Contrast-associated acute kidney injury can occur after percutaneous coronary intervention (PCI). Prediction of the contrast-associated acute kidney injury risk is important for a tailored prevention ...and mitigation strategy. We sought to develop a simple risk score to estimate contrast-associated acute kidney injury risk based on a large contemporary PCI cohort.
Consecutive patients undergoing PCI at a large tertiary care centre between Jan 1, 2012, and Dec 31, 2020, with available creatinine measurements both before and within 48 h after the procedure, were included; only patients on chronic dialysis were excluded. Patients treated between 2012 and 2017 comprised the derivation cohort and those treated between 2018 and 2020 formed the validation cohort. The primary endpoint was contrast-associated acute kidney injury, defined according to the Acute Kidney Injury Network. Independent predictors of contrast-associated acute kidney injury were derived from multivariate logistic regression analysis. Model 1 included only pre-procedural variables, whereas Model 2 also included procedural variables. A weighted integer score based on the effect estimate of each independent variable was used to calculate the final risk score for each patient. The impact of contrast-associated acute kidney injury on 1-year deaths was also evaluated.
32 378 PCI procedures were performed and screened for inclusion in the present analysis. After the exclusion of patients without paired creatinine measurements, patients on chronic dialysis, and multiple procedures, 14 616 patients were included in the derivation cohort (mean age 66·2 years, 29·2% female) and 5606 were included in the validation cohort (mean age 67·0 years, 26·4% female). Contrast-associated acute kidney injury occurred in 860 (4·3%) patients. Independent predictors of contrast-associated acute kidney injury included in Model 1 were: clinical presentation, estimated glomerular filtration rate, left ventricular ejection fraction, diabetes, haemoglobin, basal glucose, congestive heart failure, and age. Additional independent predictors in Model 2 were: contrast volume, peri-procedural bleeding, no flow or slow flow post procedure, and complex PCI anatomy. The occurrence of contrast-associated acute kidney injury in the derivation cohort increased gradually from the lowest to the highest of the four risk score groups in both models (2·3% to 34·9% in Model 1, and 2·0% to 38·8% in Model 2). Inclusion of procedural variables in the model only slightly improved the discrimination of the risk score (C-statistic in the derivation cohort: 0·72 for Model 1 and 0·74 for model 2; in the validation cohort: 0·84 for Model 1 and 0·86 for Model 2). The risk of 1-year deaths significantly increased in patients with contrast-associated acute kidney injury (10·2% vs 2·5%; adjusted hazard ratio 1·76, 95% CI 1·31–2·36; p=0·0002), which was mainly due to excess 30-day deaths.
A contemporary simple risk score based on readily available variables from patients undergoing PCI can accurately discriminate the risk of contrast-associated acute kidney injury, the occurrence of which is strongly associated with subsequent death.
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Coronary artery disease (CAD) is the leading cause of death worldwide. It is a result of the buildup of atherosclerosis within the coronary arteries. The role of the immune system in CAD is complex ...and multifaceted. The immune system responds to damage or injury to the arterial walls by initiating an inflammatory response. However, this inflammatory response can become chronic and lead to plaque formation. Neutrophiles, macrophages, B lymphocytes, T lymphocytes, and NKT cells play a key role in immunity response, both with proatherogenic and antiatherogenic signaling pathways. Recent findings provide new roles and activities referring to endothelial cells and vascular smooth muscle cells, which help to clarify the intricate signaling crosstalk between the involved actors. Research is ongoing to explore immunomodulatory therapies that target the immune system to reduce inflammation and its contribution to atherosclerosis. This review aims to summarize the pathogenic interplay between immunity and CAD and the potential therapeutic strategies, and explore immunomodulatory therapies that target the immune system to reduce inflammation and its contribution to atherosclerosis.
Aim: Periprocedural myocardial infarction (PMI), a severe complication of Percutaneous Coronary Intervention (PCI) procedures, has a negative prognostic effect, both at short and long-term follow-up. ...So far, adenosine's role in preventing PMI has shown contrasting results. A genetic variant of ADORA2A receptor, 1976 C＞T, has been suggested as a potential determinant of the interindividual response to adenosine, thus conditioning its potential benefits on PMI. In our study, we investigated whether the ADORA2A 1976 C＞T polymorphism is associated with PMI occurrence in patients undergoing coronary stenting. Methods: The study included consecutive patients undergoing PCI at the Azienda Ospedaliera-Universitaria “Maggiore della Carità,” Novara, Italy, between January 2010 and January 2016. Their genetic status was assessed using polymerase chain reaction (PCR) and restriction-fragment-length-polymorphism technique. Myonecrosis biomarkers were measured at intervals from 6 to 48 hours. PMI was defined as CKMB increased 3 times over the Upper Limit of Normal (ULN), or 50% of pre-PCI value; periprocedural myonecrosis was defined as troponin I increased 3 times over the ULN or by 50% of the baseline value. Results: We included 1,104 patients undergoing PCI, 863 (78.2%) of whom carried the ADORA2A T-allele. No difference was found for the main demographic, clinical features, or biochemistry parameters. However, C-carriers had lower statin therapy use (p=0.008) and lower HDL-cholesterol levels (p=0.01). Homozygous C/C patients had more frequent multivessel disease (p=0.03), longer lesions (p=0.01) and Type C lesions (p=0.01), thus requiring more complex procedures. After correction for baseline confounding factors at multivariate analysis, there was no difference in myocardial necrosis according to the ADORA2A genotype (p=0.40). In contrast, PMI tended to increase in the homozygous C/C population (p=0.06), but this trend was attenuated at multivariate analysis after correction for baseline confounding factors (C/C: OR95%CI=1.52 0.88–2.6, p=0.14). Conclusions: Our study showed that the polymorphism rs5751876 of the ADORA2A receptor is associated with a higher prevalence of complex coronary lesions and multivessel disease. However, it does not significantly influence the occurrence of periprocedural MI or myonecrosis.
Homocysteine (Hcy) elevation and vitamin D deficiency have emerged as potential markers of coronary artery disease (CAD). However, even tough hypovitaminosis D has been suggested to interfere with ...Hcy catabolism, no study has so far addressed the interaction of vitamin D and Hcy and their impact on CAD, that was the aim of present study. A cohort of consecutive patients undergoing coronary angiography in a single center were included and analyzed within the year 2019. Significant CAD was defined as at least 1 vessel stenosis > 50%, while severe CAD as left main and/or three-vessel disease. Hcy and vitamin D levels were assesssed at admission. We included 3150 patients undergoing coronary angiography at our centre, who were divided according to the quartiles values of vitamin D. Patients with lower levels of Vitamin D displayed a higher cardiovascular risk profile and a higher prevalence of CAD. We observed an inverse linear relationship between lower levels of vitamin D and higher Hcy (r = − 0.092, p < 0.001) and a higher prevalence of hyperhomocysteinemia in patients with lower quartiles values of vitamin D (p < 0.001). By forward conditional regression model, low vitamin D appeared as independent predictors of Homocysteine levels above the median (OR95%CI = 1.791.37–2.33, p < 0.001). In addition, patients with low vitamin D (below the median) and increased Hcy displayed a non-significantly higher rate of CAD (81% vs 77.7%, p = 0.13, adjusted OR95%CI = 1.160.88–1.54, p = 0.29) but a significant increase in the rate of severe left main/3-vessel CAD (37.4% vs 30.5%, p = 0.005, adjusted OR95%CI = 1.291.02–1.67, p = 0.04). Among patients with vitamin D levels above the median, Hcy levels did not impact on the prevalence and extent of CAD (77.7 vs 77.2%, p = 0.81, adjusted OR95%CI = 0.940.73–1.20, p = 0.60 for CAD and 31.8% vs 27.7%, p = 0.08, adjusted OR95%CI = 0.970.75–1.25, p = 0.81 for severe left main/3-vessel CAD). No significant interaction between Hcy and vitamin D with CAD or severe CAD was observed. The present study shows an independent inverse linear relationship between vitamin D and Hcy values. Moreover, the association of Hcy with the extent of CAD was significant only among patients with hypovitaminosis D, and not in the cohort of subjects with vitamin D levels above the median, suggesting that a normal vitamin D status can prevent the deleterious effects of hyperhomocysteinemia on coronary atherosclerosis, a hypothesis that certainly needs further confirmation in larger randomized trials.
Fractional flow reserve (FFR) assessed during adenosine-induced maximal hyperemia has emerged as a useful tool for the guidance of percutaneous coronary interventions (PCI). However, interindividual ...variability in the response to adenosine has been claimed as a major limitation to the use of adenosine for the measurement of FFR, carrying the risk of underestimating the severity of coronary stenoses, with potential negative prognostic consequences. Genetic variants of the adenosine receptor A2a (ADORA2A gene), located in the coronary circulation, have been involved in the modulation of the hyperemic response to adenosine. However, no study has so far evaluated the impact of the single nucleotide polymorphism rs5751876 of ADORA2A on the measurement of FFR in patients undergoing percutaneous coronary intervention that was, therefore, the aim of our study. We included patients undergoing coronary angiography and FFR assessment for intermediate (40–70%) coronary lesions. FFR measurement was performed by pressure-recording guidewire (Prime Wire, Volcano), after induction of hyperemia with intracoronary boli of adenosine (from 60 to 1440 μg, with dose doubling at each step). Restriction fragment length polymorphism (RFLP) analysis was performed to assess the presence of rs5751876 C>T polymorphism of ADORA2a receptor. We included 204 patients undergoing FFR measurement of 231 coronary lesions. A total of 134 patients carried the polymorphism (T allele), of whom 41 (30.6%) in homozygosis (T/T).Main clinical and angiographic features did not differ according to ADORA2A genotype. The rs5751876 C>T polymorphism did not affect mean FFR values (
p
= 0.91), the percentage of positive FFR (
p
= 0.54) and the duration of maximal hyperemia. However, the time to recovery to baseline FFR values was more prolonged among the T-allele carriers as compared to wild-type patients (
p
= 0.04). Based on these results, in patients with intermediate coronary stenoses undergoing FFR assessment with adenosine, the polymorphism rs5751876 of ADORA2A does not affect the peak hyperemic response to adenosine and the results of FFR. However, a more prolonged effect of adenosine was observed in T-carriers.
Acetylsalicylic acid (ASA) hypersensitivity still represents one of the major deals for patients with atherosclerotic cardiovascular disease (ASHD), especially for those requiring percutaneous ...coronary interventions in the absence of validated alternative options. Despite symptoms after ASA administration being reported in 6–20% of cases, true ASA allergy only represents a minority of the patients, pointing to the importance of challenge tests and potential strategies for tolerance induction. ASA desensitization protocols were proposed several decades ago, with accumulating the literature on their use in patients undergoing PCI either for chronic disease or acute coronary syndromes. Nevertheless, the promising results of the studies and meta-analyses have not been validated so far by the support of large-scale randomized trials or unique indications from guidelines. Therefore, ASA desensitization is still largely unapplied, leaving the management of ASA hypersensitivity to the individualized approach of cardiologists.
Vitamin D is rightly recognized as an essential key factor in the regulation of calcium and phosphate homeostasis, affecting primary adequate bone mineralization. In the last decades, a more complex ...and wider role of vitamin D has been postulated and demonstrated. Cardiovascular diseases have been found to be strongly related to vitamin D levels, especially to its deficiency. Pre-clinical studies have suggested a direct role of vitamin D in the regulation of several pathophysiological pathways, such as endothelial dysfunction and platelet aggregation; moreover, observational data have confirmed the relationship with different conditions, including coronary artery disease, heart failure, and hypertension. Despite the significant evidence available so far, most clinical trials have failed to prove any positive impact of vitamin D supplements on cardiovascular outcomes. This discrepancy indicates the need for further information and knowledge about vitamin D metabolism and its effect on the cardiovascular system, in order to identify those patients who would benefit from vitamin D supplementation.
Single Inhaler LABA/LAMA for COPD Malerba, Mario; Foci, Valentina; Patrucco, Filippo ...
Frontiers in pharmacology,
04/2019, Letnik:
10
Journal Article
Recenzirano
Odprti dostop
Chronic obstructive pulmonary disease (COPD) is a common disabling disease characterized by progressive airflow obstruction. Great efforts were spent in the development of drugs able to improve ...symptoms, quality of life, reduce exacerbations, hospitalizations and the frequency of death of patients with COPD. The cornerstones of treatment are bronchodilator drugs of two different classes: beta agonists and muscarinic antagonists. Currently the Global initiative for COPD suggests the use of long acting beta agonists (LABAs) and long acting muscarinic antagonists (LAMAs) in combination for the majority of COPD patients, thus great interest is associated with the developing of LAMA/LABA fixed combination in the maintenance treatment of stable COPD. Many LAMA/LABA fixed dose combinations have been licensed in different countries and the clinical use of these drugs stimulated the performance of many clinical trials. The purpose of this review is a complete criticism of pharmacological and clinical aspects related to the use of LAMA/LABA single inhalers for the maintenance treatment of stable COPD, with particular mention to the most debated topics and future prospects in the field.
The impact of platelet parameters on the cardiovascular risk is still debated. Gender differences in platelet volume indexes and turnover have been previously reported, potentially conditioning their ...role in the development of coronary artery disease (CAD). However, few studies have addressed, so far, the impact of gender on the immature platelet fraction (IPF) and count (IPC) and their relationship with CAD. We enrolled consecutive patients undergoing coronary angiography in a single centre. IPF and platelet indexes were measured at admission. Significant CAD was defined as the presence of at least one coronary stenosis more than 50%. A total of 2550 patients were included, 1835 (72%) were males, and 715 (28%) were females. Female patients were older (p < 0.001), with lower BMI (p = 0.002), lower prevalence of active smoking (p < 0.001), previous MI, previous PCI and CABG (p = 0.001, p = 0.001, p < 0.001), whilst a higher prevalence of renal failure (p = 0.02), acute presentation (p < 0.001) and CAD (p < 0.001). Platelet count was higher in females (p < 0.001), as well as the IPC levels (838.38 ± 562.05 vs 792.24 ± 535.66, p = 0.05) with no difference in the levels of immature platelet fraction (3.67 ± 2.68% vs 3.74 ± 2.6%, p = 0.55) or the prevalence of patients with IPF ≥ 3rd tertile (33.7% vs 35.2%, p = 0.26). At multivariate analysis, after correction for baseline confounders, gender did not emerge as an independent predictor of higher IPF (adjusted OR 95% CI = 0.82 0.64–1.06, p = 0.13). When dividing our patients according to the levels of IPF, in women we observed an inverse association between IPF ≥ 3rd tertile and coronary calcifications (p = 0.025) and a higher prevalence of restenosis (p = 0.003), but no difference in CAD (65.6% vs 66.9%, p = 0.71) or severe CAD (28.1% vs 24.7%, p = 0.31). In males, the IPF ≥ 3rd tertile related with a lower TIMI flow (p = 0.001). Males with lower IPF had a significantly higher percentage of CAD (87.7% vs 83.3%, p = 0.007; adjusted OR: 0.699 95% CI = 0.54–0.91, p = 0.008) but not for severe CAD (36.5% vs 39.9%, p = 0.134). The present study shows that among patients undergoing coronary angiography, gender is not associated to the levels of immature platelet fraction. Moreover, we found no association between IPF and the prevalence and extent of CAD in female gender, whereas in male gender the IPF was inversely related with the prevalence of CAD.
Cardiovascular disease still represents the main cause of mortality worldwide. Despite huge improvements, atherosclerosis persists as the principal pathological condition, both in stable and acute ...presentation. Specifically, acute coronary syndromes have received substantial research and clinical attention in recent years, contributing to improve overall patients' outcome. The identification of different evolution patterns of the atherosclerotic plaque and coronary artery disease has suggested the potential need of different treatment approaches, according to the mechanisms and molecular elements involved. In addition to traditional risk factors, the finer portrayal of other metabolic and lipid-related mediators has led to higher and deep knowledge of atherosclerosis, providing potential new targets for clinical management of the patients. Finally, the impressive advances in genetics and non-coding RNAs have opened a wide field of research both on pathophysiology and the therapeutic side that are extensively under investigation.
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