Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study
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SUBMITTER: Peng J
PROVIDER: S-EPMC7541318 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:Chronic inflammation plays a crucial role in coronary artery disease (CAD), but differences in specific cytokine profiles between acute coronary syndrome (ACS) and stable CAD remain unknown. We investigated cytokine differences between these two manifestations of CAD. The study included 308 patients with angiographically detected, hemodynamically significant CAD: 150 patients undergone angiography for ACS, 158 patients undergone angiography for stable CAD. To assess dynamic changes, 116 patients had index angiogram at least 3 months earlier. We measured the serum concentrations of 48 circulating cytokines. The ACS group had decreased interleukin (IL) 4 (p = 0.005), and increased IL-8 (p = 0.008), hepatocyte growth factor (HGF) (p < 0.001) and macrophage colony-stimulating factor (M-CSF) (p = 0.002) levels compared with the stable CAD group. Multivariable logistic regression revealed increased levels of HGF (OR 18.050 [95% CI 4.372-74.517], p < 0.001), M-CSF (OR 2.257 [1.375-3.705], p = 0.001) and IL-6 (OR 1.586 [1.131-2.224], p = 0.007), independently associated with ACS. In the post-angiography group, only diminished platelet-derived growth factor-BB levels in ACS-manifested patients were observed (OR 0.478, [0.279-0.818], p = 0.007). Cytokine profiles differ between ACS and stable CAD. Such differences seem to be mainly reversible within 3 months after ACS. Thus, targeting one or two cytokines only might not offer one-size fits all-therapeutic approach for CAD-associated inflammation.Trial registration: NCT03444259.
| S-EPMC11283453 | biostudies-literature
Project description:Exosomal miRNAs are currently being explored as a novel class of biomarkers in cardiovascular diseases. However, few reports have focused on the value of circulating exosomal miRNAs as biomarkers for stable coronary artery disease (SCAD). Here, we aimed to investigate whether miRNAs involved in cardiovascular diseases in circulating exosomes could serve as novel diagnostic biomarkers for SCAD. Firstly, the serum exosomes were isolated and purified by the ExoQuick reagent and identified by transmission electron microscopy, western blot, and nanoparticle tracking analysis. Then, the purified exosomes were quantified by measuring the exosome protein concentration and calculating the total protein amount. Next, eight miRNAs involved in cardiovascular diseases, miR-192-5p, miR-148b-3p, miR-125a-3p, miR-942-5p, miR-149-5p, miR-32-5p, miR-144-3p, and miR-142-5p, were quantified in circulating exosomes from the control group (n = 20) and the SCAD group (n = 20) by quantitative real-time polymerase chain reaction (qPCR). Finally, the gene targets of the differentially expressed miRNAs were predicted, and the functions and signaling pathways of these targets were analyzed using an online database. The isolated exosomes had a bilayer membrane with a diameter of about 100 nm and expressed exosomal markers including CD63, Tsg101, and Flotillin but negatively expressed Calnexin. Both the exosome protein concentration and total protein amount exhibited no significant differences between the two groups. The qPCR assay demonstrated that among the eight miRNAs, the expression levels of miR-942-5p, miR-149-5p, and miR-32-5p in the serum exosomes from the SCAD group were significantly higher than that from the control group. And the three miRNAs for SCAD diagnosis exhibited AUC values of 0.693, 0.702, and 0.691, respectively. GO categories and signaling pathways analysis showed that some of the predictive targets of these miRNAs were involved in the pathophysiology processes of SCAD. In conclusion, our findings suggest that serum exosomal miR-942-5p, miR-149-5p, and miR-32-5p may serve as potential diagnostic biomarkers for SCAD.
| S-EPMC7748912 | biostudies-literature
Project description:Synthetized by the liver and metabolized by the gut microbiota, BA are involved in metabolic liver diseases that are associated with cardiovascular disorders. Animal models of atheroma documented a powerful anti-atherosclerotic effect of bile acids (BA). This prospective study examined whether variations in circulating BA are predictive of coronary artery disease (CAD) in human. Consecutive patients undergoing coronary angiography were enrolled. Circulating and fecal BA were measured by high pressure liquid chromatography and tandem mass spectrometry. Of 406 screened patients, 80 were prospectively included and divided in two groups with (n = 45) and without (n = 35) CAD. The mean serum concentration of total BA was twice lower in patients with, versus without CAD (P = 0.005). Adjusted for gender and age, this decrease was an independent predictor of CAD. In a subgroup of 17 patients, statin therapy doubled the serum BA concentration. Decreased serum concentrations of BA were predictors of CAD in humans. A subgroup analysis showed a possible correction by statins. With respect to the anti-atherosclerotic effect of BA in animal models, and their role in human lipid metabolism, this study describe a new metabolic disturbance associated to CAD in human.
| S-EPMC8608912 | biostudies-literature
Project description:Serum phosphorus (P) concentration is associated with coronary artery calcification (CAC) as well as cardiovascular events in patients with chronic kidney disease. It has been suggested that this relationship is extended to subjects without renal dysfunction, but further explorations in diverse races and regions are still needed. We performed a cross-sectional study of 2,509 Korean subjects (Far Eastern Asian) with an estimated glomerular filtration rate of ?60 ml/min/1.73 m2 and who underwent coronary computerized tomography. Serum P concentration was divided into pre-determined 4 categories: ?3.2, 3.2< to ?3.6, 3.6< to ?4.0 and >4.0 mg/dL. Agatston score (AS), an index of CAC, was divided into 3 categories: 0, 0< to ?100, and >100. A multinomial logit model (baseline outcome: AS = 0) was applied to estimate the odds ratio (OR) for each serum P category (reference: ?3.2mg/dL). Mean age of subjects was 53.5±9.1 years and 36.9% were female. In the adjusted model, serum P concentration of 3.6< to ?4.0 mg/dL and >4.0 mg/dL showed high ORs for AS of >100 [OR: 1.58, 95% confidence interval (CI): 1.04-2.40 and OR: 2.11, 95% CI: 1.34-3.32, respectively]. A unit (mg/dL) increase in serum P concentration was associated with 50% increase in risk of AS >100 (OR: 1.50, 95% CI: 1.16-1.94). A higher serum P concentration, even within a normal range, may be associated with a higher CAC in subjects with normal renal function.
| S-EPMC4798619 | biostudies-literature
Project description:OBJECTIVES:The aim of this study was to investigate the association of serum fibrinogen with cardiovascular events (CVE) in Chinese patients with type 2 diabetes mellitus (T2DM) and stable coronary artery disease (CAD). DESIGN:An observational study. SETTING:FuWai Hospital in Beijing, China. PARTICIPANTS:A cohort of 1466 patients with?T2DM and angiographic-proven stable CAD was evaluated. OUTCOME MEASURES:Baseline serum fibrinogen levels were measured and trisected into 'low', 'middle' and 'high'. Their association with CVE was explored using Cox proportional hazard models. RESULTS:With 20.2 months (average) follow-up, 44 (3%) were lost to follow-up and 96 patients developed CVE. Compared with the patients without CVE, the ones who developed CVE had higher levels of fibrinogen. Univariable regression revealed a significant relation of fibrinogen to CVE (HR (HR) 1.25, 95% CI 1.06 to 1.47, p=0.010) per SD increase of fibrinogen at baseline. After adjusting for multiple established cardiovascular disease (CVD) risk factors, the association persisted (HR 1.30, 95%?CI 1.02 to 1.66, p=0.037). Moreover, after adjusting for CVD risk factors, the HRs for middle-serum and high-serum fibrinogen concentration, using 'low' group as reference, were 1.23 (95% CI 0.69 to 2.20) and 2.20 (95% CI 1.11 to 3.36, p=0.049). CONCLUSIONS:We first indicated that elevated fibrinogen level was independently associated with increased CVE in Chinese patients with T2DMand stable CAD.
| S-EPMC5734258 | biostudies-other
Project description:BackgroundGrowth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers.MethodsA prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death.ResultsBaseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years.ConclusionsHigher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.
| S-EPMC10412535 | biostudies-literature
Project description:BackgroundSubclinical atherosclerosis detected by increased coronary artery calcium (CAC) or arterial stiffness as reflected by cardio-ankle vascular index (CAVI) has been associated with major adverse cardiovascular events (MACEs). However, comparative data from these two assessments in the same population are still limited.MethodsFrom 2005 to 2013, patients with stable coronary artery disease (CAD), both asymptomatic and symptomatic who underwent both coronary computed tomography and CAVI were enrolled and followed for occurrence of MACEs (cardiovascular [CV] death, nonfatal myocardial infarction [MI], and nonfatal stroke) until December 2019. A cause-specific hazard model was applied to assess the associations of CAC score, and CAVI with long-term MACEs.ResultsA total of 8687 patients participated. Of them, CAC scores were 0, 1-99, 100-399, and ≥400 in 49.7%, 31.9%, 12.3%, and 6.1%, respectively. Arterial stiffness (CAVI ≥ 9.0) was associated with the magnitude of CAC in 23.8%, 36.3%, 44.5%, and 56.2%, respectively. During an average of 9.9 ± 2.4 years follow-up, MACEs occurred in 8.0% (95% CI: 7.4%, 8.6%) of subjects. After adjusting for covariables, CAC scores of 100-399 and ≥400, and CAVIs of ≥9.0 were found to independently predict the occurrence of MACEs with the hazard ratios (95% CI) of 1.70 (1.13, 1.98), 1.87 (1.33, 2.63), and 1.27 (1.06, 1.52), respectively. Other risk predictors were hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), aspirin, and statin therapy.ConclusionsA CAC score ≥100 or a CAVI ≥ 9.0 predicts the long-term occurrence of MACEs in both asymptomatic and symptomatic patients with stable CAD. These two noninvasive tests can be used as screening tools to guide treatment for the prevention of future CV events.
| S-EPMC9933115 | biostudies-literature
Project description:Background: Collateral artery growth, also termed arteriogenesis, occurs upon narrowing or occlusion of a major artery. To date, attempts to stimulate arteriogenesis in patients for therapeutic purposes have not been successful. Experimental models showed that circulating cells orchestrate arteriogenesis. In humans, a large heterogeneity exists in the arteriogenic response. We hypothesized that good arteriogenic responders (GARs) and bad arteriogenic responders (BARs) differ in gene expression profiles of circulating cells, thereby disclosing potential new therapeutic strategies for the stimulation of arteriogenesis. Methods: A total of 45 patients scheduled for percutaneous coronary intervention (PCI) for single-vessel coronary artery disease underwent intracoronary measurements of collateral flow index (CFI) to distinguish between GARs (CFI>0.21) and BARs (CFI≤0.21). Monocytes and CD34+ stem cells were collected from peripheral blood. A fraction of monocytes was further processed to obtain stimulated monocytes and macrophages. Whole genome transcriptome analysis was performed on all four cell types. Results: LPS-stimulated monocytes showed 244 genes differentially expressed (false discovery rate < 0.05) between GARs and BARs. Macrophage gene expression correlated with stimulated monocytes, while resting monocytes and stem cells revealed no differential gene expression. Stimulated monocytes from GARs showed a strongly attenuated response in several interferon- and apoptosis-related genes, which was corroborated at the protein level. Conclusions Circulating cells from GARs and BARs distinctively differ in their gene expression profiles upon stimulation. The reduced expression of interferon and apoptosis genes in GARs may lead to novel therapeutic approaches for the stimulation of collateral artery growth. Keywords: disease state analysis, stress response analysis, natural defense mechanism analysis
2008-04-17 | GSE7547 | GEO
Project description:This study aimed to develop a short-read RNA-Seq protocol to detect mRNAs, lncRNAs and circRNAs (including putative novel lncRNAs) in human plasma. This protocol was applied to plasma from patients with established stable CAD (samples collected ~4 months after an acute coronary event) and healthy controls to screen for candidate mRNA, lncRNA and circRNA biomarkers associated with the presence of coronary artery disease and the progression from CAD to HF. We hypothesised that circulating levels of non-coding RNAs in patients with stable CAD may relect progression of atherosclerotic disease or adverse myocardial remodeling, and may help identify patients at risk of future cardiovascular events. Here we demonstrate that mRNAs, lncRNAs and circRNAs can be reliably detected in human plasma by deep RNA-Seq and report novel candidate biomarkers for the presence of CAD.
2022-11-02 | GSE208194 | GEO
Project description:AimsRisk estimation is important to motivate patients to adhere to treatment and to identify those in whom additional treatments may be warranted and expensive treatments might be most cost effective. Our aim was to develop a simple risk model based on readily available risk factors for patients with stable coronary artery disease (CAD).Methods and resultsModels were developed in the CLARIFY registry of patients with stable CAD, first incorporating only simple clinical variables and then with the inclusion of assessments of left ventricular function, estimated glomerular filtration rate, and haemoglobin levels. The outcome of cardiovascular death over ∼5 years was analysed using a Cox proportional hazards model. Calibration of the models was assessed in an external study, the CORONOR registry of patients with stable coronary disease. We provide formulae for calculation of the risk score and simple integer points-based versions of the scores with associated look-up risk tables. Only the models based on simple clinical variables provided both good c-statistics (0.74 in CLARIFY and 0.80 or over in CORONOR), with no lack of calibration in the external dataset.ConclusionOur preferred model based on 10 readily available variables [age, diabetes, smoking, heart failure (HF) symptom status and histories of atrial fibrillation or flutter, myocardial infarction, peripheral arterial disease, stroke, percutaneous coronary intervention, and hospitalization for HF] had good discriminatory power and fitted well in an external dataset.Study registrationThe CLARIFY registry is registered in the ISRCTN registry of clinical trials (ISRCTN43070564).
| S-EPMC8092988 | biostudies-literature