Albuminuria as a risk factor for peripheral arterial disease in a general population: the Hisayama study.

AIMS: To elucidate the relationship between albuminuria and the prevalence of peripheral arterial disease (PAD), and to examine the effect of albuminuria on the ability to assess the likelihood of PAD in a general Japanese population. METHODS: In 3,061 community-dwelling subjects aged. 40 years, we investigated the association of urinary albumin-creatinine ratio (UACR) levels with the prevalence of PAD, defined as an ankle-brachial index < 0.9. The odds ratio for the presence of PAD was estimated using the logistic regression model. To compare the accuracy of the assessment for the likelihood of prevalent PAD between models adjusted for potential risk factors with and without UACR levels, the receiver operating characteristic (ROC) curves were plotted. RESULTS: Overall, 1.47% of the study participants had PAD. The age- and sex-adjusted prevalence of PAD increased linearly for UACR levels of < 5.6, 5.6-10.8, 10.9-29.9, 30.0-300.0, and >300.0 mg/g, being 0.34, 0.80, 2.02, 2.50, and 2.53%, respectively (p for trend <0.001). The multivariate-adjusted odds ratio for the presence of PAD was 1.85 (95% confidence interval 1.12-3.06) for every 10-fold increment in UACR. The area under the ROC curve significantly increased when UACR levels were incorporated into a model with potential risk factors for PAD (0.80 vs. 0.77, p= 0.02). CONCLUSION: Greater UACR levels are associated linearly with a higher prevalence of PAD, even within the normoalbuminuric range, in the general Japanese population, and combining UACR levels with potential risk factors substantially improves the performance to assess the likelihood of PAD.

Cadmium and peripheral arterial disease: gender differences in the 1999-2004 US National Health and Nutrition Examination Survey.

Gender differences in the association of blood and urine cadmium concentrations with peripheral arterial disease (PAD) were evaluated by using data from 6,456 US adults aged ≥40 years who participated in the 1999-2004 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial blood pressure index of <0.9 in at least one leg. For men, the adjusted odds ratios for PAD comparing the highest with the lowest quintiles of blood and urine cadmium concentrations were 1.82 (95% confidence interval (CI): 0.82, 4.05) and 4.90 (95% CI: 1.55, 15.54), respectively, with a progressive dose-response relation and no difference by smoking status. For women, the corresponding odds ratios were 1.19 (95% CI: 0.66, 2.16) and 0.56 (95% CI: 0.18, 1.71), but there was evidence of effect modification by smoking: among women ever smokers, there was a positive, progressive dose-response relation; among women never smokers, there was a U-shaped dose-response relation. Higher blood and urine cadmium levels were associated with increased prevalence of PAD, but women never smokers showed a U-shaped relation with increased prevalence of PAD at very low cadmium levels. These findings add to the concern of increased cadmium exposure as a cardiovascular risk factor in the general population.

Albuminuria and peripheral arterial disease: results from the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: The association of albuminuria with cardiovascular disease (CVD) is increasingly recognized, but its association with peripheral arterial disease (PAD) is not well characterized in subjects with or without diabetes. METHODS: Using data from the Multi-Ethnic Study of Atherosclerosis, a cohort free of clinical vascular disease, we analyzed the cross-sectional association between albuminuria and PAD in diabetic and nondiabetic subjects. A spot urine albumin-creatinine ratio (ACR) was used to define albuminuria in two ways: presence or absence of albuminuria and the degree of albuminuria (no albuminuria defined as urine ACR<17 mg/g for men and <25mg/g for women, microalbuminuria as urine ACR 17 to 249 mg/g for men and 25 to 334 mg/g for women, and macroalbuminuria as urine ACR> or =250 mg/g for men and > or =355 mg/g for women). PAD was defined by ankle-brachial index (ABI)<0.9. RESULTS: Among the 6760 subjects, aged 45-84 years, 326 (4.8%) had prevalent PAD. Eight hundred and thirteen (12.0%) subjects had microalbuminuria and 100 (1.5%) had macroalbuminuria. Among diabetic subjects, those with albuminuria (micro- and macroalbuminuria combined) were 1.90 times more likely to have PAD (95% CI: 1.19-3.04) than those with no albuminuria. After adjusting for CVD risk factors, the odds ratio modestly attenuated to 1.65 (95% CI: 1.00-2.74). For nondiabetic subjects, there were no statistically significant associations observed in the univariable and multivariable analyses. The degree of albuminuria was not associated with PAD in either diabetic or nondiabetic subjects. CONCLUSIONS: The presence, but not magnitude of albuminuria, is an important risk factor for PAD in diabetic but not in nondiabetic subjects.

Microalbuminuria is a negative correlate for cognitive function in older adults with peripheral arterial disease: results from the U.S. National Health and Nutrition Examination Survey 1999-2002.

OBJECTIVES: Microalbuminuria (MA) has been increasingly identified as a marker of cardiovascular risk. Although poor cognitive function has been implicated as a sequelae of increased cardiovascular burden, little is known about the association between MA and cognitive function. DESIGN: Population-based cross-sectional study. SETTINGS: National Health and Nutrition Examination Survey 1999-2002 in the USA. SUBJECTS: 2049 noninstitutionalized adults (>/=60 years) with nonmissing values in cognitive test, urinary albumin-to-creatinine ratio (UACR) and ankle-brachial blood pressure index (ABPI) was analysed. Participants with UACR >300 microg mg(-1) were excluded. MAIN OUTCOME MEASURES: The UACR, in the unit of microg mg(-1), was calculated by dividing the urinary albumin value by the urinary creatinine concentration. MA was defined as UACR between 30 and 300 microg mg(-1). Cognitive function was measured by a 2-min Digit Symbol Substitution Test (DSST). Peripheral artery disease (PAD) was defined as an ABPI <0.9 in either leg. RESULTS: Overall speaking, MA was inversely associated with DSST score after controlling for age, sex, race, body mass index and educational level (regression coefficient = -2.8, P = 0.002). There was an effect modification of PAD on the association between MA and the DSST score. Amongst participants with PAD, the DSST score for those with MA was lower than those without MA (beta = -6.3, P = 0.003) after multivariate adjustment. Moreover, participants with PAD in the highest quartile of UACR had significantly lower DSST score compared to those in the lowest quartile (beta = -8.7, P = 0.001). There was no association between MA and cognitive function amongst participants without PAD. We observed an additive effect of MA and PAD on DSST score. Participants with both MA and PAD had a lower mean DSST score compared to those without both conditions (beta = -6.2, P = 0.003). CONCLUSIONS: The presence of MA or a higher level of urinary albumin excretion was inversely associated with cognitive function in participants with PAD.

A summary of safety of gadofosveset (MS-325) at 0.03 mmol/kg body weight dose: Phase II and Phase III clinical trials data.

OBJECTIVE: We sought to summarize the Phase II and Phase III clinical trials safety data for gadofosveset (Vasovist, MS-325), a new magnetic resonance angiography contrast agent. MATERIALS AND METHODS: Subjects with known or suspected vascular disease were administered 0.03 mmol/kg gadofosveset (767 subjects) or placebo (49 subjects) in phase II and phase III studies. Overall safety data were pooled from 8 studies and included adverse event monitoring, clinical laboratory assays, vital signs, oxygen saturation, physical examination, and electrocardiography. The safety was monitored for 72 to 96 hours postinjection (PI), and safety comparison with x-ray angiography using iodinated contrast media also was performed in 318 subjects. In the phase II trial, 5 doses of gadofosveset and placebo were evaluated. In this study, 38 patients were administered placebo and 39 patients received 0.03 mmol/kg gadofosveset. RESULTS: In pooled data, treatment related adverse events were reported by 176 (22.9%) patients receiving gadofosveset and by 16 (32.7%) patients receiving placebo. In phase II trial, treatment-related adverse events were reported by 13 of the 39 (33.3%) patients receiving gadofosveset and 9 of the 38 (23.7%) patients receiving placebo. No severe or serious adverse events were reported in either gadofosveset or placebo groups in this phase II trial. Pooled data revealed no clinically significant trends in adverse events, laboratory assays, vital signs, or oxygen saturation. A QTc prolongation of 2.8 milliseconds was observed at 45 minutes after MS-325 injection; however, this trend was similar to that of the placebo group at the same time point (3.2 milliseconds). CONCLUSION: Gadofosveset has exhibited a good safety profile and can be safely administered as an intravenous bolus injection. The overall rate and experience of adverse events was similar to that of placebo. The safety profile of gadofosveset is comparable with that of other gadolinium contrast agents as reported in the literature.

Occult renal impairment is common in patients with peripheral vascular disease and normal serum creatinine.

OBJECTIVE: The incidence of peripheral vascular disease (PVD) and angiography/angioplasty is rising annually. The UK Small Aneurysm Trial and other trials have shown renal function is a predictor of increased mortality and failed infrainguinal bypass despite patent vessels. Renal function is classically assessed by serum creatinine (SCr). However, SCr can be normal despite significant renal impairment. A more sensitive test is creatinine clearance (CrCl) as determined by 24-hour urine collection in combination with SCr. We studied the incidence of renal impairment, as defined by CrCl, in PVD patients with normal SCr. METHODOLOGY: All patients with PVD sufficient to necessitate angiography and normal SCr (< or =120 micromol/l - men; < or =97 micromol/l - women) had their CrCl assessed prior to angiography: using both 24-hour urine collection and the Cockcroft-Gault formula. Various blood tests, a detailed history and examination were performed. A control group of arthritic patients, age and sex-matched with similar SCr, also had their CrCl determined. RESULTS: 65 of 76 patients (86%) with normal SCr had a subnormal CrCl (<100 ml/min) and 49 (65%) had a CrCl below 60 ml/min. In the control group of arthritic patients, the proportion having impaired CrCl was significantly less - 67% below 100 mls/min (p=0.0471) and only 15% below 60 mls/min (p<0.0001). The median and interquartile range CrCl of 52 [38-81] mls/min for PVD patients was significantly worse than for control patients (80 [68-119] mls/min -p<0.0001). The Cockcroft-Gault formula for calculating CrCl did not correlate well with the urinary CrCl for the control group but did for PVD patients (p<0.0001). Factors associated with a significantly reduced CrCl were age of at least 75 years, SCr of at least 85 micromol/l and a history of coronary heart disease (all p<0.05). This had a sensitivity of 88% and specificity of 82% for identifying subnormal CrCl. Statin use was associated with a significantly improved CrCl (p=0.040). CONCLUSION: Most PVD patients with normal serum creatinine have occult, significantly impaired renal function as defined by creatinine clearance. Vascular surgeons should include creatinine clearance in pre-operative assessment of renal function especially in patients over 75 years old, with a history of coronary heart disease or a serum creatinine over 85 micromol/l. The method of determining creatinine clearance could be the Cockcroft-Gault calculation or ideally 24-hour urinary creatinine clearance measurement. This would allow appropriate early referral to a nephrologist for further investigation and management. It is worth noting that statin use seems to be associated with a protective effect on renal function.

Urinary creatinine concentration is inversely related to glycaemic control and the presence of some diabetic complications in patients with newly diagnosed Type 2 diabetes.

BACKGROUND: The ratio between urinary albumin concentration (UAC) and urinary creatinine concentration (UCC) is widely used to estimate renal involvement. We examined how UAC and UCC associate with each other, with other risk factors, and with diabetic complications in a population-based sample of Type 2 diabetic patients. METHODS: A freshly voided morning urine specimen was provided by 1,284 consecutive, newly diagnosed diabetic patients aged 40 years or over in general practice. Albumin was measured by a polyethyleneglycol radioimmunoassay and creatinine by a modified Jaffe method. RESULTS: In a multivariate model including UAC, UCC, age, sex, HbA1c, and urinary glucose concentration, UAC increased with both age (P=.042) and HbA1c (P=.014), while UCC decreased (P<.001 and P<.001, respectively). In two regression models, the prevalence of diabetic retinopathy (P<.001) and relatively high resting heart rate (P<.001) increased with increasing UAC but decreased with increasing UCC (P=.002 and P=.005, respectively). CONCLUSION: The use of albumin/creatinine ratio (ACR) may introduce bias of unpredictable size and direction in comparisons of ACR with variables that are associated with UCC in their own right. In daily clinical practice, renal involvement in the individual patient can be estimated reliably with UAC or ACR measured in a freshly voided morning urine specimen, especially when considered together. However, the associations of the combined measure ACR should be interpreted with great caution in clinical and epidemiological research.

Effect of angiotensin blockade on the association between albuminuria and peripheral arterial disease in elderly Taiwanese patients with type 2 diabetes mellitus.

BACKGROUND: The aim of the present study was to examine the impact of the clinical use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) on the association between the urinary albumin/creatinine ratio (ACR) and ankle-brachial index (ABI) or peripheral arterial disease (PAD) in elderly Taiwanese patients with type 2 diabetes mellitus. METHODS AND RESULTS: Two-hundred and ninety patients (108 men, 182 women) aged > or = 65 years (mean +/- SD, 71.6 +/-4.9) were cross-sectionally studied. ACR was expressed as the natural logarithm [ln(ACR)] and divided into normoalbuminuria (< 30.0 microg/mg) and albuminuria (> or = 30.0 microg/mg). ABI was evaluated both continuously and as peripheral arterial disease (PAD) (-) and PAD (+) using the cutoff of 0.9. Statistical analyses were performed with consideration of covariates and the use of ACEI/ARB. Results showed that in patients not using ACEI/ARB, ln (ACR) negatively correlated with ABI (r = -0.261, p < 0.01) and was associated with ABI with adjusted regression coefficient of -0.0213 (p < 0.05). PAD patients had a significantly higher level of ln (ACR) than those without PAD (4.83+/-1.34 vs 3.73+/-1.29, p < 0.001) and PAD prevalence was significantly higher in those with albuminuria than in those with normoalbuminuria (22.6% vs 4.9%, p < 0.001). The multivariate-adjusted odds ratio for PAD for every 1 unit increment of ln (ACR) was 2.10 (1.31-3.38), and for albuminuria vs normoalbuminuria 3.86 (1.04-14.31) in patients not using ACEI/ARB. In patients using ACEI/ARB, none of these analyses was significant. Patients using ACEI/ARB had a significantly lower risk of PAD with a multivariate-adjusted odds ratio of 0.34 (0.12-0.97). CONCLUSIONS: ACR negatively correlates with ABI and is associated with PAD in elderly diabetic patients not treated with ACEI/ARB. The use of ACEI/ARB attenuates this association and may be associated with a lower risk of PAD.

Metals in urine and peripheral arterial disease.

Exposure to metals may promote atherosclerosis. Blood cadmium and lead were associated with peripheral arterial disease (PAD) in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). In the present study we evaluated the association between urinary levels of cadmium, lead, barium, cobalt, cesium, molybdenum, antimony, thallium, and tungsten with PAD in a cross-sectional analysis of 790 participants > or =40 years of age in NHANES 1999-2000. PAD was defined as a blood pressure ankle brachial index < 0.9 in at least one leg. Metals were measured in casual (spot) urine specimens by inductively coupled plasma-mass spectrometry. After multivariable adjustment, subjects with PAD had 36% higher levels of cadmium in urine and 49% higher levels of tungsten compared with noncases. The adjusted odds ratio for PAD comparing the 75th to the 25th percentile of the cadmium distribution was 3.05 [95% confidence interval (CI), 0.97 to 9.58]; that for tungsten was 2.25 (95% CI, 0.97 to 5.24). PAD risk increased sharply at low levels of antimony and remained elevated beyond 0.1 microg/L. PAD was not associated with other metals. In conclusion, urinary cadmium, tungsten, and possibly antimony were associated with PAD in a representative sample of the U.S. population. For cadmium, these results strengthen previous findings using blood cadmium as a biomarker, and they support its role in atherosclerosis. For tungsten and antimony, these results need to be interpreted cautiously in the context of an exploratory analysis but deserve further study. Other metals in urine were not associated with PAD at the levels found in the general population.

C-reactive protein and microalbuminuria differ in their associations with various domains of vascular disease.

C-reactive protein (CRP) and microalbuminuria (MA) have been identified as risk markers for cardiovascular disease (CVD). We questioned whether CRP and MA are similar markers of vascular disease in different regions of the vascular tree like the heart, kidneys and extremities or if they differ in their relationships with these vascular beds. Baseline levels of CRP and urinary albumin were measured in 6669 non-diabetic participants in the Prevention of Renal and Vascular ENdstage Disease (PREVEND) study, a Dutch cohort derived from the general population. We defined three domains of vascular disease; coronary heart disease (myocardial infarction or infarct pattern on the ECG), renal insufficiency (creatinine clearance <60 ml min(-1)) and peripheral artery disease (ankle brachial index <0.9 or lower limb revascularisation). The prevalence of an elevated CRP (27.7 vs. 17.9%) and MA (17.5 vs. 10.4%) were increased in subjects with vascular disease as compared with subjects without CVD. The prevalence of an elevated CRP was equal in subjects with either coronary heart disease, renal insufficiency or peripheral artery disease (28.4 vs. 29.5 vs. 26.0%, NS), whereas MA was most prevalent in subjects with coronary heart disease (22.5 vs. 12.8 vs. 14.9%, P<0.05). Using multivariate analyses, CRP was independently associated with all three domains of vascular disease, whereas MA was independently associated with coronary heart disease only. In addition, we found synergistic contributions of an elevated CRP and older age to the risk of vascular disease in all three domains. Thus, CRP and MA are risk markers for vascular disease, each showing a different risk profiling for different vascular beds.

Factors determining cardiac hypertrophy in hypertensive patients with or without peripheral vascular disease.

1. Coronary ischaemic disease and congestive heart failure are the principal causes of mortality in patients with peripheral vascular disease. Whether cardiac hypertrophy is present and even more pronounced in peripheral vascular disease than in other populations has never been explored.2.Twenty-five hypertensive patients were investigated, 11 without and 14 with peripheral vascular disease, matched for age, sex, mean arterial pressure and antihypertensive drug treatment. Cardiac mass was determined using echocardiography together with measurement of systemic blood pressure, ratio between ankle systolic pressure (ASP) and brachial systolic pressure (BSP), and standard biochemical parameters including natriuresis per 24 h.3. At the same mean arterial pressure, patients with peripheral vascular disease had a significantly higher cardiac mass (157+/-12 versus 116+/-6 g/m2; P<0.01), pulse pressure (81+/-5 versus 55+/-4 mmHg; P<0.01) and natriuresis (180+/-17 versus 144+/-6 mmol/24h; P<0. 01) than controls. Using univariate correlations, cardiac mass was positively associated with pulse pressure, mean arterial pressure and natriuresis, and negatively with the ASP/BSP ratio. On the basis of multivariate regression analysis, only natriuresis was positively correlated to cardiac mass.4. Patients with peripheral vascular disease develop a higher degree of cardiac hypertrophy in comparison with hypertensive subjects with the same level of mean arterial pressure. Sodium intake rather than mechanical factors seems to be the major modulating factor which influences the degree of cardiac hypertrophy.

Urinary levels of inorganic and organic arsenic metabolites among residents in an arseniasis-hyperendemic area in Taiwan.

In order to elucidate whether urinary levels of inorganic and organic arsenic metabolites are associated with previous exposure to high-arsenic artesian well water, a total of 302 residents of age 30 yr or older were recruited from three arseniasis-hyperendemic villages in Taiwan. Most study subjects had stopped consuming high-arsenic artesian well water for more than 20 yr. The mean total arsenic (Ast) determined by inductively coupled plasma mass spectrometer (ICPMS) was 267.05 +/- 20.95 microg/L, and the mean level of inorganic arsenic and its metabolites (Asi) was 86.08 +/- 3.43 microg/L. In the multivariate analysis, urinary dimethylarsinic acid (DMA) levels were significantly inversely associated with age, with women exhibiting significantly lower urinary amounts of arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid (MMA), organic arsenic (Aso), and Ast compared to men. After adjustment for age and sex, previous cumulative arsenic exposure through consumption of artesian well water was significantly associated with elevated urinary levels of MMA and DMA, but not As(III) + As(V), Aso and Ast. In the multivariate analysis, the percentage of Aso in Ast was significantly higher in men than women, but this was not significantly associated with age. The percentage of As(III) + As(V) in Asi increased significantly with age, while the reverse was noted with DMA in Asi. Women had a significantly higher DMA percentage but lower As(III) + As(V) and MMA percentages in Asi than men. After adjustment for age and sex, the percentages of As(III) + As(V) in Asi were significantly inversely associated with previous arsenic exposure through consumption of artesian well water. Data suggested that women seem to possess a more efficient arsenic methylation capability than men, and aging diminishes this methylation capability; furthermore, the higher the cumulative arsenic exposure, the greater is the body burden of inorganic arsenic, mainly in the form of MMA and DMA.

Platelet activation markers in patients with peripheral arterial disease--a prospective comparison of different platelet function tests.

Peripheral vascular disease (PVD) is an indicator of diffuse atherosclerosis and is associated with a greatly increased incidence of coronary heart and cerebrovascular disease. Although several studies have assessed whether in vivo platelet activation takes place in patients with PVD, no data are available comparing different platelet function tests in this patient population. We have compared prospectively four tests for the measurement of in vivo platelet activation (plasma betaTG, plasma PF4, intraplatelet betaTG and urinary excretion of 11-dehydro-TXB2) and one in vitro platelet function test (ADP-induced platelet aggregation) in 63 well-characterized patients with intermittent claudication and in 18 age- and sex-matched healthy volunteers. No statistically significant difference was found between patients and controls for plasma betaTG (20.0 +/- 11.8 vs. 18.8 +/- 9.0 ng/ml, respectively), plasma PF4 (5.2 +/- 2.9 vs. 6.3 +/- 3.5 ng/ml), betaTG/PF4 ratio (4.0 +/- 2.9 vs. 3.6 +/- 1.8), intraplatelet betaTG (4503 +/- 1482 vs. 4059 +/- 1065 ng/ml), and threshold aggregatory concentration of ADP (1.7 +/- 0.72 vs. 1.45 +/- 0.56 microM). Urinary 11-dehydro-TXB2 was instead significantly higher in the PVD group (55.4 +/- 27.5 vs. 26.7 +/- 7.0 ng/h, p <0.001). Our study shows that urinary 11-dehydro-TXB2 is a more sensitive index of in vivo platelet activation than the measurement of either platelet specific proteins or of in vitro platelet aggregation in patients with PVD.

Aggravation of the nutcracker syndrome during pregnancy.

BACKGROUND: The nutcracker syndrome is a rare condition thought to be caused by compression of the left renal vein between the descending aorta and the superior mesenteric artery. CASE: Gross hematuria appeared in the third trimester of an otherwise normal pregnancy. It continued despite treatment, and a cesarean was performed at 37 weeks' gestation. The hematuria stopped postpartum. With postpartum angiography and three-dimensional computed tomography, the diagnosis of nutcracker syndrome was finally made. CONCLUSION: Pregnancy can aggravate the nutcracker syndrome. This syndrome should be recognized as one of the diseases that causes gross hematuria.

Concentration of arsenic, selenium, zinc, iron and copper in the urine of blackfoot disease patients at different clinical stages.

Atomic absorption spectrophotometric methods were developed for the determination of arsenic, selenium, iron, zinc, and copper in the urine samples. Data collected from blackfoot disease patients at five clinical stages were compared with those from healthy controls. Spectrophotometry was also used to compare the concentrations and detection levels of these elements in blood and hair samples. The copper concentration in urine changed slightly for all clinical stages, whereas the concentrations in blood and hair showed less correlation with the stages of blackfoot disease. The zinc concentration in urine increased with the clinical stage, the fourth stage having the highest concentration. The zinc concentrations in urine were not correlated with those of blood and hair samples. Zinc appears to be associated with the occurrence of scaling and cracking of the skin of the fingers or feet, and is even closely correlated with the degree of ulceration and gangrene of blackfoot disease patients. The more advanced degrees of blackfoot disease patients were associated with a greater zinc concentration in the urine. Arsenic, which is claimed to be a major causative agent of blackfoot disease, increased from the zero stage and showed a particularly high concentration in the second stage. The arsenic concentration in urine showed a positive correlation with that in the blood and the hair. Arsenic is indicated as major causative agent of blackfoot disease. The selenium concentration decreased from the zero stage, showing its lowest value during the second stage, then increased in the later stages. Changes in the selenium concentration in the urine were the inverse of those observed for the arsenic concentration in blood and hair. The decrease of selenium is attributed to the antagonistic effect of arsenic; selenium is retained during the initial stages. Iron increased from the zero stage to the second stage and showed the highest concentration of all the measured elements. It then decreased in the advanced stages of the disease. Iron may have an interactive effect with arsenic in the initial stages, resulting in loss of haemoglobin during the advanced stages. The antagonistic effect of selenium and the interactive effect of iron on arsenic warrant further study.

Simultaneous determination of Zn, Cd, Pb, and Cu in urine of patients with blackfoot disease using anodic stripping voltammetry.

Blackfoot disease (BFD) is an endemic peripheral vascular disorder resulting in gangrene of the lower extremities, especially the feet, among residents in a limited area on the southwest coast of Taiwan. In the present study, the concentrations of zinc, cadmium, lead, and copper in urine of BFD patients with matched normal controls are investigated by differential pulse anodic stripping voltammetry (DPASV) on a hanging mercury drop electrode (HMDE). The analytical results indicate that urinary copper, cadmium, and lead of the BFD patients are significantly higher than those of the controls. In addition, the patients showed a significantly lower concentration of zinc in the urine than the normal controls. The possible connection of these elements with the etiology of the disease is discussed.

Albumin excretion rate is not increased in atherosclerotic patients with peripheral vascular disease.

In type I diabetic patients, microalbuminuria is considered predictive of nephropathy and has been found associated with an increased mobility and mortality for atherosclerosis. An association between microalbuminuria and atherosclerosis has been reported in non diabetic atherosclerotic patients with hypertension. The aim of this study is to evaluate whether albumin excretion rate (AER) is increased in a selected group of normotensive patients with documented peripheral atherosclerotic disease. We measured the AER on overnight urine collections in: 20 normotensive, non diabetic, atherosclerotic patients and in 14 healthy volunteers, matched for sex, age, body mass index. All subjects had normal renal function and negative family history of hypertension and diabetes. The AER values were 2.46 +/- 0.52 micrograms/min in controls, 3.25 +/- 0.69 micrograms/min in atherosclerotic patients, and the difference was not statistically significant. No subject (patient or control) was microalbuminuric. These results suggest that AER is not a marker of widespread vascular damage in normotensive atherosclerotic patients with normal glucose tolerance.