Statins Effects on Blood Clotting: A Review.

Statins are powerful lipid-lowering drugs that inhibit cholesterol biosynthesis via downregulation of hydroxymethylglutaryl coenzyme-A reductase, which are largely used in patients with or at risk of cardiovascular disease. Available data on thromboembolic disease include primary and secondary prevention as well as bleeding and mortality rates in statin users during anticoagulation for VTE. Experimental studies indicate that statins alter blood clotting at various levels. Statins produce anticoagulant effects via downregulation of tissue factor expression and enhanced endothelial thrombomodulin expression resulting in reduced thrombin generation. Statins impair fibrinogen cleavage and reduce thrombin generation. A reduction of factor V and factor XIII activation has been observed in patients treated with statins. It is postulated that the mechanisms involved are downregulation of factor V and activated factor V, modulation of the protein C pathway and alteration of the tissue factor pathway inhibitor. Clinical and experimental studies have shown that statins exert antiplatelet effects through early and delayed inhibition of platelet activation, adhesion and aggregation. It has been postulated that statin-induced anticoagulant effects can explain, at least partially, a reduction in primary and secondary VTE and death. Evidence supporting the use of statins for prevention of arterial thrombosis-related cardiovascular events is robust, but their role in VTE remains to be further elucidated. In this review, we present biological evidence and experimental data supporting the ability of statins to directly interfere with the clotting system.

The relationship between blood pressure and pain.

The relationship between pain and hypertension is potentially of great pathophysiological and clinical interest, but is poorly understood. The perception of acute pain initially plays an adaptive role, which results in the prevention of tissue damage. The consequence of ascending nociception is the recruitment of segmental spinal reflexes through the physiological neuronal connections. In proportion to the magnitude and duration of the stimulus, these spinal reflexes cause the activation of the sympathetic nervous system, which increases peripheral resistances, heart rate, and stroke volume. The response also involves the neuroendocrine system, and, in particular, the hypothalamic-pituitary-adrenal axis, in addition to further activation of the sympathetic system by adrenal glands. However, in proportion to an elevation in resting blood pressure, there is a contemporary and progressive reduction in sensitivity to acute pain, which could result in a tendency to restore arousal levels in the presence of painful stimuli. The pathophysiological pattern is significantly different in the setting of chronic pain, in which the adaptive relationship between blood pressure and pain sensitivity is substantially reversed. The connection between acute or chronic pain and cardiovascular changes is supported observationally, but some of this indirect evidence is confirmed by experimental models and human studies. The pain regulatory process and functional interaction between cardiovascular and pain regulatory systems are briefly reviewed. Various data obtained are described, together with their potential clinical implications.

[Loop diuretics: facts and fallacies]. / Usiamo correttamente i diuretici dell'ansa?

Refractory edema is a clinical condition which recognises different etiologies and is characterized by decreased or absent diuretic response before the therapeutic goal is reached. Several pharmacokinetic and pharmacodynamic strategies are used in this setting, and further research is needed in order to optimize drug effectiveness.

[Ultrafiltration and hemofiltration in the cardiology unit]. / Ultrafiltrazione ed emofiltrazione nel paziente cardiologico.

The utilization of renal replacement therapies in cardiac patients has received increasing attention in recent years. In fact, isolated ultrafiltration has been proposed in patients with heart failure as a means for rapidly relieving fluid overload while preserving renal function; moreover, periprocedural hemofiltration (HF) has been suggested for radiocontrast-induced nephropathy (RCIN) prophylaxis. As a matter of fact fluid overload, with the ensuing systemic and pulmonary congestion, remains a major problem in patients with heart failure, and diuretic resistance is not an uncommon feature in the more advanced stages of the syndrome. In the same way, RCIN is increasingly indicated as a major complication of the use of iodinated contrast media, accounting for a significant number of hospital-acquired acute kidney injury episodes; moreover, it is thought to be associated with short- and long-term adverse effects on patient prognosis and increased economic burden. This article is aimed at reviewing the background of renal replacement therapies in the clinical context of cardiology wards, with special regard to isolated ultrafiltration and HF, as well as the current evidence regarding the safety and efficacy of these procedures, and their economic impact. From a theoretical point of view, isolated ultrafiltration could have a number of potential heart- and kidney-related advantages if compared to standard therapy (mainly diuretics). However, currently available clinical evidence does not support these concepts for its widespread utilization. Thus, isolated ultrafiltration should be reserved for selected patients with advanced heart failure and diuretic resistance, as part of a more complex strategy devoted to the control of fluid retention. There is currently no sound evidence for routinely recommending periprocedural HF in coronary angiography procedures, even in patients at high risk for RCIN.

[Contrast-induced nephropathy. Current concepts and propositions for Italian guidelines]. / La nefropatia da mezzi di contrasto iodati. Attuali evidenze e proposte per un consenso scientifico.

Contrast-induced nephropathy is an impairment in renal function following intravascular exposure to radiographic contrast media (CM). Kidney damage may be limited to an asymptomatic increase in serum creatinine or reveal itself as acute renal failure, which can require renal replacement therapy. The aim of the present review is to describe the most recent knowledge concerning this matter. Viscosity and/or osmolality of iodinated CM might be involved in the activation of intrarenal vasoconstriction, with a subsequent decrease in glomerular filtration rate. Reduced bioavailability of physiological vasodilators, such as prostaglandins and nitric oxide, could predispose to acute renal damage. The volemic expansion and hydration of the patient, by the peri-procedural infusion of saline solutions constitutes even today the most effective prophylactic mechanism. It is probable, in fact, that in this way the dilution of CM and the inhibition of the activation of intrarenal vasoconstrictive mechanisms are obtained.

Contrast medium induced nephropathy in urological practice.

PURPOSE: Contrast medium induced nephropathy is the third cause of in-hospital acute renal failure. The first studies in this area were done with reference to urological practice only. Although various guidelines on the management of contrast medium induced nephropathy were provided by the European Society of Urogenital Radiology, more recently many investigators have focused their attention on contrast medium use in interventional vascular radiology and cardiology. We critically reviewed the literature to clarify the impact of contrast medium induced nephropathy in urology and the possible prophylactic measures against it. MATERIALS AND METHODS: A MEDLINE/PubMed, EMBASE and Cochrane Library search for 1971 to 2006 was performed. All articles related to the use of contrast medium in urological practice and contrast medium induced nephropathy were reviewed. RESULTS: Many pathological conditions frequently seen by urologists are diagnosed by imaging requiring contrast medium. A basic understanding of the risk factors for contrast medium induced nephropathy and the strategies for its prevention are useful to prepare urological patients for these procedures. Prophylaxis includes the discontinuation of potentially nephrotoxic drugs and the use of protocols for periprocedural hydration. CONCLUSIONS: The general approach to the recognition and prevention of contrast medium induced nephropathy in patients at risk should be extended to urological clinical practice since no definitive evidence based data are available regarding contrast medium induced nephropathy management in urological patients. Moreover, these patients can frequently present with the most significant risk factor for contrast medium mediated kidney damage, that is preexisting acute or chronic renal failure. Controlled trials are needed to establish the incidence of contrast medium induced nephropathy in diagnostic or interventional procedures in uroradiology.

Contrast medium administration in the elderly patient: is advancing age an independent risk factor for contrast nephropathy after angiographic procedures?

Contrast medium-induced nephropathy (CMIN) is the third leading cause of hospital-acquired acute renal dysfunction. Even if the number of patients over 75 years of age undergoing diagnostic and/or interventional procedures and requiring administration of contrast medium (CM) is growing constantly, at present there is no definitive consensus regarding the role of advancing age and related morphologic or functional renal changes as an independent risk factor for CMIN. The authors review the evidence from recent medical literature on the definition, pathophysiology, and clinical presentation of CMIN as well as therapeutic approaches to its prophylaxis. Attention is focused on advancing age as a preexisting physiologic condition that is, per se, able to predispose the patient to CM-induced renal impairment, assuming that every elderly patient is potentially at risk for CMIN.

Facts and fallacies concerning the prevention of contrast medium-induced nephropathy.

OBJECTIVE: The aim of this article is to extract from recent medical literature and nephrologic practice the facts and fallacies concerning the possible prophylaxis of contrast medium-induced nephropathy. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: A MEDLINE/PubMed search (1985 to January 2006) was conducted, including all relevant articles investigating the pathogenesis and prevention of contrast medium-induced nephropathy from a nephrologic critical point of view. DATA SYNTHESIS: Considerable efforts have been made to develop pharmacologic therapy for the prevention of contrast medium-induced nephropathy, especially in patients at risk, such as elderly subjects and those with preexisting renal impairment, hypovolemia, or dehydration. There is general consensus that hydration protocols implemented before and after imaging with contrast medium may be effective in preventing contrast medium-induced nephropathy. However, definitive and convincing data related to amounts to be infused, infusion timing, and type of solutions (half-isotonic, isotonic saline solution, or bicarbonate) are lacking. Forced diuresis with furosemide or mannitol and use of dopamine, together with concomitant hydration, have been proved to be ineffective or even more risky in the event of inadequate maintenance of euvolemia. Various direct or indirect vasodilators have been investigated (atrial natriuretic peptide, calcium channel blockers, angiotensin-converting enzyme inhibitors, and endothelin receptor antagonists), yet results have been inconsistent and inconclusive. Recent large meta-analyses concerning the protective role of antioxidant action of N-acetylcysteine have led to the conclusion that the statistical significance of the results is borderline. Preventive hemodialysis has not proved to be useful; on the contrary, it might worsen the clinical conditions by inducing hypotension. Hemofiltration, despite some positive studies, is too complex and cannot be used extensively. CONCLUSIONS: : It is believed that prevention is actually achieved by correcting hypovolemia, dehydration, or both. Normalization of body fluids is probably the true objective to be achieved by preventive measures in all patients, not only in those at risk. Because limited data have been collected in intensive care units, at present, no firm or specific recommendations can yet be provided for the critically ill.

[Serum concentration of some tumor markers in renal failure]. / Concentrazioni plasmatiche dei marcatori tumorali nell'insufficienza renale.

This study was undertaken to define the relationship between renal function and the blood level of some tumor markers. In order to evaluate the specificity of tumor markers in cronic renal failure the following alphaFP, CEA, NSE, SCC and beta2 microglobulin were studied in 40 adult patients, with cronic renal failure of different degrees (27 p.), in hemodialyzed patients (6 p.) and in 7 healthy volunteers who did not present any clinical symptoms or signs of neoplasia. The decrease in glomerular filtration rate (GFR) was accompanied by an increase in serum levels of CEA, SCC and beta2 microglobulin. The serum level of CEA, SCC increased gradually when GFR fell below 75 ml/min. The serum level of beta2 microglobulin increased when GFR fall below 30 ml/min. Serum level of CEA, SCC and beta2 microglobulin was found to be increased in hemodialyzed patients. In conclusion in cronic renal failure and in hemodialyzed patients some tumor markers (CEA, SCC and beta2 microglobulin) show a high false positive rate and may be unreliable for monitoring malignancies in uremic patients, while alphaFP and NSE appear to maintain their specificity.

[Differential diagnosis in hypokalemia. A case of Liddle syndrome]. / Diagnosi differenziale in corso di ipokaliemia. Un caso di sindrome di Liddle.

A case of Liddle's syndrome showing weakness, hypertension, metabolic alkalosis and hypokalemia, identifiable as Liddle's syndrome, allows us to face the differential diagnosis among ionic dysfunctions, as primitive and secondary hyperaldosteronism, hypercorticism and pseudohyperaldosteronism. We discuss hypokalemia due to reduced potassium pool, or referable to altered ionic redistribution without losses. Concerning the treatment of important hypokalemia, we face manners and times of intravenous administration of potassium salts, potassium-sparing diuretics and supplementation per os; besides, we stress the dietetic contribution of rich in potassium foods, for the correction of the light hypokalemia and against deficit of pool referable to the long-term diuretic therapy.

[Etiopathogenesis and clinical aspects of nephrolithiasis--at present]. / Eziopatogenesi e clinica della nefrolitiasi, oggi.

This paper deals of kidney stones, hard concretions that grow within the urinary tract, 71.5% of which have calcium contents. A high rate of recurrences underscores the importance of medical prevention with a variety of conservative (increased fluid intake and dietary modifications) and drug therapy (potassium citrate, potassium magnesium citrate, thiazides, allopurinol). In single stone formers and mild recurrent diseases, the conservative therapy may alone be effective and should be maintained in more severe recurrent disease, together with drug treatment. In particular, in idiopathic calcium oxalate nephrolithiasis, the importance of sodium restriction in the diet, that should reduce calcium excretion, has been recently shown, limiting the old assumption of the value of dietary calcium restriction; in fact normal or higher calcium intake, binding oxalate in the intestinal tract, seems to confer protection against stone formation. The urologic approach to urolithiasis has changed with the introduction of extracorporeal shock wave lithotripsy (ESWL), a technique that allows a relatively noninvasive removal of stones. Nevertheless ESWL does not change the propensity of recurrence of stone formers, and the importance of medical prevention remains paramount in the management of renal stone disease.