Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience.

AIMS/HYPOTHESIS: Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes. METHODS: A fenofibrate-associated creatinine increase (FACI) was defined as an increase in serum creatinine of at least 20% from baseline to month 4 in participants assigned to fenofibrate. Baseline patient characteristics, and baseline and 4-month drug, clinical, laboratory characteristics and study outcomes were examined by FACI status. RESULTS: Of the sample, 48% of those randomised to receive fenofibrate had at least a 20% increase in serum creatinine within 4 months. In multivariable analysis, participants who were older, male, used an ACE inhibitor at baseline, used a thiazolidinedione (TZD) at 4 months post-randomisation, had baseline CVD, and had lower baseline serum creatinine and LDL-cholesterol levels were all more likely to meet the criteria for FACI. Participants in the FACI group were also more likely to have a decrease in their serum triacylglycerol level from baseline to 4 months. No differences in study outcomes were seen by FACI criteria. CONCLUSIONS/INTERPRETATION: Several characteristics predict a rapid rise in serum creatinine upon starting fenofibrate. Participants who met the criteria for FACI also had a greater change in triacylglycerol levels. In the setting of careful renal function surveillance and reduction of fenofibrate dose as indicated, no increase in renal disease or cardiovascular outcome was seen in those individuals demonstrating FACI. TRIAL REGISTRATION: ClincalTrials.gov: NCT00000620. FUNDING: The ACCORD Trial was supported by grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035 and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; by General Clinical Research Centers and by the Clinical and Translational Science Awards. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis US and Takeda Pharmaceuticals provided study medications, equipment or supplies.

Patient assessment of lower urinary tract symptoms using the international prostate symptom score following low-dose-rate prostate brachytherapy.

PURPOSE: To correlate changes in urinary patient-reported outcomes including the International Prostate Symptom Score (IPSS), acute urinary retention and urethral stricture with urethral dose in those treated with low dose rate (LDR) prostate brachytherapy. MATERIALS AND METHODS: Patients treated with prostate LDR between 2012 and 2019 (n=117) completed IPSS urinary symptom assessments prior to treatment and at each follow-up. CT simulation was obtained with urinary catheter 1-month post-implant for dosimetric analysis. 113 patients with pre- and ≥1 post-LDR IPSS score available were analyzed. Urethral dosimetric parameters including U75, U100, U125, U150 and U200 were abstracted from post-implant dosimetry and assessed for association with urinary toxicity using bivariate logistic regression and Spearman correlation. Outcomes included clinically significant change (CSC, defined as 4 or more points or 25% rise above baseline) in IPSS score at 6 and 12 months, acute urinary retention (AUR), and urethral stricture (US). RESULTS: 89 (79%) patients were treated with LDR monotherapy (145 Gy) and 24 (21%) with LDR boost (110 Gy) with external beam radiation therapy. Twenty (18%) had baseline IPSS ≥15. Median IPSS scores were: baseline 6 (3-12; n=113), 1-month 17 (10-25; n=110), 6 months 12 (7-18; n=77), 1 year 8 (5-14; n=52). CSC-6 was observed in 59 (77%), CSC-12 in 26 (50%), AUR in 12 (11%), and US in 4 (4%). No association was identified between urethral dose parameters and CSC-6, CSC-12, AUR, or US. No correlation between urethral dose and IPSS at 6- and 12-months was identified. The IPSS ≥15 group exhibited lower rates of CSC-12 (13% v. 57%, p=0.05) but not CSC-6 (55% v. 80%, p=0.12). CONCLUSIONS: We did not find a relationship between urethral dose and IPSS elevation, AUR or US. We did identify a significantly lower change in IPSS at 12 months for those with baseline IPSS ≥15 compared to those with low baseline scores.

Predicting lower-extremity injuries among habitual runners.

This prospective study of 583 habitual runners used baseline information to examine the relationship of several suspected risk factors to the occurrence of running-related injuries of the lower extremities that were severe enough to affect running habits, cause a visit to a health professional, or require use of medication. During the 12-month follow-up period, 252 men (52%) and 48 women (49%) reported at least one such injury. The multiple logistic regression results identified that running 64.0 km (40 miles) or more per week was the most important predictor of injury for men during the follow-up period (odds ratio = 2.9). Risk also was associated with having had a previous injury in the past year (odds ratio = 2.7) and with having been a runner for less than 3 years (odds ratio = 2.2). These results suggest that the incidence of lower-extremity injuries is high for habitual runners, and that for those new to running or those who have been previously injured, reducing weekly distance is a reasonable preventive behavior.

Isradipine in prediabetic hypertensive subjects.

OBJECTIVE: Investigators from the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) previously reported that the isradipine group had a higher incidence of cardiovascular disease (CVD) events than the diuretic group. The ultimate objective of the analyses presented here was to assess how indices of glycemia (specifically, serum glucose, serum insulin, and HbA1c) might have influenced the effects of the two agents on blood pressure control and CVD events. RESEARCH DESIGN AND METHODS: Inclusion criteria included men and women > or = 40 years of age with ultrasonographically confirmed carotid atherosclerosis and a diastolic blood pressure of > 90 mmHg. Although insulin-dependent diabetic patients were excluded, the three glycemia indices had wide enough ranges to include patients who may be classified as prediabetic. A total of 883 patients were randomized either to the dihydropyridine calcium antagonist (CA) isradipine (2.5-5 mg twice a day) or to the diuretic hydrochlorothiazide (12.5-25 mg twice a day) and followed in double-blind fashion for 3 years. RESULTS: Both treatment groups had achieved comparable control of diastolic blood pressure, and there were no statistically significant differences in any of the glycemia indices, either at baseline or during follow-up. However, the excess isradipine events were noted to be clustered among those patients with elevated baseline levels of HbA1c who also experienced greater blood pressure reductions during follow-up. CONCLUSIONS: The increased cardiovascular risk associated with dihydropyridine CAs in prediabetic patients may be an explanation for the overall CA debate.

Relationship of intraabdominal fat as measured by magnetic resonance imaging to postprandial lipemia in middle-aged subjects.

Adipose distribution has been associated with coronary artery disease and its risk factors. We previously described an association between postprandial triglyceride response (pptg response) to a standard high-fat meal and extracranial carotid atherosclerosis. This study was designed to evaluate the association between intraabdominal fat and pptg response. Twenty-nine subjects were recalled for determination of intraabdominal fat by magnetic resonance imaging (MRI). Fat was quantified according to an inversion recovery protocol previously validated and the cross-sectional area of intraabdominal fat at the umbilicus was analyzed as an independent variable. We observed a strong independent correlation between intraabdominal fat and pptg response to a fatty meal (r = 0.521, P < 0.05). Baseline triglyceride was also independently correlated with postprandial triglycerides (r = 0.631, P < 0.05). In univariate analysis, intraabdominal fat was correlated with age, sex, body mass index (BMI), waist-to-hip ratio (WHR), and dietary saturated fatty acids. The association with age and BMI persisted in multivariate analyses.

Increased chronic bowel complications with split-course pelvic irradiation.

PURPOSE: To assess the possible impact of various treatment factors including split-course versus continuous course treatment on the incidence of chronic bowel complications in patients receiving adjuvant pelvic radiotherapy. METHODS AND MATERIALS: A retrospective review was performed of records of 153 patients treated with adjuvant external beam pelvic radiation therapy without brachytherapy for endometrial and colorectal carcinomas. Continuous course radiotherapy was administered in 91 patients (59%) and 62 patients (41%) received split course treatment with a planned 2 week mid-treatment break. Mean pelvic dose and daily fraction size were 51.4 and 1.71 Gray, respectively. Multiple patient and treatment variables were assessed for their possible relationship to chronic bowel complications. Univariate and multivariate statistical analyses were carried out. RESULTS: Twenty-seven patients (18%) developed chronic bowel complications at a median interval of 12 months after radiotherapy. Of all factors analyzed, only the use of split course technique was associated with a significantly higher rate of chronic bowel injury and decreased complication-free survival (p = 0.009). CONCLUSION: This study supports earlier suggestions that the use of split course rather than continuous course pelvic radiotherapy can increase late intestinal complication rates. Possible pathophysiologic mechanisms are discussed.

Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II)

We randomized 151 coronary patients to placebo or pravastatin and treated them for 3 years. B-mode ultrasound quantification of carotid artery intimal-medial thickness (IMT) was obtained at baseline and sequentially during this period. The primary outcome was the change in the mean of the maximal IMT measurements across time. Effects on individual carotid artery segments (common, bifurcation, and internal carotid) and on clinical events were also investigated. Plasma concentrations of total cholesterol were lower with active treatment than with placebo (4.80 vs 6.07 mmol/L [186 vs 235 mg/dl], respectively) as were concentrations of low-density lipoprotein cholesterol (3.11 vs 4.30 mmol/L [120 vs 167 mg/dl], respectively). Plasma concentrations of high-density lipoprotein2 cholesterol were higher with active treatment (0.16 vs 0.14 mmol/L [6.1 vs 5.5 mg/dl], respectively). Active treatment resulted in a nonsignificant 12% reduction in progression of the mean-maximum IMT (from 0.068 to 0.059 mm/year) and a statistically significant 35% reduction in IMT progression in the common carotid. Active treatment was also associated with a reduction in fatal and nonfatal coronary events [corrected] (p = 0.09) and of any fatal event plus nonfatal myocardial infarction (p = 0.04).

1996 Remington lecture: modeling multivariate longitudinal data that are incomplete.

PURPOSE: We describe the impact that missing data may have on model selection for longitudinal multivariate data. METHODS: Maximum likelihood was used to fit several models to ultrasonographic measurements from the Asymptomatic Carotid Artery Progression Study (ACAPS). Graphical techniques were used to examine evidence concerning the underlying missing data mechanisms associated with each model. RESULTS: Using statistical methodology that addressed missing data substantially increased the statistical efficiency of our analysis of ultrasonographic data. Only complex models that included segment-specific parameterizations for longitudinal correlations appeared to allow missing data to be assumed to occur at random. CONCLUSION: Ignoring the nature of missing data in conducting statistical analyses can have serious consequences when missingness is not rare. It may be necessary to fit models of high dimension with maximum likelihood techniques to address missing data appropriately, however these approaches may improve statistical efficiency.

Ten-year trends in cigarette smoking among young adults, 1986-1996: the CARDIA study. Coronary Artery Risk Development In Young Adults.

PURPOSE: To calculate ten-year smoking trends in a longitudinal cohort of young adults, and to characterize trends by race, sex, education, and birth cohort. METHODS: Data on cigarette smoking have been collected for ten years (1986-1996) from 5115 black and white men and women, aged 18-30 years, participating in the Coronary Artery Risk Development In Young Adults (CARDIA) study. Regression analysis adjusting for intra-person correlation over time and weighting for factors affecting follow-up was used to estimate change in smoking rates. RESULTS: Overall, smoking rates declined in white women (-0.50%/year, p < 0.001) and white men (-0.24%/year, p = 0.03). Rates remained stable in black women and increased in black men (0.37%/year, p = 0.01). Declining rates were generally observed in white women of all educational levels and birth cohorts and in several subgroups of white men. Increasing rates among black men could be attributed primarily to increasing rates in the youngest birth cohort. Among black men and women, prevalence of smoking in 1986 was considerably lower in the youngest birth cohort compared to the oldest; however, the increasing rates of change in smoking rates observed among the youngest birth cohorts (and decreasing rates in the oldest) lessened the disparity in prevalence rates across birth cohorts by 1996. Smoking initiation rates were highest among black men; cessation rates were highest among white women. CONCLUSIONS: These findings confirm that declines in smoking prevalence are not occurring across all groups, and reveal populations in special need of targeted interventions, particularly young black men.

Comparison of hospital and neighborhood controls in a study of coronary artery disease.

Case-control studies of risk factors for coronary artery disease (CAD) have almost invariably employed hospital controls, with minimal or no coronary artery stenosis. Although there is an important advantage in knowing the CAD status of controls, such groups are subject to bias related to hospitalization. To evaluate the generalizability of results obtained from studies using hospital controls, we compared risk factors in 342 hospital controls free of angiographic evidence for CAD, 168 neighborhood controls without symptoms of CAD, and 450 CAD patients. Coronary artery disease in cases and hospital controls was established arteriographically. No significant differences were found between the male control groups for total and low density lipoprotein (LDL) cholesterol, LDL apo-B, pack-years of smoking, body mass index, proportion with hypertension, diabetes and family history of coronary heart disease. Compared with neighborhood controls, male hospital controls had significantly lower high density lipoprotein (HDL) cholesterol, higher triglycerides and uric acid and scored higher on the Framingham Type A behavior pattern scale. Among women, the hospital control group had significantly lower LDL cholesterol and fewer pack-years of smoking, and a greater prevalence of hypertension than the neighborhood group. A greater proportion of both male and female hospital controls had left ventricular hypertrophy, and there were more current smokers among the neighborhood controls in both sexes. Age adjustment did not change these comparisons. While very few neighborhood controls were treated with beta-blockers, 32.7% of male and 41.4% of female hospital controls were so medicated. Control for beta-blocker use eliminated the difference in HDL cholesterol and triglycerides between the two male control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term exercise and its effect on balance in older, osteoarthritic adults: results from the Fitness, Arthritis, and Seniors Trial (FAST).

OBJECTIVES: To examine the effects of 18-month aerobic walking and strength training programs on static postural stability among older adults with knee osteoarthritis. DESIGN: Randomized, single-blind, clinical trial of therapeutic exercise. SETTING: Both center-based (university) and home-based. PARTICIPANTS: A cohort of 103 older adults (age = 60 years) with knee osteoarthritis who were participants in a large (n = 439) clinical trial and who were randomly assigned to undergo biomechanical testing. INTERVENTION: An 18-month center- (3 months) and home-based (15 months) therapeutic exercise program. The subjects were randomized to one of three treatment arms: (1) aerobic walking; (2) health education control; or (3) weight training. MEASUREMENTS: Force platform static balance measures of average length (Rm) of the center of pressure (COP), average velocity (Vel) of the COP, elliptical area (Ae) of the COP, and balance time (T). Measures were made under four conditions: eyes open, double- and single-leg stances and eyes closed, double- and single-leg stances. RESULTS: In the eyes closed, double-leg stance condition, both the aerobic and weight training groups demonstrated significantly better sway measures relative to the health education group. The aerobic group also demonstrated better balance in the eyes open, single-leg stance condition. CONCLUSIONS: Our results suggest that long-term weight training and aerobic walking programs significantly improve postural sway in older, osteoarthritic adults, thereby decreasing the likelihood of larger postural sway disturbances relative to a control group.

Birth weight standards for triplets under modern obstetric care in the United States, 1984-1989.

Birth data were reviewed on 3321 live-born infants from 1138 triplet pregnancies delivered in the United States between 1984-1989. The three major etiologies for the multiple gestations were fertility drugs (50%), spontaneous (38%), and in vitro methods (9%). The average length of gestation was 33.8 weeks and the mean birth weight was 1911 g. Neonatal birth weight curves for triplet infants born alive in the third trimester were plotted. From 26-35 weeks, the average triplet newborn has a weight corresponding to approximately the 30th percentile level compared with singletons. After 35 weeks, triplet birth weights fall progressively behind those of singletons, reaching the tenth percentile at 38 weeks. Multiple epidemiologic factors were analyzed to determine their effect upon neonatal birth weight and length of gestation. Factors predicting higher than average birth weight included male sex, increasing maternal age, increasing maternal height and weight, maternal weight gain, and maternal parity. The length of gestation was found to correlate with maternal age, weight gain, and parity. No significant association between fertility method and gestational age or weight could be identified. This large data base provides the first comprehensive percentile birth weight rankings for modernly managed triplet gestations in the United States population. A regression equation is presented which accurately predicts mean triplet birth weight in the third trimester and which suggests that a nearly linear weight gain of approximately 150 g per week per fetus should be expected in this period.

An analysis of the natural history of cavernous angiomas.

The advent of magnetic resonance (MR) imaging has permitted the recognition of many angiographically occult vascular malformations before the development of complications and subsequent surgical removal. This study reviews all patients at one institution who had radiographically identifiable vascular malformations believed to represent cavernous angiomas in order to obtain information on the natural history of this particular lesion. All 8131 craniospinal MR images performed at our medical center from January 1, 1986, to November 30, 1989, were reviewed, and 32 patients were identified with 76 lesions meeting the MR imaging criteria for cavernous angioma. Medical histories, physical examination records, and other data from these patients were then reviewed to determine the frequency of complications. Their mean age at latest follow-up examination (or at surgical removal of the lesion) was 37.6 years (range 16 to 72 years). Sixteen patients (50%) had a history of seizures, seven (22%) had focal neurological deficits, and three (9%) had clinically significant hemorrhage attributable to the cavernous angioma; six patients (19%) were asymptomatic. The estimated risk of hemorrhage for this population is 0.25%/person-year of exposure; the estimated risk of seizure development is 1.51%/person-year. Eight patients underwent surgical procedures, resulting in improved seizure control and/or lessened neurological deficit. Although these lesions are often excised with relative ease and minimal morbidity, the potential risks and benefits of surgery must be weighed carefully before removal of these relatively benign malformations.

Exercise and the incidence of upper respiratory tract infections.

We examined illness patterns in a cohort of 530 male and female runners who completed a monthly log for 12 months. The average number of upper respiratory tract infections (URTIs) per person per year for the cohort was 1.2. An upper respiratory tract infection was indicated by the report of any of the following symptoms; runny nose, sore throat, or cough. Using a multiple logistic regression model, the following factors were found to be associated with having one or more URTIs in the follow-up period: living alone (odds ratio = 2.27, 95% CI = 1.01, 5.09), running mileage (486-865 miles, odds ratio = 2.00, 95% CI = 1.01, 2.78; 866-1388 miles, odds ratio = 3.50, 95% CI = 1.52, 4.44; greater than 1388 miles, odds ratio = 2.96, 95% CI = 1.30, 3.68), body mass index greater than the 75th percentile (odds ratio = 0.58, 95% CI = 0.35, 0.94), and male gender (odds ratio = 0.14, 95% CI = 0.03, 0.68). A significant interaction was found to exist between gender and alcohol use, with the association between alcohol use and upper respiratory tract infections being positive in males and negative in females. These results suggest that running dosage (mileage) is a significant risk factor for upper respiratory tract infections in this group of exercisers.

Bilateral monocular diplopia associated with lid position during near work.

PURPOSE: To describe a common pattern of topographic changes and clinical signs of six patients presenting with a complaint of monocular diplopia after reading and to investigate the cause of this topographic disturbance. PATIENT POPULATION: Subject group of six patients with monocular diplopia complaints after reading and 20 patients without such complaints. Examinations performed before and after a reading period of 30 min: videokeratoscopic examination, red reflex examination, position of the lids in primary gaze and in reading position. DATA ANALYSIS: inspection of keratoscopic rings, qualitative analysis of topography maps, comparison of SAI and SRI of control and subject groups before and after reading, comparison of lid position of control and subject group. RESULTS: Half of the subject group and none of the control group developed subtle ring distortions of keratoscopic rings. SAI and SRI values increased significantly in the subject group compared with the control group (p = 0.02 and p < 0.001, respectively) corresponding to the development of a focal distortion in the entrance pupil of the videokeratoscopic image. Each subject developed a horizontal band on red reflex located at the superior, middle, or inferior aspect of the pupil after near work. Two controls developed faint bands in the red reflex outside the entrance pupil. The interpalpebral fissure in down gaze was narrower in the subject group compared with the control group (p = 0.001). CONCLUSIONS: Some individuals may develop monocular diplopia after reading. We hypothesize that during near work these corneal topographic alterations occur primarily related to the position of the lids and tear film interaction with the corneal surface.

Irradiation. A significant risk factor for carotid atherosclerosis.

Radiation exacerbates the development of atherosclerosis in the large arteries of animals and is postulated to do likewise in human beings. To study this relationship, we used high-resolution B-mode ultrasonography to measure carotid artery wall thickness in 29 previously irradiated head and neck cancer patients and compared the results with those of nine epidemiologically similar but nonirradiated head and neck cancer patients. Maximal intima-media thickness was greater in the study group (mean, 1.28 +/- SE 0.06 mm) than in the control group (mean, 0.90 +/- SE 0.05 mm). Even after the effects of age, hypertension, and tobacco consumption were controlled, these differences remained statistically significant. This study suggests that irradiation may contribute to the development of more severe and extensive carotid atherosclerosis in head and neck cancer patients who receive radiation therapy.

Prognostic significance of progression of coronary atherosclerosis.

BACKGROUND: Angiographic progression of coronary atherosclerosis is frequently observed in clinical practice and is used as an end point in clinical trials; however, its prognostic significance is unclear. METHODS AND RESULTS: Progression defined as an increase in diameter stenosis by > or = 15% of at least one coronary lesion was seen in 141 (42%) of 335 patients who underwent repeat coronary arteriography after a 2-year interval as part of clinical trial. Coronary lesions were measured quantitatively from comparable end-diastolic frames selected by a radiologist viewing each pair of films together. During a mean follow-up of 44 +/- 10 months after the second arteriogram, cardiac death occurred in 19 patients (5.7%), cardiac death or nonfatal infarction was seen in 40 cases (11.9%), and 90 patients (26.9%) underwent coronary revascularization. At least one end point event occurred in 112 of the 335 patients. Sixteen of the 19 cardiac deaths were in progressors, a relative risk of 7.3 (95% CI, 2.2-24.7; p < 0.001). The relative risk of cardiac death or nonfatal infarction for progressors was 2.3 (1.3-4.2, p = 0.009) and of any cardiac event was 1.7 (1.3-2.3, p < 0.001). A stepwise multivariable Cox regression model of time to event was used to assess the relative contribution of progression as a predictor of coronary events. Low ejection fraction (p = 0.001), progression (p = 0.001), and hypertension (p = 0.011) were retained as predictors of cardiac death. Angina and the number of diseased vessels were the strongest predictors of revascularization. CONCLUSIONS: Coronary progression is a strong, independent predictor of future coronary events, particularly cardiac death, and its use as a surrogate end point in clinical trials is justified.

Advantages and limitations of serial coronary arteriography for the assessment of progression and regression of coronary atherosclerosis. Implications for clinical trials.

BACKGROUND: Clinical trials with angiographic end points have been used to assess whether interventions influence the evolution of coronary atherosclerosis because sample size requirements are much smaller than for trials with hard clinical end points. Further studies of the variability of the computer-assisted quantitative measurement techniques used in such studies would be useful to establish better standardized criteria for defining significant change. METHODS AND RESULTS: In 21 patients who had two arteriograms 3-189 days apart, we assessed the reproducibility of repeat quantitative measurements of 54 target lesions under four conditions: 1) same film, same frame; 2) same film, different frame; 3) same view from films obtained within 1 month; and 4) same view from films 1-6 months apart. Quantitative measurements of 2,544 stenoses were also compared with an experienced radiologist's interpretation. The standard deviation of repeat measurements of minimum diameter from the same frame was very low (0.088 mm) but increased to 0.141 mm for measurements from different frames. It did not increase further for films within 1 month but increased to 0.197 mm for films 1-6 months apart. Diameter stenosis measurements were somewhat more variable. Measurement variability for minimum diameter was independent of vessel size and stenosis severity. Experienced radiologists did not systematically overestimate or underestimate lesion severity except for mild overestimation (mean 3.3%) for stenoses > or = 70%. However, the variability between visual and quantitative measurements was two to three times higher than the variability of paired quantitative measurements from the same frame. CONCLUSIONS: Changes of 0.4 mm or more for minimum diameter and 15% or more for stenosis diameter (e.g., 30-45%), measured quantitatively, are recommended as criteria to define progression and regression. Approaches to data analysis for coronary arteriographic trials are discussed.

Relationship of hospitalized stroke rate and in-hospital mortality to the decline in US stroke mortality.

Data from the National Hospital Discharge Survey was used to estimate the admission rate and in-hospital mortality for US stroke patients from 1970 to 1987. Over this period the hospital admission rate increased from 5.0 per 1,000 population to 5.5 per 1,000, while the in-hospital mortality fell from 18.6 to 10.0% of discharges. When patients experiencing general or late effects or transient ischemic attacks were excluded, the hospital admission rate increased from 2.8 to 4.8 per 1,000 and in-hospital mortality fell from 26 to 12% of discharges. Admission rates increased from 1970 to 1987 for both hemorrhagic strokes and cerebral infarctions, but fell for ill-defined cerebrovascular events, presumably reflecting increased use of computed tomography and magnetic resonance imaging during this period. Mortality for hemorrhagic strokes decreased from 45 to 30% of discharges, mortality for infarctions decreased from 24 to 13% and mortality for ill-defined events fell from 24 to 17%. There are several limitations with the use of the National Hospital Discharge Survey data to estimate changes in hospital admission rates and in-hospital mortality. However, these data suggest a greater role for decreasing case fatality in explaining nationwide declines in stroke mortality rates than has generally been acknowledged.

Association of coronary disease with segment-specific intimal-medial thickening of the extracranial carotid artery.

BACKGROUND: Several investigators have evaluated relations between risk factors and intimal-medial thickness (IMT) of the extracranial carotid arteries and between IMT and clinical cardiovascular disease. Different indexes of IMT have been used as referents. We compared the strength of association of various IMT measurements with coronary artery disease as measured at coronary angiography. METHODS AND RESULTS: We quantified the mean of the IMT for 12 sites of the extracranial carotid arteries (common carotid, bifurcation, internal carotid, near and far walls, and left and right sides [mean aggregate]) as well as for various combinations of sites (eg, segment-specific means, far walls only, maximum of any site) in 270 patients with or free of coronary artery disease. Models including age and all the indexes of IMT identified the mean aggregate as the only variable independently associated with the status of coronary atherosclerosis for the group as a whole. Next most strongly correlated was the mean common plus bifurcation. When classification algorithms were tested for ability to correctly classify case patients and control subjects, the mean bifurcation, mean common plus bifurcation, and mean aggregate were most strongly related to case-control status; however, the predictive power of the mean common was also strong. CONCLUSIONS: These data support use of the mean aggregate extracranial carotid IMT for correlation with the status of coronary atherosclerosis; however, the data also support use of the mean common plus bifurcation, since there is little increase in predictive power of the mean aggregate over this index. Use of the common carotid alone is also justifiable and may be preferable for certain analyses.