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PubMed1992

Predictors of HIV-1 disease progression in early- and late-stage patients: the U.S. Army Natural History Cohort. Military Medical Consortium for Applied Retrovirology.

HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2, N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the initial clinical evaluation. Progression was defined as the occurrence of Stage 5 disease or beyond for the early cohort and Stage 6 disease or beyond for the late cohort. The cumulative incidence of progression was 15.7% (137 events) for the early-stage cohort, and 53.7% (85 events) for the late-stage cohort. Baseline CD4+ T lymphocyte (T4) count was the most significant marker of progression: 26% of WR Stage 1 or 2 patients with T4 lymphocytes below 500/mm3 progressed, compared with 12% with T4 lymphocytes at or above 500/mm3. In late-stage individuals, 83% with T4 lymphocytes under 200/mm3 progressed, compared with 27% with T4 lymphocytes at or above 200/mm3. Older age was associated with progression in both early- and late-stage groups. Differences in the rates of disease progression were not significant between blacks and whites or between men and women. Two-year rates of progression among the late-stage patients dropped from 78 to 47% between 1986 and 1988. This contrasted with progression rates in the early-stage cohort, which remained stable: 18% for those entering follow-up in 1986 and 17% for those entering follow-up in 1988. These data indicate a significant slowing of HIV disease progression rates and mortality rates among individuals with late-stage disease that is temporally associated with the increased availability and use of therapies. With control of T4 lymphocyte count, age, and calendar time, neither gender nor race was significantly associated with progression in either early- or late-stage patients.

Adolescent↗
PubMed1981

The unpredictable progression of symptomatic coronary artery disease: a serial clinical-angiographic analysis.

To determine whether risk factors or angiographic features could be correlated with progression of coronary artery disease, we independently analyzed serial coronary angiograms in 65 symptomatic patients for progression without knowledge of their respective risk factors. An important design feature of this study was that observer variability of coronary lesion assessment was objectively evaluated and taken into account in defining progression of coronary artery disease. The reproducibility of lesion assessment varied with the severity of stenosis: moderate stenoses had the greatest intraobserver and interobserver variability. At initial study, 337 partial and 68 complete occlusions were identified. Of the 337 partial occlusions at risk of progression, 73 (22%) progressed; 13 (3.2%) of the initial lesions regressed. In the 65 patients with persistent or increasing angina, progression occurred in 51 (78%) over a mean period of 24 months. Apart from the tendency of high-grade stenosis( greater than or equal to 98%) to progress to complete occlusion, no measured clinical, laboratory, or angiographic variable showed any significant effect on progression to coronary artery disease, in this selected group of symptomatic patients these same risk factors did not predict its progression. We believe that (1) and definition of progression should incorporate the factor of observer variability and (2) therapeutic measures designed to influence progression of coronary artery disease should take into account this apparently unpredictable progression.

Aged↗
PubMed2025

Intracranial and systemic progression on amivantamab in platinum-treated epidermal growth factor receptor exon 20 insertion-mutated advanced non-small cell lung cancer.

BACKGROUND: Amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, is approved as monotherapy and as combination therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring various EGFR mutations in first-line and refractory settings. Sites of progressive disease on amivantamab monotherapy are not well understood and could be instructive for treatment management. METHODS: CHRYSALIS (NCT02609776) enrolled participants with NSCLC, including those with treated brain metastases. Brain magnetic resonance imaging was required at screening but performed per local practice after enrollment (conducted postbaseline every 6 [±1] weeks after Cycle 1 Day 1). Sites of target, non-target, and new lesion progression were reported. This analysis includes 114 participants with EGFR exon 20 insertion (Ex20ins) NSCLC after disease progression on platinum-based chemotherapy who received amivantamab monotherapy on or before June 4, 2020. RESULTS: As of March 30, 2021, the median follow-up was 12.5 months (range, 0.2-30.5). Among 114 participants, the objective response rate by blinded independent central review was 43 %; median duration of response was 10.8 months, and median progression-free survival was 6.7 months. RECIST-defined progressive disease occurred in 72/114 participants (63 %); 25/72 (35 %) continued amivantamab after progression (4.2 median additional months; range, 1.0-12.5). The most common first sites of progression were the lungs/pleura (29 %), followed by bone (21 %), brain (15 %), and lymph node (12 %). Thirteen participants (11 %) had intracranial-only first progression. Six of these 13 participants underwent stereotactic radiosurgery (SRS) while continuing amivantamab. The median duration of amivantamab treatment post-progression in these 6 participants was 4.0 months (range, 2.3-6.0). SRS was well tolerated, with 2 adverse events reported (nausea and fatigue, n = 1 each). CONCLUSIONS: Amivantamab monotherapy in post-platinum Ex20ins NSCLC demonstrated meaningful antitumor activity in participants, and intracranial-only progression was infrequent. Treatment of brain progression with SRS while continuing amivantamab appears feasible and tolerable.

Adult↗
PubMed2001

Response of patients with Alzheimer disease to rivastigmine treatment is predicted by the rate of disease progression.

BACKGROUND: Evidence suggests that disease severity predicts the response of patients with Alzheimer disease (AD) to cholinesterase inhibitor treatment, raising the question of whether disease progression also predicts response to this treatment. OBJECTIVE: To evaluate retrospectively whether rate of disease progression during placebo treatment affects response to subsequent rivastigmine tartrate therapy for patients with mild to moderately severe AD. DESIGN: A 26-week, open-label extension study following a 26-week, double-blind, randomized, placebo-controlled trial. SETTING: Outpatient research centers at 22 sites in the United States. PATIENTS: We studied 187 of 235 patients originally randomized to receive placebo treatment in the double-blind phase of the trial who continued with open-label (rivastigmine) extension therapy. INTERVENTION: Placebo treatment for 26 weeks followed by rivastigmine treatment, 2 to 12 mg/d, for 26 weeks. MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), Progressive Deterioration Scale, Mini-Mental State Examination, and Global Deterioration Scale scores. RESULTS: Rivastigmine administration during open-label extension therapy benefited patients who had progressed slowly and those who had progressed rapidly during initial double-blind placebo treatment. Slowly progressive patients responded with a mean 1.03-point improvement in the week 26 (ie, start of open-label rivastigmine treatment) ADAS-Cog score at 12 weeks of rivastigmine treatment (week 38 of treatment; P =.02 vs week 26). However, more rapidly progressive patients had a significantly larger mean 4.97-point improvement from the week 26 ADAS-Cog score at 12 weeks (with respect to week 26 of treatment and slowly progressive patient scores, P<.001 for both). Thus, a more rapid disease progression rate while receiving placebo treatment was predictive of a significantly stronger patient response to rivastigmine therapy. This relation also was observed with the other 3 outcome measures and was still apparent when accounting for disease severity. CONCLUSIONS: Rate of disease progression for patients with mild to moderate AD seems to predict response to rivastigmine treatment. Patients with more rapidly progressive disease might be particularly likely to benefit from rivastigmine therapy.

Aged↗
PubMed2003

Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial.

OBJECTIVE: To assess factors for progression in the Early Manifest Glaucoma Trial (EMGT), including the effect of EMGT treatment. SETTING/PARTICIPANTS: Two hundred fifty-five open-angle glaucoma patients randomized to argon laser trabeculoplasty plus topical betaxolol or no immediate treatment (129 treated; 126 controls) and followed up every 3 months. METHODS: Progression was determined by perimetric and photographic optic disc criteria. Patient-based risk of progression was evaluated using Cox proportional hazard regression models and was expressed as hazard ratios (HR) with 95% confidence intervals (95% CI). RESULTS: After 6 years, 53% of patients progressed. In multivariate analyses, progression risk was halved by treatment (HR = 0.50; 95% CI, 0.35-0.71). Predictive baseline factors were higher intraocular pressure (IOP) (ie, the higher the baseline IOP, the higher the risk), exfoliation, and having both eyes eligible (each of the latter 2 factors doubled the risk), as well as worse mean deviation and older age. Progression risk decreased by about 10% with each millimeter of mercury of IOP reduction from baseline to the first follow-up visit (HR = 0.90 per millimeter of mercury decrease; 95% CI, 0.86-0.94). The first IOP at that visit (3 months' follow-up) was also related to progression (HR = 1.11 per millimeter of mercury higher; 95% CI, 1.06-1.17), as was the mean IOP at follow-up (HR = 1.13 per millimeter of mercury higher; 95% CI, 1.07-1.19). The percent of patient follow-up visits with disc hemorrhages was also related to progression (HR = 1.02 per percent higher; 95% CI, 1.01-1.03). No other factors were identified. CONCLUSIONS: Patients treated in the EMGT had half of the progression risk of control patients. The magnitude of initial IOP reduction was a major factor influencing outcome. Progression was also increased with higher baseline IOP, exfoliation, bilateral disease, worse mean deviation, and older age, as well as frequent disc hemorrhages during follow-up. Each higher (or lower) millimeter of mercury of IOP on follow-up was associated with an approximate 10% increased (or decreased) risk of progression.

Adrenergic beta-Antagonists↗
PubMed2003

Scanning laser polarimetry and detection of progression after optic disc hemorrhage in patients with glaucoma.

OBJECTIVE: To examine retinal nerve fiber layer changes with scanning laser polarimetry (SLP) in the eyes of patients with glaucoma and optic disc hemorrhage. METHODS: Automated perimetry and SLP were performed in 17 eyes of 17 patients identified prospectively with optic disc hemorrhage. Criteria for visual field progression were based on decreased sensitivity seen at 3 adjacent points on the total deviation plot. Progression on SLP images was defined as a 15% or more decrease in the average thickness of the affected quadrant (superior or inferior), a 25% or more reduction in the affected quadrant ratio, an increase in the nerve fiber analyzer number of 10 or more (GDx Nerve Fiber Analyzer; Laser Diagnostic Technologies), or any change on Serial Analysis of the SLP images. MAIN OUTCOME MEASURES: Visual field progression and SLP image progression. RESULTS: The mean follow-up was 31 months (minimum, 12 months). Of the 17 eyes, 10 (59%) had visual field progression. No significant change was seen on SLP images for either the total group or the group with visual field progression. Five eyes (29%) showed progression on SLP images, 3 of which also showed visual field progression. Ten eyes showed progression on SLP images that was not confirmed on subsequent imaging. CONCLUSIONS: In eyes with visual field progression after optic disc hemorrhage, a significant change in the SLP image was not seen. Fluctuation of SLP results in patients with glaucoma necessitates confirmation of progression seen on SLP images.

Aged↗
PubMed2005

Relationship of age, sex, and ethnicity with myopia progression and axial elongation in the correction of myopia evaluation trial.

OBJECTIVE: To identify the baseline factors independently related to 3-year myopia progression and axial elongation in COMET. METHODS: A total of 469 children were enrolled, randomly assigned to progressive addition lenses with a + 2.00 diopter (D) addition or to single vision lenses and observed for 3 years. Eligible children were 6 to 11 years old, with spherical equivalent myopia of - 1.25 to - 4.50 D, bilaterally. The primary and secondary outcomes, myopia progression by cycloplegic autorefraction and axial elongation by A-scan ultrasonography, were measured annually. Multiple linear regression was used to adjust for covariates, including treatment. RESULTS: Younger baseline age (6-7 vs 11 years, 8 vs 11 years, and 9 vs 11 years, P<.001; 10 vs 11 years, P = .04), female sex (P = .01), and each ethnic group compared with African Americans (Asian, P = .02; Hispanic, P = .002; mixed, P = .002; white, P = .001) were independently associated with faster 3-year progression. Children aged 6 to 7 years had the fastest progression of all age groups, progressing by a mean (+/- SD) of 1.31 D +/- 0.13 more than children aged 11 years. Females progressed 0.16 D more than the males. Children of mixed, Hispanic, Asian, and white ethnicity progressed more than African American children by 0.49 D +/- 0.16, 0.33 D +/- 0.11, 0.32 D +/- 0.13, 0.27 D +/- 0.08, respectively. Age and ethnicity, but not sex, were independently associated with axial elongation. Among these myopic children, a 0.5 mm increase in axial length was associated with 1 D of myopia progression. CONCLUSIONS: Younger baseline age was the strongest factor independently associated with faster myopic progression and greater axial elongation at 3 years. African American children had less myopic progression and axial elongation than the other ethnic groups.

Age Factors↗
PubMed1998

Cigarette smoking and progression of atherosclerosis: The Atherosclerosis Risk in Communities (ARIC) Study.

CONTEXT: Cigarette smoking is a powerful risk factor for incident heart disease and stroke, but the relationship of active and passive smoking with the progression of atherosclerosis has not been described. OBJECTIVE: To examine the impact of active smoking and exposure to environmental tobacco smoke (ETS) on the progression of atherosclerosis. DESIGN: A longitudinal assessment of the relationship between smoking exposure evaluated at the initial visit and the 3-year change in atherosclerosis. SETTING: A population-based cohort of middle-aged adults from 4 communities in the United States. PARTICIPANTS: A total of 10914 participants from the Atherosclerosis Risk in Communities (ARIC) study enrolled between 1987 and 1989. MAIN OUTCOME MEASURE: Change in atherosclerosis from baseline to the 3-year follow-up as indexed by intimal-medial thickness of the carotid artery assessed by ultrasound and adjusted for demographic characteristics, cardiovascular risk factors, and lifestyle variables. RESULTS: Exposure to cigarette smoke was associated with progression of atherosclerosis. Relative to never smokers and after adjustment for demographic characteristics, cardiovascular risk factors, and lifestyle variables, current cigarette smoking was associated with a 50% increase in the progression of atherosclerosis (mean progression rate over 3 years, 43.0 microm for current and 28.7 microm for never smokers, regardless of ETS exposure), and past smoking was associated with a 25% increase (mean progression rate over 3 years, 35.8 microm for past smokers and 28.7 microm for never smokers). Relative to those not exposed to ETS, exposure to ETS was associated with a 20% increase (35.2 microm for those exposed to ETS vs 29.3 microm for those not exposed). The impact of smoking on atherosclerosis progression was greater for subjects with diabetes and hypertension. Although more pack-years of exposure was independently associated with faster progression (P<.001), after controlling for the number of pack-years, the progression rates of current and past smokers did not differ (P=.11). CONCLUSIONS: Both active smoking and ETS exposure are associated with the progression of an index of atherosclerosis. Smoking is of particular concern for patients with diabetes and hypertension. The fact that pack-years of smoking but not current vs past smoking was associated with progression of atherosclerosis suggests that some adverse effects of smoking may be cumulative and irreversible.

Arteriosclerosis↗
PubMedDate not supplied

Association between nocturnal blood pressure reduction and progression of visual field defect in patients with primary open-angle glaucoma or normal-tension glaucoma.

PURPOSE: To assess prospectively the relationship between nocturnal blood pressure reduction (dip) and progression of the visual field defect in patients with normal-tension glaucoma (NTG) or primary open-angle glaucoma (POAG). PATIENTS AND METHODS: The subjects studied were 38 patients with glaucoma (23 patients with NTG, 15 patients with POAG), in whom 48-h ambulatory blood pressure monitoring was conducted, who were followed for at least 4 years, and in whom reliable visual field tests were performed at least 5 times. The progression was determined by the mean deviation (MD) slope analysis system installed in the Humphrey field analyzer Statpac program. Glaucoma patients with a dip of <10% were assigned to the nondipper group, those with a dip of 10%-20% to the tipper group, and those with a dip of >20% to the extreme dipper group. The dipper group was defined as physiologic dippers, while the nondipper and the extreme dipper groups were defined as nonphysiologic dippers, to study the relationship between the disturbance of the dip and progression of the visual field defect. RESULTS: Thirteen patients showed significant progression, while 25 patients did not. There were no significant differences in the mean intraocular pressure and follow-up period between the patients with progression and those without progression. Half (7/14) of the nondippers, 20% (4/20) of the dippers, and 50% (2/4) of the extreme dippers showed progression, indicating a tendency of progression in the nondipper and the extreme dipper groups. The nonphysiologic dippers had a higher incidence of progression compared with the physiologic dippers (P = 0.05). Among the glaucoma patients in the nondipper and dipper categories only, those with progression had significantly smaller dips (P = 0.02). CONCLUSION: These results suggest that disturbance in the physiologic dip may be involved in the progression of glaucoma.

Blood Pressure↗
PubMed2005

Progression to chronic atrial fibrillation after the initial diagnosis of paroxysmal atrial fibrillation: results from the Canadian Registry of Atrial Fibrillation.

BACKGROUND: After its initial diagnosis, atrial fibrillation (AF) may progress from paroxysmal to chronic AF (CAF). The rate of progression and risk factors for progression are not clearly defined. METHODS: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled patients from 6 Canadian cities at the time of their first electrocardiographic diagnosis of AF. Comprehensive clinical and echocardiographic data were collected and patients were followed annually, carefully documenting clinical outcomes, recurrence of paroxysmal AF, and progression to CAF. Baseline clinical, electrocardiographic, and echocardiographic variables were evaluated by univariate Cox proportionate hazards analysis. A stepwise approach was used to model the association between echocardiographic and clinical variables with progression to CAF. RESULTS: A total of 757 patients with a baseline diagnosis of paroxysmal AF were evaluated. Median follow-up was 8.0 years (range 2 days to 11.1 years). The probability of progression to CAF by 1 year was 8.6% and thereafter there was a slow but steady progression to 24.7% by 5 years. By 5 years, the probability of documented recurrence of any AF (chronic or paroxysmal) was 63.2%. Increasing age, significant aortic stenosis or mitral regurgitation, left atrial enlargement, and diagnosis of cardiomyopathy were independently associated with progression to CAF. A more rapid heart rate during AF was associated with decreased risk of progression. CONCLUSIONS: After the initial diagnosis of paroxysmal AF, there is a slow but steady progression to CAF. Baseline echocardiographic variables, age, cardiomyopathy, and heart rate were independently associated with progression to CAF.

Adolescent↗
PubMed2006

Prospective evaluation of the relationship between C-reactive protein, D-dimer and progression of peripheral arterial disease.

OBJECTIVE: Elevated levels of C-reactive protein (CRP) and D-dimer (DD) have been associated with the presence and progression of various forms of atherosclerotic disease, particularly coronary heart disease. We hypothesize that there is a relationship between elevated levels of baseline CRP and DD and progression of peripheral arterial disease (PAD) in patients with symptomatic PAD. The current study is a prospective evaluation of this hypothesis. METHODS: Between 1996 and 2003, 384 subjects were enrolled in a National Institutes of Health-sponsored blinded, prospective trial evaluating the effects of multiple atherosclerotic risk factors on progression of symptomatic PAD. Baseline levels of CRP and D-dimer were obtained in 332 subjects. Subjects were followed every 6 months with clinical history and exam, ankle-brachial pressure index (ABI), and carotid artery duplex scanning (CDS). The primary study end point was a composite of ABI progression, CDS progression, stroke, myocardial infarction, amputation, and death from cardiovascular disease. Secondary end points included each of the components of the primary end point. The relationship between time to the various endpoints and baseline CRP and DD levels was examined by life-table analysis and Cox proportional hazards analysis. RESULTS: Adequate baseline samples for CRP and DD were available in 332 subjects (mean age, 67 years; 57.8% men) with mean follow-up of 38.4 months (range, 1 to 99 months). Mean baseline levels (+/- SD) for CRP were 0.8 +/- 1.14 (range, 0.03 to 13.0), and mean DD levels were 227.4 +/- 303.3 (range, 1.9 to 2744.8). Progression, as defined by the primary end point, occurred in 48.5% of subjects. Subjects with elevated CRP (highest tertile) were no more likely to have any of the progression end points than those with the lowest values (lowest tertile) (P = NS, log-rank test, for all comparisons). By univariate analysis, subjects with elevated DD (highest tertile) were significantly more likely to die from any cause compared with subjects with the lowest DD values (lowest tertile) (P = .03, log-rank test). They were, however, no more likely to reach any of the other progression end points, including the primary end point (P = NS, log-rank test for all other comparisons). Multivariate analysis showed that DD level was a significant independent variable associated with occurrence of myocardial infarction (hazard ratio, 2.3; P = .02). CONCLUSIONS: In subjects with symptomatic PAD, elevated baseline DD, a marker of thrombotic activity, was significantly associated with the occurrence of myocardial infarction. This study did not confirm a relationship between progression of PAD and baseline DD or CRP during the first 3 years. Baseline DD and CRP do not provide useful risk stratification in patients at high risk for progression of symptomatic PAD. Future studies should evaluate serial levels of these markers to assess their utility in predicting progression of symptomatic PAD.

Aged↗
PubMed2004

Central corneal pachymetry and visual field progression in patients with open-angle glaucoma.

PURPOSE: To investigate the association between corneal pachymetry and visual field progression in patients with chronic open-angle glaucoma. DESIGN: Retrospective case-control study. PARTICIPANTS: Eighty-eight patients with primary open-angle glaucoma, pseudoexfoliative glaucoma, pigmentary glaucoma, or normal-tension glaucoma, followed for an average of 8 years, who had visual field loss and progression as defined by modified Anderson criteria. Cases with progression were matched for race, diagnosis, and age at pachymetry with controls who did not have progression. METHODS: Progression was defined by use of the modified Anderson criteria. Central corneal thickness (CCT) was determined by ultrasound pachymetry. MAIN OUTCOME MEASURES: Visual field progression and corneal pachymetry. RESULTS: The mean CCT in patients with visual field progression was significantly lower than the mean CCT in patients who did not progress (529+/-36 mum vs. 547+/-35 mum; P = 0.02). Those with thinner CCT were more likely to progress than those with thicker CCT as identified by Cox proportional hazards regression analysis (P = 0.01; hazard ratio, 1.44 for a 40-mum thinner CCT; 95% confidence interval, 1.12-1.80), and CCT was the only risk factor identified to be significantly associated with visual field progression. CONCLUSIONS: In this case-control patient population, visual field progression in patients with open-angle glaucoma was significantly associated with thinner CCT.

Adult↗
PubMed1999

Determinants of retinopathy progression in type 1 diabetes mellitus.

PURPOSE: To determine the risk factors for retinopathy progression in type 1 (insulin-dependent) diabetes mellitus in a prospective cohort study. SUBJECTS AND METHODS: Subjects were 485 participants in the Sorbinil Retinopathy Trial, a randomized trial of aldose reductase inhibition among patients aged 18 to 56 years with type 1 diabetes mellitus (duration of 1 to 15 years) and no or only mild retinopathy. Retinopathy progression, assessed by seven-field stereoscopic fundus photography, was defined as worsening by two or more levels on a standardized grading scale at the end of follow-up (median, 41 months). RESULTS: The relative risks for retinopathy progression according to successively greater quintiles of total glycosylated hemoglobin level at baseline, after adjusting for age, diabetes duration, sorbinil assignment, and other variables, were 1.0, 2.0, 1.6, 3.7, and 4.4 (P trend <0.0001). Risk increased with greater baseline diastolic blood pressure: 1.0 for <70 mm Hg, 1.2 for 70 to 79 mm Hg, and 1.8 for > or =80 mm Hg (P for trend = 0.04). Diastolic blood pressure was a significant risk factor for progression in participants with mild baseline retinopathy (P for trend <0.02) but not in those without retinopathy at entry. Systolic blood pressure, by comparison, was not associated with progression. Baseline total cholesterol level was a marginally significant predictor of retinopathy progression when examined as a categorical variable (relative risks for increasing quartiles; 1.0, 1.6, 1.8, 1.9; P for trend = 0.03) but not when it was examined as a continuous variable or when hypercholesterolemic patients were compared with those with normal levels. Furthermore, when cholesterol levels were updated in subsequent visits, it was not a significant predictor of progression, and low density lipoprotein (LDL) cholesterol levels did not predict progression no matter how analyzed. Smoking was not associated with progression of retinopathy. CONCLUSIONS: Levels of hyperglycemia and diastolic blood pressure predicted progression of retinopathy in type 1 diabetes mellitus. We found only a suggestion of an association between total cholesterol level (but not of LDL cholesterol level) and progression of retinopathy; resolution of this issue will require additional studies with larger sample sizes and longer follow-up.

Adult↗
PubMed2001

Fetal weight and progression of diabetic retinopathy.

OBJECTIVE: To test the hypothesis that progression of diabetic retinopathy in pregnancy is associated with reduced fetal growth and related neonatal morbidity. METHODS: Women with type 1 diabetes (n = 205) were enrolled before 14 weeks' gestation in a prospective study of diabetes in pregnancy and treated with intensive insulin therapy. They had serial ophthalmologic evaluations before 20 weeks' gestation and in late gestation or postpartum. Subjects were divided into two groups based on whether retinopathy progressed (progression group) or remained unchanged (no progression group). RESULTS: Retinopathy progressed in 59 of 205 women (29%) and was associated with advanced White classification (P =.001): three (5%) were class B, 14 (23%) class C, 24 (41%) class D, and 18 (30%) class F-RF. Reduced fetal growth was associated with progression of retinopathy. Mean birth weight was lower (P =.02), and more infants were small for gestational age (P =.02) and had low birth weights (P =.02) in the progression group. More large-for-gestational-age infants were noted in the no-progression group (P =.04). Birth weight percentile distributions showed a shift of the curve to the left in the progression group (P =.03). There were no differences in gestational age at delivery, macrosomia, preterm delivery, respiratory distress syndrome, neonatal hypoglycemia, or neonatal death. Small for gestational age was associated with chronic hypertension (odds ratio [OR] 6.4; 95% confidence interval [CI] 1.5, 27.9) and retinopathy progression (OR 4.7; 95% CI 1.2, 23.8). CONCLUSION: Development and progression of diabetic retinopathy during pregnancy were associated with reduced fetal growth manifested as increased rate of small-for-gestational-age and low-birth-weight infants.

Adult↗
PubMed1997

Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups.

BACKGROUND: Our aim was to assess the natural history of liver fibrosis progression in hepatitis C and the factors associated with this progression. METHODS: We recruited 2235 patients from the Observatoire de l'Hépatite C (OBSVIRC) population, the Cohorte Hépatite C Pitié-Salpétrière (DOSVIRC) population, and the original METAVIR population. All the patients had a biopsy sample compatible with chronic hepatitis C as assessed by the METAVIR scoring system (grades the stage of fibrosis on a five-point scale, F0 = no fibrosis, F4 = cirrhosis, and histological activity on a four-point scale, A0 = no activity, A3 = severe activity). No patient had received interferon treatment before the liver biopsy sample was obtained. We assessed the effect of nine factors on fibrosis progression: age at biopsy; estimated duration of infection; sex; age at infection; alcohol consumption; hepatitis C virus C (HCV) genotype; HCV viraemia; cause of infection; and histological activity grade. We defined fibrosis progression per year as the ratio between fibrosis stage in METAVIR units and the duration of infection (1 unit = one stage, 4 units = cirrhosis). FINDINGS: The median rate of fibrosis progression per year was 0.133 fibrosis unit (95% CI 0.125-0.143), which was similar to the estimates from previous studies (0.146 to 0.154). Three independent factors were associated with an increased rate of fibrosis progression: age at infection older than 40 years, daily alcohol consumption of 50 g or more, and male sex. There was no association between fibrosis progression and HCV genotype. The median estimated duration of infection for progression to cirrhosis was 30 years (28-32), ranging from 13 years in men infected after the age of 40 to 42 years in women who did not drink alcohol and were infected before the age of 40. Without treatment, 377 (33%) patients had an expected median time to cirrhosis of less than 20 years, and 356 (31%) will never progress to cirrhosis or will not progress for at least 50 years. INTERPRETATION: The host factors of ageing, alcohol consumption, and male sex have a stronger association with fibrosis progression than virological factors in HCV infection.

Adult↗
PubMed1995

Progression of atherosclerosis in arteries distal to lower extremity revascularizations.

PURPOSE: The characteristics of progression of atherosclerotic occlusive disease (AOD) of the lower extremities after revascularization are unknown. Duplex scanning or angiography were used to determine progression in 150 patients after they underwent revascularization for AOD. METHODS: Follow-up studies were compared with presurgical arteriograms. Superficial femoral (SFA) and popliteal arteries were graded as less than 50% stenosis, 50% to 99% stenosis, or occluded. Tibial arteries were graded with regard to whether they were continuously patent from the popliteal trifurcation to the ankle. Progression was defined as an increase in one stenosis category. RESULTS: At a mean follow-up of 4.8 years, 18% of native arteries, 39% of extremities, and 52% of patients demonstrated progression of AOD. Overall, 21% of arteries in patients undergoing infrainguinal bypass and 14% of arteries in patients undergoing suprainguinal bypass demonstrated progression (p = 0.004). Progression was more frequently detected in examinations performed more than 4 years after baseline arteriography (66%) than in examinations performed 6 months to 2 years (45%, p = 0.032) or 2 to 4 years (44%, p = 0.029) after baseline arteriography. Thirty percent of SFAs demonstrated progression, and 32% with 50% stenosis or greater at baseline became occluded. There was no difference in SFA, popliteal, or tibial artery progression in revascularized versus nonrevascularized extremities after suprainguinal bypass. There was no difference in tibial artery progression in operated and nonoperated limbs after femoropopliteal artery bypass. CONCLUSIONS: AOD progression occurs frequently in patients requiring revascularization and is more prevalent in patients requiring femoropopliteal than in patients requiring suprainguinal bypass. AOD progression in patients undergoing vascular surgery is associated with the pattern of disease producing lower extremity ischemia and does not appear to be worsened by arterial reconstruction.

Adult↗
PubMed1997

Superficial femoral artery stenoses: characteristics of progressing lesions.

PURPOSE: The purpose of this study was to assess the effect of superficial femoral artery (SFA) stenosis morphologic characteristics and lesion location on the rate of atherosclerotic disease progression. METHODS: We identified 19 patients who required arteriography for treatment of critical leg ischemia and who had previously undergone arteriography of that leg when minimal or no symptoms were present. These initial incidental arteriographic evaluations were performed during evaluation of arterial disease in another vascular bed from 4 to 81 months (mean, 32 months) previously. Distinct SFA stenoses or occlusion on the final arteriogram (n = 98) were characterized by their location, length, stenosis severity, and morphologic appearance on the initial arteriogram. The contribution of patient-specific risk factors to disease progression was also assessed. RESULTS: Stenosis progression occurred independently among multiple lesions within the same patient (negligible intraclass correlation coefficient, r = 0.06). Lesions in the adductor canal region were more likely to occlude than lesions elsewhere in the SFA (adjusted odds ratio = 10.7; p = 0.03). Severity of initial lesion stenosis also was predictive of occlusion (adjusted odds ratio = 1.8; p = 0.04). However, most progressing lesions (93%) actually arose in areas of initially mild disease (stenoses < 50%) despite more severe initial lesions elsewhere. Increasing age (p = 0.023) and previous contralateral leg bypass (p = 0.036) were also associated with increasing rates of lesion progression. Smooth-asymmetric lesions progressed 11% more slowly than other lesion types (p = 0.003). CONCLUSIONS: Our analysis of atherosclerotic SFA lesion progression in patients with critical ischemia shows that initial stenosis severity was associated with higher occlusion rates and that smooth-asymmetric lesions progressed more slowly than lesions with other morphologic characteristics. Severe stenoses usually arose from minimally diseased regions and progressed more rapidly than preexisting, more highly stenotic lesions. Most SFA occlusions resulted from disease progression in the adductor canal region whether or not antecedent lesions were seen on arteriography and whether or not more severe stenoses were initially present elsewhere. Increased age and history of previous contralateral bypass were patient-specific predictors of lesion progression.

Aged↗
PubMed2006

Coronary artery disease progression is associated with C-reactive protein and conventional risk factors but not soluble CD40 ligand.

BACKGROUND: Coronary artery disease (CAD) is a major cause of death worldwide. Epidemiological studies have documented conventional risk factors; however, no studies to date have addressed the roles of soluble CD40 ligand (sCD40L) and monocyte chemoattractant protein-1 (MCP-1), and there have been few reports on other novel risk factors in CAD progression. The aim of the present study was to explore the roles of novel and conventional risk factors in CAD progression. METHODS: Patients with stable angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of their first catheterization between March 1999 and January 2004 were enrolled. Those who had progression of coronary atherosclerosis were classified into the progression group (n = 66). Those who did not have CAD progression were classified into the nonprogression group (n = 124). RESULTS: There were more cases of diabetes mellitus (36% versus 20%; P = 0.024) and more men (92% versus 81%; P = 0.040) in the CAD progression group than in the nonprogression group, respectively. The progression group also had poorer lipid profiles than the nonprogression group, including higher total cholesterol (188+/-42 mg/dL versus 173+/-39 mg/dL, respectively; P = 0.014) and low density lipoprotein cholesterol (122+/-38 mg/dL versus 112+/-36 mg/dL, respectively; P = 0.025). In terms of inflammatory markers, progression patients had higher baseline high-sensitivity C-reactive protein (hs-CRP) concentrations (P = 0.018), which was also related to the subsequent angiographic severity score changes; however, sCD40L (6182+/-4352 pg/mL versus 6244+/-4602 pg/mL; P = 0.961), MCP-1 (427+/-540 pg/mL versus 341+/-128 pg/mL; P = 0.580) and adhesion molecules concentrations were indifferent between the progression group and the nonprogression group, respectively. Using a multivariate logistical regression model, the ORs for predicting progression were 2.19 for diabetes mellitus, 2.04 for hypercholesterolemia and 1.52 for hs-CRP (P < 0.05). CONCLUSION: In the present study, only conventional risk factors, and particularly hs-CRP, were markers for predicting CAD progression. Novel risk factors, such as concentrations of sCD40L, MCP-1 and adhesion molecules, did not play significant roles.

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