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PubMed1996

Progression of retinopathy is related to glycaemic control even in patients with mild diabetes mellitus.

To study the progression of retinopathy in patients with mild diabetes mellitus, we examined, in a cohort study, 347 patients treated with diet alone at baseline. The patients participated in an ophthalmological screening and control programme, and diet-treated patients who were examined between January 1990 and July 1992 were included in the study and followed until October 1995. Mean follow-up was 3.4 +/- 1.1 years. The alternative classification of the Wisconsin study was used to classify retinopathy, and the mean HbA1c values for the study period, to estimate the level of glycaemic control. At baseline, 314 of the patients (90.5%) had no retinopathy, and 33 (9.5%) had mild non-proliferative diabetic retinopathy. In 296 patients there was no retinopathy progression, in 27 patients there was progression by 1 level in the retinopathy scale, and in 24 patients by 2 levels or more. In 2 patients there was progression to proliferative diabetic retinopathy. The mean HbA1c (%) was 6.5 +/- 1.3. Higher HbA1c correlated to increased progression (r = 0.16; p = 0.005), and in a multivariate analysis, HbA1c remained associated with a progression of retinopathy by 2 levels or more, with a relative risk of 1.4 per percent increase in HbA1c (95% CI 1.1-2.0; p = 0.02). Furthermore, the presence of any retinopathy at baseline was associated with progression with a relative risk of 1.7 (95% confidence interval 1.1-2.8; (p = 0.02). These data indicate that even slightly elevated levels of HbA1c might be associated with a risk of retinopathy progression.

Adult↗
PubMed2005

Prevalence of subjects with progressive bone loss at implants.

AIM: The aim of the present study was to assess the prevalence of subjects with progressive bone loss at implants with a function time of at least 5 years. MATERIAL AND METHODS: Radiographs of 1346 patients who had attended annual follow-up visits at the Brånemark Clinic, Public Dental Services, Gothenburg, Sweden were retrieved. Six hundred and sixty-two subjects fulfilled the inclusion criteria. Thus, they all had been provided with implant-supported (Brånemark System) Nobel BioCare, Gothenburg, Sweden) fixed partial or complete dentures or single-tooth replacements with a documented function time in radiographs of at least 5 years. Implants that demonstrated progressive bone loss to a level of > or =3 threads of an implant were detected. The number of subjects who exhibited one or more implants with progressive bone loss to the threshold level was recorded. RESULTS: Twenty-eight percent of 662 included subjects had one or more implants with progressive bone loss. A logistic regression analysis revealed that the individuals in this group carried a significantly larger number of implants than the subjects in whom no implants with progressive loss were detected (6 vs. 4.8). Furthermore, >30% of the subjects in the group with progressive bone loss had > or =3 identified implants and that about 33% of all such implants in this group exhibited extensive bone loss. Out of the total 3413 implants included in the study, 423 implants (12.4%) demonstrated progressive bone loss. CONCLUSION: It is suggested that the prevalence of progressive bone loss at implants assessed from subject-based data is higher than that evaluated from implant-based data.

Adult↗
PubMed2005

Disease progression: identification of high-risk groups and individuals for periodontitis.

AIMS: While the role of bacteria in the initiation of periodontitis is primary, a range of host-related factors influence the onset, clinical presentation and rate of progression of disease. The objectives of this review are (1) to present evidence for individual predictive factors associated with a patient's susceptibility to progression of periodontitis and (2) to describe the use of prognostic models aimed at identifying high-risk groups and individuals in a clinical setting. METHODS: Relevant publications in the English language were identified after Medline and PubMed database searches. Because of a paucity of longitudinal studies investigating factors including clinical, demographic, environmental, behavioural, psychosocial, genetic, systemic and microbiologic parameters to identify individuals at risk for disease progression, some association studies were also included in this review. FINDINGS AND CONCLUSIONS: Cigarette smoking is a strong predictor of progressive periodontitis, the effect of which is dose related. High levels of specific bacteria have been predictive of progressive periodontitis in some studies but not all. Diabetics with poor glycaemic control have an increased risk for progression of periodontitis. The evidence for the effect of a number of putative factors including interleukin-1 genotype, osteoporosis and psychosocial factors is inconclusive and requires further investigation in prospective longitudinal studies. Specific and sensitive diagnostic tests for the identification of individuals susceptible to disease progression are not yet a reality. While factors assessed independently may not be valuable in predicting risk of future attachment loss, the combination of factors in a multifactorial model may be useful in identifying individuals at risk for disease progression. A number of multifactorial models for risk assessment, at a subject level have been developed but require validation in prospective longitudinal studies.

Alcohol Drinking↗
PubMed2002

Insulin intervention to preserve beta cells in slowly progressive insulin-dependent (type 1) diabetes mellitus.

Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) is characterized by (1) late age of onset, with initial features of NIDDM and subsequent progression to insulin-dependent stage; (2) high predictive value of autoantibodies against glutamic acid decarboxylase (GADAb) and islet cell antibodies (ICA) for progression of beta cell failure; (3) less predominant T cell response, which may attack and eventually destroy beta-cells in affected pancreas. These findings may suggest a rationale for intervention to prevent slowly progressive beta cell dysfunction in this type of diabetes. We identified three independent risk factors for progression of beta cell failure in SPIDDM: (1) sulfonylurea treatment; (2) ICA-positive periods; and (3) initial body weight. We hypothesized that removal of the risk factors for further progression of beta cell dysfunction will have beneficial effects on intervention strategy in treating SPIDDM. In our pilot study, we used a small dose of insulin instead of sulfonylurea in the early stage of treatment of patients with SPIDDM. Insulin-treated SPIDDM patients had a sustained C peptide response (CPR), while most of sulfonylurea-treated patients progressed to an insulin-dependent state. We organized a randomized multicenter clinical trial to study early treatment to prevent the progression of beta cell dysfunction in SPIDDM (the Tokyo Study). It was demonstrated that early intervention with insulin therapy is an effective treatment modality in the early stage of SPIDDM patients who had preserved beta cell function at entry (integrated value of serum C peptide values at 0, 30, 60, 90, and 120 minutes; Sigma CPR >or= 10 ng/mL) and high GADAb (>10 U/mL). Preventive insulin treatment was ineffective in the patients who had diminished insulin reserve at entry (Sigma CPR < 10 ng/mL). Insulin intervention to preserve beta cell dysfunction in SPIDDM is effective and safe in patients with preserved beta cell function and high GADAb titers at the initiation of insulin.

Age of Onset↗
PubMed2001

Selective inactivation of p53 facilitates mouse epithelial tumor progression without chromosomal instability.

We examined the selective pressure for, and the impact of, p53 inactivation during epithelial tumor evolution in a transgenic brain tumor model. In TgT(121) mice, cell-specific inactivation of the pRb pathway in brain choroid plexus epithelium initiates tumorigenesis and induces p53-dependent apoptosis. We previously showed that p53 deficiency accelerates tumor growth due to diminished apoptosis. Here we show that in a p53(+/-) background, slow-growing dysplastic tissue undergoes clonal progression to solid angiogenic tumors in all animals. p53 is inactivated in all progressed tumors, with loss of the wild-type allele occurring in 90% of tumors. Moreover, similar progression occurs in 38% of TgT(121)p53(+/+) mice, also with loss of at least one p53 allele and inactivation of p53. Thus, the selective pressure for p53 inactivation, likely based on its apoptotic function, is high. Yet, in all cases, p53 inactivation correlates with progression beyond apoptosis reduction, from dysplasia to solid vascularized tumors. Hence, p53 suppresses tumor progression in this tissue by multiple mechanisms. Previous studies of fibroblasts and hematopoietic cells show that p53 deficiency can be associated with chromosomal instability, a mechanism that may drive tumor progression. To determine whether genomic gains or losses are present in tumors that progress in the absence of p53, we performed comparative genomic hybridization analysis. Surprisingly, the only detectable chromosomal imbalance was partial or complete loss of chromosome 11, which harbors the p53 gene and is thus the selected event. Flow cytometry confirmed that the majority of tumor cells were diploid. These studies indicate that loss of p53 function is frequent under natural selective pressures and furthermore that p53 loss can facilitate epithelial tumor progression by a mechanism in addition to apoptosis reduction and distinct from chromosomal instability.

Animals↗
PubMed2005

Central corneal thickness and progression of the visual field and optic disc in glaucoma.

AIMS: To determine whether central corneal thickness (CCT) is a significant predictor of visual field and optic disc progression in open angle glaucoma. METHODS: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 months. Progression was determined using a trend based approach called evidence of change (EOC) analysis in which sectoral ordinal scores based on the significance of regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using the event based glaucoma change probability (GCP) analysis using both total and pattern deviation. RESULTS: The sample contained 101 eyes of 54 patients (mean (SD) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseline visual fields and lower mean IOP in the follow up. In the longitudinal analysis CCT was not correlated with the EOC scores for visual field or optic disc change. In the GCP analyses, there was a tendency for groups classified as progressing to have lower CCT compared to non-progressing groups. In a multivariate analyses accounting for IOP, the opposite was found, whereby higher CCT was associated with visual field progression. None of the independent factors were predictive of optic disc progression. CONCLUSIONS: In this cohort of patients with established glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression.

Adult↗
PubMed2005

Progression of cerebral white matter lesions in Alzheimer's disease: a new window for therapy?

BACKGROUND: White matter lesions (WML) are a risk factor for Alzheimer's disease. Progression of WML is associated with vascular factors and cognitive decline in population based studies but the course of WML is unknown in Alzheimer's disease. OBJECTIVE: To investigate the prevalence and risk factors for progression of WML in Alzheimer's disease. SUBJECTS: 38 patients with Alzheimer's disease for whom blood pressure measurements and sequential brain MRIs were available. METHODS: The proportion of patients with progression of WML was calculated, stratified on baseline absence or presence of WML by analysis of variance. Odds ratios (OR) were calculated by age and sex adjusted logistic regression to quantify the relation between blood pressure and progression of WML. RESULTS: About 25% of the patients showed progression of WML. Patients with WML at baseline had significantly more progression than those without WML at baseline (adjusted mean difference = 1.2; 95% confidence interval (CI), 0.6 to 1.8). Diastolic blood pressure (DBP) was particularly related to progression of WML (OR = 5.9 (95% CI, 1.0 to 37.6) per 10 mm Hg DBP, p = 0.05). CONCLUSIONS: Alzheimer's disease patients with WML at baseline are at risk for rapid progression of WML. WML may offer a potential treatment target in this disease to ameliorate the rate of cognitive decline.

Aged↗
PubMed2002

Factors influencing HIV progression in a seroconverter cohort in Madrid from 1985 to 1999.

OBJECTIVE: To study HIV progression from seroconversion over a 15 year period and measure the population effectiveness of highly active antiretroviral therapy (HAART). METHODS: A cohort study of people with well documented dates of seroconversion. Cumulative risk of AIDS and death were calculated by extended Kaplan-Meier allowing for late entry. Cox proportional hazards models were used to study variables associated with HIV progression. To assess the impact of HAART, calendar time was divided in three periods; before 1992, 1992-6, and 1997-9. RESULTS: From January 1985 to May 2000, 226 seroconverters were identified. The median seroconversion interval was 11 months, median seroconversion date was March 1993. 202 (89%) were men, 76% of whom were homo/bisexual. A 66% reduction in progression to AIDS was observed in 1997-9 compared to 1992-96 (HR 0.34 95% CI: 0.16 to 0.70). People with primary education appeared to have faster progression to AIDS compared to those with university studies (HR 2.69 95%CI: 1.17 to 6.16). An 82% reduction in mortality from HIV seroconversion was observed in 1997-9 (HR 0.18 95% CI: 0.05 to 0.68) compared to 1992-6. Progression to death for people with primary education was twice as fast as for those with university education (p 0.0007). People without confirmation of an HIV negative test had faster progression (HR 4.47 95% CI: 1.18 to 16.92). CONCLUSIONS: The reduction in progression to AIDS and death from seroconversion from 1992-6 to 1997-9 in Madrid is likely to be attributable to HAART. HIV progression was faster in subjects with primary education; better educational level may be associated with better adherence to medication.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Calcium begets calcium: progression of coronary artery calcification in asymptomatic subjects.

PURPOSE: To test the hypothesis that the rate of coronary artery calcium progression is sex specific, namely, that it is greater in men than in women, and that it is age related, particularly in women. MATERIALS AND METHODS: This was a retrospective study of the progression of coronary artery calcium in 217 consecutive asymptomatic subjects who underwent at least two electron-beam computed tomographic studies of the heart. Calcium in the distribution of the epicardial arteries was quantified by using both the conventional coronary artery calcium score (CCS) and the calcium volume score (CVS). Linear regression models were used to judge the joint influence of various risk factors, including sex and age, on rates of coronary artery calcium progression. RESULTS: This study included 103 women and 114 men. The mean interval between the subjects' first and last studies was 25 months +/- 11 (SD). Regression analyses clearly demonstrated that the amount of coronary artery calcium present at the initial study was the most important determinant of calcium progression. This was true when coronary artery calcium was quantified by using the conventional CCS (P <.001) or CVS (P <.001). Neither sex nor age was a significant predictor of coronary artery calcium progression. Among traditional risk factors, only hypertension (P =.02) and diabetes (P =.01) were significant independent factors for calcium progression. CONCLUSION: In asymptomatic subjects, the initial CCS and CVS were the most important factors that affected rate of coronary artery calcium progression. Neither age nor sex was as important as these factors in determination of coronary artery calcium progression.

Adult↗
PubMedDate not supplied

Hypoalbuminemia as a risk factor for progressive left-ventricular hypertrophy in hemodialysis patients.

BACKGROUND: This study was performed to evaluate the changes in left-ventricular (LV) mass in the patients starting maintenance hemodialysis and the risk factors for the progression of LVH. METHODS: From June 1994 to February 1997, baseline echocardiography was obtained within six months after the initiation of hemodialysis in 111 patients with end-stage renal disease. Of the patients who had LVH on baseline echocardiography, 32 patients underwent follow-up echocardiography after 15 months (range: 9-24 months). LVH was defined as a left-ventricular mass index (LVMI) greater than 131 g/m(2) in males and 100 g/m(2) in females. Progressive LVH was defined as a follow-up LVMI greater than 105% of the baseline value. Hemoglobin, blood urea nitrogen, creatinine, cholesterol, albumin, prealbumin, parathyroid hormone, Kt/V, nPCR, fibrinogen, homocysteine and ACE gene polymorphism were also measured. RESULTS: LVH was detected in 91 of 111 (82%) ESRD patients starting maintenance hemodialysis. Of the 32 patients in whom follow-up echocardiography was performed, progressive LVH occurred in 19 patients (M:F = 12:7). Progressive LVH was associated with lower diastolic blood pressure (81 +/- 11 vs. 90 +/- 12 mm Hg, p = 0.036) and lower serum albumin (3.5 +/- 0.4 vs. 3.9 +/- 0.4 g/dl, p = 0. 009). Serum albumin was negatively (r = -0.420, p = 0.017) correlated to Delta LVMI (follow-up LVMI minus baseline LVMI). Hypoalbuminemia was an independent risk factor for progressive LVH in multiple logistic regression analysis (R.R. = 1.29, p = 0.046). The association of progressive LVH with age, gender, diabetes mellitus, smoking history or other laboratory parameters was not significant. CONCLUSION: LVH was highly prevalent in the patients starting maintenance hemodialysis for ESRD. In the follow-up echocardiography, LVH progressed in a substantial portion of the patients, and hypoalbuminemia was a risk factor for progressive LVH.

Adult↗
PubMed1998

Plaque and gingival status as indicators for caries progression on approximal surfaces.

This study aimed to (1) record the plaque and gingival status on sound and carious approximal surfaces and (2) investigate whether the two parameters could predict approximal lesion progression. For this purpose two samples were selected among 18- to 25-year-old patients at the Dental Faculty in Copenhagen. Sample 1 consisted of 45 patients, each having an approximal posterior surface requiring operative treatment and a contralateral approximal space, where both surfaces were radiographically sound. Sample 2 consisted of 25 patients, each having a posterior approximal tooth surface with an enamel/initial dentinal lesion recorded on a bitewing. Plaque and gingival status were classified using 4-point ranked scales. The recordings were performed once on each participant in sample 1. The recordings in sample 2 were repeated 5 times during a 15-month period. In order to assess lesion progression in sample 2, two serial intraoral examinations were performed, i.e. at the beginning and end of the study. Less than 10% of the sound and carious surfaces were recorded as plaque-free, while about 40% had a thick or heavy plaque accumulation. No significant difference was observed between plaque scores on sound and carious surfaces (p = 0.5), in contrast to findings representing the gingival status (p < 0.001). Tooth surfaces requiring operative treatment were associated with bleeding of the gingiva after probing. In sample 2, 3 of the 25 participants did not finish the study. On the remaining participants caries progression was observed in 9 cases (41%), while no progression was observed in 13 cases. Analyses showed that there were no significant differences between plaque scores in cases with caries progression, as compared with no caries progression (p > 0.05). Similar analyses concerning gingival status showed that bleeding of the gingiva was related to cases with progressing caries. Analyses also disclosed no direct association between plaque and gingival status (Spearman correlation coefficient 0.39). Thus, the occurrence of plaque does not have the same predictive power as bleeding after probing in decision-making as to whether or not a lesion progresses.

Adolescent↗
PubMedDate not supplied

Progression of and risk factors for dental erosion and wedge-shaped defects over a 6-year period.

It has been shown that dental erosion is not a very rare condition. Careful observation and clinical experience led us to hypothesize a progression of these lesions with time despite dietary counselling and oral hygiene instruction. The purpose of this study was to determine the progression rate and risk factors of dental erosion and wedge-shaped defects over a 6-year period. In the year 1987, 204 randomly selected persons living in Bern from two age groups (26-30 and 46-50 years) were examined for frequency and severity of dental erosion and wedge-shaped defects. In the year 1993, 55 persons could be re-examined by the same dentist using the same indices. Further, detailed case histories of the patients were recorded and the flow rate and buffering capacity of the saliva were determined. The results indicated a distinct progression of erosion on facial and occlusal surfaces and wedge-shaped defects over the 6-year period. The increase in the defects was more marked in the older age group. Surprisingly, nutritional habits did not change despite thorough informative discussion about erosive foodstuff with every patient during the first session. Multiple linear regression analysis revealed consumption of nutritional acids and age as significant risk factors explaining 28% of the variability of the progression of erosions. The significant factors for the progression of wedge-shaped defects were identified to be frequency of tooth brushing and age, explaining 21% of the variability of the progression of wedge-shaped defects. In summary, there was a definite statistically significant progression of non-carious dental hard tissue defects in our sample. This progression was correlated with age (erosion and wedge-shaped defects), consumption of dietary acids (erosion) and frequency of toothbrushing (wedge-shaped defects).

Adult↗
PubMed1998

Clinical course of newly developed or progressive patchy chorioretinal atrophy in pathological myopia.

Regional chorioretinal atrophy in the posterior fundus (patchy chorioretinal atrophy) in pathological myopia impairs vision severely when it covers the macula. The aim of this study was to assess the course of development and progression of patchy chorioretinal atrophy in pathological myopia. The location and progression of patchy chorioretinal atrophy that was either newly developed or had progressed during the follow-up period (mean 5.25 years) were analyzed. A total of 41 lesions of patchy atrophy were newly developed in 30 eyes of 25 patients. These lesions were more likely to occur in marginal regions of a posterior staphyloma but frequency per unit area was highest in the macula. There were 138 lesions of patchy chorioretinal atrophy that progressed in 75 eyes of 53 patients. Sixty percent of the lesions of patchy chorioretinal atrophy in marginal regions of a posterior staphyloma spread toward the center. Seventy percent of the lesions of patchy chorioretinal atrophy in the macula spread in all directions. Fluorescein angiography of newly developed patchy chorioretinal atrophy showed hyperfluorescence in 50% and hypofluorescence in 27%. Fluorescein angiography of progressive lesions of patchy chorioretinal atrophy showed hypofluorescence in 69%. Fluorescein angiography of some progressive areas of patchy chorioretinal atrophy, which showed a change from hyperfluorescence to hypofluorescence within several years, suggested that damage to the retinal pigment epithelium preceded the progression of the patchy chorioretinal atrophy. In conclusion, the patchy chorioretinal atrophy is most likely to occur in the macula and to enlarge in all directions. And it is suggested that the patchy chorioretinal atrophy which shows hyperfluorescence by fluorescein angiography should be kept under observation because our data suggest that this finding indicates progression in the future.

Adult↗
PubMedDate not supplied

Urinary indoxyl sulfate is a clinical factor that affects the progression of renal failure.

We recently demonstrated that indoxyl sulfate is a stimulating factor for the progression of chronic renal failure (CRF). In this study we determined whether the urine or serum levels of indoxyl sulfate are related to the progression rate of CRF in undialyzed uremic patients. Fifty-five CRF patients with a serum creatinine of >2 mg/dl who had not been treated with an oral sorbent (AST-120) were randomly enrolled in the study. We measured the serum and urine levels of indoxyl sulfate, and estimated the recent progression rate of CRF as the slope of the reciprocal serum creatinine versus time (1/S-Cr-time) plot. The mean urinary amount of indoxyl sulfate in the patients was 60 mg/day. Those with indoxyl sulfate urine levels of >60 mg/day had a significantly faster progression rate of CRF than those with <60 mg/day. Especially, those patients with indoxyl sulfate urine levels of >90 mg/day had the highest CRF progression rate and those with indoxyl sulfate urine levels of <30 mg/day had the slowest CRF progression rate. Urinary indoxyl sulfate had a significantly negative correlation with the slope of the 1/S-Cr-time plot. However, the serum level of indoxyl sulfate or the ratio of serum indoxyl sulfate to creatinine was not significantly correlated with the slope of the 1/S-Cr-time plot. In conclusion, high urine levels of indoxyl sulfate are related with a rapid progression of CRF in undialyzed uremic patients. Thus, urinary indoxyl sulfate is one of the clinical factors that affect CRF progression.

Adult↗
PubMed2003

Diabetes and progression of carotid atherosclerosis: the insulin resistance atherosclerosis study.

OBJECTIVE: We sought to determine the rate of progression of carotid atherosclerosis in persons with normal glucose tolerance, impaired glucose tolerance, and undiagnosed and diagnosed type 2 diabetes. METHODS AND RESULTS: The Insulin Resistance Atherosclerosis Study (IRAS) is an observational cohort study in which 1192 men and women were examined at a 5-year interval. Participants of 3 ethnic groups (non-Hispanic white, African American, and Hispanic) were selected from the general population to represent a range of glucose tolerance. Baseline and follow-up ultrasound studies were obtained to estimate progression of common carotid artery (CCA) and internal carotid artery (ICA) intimal-medial thickness (IMT). Baseline glucose tolerance status was defined by an oral glucose tolerance test and World Health Organization criteria. In persons with normal glucose tolerance, progression of CCA IMT was 3.8 microm/y, and ICA IMT, 17.7 microm/y. In both CCA and ICA, progression of IMT, unadjusted for cardiovascular disease (CVD) risk factors, was approximately twice the rate in persons with diabetes than in those with normal or impaired glucose tolerance. Adjustment for CVD risk factors attenuated these differences somewhat in both sites of the carotid artery. Persons with undiagnosed diabetes had a greater ICA IMT progression rate than did persons with diagnosed diabetes (33.9 microm/y vs 26.6 microm/y, P=NS). Progression rates did not differ between persons with normal and impaired glucose tolerance. CONCLUSIONS: Progression of carotid atherosclerosis is accelerated in persons with diabetes. Progression of ICA IMT is most pronounced in persons with undiagnosed diabetes. Early identification of diabetes and CVD risk factor control might reduce its atherosclerotic complications.

Anthropometry↗
PubMed1999

Heart rate variability and progression of coronary atherosclerosis.

Low heart rate (HR) variability is associated with increased risk of cardiovascular morbidity and mortality, but the causes and mechanisms of this association are not well known. This prospective study was designed to test the hypothesis that reduced HR variability is related to progression of coronary atherosclerosis. Average HR and HR variability were analyzed in 12-hour ambulatory ECG recordings from 265 qualified patients participating in a multicenter study to evaluate the angiographic progression of coronary artery disease in patients with prior coronary artery bypass surgery and low high-density lipoprotein cholesterol concentrations (<1.1 mmol/L). Participants were randomized to receive a placebo or gemfibrozil therapy. The progression of coronary atherosclerosis was estimated by quantitative, computer-assisted analysis of coronary artery stenoses from the baseline angiograms and from repeated angiograms performed an average of 32 months later. The progression of focal coronary atherosclerosis of the patients randomized to placebo therapy was more marked in the tertile with the lowest standard deviation of all normal to normal R-R intervals (SDNN, 74+/-13 ms; mean decrease in the per-patient minimum luminal diameter -0.17 mm; 95% confidence interval [CI], -0.23 to -0.12 mm) than in the middle tertile (SDNN, 107+/-7 ms; mean decrease -0.05 mm; 95% CI, -0.08 to -0.01 mm) or highest tertile (SDNN, 145+/-25 ms; mean change 0.01 mm; 95% CI, -0. 04 to 0.02 mm) (P<0.001 between the tertiles). This association was abolished by gemfibrozil. SDNN was lower (P<0.001) and minimum HR was faster (P<0.01) in the patients with marked progression than in those with regression of focal coronary atherosclerosis. In multiple regression analysis including HR variability, minimum HR, demographic and clinical variables, smoking, blood pressure, glucose, lipid measurements and lipid-modifying therapy, progression of focal coronary atherosclerosis was independently predicted by the SDNN (beta=0.24; P=0.0001). Low HR variability analyzed from ambulatory ECG predicts rapid progression of coronary artery disease. HR variability provided information on progression of focal coronary atherosclerosis beyond that obtained by traditional risk markers of atherosclerosis.

Analysis of Variance↗
PubMed2001

Natural history and topographic pattern of progression of coronary calcification in symptomatic patients: An electron-beam CT study.

Electron-beam CT may assess the progression of coronary atherosclerosis by visualizing changes in calcification. The present investigation analyzes (1) the rate of progression of calcification in symptomatic patients, (2) the topographic pattern, and (3) the influence of baseline plaque burden and risk factors. Progression of calcification during a mean (median) interval of 18 (15) months was measured in 102 symptomatic outpatients (aged 59+/-9 years, 80% male) with calcification. In 4 patient groups with a baseline total score (Agatston criteria) of 1 to 30, >30 to 100, >100 to 400, and >400, the median was 3.1, 26.1, 58.9, and 109.7, respectively, for absolute annual progression of the score (P<0.05) and 57%, 49%, 32%, and 15%, respectively, for relative progression (P<0.05). On the coronary segmental level, changes were largely restricted to typical predilection sites of coronary atherosclerosis. The presence of angiographically defined coronary narrowing influenced absolute, but not relative, progression. Of the risk factors, only low density lipoprotein cholesterol levels showed a trend, although not significant, for predicting progression. These data indicate that baseline plaque burden determines the rate of progression of calcification. This appears to be a coronary systemic process, reflecting the natural history of coronary atherosclerosis.

Aged↗
PubMed2002

Associations of extracranial carotid atherosclerosis progression with coronary status and risk factors in patients with and without coronary artery disease.

BACKGROUND: Intimal medial thickness of the extracranial carotid arteries (IMT) is related to coronary artery disease (CAD) and CAD risk factors. Few studies have explored the association of risk factors with progression of IMT, and none have evaluated their associations with IMT progression specifically in patients with and without CAD. METHODS AND RESULTS: We used coronary angiography to identify 280 patients equally divided between men and women and those with either > or =50% coronary artery stenosis or no CAD. Risk factors were measured at baseline and IMT was measured at baseline and yearly for 3 years in 241 of these individuals. Baseline risk factors and CAD status were related to IMT progression. IMT of patients with CAD progressed 3 times faster than that of patients with no CAD (mean+/-SEM, 33.7+/-7.4 versus 8.9+/-7.1 microm/year; P=0.02), and CAD status and high-density lipoprotein (HDL) cholesterol were independently associated with IMT progression. Male sex, increased waist to hip ratio, cigarette smoking, increased triglycerides, and decreased HDL cholesterol were associated with increased progression in CAD patients. CONCLUSIONS: Patients with CAD have more rapid progression of IMT than CAD-free controls, and risk factors are related to progression in them.

Carotid Artery Diseases↗