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Risk factors and progression of small vessel disease-related cerebral abnormalities.

A three year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate and clinical predictors of progression of small vessel disease related cerebral abnormalities including white matter changes and lacunes. White matter hyperintensity progression was found in 17.9% of individuals over the 3 year period. New lacunes occurred in 2.2% of subjects. The overall frequency of progression of small vessel disease related brain changes was 19%. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline predicted lesion progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study described that polymorphisms in the renin angiotensin system (RAS) increase the susceptibility for progression of cerebral small vessel disease. Homozygosity for the T allele of the M235T polymorphism of the angiotensinogen gene was associated with a 3.19-fold increased risk for lesion progression independently of arterial hypertension. These data suggest that drugs influencing the RAS system may allow to intervene with an unfavorable course of cerebral small vessel disease.

Aged↗

Progressive multifocal leukoencephalopathy associated with prolonged hemodialysis treatment.

The association of progressive multifocal leukoencephalopathy (PML) with prolonged hemodialysis treatment (PHT), not previously reported, was observed in a 56-year-old Japanese man who received PHT for 11 years. He suffered from recurrent bouts of fever and progressive neurological signs, such as irritability, speech disturbance, gait disturbance and dysphagia for seven months, and finally fell into a deep coma and died. Clinical signs and symptoms were highly suggestive of progressive dialysis encephalopathy. Necropsy revealed that the PML mainly involved the brainstem and cerebellar white matter. The aluminium content of the brain tissue was lower than that of controls. Possibly the virus causing PML is one of the causes of progressive dialysis encephalopathy, since clinically PML is not easily distinguished from progressive dialysis encephalopathy. It is essential to differentiate PML of viral etiology from progressive dialysis encephalopathy of unknown cause.

Brain↗

Low content of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor predicts progression of diabetic retinopathy.

AIMS/HYPOTHESIS: Retinopathy is the most common microvascular complication of diabetes. Our aim was to address the predictive value of pro-angiogenic and anti-angiogenic markers for progression of retinopathy. METHODS: Aqueous humor was collected at cataract surgery from 32 diabetic patients who had no or very mild retinopathy (ETDRS stage </=20) and 33 normoglycaemic control subjects. Content of pro-angiogenic vascular endothelial growth factor and angiogenic inhibitor pigment epithelium-derived factor were determined. ANGIOGENIC activity was quantified by measuring its effect on the migration of capillary endothelial cells. The predictive value of the initial level of these markers for progression of retinopathy was studied by following the probands for a maximum of 75 months. RESULTS: In the aqueous fluid content of vascular endothelial growth factor was increased in diabetic patients (mean values 492 versus 292 pg/ml; p=0.0052), and pigment epithelium-derived factor values were decreased (mean values 1740 versus 3680 ng/ml; p=0.0058) compared to control subjects. Of the diabetic patients ten progressed during follow-up (ETDRS stage >47B). This subgroup showed lower pigment epithelium-derived factor content when compared to non-progressors and control subjects. Migratory activity in samples of patients from the control group and in diabetic patients without progression was generally inhibitory due to pigment epithelium-derived factor. Inhibition was blocked by neutralizing antibodies to pigment epithelium-derived factor. In diabetic patients initial angiogenic activity was higher in those who later developed retinopathy (vs. controls p=0.00005; vs. no progressors p=0.0003). Both pigment epithelium-derived factor and migratory response predicted progression. CONCLUSION/INTERPRETATION: Pigment epithelium-derived factor is an important negative regulator of angiogenic activity of aqueous humor. Its content in the aqueous humor of diabetic patients strongly predicts who among them will develop progression of retinopathy.

Aged↗

Insulin resistance is a risk factor for progression to type 1 diabetes.

AIMS/HYPOTHESIS: Glucose homeostasis is determined by an interplay between insulin secretion and insulin action. In type 1 diabetes, autoimmune destruction of pancreatic beta cells leads to impaired insulin secretion. However, the contribution of impaired insulin action (insulin resistance) to the development of type 1 diabetes has received little attention. We investigated whether insulin resistance was a risk factor for progression to type 1 diabetes. METHODS: Islet-antibody-positive first-degree relatives of type 1 diabetes probands were followed for 4.0 years (median). Insulin secretion was measured as first-phase insulin response (FPIR) to intravenous glucose. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-R). We compared subjects who progressed (n=43) and subjects who did not progress (n=61) to diabetes, including 21 pairs matched for age, sex, islet antibodies and FPIR. RESULTS: Progressors had higher insulin resistance relative to insulin secretion at baseline (median HOMA-R : FPIR 0.033 vs 0.013, p<0.0001). According to Cox proportional hazards analysis, islet antibody number, FPIR, fasting plasma glucose, fasting serum insulin, HOMA-R and log(HOMA-R : FPIR) were each predictive of progression to diabetes. However, log(HOMA-R : FPIR) (hazard ratio 2.57 per doubling, p<0.001) was the only metabolic variable independently associated with progression. In the matched comparison, progressors had higher fasting glucose, fasting insulin, HOMA-R and HOMA-R : FPIR, both at baseline and during the follow-up pre-clinical phase. CONCLUSIONS/INTERPRETATION: Relatives positive for islet antibodies who progress most rapidly to diabetes have a subtle disturbance of insulin-glucose homeostasis years before the onset of symptoms, distinguished by greater insulin resistance for their level of insulin secretion. Taking steps to reduce this insulin resistance could therefore delay the development of type 1 diabetes.

Adolescent↗

Lipid-altering therapies and the progression of atherosclerotic disease.

Lipids play a key role in the progression of atherosclerosis, and lipid-lowering therapies have been studied for 30 years in coronary disease. Measurement of the progression of atherosclerosis through carotid intima-media thickness, coronary mean lumen diameter, and, mostly recently, intravascular ultrasound is generally accepted. This article reviews the role of lipid-lowering therapies in changing the rate of atherosclerosis progression in the coronary and carotid circulations. Statins are the primary therapy used to reduce atherosclerosis and cardiovascular events, including strokes and transient ischemic attacks, and have benefits in reducing events in patients undergoing carotid endarterectomy. In contrast, data for other agents, including fibrates and nicotinic acid, in reducing the progression of atherosclerosis are less extensive and not as well known. There is increasing interest in optimizing the whole lipid profile, as this might deliver extra benefits over and above statin therapy alone. Initial proof of this concept has recently come from studies that measured the progression of atherosclerosis and showed that adding nicotinic acid to statin therapy and, more directly, infusion of high-density lipoprotein-like particles reduced progression and indeed might induce regression of the disease. It is likely that the management of significant carotid stenosis will become ever more drug focused and will be customized to the lipid profile of each patient with intervention reserved only for late-stage symptomatic disease.

Carotid Artery, Common↗

1H magnetic resonance spectroscopy of normal appearing white matter in primary progressive multiple sclerosis.

Recent magnetic resonance imaging (MRI) and pathological studies have indicated that axonal loss is a major contributor to disease progression in multiple sclerosis. 1H magnetic resonance spectroscopy (MRS), through measurement of N-acetyl aspartate (NAA), a neuronal marker, provides a unique tool to investigate this. Patients with primary progressive multiple sclerosis have few lesions on conventional MRI, suggesting that changes in normal appearing white matter (NAWM), such as axonal loss, may be particularly relevant to disease progression in this group. To test this hypothesis NAWM was studied with MRS, measuring the concentration of N-acetyl derived groups (NA, the sum of NAA and N-acetyl aspartyl glutamate). Single-voxel MRS using a water-suppressed PRESS sequence was carried out in 24 patients with primary progressive multiple sclerosis and in 16 age-matched controls. Ratios of metabolite to creatine concentration (Cr) were calculated in all subjects, and absolute concentrations were measured in 18 patients and all controls. NA/Cr (median 1.40, range 0.86-1.91) was significantly lower in NAWM in patients than in controls (median 1.70, range 1.27-2.14; P = 0.006), as was the absolute concentration of NA (patients, median 6.90 mM, range 4.62-10.38 mM; controls, median 7.77 mM, range 6.60-9.71 mM; P = 0.032). There was no significant difference in the absolute concentration of creatine between the groups. This study supports the hypothesis that axonal loss occurs in NAWM in primary progressive multiple sclerosis and may well be a mechanism for disease progression in this group.

Adult↗

Risk factors for the progression of treated primary open-angle glaucoma: a multivariate life-table analysis.

BACKGROUND: Several factors have been reported as risk factors for the progression of primary open-angle glaucoma (POAG) but previous reports were not necessarily in agreement. We applied a multivariate life-table analysis to a large number of longitudinal data to determine the extent of the influence of various factors simultaneously. METHODS: Two hundred fifteen eyes of 215 POAG patients were included. The follow-up period ranged from 24 to 134 months (average 82.7 months). The visual field stage was determined separately in upper and lower hemifields according to the classification of Aulhorn (modified by Greve). The progression was defined as an irreversible increase of the stage in at least one hemifield. The follow-up data were analyzed with the Cox proportional hazard model. RESULTS: Mean intraocular pressure (IOP) in the follow-up period and the initial visual field stage significantly affected POAG progression (P<0.05). The risk of POAG progression was calculated to double as the mean IOP increased by 4 mmHg. Eyes with the initial visual field of stage 0-1 and moderately advanced stages had a greater risk of progression than other stages. CONCLUSION: To prevent the progression of POAG, the IOP should be kept as low as possible, particularly at the early and moderately advanced stages.

Age Factors↗

Progressive dysarthria: definition and clinical follow-up.

Progressive dysarthria is a common sign of several degenerative disorders of the central nervous system; it may also be a distinct nosographic entity. We identified nine patients in which progressive dysarthria remained the sole neurological sign for at least 2 years after onset. At least a year after hospital admission, the following diagnoses were made: two cases of corticobasal degeneration, one of frontotemporal dementia, one of primary progressive aphasia, one of motor neuron disease (MND)-dementia, one of ALS, and one of ALS-aphasia. In the remaining two patients progressive dysarthria remained the only neurological sign at latest examination. We conclude that in most cases progressive dysarthria is the presenting sign of an established neurodegenerative disease (generally degenerative dementia or motor neuron disease), although the possibility that progressive dysarthria is a distinct entity cannot be excluded. To clarify this issue, studies (probably multicenter) on more patients with longer clinical follow-up and pathological confirmation are required.

Amyotrophic Lateral Sclerosis↗

Diet after diagnosis and the risk of prostate cancer progression, recurrence, and death (United States).

OBJECTIVES: We examined post-diagnostic diet and risk of cancer progression in a cohort of men with prostate cancer from the Health Professionals Follow-up Study. METHODS: We observed 392 progression outcomes among 1,202 men diagnosed with incident localized/regional prostate cancer between 1986 and 1996. Men completed prospective dietary surveys before and after diagnosis and were followed through 2000. We examined post-diagnostic consumption of red meat, grains, vegetables, fruits, milk, tomatoes, tomato sauce, and fish as predictors of progression using Cox proportional hazard regression models adjusted for total energy, age, clinical factors, and pre-diagnostic diet. RESULTS: Men in the highest versus lowest quartile of post-diagnostic fish consumption had a multivariate hazard ratio (HR) of progression of 0.73 (95% CI 0.52-1.02); the comparable HR for tomato sauce was 0.56 (95% CI 0.38-0.82). We observed inverse linear relationships for fish and tomato sauce and risk of progression (HR = 0.83, p-value = 0.006 and HR = 0.80, p-value = 0.04 for a two serving/week increase of fish and tomato sauce, respectively). Milk and fresh tomato consumption were associated with small elevations in risk. CONCLUSIONS: These data suggest that diet after diagnosis may influence the clinical course of prostate cancer, and fish and tomato sauce may offer some protection against disease progression.

Adult↗

Does diffuse esophageal spasm progress to achalasia? A prospective cohort study.

Diffuse esophageal spasm (DES) and achalasia share both clinical and manometric characteristics. Some reports support the notion of progression of DES to achalasia. However, there are currently no prospective data in support of this theory. To assess prospectively the rate of manometric progression of DES to achalasia. Manometry tracings of DES patients diagnosed between 1992 and 2003 were independently reviewed blindly and agreed on by two esophageal experts. Patients with DES who agreed to undergo repeat esophageal manometry constituted the study cohort. Follow-up manometry tracings were evaluated blindly and independently by the same two interpreters to determine the rate of manometric progression to achalasia. Predictors of manometric progression were assessed. A total of 32 patients were diagnosed with DES between 1992-2003. Twelve patients (9M/3F; median age 62 years) agreed to participate and underwent second manometry (mean +/- SD follow-up of 4.8 +/- 3.4 years). Achalasia was diagnosed on follow-up manometry in one patient (8%), seven (58%) patients continued to have DES, three (25%) had normal motility, and one (8%) had nutcracker esophagus. There were no predictors of progression to achalasia based on the initial manometry parameters. A subgroup of DES patients with initial low esophageal body amplitude developed increase in esophageal simultaneous contractions on follow-up similar to the patient who evolved to achalasia. Following were the results. 1) Progression from DES to achalasia is uncommon. 2) DES patients with low esophageal body amplitude may develop increased simultaneous contractions over time. 3) DES remains an elusive diagnosis clinically and manometrically.

Aged↗

Do HIV disease progression and HAART response vary among injecting drug users in Europe?

Prior to HAART availability, there was no evidence of a geographical variation in HIV disease progression among injecting drug users (IDU) from different European regions. Nowadays, factors of importance regarding HIV disease progression in the face of HAART availability, such as HAART access, adherence, and the organization of care for IDU may differ across Europe. Therefore we studied HIV disease progression in a European study of IDU with known dates of HIV-seroconversion. Results show that with ongoing HAART availability, the risk of HIV disease progression has continued to decrease. When accounting for pre-AIDS death (in AIDS analyses) and non-natural deaths (suicide, overdose, accidents and homicide, in analyses of death) which are common among IDU, the risk of AIDS and death has decreased by as much as 65% and 75%, respectively, in 2000/2001. Results show little geographic variation in progression to AIDS. All-cause mortality was higher in IDU from Glasgow than elsewhere, while in the Valencian region (Spain) IDU were at a significantly lower risk of non-natural deaths. The timing of HAART initiation by treatment-naïve IDU likewise differed across Europe: IDU in Amsterdam, Innsbruck, and Edinburgh started at significantly lower CD4 counts than IDU in Paris, Geneva, Glasgow, and the Valencian region, but the subsequent short-term immune response was similar. In conclusion, the risk in progression to AIDS or natural death is similar across western Europe although IDU across Europe differ in other factors, such as the risk of non-natural death and the timing of HAART initiation.

Adult↗

Association between progression of aortic valve calcification and coronary calcification: assessment by electron beam tomography.

RATIONALE AND OBJECTIVES: It has been demonstrated that aortic valve calcification (AVC) shares many similarities with coronary atherosclerosis, including risk factors and pathologic characteristics. We sought to examine the relationship of AVC to coronary artery calcification (CC), to assess whether similar risk factors affect the process in a similar way. MATERIALS AND METHODS: The study included 620 asymptomatic persons (513 men and 107 women, mean age 59 years range [30-82]) who underwent two consecutive electron beam tomography (EBT) scans at least 1 year apart (mean 3.3 years). Calcification scores were obtained by summation of Agatston and volumetric scores. Stabilization of calcium was defined as no increase in score per year or positive percent change in score </=1%/year. Progression was defined as a positive percent change in score >1%/year. Of 106 with AVC, 105 (99%) had CC. Sixty-five patients had an AVC >10 on initial scan, and 50 (77%) demonstrated progression on the follow-up scan. Of 394 participants with CC >10 on initial scan, follow-up scans showed CC stabilization in 64 (16.2%) and CC progression in 330 (83.8%). Patients with AVC were significantly older than those with only CC (64.5 versus 56.5 years, P < .0001). The average age of the patient with AVC was 7 years older than the average age with CC. AVC (by volumetric score) progressed more rapidly in patients with diabetes (P = .036) and smoking (P = .042) than those without. RESULTS: We found no difference in the degree of change in the CC scores (by Agatston or volumetric methods) over time between men and women, or in any baseline cardiac risk factor (P > .05 for all measures). In 65 patients with both AVC and CC >10, there was a significant association between progression of AVC and CC (P = .047); the absolute rate of change of AVC was 24.5 +/- 43.2 %/year, and CC was 28.0 +/- 49.1 %/year. CONCLUSION: Virtually all patients with AVC had CC, potentially explaining the coronary risk associated with AVC. There is substantially parallel development between rates of progression of EBT-assessed AVC and CC.

Adult↗

Diabetes and progression of coronary calcium under the influence of statin therapy.

BACKGROUND: Coronary artery calcium (CAC) is a sensitive marker for the detection of coronary heart disease (CHD). Coronary artery calcification can be accurately quantified using electron beam tomography (EBT). We sought to evaluate the progression of atherosclerosis in asymptomatic persons with type 2 diabetes and measure the influence of statin therapy on CAC progression. METHODS: We evaluated 163 asymptomatic patients with type 2 diabetes (120 men, 43 women). Patients were physician referred and underwent 2 consecutive EBT scans at least 1 year apart. Demographic data, risk factors for CHD, and medication use were collected. Patients with symptoms or known CHD were excluded. RESULTS: The mean age was 65 +/- 10 years. The mean CAC score at baseline was 651 +/- 414. Only 9 (6%) of 163 of participants had scores of 0 at baseline. The time between scans averaged 27 +/- 15 months. Patients not treated with statins demonstrated a median annual increase in CAC progression of 20% (4%-44%), whereas statin-treated patients demonstrated increase of 10% (4%-25%) (P = .0001). Hemoglobin A 1c was weakly associated with CAC progression. CONCLUSIONS: Asymptomatic diabetic patients show a high prevalence of atherosclerosis based on high frequency of coronary calcification. Statin therapy induced a 50% reduction in the rate of CAC progression. As rapid CAC progression has been associated with coronary events, EBT may serve as a noninvasive method for following atherosclerosis and response to therapy.

Adult↗

Use of progressive glaucomatous optic disk change as the reference standard for evaluation of diagnostic tests in glaucoma.

PURPOSE: Progressive change in optic disk appearance has been suggested as the best available reference standard for glaucoma diagnosis. We evaluated the accuracy of scanning laser polarimetry (SLP) with variable corneal compensation to discriminate patients with documented progressive optic disk change from healthy subjects. DESIGN: Observational case-control study. METHODS: Glaucoma patients with documented evidence of progressive optic disk change as assessed by stereoscopic photographs were selected. Healthy control subjects had normal visual fields and normal clinical examination. All subjects underwent imaging with the GDx VCC scanning laser polarimeter. Receiver-operating characteristic (ROC) curves, sensitivities at fixed specificities, and likelihood ratios were calculated. RESULTS: Sixty-five eyes were healthy control patients. Seventy-one eyes had progressive optic disk change, of which 41 (58%) had abnormal visual field tests closest to the imaging date (perimetric glaucomatous optic neuropathy [GON]), and 30 (42%) eyes had normal visual fields (preperimetric GON). The GDx VCC parameter nerve fiber indicator performed best for discrimination between perimetric GON and normal eyes (AUC = 0.94; sensitivity = 93% for specificity > or =80%) as well as for the discrimination between preperimetric GON and normal eyes (AUC = 0.89; sensitivity = 83% for specificity > or =80%). CONCLUSION: SLP differentiated patients with documented progressive optic disk change from normal subjects and detected abnormalities in patients with confirmed diagnosis of preperimetric GON, suggesting that it may be useful for early glaucoma diagnosis. We suggest that progressive optic disk change should be used in the evaluation of diagnostic accuracy of imaging instruments for glaucoma.

Aged↗

Relation of coronary calcium progression and control of lipids according to National Cholesterol Education Program guidelines.

Tracking of coronary artery calcium (CAC) has been suggested for monitoring the effects of lipid control, but it is not known whether lipid control decreases progression of CAC. Seven hundred sixty-one subjects (mean age 64.5 +/- 7.3 years; 91% men; 69% positive for CAC) in an ongoing cohort study underwent baseline and follow-up (after 7.0 +/- 0.5 years) computed tomography for CAC. Subjects were stratified into low-risk (<2 risk factors), intermediate-risk (> or =2 risk factors but <20% risk of coronary heart disease over 10 years), or high-risk (> or =2 risk factors and >20% risk of coronary heart disease in 10 years or diabetes) groups. Lipid control was defined according to criteria of the National Cholesterol Education Program. Two-way analysis of covariance was used to examine the relation of low-density lipoprotein (LDL) cholesterol and risk group to change in CAC volume score. Control of levels of high-density lipoprotein (HDL) cholesterol and triglycerides was also examined in relation to progression of CAC. After adjustment for other risk factors and baseline CAC volume, CAC progression was similar between those with adequate and those with inadequate control of LDL cholesterol (p = 0.68) and across categories of optimal, intermediate, and higher risk LDL cholesterol (p = 0.40). However, higher levels of HDL cholesterol (> or =1.5 mmol/L [60 mg/dl]) were associated with less progression of CAC volume (151 vs 203 mm(3) in those with HDL cholesterol <1.0 mmol/L [40 mg/dl], p = 0.03). There was no relation between triglycerides and CAC progression (p = 0.54). Our findings do not support the use of CAC assessment for monitoring the control of LDL cholesterol, but greater progression of CAC may occur in those in whom HDL cholesterol is not controlled.

Aged↗

Progression of chronic kidney disease: can it be prevented or arrested?

Chronic kidney disease constitutes a highly prevalent health problem worldwide. Left untreated, it progresses inexorably to greater levels of severity at variable rates. The morbid impact of chronic kidney disease is heightened by its role as risk factor for cardiovascular disease. In the past two decades, considerable gains have been realized in retarding progression of chronic kidney disease by emphasizing blood pressure control and blockade of the renin-angiotensin system. Notwithstanding, the therapeutic goal of preventing or arresting chronic kidney disease progression remains unfulfilled. Currently attainable rates of decrease in glomerular filtration rate remain at 2 to 8 mL/min/y depending on the underlying disease. It is now believed that to achieve optimal therapeutic targets (proteinuria of <500 mg/day and decrease in glomerular filtration rate of 1 mL/min/y, the average age-related decline) we must introduce novel strategies and a multifaceted approach to treatment that interrupts multiple mechanisms of progression. To this end, and wherever relevant, new approaches to cause-specific treatment must be applied, such as targeted immunosuppression, intensive glycemic control, gene therapy, and enzyme replacement therapy. Furthermore, in all chronic kidney disease, we must interfere more effectively with the multitude of common mechanisms of progression. Established or putative, such approaches include aggressive blood pressure control; advanced renin-angiotensin system blockade; cytokine modulation and antifibrotic therapy; aldosterone blockade; endothelin blockade, nitric oxide modulation and vasopeptidase inhibition; antioxidant therapy; statin therapy; glycosaminoglycan therapy; anemia therapy; dietary restrictions; lifestyle changes; and pharmacogenomic profiling. Such a concerted, multifaceted approach to management might indeed prevent or arrest progression of chronic kidney disease, or even achieve regression of chronic kidney disease.

Anemia↗

Micromorphological and micronanalytical characterization of stagnating and progressing root caries lesions.

Root caries is the predominant disease of the tooth tissues in the elderly population and differs in progression and micromorphology from coronal dentin caries. Therefore, different clinical concepts are needed for the treatment of these progressing and arrested lesions. It was the aim of this study to investigate the three-dimensional structure and volume of stagnating and progressing root caries lesions and to determine the mineral composition of the different lesion zones to achieve a better understanding of the natural history of root caries lesion formation. Of 21 extracted human teeth of patients between 42 and 77 years of age with stagnating and progressing root caries lesions serial sections were cut and investigated with polarized light and scanning electron microscopy. From the polarized light micrographs 3D reconstructions were made to determine the volumes of the lesion zones and their relations expressed in a demineralization index (DI). With increasing size of the demineralizing zone the DI increased indicating an increase in the size of the translucent zone. The 3D reconstructions showed distinct differences between stagnating and progressing root caries lesions. In the hypermineralized translucent dentin not all dentin tubules were obliterated by intratubular dentin and within the translucent dentin scattered dead tracts were found. Electron dispersive X-ray (EDX) analysis showed that the intertubular dentin of the translucent dentin was also demineralized to a certain extent. The results indicate distinct morphological differences between progressing and stagnating root caries lesions which may have consequences for treatment strategies.

Adult↗

MMP-9 microsatellite polymorphism: association with the progression of intima-media thickening and constrictive remodeling of carotid atherosclerotic plaques.

Intima-media thickening (IMT) of carotid arteries and constrictive remodeling (CR) of atherosclerotic plaques are vascular pathologic characteristics that precede the onset of vascular events. SMC migration and proliferation are linked both to IMT and CR and are matrix metalloproteinase 9 (MMP-9) dependent. A genetic polymorphism (PM) of MMP-9, a CA (13-27) microsatellite in the promoter region, which accounts for differential expression of MMP-9, could be linked to progression of IMT and CR. Progression of IMT and CR of plaques in carotid arteries were studied in 55 consecutive patients with a 12-18 months follow-up. All patients were genotyped for MMP-9 PM. A positive linear relationship between the number of repeats and the progression of IMT (P=0.028) as well as of CR (P=0.018) was found. The analogous relationship was obtained when only the allele with longer microsatellite was considered. Carriers of more than 20 repeats in one allele showed faster both IMT growth (P=0.045) and stenosis progressions of plaques (P=0.019). In multivariate analysis, age, dyslipidemia, and MMP-9 PM were determinants of IMT progression, while MMP-9 PM was the only one of CR. In conclusion, the high number of CA repeats in MMP-9 promoter is positively correlated with faster IMT and CR progression.

Aged↗