CARDIOVASCULAR SCREENING THROUGH CRP

C-reactive protein (CRP) has been for long associated to cardiovascular diseases, so often studies are performed to verify its usefulness in the evaluation of cardiovascular risk. Two new studies examined the problem. In the first one, to verify whether it is possible to perform tests being able, in a sufficiently precise way, to give a prevision of cardiovascular disease, some researchers have followed 15048 women (average age more than 45)for about 10 years; 390 of them developed a cardiovascular disease during follow-up. When, to the usual risk factors (cholesterol, smoke, hypertension, age) also CRP was added, predictivity was not improved. The four traditional risk categories were then considered (<5%, 5%-10%, 10%-20%, >20%), recalculated according to RCP values. In this way, about 13% of women in each category were reclassified in the category, but 2%-10% were transferred into a higher category.

Screening for Hemocromatosis

The U.S. Preventive Services Task Force (USPSTF) periodically releases updates of guidelines, always concluding with a recommendation classified in this way:

1. The intervention is strongly recommended
2. The intervention is recommended
3. There are neither recommendations in favour, nor recommendations against
4. The intervention is not routinely recommended
I the evidence is not sufficient to give a recommendation

Starting from a systematic review of the available evidence on hemocromatosis prevention, the recourse to genetic tests in the general asymptomatic population is not recommended. This recommendation is not applied to subjects presenting signs or symptoms of the disease or to those with a family history of hemocromatosis. D recommendation.
The USPSTF based this recommendation of the fact that hemocromatosis is a rare disease and that only a little percentage of subjects with a risk genotype (C282Y homozygotes) shows the disease. Besides, a poor evidence was found on the usefulness of early bloodlettings in the improvement of morbility and mortality (no case-control trial). Since screening would imply the unnecessary cataloguing of some people, the starting of further analyses, the inevitable situation of connected anxiety, the USPSTF concludes that the potential damage deriving from a mass screening goes over the possible obtainable benefits.

As it happens in most cases, in this situation too there are no valid argumentations in favour of this screening ; now the USPSTF further reinforces this recommendation. Obviously these conclusions are not applied when we speak of a screening targeted on high-risk subjects.

Double-Balloon Enteroscopy

X-ray sensibility towards the origin of small intestine bleedings is relatively low, so people are always searching new imaging techniques. The use of video capsules improved the situation, but their use does not allow the execution of biopsies or therapeutical procedures. Recently, a new endoscopy technique was created (also defined “push-and-pull”) exploiting a particular tool: an enteroscopy surrounded by a Plexiglas transparent hose gliding on it: at the end of both tools, there are two balloons, which can be inflated if necessary. The balloons inflation allows to “catch” the bowel and to place it on the tool to display vast parts of the small intestine. The tool can be orally or rectally introduced in order to respectively explore the proximal or the distal part of the bowel. Two trials were performed to assess the reliability of this new tool, performed on patients in whom gastroscopy and colonscopy were not able to show the origin of gastrointestinal bleedings. In the first trial, performed in China, the double-balloon tool used in 152 patients revealed the bleeding origin in 76% of cases (most of them were angiodysplasias or small-intestine cancers); in the second trial, performed in Germany, the tool’s diagnostic capability reached 73% (vs 44% of traditional techniques). In this second trial, the endoscopy was orally introduced, reaching a 230-cm deepness. In both trials, an argon laser was used to coagulate the bleeding source, with no severe complication.

The tool seems to be very promising and its use in unsolved cases, both at a diagnostic and at a therapeutical level, is certainly desirable. But for the moment, we are still at an experimental level.

The Diagnosis of Pulmonary Embolism

CT angiography is becoming more and more used to perform diagnoses of pulmonary embolism, replacing perfusion lung scintigraphy, which, up to some time ago, was considered the gold standard in this diagnosis. In order to compare these two techniques, an international multicentric randomized trial was performed, involving 1417 patients with a high probability to develop pulmonary embolism (Wells score ≥ 4.5 or positive D-dimer). The subjects with scintigraphy suggesting pulmonary embolism or positive CT angiography were treated with anticoagulants; the ones with negative examinations were not treated. All the others were investigated with lower limbs US and treated with anticoagulants if found affected by deep venous thrombosis. Out of 694 patients randomized at CT angiography, 19.2% resulted positive for pulmonary embolism or DVT, compared to 14.2% of those examined with scintigraphy. Out of the remaining 561 patients examined with CT angiography, 0.4% developed thromboembolic events, compared to 1.0% of those examined with scintigraphy.

CT angiography detected 30% more of pulmonary embolism compared to perfusion lung scintigrahpy. In the scintigraphy group, however, this lack of recognition is not associated with important clinical evidences, so probably there are mild conditions of pulmonary embolism which are asymptomatic and for which it is not opportune to undergo coagulation. In practice, the authors suggest that the correct approach to pulmonary embolism diagnosis should imply the evaluation of pre-test probabilities, D-dimer dosage, lower limbs echodoppler, CT angiography if not contraindicated and perfusion scintigraphy if available.

Magnetic Resonance Elastography

Magnetic resonance elastography is a recently introduced technique in order to avoid the problem of performing liver biopsies: with this method, the difference in elasticity of liver parenchyma (and consequently the presence and the extension of a possible fibrosis) is calculated through the analysis of the passage of acoustic waves through the liver. In this trial, some French researchers have compared MR elastography with two further non-invasive approaches for the staging of liver fibrosis: transient elastography and the APRI index (relation between AST and platelets) in 141 patients with chronic liver disease undergoing liver biopsy. In 45 subjects, biopsy, MR and transient technique did not give any results, so 96 cases remained to be analyzed. MR elastography showed itself statistically better than transient elastography and APRI index in distinguishing the stage of fibrosis, keeping liver biopsy as a gold standard. The sensitiveness of the examination ranged from 85% to 100% and its specificity ranged from 95% to 97%, according to the various considered evaluation parameters: absence or presence of fibrosis in general, greater or lower fibrosis stage, presence of fibrosis or further abnormalities.

MR elastography is already available in various hospitals. Its potential use includes the examination of patients recently diagnosed with a liver disease and for whom a liver biopsy is necessary (for example, to start treatment with interferon for a HCV-related liver disease). A little warning: the examination is not reliable in patients affected by hemocromatosis.

Complications of Colonscopy

Since colonscopy is more and more spreading, because of screening diagnostic procedures, it is important to know which can be its complications. Some Californian researchers examined electronic medical records of 16.318 screening colonscopies performed on symptomatic patients. Complications (among which bleeding, intestinal perforations, diverticulitis) were identified through hospitalizations or death occurred within 30 days from colonscopy. The most frequent indication to perform the exam was represented by the detection of polyps through sigmoidoscopy (45% of cases, almost everyone together with biopsy) or from a history of previous polyps (23%, with biopsy in half cases), while only 7%was represented by primary screening. The overall incidence of severe complications was of 5%. Among the 5235 colonscopies which were not performed together with biopsy, severe complications had an incidence of 0,8‰ (0.6‰ of perforations); among the 11.083 colonscopies with biopsy, severe complications had an incidence of 7‰ (4.8‰ of bleeding with the need of surgery or transfusion). The risk of intestinal perforation was higher in subjects of 60 or more. Performing an overall analysis, 40% of all severe complications and 64% of all bleedings occurred after endoscopic removal of polups smaller than 10 mm.

The cumulative incidence of severe complications was, at least in this study, of about 1 out of 200 examinations, which is not little for a screening procedure theoretically destined to lots of people. It is necessary to underline that in this trial, colonscopy was performed not as a screening on healthy subjects but prevalently under clinical indications, with the performance of very frequent biopsies. But it is however true that the risk of perforation and of severe bleeding is high, so undergoing this procedure must be the result of an informed and well thought choice by physician and patient.

CT in Chest Pain

Multilayer CT technique has acquired more and more importance as a diagnostic non-invasive method for the diagnosis of coronary atheromasic plaques. In this prospective study, partially sponsored by the producer of the X-ray machinery, the usefulness of multilayer CT was evaluated in 103 patients with chest pain (average age 54 years old; 60% males) with no alterations at the ECG and with normal cardiac enzymes. The survey was performed immediately after hospitalization. Judging by hospitalization data and a 5-month follow-up, a board of experts blindly evaluated the results of CTs, finding the presence of an acute coronary syndrome in 14 patients. In 41 patients any presence of coronary plaques was excluded and in 73 patients a coronary stenosis higher than 50% was excluded. None of those subjects had had an acute coronary syndrome (negative predictive value 100%).

The use of CT in acute chest pain can be a valid help to exclude (or to confirm) the cardiac origin of pain. The study is interesting, but its generalization is probably not correct, since the sample was small, the age of the participants was relatively young, the coronary events were little frequent and patients with severe rhythm alterations were excluded. In any case, the use of multilayer CT in case of chest pain of doubtful origin is certainly proposable.

Non-Invasive Diagnosis of Esophageal Varices

In patients with cirrhosis the endoscopic screening is indicated to verify the possible presence of esophageal varices, in order to start a preventive therapy with beta-blockers to avoid bleeding. Esophageal varices are associated with both thrombocytopenia and splenomegaly. In a previous study, Giannini and coll. had suggested that a platelet count associated with spleen diameter measurement could be a non-invasive alternative to endoscopy to identify the patients with a high risk of varices: a ratio higher than 909 (platelet count/mm3 divided by spleen diameter in mm) had a negative predictive value of 100%. Now, the same Italian researchers have evaluated the accuracy of this ratio in 218 subjects affected by cirrhosis related to various etiology. All had undergone endoscopy for the first time, with a confirmation of esophageal varices in 54% of patients. Cutoff at 909 showed to have a sensibility of 92% and a specificity of 67% with a positive predictive value of 77% and a negative predictive value of 87%.

A ratio platelets/spleen diameter higher than 909 excludes the presence of esophageal varices with an accuracy of 87%, while a diagram by the authors shows that rising the cutoff to 1400 one could obtain a negative predictive value of 100% (it is however true that few patients present these values). The platelet count and the spleen diameter measurement through echography represent however a valid non-invasive and low-cost help in esophageal varices diagnostics.