MCP-1 Predicts Recurrent Cardiovascular Events in Patients with Persistent Inflammation.
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ABSTRACT:
SUBMITTER: Blanco-Colio LM
PROVIDER: S-EPMC7963189 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. METHODS:This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (>?70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2?days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18F-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. RESULTS:The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r?=?0.42 P?=?.02) and with 18F-FDG uptake (r?=?0.38 P?=?.05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-FDG-PET. After a median follow-up of 1077?days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR?=?1.15 P?=?.006). When the model was associated with the variables of interest, the risk predicted by 18F-FDG-PET was not significant. CONCLUSIONS:Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.
| S-EPMC7045396 | biostudies-literature
Project description:BackgroundTreatment of patients presenting with possible acute myocardial infarction (AMI) is based on timely diagnosis and proper risk stratification aided by biomarkers. We aimed at evaluating the predictive value of GDF-15 in patients presenting with symptoms suggestive of AMI.MethodsConsecutive patients presenting with suspected AMI were enrolled in three study centers. Cardiovascular events were assessed during a follow-up period of 6 months with a combined endpoint of death or MI.ResultsFrom the 1818 enrolled patients (m/f = 1208/610), 413 (22.7%) had an acute MI and 63 patients reached the combined endpoint. Patients with MI and patients with adverse outcome had higher GDF-15 levels compared with non-MI patients (967.1pg/mL vs. 692.2 pg/L, p<0.001) and with event-free patients (1660 pg/mL vs. 756.6 pg/L, p<0.001). GDF-15 levels were lower in patients with SYNTAX score ≤ 22 (797.3 pg/mL vs. 947.2 pg/L, p = 0.036). Increased GDF-15 levels on admission were associated with a hazard ratio of 2.1 for death or MI (95%CI: 1.67-2.65, p<0.001) in a model adjusted for age and sex and of 1.57 (1.13-2.19, p = 0.008) adjusted for the GRACE score variables. GDF-15 showed a relevant reclassification with regards to the GRACE score with an overall net reclassification index (NRI) of 12.5% and an integrated discrimination improvement (IDI) of 14.56% (p = 0.006).ConclusionGDF-15 is an independent predictor of future cardiovascular events in patients presenting with suspected MI. GDF-15 levels correlate with the severity of CAD and can identify and risk-stratify patients who need coronary revascularization.
| S-EPMC5542604 | biostudies-literature
Project description:Cardiovascular autonomic neuropathy (CAN) is a risk factor for cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. This study evaluated the relationship between CAN and recurrent CVD in type 2 diabetes. A total of 206 patients with type 2 diabetes who had a history of CVD within 3 years of enrollment were consecutively recruited from January 2001 to December 2009 and followed-up until December 2015. Cardiovascular autonomic function tests were performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to Valsalva maneuver and standing. We estimated the recurrence of CVD events during the follow-up period. A total of 159 (77.2%) of the 206 patients enrolled completed the follow up, and 78 (49.1%) patients had recurrent episodes of CVD, with an incidence rate of 75.6 per 1,000 patient-years. The mean age and diabetes duration were 62.5 ± 8.7 and 9.2 ± 6.9 years, respectively. Patients who developed recurrent CVD also exhibited hypertension (P = 0.004), diabetic nephropathy (P = 0.012), higher mean systolic blood pressure (P = 0.006), urinary albumin excretion (P = 0.015), and mean triglyceride level (P = 0.035) than did patients without recurrent CVD. Multivariable Cox hazard regression analysis revealed that definite CAN was significantly associated with an increased risk of recurrent CVD (hazard ratio [HR] 3.03; 95% confidence interval [CI] 1.39-6.60; P = 0.005). Definite CAN was an independent predictor for recurrent CVD in patients with type 2 diabetes who had a known prior CVD event.
| S-EPMC5065186 | biostudies-literature
Project description:Background:Cardiac Bridging Integrator 1 (cBIN1) is a membrane deformation protein that generates calcium microdomains at cardiomyocyte t-tubules, whose transcription is reduced in heart failure, and is released into blood. cBIN1 score (CS), an inverse index of plasma cBIN1, measures cellular myocardial remodeling. In patients with heart failure with preserved ejection fraction (HFpEF), CS diagnoses ambulatory heart failure and prognosticates hospitalization. The performance of CS has not been tested in patients with heart failure with reduced ejection fraction (HFrEF). Methods and Results:CS was determined from plasma of patients recruited in a prospective study. Two comparative cohorts consisted of 158 ambulatory HFrEF patients (left ventricular ejection fraction (LVEF) ? 40%, 57 ± 10 years, 80% men) and 115 age and sex matched volunteers with no known history of HF. N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were also analyzed for comparison. CS follows a normal distribution with a median of 0 in the controls, which increases to a median of 1.9 (p < 0.0001) in HFrEF patients. CS correlates with clinically assessed New York Heart Association Class (p = 0.007). During 1-year follow-up, a high CS (? 1.9) in patients predicts increased cardiovascular events (43% vs. 26%, p = 0.01, hazard ratio 1.9). Compared to a model with demographics, clinical risk factors, and NT-proBNP, adding CS to the model improved the overall continuous net reclassification improvement (NRI 0.64; 95% CI 0.18-1.10; p = 0.006). Although performance for diagnosis and prognosis was similar to CS, NT-proBNP did not prognosticate between patients whose NT-proBNP values were > 400 pg/ml. Conclusion:CS, which is mechanistically distinct from NT-proBNP, successfully differentiates myocardial health between patients with HFrEF and matched controls. A high CS reflects advanced NYHA stage, pathologic cardiac muscle remodeling, and predicts 1-year risk of cardiovascular events in ambulatory HFrEF patients. CS is a marker of myocardial remodeling in HFrEF patients, independent of volume status.
| S-EPMC7326053 | biostudies-literature
Project description:To evaluate the predictive value of carotid atherosclerotic disease (CAD) and intima-media thickness (IMT) on incident cardiovascular disease and mortality in hemodialysis patients.Multicenter, observational, prospective study including 110 patients, followed-up to 6 years. Carotid doppler ultrasonographic findings were classified in 4 degrees of severity: 1) IMT <0.9 mm, 2) IMT >0.9 mm, 3) carotid plaque with stenosis <50% and 4) plaque with stenosis >50%. The associations between IMT and CAD and cardiovascular events, total and cardiovascular mortality were assessed.83% of the patients had atherosclerotic plaques (CAD degrees 3-4). During follow-up, 29.1% of patients experienced cardiovascular events, and 28.2% died, 38.7% of cardiovascular origin. The presence of plaques was associated with cardiovascular events (p = 0.03) while calcified plaques were associated with both cardiovascular events (p = 0.01), cardiovascular mortality (p = 0.03) and non-significantly with overall mortality (p = 0.08) in the survival analysis. Carotid IMT was not associated with outcomes. Cardiovascular events correlated with CAD severity (HR 2.27, 95% CI 1.13-4.54), age (HR 1.04, 1.01-1.06), previous cardiovascular disease (HR 1.75, 1.05-4.42), dyslipidemia (HR 2.25, 1.11-4.53), lipoprotein (a) (HR 1.01, 1.00-1.02), troponin I (HR 3.89, 1.07-14.18), fibrinogen levels (HR 1.38, 0.98-1.94) and antiplatelet therapy (HR 2.14, 1.04-4.4). In an age-adjusted multivariate model, cardiovascular events were independently associated with previous coronary artery disease (HR 3.29, 1.52-7.15) and lipoprotein (a) (HR 1.01, 1.00-1.02).The presence of carotid plaques and, especially, calcified plaques, are predictors of new cardiovascular events and cardiovascular mortality in hemodialysis patients, while IMT was not. The prognostic value of calcified plaques should be confirmed in future studies.
| S-EPMC4452075 | biostudies-literature
Project description:Background: Neprilysin inhibition has demonstrated impressive benefits in heart failure treatment, and is the current focus of interest in cardiovascular (CV) and kidney diseases. However, the role of circulating neprilysin as a biomarker for CV events is unclear in hemodialysis (HD) patients. Methods: A total of 439 HD patients from the K-cohort were enrolled from June 2016 to April 2019. The plasma neprilysin level and echocardiographic findings at baseline were examined. The patients were prospectively followed up to assess the primary endpoint (composite of CV events and cardiac events). Results: Plasma neprilysin level was positively correlated with left ventricular (LV) mass index, LV end-systolic volume, and LV end-diastolic volume. Multivariate linear regression analysis revealed that neprilysin level was negatively correlated with LV ejection fraction (β = -2.14; p = 0.013). The cumulative event rate of the composite of CV events was significantly greater in neprilysin tertile 3 (p = 0.049). Neprilysin tertile 3 was also associated with an increased cumulative event rate of cardiac events (p = 0.016). In Cox regression analysis, neprilysin tertile 3 was associated with a 2.61-fold risk for the composite of CV events [95% confidence interval (CI), 1.37-4.97] and a 2.72-fold risk for cardiac events (95% CI, 1.33-5.56) after adjustment for multiple variables. Conclusions: Higher circulating neprilysin levels independently predicted the composite of CV events and cardiac events in HD patients. The results of this study suggest the importance of future studies on the effect of neprilysin inhibition in reducing CV events.
| S-EPMC8239158 | biostudies-literature
Project description:Background Cardiac fibrosis plays a crucial role in the pathogenesis of dilated cardiomyopathy (DCM). HE4 (human epididymis protein 4) is a secretory protein expressed in activated fibroblasts that exacerbates tissue fibrosis. In the present study, we investigated the clinical utility of HE4 measurement in patients with DCM and its pathophysiological role in preclinical experiments in vivo and in vitro. Methods and Results We measured serum HE4 levels of 87 patients with DCM. Endomyocardial biopsy expressed severe fibrosis only in the high HE4 group (P<0.0001). Echocardiography showed that left ventricular end-diastolic diameter tends to decrease over time (58±7.3 to 51±6.6 mm; P<0.0001) in the low HE4 group (<59.65 pmol/L [median value]). HE4 was significantly associated with risk reduction of mortality and cardiovascular hospitalization in multivariate Cox model. In vivo, HE4 was highly expressed in kidney and lung tissue of mouse, and scarcely expressed in heart. In genetically induced DCM mouse model, HE4 expression increased in kidney but not in heart and lung. In vitro, supernatant from HE4-transfected human embryonic kidney 293T cells enhanced transdifferentiation of rat neonatal fibroblasts and increased expression of fibrosis-related genes, and this was accompanied by the activation of extracellular signal-regulated kinase signaling in cardiac fibroblasts. Treatment with an inhibitor of upstream signal of extracellular signal-regulated kinase or a neutralizing HE4 antibody canceled the profibrotic properties of HE4. Conclusions HE4 functions as a secretory factor, activating cardiac fibroblasts, thereby inducing cardiac interstitial fibrosis. HE4 could be a promising biomarker for assessing ongoing fibrosis and a novel therapeutic target in DCM. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr; Unique identifier: UMIN000043062.
| S-EPMC8475713 | biostudies-literature
Project description:BackgroundThe utility of local and systemic interleukin 6 (IL-6) as a prognostic marker in incident peritoneal dialysis (PD) patients remains to be fully defined. The present study aimed to explore the capacity of systemic IL-6 concentrations to predict cardiovascular events (CVEs) and mortality in PD patients, and to evaluate the influence of neutral-pH PD solutions low in glucose degradation products (GDPs) on systemic IL-6.MethodsThe study included 175 incident participants from the balANZ trial with at least one stored serum sample. A composite CVE score was used as the primary clinical outcome measure. Multilevel linear regression and Poisson regression models were fitted to describe, respectively, the trend of serum IL-6 over time and its ability to predict composite CVE.ResultsA significant increase in serum IL-6 from baseline to 24 months was observed in the study population (mean difference: 1.68 pg/mL; p = 0.006). The type of PD solution received by patients exerted no significant effect on serum IL-6 (p = 0.12). Composite CVE was significantly and independently associated with baseline serum IL-6 (incidence rate ratio per picogram per milliliter: 1.06; 95% confidence interval: 1.02 to 1.10; p = 0.003).ConclusionsBaseline serum IL-6 was a significant independent predictor of composite CVE. Serum IL-6 concentrations increased with increasing PD duration and were not significantly modified with the use of biocompatible fluid over the study period. The present study is the first to link systemic IL-6 concentrations with CVE outcomes in incident PD patients.
| S-EPMC4335926 | biostudies-literature
Project description:The purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28-4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59-0.72). Calibration for models II-V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59-29.39)) and model V (NRI 20.00% (95%CI 5.59-34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+ . Addition of the TAC or heart valve score did not improve risk predictions.
| S-EPMC8255266 | biostudies-literature
Project description:Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke.In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes.The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10).Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)
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