005). The AUC increased from 0.770 for model A to 0.793 for model B (P = .027), 0.793 for model C (P = .387), and 0.820 for model D (P = .019). Compared with model A, the NRIs for models B, C, and D were 0.243 (-0.323 to 0.792, P = .392), 0.428 (-0.012 to 0.835, P = .048), and 0.708 (0.152-1.016, P = .001), respectively.ConclusionsLesion-specific PCATa improves risk prediction of MACE in CAD, which is better than PCATa-RCA and PCATa-LAD.Advances in knowledgeLesion-specific PCATa was superior to PCATa-RCA and PCATa-LAD for MACE prediction.
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Project description:Patients with complex coronary artery disease (CAD) often have poor clinical outcomes. This study aimed to develop a predictive model for assessing the 1-year risk of major adverse cardiovascular events (MACE) in patients with stable complex CAD, using retrospective data collected from January 2020 to September 2023 at Guangzhou Red Cross Hospital. The goal was to enable early risk stratification and intervention to improve clinical outcomes. A total of 369 patients were included and randomly divided into a training set (70%) for model development and a validation set (30%) for performance evaluation. Predictive factors were selected using least absolute shrinkage and selection operator (LASSO) regression, followed by logistic regression to construct the model and create a nomogram. Seven independent predictors were identified: functional SYNTAX score (OR 1.257, 95% CI 1.159-1.375), low-density lipoprotein cholesterol (LDL-C, OR 1.487, 95% CI 1.147-1.963, /1mmol/L), left ventricular ejection fraction (LVEF, OR 0.934, 95% CI 0.882-0.985, /1%), albumin (OR 0.889, 95% CI 0.809-0.974, /1g/L), pulse pressure ≥ 72 mmHg (OR 3.358, 95% CI 1.621-7.118), angiotensin-converting enzyme 2 (ACE2) ≥ 27.5 U/L (OR 2.503, 95% CI 1.290-5.014), and diabetes (OR 2.261, 95% CI 1.186-4.397). Among these, the functional SYNTAX score was the strongest predictor. The area under the receiver operating characteristic curve (AUC) was 0.843 for the training set and 0.844 for the validation set, with Youden indices of 0.561 and 0.601, respectively. Calibration curves and decision curve analysis demonstrated good predictive accuracy and clinical utility of the model. These findings suggest that the developed model has strong predictive performance for 1-year MACE risk in patients with complex CAD, and early risk stratification and intervention based on this model may improve clinical outcomes.
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