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PubMed1993

Health care costs of veterans with multiple sclerosis: implications for the rehabilitation of MS. VA Multiple Sclerosis Rehabilitation Study Group.

We retrospectively determined health care costs among veterans with multiple sclerosis (MS) and correlated the costs with neurologic dysfunction. Total health care costs for the 165 patients averaged $35,000/year. VA benefits and homecare together accounted for 85% of the total costs. Total health care costs correlated with two measures of neurologic dysfunction, the Expanded Disability Status Scale (EDSS) (r = 0.61, p < 0.001) and the Incapacity Status Scale (ISS) (r = 0.64, p < 0.001). The costs of VA benefits, homecare, and hospitalizations also correlated with the EDSS, ISS, and other measures of neurologic dysfunction whereas the cost of outpatient clinic visits did not. In a period of three years, there were 40 hospitalizations, at a total cost of $412,800, that were potentially preventable with appropriate outpatient management. Improving selfcare and avoiding preventable hospitalizations might lower the considerable health care costs of MS.

Activities of Daily Living↗
PubMedDate not supplied

Temporal lobe pathology in amyotrophic lateral sclerosis. Do amyotrophic lateral sclerosis and Alzheimer's disease share a common etiological factor?

An autopsy study was performed on temporal lobe samples from 20 non-demented patients with amyotrophic lateral sclerosis (ALS), 17 age-matched non-demented controls and 4 Alzheimer's disease (AD) patients. Formalin fixed, paraffin embedded sections from the hippocampus with adjacent parahippocampal gyrus and from the superior temporal gyrus were stained with conventional and immunohistochemical stains. Immunohistochemical staining for the A4 protein was enhanced by pretreatment with 0.25% pepsin before 100% formic acid. The incidence and severity of AD-like pathological changes were similar in ALS patients and non-demented controls. In both groups, pathological changes increased with age. This study does not support the hypothesis that ALS and AD share an etiopathogenetic background.

Aged↗
PubMed1996

The Amyotrophic Lateral Sclerosis Functional Rating Scale. Assessment of activities of daily living in patients with amyotrophic lateral sclerosis. The ALS CNTF treatment study (ACTS) phase I-II Study Group.

OBJECTIVES: To test the utility of a new, easy to administer instrument for assessing activities of daily living in patients with amyotrophic lateral sclerosis (ALS), to validate its accuracy, and to assess its ability to record disease progression in patients with ALS against other functional scales, quantitative isometric muscle testing, and global assessment scales. DESIGN: Serial assessments of patients who presented to four ALS treatment centers in two multicenter studies. PATIENTS: Study 1 (cross-sectional) evaluated 75 consecutive patients who presented to four ALS treatment centers during a 2-month period. Study 2 (longitudinal) evaluated the progression of 53 patients who were enrolled in a multicenter, phase I-II clinical trial of recombinant human ciliary neurotrophic factor for treatment of ALS. OUTCOME MEASURES: The ALS Functional Rating Scale (ALSFRS) was compared with quantitative myometry and with other measures of daily function in patients with ALS both cross-sectionally and longitudinally. RESULTS: The first study of 75 patients evaluated the internal consistency, the test-retest reliability, and the construct validity of the ALSFRS. Internal consistency and test-retest reliability were high. Patient self-rating of upper- and lower-extremity-dependent tasks were highly correlated with measures of upper- and lower-extremity strength, respectively. Thus, the ALSFRS has good construct validity. In the second study, ALSFRS scores declined in tandem with deterioration in motor and pulmonary function, indicating its sensitivity to change. CONCLUSIONS: The ALSFRS is a useful instrument for evaluation of functional status and functional change in patients with ALS. Its results are in close agreement with objective measures of muscle strength and pulmonary function. The ALSFRS may be used as a screening measure for entry into clinical trials, as a surrogate measure of function in situations in which muscle strength cannot be measured directly, or as an adjunct to myometry.

Activities of Daily Living↗
PubMed1996

[EDMUS--a new European databank for multiple sclerosis. A brief introduction of ongoing and planned multicenter studies within the scope of the "European Concentrated Action for Multiple Sclerosis"].

EDMUS, the European Database for Multiple Sclerosis (MS), was established on the occasion of the first European Concerted Action for MS under the auspices of the European Community. The system is user-friendly and makes it possible to record and retrieve data relevant to MS. Within the framework of another European Concerted Action, several international multicenter trials are currently in progress. EVALUED, a validation of the EDMUS system, assesses the interrater variability; PRIMS examines the influence of pregnancy and the post-partum period on the course of MS; and PRESTIMUS investigates predictive factors in suspected MS. Further, planned studies include ERAZMUS (early azathioprine and interferon-beta treatment in MS) and AZASTOP, which is designed to evaluate the effect of stopping azathioprine treatment.

Azathioprine↗
PubMed1995

Natural history of amyotrophic lateral sclerosis. Observations with the Charing Cross Amyotrophic Lateral Sclerosis Rating Scales.

Natural history data increase the descriptive knowledge about amyotrophic lateral sclerosis (ALS), help define primary outcome variables and numbers of patients needed on clinical trials, and may give valuable predictive information. Global scores do not adequately represent the clinical variability of ALS. The Charing Cross Quantitative and Qualitative ALS Rating Scales assess disease severity and progression by validated regional scores (bulbar, respiration, upper limb, lower limb) and activities of daily living. The main stages in the development of these scales are summarized. Interval, or quantitative, scales provide accurate and sensitive measurements of the evolution of the disease and are useful for phase II therapeutic trials. The deterioration rates of regional scores in individual patients may not be linear. Rates of disease progression in ALS vary (1) among patients, (2) among topographical regions within a single patient, and (3) at different stages of the disease in a single region in the same patient. The deterioration rates of the regional scores of an ALS population depend critically on whether deaths are included or excluded from the population mean scores. Qualitative scales with simple scores are best suited for large-scale, phase III trials and for life table analysis of times to failure.

Amyotrophic Lateral Sclerosis↗
PubMed1996

[Multiple sclerosis: therapy with recombinant beta-1b interferon: initial results with 30 multiple sclerosis patients in northwest Switzerland].

Recombinant interferon beta-1b has been registered with the Swiss health authorities since August 1995. Due to a special arrangement with health insurances it has been possible to prescribe this medication since spring 1995. We report on our experience with the first 30 consecutively treated multiple sclerosis patients. Indication, adverse event profile and clinical response to treatment are described. The most common side effects were local injection site reactions (63%), influenza-like symptoms (50%) and fatigue (33%). As compared to the prestudy period we observed a 49% reduction in the exacerbation rate. Compliance was excellent, possibly due to strict selection and extensive information about possible effects and side effects.

Adjuvants, Immunologic↗
PubMed1997

[Interferon-beta 1B in the treatment of remittent-recurrent multiple sclerosis. Clinical experience of the Valencia group. Multiple sclerosis study group of the city of Valencia].

INTRODUCTION: Recombinant beta-1B interferon has been used in our country since the end of 1995 for treatment of remittent-recurrent multiple sclerosis (RRME). At the present time there are still gaps in the effectiveness, side-effects and management of patients on this treatment. OBJECTIVE: To determine the evolution, side-effects and practical difficulties involved in the management of patients with RRME given interferon beta-1B and prospectively followed up one year after starting treatment. MATERIAL AND METHODS: This paper gives a prospective description of 41 treated patients with an average follow-up of 254 days. RESULTS: The patients tolerated and followed their treatment well. Treatment was only withdrawn in two cases. We observed a 40% reduction in the annual incidence of exacerbations (with respect to previous years) and there was improvement on the amplified dysfunction scale of Kurtzke in the patients whose exacerbations were treated with megadoses of steroids. The side-effects were those we expected, apart from an increase in thyroid complications and the appearance of a depressive syndrome. Treatment did not have to be changed because of the side-effects. In two patients with serious side-effects (thyroiditis and a depressive syndrome) the symptoms disappeared when treatment was stopped. CONCLUSION: The results and side-effects were similar to those published. We had fewer patients who withdrew from the trial. There were no cases of patients not following the prescribed treatment.

Adjuvants, Immunologic↗
PubMed1998

Cytokine production and surface marker expression in acute and stable multiple sclerosis: altered IL-12 production and augmented signaling lymphocytic activation molecule (SLAM)-expressing lymphocytes in acute multiple sclerosis.

Ag-stimulated IL-2 production and mitogen-stimulated type 1 and type 2 cytokine production by PBMC, as well as expression of Th1- and Th2-associated phenotypical markers, of B7-1, B7-2, and CD95 (Fas) on the surface of immune cells, and the serum concentration of soluble Apo-1/Fas were evaluated in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). Results showed that 1) Ag-stimulated IL-2 production is reduced in MS patients compared with that in HC; 2) mitogen-stimulated type 1 cytokine production is increased, and IL-10 production is reduced in MS patients compared with those in HC, and in AMS patients compared with those in SMS; 3) whereas production of the metabolically active p70 heterodimers is comparable in SMS, AMS, and HC, production of the p70 heterodimer and the p40 chains (total IL-12) is increased in SMS compared with that in AMS and HC; 4) CD4+, CD4+ SLAM+, and CD4+ CD7+ lymphocytes (preferentially type 1 cytokine-producing lymphocytes) are increased in MS compared with levels in HC; 5) B7-2- as well as Fas+-expressing monocytes are augmented in MS compared with those in HC, and serum soluble Apo-1/Fas is augmented in AMS compared with SMS and HC. These results confirm that a complex imbalance in both cytokine production and the Fas system is present in MS and indicate that different cytokine profiles may be observed in patients with acute or stable disease. The data also suggest that peculiar phenotypic populations are over-represented in MS patients, and for the first time show that SLAM expression is correlated with dysregulation of type 1 and type 2 cytokine production in human pathology.

Acute Disease↗
PubMed1998

Hypointense multiple sclerosis lesions on T1-weighted spin echo magnetic resonance images: their contribution in understanding multiple sclerosis evolution.

The predictive value of T2-weighted imaging in multiple sclerosis is only moderate, due to low specificity of high signal on such images. Among new MR techniques with acclaimed higher pathological specificity, hypointense lesions on moderately T1-weighted spin echo images show improved correlation with disability. The degree of hypointensity of so called black holes correlates with loss of magnetisation transfer, a marker of matrix destruction. Severe tissue loss is also shown histopathologically in a post-mortem MR study of black holes. In this review unresolved issues regarding black holes are discussed including standardisation of sequences, definition of hypointensity, interobserver variation in measuring lesion load with this technique, and significance of acute black holes. The role of black holes in monitoring treatment efficacy is as yet unexplored.

Brain↗
PubMed1998

Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group.

BACKGROUND: Previous trials of interferon beta in multiple sclerosis (MS) have shown efficacy, but the degree of clinical benefit remains uncertain, and the optimum dose is not known. We undertook a double-blind, placebo-controlled study in relapsing/remitting MS to investigate the effects of subcutaneous interferon beta-1a. METHODS: 560 patients with Kurtzke expanded disability status scale (EDSS) scores of 0-5.0, from 22 centres in nine countries, were randomly assigned subcutaneous recombinant interferon beta-1a 22 microg (n=189), or 44 microg (n=184), or placebo (n=187) three times a week for 2 years. Neurological examinations were done every 3 months. All patients had MRI twice yearly and 205 had monthly scans in the first 9 months of treatment. Analysis was by intention to treat. FINDINGS: Clinical data on 533 (95%) patients were available at 2 years. The relapse rate was significantly lower at 1 and 2 years with both doses of interferon beta-1a than with placebo (mean number per patient 1.82 for 22 microg group, 1.73 for 44 microg group vs 2.56 for placebo group: risk reductions 27% [95% CI 14-39] and 33 [21-44]). Time to first relapse was prolonged by 3 and 5 months in the 22 microg and 44 microg groups respectively, and the proportion of relapse-free patients was significantly increased (p<0.05). Interferon beta-1a delayed progression in disability, and decreased accumulated disability during the study. The accumulation of burden of disease and number of active lesions on MRI was lower in both treatment groups than in the placebo group. INTERPRETATION: Subcutaneous interferon beta-1a is an effective treatment for relapsing/remitting MS in terms of relapse rate, defined disability, and all MRI outcome measures in a dose-related manner, and it is well tolerated. Longer-term benefits may become clearer with further follow-up and investigation.

Adult↗
PubMed2001

Evidence of 5-lipoxygenase overexpression in the skin of patients with systemic sclerosis: a newly identified pathway to skin inflammation in systemic sclerosis.

OBJECTIVE: Leukotrienes are a family of arachidonic acid derivatives with potent proinflammatory and profibrotic properties, and 5-lipoxygenase (5-LOX) catalyzes two key steps in the leukotriene biosynthetic pathway. Since inflammatory cell infiltrates and excessive fibrosis are hallmarks of systemic sclerosis (SSc) skin lesions, we undertook the present study to investigate the expression of 5-LOX in skin biopsy specimens from patients with SSc. METHODS: Expression of 5-LOX in skin sections from 10 SSc patients and 8 healthy controls was examined by in situ hybridization with specific riboprobes and by immunohistochemistry analysis with 5-LOX monoclonal antibodies. Synthesis of 5-LOX by cultured dermal fibroblasts from 7 patients with SSc and 4 controls was measured by fluorescence-activated cell sorter analysis. In addition, concentrations of leukotriene B4 (LTB4) and LTE4 in fibroblast supernatants after stimulation were determined using enzyme immunoassays. RESULTS: Expression of 5-LOX was found in all skin sections from SSc patients as well as from controls. However, the number and percentage of 5-LOX-positive cells were significantly higher in SSc skin sections compared with control sections. Expression of 5-LOX was seen in cells within perivascular inflammatory infiltrates as well as in fibroblasts throughout the skin. The experiments with cultured skin fibroblasts revealed that 5-LOX was constitutively expressed in these cells, which resulted in the production of leukotrienes after cell stimulation. Whereas no difference was found for LTE4, SSc fibroblasts produced significantly higher amounts of LTB4 after stimulation, compared with healthy control fibroblasts. CONCLUSION: The results of this study suggest that the 5-LOX pathway may be of significance in the pathogenesis of SSc and may represent a target for new treatment strategies.

Arachidonate 5-Lipoxygenase↗
PubMed1995

Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease-modifying interventions. The American College of Rheumatology Committee on Design and Outcomes in Clinical Trials in Systemic Sclerosis.

OBJECTIVE: To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death. METHODS: A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring. Delphi and nominal group techniques were used. RESULTS: Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included because they are at greatest risk for the development of severe organ damage and death. Patients should be excluded if they have other connective tissue diseases, SSc-like illnesses related to exposures or ingestions, severe existing internal organ damage, an unacceptable risk of side effects, or concurrent therapies that might independently influence the outcome. Randomized, double-blind, placebo-controlled trials are preferred. The treatment and followup period must be long enough to permit observation of any disease modification, which is likely to require 18-36 months, unless an extraordinarily effective therapy is identified. Responses selected should be quantitative, consistently and accurately reflect activity of SSc in major target organs (not solely the skin), be sensitive to change, and be standardized, with limited variability. An example of a set of responses is given. Surrogate responses are desirable, but none have been validated as correlating with organ damage. CONCLUSION: Guidelines have been established for trials of disease-modifying interventions in SSc. These guidelines will need to be altered as additional information becomes available. Any given protocol will be individualized based on the nature of the intervention and objectives of the study. Nonetheless, each study team should develop a protocol that meets the spirit of these guidelines.

Clinical Protocols↗
PubMed1996

Heterogeneity of collagen synthesis in normal and systemic sclerosis skin fibroblasts. Increased proportion of high collagen-producing cells in systemic sclerosis fibroblasts.

OBJECTIVE: The goal of this study was to quantitatively analyze the distribution of collagen synthesis in normal and systemic sclerosis (SSc) fibroblast populations in order to determine the extent of activation in SSc populations. METHODS: We used quantitative in situ hybridization to assess the population distribution of type I collagen synthesis. Fibroblast cultures were derived from both clinically involved and uninvolved skin regions of patients with SSc, and from healthy adults, and assessed for levels of alpha 1(I) procollagen messenger RNA (mRNA). RESULTS: Dermal fibroblasts from both patients with SSc and normal adults were heterogeneous for distribution of alpha 1(I) procollagen mRNA when assessed by in situ hybridization, with a wide range of grains per cell. In contrast, clones of neonatal fibroblasts showed a relatively homogeneous distribution of grain counts. Involved SSc skin fibroblasts had a larger proportion of cells in the high collagen-producing mRNA subpopulation (mean +/- SEM 28.4 +/- 6.85%), compared with normal fibroblasts (1.75 +/- 1.44%) and uninvolved fibroblasts (9.6 +/- 6.73%). Conversely, within the low collagen-producing mRNA subpopulation, involved fibroblasts had a smaller proportion of cells (mean +/- SEM 14.0 +/- 5.63%) than did uninvolved fibroblasts (37.8 +/- 13.69%), while normal fibroblasts had a majority of the cells in this subpopulation (53.5 +/- 8.68%). CONCLUSION: These results suggest that only a specific subset of fibroblasts are activated in SSc, as evidence by an increased proportion of cells with high levels of alpha 1(I) procollagen mRNA. Differences between the SSc and normal fibroblast populations appeared to be quantitative rather than qualitative. This may be a result of either clonal selection or selective activation in the pathogenesis of SSc.

Adult↗
PubMed2006

A novel autoantigen to differentiate limited cutaneous systemic sclerosis from diffuse cutaneous systemic sclerosis: the interferon-inducible gene IFI16.

OBJECTIVE: To investigate the presence and clinical significance of autoantibodies against the interferon-inducible gene IFI16 in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and other autoimmune diseases. METHODS: Immunohistochemical analysis was used to evaluate the expression of IFI16 in skin biopsy specimens obtained from patients with SSc and patients with SLE. Levels of antibodies against IFI16 in sera from 82 patients with SSc and 100 patients with SLE were determined by enzyme-linked immunosorbent assay. Other autoimmune diseases such as primary Sjögren's syndrome (SS), rheumatoid arthritis (RA), chronic urticaria, and hepatitis C virus (HCV) infection were also examined. RESULTS: Expression of IFI16 was greatly increased and was ubiquitous in all layers of the epidermis and in the dermal inflammatory infiltrates of lesional skin from both patients with SLE and patients with SSc. Patients with SLE, those with primary SS, and those with SSc exhibited significantly higher anti-IFI16 IgG antibody levels compared with normal controls (for SLE, P < 0.002; for primary SS, P < 0.001; for SSc, P < 0.0005). Anti-IFI16 titers above the ninety-fifth percentile for control subjects were observed in 26% of the patients with SLE, 50% of those with primary SS, and 21% of those with SSc (28% of patients with limited cutaneous SSc [lcSSc] versus 4% of patients with diffuse cutaneous SSc [dcSSc]). In contrast, the prevalence of anti-IFI16 was 4% in patients with RA, 5% in those with chronic urticaria, and 13% in those with HCV infection. CONCLUSION: The results of this study provide evidence that an IFN-inducible gene, IFI16, may be involved in the pathophysiologic mechanisms of connective tissue disorders such as SSc. Moreover, a strict correlation with lcSSc was also demonstrated, thus providing a novel tool in the differential diagnosis of lcSSc from dcSSc.

Adult↗
PubMed2024

Adeno-Associated Virus Type 5 Infection via PDGFR&#x3b1; Is Associated With Interstitial Lung Disease in Systemic Sclerosis and Generates Composite Peptides and Epitopes Recognized by the Agonistic Immunoglobulins Present in Patients With Systemic Sclerosis.

OBJECTIVE: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFR&#x3b1; is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFR&#x3b1; exposing epitopes that may induce the immune responses to the virus-PDGFR&#x3b1; complex. METHODS: The binding of monomeric human PDGFR&#x3b1; to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFR&#x3b1; locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFR&#x3b1; were evaluated by SPR using SSc monoclonal anti-PDGFR&#x3b1; antibodies and immunoaffinity-purified anti-PDGFR&#x3b1; antibodies from sera of patients with SSc. RESULTS: AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P <&#x2009;0.001). In SSc lungs, AAV5 localized&#x2009;in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFR&#x3b1; was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFR&#x3b1; antibodies identified spatially contiguous epitopes derived from PDGFR&#x3b1; and AAV5 that interacted with SSc agonistic antibodies to PDGFR&#x3b1;. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls. CONCLUSION: These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.

Humans↗
PubMed1994

HLA-DQB1 associations with anti-topoisomerase-1 antibodies in patients with systemic sclerosis and their first degree relatives. United Kingdom Systemic Sclerosis Study Group.

The frequency and functional properties of anti-topoisomerase-1 antibodies (ATA) have been studied in 58 systemic sclerosis (SSc) probands, 218 first degree relatives and 22 spouses. The dependence of ATA on the presence of certain HLA-DRB1 and HLA-DQB1 alleles was examined. ATA were detected by immunodiffusion, by absorption or inhibition of topoisomerase-1 enzymic activity, by immunoblotting of a K562 cell extract and by immunoprecipitation of 35S radiolabelled cell lines. HLA class II typing for HLA-DRB1 and HLA-DQB1 was performed by oligonucleotide typing in 49 families. Six probands and two relatives had ATA. The relatives with ATA had SSc. All eight individuals with ATA directly inhibited topoisomerase-1 function. Four of the eight had limited skin disease and four had diffuse skin involvement. The seven who were genotyped had at least one HLA-DQB1 allele encoding for tyrosine at position 30 of the first domain. Therefore, ATA are not widely dispersed within families, but rather are only present in those with SSc, and certain genetic requirements appear necessary for their generation.

Alleles↗
PubMed2004

Randomized, controlled trial of secondary prevention of coronary sclerosis in normocholesterolemic patients using pravastatin: final 5-year angiographic follow-up of the Prevention of Coronary Sclerosis (PCS) study.

BACKGROUND: The potential benefit of cholesterol-lowering therapy for normocholesterolemic patients with coronary artery disease (CAD) has not been clarified. The Prevention of Coronary Sclerosis (PCS) Study was designed to evaluate the effect of pravastatin on secondary prevention of progression of CAD in normocholesterolemic patients for a period of 5 years. METHODS: A total of 329 patients with CAD were enrolled. Normocholesterolemic patients were defined by a serum total cholesterol (TC) level of 180-219 mg/dl. Patients in this group were randomized into pravastatin and dietary control groups. Patients whose serum TC level fell outside the normal range were divided into a high-cholesterol reference group (TC > or = 220 mg/dl) and a low-cholesterol reference group (TC < 180 mg/dl). Patients in the pravastatin and high-cholesterol groups received pravastatin 10 mg/day. Coronary angiography was performed at baseline, 2 years, and 5 years and analyzed by quantitative coronary arteriography. Angiographic coronary progression was evaluated by minimum obstruction diameter (MOD) and mean segment diameter (MSD). RESULTS: At 5 years, change in MOD was significantly (change, P=0.033; change/years, P=0.032) less in the pravastatin group (-0.04 +/- 0.17 mm) than in the dietary control group (-0.16 +/- 0.27 mm). Although a similar trend was observed in the MSD results, the differences were not significant. CONCLUSION: Long-term angiographic data show that cholesterol-lowering therapy by pravastatin prevents progression of coronary atherosclerosis in normocholesterolemic patients with CAD.

Adult↗