Hypertension and correlates among Montenegrin schoolchildren-a cross-sectional study.

OBJECTIVES: In one of the few national studies of children in a former Eastern bloc country emerging as a Western democracy and the first such study ever in Montenegro, this study establishes the prevalence and correlates of childhood hypertension (CH). STUDY DESIGN: A cross-sectional national study. METHODS: The study was conducted with 3254 children aged 7-13 years (50.3% male) from 39 elementary schools. We used a structured questionnaire to gather sociodemographic information as well as data on factors potentially related to CH. Children's nutritional status was assessed using the criteria of the International Obesity Task Force. Waist circumference was also measured. Blood pressure was measured in schools using an oscillometric monitor. CH was defined as an average systolic blood pressure and/or diastolic blood pressure greater than or equal to the 95th percentile for sex, age, and height. RESULTS: The prevalence of CH was 10.4% with no differences between boys and girls. Multiple regression revealed that the odds for child hypertension were lowered by 10% for each year of age. On the other hand, rural environment and child obesity raised the odds of hypertension by 38% and 68%, respectively. CONCLUSIONS: We found hypertension in one out of ten Montenegrin schoolchildren, with no gender differences. Obesity and rural areas may be unfriendly to children's blood pressure.

Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative.

AIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.

Use of atorvastatin in systemic lupus erythematosus in children and adolescents.

OBJECTIVE: Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE. METHODS: A total of 221 participants with pediatric SLE (ages 10-21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n=113) or placebo (n=108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes. RESULTS: Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P=0.24). The atorvastatin group achieved lower hsCRP (P=0.04), total cholesterol (P<0.001), and low-density lipoprotein (P<0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023-0.0144 mm/year; P<0.05). Serious adverse events and critical safety measures did not differ between groups. CONCLUSION: Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.

Manual or semi-automated edge detection of the maximal far wall common carotid intima-media thickness: a direct comparison.

BACKGROUND: Automated edge detection is thought to be superior to manual edge detection in quantification of the far wall common carotid intima-media thickness (CIMT), yet published evidence making a direct comparison is not available. METHODS: Data were used from the METEOR study, a randomized placebo-controlled trial among 984 individuals showing that rosuvastatin attenuated the rate of change of 2 year change in CIMT among low-risk individuals with subclinical atherosclerosis. For this post hoc analysis, CIMT images of the far wall of the common carotid artery were evaluated using manual and semi-automated edge detection and reproducibility, relation to cardiovascular risk factors, rates of change over time and effects of lipid-lowering therapy were assessed. RESULTS: Reproducibility was high for both reading methods. Direction, magnitude and statistical significance of risk factor relations were similar across methods. Rate of change in CIMT in participants assigned to placebo was 0.0066 mm per year (SE: 0.0027) for manually and 0.0072 mm per year (SE: 0.0029) for semi-automatically read images. The effect of lipid-lowering therapy on CIMT changes was -0.0103 mm per year (SE: 0.0032) for manual reading and -0.0111 mm per year (SE: 0.0034) for semi-automated reading. CONCLUSION: Manual and semi-automated readings of the maximal far wall of the common CIMT images both result in high reproducibility, show similar risk factor relations, rates of change and treatment effects. Hence, choices between semi-automated and manual reading software for CIMT studies likely should be based on logistical and cost considerations rather than differences in expected data quality when the choice is made to use far wall common CIMT measurements.

Increased age, high body mass index and low HDL-C levels are related to an echolucent carotid intima-media: the METEOR study.

INTRODUCTION: Echolucent plaques are related to a higher cardiovascular risk. Studies to investigate the relationship between echolucency and cardiovascular risk in the early stages of atherosclerosis are limited. We studied the relationship between cardiovascular risk factors and echolucency of the carotid intima-media in low-risk individuals. METHODS: Data were analysed from the Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin (METEOR) study, a randomized placebo-controlled trial including 984 individuals which showed that rosuvastatin attenuated the rate of change of carotid intima-media thickness (CIMT). In this post hoc analysis, duplicate baseline ultrasound images from the far wall of the left and right common carotid arteries were used for the evaluation of the echolucency of the carotid intima-media, measured by grey-scale median (GSM) on a scale of 0-256. Low GSM values reflect echolucent, whereas high values reflect echogenic structures. The relationship between baseline GSM and cardiovascular risk factors was evaluated using linear regression models. RESULTS: Mean baseline GSM (± SD) was 84 ± 29. Lower GSM of the carotid intima-media was associated with older age, high body mass index (BMI) and low levels of high-density lipoprotein cholesterol (HDL-C) [beta -4.49, 95% confidence interval (CI) -6.50 to -2.49; beta -4.51, 95% CI -6.43 to -2.60; beta 2.45, 95% CI 0.47 to 4.42, respectively]. Common CIMT was inversely related to GSM of the carotid intima-media (beta -3.94, 95% CI -1.98 to -5.89). CONCLUSION: Older age, high BMI and low levels of HDL-C are related to echolucency of the carotid intima-media. Hence, echolucency of the carotid intima-media may be used as a marker of cardiovascular risk profile to provide more information than thickness alone.

Intensive glucose control and macrovascular outcomes in type 2 diabetes.

AIMS/HYPOTHESIS: Improved glucose control in type 2 diabetes is known to reduce the risk of microvascular events. There is, however, continuing uncertainty about its impact on macrovascular disease. The aim of these analyses was to generate more precise estimates of the effects of more-intensive, compared with less-intensive, glucose control on the risk of major cardiovascular events amongst patients with type 2 diabetes. METHODS: A prospectively planned group-level meta-analysis in which characteristics of trials to be included, outcomes of interest, analyses and subgroup definitions were all pre-specified. RESULTS: A total of 27,049 participants and 2,370 major vascular events contributed to the meta-analyses. Allocation to more-intensive, compared with less-intensive, glucose control reduced the risk of major cardiovascular events by 9% (HR 0.91, 95% CI 0.84-0.99), primarily because of a 15% reduced risk of myocardial infarction (HR 0.85, 95% CI 0.76-0.94). Mortality was not decreased, with non-significant HRs of 1.04 for all-cause mortality (95% CI 0.90-1.20) and 1.10 for cardiovascular death (95% CI 0.84-1.42). Intensively treated participants had significantly more major hypoglycaemic events (HR 2.48, 95% CI 1.91-3.21). Exploratory subgroup analyses suggested the possibility of a differential effect for major cardiovascular events in participants with and without macrovascular disease (HR 1.00, 95% CI 0.89-1.13, vs HR 0.84, 95% CI 0.74-0.94, respectively; interaction p = 0.04). CONCLUSIONS/INTERPRETATION: Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes. The analyses suggest that glucose-lowering regimens should be tailored to the individual.

Intensive lipid lowering may reduce progression of carotid atherosclerosis within 12 months of treatment: the METEOR study.

BACKGROUND: In several statin trials, vascular event rates for treatment groups begin to separate 1 year after commencement of treatment. For atherosclerosis progression, the temporal sequence of the effect has not been defined. We used data from the Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin (METEOR) trial to determine the earliest time point at which significant differences in atherosclerosis progression rates could be detected after initiation of statin therapy. METHODS: The METEOR trial was a double-blind, randomized placebo-controlled trial that studied the effect of LDL-C lowering with 40 mg rosuvastatin on the rate of change of carotid intima media thickness (CIMT) measured by B-mode ultrasound amongst 984 low risk subjects. Ultrasound assessments were made at baseline and every 6 months up to 2 years. RESULTS: Rosuvastatin treatment was associated with a 49% reduction in LDL-C-C, a 34% reduction in total cholesterol, an 8.0% increase in HDL-C and a 16% reduction in triglycerides (all P < 0.0001 compared with placebo). The difference in rate of mean maximum CIMT progression between the rosuvastatin and placebo groups (based on near and far wall measurements from both left and right common carotid and internal carotid segments and carotid bifurcation) was not statistically significant after 6 months (0.0023 mm year(-1) and 0.0106 mm year(-1), respectively P = 0.34). After 12 months, CIMT progression rates were significantly different between the groups: 0.0032 mm year(-1) and 0.0133 mm year(-1) in the rosuvastatin-treated and placebo-treated groups, respectively (P = 0.049). This divergence grew with further follow-up: -0.0009 mm year(-1) and 0.0131 mm year(-1) after 18 months (P < 0.001) and -0.0014 mm year(-1) and 0.0131 mm year(-1) after 24 months of treatment (P < 0.001). Results were stronger for the mean common CIMT progression (based on near and far wall measurements from both left and right common carotid segments). CONCLUSION: Aggressive LDL-C lowering seems to exert its beneficial effect on atherosclerosis progression during the first 12 months of treatment. This parallels the timing of event reduction seen in clinical trials and suggests that the efficacy of lipid lowering treatment on CIMT progression can be evaluated in trials with a duration of 1 year, given sufficient sample size, high precision of measurements and a treatment effect comparable to that seen in METEOR.

Wilson's disease: identification of an abnormal copper-binding protein.

The metal-binding protein metallothionein was isolated from the livers of Wilson's disease patients and control subjects. The metals were removed from the native protein to produce the apoprotein, and copperthionein was prepared by equilibrium dialysis. Copperthionein from Wilson's disease patients had a copper-binding constant four times as great as that of the protein from control subjects. These results suggest that the alterations in copper homeostasis in Wilson's disease result from the synthesis of an abnormal metal-binding protein with an increased affinity for copper.

Effects of lovastatin and warfarin on early carotid atherosclerosis: sex-specific analyses. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group.

BACKGROUND: Few clinical trials have documented the efficacy of preventive treatment in asymptomatic women. METHODS AND RESULTS: Lovastatin and minidose warfarin were evaluated in a factorially designed, placebo-controlled, randomized trial. The primary outcome was 3-year change in the mean maximum intimal-medial thickness of the carotid arteries as measured by B-mode ultrasonography. Participants (n=919) were randomized to 1 of 4 treatment groups: lovastatin alone, warfarin alone, lovastatin+warfarin combination, or a double-placebo group. Eligible participants were asymptomatic for cardiovascular disease, with evidence of early carotid atherosclerosis and moderately elevated LDL cholesterol level. Almost half (n=445) of the participants were women. To avoid confounding, 117 women taking estrogen were excluded from analysis. Both sexes experienced reductions in disease progression with lovastatin; there was no evidence of an overall sex x treatment interaction (P=0.72). When estimates of the sex-specific results were examined post hoc, women experienced disease regression to the greatest extent with the lovastatin + warfarin combination (P=0.02), although the women on lovastatin alone also had a reduction in progression (P=0.09). Men experienced the greatest reduction with lovastatin alone (P=0.02), although there is a suggestion that warfarin may also reduce progression to some extent. CONCLUSIONS: Lovastatin is beneficial in reducing disease progression in women and men. Warfarin has no effect in women, although it may reduce progression in men. In men, warfarin does not add to the benefit of lovastatin and has no advantage over lovastatin alone.

Urban legend versus rural reality: patients' experience of attendance at accident and emergency departments in west Wales.

OBJECTIVES: To investigate why and how patients decide to attend accident and emergency (A&E) departments, and to assess their satisfaction with the experience, in a predominantly rural west Wales population. METHODS: This was a semi-structured follow up telephone interview of patients who walked in to A&E in one of four general hospitals in west Wales and were triaged as Manchester Triage score 4 or 5. Patients were recruited by nurses during the period July-November 2002. The study sample consisted of 176 male and 145 female patients, mean (SD) age 36.6 (20.0) years. The main outcome measure was a quantitative and qualitative description of the recalled experiences of A&E attenders, the circumstances of their attendance, and their satisfaction with the experience. RESULTS: Of the study sample, 78% attended with injury or illnesses of recent origin, and 50% with actual or presumed musculoskeletal injury, 73% of which were sustained within 10 miles of home. Travel to hospital was by private transport for 86%, average distance 7.4 miles. The majority (90%) were registered with a local GP, but 32% felt A&E was the obvious choice, and a further 44% considered their GP inaccessible to their needs. Patients' reasons for seeking health care at A&E were similar to those described in an English urban study. Waiting times were rarely excessive; 80% left within 2 hours, and patient satisfaction was generally high. Among the 87 patients (27%) who reported a less satisfactory experience, 48 (55%) of these complained of dismissive attitudes of doctors. CONCLUSIONS: Anecdotal accounts of abuse of A&E services and unreasonable patient expectations gain the status of "urban legends" within the medical profession. Among the predominantly settled rural population in west Wales, there is little evidence of unreasonable patient expectations, and most patients report high satisfaction levels. Patients' bad experiences most frequently arise from a dismissive attitude on the part of medical staff. These attitudes are often consequent on an A&E culture that views some patients' attendances as less appropriate than others.

Multiple metabolic syndrome is associated with lower heart rate variability. The Atherosclerosis Risk in Communities Study.

OBJECTIVE: To test at the population level whether people with multiple metabolic syndrome (MMS) disorders have reduced cardiac autonomic activity (CAA). RESEARCH DESIGN AND METHODS: We examined the association between the level of CAA and MMS disorders, at the degree of clustering and the segregate combination levels, using a random sample of 2,359 men and women aged 45-64 years from the biracial, population-based Atherosclerosis Risk in Communities (ARIC) Study. Supine resting 2-min beat-to-beat heart rate data were collected. High-frequency (HF) (0.15-0.35 Hz) and low-frequency (LF) (0.025-0.15 Hz) spectral powers, the ratio of LF to HF, and the SD of all normal R-R intervals (SDNN) were used as the conventional indices of heart rate variability (HRV) to measure CAA. The MMS disorders included hypertension, type 2 diabetes, and dyslipidemia. RESULTS: HRV indices were significantly lower in individuals with MMS disorders. The multivariable adjusted mean HF was 0.85 (beat/min)2 in subjects with all three MMS disorders, in contrast to 1.31 (beat/min)2 in subjects without any MMS disorder. At the segregated combination level, the multivariable adjusted means +/- SEM of HF were 1.34 +/- 0.05, 1.16 +/- 0.05, 1.01 +/- 0.17, and 1.34 +/- 0.05 (beat/min)2, respectively, for subjects without any MMS disorder, with hypertension only, with diabetes only, and with dyslipidemia only, and the means +/- SEM of HF were 0.93 +/- 0.04, 0.70 +/- 0.15, and 1.20 +/- 0.05 (beat/min)2, respectively, for subjects with diabetes and hypertension, diabetes and dyslipidemia, and hypertension and dyslipidemia. An increase in fasting insulin of 1 SD was associated with 88% higher odds of having a lower HF. The pattern of associations was similar for LF and SDNN. CONCLUSIONS: These findings suggest that MMS disorders adversely affect cardiac autonomic control and a reduced cardiac autonomic control may contribute to the increased risk of subsequent cardiovascular events in individuals who exhibit MMS disorders.

Acoustic shadowing on B-mode ultrasound of the carotid artery predicts ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: We examined the relationship of carotid artery lesions (CALs), with and without acoustic shadowing (AS), to incident ischemic stroke events in the Atherosclerosis Risk in Communities study cohort. METHODS: The study population consisted of 13 123 men and women aged 45 to 64 years, and free of stroke, examined during 1986-1989. Over an average follow-up time of 8.0 years, 226 incident ischemic stroke cases (thromboembolic brain infarctions) were identified and classified by a standardized protocol. Three levels of exposure were defined on the basis of the presence of B-mode ultrasound-detected CALs and AS in a 3-cm segment of the carotid arteries centered at the bifurcation. RESULTS: The hazard ratio for ischemic stroke adjusted for age, ethnicity, and study site for women with a CAL without AS, compared with those without a CAL, was 1.92 (95% CI, 1.23, 3.01), and the hazard ratio comparing those with a CAL with AS with those without a CAL was 4.01 (95% CI, 2.28, 7.06). The corresponding hazard ratios for men were 1.99 (95% CI, 1.36, 2.91) and 2.23 (95% CI, 1.32, 3.79). Although adjustment for diabetes, hypertension medication, systolic blood pressure, left ventricular hypertrophy score, fibrinogen, von Willebrand factor antigen, and smoking status attenuated these associations somewhat, when compared with no evidence of CALs, CALs with AS remained statistically significant predictors of ischemic stroke in women, while CALs without AS were predictive of ischemic stroke in men. CONCLUSIONS: B-mode ultrasound-detected CALs and AS serve as markers of atherosclerosis and thus are predictive of ischemic stroke.

Determination of zinc availability in foods by the extrinsic label technique.

The absorption of intrinsic 65Zn and extrinsic 65Zn from corn and liver was measured in rats. No significant difference between the absorption of intrinsic- and extrinsic-label was observed. These results indicate that endogenous zinc and exogenous 65Zn enter a common pool prior to being absorbed from the intestine. Since extrinsic 65Zn enters a common pool with intrinsic zinc, whole-body absorption of extrinsic 65Zn can be used to obtain an accurate estimate of the availability of zinc in food. The availability of zinc in human breast milk, in cow's milk, in infant formulas, and in reconstituted dry milk was analyzed by use of the extrinsic label. The zinc in human breast milk was most available (59%) while the zinc in the infant formulas was the least available (26 to 37%). Zinc from both raw and cooked corn was more available than zinc from either cooked or uncooked rat liver.

Zinc turnover in mice during pregnancy, lactation, and growth.

The turnover of 65Zn was examined in mice. During pregnancy, lactation, and growth, the loss of 65Zn from the body was twice as great as that observed in mature, nonpregnant animals. The results of this study emphasize the need for consideration of zinc losses in the formulation of the minimum daily requirement for zinc in humans and other mammalian species.

Relative zinc availability in human breast milk, infant formulas, and cow's milk.

The concentration and bioavailability of zinc was analyzed in 10 varieties of milk. The concentration of zinc averaged 4.1 microgram/ml in unprocessed (raw) cow's milk; fortified infant formulas contained about 3 to 5 microgram Zn/ml; human breast milk and processed cow's milk contained approximately 2 microgram Zn/ml; sweetened condensed milk contained 1.3 microgram Zn/ml, and reconstituted nonfat dry milk contained 0.4 microgram Zn/ml. The mean values for zinc bioavailability to rats were as follows: sweetened condensed milk = 66%; human breast milk 59.2%, processed cow's milk = 43.7 to 50.9%; unprocessed (raw) cow's milk = 42%; nonfat dry milk = 41.2%, and infant formulas = 26.8 to 39.5%. Assuming similar absorption of zinc in rats and humans, our experimental results provide some guidelines for estimating the quantity of zinc that would actually be absorbed from various types of milk.

Impaired handling of orally administered zinc in pancreatic insufficiency.

Five patients with pancreatic insufficiency were evaluated for presence of impaired handling of orally administered zinc. Six hospital employees, eight alcoholic cirrhotics, and four patients with small bowel disease served as healthy or chronically ill controls. Two zinc tolerance tests (ZTT) were performed on each subject, one test using zinc sulfate and the other using zinc dipicolinate, a putative zinc binding ligand. Healthy controls demonstrated normal ZTT curves, with no significant difference between the two forms of zinc. Chronically ill controls had significantly depressed ZTT curves compared to healthy controls with both forms of zinc administered. In contrast, pancreatic insufficiency patients had significantly depressed ZTT curves with zinc sulfate but not with zinc dipicolinate, demonstrating a 40% reduction in the area under the curve with zinc sulfate compared to healthy controls. Our study shows impaired handling of orally administered zinc sulfate but not zinc dipicolinate in patients with pancreatic insufficiency and suggests normal pancreatic function may play a role in zinc metabolism in man.

Evaluation of magnetic resonance imaging for quantification of intraabdominal fat in human beings by spin-echo and inversion-recovery protocols.

We evaluated two magnetic resonance imaging (MRI) methods, spin echo and inversion recovery (IR), for quantification of intraabdominal fat in a subgroup of participants from the Atherosclerosis Risk in Communities (ARIC) Study. Both methods were used previously to quantify visceral fat, and the IR but not the spin echo method has been validated by comparison with computed tomography in human beings. In the present study, the reliability of both methods was excellent: reliability coefficients comparing two readers on the same scan were 0.9574 for IR (n = 158) and 0.9254 for spin echo (n = 47) when random effects models with log-transformed data were used. A comparison of visceral fat areas in 47 subjects with both IR and spin echo indicated that IR gave a slightly higher mean area than did spin echo: 134.9 compared with 129.8 cm2. However, a mixed-model analysis of variance (ANOVA) of the log-transformed data showed no statistical difference between either method or readers in the comparison of IR and spin echo. These data suggest that the IR and spin echo protocols evaluated in this communication are comparable with one another and reliable for estimation of intraabdominal fat.

Changes in survival after transient ischemic attacks: observations comparing the 1970s and 1980s.

We compared survival following transient ischemic attack (TIA) in 2 prospective cohorts of TIA patients admitted to Wake Forest University Medical Center. The 1st consisted of 177 patients admitted between 1961 and 1973, and the 2nd of 185 patients admitted between 1980 and 1983. Patients in the 2nd cohort had significantly greater longevity than patients in the 1st cohort, both univariately and after adjustment for cerebrovascular risk factors. The adjusted 1-year survival estimate increased from 91% in the 1st cohort to 98% in the 2nd, and the adjusted 3-year survival estimate increased from 83% in the 1st to 94% in the 2nd. The underlying causes for this dramatic improvement in survival may include early identification and aggressive management of TIAs or coexisting diseases, improved management of subsequent completed strokes or myocardial infarctions, or unadjusted differences in these cohorts. The data imply that reports of TIA survival from different periods may not be comparable.

Associations of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study.

The resting ankle-brachial index (ABI) is a non-invasive method to assess the patency of the lower extremity arterial system and to screen for the presence of peripheral occlusive arterial disease. To determine how the ABI is associated with clinical coronary heart disease (CHD), stroke, preclinical carotid plaque and far wall intimal-medial thickness (IMT) of the carotid and popliteal arteries, we conducted analyses in 15 106 middle-aged adults from the baseline examination (1987-1989) of the Atherosclerosis Risk in Communities (ARIC) Study. The prevalence of clinical CHD, stroke/transient ischemic attack (TIA) and preclinical carotid plaque increased with decreasing ABI levels, particularly at those of < 0.90. Individuals with ABI < 0.90 were twice as likely to have prevalent CHD as those with ABI > 0.90 (age-adjusted odds ratio (OR) ranging from 2.2 (95% CI: 1.0-5.1) in African-American men to 3.3 (95% CI: 2.1-5.0) in white men). Men with ABI < 0.90 were more than four times as likely to have stroke/TIA as those with ABI > 0.90 (age-adjusted OR: 4.2 (95% CI: 1.8-9.5) in African-American men and 4.9 (95% CI: 2.6-9.0) in white men). In women the association was weaker and not statistically significant. Among those free of clinical cardiovascular disease, individuals with ABI < or = 0.90 had statistically significantly higher prevalence of preclinical carotid plaque compared to those with ABI > 0.90 (age-adjusted ORs ranging from 1.5 (95% CI: 1.0-1.9) in white women to 2.6 (95% CI: 1.0-6.6) in african-american men). The ABI was also inversely associated with far wall IMT of the carotid arteries (in both men and women) and the popliteal arteries (in men only). The associations of ABI with clinical CHD, stroke, preclinical carotid plaque and IMT of the carotid and popliteal arteries were attenuated and often not statistically significant after further adjustment for LDL cholesterol, cigarette smoking, hypertension and diabetes. These data demonstrate that low ABI levels, particularly those of < 0.90, are indicative of generalized atherosclerosis.

Weight changes in women with metastatic breast cancer treated with megestrol acetate: a comparison of standard versus high-dose therapy.

One hundred seventy-two patients with advanced breast cancer were randomized to receive 160 or 800 mg megestrol acetate per day. Patients were monitored monthly for weight, blood pressure, performance status, edema, measurement of clinically evident lesions, and toxicities. Pretreatment characteristics were similar in both arms. Weight gain was the most commonly seen side effect, with 52% of patients gaining in excess of 10 lb and 28% gaining more than 20 lb. Median weight gain for standard-dose treatment was 5 lb compared with 18 lb for high-dose treatment. There was no dose modification for excessive weight gain in any of the patients receiving the standard dose but doses were modified in 15% of those receiving high-dose megestrol acetate. Weight gains for both groups were analyzed at 30, 90, and 180 days after study entry. Treatment arm, age, prior therapy, response to prior endocrine therapy, race, performance status, dominant disease site, and number of disease sites were included in the analysis. At 30 days, patients taking high-dose megestrol acetate had a mean weight gain of 2.5 lb whereas patients taking the standard dose had stable weights. Factors predictive of weight gain were younger age (P = .0012) and fewer disease sites (P = .017). At 90 and 180 days, patients taking high-dose megestrol acetate had consistently gained more weight than those taking the standard dose (9.0 and 16.0 lb v 2.5 and 9.0 lb, respectively). Significant covariables were treatment arm (P = .0006) and younger age (P = .0211). Probability of gaining 20 lb was dependent only on treatment dose (P = .0002), and median time to a 20-lb weight gain was 217 days. Increases in systolic and diastolic blood pressures were seen in both groups, but the differences were not significant. Megestrol acetate is associated with weight gain in women with advanced breast cancer, and the amount of weight gained correlates directly with dose of megestrol acetate, length of treatment, and age of patient.