Abstract
Aims
The CLIMA study, on the relationship between coronary plaque morphology of the left anterior descending artery and twelve months clinical outcome, was designed to explore the predictive ...value of multiple high-risk plaque features in the same coronary lesion minimum lumen area (MLA), fibrous cap thickness (FCT), lipid arc circumferential extension, and presence of optical coherence tomography (OCT)-defined macrophages as detected by OCT. Composite of cardiac death and target segment myocardial infarction was the primary clinical endpoint.
Methods and results
From January 2013 to December 2016, 1003 patients undergoing OCT evaluation of the untreated proximal left anterior descending coronary artery in the context of clinically indicated coronary angiogram were prospectively enrolled at 11 independent centres (clinicaltrial.gov identifier NCT02883088). At 1-year, the primary clinical endpoint was observed in 37 patients (3.7%). In a total of 1776 lipid plaques, presence of MLA <3.5 mm2 hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.1–4.0, FCT <75 µm (HR 4.7, 95% CI 2.4–9.0), lipid arc circumferential extension >180° (HR 2.4, 95% CI 1.2–4.8), and OCT-defined macrophages (HR 2.7, 95% CI 1.2–6.1) were all associated with increased risk of the primary endpoint. The pre-specified combination of plaque features (simultaneous presence of the four OCT criteria in the same plaque) was observed in 18.9% of patients experiencing the primary endpoint and was an independent predictor of events (HR 7.54, 95% CI 3.1–18.6).
Conclusion
The simultaneous presence of four high-risk OCT plaque features was found to be associated with a higher risk of major coronary events.
Cystatin C and Cardiovascular Risk Taglieri, Nevio; Koenig, Wolfgang; Kaski, Juan Carlos
Clinical chemistry,
11/2009, Letnik:
55, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Patients with chronic kidney disease (CKD) are at high risk for developing cardiovascular disease (CVD) and cardiovascular events. Cystatin C, a protease inhibitor synthesized in all nucleated cells, ...has been proposed as a replacement for serum creatinine for the assessment of renal function, particularly to detect small reductions in glomerular filtration rate.
This report presents a review of the role of cystatin C as a predictor of cardiovascular risk.
Patients with higher circulating cystatin C concentrations appear to have an increased cardiovascular risk profile, i.e., they are older and have a higher prevalence of systemic hypertension, dyslipidemia, documented CVD, increased body mass index, and increased concentrations of C-reactive protein. Prospective studies have shown, in various clinical scenarios, that patients with increased cystatin C are at a higher risk of developing both CVD and CKD. Importantly, cystatin C appears to be a useful marker for identifying individuals at a higher risk for cardiovascular events among patients belonging to a relatively low-risk category as assessed by both creatinine and estimated glomerular filtration rate values. Of interest, elastolytic proteases and their inhibitors, in particular cystatin C, have been shown to be directly involved in the atherosclerotic process. Increased concentrations of cystatin C appear to be indicative of preclinical kidney disease associated with adverse outcomes. Clinical studies involving direct glomerular filtration rate measurements are required to ascertain both the true role of this promising marker in renal disease and whether atherogenic factors like inflammation can account for increases in cystatin C concentrations, thus explaining its predictive value in CVD.
Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous entity with relevant long-term major cardiovascular events. Several trials have demonstrated that dual ...antiplatelet therapy (DAPT), β-blocker, renin-angiotensin-aldosterone system (RAAS) inhibitor and statin therapy improve the prognosis in patients with obstructive myocardial infarction (ob-MI). However, evidence on the best medical therapy for secondary prevention in MINOCA patients is lacking.
To investigate the effects of secondary prevention treatments at discharge on mid-term outcomes in MINOCA.
Patients with acute myocardial infarction (MI) undergoing early coronary angiography between 2016 and 2018 were extracted from a clinical database. The diagnosis of MINOCA was made according to 2016 ESC MINOCA Position Paper criteria. Second-level diagnostic work-up including cardiac magnetic resonance was performed to exclude non-ischemic troponin elevation cause. The relationship between treatments and outcomes was evaluated by using Kaplan-Meier survival analysis and Cox regression models. All confirmed MINOCA were followed in our outpatient clinics. The primary end-points were all-cause mortality, re-hospitalization for MI and a composite outcome including all-cause mortality, hospitalization for MI and ischemic stroke (MACE).
Out of 1,141 AMI who underwent coronary angiography, 134 were initially diagnosed as MINOCA. Patients with MINOCA were less likely to receive secondary prevention treatments than patients with obstructive coronary artery disease (CAD) MI (respectively, 42.1% vs 81.8% for DAPT; 75.5% vs 89.6% for β-blockers; 64.7% vs 80.3% for RAAS inhibitor and 63.9% vs 83% for statins). Based on the diagnostic work-up completed during the first month after discharge, a final sample of 88 patients had confirmed MINOCA. During an average follow-up of 19.35 ± 10.65 months, all-cause mortality occurred in 11 (12.5%) patients, recurrence of MI in 4 (4.5%), and MACE in 15 (17.0%) patients. Patients treated with RAAS inhibitors and statins had a significantly longer survival. On the contrary, no increase in survival was found in patients treated with β-blockers or DAPT. Cox multivariable analysis, including all secondary prevention drugs, showed that only RAAS inhibitors were associated with reduced all cause-mortality and MACE.
This prospective study suggests that RAAS inhibitor therapy provides mid-term beneficial effects on outcomes in MINOCA patients; in contrast, dual antiplatelet, β-blocker and statin therapy had no effects on mortality and MACE. These results should be considered preliminary and warrant confirmation from larger studies.
Enzyme replacement therapy (ERT) is a mainstay of treatment for Anderson-Fabry disease (AFD), a pathology with negative effects on the heart and kidneys. However, no reliable biomarkers are available ...to monitor its efficacy. Therefore, we tested a panel of four microRNAs linked with cardiac and renal damage in order to identify a novel biomarker associated with AFD and modulated by ERT. To this end, 60 patients with a definite diagnosis of AFD and on chronic ERT, and 29 age- and sex-matched healthy individuals, were enrolled by two Italian university hospitals. Only miR-184 met both conditions: its level discriminated untreated AFD patients from healthy individuals (c-statistic = 0.7522), and it was upregulated upon ERT (P < 0.001). On multivariable analysis, miR-184 was independently and inversely associated with a higher risk of cardiac damage (odds ratio = 0.86; 95% confidence interval CI = 0.76-0.98; P = 0.026). Adding miR-184 to a comprehensive clinical model improved the prediction of cardiac damage in terms of global model fit, calibration, discrimination, and classification accuracy (continuous net reclassification improvement = 0.917, P < 0.001; integrated discrimination improvement IDI = 0.105, P = 0.017; relative IDI = 0.221, 95% CI = 0.002-0.356). Thus, miR-184 is a circulating biomarker of AFD that changes after ERT. Assessment of its level in plasma could be clinically valuable in improving the prediction of cardiac damage in AFD patients.
To evaluate the role of the ECG in the differential diagnosis between Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM).
In this multicentre retrospective study, 111 AFD patients ...with left ventricular hypertrophy were compared with 111 patients with HCM, matched for sex, age and maximal wall thickness by propensity score. Independent ECG predictors of AFD were identified by multivariate analysis, and a multiparametric ECG score-based algorithm for differential diagnosis was developed.
Short PR interval, prolonged QRS duration, right bundle branch block (RBBB), R in augmented vector left (aVL) ≥1.1 mV and inferior ST depression independently predicted AFD diagnosis. A point-by-point ECG score was then derived with the following diagnostic performances: c-statistic 0.80 (95% CI 0.74 to 0.86) for discrimination, the Hosmel-Lemeshow χ
6.14 (p=0.189) for calibration, sensitivity 69%, specificity 84%, positive predictive value 82% and negative predictive value 72%. After bootstrap resampling, the mean optimism was 0.025, and the internal validated c-statistic for the score was 0.78.
Standard ECG can help to differentiate AFD from HCM while investigating unexplained left ventricular hypertrophy. Short PR interval, prolonged QRS duration, RBBB, R in aVL ≥1.1 mV and inferior ST depression independently predicted AFD. Their systematic evaluation and the integration in a multiparametric ECG score can support AFD diagnosis.
Abstract Background Limited data exist on renal complications of transcatheter aortic valve implantation (TAVI) within a comprehensive program using different valves with transfemoral, transapical, ...and trans-subclavian approach. Methods Prospective single-center registry of 102 consecutive patients undergoing TAVI using both approved bioprostheses and different access routes. The main objective was to assess the incidence, predictors and the clinical impact of acute kidney injury (AKI). AKI was defined according to the valve academic research consortium (VARC) indications. Results Mean age was 83.7 ± 5.3 years, logistic EuroSCORE 22.6 ± 12.4%, and STS score 8.2 ± 4.1%. Chronic kidney disease at baseline was present in 87.3%. Periprocedural AKI developed in 42 patients (41.7%): 32.4% stage 1, 4.9% stage 2 and 3.9% stage 3. The incidence of AKI was 66.7% in transapical, 30.3% in transfemoral, and 50% in trans-subclavian procedures. The only independent predictor of AKI was transapical access, with a hazard ratio (HR) between 4.57 and 5.18 based on the model used. Cumulative 1-year survival was 88.2%. At Cox regression analysis, the only independent predictor of 30-day mortality was diabetes mellitus (HR 7.05, 95% CI 1.07–46.32; p = 0.042), whilst the independent predictors of 1-year death were baseline glomerular filtration rate < 30 mL/min (HR 5.74, 95% CI 1.42–23.26; p = 0.014) and post-procedural AKI 3 (HR 8.59, 95% CI 1.61–45.86, p = 0.012). Conclusions TAVI is associated with a high incidence of AKI. Although in the majority of the cases AKI is of mild entity and reversible, AKI 3 holds a strong negative impact on 1-year survival. The incidence of AKI is higher with transapical access.
Cardiac allograft vasculopathy (CAV) remains the major cause of late graft-related death after heart transplantation (HT). Identification of patients at risk of cardiovascular events has relevant ...implications in appropriately guiding resources and intensity of follow-up. In this context, the prognostic relevance of serial coronary imaging long-term after HT is unexplored.
Recipients with intravascular ultrasound (IVUS) and coronary angiography performed 1 and 5 years after HT were monitored for subsequent 1 to 10 years to analyze the association of serial coronary imaging with cardiovascular death and major cardiovascular events (MACEs).
Included were 131 patients. The MACE incidence was 31.8 per 1,000 patient-years, and cardiovascular mortality was 17.4 per 1,000 patient-years. Progression of coronary lesions detected by angiography and changes in IVUS-defined parameters, including an increase in maximal intimal thickness (MIT) ≥0.35 mm and vascular remodeling, predicted MACE occurrence. However, only MIT change ≥0.35 mm also predicted cardiovascular mortality. Among patients with normal or stable angiography, an MIT change ≥0.35 mm identified those with a significantly higher MACE rate (80 vs 13 events/1,000 patient-years). Worsening metabolic parameters appeared associated with the increasing severity of CAV development.
Combined imaging analysis of progression of angiographic lesions and IVUS-detected MIT between 1 and 5 years post-HT allows discriminating patients at high, intermediate, and low risk for adverse long-term cardiovascular outcomes. The metabolic syndrome milieu is confirmed as a key risk factor for long-term CAV progression and adverse prognosis.
To compare arterial inflammation (AI) between people living with HIV (PLWH) and uninfected people as assessed by 18F-Fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET).
We prospectively ...enrolled 20 PLWH and 20 uninfected people with no known cardiovascular disease and at least 3 traditional cardiovascular risk factors. All patients underwent 18F-FDG-PET/computed tomography (CT) of the thorax and neck. Biomarkers linked to inflammation and atherosclerosis were also determined. The primary outcome was AI in ascending aorta (AA) measured as mean maximum target-to-background ratio (TBRmax). The independent relationships between HIV status and both TBRmax and biomarkers were evaluated by multivariable linear regression adjusted for body mass index, creatinine, statin therapy, and atherosclerotic cardiovascular 10-year estimated risk (ASCVD).
Unadjusted mean TBRmax in AA was slightly higher but not statistically different (P = .18) in PLWH (2.07; IQR 1.97, 2.32) than uninfected people (2.01; IQR 1.85, 2.16). On multivariable analysis, PLWH had an independent risk of increased mean log-TBRmax in AA (coef = 0.12; 95%CI 0.01,0.22; P = .032). HIV infection was independently associated with higher values of interleukin-10 (coef = 0.83; 95%CI 0.34, 1.32; P = .001), interferon-γ (coef. = 0.90; 95%CI 0.32, 1.47; P = .003), and vascular cell adhesion molecule-1 (VCAM-1) (coef. = 0.75; 95%CI: 0.42, 1.08, P < .001).
In patients with high cardiovascular risk, HIV status was an independent predictor of increased TBRmax in AA. PLWH also had an increased independent risk of IFN-γ, IL-10, and VCAM-1 levels.
Previous angiographic studies have suggested that the future risk for major adverse cardiovascular events (MACEs) is related to coronary stenosis severity. The aim of this study was to use the ...grayscale and virtual histology (VH)–intravascular ultrasound (IVUS) data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study to identify underlying lesion morphologic characteristics that might explain these findings. In PROSPECT, patients presenting with acute coronary syndromes in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and VH-IVUS and were followed for a median of 3.4 years for the incidence of MACEs. Overall, 3,115 nonculprit lesions detected by IVUS were divided into quartiles according to baseline angiographic diameter stenosis. From the first to fourth quartiles, there were increases in the prevalence of lesions with IVUS minimum luminal areas ≤4 mm2 , IVUS plaque burden ≥70%, and VH-IVUS thin-cap fibroatheroma (13.4%, 22.0%, 24.2%, and 30.3%, respectively, p <0.001), along with an increased frequency of plaque ruptures and greater necrotic core volumes. The incidence of lesions with plaque burden ≥70%, minimum luminal area ≤4 mm2 , and VH thin-cap fibroatheroma was highest in the fourth quartile (0%, 0.4%, 0.4%, and 2.8% in the first through fourth quartiles, respectively, p <0.001). Three-year MACE rates were also highest in the fourth quartile (0.3%, 0.7%, 1.3%, and 5.1%, respectively, p <0.001). In conclusion, increasing angiographic diameter stenosis was associated with an increased frequency of grayscale and VH-IVUS lesion morphologic features that have been associated with adverse events and that may, in part, explain why future MACEs were related to baseline lesion severity.