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PubMed2003

Relationships between low-density lipoprotein particle size, plasma lipoproteins, and progression of coronary artery disease: the Diabetes Atherosclerosis Intervention Study (DAIS).

BACKGROUND: The Diabetes Atherosclerosis Intervention Study showed that treatment with fenofibrate decreases progression of coronary atherosclerosis in subjects with type 2 diabetes. We determined whether on-treatment plasma lipid concentrations and LDL particle size contribute to the favorable effect of fenofibrate on the progression of coronary artery disease (CAD). METHODS AND RESULTS: A total of 418 subjects with type 2 diabetes were randomly assigned to 200 mg micronized fenofibrate daily or placebo. The mean follow-up time was 39.6 months. LDL peak particle diameter (LDL size) was determined by polyacrylamide gradient gel electrophoresis from 405 subjects at baseline and at the end of the study. Progression of CAD was measured with quantitative coronary angiography. LDL size increased significantly more in the fenofibrate group than in the placebo group (0.98+/-1.04 versus 0.32+/-0.92 nm, P<0.001). In the combined group, small LDL size was significantly associated with progression of CAD measured as the increase of percentage diameter stenosis (r=-0.16, P=0.002) and decreases in minimum (r=-0.11, P=0.030) and mean (r=-0.10, P=0.045) lumen diameter. High on-treatment LDL cholesterol, apolipoprotein B, and triglyceride concentrations were also associated with the progression of CAD. In regression analyses, small LDL size added to the effect of LDL cholesterol and apolipoprotein B on the progression of CAD. Similar associations were observed in the fenofibrate group, whereas in the placebo group, lipoprotein variables were not significantly correlated with the progression of CAD. CONCLUSIONS: Changes in LDL size and plasma lipid levels account for part of the antiatherogenic effect of fenofibrate in type 2 diabetes.

Adult↗
PubMed2004

Relationship between cardiovascular risk as predicted by established risk scores versus plaque progression as measured by serial intravascular ultrasound in left main coronary arteries.

BACKGROUND: Intravascular ultrasound (IVUS) is increasingly used as an end point in studies aimed at reducing progression or inducing regression of coronary artery disease. However, data linking serial changes by IVUS with clinical outcomes are scarce. METHODS AND RESULTS: In the absence of a validated risk score for secondary prevention, we compared 3 established risk scores for primary prevention--PROCAM, SCORE, and Framingham--with plaque progression and lumen reduction as assessed with serial IVUS (follow-up, 18+/-9 months) in atherosclerotic left main coronary arteries of 56 patients with established atherosclerosis. For all 3 algorithms, patients at highest estimated risk of events showed greater plaque progression than patients at lowest risk (P<0.05 to <0.01). There were positive linear relationships between the risk of clinical events and plaque progression (r=0.41 to 0.60; P<0.002 to <0.0001). This translated into a greater decrease in lumen dimensions with increasing risk (P<0.05, PROCAM and SCORE). Risk prediction using the PROCAM algorithm showed the strongest relation with serial IVUS. During follow-up, 18 patients suffered from adverse cardiovascular events; these patients had an annual plaque progression that was significantly greater than other patients (25.2+/-19.4% versus 5.9+/-15.6%, P<0.001). CONCLUSIONS: There was a positive linear relationship between the estimated risk of clinical events derived from all 3 established risk-score algorithms and the extent of plaque progression measured by serial IVUS. This translated into stenosis progression (reduction in lumen dimensions) with increasing clinical risk.

Aged↗
PubMed2000

Rate of change in aortic valve area during a cardiac cycle can predict the rate of hemodynamic progression of aortic stenosis.

BACKGROUND: The ability to predict the rate of hemodynamic progression in an individual patient with valvular aortic stenosis has been elusive. The purpose of the present study was to evaluate whether the rate of change in aortic valve area (AVA) measured during the ejection phase of a cardiac cycle predicts the rate of hemodynamic progression in patients with asymptomatic aortic stenosis. METHODS AND RESULTS: In 84 adults with initially asymptomatic aortic stenosis and a baseline AVA of > or =0.9 cm(2), annual echocardiographic data were obtained prospectively (mean follow-up 2.8+/-1.3 years). With the initial echocardiogram, the ratio of AVA measured at mid-acceleration and mid-deceleration to the AVA at peak velocity was calculated. The primary outcome variable was the annual rate of change in AVA (rate of progression), with rate of progression classified as rapid (a reduction in AVA of > or =0.2 cm(2)/y) or slow (<0.2 cm(2)/y). Rapid progression was significantly associated with an AVA ratio of > or =1.25 (P=0.004, risk ratio 3.1, 95% CI 1.2 to 7.9). The sensitivity, specificity, and positive predictive value of AVA ratio of > or =1.25 for the prediction o rapid progression of valvar aortic stenosis was 64%, 72%, and 80% respectively. The decrease in ejection fraction measured from the initial to final echocardiogram was small but greater for patients with an AVA ratio of > or =1.25 (-4+/-7% versus +2+/-7%, P<0.001). CONCLUSIONS: A flow-dependent change in AVA can be measured during a routine transthoracic echocardiographic study. The rate of change in AVA is an additional measure of disease severity and may be used to predict an individual's risk for subsequent rapid disease progression.

Aged↗
PubMed1997

Lipoprotein oxidation and progression of carotid atherosclerosis.

BACKGROUND: Epidemiological studies and animal experiments have provided evidence supporting the role of lipid peroxidation in atherogenesis and cardiovascular diseases. Direct evidence linking lipid oxidation to atherosclerotic progression in humans, however, has been lacking. We investigated the association of lipid oxidation products with the progression of early carotid atherosclerosis in hypercholesterolemic men from eastern Finland. METHODS AND RESULTS: Twenty subjects with a fast progression and 20 with no progression of carotid atherosclerosis in 3 years were selected from > 400 participants in the Kuopio Atherosclerosis Prevention Study. Progression of carotid atherosclerosis was assessed by high-resolution B-mode ultrasonography. Serum 7 beta-hydroxycholesterol, a major oxidation product of cholesterol in membranes and lipoproteins, and seven other cholesterol oxidation products were measured by isotope dilution-mass spectrometry, lipid hydroperoxides in LDL fluorometrically as thiobarbituric acid-reactive substances (TBARS) and oxidation susceptibility of LDL and VLDL kinetically. High concentrations of serum 7 beta-hydroxycholesterol (beta = 47, P = .0005), cigarette smoking (beta = .35, P = .0167), and LDL TBARS (beta = .23, P = .0862) and an increased oxidation susceptibility of VLDL + LDL (beta = .22 P = .1114) were the strongest predictors of a 3-year increase in carotid wall thickness of more than 30 variables tested in step-up least-squares regression models. A 10-variable model explained 60% of the atherosclerotic progression. In a multivariate logistic model, the risk of experiencing a fast progression increased by 80% (P = .013) per unit (microgram/L) of 7 beta-hydroxycholesterol. CONCLUSIONS: The findings of this study provide further evidence to support an association between lipid oxidation and atherogenesis in humans.

Arteriosclerosis↗
PubMedDate not supplied

Prospective study of atherosclerotic disease progression in the renal artery.

BACKGROUND: The aim of this study was to determine the incidence of and the risk factors associated with progression of renal artery disease in individuals with atherosclerotic renal artery stenosis (ARAS). METHODS AND RESULTS: Subjects with >/=1 ARAS were monitored with serial renal artery duplex scans. A total of 295 kidneys in 170 patients were monitored for a mean of 33 months. Overall, the cumulative incidence of ARAS progression was 35% at 3 years and 51% at 5 years. The 3-year cumulative incidence of renal artery disease progression stratified by baseline disease classification was 18%, 28%, and 49% for renal arteries initially classified as normal, <60% stenosis, and >/=60% stenosis, respectively (P=0.03, log-rank test). There were only 9 renal artery occlusions during the study, all of which occurred in renal arteries having >/=60% stenosis at the examination before the detection of occlusion. A stepwise Cox proportional hazards model included 4 baseline factors that were significantly associated with the risk of renal artery disease progression during follow-up: systolic blood pressure >/=160 mm Hg (relative risk [RR]=2.1; 95% CI, 1.2 to 3.5), diabetes mellitus (RR=2.0; 95% CI, 1.2 to 3.3), and high-grade (>60% stenosis or occlusion) disease in either the ipsilateral (RR=1.9; 95% CI, 1.2 to 3.0) or contralateral (RR=1.7; 95% CI, 1.0 to 2.8) renal artery. CONCLUSIONS: Although renal artery disease progression is a frequent occurrence, progression to total renal artery occlusion is not. The risk of renal artery disease progression is highest among individuals with preexisting high-grade stenosis in either renal artery, elevated systolic blood pressure, and diabetes mellitus.

Aged↗
PubMed2005

Progression of coronary artery calcium and occurrence of myocardial infarction in patients with and without diabetes mellitus.

Progression of coronary artery calcium, a marker of atherosclerosis, can be slowed with statins, and continued progression of calcium is associated with an increased risk of myocardial infarction. However, it is not known whether statins are effective in slowing calcium progression in diabetes mellitus. In a retrospective study, we examined 1153 nondiabetic and 157 diabetic subjects who underwent sequential electron beam tomography scans at a minimum 1-year interval to assess progression of coronary calcium. A yearly score increase >15% was considered evidence of true progression. The use of statins and occurrence of myocardial infarction were recorded. There was no difference in baseline calcium score between diabetic and nondiabetic patients. Diabetic patients with no coronary calcium on the baseline scans developed it more often than nondiabetic subjects (42% versus 25%; P=0.046) during follow-up. Calcium progression was 33% greater in diabetic patients than nondiabetic subjects (P<0.001) if no statin therapy was provided and 17.7% greater when statins were used (P<0.001). Among the 49 subjects who experienced a myocardial infarction, the calcium score increased on average 20% more in diabetic than nondiabetic patients (P<0.001). In logistic models, diabetes mellitus and systemic hypertension were the best predictors of calcium progression (odds ratio, 3.1 and 1.9, respectively), whereas baseline calcium score percentile and statin therapy were the best predictors of infarction. These findings support the notion that diabetes mellitus causes accelerated atherosclerosis, even in the presence of statin therapy, and provide evidence that coronary calcium monitoring is an effective method to assess treatment efficacy.

Adult↗
PubMed2005

Cilostazol prevents the progression of the symptomatic intracranial arterial stenosis: the multicenter double-blind placebo-controlled trial of cilostazol in symptomatic intracranial arterial stenosis.

BACKGROUND AND PURPOSE: Cilostazol, a phosphodiesterase inhibitor, has been reported to reduce restenosis rate after coronary angioplasty and stenting. This study was performed to investigate the effect of cilostazol on the progression of intracranial arterial stenosis (IAS). METHODS: We randomized 135 patients with acute symptomatic stenosis in the M1 segment of middle cerebral artery or the basilar artery to either cilostazol 200 mg per day or placebo for 6 months. Aspirin 100 mg per day was also given to all patients. Patients with potential embolic sources in the heart or extracranial arteries were excluded. IAS was assessed by magnetic resonance angiogram (MRA) and transcranial Doppler (TCD) at the time of recruitment and 6 months later. The primary outcome was the progression of symptomatic IAS on MRA and secondary outcomes were clinical events and progression on TCD. RESULTS: Thirty-eight patients were prematurely terminated. Dropout rates and reasons for dropouts were similar between the cilostazol and placebo groups. There was no stroke recurrence in either cilostazol or placebo group, but there was 1 death and 2 coronary events in each group. In cilostazol group, 3 (6.7%) of 45 symptomatic IAS progressed and 11 (24.4%) regressed. In placebo group, 15 (28.8%) of symptomatic IAS progressed and 8 (15.4%) regressed. Progression of symptomatic IAS in cilostazol group was significantly lower than that in placebo group (P=0.008) CONCLUSIONS: Our study suggests that symptomatic IAS is a dynamic lesion and cilostazol may prevent its progression.

Aged↗
PubMed2005

Incidence and clinical features of disease progression in adult moyamoya disease.

BACKGROUND AND PURPOSE: The progression of occlusive lesions in the major intracranial arteries was believed to be very rare in adult patients with moyamoya disease. The present study aims to clarify the incidence and clinical features of disease progression in adult moyamoya disease. METHODS: For the past 15 years, 120 adult Japanese patients were diagnosed with moyamoya disease. Of these, 63 patients were enrolled in this historical prospective cohort study on a total of 86 nonoperated hemispheres. All were followed up with a mean period of 73.6 months. MRI and magnetic resonance angiography were repeated every 6 to 12 months, and cerebral angiography was performed when disease progression was suspected on MRI and magnetic resonance angiography. RESULTS: Disease progression occurred in 15 of 86 nonoperated hemispheres (17.4% per hemisphere) or in 15 of 63 patients (23.8% per patient) during the follow-up period. Occlusive arterial lesions progressed in both anterior and posterior circulations, in both symptomatic and asymptomatic patients, and in both bilateral and unilateral types. Eight of 15 patients developed ischemic or hemorrhagic events in relation to disease progression. Multivariate analysis revealed that the odds ratio conferred by a male patient was 0.20 (95% CI, 0.04 to 0.97). CONCLUSIONS: The incidence of disease progression in adult moyamoya disease is much higher than recognized before, and female patients may be at higher risk for it than male patients. Careful follow-up would be essential to prevent additional stroke occurrence in medically treated adult patients with moyamoya disease, even if they are asymptomatic or are diagnosed as having unilateral moyamoya disease.

Adult↗
PubMed2002

Determinants of accelerated progression of arterial stiffness in normotensive subjects and in treated hypertensive subjects over a 6-year period.

BACKGROUND: Elastic artery stiffness, a result of arterial aging, is an independent indicator of cardiovascular risk. The aim of the present longitudinal study was to compare the progression of aortic stiffness over a 6-year period in treated hypertensive subjects and normotensive subjects, and to evaluate the determinants of this progression. METHODS AND RESULTS: Data for the present analysis were gathered from 483 subjects who had 2 health checkups at the Centre d'Investigations Préventives et Cliniques, the first one in 1992--1993 and the second one in 1998--1999. Carotid-femoral pulse wave velocity (PWV) was used to evaluate aortic stiffness in 187 hypertensive subjects who were under treatment at the time of the first visit and throughout the follow-up period, and in 296 subjects who were classified as normotensive during the first visit and who remained treatment-free throughout the follow-up period. In both populations, PWV progression was higher in older subjects. Annual rates of progression in PWV in treated hypertensives were significantly higher than in normotensives. Only treated hypertensives with well-controlled blood pressure levels at the time of both visits had a PWV progression similar to that of normotensives. In treated hypertensives, high heart rate and high creatinine during the first visit were associated with an accelerated progression in PWV. CONCLUSIONS: The presence of high blood pressure, high heart rate, and high serum creatinine were the major determinants of accelerated progression of aortic stiffness in treated hypertensives. This is the first longitudinal study to evaluate the determinants of arterial aging over an extended period of time.

Aging↗
PubMed2001

Effect of an aggressive lipid-lowering strategy on progression of atherosclerosis in the left main coronary artery from patients in the post coronary artery bypass graft trial.

BACKGROUND: The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of two lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol levels to a mean yearly cholesterol level from 93 to 97 mg/dL compared with a moderate reduction to a level of 132 to 136 mg/dL decreased the progression of atherosclerosis in saphenous vein grafts. Low-dose anticoagulation did not affect progression. This secondary analysis tested the hypothesis that a similar decrease in progression of atherosclerosis would also be present in native coronary arteries as measured in the left main coronary artery (LMCA). METHODS AND RESULTS: A sample of 402 patients was randomly selected from 1102 patients who had baseline and follow-up views of the LMCA suitable for analysis. Patients treated with the aggressive lipid-lowering strategy had less progression of atherosclerosis in the LMCA as measured by changes in minimum (P=0.0003) lumen diameter or the maximum percent stenosis (P=0.001), or the presence of substantial progression (P=0.008), or vascular occlusion (P=0.005) when compared with the moderate strategy. CONCLUSIONS: A strategy of aggressive lipid lowering results in significantly less atherosclerosis progression than a moderate approach in LMCAs.

Anticholesteremic Agents↗
PubMed2004

Progressive cone dystrophy associated with mutation in CNGB3.

PURPOSE: To determine the molecular basis for phenotypic variability in a three-generation consanguineous family containing a single individual with complete achromatopsia and three individuals with progressive cone dystrophy. METHODS: Four affected individuals underwent ophthalmic examination, electrophysiological assessment, color fundus photography, and psychophysical testing. Blood samples were obtained for DNA extraction and mutation screening of the cone-specific cGMP-gated (CNG) channel protein gene CNGB3 was undertaken. RESULTS: The clinical findings in one family member were consistent with a diagnosis of complete achromatopsia, with nystagmus, photophobia, and poor visual acuity from early infancy and complete color-blindness, normal fundi, and absent cone responses with normal rod responses on electroretinography (ERG). Mutation analysis revealed her to be homozygous for the common CNGB3 achromatopsia mutation, 1148delC (Thr383fs). In contrast, the three other symptomatic individuals in the family had findings consistent with progressive cone dystrophy. Their visual problems began later in childhood (ranging from 3 to 14 years of age) and there was evidence of progressive deterioration in cone function. All three had a marked tritanopic color vision defect and fundoscopy revealed bilateral macular atrophy. Electrophysiological testing of these three subjects demonstrated clear evidence of progressive deterioration of cone responses over time; rod responses were normal. All three individuals with this progressive phenotype were found to be compound heterozygotes for the 1148delC (Thr383fs) frameshift mutation and a novel Arg403Gln missense mutation in CNGB3. CONCLUSIONS: Mutations in CNGB3, which have been shown to cause achromatopsia, are now shown to be associated with autosomal recessive progressive cone dystrophy. In this study, a novel Arg403Gln mutation was identified, located in the middle of the pore domain of the cone CNG cation channel beta-subunit, which when associated with the nonsense mutation Thr383fs, resulted in progressive cone dystrophy.

Adult↗
PubMed2004

Predictive factors of the optic nerve head for development or progression of glaucomatous visual field loss.

PURPOSE: To evaluate which morphologic features of the optic disc are predictive factors for the development or progression of visual field loss in chronic open-angle glaucoma. METHODS: The prospective observational clinical study included 763 eyes of 416 white subjects with ocular hypertension and chronic open-angle glaucoma. During the follow-up time (mean, 67.4 months; median, 65.1; range, 6.2-104.5), all patients underwent repeated qualitative and morphometric evaluation of color stereo optic disc photographs and white-on-white visual field examination. Progression of glaucomatous visual field damage was defined by point-wise regression analysis for each of the 59 locations in the visual field. Outcome measures were qualitative and quantitative morphologic optic nerve head parameters. RESULTS: Development or progression of glaucomatous visual field defects was detected in 106 (13.9%) eyes. At baseline of the study, neuroretinal rim area was significantly (P < 0.002) smaller, the beta zone of parapapillary atrophy (P < 0.003, nasal sector) was significantly larger, and age was significantly higher (P < 0.003) in the progressive study group than in the nonprogressive study group. Both study groups did not vary significantly in size of the optic disc and the alpha zone of parapapillary atrophy. Cox proportional hazard regression analysis revealed that the progression of glaucomatous visual field loss depended significantly on the area of the neuroretinal rim (P < 0.001) and age (P < 0.001), but was independent of diameter of the retinal arterioles and veins. CONCLUSIONS: Morphologic predictive factors for development or progression of glaucomatous visual field defects in whites are small neuroretinal rim area and large beta zone of parapapillary atrophy. Age is an additional nonmorphologic parameter. Progression of glaucomatous optic nerve head changes is independent of the size of the optic disc and alpha-zone of parapapillary atrophy and retinal vessel diameter.

Chronic Disease↗
PubMed2005

Detecting progression of nuclear sclerosis by using human grading versus semiautomated computer grading.

PURPOSE: To assess indices of nuclear sclerosis derived from digitized images made from color (slide) photographs. METHODS: Film-based slit lamp images taken at baseline and at 5- and 10-year follow-up examinations of the Beaver Dam Eye Study cohort were digitized, and optical traces were taken along an axis through the center of the cornea and lens. Four indices of the severity of sclerosis were calculated based on the optical densities. The associations of the original Beaver Dam grades and these indices to age, vision, and change in severity of sclerosis over two subsequent visits were compared. RESULTS: At baseline photographs, the Spearman correlation between age and severity was 0.65 for the original film-based grading (n = 4518 right eyes) and varied between 0.46 and 0.71 for the measures from digitized images. Correlations of the indices to visual acuity were 0.38 for the film-based grading and ranged from 0.32 to 0.38 for the other indices. The authors assume that nuclear sclerosis does not regress and the percentage of regression is a reflection of error in grading. The percentage of regression and progression of sclerosis over 5- and 10-year intervals was determined for each index. After 5 years, 48.2% progressed and 4.9% regressed, using the Beaver Dam grades; progression occurred in 4.9% to 9.9%, and regression occurred in 4.5% to 7.0% for the other indices. After 10 years, 61.9% progressed and 3.2% regressed using the Beaver Dam grades; progression occurred in 8.0% to 19.7%, and regression occurred in 2.6% to 9.7% for the other indices. CONCLUSIONS: Semiautomated grading of the digitized images can be used to process thousands of images with little oversight by a trained grader. Indices of sclerosis that closely parallel human grading in their relationships to age and visual acuity can be easily computed. However, the indices appear to identify significantly less progression of nuclear sclerosis than does human grading. Further development to define a useful metric for identifying severity and progression of nuclear sclerosis is needed.

Adult↗
PubMed2005

Unsupervised machine learning with independent component analysis to identify areas of progression in glaucomatous visual fields.

PURPOSE: To determine whether a variational Bayesian independent component analysis mixture model (vB-ICA-mm), a form of unsupervised machine learning, can be used to identify and quantify areas of progression in standard automated perimetry fields. METHODS: In an earlier study, it was shown that a model using vB-ICA-mm can separate normal fields from fields with six different patterns of visual field loss related to glaucomatous optic neuropathy (GON) along maximally independent axes. In the present study, an independent group of 191 patient eyes (66 with ocular hypertension (OHT), 12 with suspected glaucoma by field, 61 with suspected glaucoma by disc, and 52 with glaucoma) with five or more standard visual fields under observation for a mean of 6.24 +/- 2.65 years and 8.11 +/- 2.42 visual fields were evaluated with the vB-ICA-mm. In addition, eyes with progressive GON (PGON) were identified (n = 39). Each participant had a series of fields tested, with each field entered independently and placed along the axes of the previously developed model. This allowed change in one pattern of visual field defect (along one axis) to be assessed relative to results other areas of that same field (no change along other axes). Progression was based on a slope falling outside the 5th and the 95th percentile limits of all slopes, with at least two axes not showing such a deviation in a given individual's series of fields. Fields were also scored using Advanced Glaucoma Intervention Study (AGIS) and the Early Manifest Glaucoma Treatment Trial (EMGT) criteria. RESULTS: Thirty-two of 191 eyes progressed on vB-ICA-mm by this definition. Of the 32, 22 had field loss at baseline, 7 had only GON, 3 were OHTs and 12 were from the 39 eyes (31%) with PGON. The vB-ICA-mm identified a higher percentage of progressing eyes in each diagnostic category than did AGIS or and the EMGT. CONCLUSIONS: The vB-ICA-mm can quantitatively identify progression in eyes with glaucoma by evaluating change in one or more patterns of the visual field loss while other areas or patterns remain stable. This may enable each eye to contribute to the determination of whether change is caused by true progression or by variability.

Adult↗
PubMed1997

Severe life stress as a predictor of early disease progression in HIV infection.

OBJECTIVE: Although there is evidence that stress is associated with alterations in immunity, the role of emotional factors in the onset and course of immune-based diseases such as cancer and AIDS has not been established. This prospective study was designed to test the hypothesis that stressful life events accelerate the course of HIV disease. METHOD: Ninety-three HIV-positive homosexual men who were without clinical symptoms at the time of entry into the study were studied for up to 42 months. Subjects received comprehensive medical, neurological, neuropsychological, and psychiatric assessments every 6 months, including assessment of stressful life events during the preceding 6-month interval. Several statistical approaches were used to assess the relation between stress and disease progression. RESULTS: The time of the first disease progression was analyzed with a proportional hazard survival method, which demonstrated that the more severe the life stress experienced, the greater the risk of early HIV disease progression. Specifically, for every one severe stress per 6-month study interval, the risk of early disease progression was doubled. Among a subset of 66 subjects who had been in the study for at least 24 months, logistic regression analyses showed that higher severe life stress increased the odds of developing HIV disease progression nearly fourfold. the degree of disease progression was also predicted by severe life stress when a proportional odds logistic regression model was used for analysis. CONCLUSIONS: This report presents the first evidence from a prospective research study that severe life event stress is associated with an increased rate of early HIV disease progression.

Adult↗
PubMed2004

Evaluation of possible effects of continued drug use on HIV progression among women.

Data from a prospective, multi-centred study of HIV infection in women (HIV Epidemiology Research Study [HERS]) was analysed to investigate the effect of continued injection drug use behaviours on progression to AIDS. All women enrolled in the HERS had at enrollment and at six-month intervals, a face-to-face interview which included specific injection drug use, a physical exam, and specimen collection that included T-cell subset analysis and HIV plasma RNA detection. Six hundred and thirty-nine HIV-infected women contributed 3021 person years of observation during 7.25 years of follow-up, and 299 of these women progressed to AIDS (46.8%). In multivariable analysis, there was no significantly increased risk of progression to AIDS for women reporting pre-baseline injection drug use [hazard ratio (HR)=1.07 (0.78, 1.47)] or reported injection drug use during follow-up [HR=0.89 (0.66, 1.21)] compared with never injecting. In a separate multivariable-model, comparing women who reported no injection in past six months to active injection drug users, the frequency of injection during the previous six months measured by daily injection [HR=0.97 (0.61, 1.55)] or less than daily injection [HR=0.84 (0.54, 1.33)] was not associated with progression to AIDS. Being in drug treatment was independently associated with a slower progression to AIDS [HR=0.41 (0.28, 0.59)]. Neither injection drug use, nor frequency of injection drug use was associated with progression to AIDS among HIV infected women. Initiation of antiretroviral therapy among drug users should be based on readiness for treatment rather than concern about faster progression.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Primary progressive multiple sclerosis: a distinct syndrome?

Multiple sclerosis (MS) has long been recognised to have both a relapsing-remitting and progressive course. More recently patients with progressive disease have been further sub-divided into those with a progressive course from onset (primary progressive MS) and those with progressive decline following an initially relapsing-remitting period (secondary progressive MS). Diversity in MS may not however be restricted to clinical course. There is growing evidence that the subgroups of MS also differ with respect to clinical features, epidemiology, pathogenesis, genetics and neuroimaging appearances. In this review we outline the criteria variously applied in the classification of MS patients, addressing the need for a clear nomenclature. We evaluate the proposition that primary progressive MS has a profile distinct from other MS categories, contrasting the separate differential diagnoses and examining the implications for future therapeutic trials.

Disease Progression↗
PubMed2002

Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation.

To identify the role of iron overload in the natural history of liver fibrosis, we reviewed serial hepatic biopsy specimens taken annually from patients cured of thalassemia major by bone marrow transplantation. The patients underwent transplantation between 1983 and 1989 and did not receive any chelation or antiviral therapy. Two hundred eleven patients (mean age, 8.7 +/- 4 years) were evaluated for a median follow-up of 64 months (interquartile range, 43-98 months) by a median number of 5 (interquartile range, 3-6) biopsy samples per patient. Hepatic iron concentration was stratified by tertiles (lower, 0.5-5.6 mg/g; medium, 5.7-12.7 mg/g; upper, 12.8-40.6 mg/g dry weight). Forty-six (22%) patients showed signs of liver fibrosis progression; the median time to progression was 51 months (interquartile range, 36-83 months). In a multivariate Cox proportional hazard model, the risk for fibrosis progression correlated to medium hepatic iron content (hazard rate, 1.9; 95% confidence interval [CI], 0.74-5.0), high hepatic iron content (hazard rate, 8.7; 95% CI, 3.6-21.0) and hepatitis C virus (HCV) infection (hazard rate, 3.1; 95% CI, 1.5-6.5). A striking increase in the risk for progression was found in the presence of both risk factors. None of the HCV-negative patients with hepatic iron content lower than 16 mg/g dry weight showed fibrosis progression, whereas all the HCV-positive patients with hepatic iron concentration greater than 22 mg/g dry weight had fibrosis progression in a minimum follow-up of 4 years. Thus, iron overload and HCV infection are independent risk factors for liver fibrosis progression, and their concomitant presence results in a striking increase in risk.

Adolescent↗