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PubMed2006

Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis.

OBJECTIVES: This study sought to examine the association between the metabolic syndrome (MS) and the progression of aortic stenosis (AS). BACKGROUND: It has been suggested that aortic valve sclerosis and its progression to AS are caused by an atherosclerotic process. Metabolic syndrome is associated with a higher risk of vascular atherosclerosis. Thus, we hypothesized that the atherogenic features of MS could negatively influence disease progression and prognosis in patients with AS. METHODS: We retrospectively analyzed the data of 105 consecutive patients (age 69 +/- 12 years, 64 men) with at least moderate AS. Of these patients, 40 (38%) had MS identified according to the modified clinical criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III. The hemodynamic progression of AS was assessed by the measurement of the annualized decrease in valve area during the follow-up period of the study, which averaged 28 +/- 13 months. Event-free survival was defined as the absence of death or aortic valve replacement during follow-up. RESULTS: The hemodynamic progression of the stenosis was twice as fast (-0.14 +/- 0.13 cm2/year vs. -0.08 +/- 0.08 cm2/year, p = 0.008) and the three-year event-free survival was markedly lower (44 +/- 8% vs. 69 +/- 6%, p = 0.002) among patients with MS. In multivariate analysis, MS was found to be a strong independent predictor of both stenosis progression (p = 0.006) and event-free survival (odds ratio 3.85, 95% CI 1.96 to 7.58, p < 0.001). CONCLUSIONS: The present study is the first to report that MS is associated with a faster disease progression and worse outcome in patients with AS. Such findings open new avenues of research and provide a strong impetus for the elaboration of additional prospective studies focusing on this association.

Aged↗
PubMed2006

Myeloperoxidase predicts progression of carotid stenosis in states of low high-density lipoprotein cholesterol.

OBJECTIVES: We investigated the effect of myeloperoxidase (MPO) on progression of carotid stenosis in states of high and low high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels. BACKGROUND: Myeloperoxidase is pivotally involved in the pathogenesis of atherosclerosis. In vitro data suggest that MPO exerts deleterious effects via oxidative modulation of lipoproteins. METHODS: We prospectively studied 1,019 of 1,268 consecutive patients who were asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of median 7.5 months (range 6 to 9 months), categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. The MPO, HDL-C, and LDL-C levels were measured at baseline, grouped by medians, and correlated with progression of carotid atherosclerosis. RESULTS: Progression of carotid atherosclerosis was found in 100 of 1,019 patients (9.8%). Myeloperoxidase (p = 0.014) but not HDL-C (p = 0.95) or LDL-C (p = 0.30) were associated with progressive disease. However, MPO > or =310 ng/ml was significantly associated with progressive disease (adjusted odds ratio [OR] 2.57, 95% confidence interval [CI] 1.39 to 4.75) only in patients with HDL-C levels <49 mg/dl. Otherwise, in patients with higher HDL-C levels (> or =49 mg/dl), MPO > or =310 ng/ml did not predict disease progression (adjusted OR 1.42, 95% CI 0.72 to 2.78). No interaction of MPO with LDL-C was observed. CONCLUSIONS: Myeloperoxidase was associated with progression of carotid atherosclerosis in patients with HDL cholesterol levels below 49 mg/dl.

Aged↗
PubMed2006

Relation between lipoprotein(a) and fibrinogen and serial intravascular ultrasound plaque progression in left main coronary arteries.

OBJECTIVES: Patients with elevated lipoprotein(a) [Lp(a)] and fibrinogen levels have an increased risk of coronary heart disease and adverse cardiovascular events. There is evidence that coronary plaque progression is linked to a higher risk for future cardiovascular events. BACKGROUND: There are no data demonstrating a relation between Lp(a), fibrinogen, and directly measured coronary plaque progression over time. METHODS: We performed a retrospective analysis of serial intravascular ultrasound (IVUS) studies of 60 left main stems (18 +/- 9 months apart) to evaluate plaque progression in relation to Lp(a) and fibrinogen levels and association with adverse cardiovascular events. RESULTS: There was a positive correlation between Lp(a) (r = 0.58; p < 0.0001), fibrinogen (r = 0.48; p < 0.0001), and changes in plaque-plus-media area. Patients with plaque progression (n = 41) had higher Lp(a) (30 +/- 26 mg/dl vs. 14 +/- 9 mg/dl; p < 0.0012) and fibrinogen (295 +/- 88 mg/dl vs. 240 +/- 72 mg/dl; p = 0.019) levels than patients with plaque regression (n = 19). Multivariate linear regression analysis showed Log Lp(a) (regression coefficient = 9.45; p = 0.0008) but not fibrinogen to be independently associated with plaque progression. A total of 19 patients suffered from adverse cardiovascular events; they had higher Lp(a) (44 +/- 30 mg/dl vs. 16 +/- 12 mg/dl; p < 0.0001) and fibrinogen (342 +/- 73 mg/dl vs. 248 +/- 76 mg/dl; p < 0.0001) levels. Multivariate logistic regression analysis showed Log Lp(a) (odds ratio 10.20, 95% confidence interval 2.36 to 44.13; p = 0.0019) and fibrinogen (odds ratio 1.01, 95% confidence interval 1.00 to 1.03; p = 0.018) were independently associated with adverse cardiovascular events. CONCLUSIONS: Serial IVUS showed a positive correlation between Lp(a) and fibrinogen levels and plaque progression. Lp(a), but not fibrinogen, remains independently associated with plaque progression. In addition, the present data suggest a considerable incremental value of Lp(a) in predicting cardiovascular risk.

Aged↗
PubMed2006

Estimated progression rates in three United Kingdom hepatitis C cohorts differed according to method of recruitment.

OBJECTIVES: To estimate hepatitis C virus (HCV) progression rates between disease stages prior to cirrhosis, using data from liver biopsies in three observational cohorts. To demonstrate how the method of cohort recruitment can influence the estimation of HCV-progression rates. STUDY DESIGN AND SETTING: Data came from three United Kingdom observational cohorts, assembled from different referral sources. In total, 987 HCV-infected patients with an estimated (or known) date of infection and at least one histologically scored liver biopsy were eligible for inclusion in the analysis. Liver biopsy scores were used to determine the stage of HCV-related liver disease. A three-state continuous time Markov model was used to estimate covariate-specific average probabilities of progression of disease. RESULTS: After adjusting for confounders, considerably different rates of disease progression were estimated in the three cohorts. For a group of patients with the same demographics, the estimated 20-year probability of progression to cirrhosis was 12% (95% confidence interval CI = 6-22) in a hospital-based cohort, 6% (95% CI = 3-13) in a posttransfusion cohort, and 23% (95% CI = 14-37) in a cohort recruited from a tertiary referral center. CONCLUSION: Researchers using estimates of disease progression should be aware that the method of cohort recruitment has considerable influence on the progression rates that are derived.

Cohort Studies↗
PubMed2004

Multiple ways that drug abuse might influence AIDS progression: clues from a monkey model.

Whether opiates and other drugs of abuse affect AIDS progression has been an unresolved issue for two decades. Credible evidence has suggested that opiates may exacerbate, retard or have 'no effect' on progression of AIDS. Differences may exist in AIDS-progression outcomes after opiate exposures that relate to neural versus, strictly, somatic AIDS; but it is also likely that conditional variables inherent to drug dependency and the nature of the infectious agents involved allow for differing outcomes. Data from epidemiological studies, and from in vitro and basic immunological studies regarding opiate effects on AIDS progression must be interpreted in light of the conditionality of opiate effects. Caution is sounded, also, about interpreting common depressive immunological effects of opiates as indicators of influence over AIDS progression. Current evidence from the monkey model of AIDS indicates that opiates can, under certain defined conditions, retard AIDS progression. The clinical relevance of these data remains to be defined. Importantly, such data imply that opioids and the endogenous opioid system may represent therapeutic tools and targets for altering AIDS progression.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Disease progression in vascular cognitive impairment: cognitive, functional and behavioural outcomes in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) cohort study.

BACKGROUND AND PURPOSE: Empirical studies to clarify the outcomes in Vascular Cognitive Impairment (VCI) are needed. We compared cognitive, functional, and behavioural outcomes in patients with VCI to patients with no cognitive impairment (NCI), and Alzheimer's disease (AD). METHODS: Secondary analysis of the Consortium to Investigate Vascular Impairment of Cognition (CIVIC), a multi-centre Canadian memory clinic 30-month cohort study. RESULTS: Of 1347 patients, 938 were eligible for follow-up, of whom 239 (24.5%) were lost and 29 (3%) had died. Of the remaining 697 patients, 125 had NCI, 229 had VCI, and 343 had AD at baseline. Compared to people with NCI, of whom 20-40% showed progression based on cognitive and functional measures, those with VCI were more likely to progress (50-65%), as were people with AD (50-80%) (p<0.01). More people with VCI showed progression of affective symptoms (30%) than those with NCI (12%) or AD (15% p<0.01). Progression of impaired judgment (rated clinically) in VCI (15%) was similar to AD (11%) but more common than in NCI (4%, p<0.01). CONCLUSIONS: Most people with VCI show readily detectable progression by 30 months. Depressive symptoms were more common and more progressive in VCI than in Alzheimer's disease, whereas clinical evidence of progressive executive dysfunction was common in both AD and VCI.

Aged↗
PubMed2006

Genetic influence on the progression of radiographic knee osteoarthritis: a longitudinal twin study.

OBJECTIVE: Genetic influences on rates of osteoarthritis (OA) progression are unknown. Our aim was to estimate the heritability of progression of radiographic knee OA using a longitudinal twin study. METHODS: Unselected monozygotic (MZ) and dizygotic (DZ) twin pairs from the TwinsUK registry were utilized. Anteroposterior radiographs were performed on both knees at baseline and follow-up using the same protocol. Radiographic features of knee OA including osteophyte and joint space narrowing (JSN) were assessed on a four-point scale using a standard atlas. Progression of knee osteophyte and JSN was defined as the difference in the corresponding score between follow-up and baseline > or =1. Liability threshold modelling using logistic regression was utilized for heritability estimation. RESULTS: A total of 114 MZ pairs and 195 DZ pairs were studied. The average follow-up time was 7.2 years. Medial progression of osteophyte and JSN was more common than lateral progression. Prevalence of progression was generally higher in the MZs than the DZs. Similarly, concordances and tetrachoric correlations for both osteophyte and JSN were higher in the MZs than the DZs although only significant for overall and medial JSN and osteophyte. The heritability estimates were 69% [95% confidence interval (CI) 42-97%] and 80% (95% CI 50-100%) for medial osteophyte and JSN, respectively. The estimates were reduced by 7-15% after adjustment for age, body mass index (BMI), and the severity of osteophyte/JSN at baseline. CONCLUSION: Our data documented a substantial genetic influence on the progression of knee OA--as seen in the medial compartment, providing a solid basis to search for genes involved in this highly relevant clinical trait.

Aged↗
PubMed2004

Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study.

PURPOSE: To investigate the risk factors associated with visual field (VF) progression in the Advanced Glaucoma Intervention Study (AGIS) with pointwise linear regression (PLR) analysis of serial VFs. DESIGN: Prospective, multicenter, randomized clinical trial. PARTICIPANTS: Five hundred nine eyes of 401 patients from the AGIS with a baseline VF score of or=7 VF examinations, and >or=3 years of follow-up were selected. MAIN OUTCOME MEASURE: Visual field progression. METHODS: This is a cohort study of patients enrolled in a prospective randomized clinical trial (AGIS). Worsening of a test location on PLR analysis was defined as a change of threshold sensitivity of >or=1.00 decibels a year, with P<or=0.01. Visual field progression was defined as worsening of at least 2 test locations within a Glaucoma Hemifield Test cluster with PLR analysis. Multivariate logistic regression was used to determine risk factors associated with VF worsening. Intraocular pressure (IOP) fluctuation was defined as standard deviation of the IOP at all visits after the initial surgery. RESULTS: The mean (+/- standard deviation) follow-up time and baseline AGIS score were 7.4 (+/-1.7) years and 7.7 (+/-4.4), respectively. Visual field progression was detected with PLR analysis in 151 eyes (30%). Older age at the initial intervention (P = 0.0012; odds ratio [OR], 1.30; 95% confidence interval [CI], 1.11-1.50), larger IOP fluctuation (P = 0.0013; OR, 1.31; 95% CI, 1.12-1.54), increasing number of glaucoma interventions (P = 0.01; OR, 1.74; 95% CI, 1.14-2.64), and longer follow-up (P = 0.02; OR, 1.19; 95% CI, 1.03-1.38) were associated with increased odds of VF progression. When regression analyses were repeated in eyes with and without a history of cataract extraction, IOP fluctuation was the only variable to be consistently associated with VF progression. CONCLUSION: Both increasing age and greater IOP fluctuation increase the odds of VF progression by 30% (for each 5-year increment in age and 1-mmHg increase in IOP fluctuation). The higher risk conferred by IOP fluctuation was consistently observed in eyes with and without a history of cataract extraction.

Adult↗
PubMed2004

Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 1. Retinitis progression.

PURPOSE: To describe the course of cytomegalovirus (CMV) retinitis in patients with AIDS in the era of highly active antiretroviral therapy (HAART). DESIGN: Multicenter, prospective, observational study. PARTICIPANTS: Two hundred seventy-one patients with AIDS and CMV retinitis. METHODS: Follow-up every 3 months with medical history, ophthalmologic examination, laboratory testing, and fundus photographs. Photographs were evaluated for relapse of the retinitis (progression) by graders at a centralized reading center. MAIN OUTCOME MEASURE: Retinitis progression (movement of the border of a CMV lesion > or =750 microm over a > or =750-microm front or occurrence of a new lesion one-quarter disc area or more in size). RESULTS: The overall rate of retinitis progression was 0.10/person-year (PY); among those with CD4+ T-cell counts of <50/microl, it was 0.58/PY, compared to 0.02/PY among those with CD4+ T-cell counts of > or =200/microl (P<0.0001). In the multivariate analysis, significant risk factors for retinitis progression included a low CD4+ T-cell count, positive CMV load, longer time from AIDS diagnosis, and low Karnofsky score. CONCLUSIONS: Compared with the rate of retinitis progression (approximately 3.0/PY) reported in the pre-HAART era, the rate of retinitis progression was reduced among patients in the HAART era, even among those with low CD4+ T-cell counts, who might be expected to behave most like patients from the pre-HAART era. However, these events also occurred among patients with high CD4+ T-cell counts and presumed immune recovery. Continued ophthalmologic follow-up of patients with immune recovery is recommended to detect early retinitis progression.

AIDS-Related Opportunistic Infections↗
PubMed2005

Progression in intima media thickness--the significance of hormonal biomarkers of chronic stress.

OBJECTIVE: The pathophysiological pathways from stress caused by psychosocial stress to IHD has not been dealt with very extensively. The objective of this study was to analyse the association between cortisol levels and progression in intima media thickness (IMT). METHODS AND RESULTS: In 1998 and 2002, 95 participants went through a clinical investigation including ultrasound of the artery carotis communis. Progression in IMT was analysed in relation to levels of salivary cortisol in 1998 and the average levels of salivary cortisol in 1998/2002. Further, the significance of conventional coronary risk factors, testosterone and dehydro-epiandrosterone sulphate (DHEAS) were evaluated. Among the men, only age and HDL-cholesterol (negative) were significantly correlated with progression in IMT. Among the women, awakening cortisol response was significantly correlated with progression in IMT. Testosterone and DHEAS were borderline significantly associated (negatively) with progression in IMT in both genders. CONCLUSION: Progression in atherosclerosis were determined by different risk factors in women and men. The awakening cortisol response was of great importance to IMT progression in women but not in men.

Adult↗
PubMed2005

Influence of social support on progression of coronary artery disease in women.

There is strong and consistent evidence across numerous studies that social isolation or lack of social support is an independent risk factor for incident coronary heart disease. However, the impact of social isolation or lack of social support on the progression of coronary atherosclerosis in women has not been well documented. Among 292 women, aged 30-65 years, consecutively hospitalized with acute myocardial infarction or unstable angina between 1991 and 1994 enrolled in the female coronary risk study, 102 women were available to study disease progression over an average of 3.2 years. Three aspects of social support were studied: emotional support, social integration, and interpersonal social relations. Quantitative coronary angiography was performed 3-6 months following index hospitalization and repeated 3 years later. Progression of coronary atherosclerosis was evaluated as the change in mean luminal diameter from first to second measurements of 10 pre-defined coronary segments. Mixed model ANOVA was used to analyze the impact of social support on progression of coronary atherosclerosis. Significantly greater coronary atherosclerosis progression was found among women who lacked emotional support (mean coronary artery luminal diameter narrowing by 0.15 mm), with social isolation (0.14 mm), and lack of interpersonal social relations (0.13 mm), whereas women with high levels of support progressed less. It was 0.05 mm in women with high levels of emotional support, 0.07 mm for socially integrated women, and 0.04 mm in women with adequate interpersonal social relations. These associations were independent of conventional clinical and lifestyle factors such as age, smoking history, body mass index, menopausal status, and diagnosis of index event of acute myocardial infarction. The results of our study suggest that lack of emotional support, social isolation, and lack of interpersonal social relations are important risk factors for accelerated progression of coronary atherosclerosis in middle-aged women.

Adult↗
PubMed2002

Progression of visual field loss in untreated glaucoma patients and glaucoma suspects in St. Lucia, West Indies.

PURPOSE: A 1986-1987 survey found 8.8% prevalence of open-angle glaucoma in the black population of St. Lucia, West Indies. This follow-up study assessed visual field loss progression in untreated glaucoma patients and glaucoma suspects 10 years later. DESIGN: Cohort study. METHODS: Subjects were 205 glaucoma patients and suspects; 1987 data included age, sex, visual acuity, and visual fields measured by automated threshold perimetry (Humphrey C 30-2 test), and 1997 data included intraocular pressure, visual acuity, and visual fields measured by the same test. Exclusion criteria included field unreliability, field improvement due to vision improvement, nonglaucomatous vision deterioration, glaucoma treatment since 1988, and scoring of a visual field as end stage in 1987. Visual fields were scored by algorithms for the Advanced Glaucoma Intervention Study (AGIS) and Collaborative Initial Glaucoma Treatment Study (CIGTS). RESULTS: By AGIS criteria, 55% of 146 right eyes and 52% of 141 left eyes showed progression of visual field loss. In linear regressions, progression severity was unassociated with sex, intraocular pressure, or baseline visual field score, but was positively associated with age (P <.001, right; P =.002, left). The cumulative probability of reaching end stage in 10 years in at least one eye was approximately 16% by AGIS criteria. By CIGTS criteria, 73% of 146 right eyes and 72% of 141 left eyes progressed. CONCLUSIONS: These data provide a unique opportunity to study progression of untreated glaucoma. The percentage of eyes showing visual field loss progression and the percentage reaching end stage were considerably higher than in studies of visual field progression in treated eyes.

Adult↗
PubMed2000

Interocular difference in progression of glaucoma correlates with interocular differences in retrobulbar circulation.

PURPOSE: To evaluate the correlation between interocular difference in progression of glaucomatous damage and interocular differences in retrobulbar blood flow. METHODS: On the basis of a retrospective analysis of visual fields, progressive damage was identified in 20 patients with primary open-angle glaucoma. As a parameter of interocular difference in progression of visual field damage, the angle (gamma) between the regression lines of the visual field index mean defect over time per eye was calculated for each subject. The relationship between the angle gamma and interocular differences in intraocular pressure and retrobulbar color Doppler imaging parameters was analyzed by a multiple linear regression analysis in a stepwise forward approach. RESULTS: With larger interocular differences in progression of glaucomatous damage, lower mean blood flow velocities in the ophthalmic artery (partial r = -.69; P <. 0016), higher resistivity indices in the central retinal artery (partial r =.48; P <.0456), and higher peak systolic velocities in the ophthalmic artery (partial r =.52; P <.0285) were noted in the eyes with more marked progression of damage (multiple r =.71; P <. 0099). Interocular differences in progression of visual field damage were not related to intraocular pressure or extent of visual field damage. CONCLUSION: Independent of the extent of the interocular difference in glaucomatous damage and intraocular pressure, interocular difference in progression of glaucomatous visual field damage correlates with interocular difference in retrobulbar hemodynamic parameters.

Blood Circulation↗
PubMed1997

Differential expression of galectin 3 and galectin 1 in colorectal cancer progression.

BACKGROUND & AIMS: Galectins are beta-galactoside-binding proteins possibly involved in tumor progression. The aim of this study was to determine the pattern of galectin 3 and galectin 1 expression and involvement in colorectal cancer progression. METHODS: Galectin 3 expression was examined immunohistochemically in 39 samples of normal mucosae, 25 adenomas, 87 carcinomas, and 39 lymph node metastases. Galectin 1 was analyzed in 25 samples of mucosae, 15 adenomas, 25 carcinomas, and 11 metastases. Western blot analysis was also performed. RESULTS: All normal mucosae showed strong nuclear galectin 3 expression, which was down-regulated in the neoplastic progression, because only 60% of adenomas, 48% of carcinomas, and 44% of metastases were strongly positive (P < 0.0001). Cytoplasmic expression was down-regulated in adenomas (16%) but increased again in carcinomas (64%) (P < 0.0001). Galectin 1 expression was mainly detected in stromal cells and correlated with tumor progression from normal mucosae to adenomas and carcinomas (P < 0.0001). CONCLUSIONS: Galectin 3 expression is down-regulated in the initial stages of neoplastic progression, whereas a dissociated cytoplasmic expression increases in later phases of tumor progression. Galectin 1 in colorectal mucosa is predominantly a stromal product whose overexpression is associated with the neoplastic progression of colorectal cancer.

Adenoma↗
PubMed1998

The 5A/6A polymorphism in the promoter of the stromelysin-1 (MMP-3) gene predicts progression of angiographically determined coronary artery disease in men in the LOCAT gemfibrozil study. Lopid Coronary Angiography Trial.

The relationship between the 5A/6A stromelysin-1 promoter polymorphism and progression of angiographically determined coronary artery disease (CAD) has been examined in men treated for 32 months with gemfibrozil or placebo in the Lopid Coronary Angiography Trial (LOCAT). The frequency of the 5A allele was 0.40 (95%, CI, 0.36-0.43), and in the sample as a whole 12% of the men were homozygous for the 5A allele. In the placebo group, diffuse progression of disease was, on average, completely prevented in men with the genotype 5A/5A as measured by a 0.30% increase in mean average diameter of the coronary artery segments (ADS), compared with a mean 1.79% decrease in the combined group with the genotype 5A6A or 6A6A (mean +/- S.E.M., +0.007 +/- 0.020 mm vs. -0.043 +/- 0.0.08 mm, P = 0.03). A similar relationship with genotype was seen for disease progression determined by the mean minimal luminal diameter (MLD); with the 5A5A group decreasing by an average of 1.72% compared with 5.54% in the 5A/6A plus 6A/6A group (-0.029 +/- 0.034 mm vs. -0.102 +/- 0.013 mm, P = 0.06). In the gemfibrozil-treated group, the effect on disease progression associated with the 5A/6A alleles was of a similar pattern as in the placebo group, but the effect was less marked and was not statistically significant. This study confirms the previously reported beneficial effect on disease progression associated with the 5A allele and raises the possibility that patients with CAD who are homozygous for the 6A allele, and who represent 25-30% of the population, may be at particular risk of rapid progression of disease and may require particularly aggressive lipid lowering therapy to prevent disease progression.

Aged↗
PubMed2001

Magnetisation transfer ratio histogram analysis of primary progressive and other multiple sclerosis subgroups.

INTRODUCTION: Global magnetisation transfer ration (MTR) histogram analysis in the brain offers a method for evaluating pathological change both as a result of lesions and microscopic changes in normal appearing tissues. METHODS: 39 controls and 83 MS patients (46 primary progressive, 11 benign, 10 relapsing-remitting, 16 secondary progressive) were studied to explore the relationship of six conventional MTR histogram parameters with MS clinical subgroups and disability. Principal component (PC) analysis, which makes use of all the histogram data, was also used to examine the relationship between the MTR histogram and disability. RESULTS: When primary progressive patients were compared to controls, there were abnormalities of average MTR, and MTR at the 25th, 50th and 75th percentile. Disabled relapsing onset patients exhibited abnormalities in the same four parameters. Benign and nondisabled relapsing onset patients exhibited no significant abnormalities. Modest correlations were observed between disability and individual MTR parameters in relapse onset but not primary progressive patients--PC analysis revealed stronger and significant associations with disability in both subgroups. (r=0.40 for primary progressive and r=0.51 for relapsing onset). CONCLUSION: A number of MTR parameters are abnormal in primary progressive MS. MTR abnormalities are seen in disabled patients, whether of relapsing or primary progressive onset. The improved correlation with disability obtained by PC analysis suggests a useful role of this method for following clinically relevant pathological changes depicted in the MTR histogram.

Adult↗
PubMed2002

[Analysis of heart rate as a risk factor associated with the progression of chronic renal failure].

BACKGROUND: An increased heart rate is associated with an increased risk of cardiovascular and non-cardiovascular death. However, the possible relationship between heart rate and the rate of progression of renal disease has not been assessed so far. PATIENTS AND METHOD: Twenty-four-hour ambulatory blood pressure and heart rate recordings at baseline conditions were obtained in 24 patients with non-diabetic chronic renal failure and hypertension. The rate of progression of renal disease was estimated on the basis of the slope of the reciprocal of serum creatinine concentration against time. RESULTS: After a mean follow-up of 38 months, the rate of progression of renal failure was 0.004 (0.039) dL/mg/month. Progression of renal disease showed no correlation with baseline ambulatory systolic or diastolic blood pressures, and did not differ between dipper and non-dipper patients. Twenty-four-hour (r = 0.40, p = 0.05) and day-time (r = 0.534, p = 0.007) heart rates showed a relationship with the progression of renal failure. Proteinuria displayed a correlation with night-time heart rate (r = 0.405, p = 0.05) but not with the progression of renal failure. CONCLUSIONS: Baseline ambulatory heart rate, especially day-time heart rate, is associated with the decline of renal function in non-diabetic patients with chronic renal failure, suggesting that heart rate is a risk factor (or marker) for renal disease progression. Prospective controlled studies with a larger sample of patients are needed to confirm these findings and to investigate the possible mechanisms involved in this association.

Adult↗
PubMed1998

Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus.

BACKGROUND: Retinopathy commonly occurs in people with type 1 diabetes. Strict glycaemic control can decrease development and progression of retinopathy only partially. Blood pressure is also a risk factor for microvascular complications. Antihypertensive therapy, especially with inhibitors of angiotensin-converting enzyme (ACE), can slow progression of nephropathy, but the effects on retinopathy have not been established. We investigated the effect of lisinopril on retinopathy in type 1 diabetes. METHODS: As part of a 2-year randomised double-blind placebo-controlled trial, we took retinal photographs at baseline and follow-up (24 months) in patients aged 20-59 in 15 European centres. Patients were not hypertensive, and were normoalbuminuric (85%) or microalbuminuric. Retinopathy was classified from photographs on a five-level scale (none to proliferative). FINDINGS: The proportion of patients with retinopathy at baseline was 65% (117) in the placebo group and 59% (103) in the lisinopril group (p = 0.2). Patients on lisinopril had significantly lower HbA1c at baseline than those on placebo (6.9% vs 7.3 p = 0.05). Retinopathy progressed by at least one level in 21 (13.2%) of 159 patients on lisinopril and 39 (23.4%) of 166 patients on placebo (odds ratio 0.50 [95% CI 0.28-0.89], p = 0.02). This 50% reduction was the same when adjusted for centre and glycaemic control (0.55 [0.30-1.03], p = 0.06). Lisinopril also decreased progression by two or more grades (0.27 [0.07-1.00], p = 0.05), and progression to proliferative retinopathy (0.18 [0.04-0.82], p = 0.03). Progression was not associated with albuminuric status at baseline. Treatment reduced retinopathy incidence (0.69 [0.30-1.59], p = 0.4). INTERPRETATION: Lisinopril may decrease retinopathy progression in non-hypertensive patients who have type 1 diabetes with little or no nephropathy. These findings need to be confirmed before changes to clinical practice can be advocated.

Adult↗