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Biomedical subjects

Amir Lerman

Publications and source records attributed to Amir Lerman.

At least 55 records · Page 3Linked to original sources
PubMed2005

Application of evidence-based medical therapy is associated with improved outcomes after percutaneous coronary intervention and is a valid quality indicator.

OBJECTIVES: We sought to determine whether the prescription of evidence-based medications at discharge after successful percutaneous coronary intervention (PCI) can predict long-term clinical outcome. BACKGROUND: The association of standard-of-care drug utilization and long-term mortality and morbidity after PCI is not well studied. METHODS: We performed a retrospective cohort study of successful PCI procedures performed on 7,745 patients between March 1, 1998, and December 31, 2004. Discharge medications were analyzed, and a medication score (MEDS) was developed. A MEDS of 1 was assigned for each of the following medication classes: 1) antiplatelet, 2) lipid-lowering, 3) beta-blocker, and 4) angiotensin-converting enzyme (ACE) inhibitor. The outcomes measured were long-term death, myocardial infarction, and revascularization. RESULTS: Patients with MEDS of 3 to 4 had higher-risk profiles based upon standard clinical and angiographic criteria. Despite this, at a median follow-up of 36 months, patients with a MEDS of 3 or 4 were at lower risk of death than those with a MEDS of 0 or 1 (8.9%, 7.5%, and 13% for MEDS of 4, 3, and 0 to 1, respectively; p = 0.014). After adjustment for covariates, a MEDS of 3 to 4 was associated with significantly lower mortality or myocardial infarction in follow-up than a MEDS of 0 to 1 (hazard ratios of 0.72 and 0.67 for MEDS of 3 and 4, respectively; p < 0.01). There was no association between MEDS and target vessel revascularization. CONCLUSIONS: After successful PCI, the use of multiple evidence-based classes of cardiovascular medications--antiplatelet, lipid-lowering, beta-blockers, and ACE inhibitors--is associated with improved outcome free of death or MI.

Aged↗
PubMed2005

Pathways of renal fibrosis and modulation of matrix turnover in experimental hypercholesterolemia.

Dyslipidemia often accompanies and accelerates renal disease, partly by promoting fibrosis. However, the mechanisms mediating this effect are unclear. We hypothesized that hypercholesterolemia modulates several interlinked pathways that promote deposition and blunt degradation of extracellular matrix, and that these could be manipulated by reversal of hypercholesterolemia. Fourteen pigs were fed a 16-week 2% high-cholesterol diet (HC-HC; n=7) or normal diet (n=7), whereas in 7 others, a 10-week HC was followed by a 6-week normal diet (HC-N). Renal endothelial function was assessed in vivo with electron-beam computed tomography, and renal tissue was then studied ex vivo using Western blot, real-time quantitative polymerase chain reaction, gelatin zymography, and immunostaining. HC-HC kidneys showed endothelial dysfunction, accompanied by increased intrarenal oxidative stress, inflammation, activation of the endothelin and transforming-growth factor-beta systems, and decreased matrix metalloproteinase expression and activity. Accordingly, HC-HC kidneys showed increased collagen IV expression and fibrosis. A lipid-lowering dietary intervention reversed most of these changes. In conclusion, this study indicates that renal fibrosis in early atherosclerosis is a result of a simultaneous increase in extracellular matrix deposition and blunted matrix metalloproteinase-mediated degradation, overall promoting perivascular and tubulointerstitial fibrosis. Notably, many of these pathways may be reversible in hypercholesterolemia, and crucial targets could potentially be identified for early interventions to preserve the kidney.

Animals↗
PubMed2005

Kidney in early atherosclerosis.

Atherosclerosis represents one of the major causes of premature death in the United States today, and it is frequently associated with, exacerbates, and is aggravated by chronic kidney disease (CKD). Atherosclerosis integrates the response to a number of insults, and consequently, the accelerated atherosclerosis found in CKD patients is associated with activation of a variety of humoral and tissue mechanisms. Hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome, and additional nontraditional risk factors can damage the kidney directly and by promoting intrarenal atherogenesis, even in the absence of obstructive lesions in the renal artery. Evidence indicates that increased oxidative stress and inflammation may mediate a large part of the effects of risk factors on the kidney. In turn, progressive deterioration of renal function in CKD may lead to dyslipidemia or accumulation of uremic toxins, which can induce production of free radicals and activate proinflammatory and fibrogenic factors, leading to vascular endothelial cell dysfunction and injury, and favoring development of atherosclerosis. Therefore, the kidney can be a villain or a victim during atherogenesis. The purpose of this review is to provide new insights into the mechanisms by which atherogenic factors may instigate early renal injury.

Atherosclerosis↗
PubMed2005

Myocardial bridging.

Myocardial bridging, a congenital coronary anomaly, is a clinical condition with several possible manifestations, and its clinical relevance is debated. This article reviews current knowledge about the anatomy, pathophysiology, clinical relevance, and treatment of myocardial bridging. Myocardial bridging is present when a segment of a major epicardial coronary artery, the 'tunnelled artery', runs intramurally through the myocardium. With each systole, the coronary artery is compressed. Myocardial bridging has been associated with angina, arrhythmia, depressed left ventricular function, myocardial stunning, early death after cardiac transplantation, and sudden death. Evidence indicates that the intima beneath the bridge is protected from atherosclerosis, and the proximal segment is more susceptible to development of atherosclerotic lesions because of haemodynamic disturbances. New techniques (e.g. intravascular ultrasonography and intracoronary Doppler studies) have revealed new characteristics and pathophysiologic processes such as diastolic flow abnormalities. Medical treatment generally includes beta-blockers. Nitrates should be avoided because symptoms may worsen. Intracoronary stents and surgery have been attempted in selected patients. Additional research is needed to define patients in whom myocardial bridging is potentially pathologic, and randomized multicentre long-term follow-up studies are needed to assess the natural history, patient selection, and therapeutic approaches.

Autopsy↗
PubMed2005

Effects of proteasome inhibition on the kidney in experimental hypercholesterolemia.

Hypercholesterolemia (HC) and atherosclerosis often accompany and aggravate renal disease. Proteasome inhibitors (PSI) can decrease proliferation and inflammation, likely by reducing activation of the proinflammatory NF-kappaB. However, chronic proteasome inhibition has never been demonstrated in the HC kidney. Four groups of pigs (n = 7 each) were studied after a 12-wk normal (N) or 2% HC diet alone or supplemented (N+PSI and HC+PSI) with MLN-273 (0.08 mg/kg subcutaneously twice weekly). Renal hemodynamics and function were quantified in vivo using electron-beam computed tomography at baseline and after vasodilator challenge using acetylcholine. Renal tissue was studied ex vivo using immunoblotting, PCR, and immunohistochemistry. Serum cholesterol was similarly elevated in HC and HC+PSI. Basal renal blood flow was similar among the groups, whereas GFR was decreased in both N+PSI and HC+PSI. The blunted renovascular and functional responses to acetylcholine in HC were normalized in HC+PSI (suggesting renal endothelial function improvement), which was accompanied by decreased renal endothelin, NF-kappaB, and augmented endothelial nitric oxide synthase expression. In parallel, HC+PSI animals also showed elevated NAD(P)H oxidase expression and circulating oxidized LDL, suggesting a potential for increased oxidative stress. This study shows that chronic PSI intervention in HC improves renal endothelial functional responses to challenge, possibly by modulating nitric oxide availability and endothelin. Furthermore, PSI may decrease intrarenal inflammation through modulation of the NF-kappaB pathway but may potentially increase oxidative stress, which warrants further investigation. This study may support a role for the ubiquitin/proteasome system in the kidney in HC and early atherosclerosis.

Acetylcholine↗
PubMed2005

Intravascular ultrasound-guided treatment for angiographically indeterminate left main coronary artery disease: a long-term follow-up study.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of an intravascular ultrasound (IVUS)-guided strategy for patients with angiographically indeterminate left main coronary artery (LMCA) disease. BACKGROUND: The assessment of LMCA lesions using coronary angiography is often challenging; IVUS provides useful information for assessment of coronary disease. METHODS: Intravascular ultrasound was performed on 121 patients with angiographically normal LMCAs to determine the lower range of normal minimum lumen area (MLA), defined as the mean - 2 SD. We conducted IVUS studies on 214 patients with angiographically indeterminate LMCA lesions, and deferral of revascularization was recommended when the MLA was larger than this predetermined value. RESULTS: The lower range of normal LMCA MLA was 7.5 mm(2). Of the patients with angiographically indeterminate LMCAs, 83 (38.8%) had an MLA <7.5 mm(2), and 131 (61.2%) an MLA > or =7.5 mm(2). Left main coronary artery revascularization was performed in 85.5% (71 of 83) of patients with an MLA <7.5 mm(2) and deferred in 86.9% (114 of 131) of patients with an MLA > or =7.5 mm(2). Long-term follow-up (mean 3.3 +/- 2.0 years) showed no significant difference in major adverse cardiac events (target vessel revascularization, acute myocardial infarction, and death) between patients with an MLA <7.5 mm(2) who underwent revascularization and those with an MLA > or =7.5 mm(2) deferred for revascularization (p = 0.28). Based on outcome, the best cut-off MLA by receiver operating characteristic was 9.6 mm(2). Multivariate predictors of cardiac events were age, smoking, and number of non-LMCA vessels diseased. CONCLUSIONS: Intravascular ultrasound is an accurate method to assess angiographically indeterminate lesions of the LMCA. Furthermore, deferring revascularization for patients with a minimum lumen area > or =7.5 mm(2) appears to be safe.

Aged↗
PubMed2005

Angina pectoris with a normal coronary angiogram.

Angina in the setting of a normal angiogram (NOCAD) occurs in 20-30% of patients undergoing coronary angiography. The etiologies of NOCAD can be anatomically classified into three groups: epicardial disease, coronary microvascular dysfunction, and noncoronary disease. Epicardial disease resulting in NOCAD includes endothelial dysfunction, coronary artery spasm, and coronary artery bridging. Microvascular dysfunction may be secondary to hypertension, cardiomyopathy, infiltrative disease, valvular disease, or idiopathic. Noncoronary artery disease states involving other organs systems such as the pulmonary, gastrointestinal, or musculoskeletal systems can also result in NOCAD. This review focuses on the coronary etiologies of NOCAD. The pathophysiology of disease is discussed as well as a systematic diagnostic strategy. Potential therapeutic options and prognosis are also reviewed.

Clinical Trials as Topic↗
PubMed2005

Effect of lesion length on fractional flow reserve in intermediate coronary lesions.

BACKGROUND: Fractional flow reserve (FFR) has become a gold standard in physiological assessment of coronary artery stenosis. An FFR < 0.75 is considered as a reliable physiological parameter indicating functionally significant lesion. Lesion length (LL) may affect the translesional hemodynamics. However, the effect of LL on FFR has not been adequately assessed. We sought to evaluate the effect of LL on FFR in patients with angiographically intermediate coronary artery disease. METHODS: We performed FFR measurements by pressure guidewire in 63 intermediate-grade lesions (63 patients) by visual assessment. Lesion length and percent diameter stenosis (%DS) at the lesion site were determined by performing off-line quantitative coronary angiography analysis. RESULTS: Overall, there was a moderate inverse correlation between FFR and %DS (r = -0.55, P < .001). In addition, there was a weak inverse correlation between LL and FFR (r = -0.31, P < .001). Using a receiver operating characteristic curve analysis, an LL > or = 10 mm was identified as the best cutoff value for predicting an FFR < 0.75 (sensitivity 95%, specificity 66%, positive predictive power 48%, and negative predictive power 97%). The correlation between FFR and %DS was significantly improved for LL > or = 10 mm, as compared with LL < 10 mm (r = -0.78, P < .001; r = 0.16, P = NS; respectively). Similar improvement with LL was also observed for intermediate lesions by quantitative coronary angiography (%DS 50%-70%; r = 0.19, P = NS for LL < 10 mm; r = -0.74, P < .001 for LL > or = 10 mm). CONCLUSIONS: This study demonstrates that LL differentially affects the correlation between the functional assessment (FFR) and the "anatomic" severity (%DS) of coronary lesions and suggests that LL has a significant impact on the physiological significance of intermediate-grade coronary lesions.

Aged↗
PubMed2005

Experimental hypercholesterolemia differentially affects adventitial vasa vasorum and vessel structure of the left internal thoracic and coronary arteries.

OBJECTIVE: Atherosclerosis is a chronic and diffuse disease that affects all vascular beds. However, some vascular beds are more prone to atherosclerosis than others. Recent evidence suggests a role for the vasa vasorum in the atherosclerotic process. We hypothesized that there is a difference in adventitial vasa vasorum structure between the left internal thoracic artery and the coronary artery. Hence the current study was designed to characterize and compare the structure of the adventitial vasa vasorum in the left internal thoracic and coronary arteries. METHODS: Samples of vessels were obtained from female crossbred domestic pigs maintained on a normal (n = 6) or high-cholesterol (n = 6) diet for 12 weeks. The samples were scanned with micro-computed tomography, and the tomographic images were reconstructed and analyzed to obtain lumen area, vessel wall area, vasa vasorum count, vasa vasorum density, mean diameter of first- and second-order vasa vasorum, and second-order/first-order vasa vasorum ratio. RESULTS: Vasa vasorum density was significantly higher in the coronary arteries versus that seen in the left internal thoracic arteries in the normal group, as well as in the high-cholesterol group. The higher vasa vasorum density in the high-cholesterol group versus that in the normal group was significant for both vessels, being more pronounced in the left internal thoracic artery. Lumen area and second-order/first-order vasa vasorum ratio were higher in the high-cholesterol group than in the normal group only in the left internal thoracic artery. CONCLUSION: This study demonstrated that low vasa vasorum spatial density and higher lumen area observed in the left internal thoracic artery compared with that seen in the native coronary artery can be the structural background for the low incidence of atherosclerosis in this vessel.

Animals↗
PubMed2005

Therapeutic uses of autologous endothelial cells for vascular disease.

Endothelial cells play important structural and functional roles in vascular homoeostasis. Perturbations in endothelial cell number and function are directly involved with the initiation and progression of multiple cardiovascular diseases, including atherosclerosis, hypertension and congestive heart failure. Attempts to modify these disorders have included pharmacological strategies to improve vascular and thus endothelial function. A goal of biological approaches to these disorders is the delivery of endothelial cells that might act to provide beneficial endothelial-derived factors. However, this approach has generally been limited by the lack of readily available autologous endothelial cells for delivery. The isolation of circulation-derived endothelial progenitor cells allows for direct access to autologous endothelial cells for preclinical and clinical studies. Preclinical studies using autologous endothelial cells have demonstrated beneficial effects when delivered in animal models of vascular injury and grafting. These effects are related to the endothelial nature of the cells and may be paracrine in nature. Ongoing studies are aimed at defining the nature of these effects and optimizing delivery strategies cognizant of these mechanisms.

Animals↗
PubMed2005

The ubiquitin-proteasome system--micro target for macro intervention?

The ubiquitin-proteasome system is the two sequential labeling and degradation system that accounts for the degradation of 80-90% of all intracellular proteins. Based on the diversity of its substrates, it is integrated in many different biological processes, especially inflammation and cell proliferation. Given the significance of these two processes for primary atherosclerosis and restenosis, the ubiquitin-proteasome system may be an amendable target in cardiovascular therapy. This review provides background information on the ubiquitin-proteasome system, currently available data on its involvement in cardiovascular diseases, and a future perspective on the targeted use proteasome inhibitors, including drug-eluting stents.

Apoptosis↗
PubMed2005

Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension.

An enormous number of studies in the last two decades have been devoted to investigating the role of the endothelium in cardiovascular diseases. Nonetheless, the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, molecular genetic tests and invasive and non-invasive tools with and without pharmacological and physiological stimuli have been introduced. Furthermore newer pharmacological tools have been proposed. However, the application of these methodologies should fulfil a number of requirements in order to provide conclusive answers in this area of research. Thus, the most relevant methodological issues in the research on endothelial function and dysfunction are summarized in this paper.

Endothelium, Vascular↗
PubMed2004

Differential effect of experimental hypertension and hypercholesterolemia on adventitial remodeling.

OBJECTIVE: Intima-media remodeling, as frequently assessed by changes in the external elastic lamina-to-lumen area (EELLA), is well-described in coronary artery disease in contrast to adventitial remodeling, especially in the early disease stage. METHOD AND RESULTS: Female domestic pigs were randomized to one of the following 12-week treatment groups: normal diet (N; n=6), high-cholesterol diet (HC; n=6), or renovascular hypertension (HT; n=4). Low-density lipoprotein (LDL) cholesterol serum concentration was higher in HC than in N and HT (395.5+/-106 versus 38.6+/-14 and 37.2+/-6.8 mg/dL; P<0.05 for both). Mean arterial pressure was higher in HT than in N and HC (141.3+/-21 versus 107.4+/-8.9 and 109.4+/-7.8 mm Hg; P<0.05 for both). EELLA ratio, as assessed by morphometry, was similar in N, HC, and HTN (1.03+/-0.32 versus 0.95+/-0.29 and 1.01+/-0.09; P<0.05 for both). Coronary vasa vasorum density, as assessed by 3-dimensional micro-computed tomography, was higher in HC than in N and HT (3.4+/-1.0 versus 1.9+/-0.3 and 2.0+/-1.2; P<0.05 for both). In contrast, immunostaining showed a higher collagen III content and the presence of adventitial myofibroblasts in HT compared with N and HC. CONCLUSIONS: The current study suggests that adventitial remodeling precedes intima and media remodeling of coronary arteries early after exposure to hypercholesterolemia and hypertension, with distinct qualitative differences between them. Intima-media remodeling is well-described in coronary artery disease in contrast to adventitial remodeling. Results of the current study on coronary arteries of pigs, randomized to 12 weeks of normal diet (N), hypercholesterolemic diet (HC), or renovascular hypertensive (HT), indicate that adventitial remodeling precedes intima-media remodeling early after risk factor exposure with distinct qualitative differences.

Actins↗